CN117479843A - Compositions that enhance the cooling effect - Google Patents

Abstract

The present disclosure relates generally to cooling modifying compositions that enhance the cooling effect of cooling compounds such as menthol, piperlongumine, and the like. In some forms, the present disclosure provides for the use of such cooling degree modifying compositions for the cooling effect of cooling compounds. In some other aspects, the present disclosure provides compositions (e.g., edible compositions or oral care compositions) comprising a cooling compound (e.g., menthol, piperlongum, etc.) and a cooling modifying composition of the present disclosure. In some embodiments, such compositions are in the form of a food product, beverage product, or oral care product, such as a toothpaste, mouthwash, tooth whitening composition, chewing gum, dentifrice, or the like. In some other embodiments, such compositions are in the form of a body care product, such as a cosmetic product, a skin care product, or a hair care product.

Description

Translated fromChinese

增强清凉效果的组合物Compositions that enhance the cooling effect

相关申请的交叉引用Cross-references to related applications

本申请要求2021年5月28日提交的美国临时申请No.63/194,584和2021年6月21日提交的欧洲申请No.21180525.4的优先权。这些申请的全部内容通过引用方式明确并入本文。This application claims priority from U.S. Provisional Application No. 63/194,584, filed on May 28, 2021, and European Application No. 21180525.4, filed on June 21, 2021. The entire contents of these applications are expressly incorporated herein by reference.

技术领域Technical field

本公开概括而言涉及增强清凉化合物例如薄荷醇、荜澄茄醇等的清凉效果的清凉度修饰(coolness-modifying)组合物。在一些形态中，本公开提供了此类清凉度修饰组合物对于清凉化合物的清凉效果的用途。在一些其他形态中，本公开提供了组合物(例如可食用组合物或口腔护理组合物)，其包含清凉化合物(例如薄荷醇、荜澄茄醇等)和本公开的清凉度修饰组合物。在一些实施方案中，此类组合物是食物产品、饮料产品或口腔护理产品的形式，例如牙膏、漱口水、牙齿增白组合物、口香糖、洁齿剂等。在一些实施方案中，此类组合物呈身体护理产品的形式，例如美容产品、皮肤护理产品或头发护理产品。The present disclosure relates generally to coolness-modifying compositions that enhance the cooling effects of cooling compounds such as menthol, piperitaol, and the like. In some forms, the present disclosure provides the use of such cooling degree modifying compositions for the cooling effect of cooling compounds. In some other forms, the present disclosure provides compositions (eg, edible compositions or oral care compositions) comprising a cooling compound (eg, menthol, peppermint, etc.) and a cooling degree modifying composition of the present disclosure. In some embodiments, such compositions are in the form of food products, beverage products, or oral care products, such as toothpastes, mouthwashes, tooth whitening compositions, chewing gum, dentifrices, and the like. In some embodiments, such compositions are in the form of body care products, such as beauty products, skin care products, or hair care products.

背景技术Background technique

由于某些热感觉神经元的协调努力，我们的感觉系统能够检测环境温度的细微变化。TRP通道家族的温度敏感蛋白通常存在于热刺激转化为神经元活动的部位。值得注意的是，这些通道响应的温度范围涵盖了整个所感知的温度范围，从温暖到令人痛苦的炎热，从宜人的清凉到令人难以忍受的寒冷。此外，许多这些通道是配体的受体，这些配体可引发不同的心理物理感觉，例如与辣椒素相关的热感和与薄荷醇相关的冷感。Thanks to the coordinated efforts of certain thermal sensory neurons, our sensory systems are able to detect subtle changes in ambient temperature. Temperature-sensitive proteins of the TRP channel family are typically found at sites where thermal stimulation is converted into neuronal activity. Remarkably, these channels respond to temperatures that span the entire range of perceived temperatures, from warm to painfully hot, and from pleasantly cool to unbearably cold. Furthermore, many of these channels are receptors for ligands that elicit different psychophysical sensations, such as the heat sensation associated with capsaicin and the cold sensation associated with menthol.

薄荷醇以产生口腔清凉感的方式调节TRPM8受体。这就是为什么含有薄荷醇的天然产品例如薄荷提取物往往会在口腔中产生清凉效果。出于同样的原因，薄荷醇经常被用作其中需要赋予清凉效果的龋齿非提取调味剂中的成分。即便如此，薄荷醇可能会有苦味或涩味，一些用户可能会有反感。因此，可能需要开发增强薄荷醇的清凉效果的策略，从而允许降低薄荷醇的浓度并同时减少不期望的涩味或苦味。Menthol modulates TRPM8 receptors in a way that produces a cooling sensation in the mouth. This is why natural products containing menthol such as peppermint extract tend to have a cooling effect in the mouth. For the same reason, menthol is often used as an ingredient in carious non-extract flavorings where it is necessary to impart a cooling effect. Even so, menthol can have a bitter or astringent taste, which some users may find objectionable. Therefore, there may be a need to develop strategies to enhance the cooling effects of menthol, allowing for lower menthol concentrations while simultaneously reducing undesirable astringency or bitterness.

某些合成化合物可用于增强清凉效果。这些可以单独使用或与薄荷醇组合使用。但此类化合物通常会带来某些类似于薄荷醇的异味。因此，持续需要发现增强薄荷醇在食物、饮料和口腔护理产品中的清凉效果而不导致苦味或涩味感觉的新组合物。薄荷醇和其他清凉剂提供的清凉感觉的增强也有助于其他消费品例如身体护理产品的吸引力和可接受性。Certain synthetic compounds can be used to enhance the cooling effect. These can be used alone or in combination with menthol. But such compounds often impart some off-flavor similar to menthol. Accordingly, there is a continuing need to discover new compositions that enhance the cooling effects of menthol in foods, beverages, and oral care products without causing bitter or astringent sensations. The enhanced cooling sensation provided by menthol and other cooling agents also contributes to the appeal and acceptability of other consumer products such as body care products.

发明内容Contents of the invention

本公开涉及以下发现：某些组合物在增强食物、饮料或口腔护理产品中的清凉感觉(例如薄荷醇的清凉感觉)方面表现出意想不到的效果。The present disclosure relates to the discovery that certain compositions exhibit unexpected effects in enhancing the cooling sensation (eg, the cooling sensation of menthol) in foods, beverages, or oral care products.

在第一形态中，本公开提供了清凉度修饰组合物，该组合物包含清凉度增强化合物，其中该清凉度增强化合物是黄烷酮、二氢查尔酮或它们的组合。在一些实施方案中，清凉度修饰组合物还包含高强度甜味剂。在一些实施方案中，高强度甜味剂是三氯蔗糖、糖精钠或它们的组合。在一些实施方案中，组合物包含调味剂(flavoring)，例如薄荷调味剂。In a first form, the present disclosure provides a cooling-modifying composition comprising a cooling-enhancing compound, wherein the cooling-enhancing compound is a flavanone, a dihydrochalcone, or a combination thereof. In some embodiments, the coolness modifying composition further includes a high intensity sweetener. In some embodiments, the high-intensity sweetener is sucralose, sodium saccharin, or combinations thereof. In some embodiments, the compositions include flavoring, such as mint flavoring.

在第二形态中，本公开提供了黄烷酮用于增强风味化(flavored，已调味)产品的清凉感觉的用途。在一些实施方案中，风味化产品包含清凉化合物，例如薄荷醇或荜澄茄醇。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。在一些实施方案中，黄烷酮是柚皮素、橙皮素或它们的组合。In a second form, the present disclosure provides the use of flavanones to enhance the cooling sensation of flavored products. In some embodiments, the flavored product includes cooling compounds, such as menthol or piperitaol. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition. In some embodiments, the flavanone is naringenin, hesperetin, or a combination thereof.

在第三形态中，本公开提供了二氢查尔酮用于增强风味化产品的清凉感觉的用途。在一些实施方案中，风味化产品包含清凉化合物，例如薄荷醇或荜澄茄醇。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。在一些实施方案中，二氢查耳酮是根皮素。In a third form, the present disclosure provides the use of dihydrochalcones to enhance the cooling sensation of flavored products. In some embodiments, the flavored product includes cooling compounds, such as menthol or piperitaol. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition. In some embodiments, the dihydrochalcone is phloretin.

在第四形态中，本公开提供了增强风味化产品中清凉化合物的清凉感觉的方法，包括将清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)与黄烷酮在风味化产品中组合。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。在一些实施方案中，黄烷酮是柚皮素、橙皮素或它们的组合。In a fourth aspect, the present disclosure provides a method for enhancing the cooling sensation of a cooling compound in a flavored product, comprising combining a cooling compound (such as menthol, peppermint, or a combination thereof) with a flavanone in a flavored product. combination. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition. In some embodiments, the flavanone is naringenin, hesperetin, or a combination thereof.

在第五形态中，本公开提供了增强风味化产品中清凉化合物的清凉感觉的方法，包括将清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)与二氢查耳酮在风味化产品中组合。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。在一些实施方案中，二氢查耳酮是根皮素。In a fifth aspect, the present disclosure provides a method of enhancing the cooling sensation of a cooling compound in a flavored product, comprising combining a cooling compound (such as menthol, peppermint, or a combination thereof) with a dihydrochalcone in a flavored product. product mix. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition. In some embodiments, the dihydrochalcone is phloretin.

在第六形态中，本公开提供了第一形态的清凉度修饰组合物用于增强风味化产品的清凉感觉的用途。在一些实施方案中，风味化产品包含清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。In a sixth aspect, the present disclosure provides use of the cooling degree modifying composition of the first aspect for enhancing the cooling sensation of a flavored product. In some embodiments, the flavored product includes a cooling compound (eg, menthol, peppermint, or combinations thereof). In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition.

在第七形态中，本公开提供了增强风味化产品的清凉感觉的方法，该方法包括将第一形态的清凉度修饰组合物与清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)组合在风味化产品中。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白产品。In a seventh form, the present disclosure provides a method of enhancing the cooling sensation of a flavored product, the method comprising combining the cooling degree modifying composition of the first form with a cooling compound (such as menthol, peppermint, or a combination thereof) Combined in flavored products. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening product.

在第八形态中，本公开提供了风味化产品，其包含第一形态的清凉度修饰组合物和清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白产品。In an eighth form, the present disclosure provides a flavored product comprising the coolness modifying composition of the first form and a cooling compound (eg, menthol, peppermint, or a combination thereof). In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening product.

在第九形态中，本公开提供了黄烷酮用于增强身体护理产品的清凉感觉的用途。在一些实施方案中，身体护理产品包含清凉化合物，例如薄荷醇或荜澄茄醇。在一些实施方案中，身体护理产品是洗发液(香波)、沐浴液(body wash)、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂(除臭剂)、润肤露、润肤油、防晒霜或助晒剂(bronzer)。In a ninth aspect, the present disclosure provides the use of flavanones to enhance the cooling sensation of body care products. In some embodiments, body care products include cooling compounds, such as menthol or piperitaol. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant , body lotion, body oil, sunscreen or bronzer.

在第十形态中，本公开提供了二氢查尔酮用于增强身体护理产品的清凉感觉的用途。在一些实施方案中，身体护理产品包含清凉化合物，例如薄荷醇或荜澄茄醇。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In a tenth aspect, the present disclosure provides use of dihydrochalcones to enhance the cooling sensation of body care products. In some embodiments, body care products include cooling compounds, such as menthol or piperitaol. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在第十一形态中，本公开提供了增强身体护理产品中清凉化合物的清凉感觉的方法，包括将清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)与黄烷酮组合在身体护理产品中。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In an eleventh aspect, the present disclosure provides a method of enhancing the cooling sensation of a cooling compound in a body care product, comprising combining a cooling compound (such as menthol, peppermint, or a combination thereof) with a flavanone in a body care product. in the product. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在第十二形态中，本公开提供了增强身体护理产品中清凉化合物的清凉感觉的方法，包括将清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)与二氢查尔酮组合在身体护理产品中。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In a twelfth aspect, the present disclosure provides a method of enhancing the cooling sensation of a cooling compound in a body care product, comprising combining a cooling compound (eg, menthol, peppermint, or a combination thereof) with a dihydrochalcone in a body care product. In body care products. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在第十三形态中，本公开提供了第一形态的清凉度修饰组合物用于增强身体护理产品的清凉感觉的用途。在一些实施方案中，身体护理产品包含清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In a thirteenth aspect, the present disclosure provides use of the cooling degree modifying composition of the first aspect for enhancing the cooling sensation of a body care product. In some embodiments, the body care product includes a cooling compound (eg, menthol, peppermint, or combinations thereof). In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在第十四形态中，本公开提供了增强身体护理产品的清凉感觉的方法，该方法包括将第一形态的清凉度修饰组合物与清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)组合在身体护理产品中。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In a fourteenth form, the present disclosure provides a method of enhancing the cooling sensation of a body care product, the method comprising combining the cooling degree modifying composition of the first form with a cooling compound such as menthol, piperitaol, or a combination thereof ) combined in body care products. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在第十五形态中，本公开提供了身体护理产品，其包含第一形态的清凉度修饰组合物和清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In a fifteenth aspect, the present disclosure provides a body care product comprising the coolness modifying composition of the first form and a cooling compound (eg, menthol, peppermint, or a combination thereof). In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

进一步的形态及其实施方案在下文的详细描述、附图、摘要和权利要求中阐述。Further aspects and embodiments thereof are set forth in the detailed description, drawings, abstract and claims below.

附图说明Description of the drawings

图1示出了根据本文公开的某些形态的牙膏组合物的感官评价结果。具有不同字母的值显著不同，p<0.0001。Figure 1 shows the results of sensory evaluation of toothpaste compositions according to certain forms disclosed herein. Values with different letters are significantly different, p<0.0001.

图2示出了根据本文公开的某些形态的无醇漱口水组合物的感官评价结果。带星号的值显著不同，p<0.0001。Figure 2 shows the results of sensory evaluation of alcohol-free mouthwash compositions according to certain forms disclosed herein. Values with an asterisk are significantly different, p<0.0001.

图3示出了在淋浴的起泡步骤中，与参考组合物相比，使用根据本文公开的一些形态的沐浴露在身体的各个部位引起的清凉感觉。Figure 3 illustrates the cooling sensation induced on various parts of the body during the lathering step of a shower using body wash according to some forms disclosed herein compared to a reference composition.

图4示出了在淋浴后1小时，与参考组合物相比，使用根据本文公开的一些形态的沐浴露在身体的各个部位引起的清凉感觉。Figure 4 illustrates the cooling sensation induced in various areas of the body using some forms of shower gel according to the disclosure compared to a reference composition 1 hour after showering.

具体实施方式Detailed ways

以下详细描述阐述了本文提供的各种形态和实施方案。该描述将从相关领域的普通技术人员的角度来阅读。因此，这些普通技术人员所熟知的信息不一定包括在内。The following detailed description sets forth the various forms and embodiments provided herein. This description will be read from the perspective of a person of ordinary skill in the relevant art. Therefore, information that would be familiar to a person of ordinary skill may not necessarily be included.

定义definition

除非本文另有规定，否则以下术语和短语具有以下指示的含义。本公开可以采用本文未明确定义的其他术语和短语。此类其他术语和短语对于本领域普通技术人员而言具有在本公开的语境中所具有的含义。在某些情况下，术语或短语可以单数或复数定义。在这种情况下，应理解，除非明确指出相反的意思，否则单数形式的任何术语都可以包括其复数形式，反之亦然。Unless otherwise specified herein, the following terms and phrases have the meanings indicated below. This disclosure may employ other terms and phrases not expressly defined herein. Such other terms and phrases have the meaning they have to one of ordinary skill in the art in the context of this disclosure. In some cases, a term or phrase may be defined in the singular or plural. In this case, it will be understood that any term in the singular may include its plural form and vice versa, unless the contrary meaning is expressly stated.

本文中的“甜味剂”、“甜味调味剂”、“甜风味实体”或“甜味化合物”是指在受试者中引起可检测到的甜味的化合物或其摄取上可接受的盐，例如体外激活T1R2/T1R3受体的化合物。As used herein, a "sweetener," "sweet flavoring agent," "sweet flavor entity," or "sweet compound" refers to a compound that causes a detectable sweetness in a subject or is ingestively acceptable Salts, such as compounds that activate T1R2/T1R3 receptors in vitro.

“清凉感觉”是指可摄取物品在人体内产生的环境温度降低的感觉，通常通过TRPM8受体的调节进行。The "cooling sensation" refers to the feeling of lowering the ambient temperature produced by ingestible items in the human body, usually through the regulation of TRPM8 receptors.

“清凉化合物”是指调节TRPM8受体的化合物。在本文提出的任何实施方案的一些实施方案中，清凉化合物是薄荷醇。注意，如本文所用，“薄荷醇”是指(-)-薄荷醇。在本文提出的任何实施方案的一些实施方案中，清凉化合物是荜澄茄醇。清凉化合物的非限制性例子包括N-乙基-对薄荷基-3-甲酰胺、异胡薄荷醇、3-(L-薄荷氧基)丙烷-1,2-二醇、顺式/反式-对薄荷烷-3,8-二醇、3-(L-薄荷氧基)-2-甲基丙烷-1,2-二醇、2-[2-(对薄荷烷-3-基氧基)乙氧基]乙醇、薄荷氧基乙醇、(1R,2R,4R)-1-(2-羟基-4-甲基环己基)乙烯酮、(1R,2R,5R)-N-乙基-5-甲基-2-(丙-1-烯-2-基)-环己烷甲酰胺、N-(3-羟基-4-甲氧基苯基)-2-异丙基-5,5-二甲基-环己烷甲酰胺、N-[4-(氰基甲基)苯基]-2-异丙基-5,5-二甲基-环己烷甲酰胺、N-(2-羟基-2-苯基乙基)-2-异丙基-5,5-二甲基-环己烷-1-甲酰胺、L-薄荷醇乳酸酯、(-)-薄荷醇乙二醇碳酸酯、(-)-薄荷酮1,2-甘油缩酮、D/L-薄荷酮1,2-甘油缩酮、(-)-薄荷基1-丙二醇碳酸酯、(-)-薄荷基2-丙二醇碳酸酯、D/L-薄荷基1-丙二醇碳酸酯、D/L-薄荷基2-丙二醇碳酸酯、(1R,2S,5R)-N-(4-甲氧基苯基)-5-甲基-2-(1-甲基乙基)环己烷甲酰胺、薄荷基乙酰胺基草酸酯、(E)-3-苯并[1,3]二氧杂环戊烯-5-基-N,N-二苯基-2-丙烯酰胺、3,4-亚甲基二氧基肉桂酸、N,N-二苯基酰胺、N,N-二甲基(-)-薄荷基琥珀酰亚胺、(1R,2S,5R)-N-(4-(氨基甲酰基甲基)苯基)-薄荷基甲酰胺、(-)-薄荷基吡咯烷酮甲酸酯、L-去氧肾上腺素(L-phenylephrine)对薄荷烷甲酰胺、(1R,2S,5R)-N-(4-(氰基甲基)-苯基)薄荷基甲酰胺、(1R,2S,5R)-N-(2-(吡啶-2-基)乙基)薄荷基甲酰胺、6-异丙基-3,9-二甲基-1,4-二氧杂螺[4.5]癸-2-酮、(1R,2R,4S)-二氢伞柳醇、N-乙基-对薄荷烷-3-甲酰胺、2-异丙基-N,2,3-三甲基正丁酰胺(butyramide)、3-(对薄荷烷-3-甲酰氨基)乙酸乙酯、N-乙基-2,2-二异丙基丁酰胺(butanamide)、N-(1,1-二甲基-2-羟基乙基)-2,2-二甲基丁酰胺、N-环丙基-5-甲基-2-异丙基-环己烷碳甲酰胺、乙酰乙酸(-)-薄荷酯、琥珀酸(-)-薄荷酯、(S)-3-羟基丁酸(-)-薄荷酯、戊二酸(-)-薄荷酯、1-[2-羟基苯基]-4-[2-硝基苯基]-1,2,3,6-四氢嘧啶-2-酮、戊二酸二-(-)-薄荷酯，和N-(2-羟基乙基)-2,3-二甲基-2-异丙基丁酰胺。"Cooling compounds" refer to compounds that modulate TRPM8 receptors. In some embodiments of any of the embodiments presented herein, the cooling compound is menthol. Note that as used herein, "menthol" refers to (-)-menthol. In some embodiments of any of the embodiments presented herein, the cooling compound is piperol. Non-limiting examples of cooling compounds include N-ethyl-p-menthyl-3-carboxamide, isopulegol, 3-(L-menthoxy)propane-1,2-diol, cis/trans -p-menthane-3,8-diol, 3-(L-menthenyloxy)-2-methylpropane-1,2-diol, 2-[2-(p-menthane-3-yloxy) )ethoxy]ethanol, menthoxyethanol, (1R,2R,4R)-1-(2-hydroxy-4-methylcyclohexyl)ketene, (1R,2R,5R)-N-ethyl- 5-Methyl-2-(prop-1-en-2-yl)-cyclohexanecarboxamide, N-(3-hydroxy-4-methoxyphenyl)-2-isopropyl-5,5 -Dimethyl-cyclohexanecarboxamide, N-[4-(cyanomethyl)phenyl]-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-(2 -Hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethyl-cyclohexane-1-carboxamide, L-menthol lactate, (-)-menthol ethylene glycol Alcohol carbonate, (-)-menthone 1,2-glycerol ketal, D/L-menthone 1,2-glycerol ketal, (-)-menthyl 1-propylene glycol carbonate, (-)-menthyl 2-Propylene glycol carbonate, D/L-menthyl 1-propanediol carbonate, D/L-menthyl 2-propanediol carbonate, (1R,2S,5R)-N-(4-methoxyphenyl)- 5-Methyl-2-(1-methylethyl)cyclohexanecarboxamide, menthyl acetamidooxalate, (E)-3-benzo[1,3]dioxole- 5-yl-N,N-diphenyl-2-acrylamide, 3,4-methylenedioxycinnamic acid, N,N-diphenylamide, N,N-dimethyl(-)- Menthyl succinimide, (1R,2S,5R)-N-(4-(carbamoylmethyl)phenyl)-menthylcarboxamide, (-)-menthylpyrrolidonecarboxylate, L-des Oxyephrine (L-phenylephrine) p-menthane carboxamide, (1R,2S,5R)-N-(4-(cyanomethyl)-phenyl)menthyl carboxamide, (1R,2S,5R)- N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, 6-isopropyl-3,9-dimethyl-1,4-dioxaspiro[4.5]dec-2-one , (1R,2R,4S)-dihydrocymensulfide, N-ethyl-p-menthane-3-carboxamide, 2-isopropyl-N,2,3-trimethyl-n-butyramide (butyramide) , 3-(p-menthane-3-carboxylamino)ethyl acetate, N-ethyl-2,2-diisopropylbutanamide (butanamide), N-(1,1-dimethyl-2- Hydroxyethyl)-2,2-dimethylbutanamide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexanecarbonamide, (-)-menthyl acetoacetate, succinic acid (-)-Menthyl ester, (S)-3-hydroxybutyric acid (-)-menthyl ester, (-)-menthyl glutarate, 1-[2-hydroxyphenyl]-4-[2-nitro Phenyl]-1,2,3,6-tetrahydropyrimidin-2-one, di-(-)-menthyl glutarate, and N-(2-hydroxyethyl)-2,3-dimethyl -2-Isopropylbutanamide.

“黄烷酮”是指具有黄烷酮核心结构的化合物。非限制性例子包括艾纳香素(blumeatin)、紫铆素(butin)、圣草酚(eriodictyol)、橙皮素(hesperetin)、橙皮苷(hesperidin)、高圣草酚(homoeriodictyol)、异野樱素(isosakuranetin)、柚皮素(naringenin)、柚皮苷(naringin)、松属素(pinocembrin)、枸橘苷(poncirin)、樱花素(sakuranetin)、野樱黄苷(sakuranin)、7-O-甲基圣草酚(sterubin)和球松素(pinostrobin)。在一些实施方案中，黄烷酮是柚皮素。在一些实施方案中，黄烷酮是橙皮素。"Flavone" refers to a compound with a flavanone core structure. Non-limiting examples include blumeatin, butin, eriodictyol, hesperetin, hesperidin, homoeriodictyol, iso Isosakuranetin, naringenin, naringin, pinocembrin, poncirin, sakuranetin, sakuranin, 7 -O-Methyl eriodictyol (sterubin) and pinospin (pinostrobin). In some embodiments, the flavanone is naringenin. In some embodiments, the flavanone is hesperetin.

“二氢查耳酮”是指具有二氢查耳酮核心结构的化合物。非限制性例子包括阿司巴汀(aspalathin)、柚皮苷二氢查耳酮、橙皮素二氢查耳酮、橙皮素二氢查耳酮4’-O-葡糖苷、新橙皮素二氢查耳酮、诺瑟法根(nothofagin)和根皮素(phloretin)。在一些实施方案中，二氢查耳酮是根皮素。"Dihydrochalcone" refers to a compound having a dihydrochalcone core structure. Non-limiting examples include aspalathin, naringin dihydrochalcone, hesperetin dihydrochalcone, hesperetin dihydrochalcone 4'-O-glucoside, hesperidin Dihydrochalcone, nothofagin and phloretin. In some embodiments, the dihydrochalcone is phloretin.

如本文所用，单数形式的“一个”、“一种”和“该”包括复数指示物，除非上下文另外明确指出。例如，提及“一个取代基”涵盖单个取代基以及两个或更多个取代基，等等。As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, reference to "a substituent" encompasses a single substituent as well as two or more substituents, and so on.

如本文所用，“例如”、“如”、“诸如”或“包括”旨在引入进一步阐明更一般主题的例子。除非另外明确指出，否则提供这样的例子仅是为了帮助理解本公开中示出的实施方案，并且并不意味着以任何方式进行限制。这些短语也不表示对于所公开的实施方案的任何种类的偏好。As used herein, "such as," "such as," "such as," or "including" are intended to introduce examples that further illustrate the more general subject matter. Unless expressly stated otherwise, such examples are provided solely to assist in understanding the embodiments illustrated in the present disclosure and are not meant to be limiting in any way. These phrases also do not imply any kind of preference for the disclosed embodiments.

如本文所用，“包括”、“包含”、“含”和“含有(comprised of)”是指开放的组，意味着该组除了明确陈述的那些之外还可以包括其他成员。例如，短语“包含A”表示必须存在A，但是也可以存在其他成员。术语“包括”、“具有”和“含有(composed of)”及其语法变体具有相同的含义。相反，“由……组成(consist of)”或“由……构成”或“构成为”是指封闭的组。例如，短语“由A组成”是指有且仅有A存在。As used herein, "includes," "includes," "contains," and "comprised of" refer to an open group, meaning that the group may include other members in addition to those expressly stated. For example, the phrase "contains A" means that A must be present, but other members can also be present. The terms "including", "having" and "composed of" and their grammatical variations have the same meaning. In contrast, "consist of" or "consisting of" or "consisting of" refers to a closed group. For example, the phrase "consists of A" means that there is and only A present.

如本文所用，“视情况/可选地/任选地(optionally)”是指随后描述的事件可以发生或可以不发生。在一些实施方案中，可选事件不发生。在一些其他实施方案中，可选事件的确发生一次或多次。As used herein, "optionally" means that the subsequently described event may or may not occur. In some embodiments, optional events do not occur. In some other embodiments, optional events do occur one or more times.

如本文所用，“或”将被给予其最广泛的合理解释，并且不限于“要么/要么”构造。因此，短语“包含A或B”是指A可以存在而B不存在，或者B存在而A不存在，或者A和B都存在。此外，例如，如果A定义了可以具有多个成员(例如，A₁和A₂)的一类，则可以同时存在该类的一个或多个成员。As used herein, "or" is to be given its broadest reasonable interpretation and is not limited to an "either/or" construction. Thus, the phrase "comprises A or B" means that A can exist without B, or B exists without A, or both A and B exist. Furthermore, for example, if A defines a class that can have multiple members (e.g., A₁ and A₂ ), then one or more members of the class can exist at the same time.

其他术语在本说明书的其他部分中定义，即使未包括在本小节中。Other terms are defined elsewhere in this specification even if not included in this subsection.

清凉度增强化合物Cooling Enhancement Compound

在某些形态中，本公开提供了黄烷酮用于增强风味化产品的清凉感觉的用途。在一些实施方案中，风味化产品包含薄荷醇、荜澄茄醇或它们的组合。在相关形态中，本公开提供了增强风味化产品中薄荷醇的清凉感觉的方法，包括将薄荷醇与黄烷酮组合在风味化产品中。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。在一些实施方案中，黄烷酮是柚皮素、橙皮素或它们的组合。在一些实施方案中，黄烷酮是柚皮素。In certain forms, the present disclosure provides the use of flavanones to enhance the cooling sensation of flavored products. In some embodiments, the flavored product includes menthol, peppermint, or combinations thereof. In a related form, the present disclosure provides methods of enhancing the cooling sensation of menthol in a flavored product, including combining menthol with flavanones in the flavored product. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition. In some embodiments, the flavanone is naringenin, hesperetin, or a combination thereof. In some embodiments, the flavanone is naringenin.

在某些其他形态中，本公开提供了黄烷酮用于增强身体护理产品的清凉感觉的用途。在一些实施方案中，身体护理产品包含清凉化合物，例如薄荷醇或荜澄茄醇。在相关形态中，本公开提供了增强身体护理产品中清凉化合物(例如薄荷醇或荜澄茄醇)的清凉感觉的方法，包括将清凉化合物与黄烷酮组合在身体护理产品中。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In certain other forms, the present disclosure provides the use of flavanones to enhance the cooling sensation of body care products. In some embodiments, body care products include cooling compounds, such as menthol or piperitaol. In a related form, the present disclosure provides methods of enhancing the cooling sensation of a cooling compound, such as menthol or piperitaol, in a body care product, comprising combining the cooling compound with a flavanone in the body care product. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在涉及用途或引入至风味化产品的形态中，风味化产品可以是任何合适的食物产品、饮料产品或口腔护理产品，下文进一步详细描述它们中的每一者。如下文更详细地阐述，风味化产品可包含任何种类的其他组分，包括调味剂、天然和人工甜味剂等。In the form in which use or incorporation into a flavored product occurs, the flavored product may be any suitable food product, beverage product, or oral care product, each of which is described in further detail below. As explained in more detail below, flavored products may contain any variety of other ingredients, including flavoring agents, natural and artificial sweeteners, and the like.

在涉及用途或引入至身体护理产品的形态中，身体护理产品可以是适合在头发、皮肤等上使用的任何合适的产品，其将在下面进一步详细描述。如下文更详细地阐述，身体护理产品可包含任何种类的其他组分，例如通常包含在身体护理产品中的组分。In terms of use or incorporation into body care products, the body care product may be any suitable product suitable for use on hair, skin, etc., as will be described in further detail below. As explained in more detail below, body care products may contain any kind of other ingredients, such as those typically included in body care products.

黄烷酮可以以任何合适的浓度存在于风味化产品或身体护理产品中。在一些实施方案中，风味化产品或身体护理产品中黄烷酮的浓度范围为1ppm至1000ppm，或5ppm至500ppm，或10ppm至300ppm，或20ppm至200ppm。Flavanones may be present in any suitable concentration in flavored or body care products. In some embodiments, the concentration of flavanones in the flavored or body care product ranges from 1 ppm to 1000 ppm, or 5 ppm to 500 ppm, or 10 ppm to 300 ppm, or 20 ppm to 200 ppm.

在一些实施方案中，风味化产品还包含高强度甜味剂。在一些此类实施方案中，高强度甜味剂是糖精钠或三氯蔗糖。在一些实施方案中，高强度甜味剂是糖精钠。糖精钠可以任何合适的浓度存在。在一些实施方案中，糖精钠的浓度范围为10ppm至10000ppm，或50ppm至5000ppm，或100ppm至3000ppm。In some embodiments, the flavored product also contains a high intensity sweetener. In some such embodiments, the high-intensity sweetener is sodium saccharin or sucralose. In some embodiments, the high-intensity sweetener is saccharin sodium. Sodium saccharin may be present in any suitable concentration. In some embodiments, the concentration of sodium saccharin ranges from 10 ppm to 10,000 ppm, or from 50 ppm to 5,000 ppm, or from 100 ppm to 3,000 ppm.

在一些实施方案中，风味化产品或身体护理产品包含薄荷醇，即(-)-薄荷醇。薄荷醇可以任何合适的浓度存在。在一些实施方案中，薄荷醇以10ppm至20000ppm，或50ppm至10000ppm，或100ppm至7000ppm，或500ppm至5000ppm的浓度存在。In some embodiments, a flavored or body care product includes menthol, ie, (-)-menthol. Menthol can be present in any suitable concentration. In some embodiments, menthol is present at a concentration of 10 ppm to 20,000 ppm, or 50 ppm to 10,000 ppm, or 100 ppm to 7,000 ppm, or 500 ppm to 5,000 ppm.

薄荷醇可以相对于黄烷酮的相对浓度(w/w)以任何合适的比例存在。在一些实施方案中，风味化产品中薄荷醇与黄烷酮的w/w比在1:1至200:1、或5:1至100:1、或10:1至80:1的范围内。Menthol may be present in any suitable ratio relative to the relative concentration of flavanones (w/w). In some embodiments, the w/w ratio of menthol to flavanones in the flavored product ranges from 1:1 to 200:1, or from 5:1 to 100:1, or from 10:1 to 80:1 .

在一些实施方案中，风味化产品或身体护理产品包含荜澄茄醇，其也称为(3S,3aR,3bR,4S,7R,7aR)-八氢-3,7-二甲基-4-(1-甲基乙基)-1H-环戊[1.3]环丙[1.2]苯-3-醇。荜澄茄醇可以以任何合适的浓度存在于风味化产品或身体护理产品中。在一些实施方案中，风味化产品或身体护理产品中荜澄茄醇的浓度范围为1ppm至1000ppm，或5ppm至500ppm，或10ppm至300ppm，或20ppm至200ppm。In some embodiments, the flavored or body care product includes piperol, also known as (3S,3aR,3bR,4S,7R,7aR)-octahydro-3,7-dimethyl-4- (1-Methylethyl)-1H-cyclopent[1.3]cycloprop[1.2]benzen-3-ol. Pepperonol may be present in any suitable concentration in a flavored or body care product. In some embodiments, the concentration of pepperonol in the flavored or body care product ranges from 1 ppm to 1000 ppm, or 5 ppm to 500 ppm, or 10 ppm to 300 ppm, or 20 ppm to 200 ppm.

其它化合物和添加剂可以包含在风味化产品或身体护理产品中，如下文更详细地阐述。例如，在一些实施方案中，风味化产品或身体护理产品包含二氢查尔酮，例如根皮素，或任何其他清凉化合物，例如上述那些化合物中的任一种。Other compounds and additives may be included in flavored or body care products, as explained in greater detail below. For example, in some embodiments, a flavored or body care product includes a dihydrochalcone, such as phloretin, or any other cooling compound, such as any of those described above.

在至少另一个形态中，本公开提供了二氢查尔酮用于增强风味化产品的清凉感觉的用途。在一些实施方案中，风味化产品包含薄荷醇、荜澄茄醇或它们的组合。在相关形态中，本公开提供了增强风味化产品中薄荷醇的清凉感觉的方法，包括将薄荷醇与二氢查尔酮组合在风味化产品中。在一些实施方案中，风味化产品是食物产品或饮料产品。在一些其他实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水、洁齿剂、口香糖或牙齿增白组合物。In at least another form, the present disclosure provides the use of dihydrochalcones to enhance the cooling sensation of flavored products. In some embodiments, the flavored product includes menthol, piperitaol, or combinations thereof. In a related form, the present disclosure provides methods of enhancing the cooling sensation of menthol in a flavored product, including combining menthol with dihydrochalcones in the flavored product. In some embodiments, the flavored product is a food product or beverage product. In some other embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, dentifrice, chewing gum, or tooth whitening composition.

在某些其他形态中，本公开提供了二氢查尔酮用于增强身体护理产品的清凉感觉的用途。在一些实施方案中，身体护理产品包含清凉化合物，例如薄荷醇或荜澄茄醇。在相关形态中，本公开提供了增强身体护理产品中清凉化合物(例如薄荷醇或荜澄茄醇)的清凉感觉的方法，包括将清凉化合物与二氢查尔酮组合在身体护理产品中。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In certain other forms, the present disclosure provides the use of dihydrochalcones to enhance the cooling sensation of body care products. In some embodiments, body care products include cooling compounds, such as menthol or piperitaol. In a related form, the present disclosure provides methods of enhancing the cooling sensation of a cooling compound, such as menthol or lemongrass, in a body care product, comprising combining the cooling compound with a dihydrochalcone in the body care product. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在涉及用途或引入至风味化产品的形态中，风味化产品可以是任何合适的食物产品、饮料产品或口腔护理产品，下文进一步详细描述它们中的每一者。如下文更详细地阐述，风味化产品可包含任何种类的其他组分，包括调味剂、天然和人工甜味剂等。In the form in which use or incorporation into a flavored product occurs, the flavored product may be any suitable food product, beverage product, or oral care product, each of which is described in further detail below. As explained in more detail below, flavored products may contain any variety of other ingredients, including flavoring agents, natural and artificial sweeteners, and the like.

在涉及用途或引入至身体护理产品的形态中，身体护理产品可以是适合在头发、皮肤等上使用的任何合适的产品，其将在下面进一步详细描述。如下文更详细地阐述，身体护理产品可包含任何种类的其他组分，例如通常包含在身体护理产品中的组分。In terms of use or incorporation into body care products, the body care product may be any suitable product suitable for use on hair, skin, etc., as will be described in further detail below. As explained in more detail below, body care products may contain any kind of other ingredients, such as those typically included in body care products.

二氢查耳酮可以以任何合适的浓度存在于风味化产品或身体护理产品中。在一些实施方案中，风味化产品或身体护理产品中二氢查耳酮的浓度范围为1ppm至1000ppm，或5ppm至500ppm，或10ppm至300ppm，或20ppm至200ppm。Dihydrochalcones may be present in any suitable concentration in flavored or body care products. In some embodiments, the concentration of dihydrochalcone in the flavored or body care product ranges from 1 ppm to 1000 ppm, or 5 ppm to 500 ppm, or 10 ppm to 300 ppm, or 20 ppm to 200 ppm.

在一些实施方案中，风味化产品还包含高强度甜味剂。在一些此类实施方案中，高强度甜味剂是糖精钠或三氯蔗糖。在一些实施方案中，高强度甜味剂是糖精钠。糖精钠可以任何合适的浓度存在。在一些实施方案中，糖精钠的浓度范围为10ppm至10000ppm，或50ppm至5000ppm，或100ppm至3000ppm。In some embodiments, the flavored product also contains a high intensity sweetener. In some such embodiments, the high-intensity sweetener is sodium saccharin or sucralose. In some embodiments, the high-intensity sweetener is saccharin sodium. Sodium saccharin may be present in any suitable concentration. In some embodiments, the concentration of sodium saccharin ranges from 10 ppm to 10,000 ppm, or from 50 ppm to 5,000 ppm, or from 100 ppm to 3,000 ppm.

在一些实施方案中，风味化产品或身体护理产品包含薄荷醇，即(-)-薄荷醇。薄荷醇可以任何合适的浓度存在。在一些实施方案中，薄荷醇以10ppm至20000ppm，或50ppm至10000ppm，或100ppm至7000ppm，或500ppm至5000ppm的浓度存在。In some embodiments, a flavored or body care product includes menthol, ie, (-)-menthol. Menthol can be present in any suitable concentration. In some embodiments, menthol is present at a concentration of 10 ppm to 20,000 ppm, or 50 ppm to 10,000 ppm, or 100 ppm to 7,000 ppm, or 500 ppm to 5,000 ppm.

薄荷醇可以相对于二氢查耳酮的相对浓度(w/w)以任何合适的比例存在。在一些实施方案中，风味化产品中薄荷醇与二氢查耳酮的w/w比为1:1至200:1，或5:1至100:1，或10:1至80:1。Menthol may be present in any suitable ratio relative to the relative concentration (w/w) of dihydrochalcone. In some embodiments, the w/w ratio of menthol to dihydrochalcone in the flavored product is from 1:1 to 200:1, or from 5:1 to 100:1, or from 10:1 to 80:1.

在一些实施方案中，风味化产品或身体护理产品包含荜澄茄醇，其也称为(3S,3aR,3bR,4S,7R,7aR)-八氢-3,7-二甲基-4-(1-甲基乙基)-1H-环戊[1.3]环丙[1.2]苯-3-醇。荜澄茄醇可以以任何合适的浓度存在于风味化产品或身体护理产品中。在一些实施方案中，风味化产品中荜澄茄醇的浓度范围为1ppm至1000ppm，或5ppm至500ppm，或10ppm至300ppm，或20ppm至200ppm。In some embodiments, the flavored or body care product includes piperol, also known as (3S,3aR,3bR,4S,7R,7aR)-octahydro-3,7-dimethyl-4- (1-Methylethyl)-1H-cyclopent[1.3]cycloprop[1.2]benzen-3-ol. Pepperonol may be present in any suitable concentration in a flavored or body care product. In some embodiments, the concentration of pepperoniol in the flavored product ranges from 1 ppm to 1000 ppm, or 5 ppm to 500 ppm, or 10 ppm to 300 ppm, or 20 ppm to 200 ppm.

其它化合物和添加剂可以包含在风味化产品或身体护理产品中，如下文更详细地阐述。例如，在一些实施方案中，风味化产品或身体护理产品包含黄烷酮，例如柚皮素，或任何其他清凉化合物，例如上述那些化合物中的任何化合物。Other compounds and additives may be included in flavored or body care products, as explained in greater detail below. For example, in some embodiments, a flavored or body care product includes a flavanone, such as naringenin, or any other cooling compound, such as any of those described above.

清凉度修饰组合物Coolness modifying composition

为了递送至或引入至风味化产品或身体护理产品的目的，(根据上述任何实施方案的)清凉度增强化合物都可以包括在任何合适的组合物中。The cooling-enhancing compound (according to any of the above embodiments) may be included in any suitable composition for the purpose of delivery to or incorporation into a flavored or body care product.

在某些形态中，本公开提供了清凉度修饰组合物，该组合物包含从由黄烷酮、二氢查尔酮以及它们的任何组合构成的群组中选出的清凉度增强化合物。In some forms, the present disclosure provides a cooling-modifying composition comprising a cooling-enhancing compound selected from the group consisting of flavanones, dihydrochalcones, and any combination thereof.

清凉度修饰组合物可包含清凉度增强化合物的任何组合。在一些另外的此类实施方案中，清凉度增强组合物包含(根据上述任何实施方案的)黄烷酮和(根据上述任何实施方案的)二氢查尔酮的组合。The coolness modifying composition may contain any combination of coolness enhancing compounds. In some additional such embodiments, the cooling-enhancing composition comprises a combination of a flavanone (according to any of the above embodiments) and a dihydrochalcone (according to any of the above embodiments).

清凉度修饰组合物可包含清凉度增强化合物的任何组合。在一些实施方案中，清凉度增强组合物包含(根据上述任何实施方案的)黄烷酮。在一些其他此类实施方案中，清凉度增强组合物包含(根据上述任何实施方案的)二氢查耳酮。在一些其他此类实施方案中，清凉度增强组合物包含(根据上述任何实施方案的)黄烷酮和(根据上述任何实施方案的)二氢查尔酮的组合。The coolness modifying composition may contain any combination of coolness enhancing compounds. In some embodiments, the cooling-enhancing composition comprises a flavanone (according to any of the above embodiments). In some other such embodiments, the cooling-enhancing composition comprises dihydrochalcone (according to any of the above embodiments). In some other such embodiments, the cooling-enhancing composition comprises a combination of a flavanone (according to any of the above embodiments) and a dihydrochalcone (according to any of the above embodiments).

在前述实施方案中，当清凉度修饰组合物包含清凉度增强化合物的组合时，清凉度增强化合物可以以任何合适的相对量存在。在一些实施方案中，当清凉度修饰组合物包含清凉度增强化合物的组合时，任意两种清凉度增强化合物的比例(w/w)的范围为1:20至20:1，或1:10至10:1，或1:5至5:1，或1:3至3:1，或1:2至2:1，或2:3至3:2。In the foregoing embodiments, when the cooling-modifying composition includes a combination of cooling-enhancing compounds, the cooling-enhancing compounds may be present in any suitable relative amounts. In some embodiments, when the cooling-modifying composition includes a combination of cooling-enhancing compounds, the ratio (w/w) of any two cooling-enhancing compounds ranges from 1:20 to 20:1, or 1:10 to 10:1, or 1:5 to 5:1, or 1:3 to 3:1, or 1:2 to 2:1, or 2:3 to 3:2.

此外，清凉度增强化合物可以任何合适的浓度存在于清凉度修饰组合物中。在其中清凉度修饰组合物是适合人类摄取的风味化产品的实施方案中，清凉度增强化合物以1ppm至1000ppm，或5ppm至500ppm，或10ppm至300ppm，或20ppm至200ppm的浓度存在。Furthermore, the cooling-enhancing compound may be present in the cooling-modifying composition at any suitable concentration. In embodiments where the coolness modifying composition is a flavored product suitable for human ingestion, the coolness enhancing compound is present at a concentration of 1 ppm to 1000 ppm, or 5 ppm to 500 ppm, or 10 ppm to 300 ppm, or 20 ppm to 200 ppm.

清凉度修饰组合物可包含任意数量的附加成分，例如通常用作口腔护理产品例如牙膏、漱口水和口香糖以及身体护理产品中的添加剂和赋形剂的成分。The coolness modifying composition may contain any number of additional ingredients, such as ingredients commonly used as additives and excipients in oral care products such as toothpastes, mouthwashes and chewing gums, and body care products.

在一些实施方案中，清凉度修饰组合物包含薄荷醇，即(-)-薄荷醇。薄荷醇可以任何合适的浓度存在。在一些实施方案中，当清凉度修饰组合物是适合人类摄取的风味化产品时，薄荷醇以10ppm至20000ppm，或50ppm至10000ppm，或100ppm至7000ppm，或500ppm至5000ppm的浓度存在。在一些实施方案中，当清凉度修饰组合物是适合施用于人类皮肤或毛发的身体护理产品时，基于组合物的总重量，薄荷醇以10ppm至20000ppm，或50ppm至10000ppm，或100ppm至7000ppm，或500ppm至5000ppm的浓度存在。薄荷醇可以相对于清凉度增强化合物的相对浓度(w/w)以任何合适的比例存在。在一些实施方案中，清凉度修饰组合物中薄荷醇与清凉度增强化合物的w/w比为1:1至200:1，或5:1至100:1。In some embodiments, the coolness modifying composition includes menthol, ie, (-)-menthol. Menthol can be present in any suitable concentration. In some embodiments, when the coolness modifying composition is a flavored product suitable for human ingestion, menthol is present at a concentration of 10 ppm to 20,000 ppm, or 50 ppm to 10,000 ppm, or 100 ppm to 7,000 ppm, or 500 ppm to 5,000 ppm. In some embodiments, when the coolness modifying composition is a body care product suitable for application to human skin or hair, the menthol is present at 10 ppm to 20,000 ppm, or 50 ppm to 10,000 ppm, or 100 ppm to 7,000 ppm, based on the total weight of the composition. Or present at a concentration of 500ppm to 5000ppm. Menthol may be present in any suitable ratio relative to the relative concentration (w/w) of the cooling-enhancing compound. In some embodiments, the w/w ratio of menthol to cooling-enhancing compound in the cooling-modifying composition is from 1:1 to 200:1, or from 5:1 to 100:1.

在一些实施方案中，清凉度修饰组合物包含荜澄茄醇。荜澄茄醇可以以任何合适的浓度存在于风味化产品或本体产品中。在一些实施方案中，风味化产品或身体护理产品中荜澄茄醇的浓度范围为1ppm至1000ppm，或5ppm至500ppm，或10ppm至300ppm，或20ppm至200ppm。In some embodiments, the coolness modifying composition includes piperitaol. Pepperonol may be present in any suitable concentration in a flavored or bulk product. In some embodiments, the concentration of lemongrass in the flavored or body care product ranges from 1 ppm to 1000 ppm, or 5 ppm to 500 ppm, or 10 ppm to 300 ppm, or 20 ppm to 200 ppm.

在一些实施方案中，清凉度修饰组合物包含其他清凉剂，例如N-乙基-对薄荷基-3-甲酰胺。N-乙基-对薄荷基-3-甲酰胺可以任何合适的浓度存在。在一些实施方案中，当清凉度修饰组合物是适合于人类摄取的风味化产品时，N-乙基-对薄荷基-3-甲酰胺以1ppm至20000ppm，或5ppm至10000ppm，或10ppm至7000ppm，或50ppm至5000ppm的浓度存在。在一些实施方案中，当清凉度修饰组合物是适合施用于人类皮肤或毛发的身体护理产品时，基于组合物的总重量，N-乙基-对薄荷基-3-甲酰胺以1ppm至20000ppm，或5ppm至10000ppm，或10ppm至7000ppm，或50ppm至5000ppm的浓度存在。N-乙基-对薄荷基-3-甲酰胺可以相对于清凉度增强化合物的相对浓度(w/w)以任何合适的比例存在。在一些实施方案中，清凉度修饰组合物中薄荷醇与清凉度增强化合物的w/w比为1:1至200:1，或5:1至100:1。In some embodiments, the coolness modifying composition includes other cooling agents, such as N-ethyl-p-menthyl-3-carboxamide. N-ethyl-p-menthyl-3-carboxamide may be present at any suitable concentration. In some embodiments, when the coolness modifying composition is a flavored product suitable for human ingestion, N-ethyl-p-menthyl-3-carboxamide is present at 1 ppm to 20,000 ppm, or 5 ppm to 10,000 ppm, or 10 ppm to 7,000 ppm , or exist at a concentration of 50ppm to 5000ppm. In some embodiments, when the coolness modifying composition is a body care product suitable for application to human skin or hair, N-ethyl-p-menthyl-3-carboxamide is present at 1 ppm to 20,000 ppm based on the total weight of the composition. , or exist in a concentration of 5ppm to 10000ppm, or 10ppm to 7000ppm, or 50ppm to 5000ppm. N-ethyl-p-menthyl-3-carboxamide may be present in any suitable ratio relative to the relative concentration (w/w) of the cooling-enhancing compound. In some embodiments, the w/w ratio of menthol to cooling-enhancing compound in the cooling-modifying composition is from 1:1 to 200:1, or from 5:1 to 100:1.

在一些实施方案中，清凉度修饰组合物包含清凉化合物。在一些实施方案中，清凉化合物是薄荷醇。在一些实施方案中，清凉化合物是荜澄茄醇。在一些实施方案中，清凉化合物是N-乙基-对薄荷基-3-甲酰胺。在一些实施方案中，清凉化合物是：薄荷醇、荜澄茄醇、N-乙基-对薄荷基-3-甲酰胺、异胡薄荷醇、3-(L-薄荷氧基)丙烷-1,2-二醇、顺式/反式-对薄荷烷-3,8-二醇、3-(L-薄荷氧基)-2-甲基丙烷-1,2-二醇、2-[2-(对薄荷烷-3-基氧基)乙氧基]乙醇、薄荷氧基乙醇、(1R,2R,4R)-1-(2-羟基-4-甲基环己基)乙烯酮、(1R,2R,5R)-N-乙基-5-甲基-2-(丙-1-烯-2-基)-环己烷甲酰胺、N-(3-羟基-4-甲氧基苯基)-2-异丙基-5,5-二甲基-环己烷甲酰胺、N-[4-(氰基甲基)苯基]-2-异丙基-5,5-二甲基-环己烷甲酰胺、N-(2-羟基-2-苯基乙基)-2-异丙基-5,5-二甲基-环己烷-1-甲酰胺、L-薄荷醇乳酸酯、(-)-薄荷醇乙二醇碳酸酯、(-)-薄荷酮1,2-甘油缩酮、D/L-薄荷酮1,2-甘油缩酮、(-)-薄荷醇1-丙二醇碳酸酯、(-)-薄荷基2-丙二醇碳酸酯、D/L-薄荷基1-丙二醇碳酸酯、D/L-薄荷基2-丙二醇碳酸酯、(1R,2S,5R)-N-(4-甲氧基苯基)-5-甲基-2-(L-甲基乙基)环己烷甲酰胺、薄荷基乙酰胺基草酸酯、(E)-3-苯并[1,3]二氧杂环戊烯-5-基-N,N-二苯基-2-丙烯酰胺、3,4-亚甲基二氧基肉桂酸、N,N-二苯基酰胺、N,N-二甲基(-)-薄荷基琥珀酰亚胺、(1R,2S,5R)-N-(4-(氨基甲酰基甲基)苯基)-薄荷基甲酰胺、(-)-薄荷基吡咯烷酮甲酸酯、L-去氧肾上腺素对薄荷烷甲酰胺、(1R,2S,5R)-N-(4-(氰基甲基)-苯基)薄荷基甲酰胺、(1R,2S,5R)-N-(2-(吡啶-2-基)乙基)薄荷基甲酰胺、6-异丙基-3,9-二甲基-1,4-二氧杂螺[4.5]癸-2-酮、(1R,2R,4S)-二氢伞柳醇、N-乙基-对薄荷烷-3-甲酰胺、2-异丙基-N,2,3-三甲基正丁酰胺、3-(对薄荷烷-3-甲酰氨基)乙酸乙酯、N-乙基-2,2-二异丙基丁酰胺、N-(1,1-二甲基-2-羟基乙基)-2,2-二甲基丁酰胺、N-环丙基-5-甲基-2-异丙基-环己烷碳甲酰胺、乙酰乙酸(-)-薄荷酯、琥珀酸(-)-薄荷酯、(S)-3-羟基丁酸(-)-薄荷酯、戊二酸(-)-薄荷酯、1-[2-羟基苯基]-4-[2-硝基苯基]-1,2,3,6-四氢嘧啶-2-酮、戊二酸二-(-)-薄荷酯、N-(2-羟基乙基)-2,3-二甲基-2-异丙基丁酰胺，或它们的任何组合。In some embodiments, the cooling modifying composition includes a cooling compound. In some embodiments, the cooling compound is menthol. In some embodiments, the cooling compound is piperitaol. In some embodiments, the cooling compound is N-ethyl-p-menthyl-3-carboxamide. In some embodiments, the cooling compound is: menthol, peppermint, N-ethyl-p-menthyl-3-carboxamide, isopulegol, 3-(L-menthoxy)propane-1, 2-diol, cis/trans-p-menthane-3,8-diol, 3-(L-menthoxy)-2-methylpropane-1,2-diol, 2-[2- (p-menthan-3-yloxy)ethoxy]ethanol, menthoxyethanol, (1R,2R,4R)-1-(2-hydroxy-4-methylcyclohexyl)ketene, (1R, 2R,5R)-N-ethyl-5-methyl-2-(prop-1-en-2-yl)-cyclohexanecarboxamide, N-(3-hydroxy-4-methoxyphenyl) -2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-[4-(cyanomethyl)phenyl]-2-isopropyl-5,5-dimethyl- Cyclohexanecarboxamide, N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethyl-cyclohexane-1-carboxamide, L-menthol lactic acid Esters, (-)-menthol glycol carbonate, (-)-menthol 1,2-glycerol ketal, D/L-menthol 1,2-glyceryl ketal, (-)-menthol 1- Propylene glycol carbonate, (-)-menthyl 2-propylene glycol carbonate, D/L-menthyl 1-propylene glycol carbonate, D/L-menthyl 2-propylene glycol carbonate, (1R,2S,5R)-N- (4-Methoxyphenyl)-5-methyl-2-(L-methylethyl)cyclohexanecarboxamide, menthyl acetamidooxalate, (E)-3-benzo[1 ,3]dioxol-5-yl-N,N-diphenyl-2-acrylamide, 3,4-methylenedioxycinnamic acid, N,N-diphenylamide, N ,N-Dimethyl(-)-menthylsuccinimide, (1R,2S,5R)-N-(4-(carbamoylmethyl)phenyl)-menthylformamide, (-)- Menthyl pyrrolidone formate, L-phenylephrine p-menthane carboxamide, (1R,2S,5R)-N-(4-(cyanomethyl)-phenyl)menthyl carboxamide, (1R, 2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, 6-isopropyl-3,9-dimethyl-1,4-dioxaspiro[4.5] Decan-2-one, (1R,2R,4S)-dihydromymensulfide, N-ethyl-p-menthane-3-carboxamide, 2-isopropyl-N,2,3-trimethyln- Butanamide, 3-(p-menthane-3-carboxamido)ethyl acetate, N-ethyl-2,2-diisopropylbutanamide, N-(1,1-dimethyl-2-hydroxy Ethyl)-2,2-dimethylbutanamide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexanecarbonamide, (-)-menthyl acetoacetate, succinic acid ( -)-Menthyl ester, (S)-3-Hydroxybutyrate (-)-Menthyl ester, (-)-Menthyl glutarate, 1-[2-hydroxyphenyl]-4-[2-nitrobenzene base]-1,2,3,6-tetrahydropyrimidin-2-one, di-(-)-menthyl glutarate, N-(2-hydroxyethyl)-2,3-dimethyl-2 -Isopropylbutanamide, or any combination thereof.

在一些实施方案中，清凉化合物可以是WO 2021/074281中提出的清凉化合物，例如(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)(1,2,3-噻二唑-5-基)甲酮、(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)(硫杂环丁烷-3-基)甲酮、(2,2-二甲基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2-乙氧基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2-甲氧基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2-甲基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2S)-2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、(5-甲基四氢呋喃-3-基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(E)-1-(2-(5-(3,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-2-烯-1-酮、(E)-2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-2-烯-1-酮、(E)-2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)戊-3-烯-1-酮、(R)-2-(甲基硫代)-1-((R)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、(S)-2-(甲基硫代)-1-((R)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、(S)-2-(甲基硫代)-1-((S)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、(S)-2-甲基-1-((R)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、(四氢呋喃-3-基)(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)甲酮、1-(2-(1H-苯并[d]咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(1-甲基-1H-吡唑-4-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,2-二氟苯并[d][1,3]二氧杂环戊二烯-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,3-二氢苯并呋喃-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,3-二氢苯并呋喃-6-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,5-二甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-氯苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-环丙基恶唑-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-羟基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3-((二甲基氨基)甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3,5-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3,5-二甲基异恶唑-4-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3-氯-4-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3-甲基呋喃-2-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-((1,1-二氧化硫代吗啉代)甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(1-羟基乙基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(二氟甲氧基)-3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(二氟甲基)噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(甲基磺酰基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(叔丁基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-环丁基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-环丙基-2-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-羟基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-异丙基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-甲基-3-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(5-((二甲基氨基))甲基)噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(5-甲基呋喃-2-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(5-甲基吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(6-甲基吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(苯并[b]噻吩-6-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-甲基-5-苯基-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)-2-((三氟甲基)硫基)乙-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)己-3,5-二烯-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)戊-4-烯-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(2-(5-(2,3-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2,5-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2-氟-4-甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2-氟-4-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2-甲氧基嘧啶-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-(甲基氨基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-3-烯-1-酮、1-(2-(5-(3,4-二甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3,4-二甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-氟-4-(甲氧基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-氟-4-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-甲氧基异噻唑-4-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-((甲基氨基)甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(2-甲氧基乙基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(氨基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(二甲基氨基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-乙酰基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氨基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氯-3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氯苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-乙基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氟苯基)-4H-1,2,4-三唑-3-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-甲氧基-2-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-甲基-6-(甲基硫代)吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(5-(甲氧基甲基)噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(6-甲氧基吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(苯并[d][1,3]二氧杂环戊二烯-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(2-(5-苄基-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-溴-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、2-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲腈、2-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-羰基)环丙烷-1-甲腈、2-(5-甲基呋喃-2-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(烯丙基硫基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(二甲基氨基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-(二甲基氨基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(乙基硫基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(呋喃-2-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙烷-1-酮、2-(呋喃-2-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(呋喃-3-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(呋喃-3-基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基氨基)-N-(4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙酰胺、2-(甲基亚磺酰基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基磺酰基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(甲基磺酰基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(2-(对甲苯基)-2H-四唑-5-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(3-苯基-1,2,4-恶二唑-5-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(1-(三氟甲基)-1H-吡唑-4-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(4-(吗啉代甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(5-(三氟甲基)呋喃-2-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(5-(三氟甲基))噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(5-甲基噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(间甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(邻甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(吡啶-4-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(嘧啶-5-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(喹喔啉-6-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(甲基硫代)-1-(2-(5-(2-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(2,3,4-三氟苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(2,4,5-三氟苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(3-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-(三氟甲氧基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-丙基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-乙烯基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(5-甲基噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1,3,4-恶二唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)氮杂环庚基-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-4H-1,2,4-三唑-3-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)异恶唑-3-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)恶唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)噻唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基-1H-咪唑-2-基)吡咯烷-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基-4H-1,2,4-三唑-3-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基恶唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(4-(5-(对甲苯基)-1H-咪唑-2-基)噻唑烷-3-基)丙-1-酮、2,2,3-三甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮、2,2,3-三甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2,2-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮、2,2-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2,3-二甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2,3-二甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2,5-二氟-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯甲腈、2-氨基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-环丁基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-环戊基-2-乙氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-环丙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-环丙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-环丙基-2-甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-乙氧基-1-(2-(5-(3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-乙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-2-烯-1-酮、2-乙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-氟-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲腈、2-巯基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲氧基-1-(2-(4-苯基-1H)-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲氧基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基))哌啶-1-基)丁-3-烯-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1,3-二酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)戊-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-2-烯-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-3-(甲基硫代)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-亚甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、3-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯甲腈、3,3,3-三氟-2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、3,3,4,4,4-五氟-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、3,3-二氟-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、3-氟-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲腈、3-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-2-烯-1-酮、3-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯甲腈、4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲醛、4,4,4-三氟-2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、二环[1.1.1]戊-1-基(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、环丁基(2-(5-(3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)甲酮、环戊基(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、环丙基(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲酸甲酯、N-(2-羟基乙基)-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯磺酰胺、2-(甲基硫代)-1-(2-(5-(3-硝基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、N-(4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯基)甲磺酰胺、2-(甲基硫代)-1-(2-(5-(4-硝基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(仲丁基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(仲丁基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(异丙基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(异丙基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((1-(甲基硫代)乙基)亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((1-(甲基硫代)乙基)磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-(甲基硫代)丙-2-基)亚磺酰)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶,1-((2-(甲基硫代)丙-2-基)磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(丁-3-烯-2-基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(丁-3-烯-2-基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(戊-3-烯-2-基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(戊-3-烯-2-基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-甲基丁-3-烯-2-基)亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-甲基丁-3-烯-2-基)磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(2-(5-(4-(羟基甲基)-苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、2-(甲基磺酰基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲磺酰基)丙-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲磺酰基)丙-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)-丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(2-羟基-6-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(5-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(4-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(3-羟基-2-(5-(4-(羟基甲基)-苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲硫基)丙-1-酮、1-(2-羟基-6-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(5-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(4-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(3-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲醛、4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲酸、4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲酸、(2,2-二甲基环丙基)(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)甲酮、1-(2-(5-溴-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(2-(5-(4-氯苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、2-(4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙腈、2-(4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙腈、2-(4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙腈、2,3-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(5-(邻甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(5-(间甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(异丙基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(仲丁基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、2-甲基-1-(2-(5-(5-甲基噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌嗪-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(对甲苯基)恶唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-1-(2-(4-(对甲苯基)恶唑-2-基)哌啶-1-基)丁-1-酮，或它们的任何组合。In some embodiments, the cooling compound may be a cooling compound proposed in WO 2021/074281, such as (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2, 3-thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone , (2,2-dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl) (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazole- 2-yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2S)-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (5-methyltetrahydrofuran -3-yl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (E)-1-(2-(5-(3,4-di Fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-2-en-1-one, (E)-2-methyl-1-(2-( 5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, (E)-2-methyl-1-(2-(5- (p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pent-3-en-1-one, (R)-2-(methylthio)-1-((R) -2-(5-(p-Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-(( R)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1- ((S)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-methyl-1-(( R)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (tetrahydrofuran-3-yl)(2-(5-(p- Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-2 -(Methylthio)propan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidine-1- methyl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxolane- 5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydro) Benzofuran-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2, 3-Dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4 -(2,5-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4 -(2-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2- Cyclopropyloxazol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-( 2-Fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxybenzene) base)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino) )Methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5 -Difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5- Dimethylisoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4- (3-Chloro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4 -(3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4 -(4-((1,1-Dioxythiomorpholino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -Ketone, 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propanyl -1-one, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-( Methylthio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl) -2-(Methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl )-2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl )-2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclobutylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl )-2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2- (Methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio Generation) propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio) Propan-1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2- (Methylthio)propan-1-one, 1-(2-(4-(5-((dimethylamino))methyl)thiophen-2-yl)-1H-imidazol-2-yl)piper Din-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piper Din-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piper Din-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piper Din-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(benzo[b]thiophen-6-yl)-1H-imidazol-2-yl) Piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazol-2-yl)piperidin-1 -yl)-2-(methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((tri Fluoromethyl)thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2- (4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)hex-3,5-dien-1-one, 1-(2-(4-phenyl-1H-imidazole-2) -yl)piperidin-1-yl)pent-4-en-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1- Ketone, 1-(2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one , 1-(2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1 -(2-(5-(2-Fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one , 1-(2-(5-(2-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1- Ketone, 1-(2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -Ketone, 1-(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -Ketone, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1- Ketone, 1-(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-3-en-1-one , 1-(2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1- Ketone, 1-(2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1- Ketone, 1-(2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio Generation) propan-1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan -1-one, 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio )Propan-1-one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propanyl -1-one, 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(5-(4-(2-methoxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(Methylthio)propan-1-one, 1-(2-(5-(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(Methylthio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(5-(4-acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-( Methylthio)propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio )Propan-1-one, 1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio )Propan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -one, 1-(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio)propan-1 -Ketone, 1-(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio) Propan-1-one, 1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan- 1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(Methylthio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidine-1 -yl)-2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidine- 1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(benzo[d][1,3]dioxol-5-yl) -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazole-2) -yl)piperidin-1-yl)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio )Propan-1-one, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 2-( 2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-(2-(4-phenyl-1H- Imidazol-2-yl)piperidin-1-carbonyl)cyclopropane-1-carbonitrile, 2-(5-methylfuran-2-yl)-1-(2-(4-phenyl-1H-imidazole- 2-yl)piperidin-1-yl)propan-1-one, 2-(allylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piper Din-1-yl)propan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1 -one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(ethylsulfide base)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-2-yl)-1- (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl) base-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-3-yl)-1-(2-(4-phenyl-1H-imidazole-2- yl)piperidin-1-yl)ethan-1-one, 2-(furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine- 1-yl)propan-1-one, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H -imidazol-5-yl)phenyl)acetamide, 2-(methylsulfinyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine-1- yl)propan-1-one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2 -(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1 -(2-(2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-( 3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-( 1-(Trifluoromethyl)-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1 -(2-(4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio) -1-(2-(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methyl thio)-1-(2-(4-(5-(trifluoromethyl))thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one , 2-(methylthio)-1-(2-(4-(5-methylthiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one , 2-(methylthio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methyl Thio)-1-(2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1- (2-(4-(pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-( 4-(pyridin-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyrimidine) -5-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(quinoxaline-6 -yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)- 1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piper Din-1-yl)ethan-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl )piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazole-2- yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl))-1H-imidazole-2 -yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazole) -2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H- Imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-propylphenyl)-1H-imidazole-2 -yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl) Piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepanyl- 1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan- 1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan -1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)isoxazol-3-yl)piperidin-1-yl)propan-1-one, 2- (Methylthio)-1-(2-(5-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1 -(2-(5-(p-tolyl)thiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl) -1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl) Pyrrolidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidine -1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(4-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3- Trimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2,3-tri Methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2 -(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2-dimethyl-1-(2-(5 -(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H- Imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidine-1 -yl)butan-1-one, 2,5-difluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazole-4- base) benzonitrile, 2-amino-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl -1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2- (4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazole-2- base)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1 -one, 2-cyclopropyl-2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-ethyl Oxy-1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-ethyl-1-(2- (4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazole) -2-yl)piperidin-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)- 1H-imidazol-5-yl)benzonitrile, 2-mercapto-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one , 2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2- (4-phenyl-1H)-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-(p-tolyl)-1H- Imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl) Butan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1- (2-(5-(p-tolyl)-1H-imidazol-2-yl))piperidin-1-yl)but-3-en-1-one, 2-methyl-1-(2-(5 -(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazole) -2-yl)piperidin-1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine -1-yl)pentan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-ene -1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl- 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-3 -(Methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2 -(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propionyl) )piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazole- 2-yl)piperidin-1-yl)propan-1-one, 3,3,4,4,4-pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piper Din-1-yl)butan-1-one, 3,3-difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one , 3-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl- 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl) Base-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl) -1H-imidazol-4-yl)benzonitrile, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzene Formaldehyde, 4,4,4-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, bicyclo [1.1.1]pentyl-1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2-(5-(3-fluoro Phenyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methyl Ketone, cyclopropyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, 4-(2-(1-(2-(methylthio)propanol) Acyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid methyl ester, N-(2-hydroxyethyl)-4-(2-(1-(2-(methylthio)) Propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzenesulfonamide, 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H -imidazol-2-yl)piperidin-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl) -1H-imidazol-4-yl)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 1-(sec-butylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec- Butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfinyl)-2-(5-(p-tolyl)- 1H-imidazol-2-yl)piperidine, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-( Methylthio)ethyl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl) Sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfinyl)-2 -(5-(p-Tolyl)-1H-imidazol-2-yl)piperidine,1-((2-(methylthio)propan-2-yl)sulfonyl)-2-(5-(p Tolyl)-1H-imidazol-2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl )piperidine, 1-(but-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-ene -2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-( 5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-toluene) base)-1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazole -2-yl)piperidine, 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan -1-one, 2-(methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1 -(4-Hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-( 5-Hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(4- Hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5 -(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-(hydroxymethyl)benzene) base)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl) -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H -imidazol-2-yl)piperidin-1-yl)-2-(methanesulfonyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazole- 2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazole-2- yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine-1 -yl)-2-(methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl )-2-(methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-Methylbutan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methanesulfonyl) )Propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfenyl) Acyl)-propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfenyl) Acyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl )Propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl) Propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propanyl -1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(Methylthio)propan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidine-1- base)-2-(methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl) Piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl))-1H-imidazole-2 -yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl))-1H-imidazole-2 -yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl))-1H-imidazole-2 -yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl))-1H-imidazole-2 -yl)piperidin-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazole-5 -yl)benzaldehyde, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, 4-(2- (1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2- Methylbutan-1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-( 2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methyl) Butyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazole- 2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl )Butan-1-one, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-( 2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonate) Acyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazole- 2-yl)piperidine, 2-methyl-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1 -one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-( Methylthio)-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-( 4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one, or any combination thereof.

在一些实施方案中，清凉化合物可以是2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2,2-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮，或它们的组合。In some embodiments, the cooling compound can be 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2 -(Methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2,2-dimethyl -1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, or combinations thereof.

在一些实施方案中，清凉化合物可以是1-异丙基-3,3,5,7-四甲基八氢苯并[c]异恶唑、5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑(包括(3aR,5R,7S,7aR)-5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑、(3aR,5R,7R,7aR)-5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑、(3aR,5R,7S,7aS)-5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑，或它们的任何组合。In some embodiments, the cooling compound may be 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1, 3,3,5,7-Pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5 ,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyl Octahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c ]isoxazole, or any combination thereof.

适用于风味化产品的清凉度修饰组合物Coolness modifying compositions suitable for flavored products

在任何前述实施方案的一些实施方案中，清凉度修饰组合物包含甜味剂，例如低热量、零热量或高强度甜味剂。术语“高强度甜味剂”是指比蔗糖甜例如至少10倍、或至少20倍、或至少50倍、或至少100倍、或至少250倍、或至少500倍、或至少750倍、或至少1000倍、或至少2500倍、或至少5000倍、或至少7500倍、或至少10000倍的甜味剂。在本文中，说甜味剂比蔗糖甜x倍是指在所述甜味剂的水溶液中相对于蔗糖重量1/x的浓度产生与蔗糖相当的甜度。合适的甜味剂的例子在下面更详细地阐述。在一些实施方案中，甜味剂是三氯蔗糖，其是指1,6-二氯-1,6-二脱氧基-β-D-呋喃果糖基-4-氯-4-脱氧-α-D-吡喃半乳糖苷。在一些实施方案中，甜味剂是糖精钠。糖精钠可以任何合适的浓度存在。在一些实施方案中，糖精钠的浓度范围为10ppm至10000ppm，或50ppm至5000ppm，或100ppm至3000ppm。糖精钠可以具有相对于清凉度增强化合物的任何合适的相对浓度。在一些实施方案中，清凉度修饰组合物中糖精钠相对于清凉度增强化合物的比(w/w)范围为1:1至1000:1，或5:1至500:1。In some embodiments of any of the preceding embodiments, the coolingness modifying composition includes a sweetener, such as a low-calorie, zero-calorie, or high-intensity sweetener. The term "high-intensity sweetener" means one that is sweeter than sucrose, for example, at least 10 times, or at least 20 times, or at least 50 times, or at least 100 times, or at least 250 times, or at least 500 times, or at least 750 times, or at least 1000 times, or at least 2500 times, or at least 5000 times, or at least 7500 times, or at least 10000 times the sweetener. As used herein, to say that a sweetener is x times sweeter than sucrose means that a concentration of 1/x relative to the weight of sucrose in an aqueous solution of said sweetener produces a sweetness comparable to that of sucrose. Examples of suitable sweeteners are set out in more detail below. In some embodiments, the sweetener is sucralose, which refers to 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α- D-galactopyranoside. In some embodiments, the sweetener is sodium saccharin. Sodium saccharin may be present in any suitable concentration. In some embodiments, the concentration of sodium saccharin ranges from 10 ppm to 10,000 ppm, or from 50 ppm to 5,000 ppm, or from 100 ppm to 3,000 ppm. The sodium saccharin may have any suitable relative concentration relative to the cooling-enhancing compound. In some embodiments, the ratio (w/w) of sodium saccharin relative to the cooling-enhancing compound in the cooling-modifying composition ranges from 1:1 to 1000:1, or from 5:1 to 500:1.

在一些实施方案中，清凉度修饰组合物包含葡糖基化天然甜菊醇糖苷。如本文所用，术语“天然甜菊醇糖苷”是指天然存在于植物物种甜叶菊(Stevia rebaudiana)、墨西哥甜叶菊(Stevia phlebophylla)或掌叶覆盆子(Rubus chingii)中的甜菊醇糖苷。此类化合物是二萜甜菊醇的糖苷。一些非限制性例子包括甜菊苷、莱鲍迪苷A、莱鲍迪苷C、杜尔可苷A等。如本文所用，术语“葡糖基化天然甜菊醇糖苷”是指通过对天然甜菊醇糖苷进行酶促葡糖基化以增加葡糖基化程度而获得的化合物。如本文所用，术语“GSG”可与“葡糖基化天然甜菊醇糖苷”互换使用。In some embodiments, the coolness modifying composition comprises glucosylated natural steviol glycosides. As used herein, the term "natural steviol glycoside" refers to steviol glycosides naturally occurring in the plant species Stevia rebaudiana, Stevia phlebophylla, or Rubus chingii. Such compounds are glycosides of the diterpene steviol. Some non-limiting examples include stevioside, rebaudioside A, rebaudioside C, dulcoside A, and the like. As used herein, the term "glucosylated natural steviol glycosides" refers to compounds obtained by enzymatic glycosylation of natural steviol glycosides to increase the degree of glycosylation. As used herein, the term "GSG" is used interchangeably with "glucosylated natural steviol glycoside."

在存在GSG的实施方案中，可以使用任何合适的GSG。因此，GSG可以具有任何合适程度的额外葡糖基化，以及合适类型的葡糖基化。在一些实施方案中，用于清凉度修饰组合物中的GSG具有至少1.0的葡糖基化度，这意味着对于每摩尔天然甜菊醇糖苷已将至少一摩尔葡萄糖以酶促方式添加至天然甜菊醇糖苷。在一些其他实施方案中，用于清凉度修饰组合物中的GSG具有至少1.1，或至少1.2，或至少1.3，或至少1.4，或至少1.5，或至少1.6，或至少1.7，或至少1.8，或至少1.9，或至少2.0，或至少2.1，或至少2.2，或至少2.3，或至少2.4，或至少2.5的葡糖基化度。葡糖基化可以是任何合适的类型。例如，在一些实施方案中，以酶促方式添加至天然甜菊醇糖苷的葡萄糖是α-葡萄糖、β-葡萄糖或它们的组合。在一些实施方案中，以酶促方式添加至天然甜菊醇糖苷的葡萄糖是α-葡萄糖。在一些实施方案中，以酶促方式添加至天然甜菊醇糖苷的葡萄糖是β-葡萄糖。在一些实施方案中，以酶促方式添加至天然甜菊醇糖苷的葡萄糖是α-葡萄糖和β-葡萄糖的组合。通过酶促葡糖基化添加的葡萄糖可以通过任何合适的连接掺入。通常，所添加的葡萄糖单元与天然甜菊醇糖苷上已经存在的其他葡萄糖单元相连。在一些实施方案中，酶促添加的葡萄糖单元通过1,6键添加，意味着葡萄糖单元通过所添加的葡萄糖单元的1-位和已经存在于天然甜菊醇糖苷上的葡萄糖单元的6-位添加。在一些其他实施方案中，酶促添加的葡萄糖单元通过1,4键添加。在一些其他实施方案中，酶促添加的葡萄糖单元通过1,2键添加。In embodiments where GSG is present, any suitable GSG may be used. Thus, GSG can have any suitable degree of additional glycosylation, as well as suitable types of glycosylation. In some embodiments, the GSG used in the coolness modifying composition has a degree of glucosylation of at least 1.0, meaning that for every mole of natural steviol glycosides, at least one mole of glucose has been enzymatically added to the natural stevia. Alcohol glycosides. In some other embodiments, the GSG used in the coolness modifying composition has at least 1.1, or at least 1.2, or at least 1.3, or at least 1.4, or at least 1.5, or at least 1.6, or at least 1.7, or at least 1.8, or A degree of glucosylation of at least 1.9, or at least 2.0, or at least 2.1, or at least 2.2, or at least 2.3, or at least 2.4, or at least 2.5. Glycosylation can be of any suitable type. For example, in some embodiments, the glucose enzymatically added to the native steviol glycoside is alpha-glucose, beta-glucose, or a combination thereof. In some embodiments, the glucose enzymatically added to the native steviol glycoside is alpha-glucose. In some embodiments, the glucose enzymatically added to the native steviol glycoside is beta-glucose. In some embodiments, the glucose enzymatically added to the native steviol glycoside is a combination of alpha-glucose and beta-glucose. Glucose added by enzymatic glucosylation can be incorporated through any suitable linkage. Typically, the added glucose units are linked to other glucose units already present on the natural steviol glycoside. In some embodiments, the enzymatically added glucose unit is added through the 1,6 bond, meaning that the glucose unit is added through the 1-position of the added glucose unit and the 6-position of the glucose unit already present on the native steviol glycoside . In some other embodiments, the enzymatically added glucose units are added via 1,4 linkages. In some other embodiments, the enzymatically added glucose units are added via 1,2 linkages.

在存在GSG的实施方案中，GSG可以以任何合适的浓度存在。在一些实施方案中，GSG以1ppm至100ppm，或1pm至50ppm，或1ppm至30ppm，或1ppm至20ppm，或1ppm至10ppm的浓度范围存在于清凉度修饰组合物中。In embodiments where GSG is present, GSG may be present at any suitable concentration. In some embodiments, GSG is present in the coolness modifying composition at a concentration ranging from 1 ppm to 100 ppm, or 1 pm to 50 ppm, or 1 ppm to 30 ppm, or 1 ppm to 20 ppm, or 1 ppm to 10 ppm.

在一些实施方案中，清凉度修饰组合物包含4-氨基-5,6-二甲基噻吩并[2,3-d]嘧啶-2(1H)-酮，或可使用其任何合适的盐。在一些实施方案中，本文公开的清凉度修饰组合物包含4-氨基-5,6-二甲基噻吩并[2,3-d]嘧啶-2(1H)-酮的盐酸盐。In some embodiments, the coolness modifying composition contains 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one, or any suitable salt thereof may be used. In some embodiments, the coolness modifying compositions disclosed herein comprise the hydrochloride salt of 4-amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one.

在任何前述实施方案的一些实施方案中，清凉度修饰组合物还包含内酯。可以使用任何合适的内酯或多种内酯的组合。在一些实施方案中，内酯包含在环中具有3至8个成员的内酯环，例如3元内酯环、4元内酯环、5元内酯环、6元内酯环、7元内酯环或8元内酯环。In some embodiments of any of the preceding embodiments, the coolness modifying composition further comprises a lactone. Any suitable lactone or combination of lactones may be used. In some embodiments, the lactone includes a lactone ring having 3 to 8 members in the ring, such as a 3-membered lactone ring, a 4-membered lactone ring, a 5-membered lactone ring, a 6-membered lactone ring, a 7-membered lactone ring, Lactone ring or 8-membered lactone ring.

在在一些实施方案中，内酯包含具有或不具有不饱和键(不包括环上的氧代取代基中的不饱和度)例如碳-碳双键的5元内酯环。在一些实施方案中，内酯包含具有至少一个不饱和键(例如一个碳-碳双键)的5元内酯环。包含具有至少一个不饱和键的5元内酯环的内酯的非限制性例子包括当归内酯α、当归内酯β、薄荷内酯、5,5-二甲基-2(5H)-呋喃酮、5-乙基-2(5H)-呋喃酮，5-戊基-2(5H)-呋喃酮、5-己基-2(5H)-呋喃酮、5-戊基-2(3H)-呋喃酮、4-甲基-3-戊基-2(5H)-呋喃酮和2(5H)-呋喃酮。在一些实施方案中，内酯包含没有任何不饱和键的5元内酯环。此类内酯的非限制性例子包括丁内酯γ、戊内酯γ、己内酯γ、庚内酯γ、辛内酯γ、十一内酯γ、癸内酯γ、二氢茉莉酮内酯和二氢薄荷内酯(3,6-二甲基-六氢-2(3H)-苯并呋喃酮)。在一些实施方案中，内酯是二氢薄荷内酯。In some embodiments, the lactone includes a 5-membered lactone ring with or without unsaturation (excluding unsaturation in the oxo substituents on the ring), such as a carbon-carbon double bond. In some embodiments, the lactone includes a 5-membered lactone ring having at least one unsaturated bond (eg, one carbon-carbon double bond). Non-limiting examples of lactones containing a 5-membered lactone ring with at least one unsaturated bond include angelicalide alpha, angelicalide beta, menthyl lactone, 5,5-dimethyl-2(5H)-furan Ketone, 5-ethyl-2(5H)-furanone, 5-pentyl-2(5H)-furanone, 5-hexyl-2(5H)-furanone, 5-pentyl-2(3H)- Furanone, 4-methyl-3-pentyl-2(5H)-furanone and 2(5H)-furanone. In some embodiments, the lactone contains a 5-membered lactone ring without any unsaturated bonds. Non-limiting examples of such lactones include butyrolactone gamma, valerolactone gamma, caprolactone gamma, enantolactone gamma, octalactone gamma, undecanolide gamma, decanolide gamma, dihydrojasmone lactone and dihydromethrolactone (3,6-dimethyl-hexahydro-2(3H)-benzofuranone). In some embodiments, the lactone is dihydromethrolactone.

在一些实施方案中，内酯包含具有或不具有不饱和键的6元内酯环。在一些实施方案中，内酯包含具有至少一个不饱和键的6元内酯环。包含具有至少一个不饱和键的6元内酯环的内酯的非限制性例子包括δ-2-癸烯内酯、香豆素和6-甲基香豆素。在一些其他实施方案中，内酯包括没有任何不饱和键的6元内酯环。包括没有任何不饱和键的6元内酯环的内酯的非限制性例子包括癸内酯δ、十二内酯δ和环己基内酯。In some embodiments, the lactone includes a 6-membered lactone ring with or without unsaturated bonds. In some embodiments, the lactone includes a 6-membered lactone ring with at least one unsaturated bond. Non-limiting examples of lactones containing a 6-membered lactone ring with at least one unsaturated bond include delta-2-decene lactone, coumarin, and 6-methylcoumarin. In some other embodiments, the lactone includes a 6-membered lactone ring without any unsaturated bonds. Non-limiting examples of lactones including a 6-membered lactone ring without any unsaturated bonds include decanolide delta, laurolactone delta and cyclohexyl lactone.

例如，在一些实施方案中，清凉度修饰组合物包含有热量的糖，例如蔗糖、葡萄糖、果糖(例如以高果糖玉米糖浆的形式)或它们的任何组合。在一些实施方案中，清凉度修饰组合物包含一种或多种莱鲍迪苷(例如莱鲍迪苷A、莱鲍迪苷D、莱鲍迪苷E、莱鲍迪苷M或它们的任何组合)。一般而言，莱鲍迪苷(例如莱鲍迪苷A)的浓度为上述三氯蔗糖的浓度的约20至50倍高。在一些实施方案中，清凉度修饰组合物包含一种或多种高强度人工甜味剂，例如乙酰磺胺酸钾、阿斯巴甜、环己氨基磺酸盐(cyclamate)、纽甜等。当任何此类人造高强度甜味剂存在于清凉度修饰组合物中时，它们的浓度将与对于上述三氯蔗糖所述的浓度大致相同。在一些其他实施方案中，清凉度修饰组合物包含一种或多种低热量碳水化合物或糖醇，例如稀少糖(allulose)、木糖醇、赤藓糖醇等。在一些其他实施方案中，清凉度修饰组合物包含罗汉果苷，例如作为罗汉果汁或提取物，或作为罗汉果苷III、罗汉果苷IV、罗汉果苷V、赛门苷I、异罗汉果苷V、罗汉果苷IV_E、异罗汉果苷IV_E，异罗汉果苷IV、罗汉果苷III_E、11-氧代罗汉果苷V、赛门苷I的1,6-α异构体中的一种或多种，以及它们的任何组合。美国专利申请公开号2017/0119032中描述了可适当地包含在清凉度修饰组合物中的其他罗汉果苷化合物。For example, in some embodiments, the coolness modifying composition includes a caloric sugar, such as sucrose, glucose, fructose (eg, in the form of high fructose corn syrup), or any combination thereof. In some embodiments, the coolness modifying composition includes one or more rebaudioside (e.g., rebaudioside A, rebaudioside D, rebaudioside E, rebaudioside M, or any thereof combination). Generally speaking, the concentration of rebaudioside (eg, rebaudioside A) is about 20 to 50 times higher than the concentration of sucralose described above. In some embodiments, the coolness modifying composition includes one or more high-intensity artificial sweeteners, such as acesulfame potassium, aspartame, cyclamate, neotame, and the like. When any such artificial high intensity sweeteners are present in the coolness modifying composition, their concentrations will be approximately the same as those described above for sucralose. In some other embodiments, the coolness modifying composition includes one or more low-calorie carbohydrates or sugar alcohols, such as allulose, xylitol, erythritol, and the like. In some other embodiments, the coolness modifying composition comprises mogroside, for example, as mogroside juice or extract, or as mogroside III, mogroside IV, mogroside V, samenoside I, isomogroside V, mogroside IV_E , isomogroside IV_E , one or more of the 1,6-α isomers of isomogroside IV, mogroside III_E , 11-oxomogroside V, and saimenoside I, and their any combination of. Other mogroside compounds that may be suitably included in the coolness modifying composition are described in US Patent Application Publication No. 2017/0119032.

各种其他甜味剂也可以包含在清凉度修饰组合物中。非限制性例子包括D-阿洛酮糖、L-核糖、D-塔格糖、L-葡萄糖、L-岩藻糖、L-阿拉伯糖、D-松二糖、D-白菌二糖、异麦芽酮糖醇、乳糖醇、甘露糖醇、山梨糖醇、麦芽糊精、糖精、阿力甜、环己氨基磺酸(cyclamicacid)、塔格糖、麦芽糖、半乳糖、甘露糖、乳糖、D-色氨酸、甘氨酸、麦芽糖醇、乳糖醇、异麦芽酮糖醇、氢化淀粉水解产物(HSH)、化学改性的罗汉果苷(如葡糖基化罗汉果苷)、胍甜味剂(carrelame)和其他胍基甜味剂、蜂蜜、菊芋(Jerusalem artichoke)糖浆、甘草根、罗汉果(果实、粉末或提取物)、蛋黄果(lucuma)(果实、粉末或提取物)、枫树树液(包括例如从糖枫(Acer saccharum)、黑枫(Acer nigrum)、美国红枫(Acer rubrum)、银枫(Acersaccharinum)、挪威枫(Acer platanoides)、梣叶槭(Acer negundo)、大叶枫(Acermacrophyllum)、粗齿枫(Acer grandidentatum)、落基山枫(Acer glabrum)、色木槭(Acermono)提取的树液)、枫树糖浆、枫糖、胡桃树液(包括例如从白胡桃(Juglans cinerea)、黑胡桃(Juglans nigra)、鬼胡桃(Juglans ailatifolia)、胡桃(Juglans regia)提取的树液)、桦树树液(包括例如从纸桦(Betula papyrifera)、加拿大黄桦(Betulaalleghaniensis)、山桦(Betula lenta)、河桦(Betula nigra)、灰色桦木(Betulapopulifolia)、垂枝桦(Betula pendula)提取的树液)、美国梧桐(sycamore)树液(例如从一球悬铃木(Platanus occidentalis)提取的树液)、铁木树液(例如从美洲铁木(Ostryavirginiana)提取的树液)、未精制蔗糖(mascobado)、糖蜜(molasses)(举例而言例如黑糖蜜(blackstrap molasses))、糖蜜糖、莫纳甜、莫奈林(monellin)、甘蔗糖(cane sugar)(也称为天然糖、未精制苷蔗糖或蔗糖(sucrose))、棕榈糖、墨西哥粗糖(panocha)、墨西哥粗糖条(piloncillo)、红糖砖(rapadura)、原糖、大米糖浆、高粱、高粱糖浆、木薯糖浆(也称为木薯淀粉糖浆)、奇异果甜蛋白(thaumatin)、雪莲果(yacon root)、麦芽糖浆、大麦麦芽糖浆、大麦麦芽粉、甜菜糖、甘蔗糖(cane sugar)、结晶果汁结晶、焦糖、卡必醇、角豆(carob)糖浆、蓖麻糖、氢化淀粉水纯露(hydrolates)、水解的罐装果汁、水解淀粉、转化糖、茴香脑、阿拉伯半乳聚糖、浓缩葡萄汁(arrope)、糖浆、P-4000、乙酰磺胺酸钾(也称为乙酰舒泛钾或ace-K)、阿力甜(也称为阿力糖(aclame))、爱德万甜、阿斯巴甜、白云参苷(baiyunosdie)、纽甜、苯甲酰胺衍生物、bernadame、阿斯巴甜别名(canderel)、胍甜味剂(carrelame)和其他胍基甜味剂、植物纤维、玉米糖、偶联糖、仙茅甜蛋白、环己氨基磺酸盐(cyclamates)、青钱柳苷I(cyclocaryoside I)、德梅拉拉糖(demerara)、葡聚糖、糊精、糖化麦芽(diastaticmalt)、甘素(dulcin)、甜精(sucrol)、乙氧基苯脲(valzin)、杜尔可苷A、杜尔可苷B、艾木林(emulin)、甘草次酸(enoxolone)、麦芽糊精、糖精、草蒿脑(estragole)、乙基麦芽酚、羟苯基甘胺酸(glucin)、葡萄糖酸、葡萄糖酸内酯、葡糖胺、葡萄糖醛酸、甘油、甘氨酸、glycyphillin、甘草甜素、甘草次酸单葡糖醛酸化物、金黄糖、黄糖、金黄糖浆、砂糖、绞股蓝、贺兰甜精(hernandulcin)、异构化液体糖、jallab、菊苣根膳食纤维、犬尿氨酸衍生物(包括N'-甲酰基-犬尿氨酸、N'-乙酰基-犬尿氨酸、6-氯-犬尿氨酸)、半乳糖醇、利体素(litesse)、健美原蔗金砂糖(ligicane)、利卡新(lycasin)、N-(4-氰基苯基)-N-(2,3-亚甲二氧苄基)胍乙酸(lugduname)、胍、法勒南糖浆(falernum)、马槟榔甜蛋白I、马槟榔甜蛋白II、麦芽酚、结晶麦芽糖醇(maltisorb)、麦芽糊精、麦芽三糖醇(maltotriol)、甘露糖胺、神秘果蛋白(micraculin)、水饴(mizuame)、罗汉果苷(包括例如罗汉果苷IV、罗汉果苷V和新罗汉果苷)、无患子倍半萜苷(mukurozioside)、纳米糖(nano sugar)、柚皮苷二氢查尔酮、新橙皮苷二氢查尔酮、粗糖(nib sugar)、黑寡糖、诺布糖(norbu)、杏仁糖浆、欧亚水龙骨甜素(osladin)、派克梅兹(pekmez)、潘塔亭(pentadin)、巴西甘草甜素I(periandrin I)、紫苏醛、紫苏葶(perillartine)、petphyllum、苯丙氨酸、假秦艽苷I(phloisosideside I)、phlorodizin、叶甜素(phyllodulcin)、氢化葡萄糖浆(polyglycitol syrup)、多足蕨苷A(polypodoside A)、蝶卡苷A(pterocaryoside A)、蝶卡苷B、润贝安娜(rebiana)、精制糖浆、摩擦糖浆(rub syrup)、甜叶悬钩子苷(rubusoside)、蓨蕨素A(selligueain A)、舒格糖(shugr)、赛门苷I、罗汉果(siraitia grosvenorii)、大豆低聚糖、善品糖(Splenda)、SRIoxime V、甜菊醇糖苷、甜菊醇双糖苷、甜菊苷、叉柱花素(strogins)1、2和4、蔗糖酸(sucronic acid)、sucrononate、糖、对硝基苯基脲基丙酸钠(suosan)、根皮苷(phloridzin)、超级阿斯巴甜、四糖、苏糖醇、糖蜜(treacle)、三叶苷(trilobtain)、色氨酸及衍生物(6-三氟甲基-色氨酸、6-氯-D-色氨酸)、香草糖、庚七醇、桦树糖浆、阿斯巴甜-乙酰磺胺酸、艾苏格(assugrin)、以及它们任意两种或更多种的组合或共混物。Various other sweeteners may also be included in the coolness modifying composition. Non-limiting examples include D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-arabinose, D-turanose, D-corybiose, Isomalt, lactitol, mannitol, sorbitol, maltodextrin, saccharin, alitame, cyclamicacid, tagatose, maltose, galactose, mannose, lactose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrogenated starch hydrolyzate (HSH), chemically modified mogroside (such as glucosylated mogroside), guanidine sweetener (carrelame) ) and other guanidine-based sweeteners, honey, Jerusalem artichoke syrup, licorice root, monk fruit (fruit, powder or extract), lucuma (fruit, powder or extract), maple sap ( Includes, for example, sugar maple (Acer saccharum), black maple (Acer nigrum), American red maple (Acer rubrum), silver maple (Acersaccharinum), Norway maple (Acer platanoides), ash leaf maple (Acer negundo), big leaf maple (Acermacrophyllum) ), sap extracted from Acer grandidentatum, Acer glabrum, Acermono), maple syrup, maple syrup, walnut sap (including, for example, from Juglans cinerea) , black walnut (Juglans nigra), ghost walnut (Juglans ailatifolia), walnut (Juglans regia) sap extracted), birch sap (including, for example, from paper birch (Betula papyrifera), Canadian yellow birch (Betula alleghaniensis), mountain birch (Betula lenta), river birch (Betula nigra), gray birch (Betulapopulifolia), weeping birch (Betula pendula)), sycamore (sycamore) sap (for example, from Platanus occidentalis) sap), ironwood sap (for example, sap extracted from Ostrya virginiana), unrefined sucrose (mascobado), molasses (for example, blackstrap molasses), molasses sugar, Monatin, monellin, cane sugar (also called natural sugar, unrefined glycoside sucrose or sucrose), palm sugar, panocha, piloncillo , brown sugar brick (rapadura), raw sugar, rice syrup, sorghum, sorghum syrup, cassava syrup (also known as tapioca syrup), thaumatin, yacon root, maltose syrup, barley maltose syrup , barley malt powder, beet sugar, cane sugar, crystallized fruit juice crystals, caramel, carbitol, carob syrup, castor sugar, hydrogenated starch hydrosols, hydrolyzed cans Fruit juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, grape juice concentrate (arrope), syrup, P-4000, acesulfame potassium (also known as acesulfame potassium or ace-K), aliquots Sweet (also known as aclame), Advantame, aspartame, baiyunosdie, neotame, benzamide derivatives, bernadame, aspartame alias (canderel), Guanidine sweetener (carrelame) and other guanidine-based sweeteners, plant fiber, corn sugar, conjugated sugar, curculioprotein, cyclamates, cyclocaryoside I, Demerara, dextran, dextrin, diastatic malt, dulcin, sucrol, valzin, dulcoside A, dulcoside A Ercoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, hydroxyphenylglycine (glucin), gluconic acid, glucose Acid lactone, glucosamine, glucuronic acid, glycerin, glycine, glycyphillin, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, brown sugar, golden syrup, sugar, Gynostemma pentaphyllum, Helan sweetener ( hernandulcin), isomerized liquid sugar, jallab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, 6-chloro- Kynurenine), galactitol, litesse, ligicane, lycasin, N-(4-cyanophenyl)-N-(2,3 -Methylenedioxybenzyl)guanidine acetic acid (lugduname), guanidine, falernum, capersin I, capersin II, maltol, crystalline maltitol (maltisorb), maltodextrin, Maltotriol, mannosamine, micraculin, mizuame, mogrosides (including, for example, mogroside IV, mogroside V and neomogroside), soapberry sesquiterpene glycosides (mukurozioside), nano sugar, naringin dihydrochalcone, neohesperidin dihydrochalcone, nib sugar, black oligosaccharide, norbu sugar, almond syrup, Osladin, pekmez, pentadin, periandrin I, perillaldehyde, perillartine, petphyllum, phenylalanine, Phloisoside I, phlorodizin, phyllodulcin, polyglycitol syrup, polypodoside A, pterocaryoside A, pterocaryoside B, rebiana, refined syrup, rub syrup, rubusoside, selligueain A, shugr, simonoside I, siraitia grosvenorii), soybean oligosaccharides, Splenda, SRIoxime V, steviol glycosides, steviol diglycosides, stevioside, strogins 1, 2 and 4, sucronic acid, sucrononate, sugar, sodium p-nitrophenylureidopropionate (suosan), phlorizin (phloridzin), super aspartame, tetrasaccharide, threitol, molasses (treacle), trilobtain (trilobtain), Tryptophan and its derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, heptanol, birch syrup, aspartame-acesulfame, moxa Assugrin, and combinations or blends of any two or more thereof.

在某些实施方案中，清凉度修饰组合物可以包含食物和饮料产品中常用的任何附加成分或多种成分的组合，包括但不限于：In certain embodiments, the coolness modifying composition may include any additional ingredient or combination of ingredients commonly used in food and beverage products, including, but not limited to:

酸，包括例如柠檬酸、磷酸、抗坏血酸、硫酸氢钠、乳酸或酒石酸；Acids, including, for example, citric acid, phosphoric acid, ascorbic acid, sodium bisulfate, lactic acid or tartaric acid;

苦味成分，包括例如咖啡因、奎宁、绿茶、儿茶素、多酚、罗布斯塔咖啡生豆提取物、咖啡生豆提取物、氯化钾、薄荷醇或蛋白质(例如来自植物、藻类或真菌的蛋白质和蛋白质分离物)；Bitter ingredients including, for example, caffeine, quinine, green tea, catechins, polyphenols, robusta green coffee bean extract, green coffee bean extract, potassium chloride, menthol or proteins (e.g. from plants, algae or fungal proteins and protein isolates);

着色剂，包括例如焦糖色、红色#40、黄色#5、黄色#6、蓝色#1、红色#3、紫色胡萝卜、黑色胡萝卜汁、紫色地瓜、蔬菜汁、果汁、β-胡萝卜素、姜黄姜黄素或二氧化钛；Colorants, including, for example, caramel, red #40, yellow #5, yellow #6, blue #1, red #3, purple carrot, black carrot juice, purple sweet potato, vegetable juice, fruit juice, beta carotene, turmeric curcumin or titanium dioxide;

防腐剂，包括例如苯甲酸钠、苯甲酸钾、山梨酸钾、偏亚硫酸氢钠、山梨酸或苯甲酸；Preservatives including, for example, sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfite, sorbic acid or benzoic acid;

抗氧化剂，包括例如抗坏血酸、EDTA钙二钠、α-生育酚、混合生育酚、迷迭香提取物、葡萄籽提取物、白藜芦醇或六偏磷酸钠；Antioxidants, including, for example, ascorbic acid, calcium disodium EDTA, alpha-tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol or sodium hexametaphosphate;

维生素或功能性成分，包括例如白藜芦醇、Co-Q10、ω3脂肪酸、茶氨酸、氯化胆碱(胞磷胆碱(Citocoline))、纤维醇、菊粉(菊苣根)、牛磺酸、人参提取物、瓜拉那提取物、生姜提取物、L-苯丙氨酸、L-肉碱、L-酒石酸盐、D-葡萄糖醛酸内酯、肌醇、生物类黄酮、紫锥菊、银杏(Ginkgo Biloba)、马黛茶(yerba mate)、亚麻籽油、藤黄果(Garcinia cambogia)皮提取物、白茶提取物、核糖、奶蓟草(milk thistle)提取物、葡萄籽提取物、盐酸吡多醇(维生素B6)、氰钴胺(维生素B12)、烟酰胺(维生素B3)、生物素、乳酸钙、泛酸钙(泛酸)、磷酸钙、碳酸钙、氯化铬、多烟酸铬、硫酸铜、叶酸、焦磷酸铁、铁、乳酸镁、碳酸镁、硫酸镁、磷酸一钾、磷酸一钠、磷、碘化钾、磷酸钾、核黄素、硫酸钠、葡萄糖酸钠、聚磷酸钠、碳酸氢钠、硫胺素单硝酸盐、维生素D3、维生素A棕榈酸酯、葡萄糖酸锌、乳酸锌或硫酸锌；Vitamins or functional ingredients including, for example, resveratrol, Co-Q10, omega 3 fatty acids, theanine, choline chloride (Citocoline), inositol, inulin (chicory root), taurine Acid, ginseng extract, guarana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-glucuronolactone, inositol, bioflavonoids, echinacea, Ginkgo Biloba, yerba mate, flaxseed oil, Garcinia cambogia peel extract, white tea extract, ribose, milk thistle extract, grape seed extract, Pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12), nicotinamide (vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate , copper sulfate, folic acid, ferric pyrophosphate, iron, magnesium lactate, magnesium carbonate, magnesium sulfate, monopotassium phosphate, monosodium phosphate, phosphorus, potassium iodide, potassium phosphate, riboflavin, sodium sulfate, sodium gluconate, sodium polyphosphate , sodium bicarbonate, thiamine mononitrate, vitamin D3, vitamin A palmitate, zinc gluconate, zinc lactate or zinc sulfate;

起云剂，包括例如酯胶、溴化植物油(BVO)或蔗糖乙酸异丁酸酯(SAIB)；Clouding agents, including for example ester gum, brominated vegetable oil (BVO) or sucrose acetate isobutyrate (SAIB);

缓冲液，包括例如柠檬酸钠、柠檬酸钾或盐；Buffers including, for example, sodium citrate, potassium citrate or salt;

风味剂(flavors，食用香精)，包括例如丙二醇、乙醇、甘油、阿拉伯胶(金合欢胶)、麦芽糊精、改性玉米淀粉、右旋糖、天然调味料、具有其他天然调味料的天然调味料(天然调味料WONF)、天然和人工调味料、人工调味料、二氧化硅、碳酸镁或磷酸三钙；或者Flavors (food flavors), including, for example, propylene glycol, ethanol, glycerin, acacia gum (acacia gum), maltodextrin, modified corn starch, dextrose, natural flavorings, natural flavorings with other natural flavorings (natural flavoring WONF), natural and artificial flavourings, artificial flavourings, silica, magnesium carbonate or tricalcium phosphate; or

淀粉和稳定剂，包括例如果胶、黄原胶、羧甲基纤维素(CMC)、聚山梨酯60、聚山梨酯80、中链甘油三酸酯、纤维素凝胶、纤维素胶、酪蛋白酸钠、改性食品淀粉、阿拉伯胶(金合欢胶)、菊粉或角叉菜胶。Starches and stabilizers including, for example, pectin, xanthan gum, carboxymethylcellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, casein Sodium proteinate, modified food starch, acacia gum (acacia gum), inulin or carrageenan.

当溶解或悬浮在水性介质中时，清凉度修饰组合物可以具有任何合适的pH值，例如从较低pH值到中性pH值。较低和中性的pH值包括但不限于1.5至9.0，或2.5至8.5；3.0至8.0；3.5至7.5，和4.0至7的pH值。When dissolved or suspended in an aqueous medium, the coolness modifying composition may have any suitable pH, for example, from a lower pH to a neutral pH. Lower and neutral pH values include, but are not limited to, pH values of 1.5 to 9.0, or 2.5 to 8.5; 3.0 to 8.0; 3.5 to 7.5, and 4.0 to 7.

在某些实施方案中，根据任何前述实施方案提出的清凉度修饰组合物还包括一种或多种另外的风味修饰化合物，例如增强甜味的化合物(例如橙皮素、柚皮素等)、阻断苦味的化合物、增强鲜味的化合物、减少酸味或甘草味的化合物、增强咸味的化合物、增强清凉效果的化合物，或前述化合物的任何组合。In certain embodiments, the coolness modifying composition according to any of the preceding embodiments further includes one or more additional flavor modifying compounds, such as sweet taste enhancing compounds (e.g., hesperetin, naringenin, etc.), Compounds that block bitter taste, enhance umami taste, reduce sour or licorice taste, enhance salty taste, enhance cooling effect, or any combination of the foregoing.

在一些实施方案中，本文公开的清凉度修饰组合物包含一种或多种甜味增强化合物。此类甜味增强化合物包括但不限于天然衍生的化合物，例如橙皮素、柚皮素、野漆树苷、葡糖基化甜菊醇糖苷、甘草衍生的葡糖醛酸、香橙素(aromadendrin)-3-O-乙酸酯或其他类似黄酮醇或类黄酮，或合成的化合物，例如美国专利号8,541,421；8,815,956；9,834,544；8,592,592；8,877,922；9,000,054；和9,000,051，以及美国专利申请公开号2017/0119032中所述的任何化合物。一些合适的例子包括3-((4-氨基-2,2-二氧代-1H-苯并[c][1,2,6]噻二嗪-5-基)氧基)-2,2-二甲基-N-丙基-丙酰胺、N-(1-((4-氨基-2,2-二氧代-1H-苯并[c][1,2,6]噻二嗪-5-基)氧基)-2-甲基-丙-2-基)异烟酰胺或它们的任何组合。In some embodiments, the coolingness modifying compositions disclosed herein comprise one or more sweet taste enhancing compounds. Such sweetness enhancing compounds include, but are not limited to, naturally derived compounds such as hesperetin, naringenin, anardin, glucosylated steviol glycosides, licorice derived glucuronic acid, aromandrin -3-O-acetate or other similar flavonols or flavonoids, or synthetic compounds, such as U.S. Patent Nos. 8,541,421; 8,815,956; 9,834,544; 8,592,592; 8,877,922; 9,000,054; and 9,000,051, and U.S. Patent Application Publication No. 2017/0119032 any compound described in. Some suitable examples include 3-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2 -Dimethyl-N-propyl-propionamide, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazine- 5-yl)oxy)-2-methyl-prop-2-yl)isonicotinamide or any combination thereof.

在一些进一步的实施方案中，本文公开的清凉度修饰组合物包含一种或多种其他鲜味或浓厚味增强化合物。此类鲜味增强化合物包括但不限于天然衍生的化合物，例如(E)-3-(3,4-二甲氧基苯基)-N-(4-甲氧基苯乙基)丙烯酰胺(ericamide)，或合成的化合物，例如美国专利号8,735,081；8,124,121；和8,968,708中所述的任何化合物。In some further embodiments, the coolness modifying compositions disclosed herein comprise one or more other umami or kokumi enhancing compounds. Such umami-enhancing compounds include, but are not limited to, naturally derived compounds such as (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenylethyl)acrylamide ( ericamide), or synthetic compounds, such as any of the compounds described in U.S. Patent Nos. 8,735,081; 8,124,121; and 8,968,708.

在一些进一步的实施方案中，本文公开的清凉度修饰组合物包含一种或多种清凉增强化合物。此类清凉增强化合物包括但不限于天然衍生的化合物，例如薄荷醇或其类似物，或合成的化合物，例如美国专利号9,394,287和10,421,727中所述的任何化合物。例子包括N-乙基-N-(噻吩-2-基甲基)-2-(对甲苯基氧基)乙酰胺；N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)-2-(对甲苯基氧基)乙酰胺；2-(4-氟苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)乙酰胺；2-(2-羟基-4-甲基苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)-乙酰胺；2-((2,3-二氢-1H-茚-5-基)氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)-乙酰胺；2-((2,3-二氢-1H-茚-5-基)氧基)-N-(1H-吡唑-3-基)-N-(噻唑-5-基甲基)-乙酰胺；5-甲氧基-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)苯并呋喃-2-甲酰胺；2-(4-乙基苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)乙酰胺；以及它们的任何组合。In some further embodiments, the coolingness modifying compositions disclosed herein comprise one or more cooling enhancing compounds. Such cooling-enhancing compounds include, but are not limited to, naturally derived compounds, such as menthol or analogs thereof, or synthetic compounds, such as any of the compounds described in U.S. Patent Nos. 9,394,287 and 10,421,727. Examples include N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide; N-(1H-pyrazol-3-yl)-N-(thiophene-2 -ylmethyl)-2-(p-tolyloxy)acetamide; 2-(4-fluorophenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-yl) Methyl)acetamide; 2-(2-hydroxy-4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide; 2-((2,3-Dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide ;2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiazol-5-ylmethyl)-ethyl Amide; 5-methoxy-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)benzofuran-2-carboxamide; 2-(4-ethylphenoxy yl)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide; and any combination thereof.

其他示例性清凉增强化合物包括但不限于(E/Z)-2-甲基-2-丁烯醛、(E/Z)-2-异丙基-5-甲基-2-己烯醛)以及它们的任何组合。Other exemplary cooling enhancing compounds include, but are not limited to (E/Z)-2-methyl-2-butenal, (E/Z)-2-isopropyl-5-methyl-2-hexenal) and any combination of them.

在一些进一步的实施方案中，本文公开的清凉度修饰组合物包含一种或多种苦味阻断化合物。此类苦味阻断化合物包括但不限于天然衍生的化合物，例如薄荷醇或其类似物，或合成化合物，例如美国专利号8,076,491；8,445,692；和9,247,759中所述的任何化合物。In some further embodiments, the coolness modifying compositions disclosed herein comprise one or more bitter blocking compounds. Such bitter blocking compounds include, but are not limited to, naturally derived compounds, such as menthol or analogs thereof, or synthetic compounds, such as any of the compounds described in U.S. Patent Nos. 8,076,491; 8,445,692; and 9,247,759.

在一些进一步的实施方案中，本文公开的口感修饰组合物包含一种或多种口感修饰化合物。此类口感修饰化合物包括但不限于单宁、纤维素材料、竹粉等。In some further embodiments, the mouthfeel modifying compositions disclosed herein comprise one or more mouthfeel modifying compounds. Such taste-modifying compounds include, but are not limited to, tannins, cellulosic materials, bamboo powder, etc.

在一些进一步的实施方案中，本文公开的清凉度修饰组合物包含一种或多种风味掩蔽化合物。此类风味掩蔽化合物包括但不限于纤维素材料、从真菌中提取的材料、从植物中提取的材料、柠檬酸、碳酸(或碳酸盐)等。In some further embodiments, the coolness modifying compositions disclosed herein comprise one or more flavor masking compounds. Such flavor masking compounds include, but are not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like.

在某些实施方案中，本文公开的清凉度修饰组合物可以包含仙客来醛(cyclosal)。当仙客来醛存在时，其相对浓度与内酯相似。In certain embodiments, the coolness modifying compositions disclosed herein can include cyclosal. When cyclamen aldehyde is present, its relative concentration is similar to lactones.

清凉度修饰组合物可以是任何合适的形式。例如，在一些实施方案中，组合物呈固体形式，例如固体粉末。在一些此类实施方案中，组合物还包含固体载体，例如碳水化合物。在一些其他实施方案中，清凉度修饰组合物呈液体溶液或悬浮液的形式。这种液体形式可以是水性或非水性的，或者也可以是乳液，例如水包油或油包水乳液。在一些实施方案中，将清凉度修饰组合物掺入到风味产品例如食物或饮料产品中，或口腔护理产品例如牙膏或漱口水中。The coolness modifying composition may be in any suitable form. For example, in some embodiments, the composition is in solid form, such as a solid powder. In some such embodiments, the composition also includes a solid carrier, such as a carbohydrate. In some other embodiments, the coolness modifying composition is in the form of a liquid solution or suspension. The liquid form may be aqueous or non-aqueous, or it may be an emulsion, such as an oil-in-water or water-in-oil emulsion. In some embodiments, the coolness modifying composition is incorporated into flavored products, such as food or beverage products, or oral care products, such as toothpaste or mouthwash.

在一些实施方案中，清凉度修饰组合物包含一种或多种调味剂(flavorings)，或在H.Mitchell,SWEETENERS AND SUGAR ALTERNATIVES IN FOOD TECHNOLOGY,BackwellPublishing Ltd.,2006中描述的任何其他添加剂。如本文所用，术语“调味剂”包括技术人员已知的那些风味剂(flavors)，例如天然和人工风味剂。这些调味剂可以选自合成调味油和调味芳香物质或来自植物、叶子、花朵、果实等的油，油性树脂和提取物，以及它们的组合。非限制性的代表性调味油包括留兰香油、肉桂油、鹿蹄草油(水杨酸甲酯)、胡椒薄荷油、日本薄荷油、丁香油、月桂油、茴香油、桉树油、百里香油、雪松叶油、肉豆蔻油、多香果、鼠尾草油、肉豆蔻(mace)、苦杏仁油和决明子油。有用的调味剂还有人造的、天然的和合成的水果风味剂，例如香草，和柑橘油，包括柠檬、橙子、酸橙、葡萄柚、日本柚(yazu)、酢橘(sudachi)，以及水果香精(essences)，包括苹果、梨、桃、葡萄、蓝莓、草莓、树莓、樱桃、李子、菠萝、西瓜、杏、香蕉、甜瓜、杏、梅、樱桃、树莓、黑莓、热带水果、芒果、山竹、石榴、木瓜等。其他潜在的风味剂包括牛奶风味剂，黄油风味剂，奶酪风味剂，奶油风味剂和酸奶风味剂；香草风味剂；茶或咖啡风味剂，例如绿茶风味剂，乌龙茶风味剂，茶风味剂，可可风味剂，巧克力风味剂和咖啡风味剂；薄荷风味剂，例如胡椒薄荷风味剂，留兰香风味剂和日本薄荷风味剂；香料风味剂，例如阿魏风味剂，印度藏茴香风味剂，大茴香风味剂，当归风味剂，茴香风味剂，多香果风味剂，肉桂风味剂，甘菊风味剂，芥末风味剂，小豆蔻风味剂，香菜风味剂，小茴香风味剂，丁香风味剂，胡椒风味剂，胡荽风味剂，黄樟风味剂，咸味风味剂，川椒风味剂，紫苏风味剂，杜松子风味剂，生姜风味剂，八角茴香风味剂，辣根风味剂，百里香风味剂，龙蒿风味剂，莳萝风味剂，菜椒风味剂，肉豆蔻风味剂，罗勒风味剂，马郁兰风味剂，迷迭香风味剂，月桂叶风味剂和芥末(日本辣根)风味剂；酒香风味剂，例如红酒风味剂，威士忌风味剂，白兰地风味剂，朗姆酒风味剂，杜松子酒风味剂和利口酒风味剂；花香风味剂；以及蔬菜风味剂，例如洋葱风味剂，大蒜风味剂，卷心菜风味剂，胡萝卜风味剂，芹菜风味剂，蘑菇风味剂，和番茄风味剂。这些调味剂可以液体或固体形式使用，并且可以单独或混合使用。常用的风味剂包括薄荷，例如胡椒薄荷、薄荷醇、留兰香、人造香草、肉桂衍生物以及各种水果风味剂，无论是单独使用还是混合使用。风味剂还可以提供口气清新的特性，特别是与清凉剂结合使用时的薄荷风味剂。In some embodiments, the coolness modifying composition includes one or more flavorings, or any other additives described in H. Mitchell, SWEETENERS AND SUGAR ALTERNATIVES IN FOOD TECHNOLOGY, Backwell Publishing Ltd., 2006. As used herein, the term "flavor" includes those flavors known to those skilled in the art, such as natural and artificial flavors. These flavoring agents may be selected from synthetic flavoring oils and flavoring aromatics or oils, oleoresins and extracts from plants, leaves, flowers, fruits, etc., and combinations thereof. Non-limiting representative flavoring oils include spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil , cedar leaf oil, nutmeg oil, allspice, sage oil, nutmeg (mace), bitter almond oil and cassia seed oil. Useful flavoring agents are also artificial, natural and synthetic fruit flavors, such as vanilla, and citrus oils, including lemon, orange, lime, grapefruit, yazu, sudachi, and fruit Essences, including apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, watermelon, apricot, banana, melon, apricot, plum, cherry, raspberry, blackberry, tropical fruits, mango , mangosteen, pomegranate, papaya, etc. Other potential flavors include milk flavours, butter flavours, cheese flavours, cream flavors and yogurt flavours; vanilla flavours; tea or coffee flavours, such as green tea flavours, oolong tea flavours, tea flavours, cocoa Flavors, chocolate flavor and coffee flavor; mint flavors, such as peppermint flavor, spearmint flavor and Japanese mint flavor; spice flavors, such as asafoetida, fennel flavor, anise Flavor, Angelica Flavor, Fennel Flavor, Allspice Flavor, Cinnamon Flavor, Chamomile Flavor, Mustard Flavor, Cardamom Flavor, Coriander Flavor, Cumin Flavor, Clove Flavor, Pepper Flavor agent, coriander flavor, sassafras flavor, salty flavor, Szechuan pepper flavor, perilla flavor, juniper berry flavor, ginger flavor, star anise flavor, horseradish flavor, thyme flavor, Tarragon flavor, dill flavor, bell pepper flavor, nutmeg flavor, basil flavor, marjoram flavor, rosemary flavor, bay leaf flavor and wasabi (Japanese horseradish) flavor; wine aroma Flavors, such as red wine flavor, whiskey flavor, brandy flavor, rum flavor, gin flavor, and liqueur flavor; floral flavors; and vegetable flavors, such as onion flavor, garlic flavor , cabbage flavor, carrot flavor, celery flavor, mushroom flavor, and tomato flavor. These flavoring agents may be used in liquid or solid form, and may be used alone or in mixtures. Commonly used flavors include mints such as peppermint, menthol, spearmint, artificial vanilla, cinnamon derivatives, and various fruit flavors, either alone or in combination. Flavors can also provide breath freshening properties, especially mint flavors when combined with a cooling agent.

风味剂还可以提供口气清新的特性，特别是与清凉剂结合使用时的薄荷风味剂。这些调味剂可以以液体或固体形式使用，并且可以单独或混合使用。其他有用的调味剂包括醛和酯，例如乙酸肉桂酯、肉桂醛、柠檬醛二乙基乙缩醛、乙酸二氢香芹酯、甲酸丁香酚酯、对甲基茴香醚等。通常，可以使用任何调味剂或食品添加剂，例如由美国国家科学院(National Academy of Sciences)在Chemicals Used in Food Processing,publication1274,pages 63-258中所述的那些。Flavors can also provide breath freshening properties, especially mint flavors when combined with a cooling agent. These flavoring agents may be used in liquid or solid form and may be used alone or in mixtures. Other useful flavoring agents include aldehydes and esters such as cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarvyl acetate, eugenol formate, p-methylanisole, and the like. Generally, any flavoring or food additive may be used, such as those described by the National Academy of Sciences in Chemicals Used in Food Processing, publication 1274, pages 63-258.

醛调味剂的其他例子包括但不限于乙醛(苹果)，苯甲醛(樱桃、杏仁)，茴香醛(甘草、茴香)，肉桂醛(肉桂)，柠檬醛，即α-柠檬醛(柠檬，酸橙)，橙花醛，即β-柠檬醛(柠檬、酸橙)，癸醛(橙、柠檬)，乙基香草醛(香草、奶油)，洋茉莉醛，即胡椒醛(香草、奶油)，香草醛(香草、奶油)，α-戊基肉桂醛(辛辣的果味风味剂)，丁醛(黄油、奶酪)，戊醛(黄油、奶酪)，香茅醛(改性产物、多种类型)，癸醛(柑橘类水果)，醛C-8(柑橘类水果)，醛C-9(柑橘类水果)，醛C-12(柑橘类水果)，2-乙基丁醛(浆果)，己烯醛，即反式-2(浆果)，甲苯基甲醛(樱桃、杏仁)，藜芦醛(香草)，2,6-二甲基-5-庚烯，即甜瓜醛(甜瓜)，2,6-二甲基辛醛(绿色水果)，和2-十二碳烯醛(柑橘、桔)，樱桃，葡萄，草莓酥饼，以及它们的混合物。这些调味剂的列表仅是示例性的，并不意味着通常限制术语“调味剂”或一般公开的范围。Other examples of aldehyde flavoring agents include, but are not limited to, acetaldehyde (apple), benzaldehyde (cherry, almond), anisaldehyde (licorice, anise), cinnamaldehyde (cinnamon), citral, i.e. alpha-citral (lemon, sour Orange), neraldehyde, which is β-citral (lemon, lime), decanal (orange, lemon), ethyl vanillin (vanilla, cream), jasmine aldehyde, which is piperonal (vanilla, cream), Vanillin (vanilla, cream), α-amylcinnamaldehyde (spicy fruity flavor), butyraldehyde (butter, cheese), valeraldehyde (butter, cheese), citronellal (modified products, various types ), Decanal (citrus fruits), Aldehyde C-8 (citrus fruits), Aldehyde C-9 (citrus fruits), Aldehyde C-12 (citrus fruits), 2-ethylbutyraldehyde (berries), Hexenal, trans-2 (berry), Tolylcarbaldehyde (cherry, almond), Veratraldehyde (vanilla), 2,6-Dimethyl-5-heptene, melonaldehyde (melon), 2 , 6-dimethyloctanal (green fruits), and 2-dodecenal (citrus, tangerines), cherries, grapes, strawberry shortcake, and mixtures thereof. These lists of flavoring agents are illustrative only and are not intended to limit the scope of the term "flavoring agent" or the general disclosure in general.

在某些实施方案中，薄荷调味剂，包括薄荷醇和相关化合物，或其他清新口气的化合物，可以与清凉剂组合，例如美国专利号9,394,287和9,732,071中所述的那些。清凉剂的其他例子包括5-甲基-2-(丙烷-2-基)环己基-N-乙基草氨酸酯、N-乙基-对-薄荷烷甲酰胺(WS-3，也称为薄荷烷-3-羧酸-N-乙酰胺)、N-2,3-三甲基-2-异丙基丁酰胺(WS-23)、乳酸薄荷酯(ML)、薄荷酮甘油缩醛(/>MGA)、琥珀酸单薄荷酯戊二酸单薄荷酯、O-薄荷基-甘油、琥珀酰胺酸薄荷基-N,N-二甲酯、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、N-(2-(吡啶-2-基)乙基)-3-对薄荷烷甲酰胺、薄荷醇和薄荷醇衍生物(例如L-薄荷醇、D-薄荷醇、外消旋薄荷醇、异薄荷醇、新异薄荷醇、新薄荷醇)、薄荷基醚(例如(1-薄荷氧基)-1,2-丙二醇、(1-薄荷氧基)-2-甲基-1,2-丙二醇、1-薄荷基-甲基醚)、薄荷酯(例如甲酸薄荷酯、乙酸薄荷酯、异丁酸薄荷酯、乳酸薄荷酯、L-薄荷基-L-乳酸酯、L-薄荷基-D-乳酸酯、薄荷基-(2-甲氧基)乙酸酯、薄荷基-(2-甲氧基乙氧基)乙酸酯、焦谷氨酸薄荷酯)、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、N-(2-(吡啶-2)-基)乙基)-3-对薄荷烷甲酰胺、碳酸薄荷酯(例如碳酸薄荷基丙二醇酯、碳酸薄荷基乙二醇酯、碳酸薄荷基甘油酯或它们的混合物)、薄荷烷羧酸酰胺(例如薄荷烷羧酸-N-乙基酰胺[WS3]、N-α.-(薄荷烷-羰基)甘氨酸乙酯[WS5]、薄荷烷羧酸-N-(4-氰基苯基)酰胺、薄荷烷羧酸-N-(烷氧基烷基)酰胺)、薄荷酮和薄荷酮衍生物(例如L-薄荷酮甘油缩酮)、2,3-二甲基-2-(2-丙基)-丁酸衍生物(例如2,3-二甲基-2-(2-丙基)-丁酸-N-甲基酰胺[WS23])、异胡薄荷醇或其酯(1-(-)-异胡薄荷醇、1-(-)-异胡薄荷醇乙酸酯)、薄荷烷衍生物(例如对薄荷烷-3,8-二醇)、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、N-(2-(吡啶-2-基)乙基)-3-对薄荷烷甲酰胺、荜澄茄醇或含有荜澄茄醇的合成或天然混合物、环烷基二酮衍生物的吡咯烷酮衍生物(例如3-甲基-2(1-吡咯烷基)-2-环戊烯-1-酮)或四氢嘧啶-2-酮(例如伊西林(Icilin)或相关化合物，例如WO 2004/026840中描述的那些)、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺、N-(2-(吡啶-2-基)乙基)-3-对薄荷烷甲酰胺、薄荷基醚(例如(1-薄荷氧基)-1,2-丙二醇、(1-薄荷氧基)-2-甲基-1,2-丙二醇)、更具极性的薄荷酯(例如乳酸薄荷酯、L-薄荷基-L-乳酸酯、L-薄荷基-D-乳酸酯、薄荷基-(2-甲氧基)乙酸酯、薄荷基-(2-甲氧基乙氧基)乙酸酯、焦谷氨酸薄荷酯)、碳酸薄荷酯(例如碳酸薄荷基丙二醇酯、碳酸薄荷基乙二醇酯、碳酸薄荷基甘油酯)、薄荷醇与二羧酸或其衍生物的半酯(例如琥珀酸单薄荷酯、戊二酸单薄荷酯、丙二酸单薄荷酯、O-薄荷基琥珀酸酯-N,N-(二甲基)酰胺、O-薄荷基琥珀酸酯酰胺)、3,4-亚甲基二氧肉桂酸-N-环己基-N-2-吡啶酰胺、异丙基-(5-甲氧基-2-吡啶-2-基-嘧啶-4-基)-胺、3,4,6,7,11b,12-六氢-3,3-二甲基-螺[13H-二苯并[a,f]喹嗪-1-3,2'-[1,3]二硫杂环戊烷]-1(2H)-酮、5,6,10b,11-四氢-3-甲基-螺[12H-苯并[a]呋喃并[3,4-f]喹嗪-1-2,2'-[1,3]二硫杂环戊烷]-1(3H)-酮。最优选的清凉化合物是从由如下构成的群组中选出的化合物：5-甲基-2-(丙烷-2-基)环己基-N-乙基草氨酸酯、N-乙基-对-薄荷烷甲酰胺(WS-3，也称为薄荷烷-3-羧酸-N-乙基酰胺)、乳酸薄荷酯(/>ML)、薄荷酮甘油缩醛(/>MGA)、N-(4-氰基甲基苯基)-对薄荷烷甲酰胺和(1-薄荷氧基)-1,2-丙二醇。In certain embodiments, mint flavorings, including menthol and related compounds, or other breath-freshening compounds, may be combined with cooling agents, such as those described in U.S. Patent Nos. 9,394,287 and 9,732,071. Other examples of cooling agents include 5-methyl-2-(propan-2-yl)cyclohexyl-N-ethyloxamate, N-ethyl-p-menthane carboxamide (WS-3, also known as Menthane-3-carboxylic acid-N-acetamide), N-2,3-trimethyl-2-isopropylbutanamide (WS-23), menthyl lactate ( ML), menthone glycerol acetal (/> MGA), monomenthyl succinate Mononethyl glutarate, O-menthyl-glycerol, menthyl succinic acid-N,N-dimethyl ester, N-(4-cyanomethylphenyl)-p-menthane carboxamide, N-( 2-(Pyridin-2-yl)ethyl)-3-p-menthanecarboxamide, menthol and menthol derivatives (such as L-menthol, D-menthol, racemic menthol, isomenthol, new Isomenthol, neomenthol), menthyl ethers (such as (1-menthyloxy)-1,2-propanediol, (1-menthyloxy)-2-methyl-1,2-propanediol, 1-menthol -methyl ether), menthyl esters (such as menthyl formate, menthyl acetate, menthyl isobutyrate, menthyl lactate, L-menthyl-L-lactate, L-menthyl-D-lactate) , Menthyl-(2-methoxy)acetate, Menthyl-(2-methoxyethoxy)acetate, Menthyl pyroglutamic acid), N-(4-cyanomethylbenzene) base)-p-menthanecarboxamide, N-(2-(pyridin-2)-yl)ethyl)-3-p-menthanecarboxamide, menthyl carbonate (such as menthyl propylene glycol carbonate, menthyl ethylene glycol carbonate) alcohol ester, menthyl glyceryl carbonate or their mixture), menthane carboxylic acid amide (such as menthane carboxylic acid-N-ethyl amide [WS3], N-α.-(menthane-carbonyl)glycine ethyl ester [ WS5], menthane carboxylic acid-N-(4-cyanophenyl)amide, menthane carboxylic acid-N-(alkoxyalkyl)amide), menthone and menthone derivatives (such as L-menthone Glycerol ketal), 2,3-dimethyl-2-(2-propyl)-butyric acid derivatives (such as 2,3-dimethyl-2-(2-propyl)-butyric acid-N- Methylamide [WS23]), isopulegol or its esters (1-(-)-isopulegol, 1-(-)-isopulegol acetate), menthane derivatives (e.g. p-menthol alkyl-3,8-diol), N-(4-cyanomethylphenyl)-p-menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)-3-p-menthane Formamide, piperol or synthetic or natural mixtures containing piperol, pyrrolidone derivatives of cycloalkyldione derivatives (e.g. 3-methyl-2(1-pyrrolidinyl)-2-cyclopenta en-1-one) or tetrahydropyrimidin-2-one (e.g. Icilin or related compounds such as those described in WO 2004/026840), N-(4-cyanomethylphenyl)-p Menthane carboxamide, N-(2-(pyridin-2-yl)ethyl)-3-p-menthane carboxamide, menthyl ether (such as (1-menthenyloxy)-1,2-propanediol, (1 -menthoxy)-2-methyl-1,2-propanediol), more polar menthyl esters (e.g., menthyl lactate, L-menthyl-L-lactate, L-menthyl-D-lactate acid ester, menthyl-(2-methoxy)acetate, menthyl-(2-methoxyethoxy)acetate, menthyl pyroglutamate), menthyl carbonate (such as menthyl carbonate) Propylene glycol ester, menthyl glycol carbonate, menthyl glyceryl carbonate), half esters of menthol and dicarboxylic acid or its derivatives (such as monomenthyl succinate, monomenthyl glutarate, monomalonate Menthyl ester, O-menthyl succinate-N,N-(dimethyl)amide, O-menthyl succinate amide), 3,4-methylenedioxycinnamic acid-N-cyclohexyl-N -2-pyridinamide, isopropyl-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine, 3,4,6,7,11b,12-hexahydro-3 ,3-dimethyl-spiro[13H-dibenzo[a,f]quinolizine-1-3,2'-[1,3]dithiolan]-1(2H)-one, 5 ,6,10b,11-tetrahydro-3-methyl-spiro[12H-benzo[a]furo[3,4-f]quinolizine-1-2,2'-[1,3]disulfide Heterocyclopentane]-1(3H)-one. The most preferred cooling compounds are those selected from the group consisting of: 5-methyl-2-(propan-2-yl)cyclohexyl-N-ethyloxamate, N-ethyl- p-menthanecarboxamide (WS-3, also known as menthane-3-carboxylic acid-N-ethylamide), menthyl lactate (/> ML), menthone glycerol acetal (/> MGA), N-(4-cyanomethylphenyl)-p-menthanecarboxamide and (1-menthoxy)-1,2-propanediol.

其他合适的清凉剂包括但不限于WO 2021/074281中提出的那些，例如(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)(1,2,3-噻二唑-5-基)甲酮、(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)(硫杂环丁烷-3-基)甲酮、(2,2-二甲基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2-乙氧基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2-甲氧基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2-甲基环丙基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(2S)-2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、(5-甲基四氢呋喃-3-基)(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、(E)-1-(2-(5-(3,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-2-烯-1-酮、(E)-2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-2-烯-1-酮、(E)-2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)戊-3-烯-1-酮、(R)-2-(甲基硫代)-1-((R)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、(S)-2-(甲基硫代)-1-((R)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、(S)-2-(甲基硫代)-1-((S)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、(S)-2-甲基-1-((R)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、(四氢呋喃-3-基)(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)甲酮、1-(2-(1H-苯并[d]咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(1-甲基-1H-吡唑-4-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,2-二氟苯并[d][1,3]二氧杂环戊二烯-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,3-二氢苯并呋喃-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,3-二氢苯并呋喃-6-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2,5-二甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-氯苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-环丙基恶唑-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(2-羟基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3-((二甲基氨基)甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3,5-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3,5-二甲基异恶唑-4-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3-氯-4-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(3-甲基呋喃-2-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-((1,1-二氧化硫代吗啉代)甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(1-羟基乙基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(二氟甲氧基)-3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(二氟甲基)噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(甲基磺酰基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-(叔丁基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-环丁基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-环丙基-2-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-羟基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-异丙基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(4-甲基-3-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(5-((二甲氨基)甲基)噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(5-甲基呋喃-2-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(5-甲基吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(6-甲基吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-(苯并[b]噻吩-6-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-甲基-5-苯基-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)-2-((三氟甲基)硫基)乙-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)己-3,5-二烯-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)戊-4-烯-1-酮、1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(2-(5-(2,3-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2,5-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2-氟-4-甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2-氟-4-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(2-甲氧基嘧啶-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-(甲基氨基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3,4-二氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-3-烯-1-酮、1-(2-(5-(3,4-二甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3,4-二甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-氟-4-(甲氧基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-氟-4-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-甲氧基异噻唑-4-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(3-甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-((甲基氨基)甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(2-甲氧基乙基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(氨基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(二甲基氨基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-乙酰基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氨基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氯-3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氯苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-乙基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-氟苯基)-4H-1,2,4-三唑-3-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-甲氧基-2-甲基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-甲氧基苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(4-甲基-6-(甲基硫代)吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(5-(甲氧基甲基)噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(6-甲氧基吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(苯并[d][1,3]二氧杂环戊二烯-5-基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(2-(5-苄基-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-(5-溴-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、2-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲腈、2-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-羰基)环丙烷-1-甲腈、2-(5-甲基呋喃-2-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(烯丙基硫基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(二甲基氨基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-(二甲基氨基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(乙基硫基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(呋喃-2-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(呋喃-2-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(呋喃-3-基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(呋喃-3-基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基氨基)-N-(4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙酰胺、2-(甲基亚磺酰基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基磺酰基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(甲基磺酰基)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(2-(对甲苯基)-2H-四唑-5-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(3-苯基-1,2,4-恶二唑-5-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(1-(三氟甲基)-1H-吡唑-4-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(4-(吗啉代甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(5-(三氟甲基)呋喃-2-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(5-(三氟甲基)噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(5-甲基噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(间甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(邻甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(吡啶-3-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(吡啶-4-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(嘧啶-5-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(喹喔啉-6-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(噻吩-3-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-(甲基硫代)-1-(2-(5-(2-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(2,3,4-三氟苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(2,4,5-三氟苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(3-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-(三氟甲氧基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-(三氟甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-丙基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(4-乙烯基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(5-甲基噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1,3,4-恶二唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)氮杂环庚烷-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-4H-1,2,4-三唑-3-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)异恶唑-3-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)恶唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)噻唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基-1H-咪唑-2-基)吡咯烷-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基-4H-1,2,4-三唑-3-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(5-苯基恶唑-2-基)哌啶-1-基)丙-1-酮、2-(甲基硫代)-1-(4-(5-(对甲苯基)-1H-咪唑-2-基)噻唑烷-3-基)丙-1-酮、2,2,3-三甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮、2,2,3-三甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2,2-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮、2,2-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2,3-二甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2,3-二甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2,5-二氟-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯甲腈、2-氨基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-环丁基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-环戊基-2-乙氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-环丙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-环丙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-环丙基-2-甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)乙-1-酮、2-乙氧基-1-(2-(5-(3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-乙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-2-烯-1-酮、2-乙基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-氟-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲腈、2-巯基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲氧基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲氧基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1,3-二酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)戊-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-2-烯-1-酮、2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-3-(甲基硫代)-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-亚甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、3-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯甲腈、3,3,3-三氟-2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、3,3,4,4,4-五氟-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、3,3-二氟-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、3-氟-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲腈、3-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-2-烯-1-酮、3-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、4-(2-(1-(2-(甲基硫代))丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯甲腈，4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲醛、4,4,4-三氟-2-甲基-1-(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、二环[1.1.1]戊-1-基(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、环丁基(2-(5-(3-氟苯基)-1H-咪唑-2-基)哌啶-1-基)甲酮、环戊基(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、环丙基(2-(4-苯基-1H-咪唑-2-基)哌啶-1-基)甲酮、4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲酸甲酯、N-(2-羟基乙基)-4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯磺酰胺、2-(甲基硫代)-1-(2-(5-(3-硝基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、N-(4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-4-基)苯基)甲磺酰胺、2-(甲基硫代)-1-(2-(5-(4-硝基苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(仲丁基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(仲丁基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(异丙基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(异丙基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((1-(甲基硫代)乙基)亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((1-(甲基硫代)乙基)磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-(甲基硫代)丙-2-基)亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-(甲基硫代)丙-2-基)磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(丁-3-烯-2-基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(丁-3-烯-2-基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(戊-3-烯-2-基亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(戊-3-烯-2-基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-甲基丁-3-烯-2-基)亚磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-((2-甲基丁-3-烯-2-基)磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(2-(5-(4-(羟基甲基)-苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、2-(甲基磺酰基)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮□1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑)-2-基)哌啶-1-基)-2-(甲基磺酰基)丙-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲磺酰基)丙-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)-丙-1-酮、1-(4-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(5-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(2-羟基-6-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(3-羟基-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基亚磺酰基)丙-1-酮、1-(2-羟基-6-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(5-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(4-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(3-羟基-2-(5-(4-(羟基甲基)-苯基)-1H-咪唑-2-基)哌啶-1-基)-2-(甲基硫代)丙-1-酮、1-(2-羟基-6-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(5-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(4-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(3-羟基-2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲醛、4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲酸、4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯甲酸、(2,2-二甲基环丙基)(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)甲酮、1-(2-(5-溴-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(2-(5-(4-氯苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、2-(4-(2-(1-(2-(甲基硫代)丙酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙腈、2-(4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙腈、2-(4-(2-(1-(2-甲基丁酰基)哌啶-2-基)-1H-咪唑-5-基)苯基)乙腈、2,3-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-甲基-1-(2-(5-(邻甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮,2-甲基-1-(2-(5-(间甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、1-(2-(5-(4-(羟基甲基)苯基)-1H-咪唑-2-基)哌啶-1-基)-2-甲基丁-1-酮、1-(异丙基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、1-(仲丁基磺酰基)-2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶、2-甲基-1-(2-(5-(5-甲基噻吩-2-基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌嗪-1-基)丙-1-酮、2-(甲基硫代)-1-(2-(4-(对甲苯基)恶唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-1-(2-(4-(对甲苯基)恶唑-2-基)哌啶-1-基)丁-1-酮或它们的任何组合，通常为2-甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-1-酮、2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2-甲基-2-(甲基硫代)-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丙-1-酮、2,2-二甲基-1-(2-(5-(对甲苯基)-1H-咪唑-2-基)哌啶-1-基)丁-3-烯-1-酮或它们的组合。Other suitable cooling agents include, but are not limited to, those set forth in WO 2021/074281, such as (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(1,2,3- Thiadiazol-5-yl)methanone, (2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)(thietan-3-yl)methanone, ( 2,2-Dimethylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-ethoxycyclopropyl)(2 -(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2-methoxycyclopropyl)(2-(4-phenyl-1H-imidazole-2- yl)piperidin-1-yl)methanone, (2-methylcyclopropyl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (2S )-2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (5-methyltetrahydrofuran-3 -yl)(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, (E)-1-(2-(5-(3,4-difluorobenzene) base)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-2-en-1-one, (E)-2-methyl-1-(2-(5- (p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, (E)-2-methyl-1-(2-(5-(p- Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pent-3-en-1-one, (R)-2-(methylthio)-1-((R)-2 -(5-(p-Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-((R) -2-(5-(p-Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-(methylthio)-1-(( S)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, (S)-2-methyl-1-((R) -2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, (tetrahydrofuran-3-yl)(2-(5-(p-tolyl) )-1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-2-( Methylthio)propan-1-one, 1-(2-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl) -2-(Methylthio)propan-1-one, 1-(2-(4-(2,2-difluorobenzo[d][1,3]dioxolane-5- base)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3-dihydrobenzo Furan-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2,3- Dihydrobenzofuran-6-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-( 2,5-Dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-( 2-Chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-cyclopropyl) Oxazol-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2- Fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(2-hydroxyphenyl) -1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3-((dimethylamino)methyl) base)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-di Fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3,5-dimethyl) Isoxazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-(3 -Chloro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-( 3-methylfuran-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(4-( 4-((1,1-Dioxidethiomorpholino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one , 1-(2-(4-(4-(1-hydroxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -Ketone, 1-(2-(4-(4-(difluoromethoxy)-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(4-(4-(difluoromethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2 -(Methylthio)propan-1-one, 1-(2-(4-(4-(methylsulfonyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(4-(4-(tert-butyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(4-(4-cyclobutylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2- (Methylthio)propan-1-one, 1-(2-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(4-(4-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl methylthio)propan-1-one, 1-(2-(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio) Propan-1-one, 1-(2-(4-(4-isopropylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan- 1-one, 1-(2-(4-(4-methyl-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thiophen-1-one, 1-(2-(4-(5-((dimethylamino)methyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidine-1- base)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylfuran-2-yl)-1H-imidazol-2-yl)piperidine-1- base)-2-(methylthio)propan-1-one, 1-(2-(4-(5-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidine-1- base)-2-(methylthio)propan-1-one, 1-(2-(4-(6-methylpyridin-3-yl)-1H-imidazol-2-yl)piperidine-1- base)-2-(methylthio)propan-1-one, 1-(2-(4-(benzo[b]thiophen-6-yl)-1H-imidazol-2-yl)piperidine-1 -yl)-2-(methylthio)propan-1-one, 1-(2-(4-methyl-5-phenyl-1H-imidazol-2-yl)piperidin-1-yl)- 2-(Methylthio)propan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)-2-((trifluoromethyl) Thio)ethan-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(4-phenyl) Base-1H-imidazol-2-yl)piperidin-1-yl)hex-3,5-dien-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piper Din-1-yl)pent-4-en-1-one, 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1- (2-(5-(2,3-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-( 2-(5-(2,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2 -(5-(2,5-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2- (5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-( 2-(5-(2-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1- (2-(5-(2-methoxypyrimidin-5-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1 -(2-(5-(3-(methylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1 -(2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1- (2-(5-(3,4-difluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbut-3-en-1-one, 1-( 2-(5-(3,4-dimethoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1- (2-(5-(3,4-dimethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1- (2-(5-(3-fluoro-4-(methoxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan- 1-one, 1-(2-(5-(3-fluoro-4-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propane -1-one, 1-(2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one , 1-(2-(5-(3-methoxyisothiazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -one, 1-(2-(5-(3-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one , 1-(2-(5-(4-((methylamino)methyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propanyl -1-one, 1-(2-(5-(4-(2-methoxyethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(5-(4-(aminomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl methylthio)propan-1-one, 1-(2-(5-(4-acetylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio )Propan-1-one, 1-(2-(5-(4-aminophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -Ketone, 1-(2-(5-(4-chloro-3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1 -(2-(5-(4-ethylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2 -(5-(4-Fluorophenyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1 -(2-(5-(4-methoxy-2-methylphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1- Ketone, 1-(2-(5-(4-methoxyphenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(4-methyl-6-(methylthio)pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methyl Thio)propan-1-one, 1-(2-(5-(5-(methoxymethyl)thiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)- 2-(methylthio)propan-1-one, 1-(2-(5-(6-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl) -2-(Methylthio)propan-1-one, 1-(2-(5-(benzo[d][1,3]dioxol-5-yl)-1H-imidazole -2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piper Din-1-yl)propan-1-one, 1-(2-(5-benzyl-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1 -one, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 2-(2-(1 -(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 2-(2-(4-phenyl-1H-imidazole-2- yl)piperidine-1-carbonyl)cyclopropane-1-carbonitrile, 2-(5-methylfuran-2-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2-(allylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine-1- yl)propan-1-one, 2-(dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2 -(Dimethylamino)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(ethylthio)-1 -(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(furan-2-yl)-1-(2-( 4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(furan-2-yl)-1-(2-(4-phenyl-1H-imidazole) -2-yl)piperidin-1-yl)propan-1-one, 2-(furan-3-yl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidine- 1-yl)ethan-1-one, 2-(furan-3-yl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan -1-one, 2-(methylamino)-N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazole-5- base)phenyl)acetamide, 2-(methylsulfinyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1 -one, 2-(methylsulfonyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-(methylsulfonate Acyl)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-( 2-(p-tolyl)-2H-tetrazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(3-phenyl- 1,2,4-oxadiazol-5-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(1-(trifluoro Methyl)-1H-pyrazol-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-( 4-(4-(morpholinomethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2 -(4-(5-(trifluoromethyl)furan-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)- 1-(2-(4-(5-(trifluoromethyl)thiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methyl Thio)-1-(2-(4-(5-methylthiophen-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methyl Thio)-1-(2-(4-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1- (2-(4-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4- (Pyridin-3-yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyridin-4) -yl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(pyrimidin-5-yl)- 1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(quinoxalin-6-yl)-1H- Imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-(thiophen-3-yl)-1H-imidazole-2- yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl) Ethyl-1-one, 2-(methylthio)-1-(2-(5-(2-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl )Propan-1-one, 2-(methylthio)-1-(2-(5-(2,3,4-trifluorophenyl)-1H-imidazol-2-yl)piperidine-1- yl)propan-1-one, 2-(methylthio)-1-(2-(5-(2,4,5-trifluorophenyl)-1H-imidazol-2-yl)piperidine-1 -yl)propan-1-one, 2-(methylthio)-1-(2-(5-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine- 1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)piper Din-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-propylphenyl)-1H-imidazol-2-yl)piperidine- 1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-(4-vinylphenyl)-1H-imidazol-2-yl)piperidin-1-yl )Propan-1-one, 2-(methylthio)-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl )Propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1,3,4-oxadiazol-2-yl)piperidin-1-yl )Propan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)azepan-1-yl)propan- 1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2- (Methylthio)-1-(2-(5-(p-tolyl)-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan-1-one, 2 -(Methylthio)-1-(2-(5-(p-tolyl)isoxazol-3-yl)piperidin-1-yl)propan-1-one, 2-(methylthio) -1-(2-(5-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5 -(p-tolyl)thiazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazole-2) -yl)piperidin-1-yl)propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-1H-imidazol-2-yl)pyrrolidin-1-yl )propan-1-one, 2-(methylthio)-1-(2-(5-phenyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl)propan -1-one, 2-(methylthio)-1-(2-(5-phenyloxazol-2-yl)piperidin-1-yl)propan-1-one, 2-(methylthio) Generation)-1-(4-(5-(p-tolyl)-1H-imidazol-2-yl)thiazolidin-3-yl)propan-1-one, 2,2,3-trimethyl-1- (2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2,3-trimethyl-1-( 2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,2-dimethyl-1-(2-(5-(p- Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl) -1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2,3-dimethoxy-1-(2-(4-phenyl-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2,3-dimethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1 -Ketone, 2,5-difluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-4-yl)benzonitrile, 2-Amino-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclobutyl-1-(2- (4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclopentyl-2-ethoxy-1-(2-(4-phenyl- 1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidine-1 -yl)ethan-1-one, 2-cyclopropyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-cyclo Propyl-2-methoxy-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)ethan-1-one, 2-ethoxy-1-( 2-(5-(3-fluorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-ethyl-1-(2-(4-phenyl- 1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 2-ethyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piper Din-1-yl)butan-1-one, 2-fluoro-4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazole-5- base) benzonitrile, 2-mercapto-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy -1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methoxy-1-(2-(4-phenyl- 1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methoxy-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piper Din-1-yl)propan-1-one, 2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2 -Methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(5-( p-Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)but-3-en-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H -imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine- 1-yl)butan-1,3-dione, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)pentan-1 -one, 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)prop-2-en-1-one, 2-methyl Base-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio) -1-(2-(5-(p-Tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-3-(methylthio)- 1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 2-methylene-1-(2-(5-(p-tolyl) )-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl) -1H-imidazol-4-yl)benzonitrile, 3,3,3-trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidine-1 -yl)propan-1-one, 3,3,4,4,4-pentafluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan- 1-one, 3,3-difluoro-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 3-fluoro-4-( 2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzonitrile, 3-methyl-1-(2-(4- Phenyl-1H-imidazol-2-yl)piperidin-1-yl)but-2-en-1-one, 3-methyl-1-(2-(4-phenyl-1H-imidazole-2- yl)piperidin-1-yl)butan-1-one, 4-(2-(1-(2-(methylthio))propionyl)piperidin-2-yl)-1H-imidazole-4- base) benzonitrile, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzaldehyde, 4,4,4 -Trifluoro-2-methyl-1-(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, bicyclo[1.1.1]pentan- 1-yl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclobutyl(2-(5-(3-fluorophenyl)-1H-imidazole) -2-yl)piperidin-1-yl)methanone, cyclopentyl(2-(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, cyclopropyl(2 -(4-phenyl-1H-imidazol-2-yl)piperidin-1-yl)methanone, 4-(2-(1-(2-(methylthio)propionyl)piperidine-2- methyl)-1H-imidazol-5-yl)benzoate, N-(2-hydroxyethyl)-4-(2-(1-(2-(methylthio)propionyl)piperidine-2 -(yl)-1H-imidazol-4-yl)benzenesulfonamide, 2-(methylthio)-1-(2-(5-(3-nitrophenyl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, N-(4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazole-4- base)phenyl)methanesulfonamide, 2-(methylthio)-1-(2-(5-(4-nitrophenyl)-1H-imidazol-2-yl)piperidin-1-yl) Propan-1-one, 1-(sec-butylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2 -(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(isopropylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl )piperidine, 1-(isopropylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl) )sulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((1-(methylthio)ethyl)sulfonyl)-2-( 5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)prop-2-yl)sulfinyl)-2-(5-(p-toluene) base)-1H-imidazol-2-yl)piperidine, 1-((2-(methylthio)propan-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazole -2-yl)piperidine, 1-(but-3-en-2-ylsulfinyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-( But-3-en-2-ylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfinyl) )-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine, 1-(pent-3-en-2-ylsulfonyl)-2-(5-(p-tolyl) -1H-imidazol-2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfinyl)-2-(5-(p-tolyl)-1H-imidazole- 2-yl)piperidine, 1-((2-methylbut-3-en-2-yl)sulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine , 1-(2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2- (Methylsulfonyl)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)propan-1-one, 1-(4-hydroxy-2 -(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one, 1-(5-hydroxy-2-( 5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan-1-one□1-(4-hydroxy-2-(5- (p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)- 1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(2-(5-(4-(hydroxymethyl)phenyl))-1H-imidazole- 2-yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazole-2- yl)piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl) Piperidin-1-yl)-2-(methylsulfonyl)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine -1-yl)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine-1 -yl)-2-methylbutan-1-one, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazole)-2-yl)piperidin-1-yl)-2 -(methylsulfonyl)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-( Methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan -1-one, 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methanesulfonyl)propan-1- Ketone, 1-(2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)-propan- 1-one, 1-(4-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1 -Ketone, 1-(5-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1- Ketone, 1-(2-hydroxy-6-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one , 1-(3-hydroxy-2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylsulfinyl)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio)propan- 1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-(methylthio Generation) propan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2- (Methylthio)propan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)-phenyl)-1H-imidazol-2-yl)piperidine-1- base)-2-(methylthio)propan-1-one, 1-(2-hydroxy-6-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piper Din-1-yl)-2-methylbutan-1-one, 1-(5-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piper Din-1-yl)-2-methylbutan-1-one, 1-(4-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piper Din-1-yl)-2-methylbutan-1-one, 1-(3-hydroxy-2-(5-(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piper Din-1-yl)-2-methylbutan-1-one, 4-(2-(1-(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzene Formaldehyde, 4-(2-(1-(2-(methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, 4-(2-(1-( 2-Methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)benzoic acid, (2,2-dimethylcyclopropyl)(2-(5-(p-tolyl)- 1H-imidazol-2-yl)piperidin-1-yl)methanone, 1-(2-(5-bromo-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan- 1-one, 1-(2-(5-(4-chlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 2-(4 -(2-(1-(2-(Methylthio)propionyl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1 -(2-methylbutyryl)piperidin-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2-(4-(2-(1-(2-methylbutyryl)piper Din-2-yl)-1H-imidazol-5-yl)phenyl)acetonitrile, 2,3-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl) Piperidin-1-yl)butan-1-one, 2-methyl-1-(2-(5-(o-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1 -Ketone, 2-methyl-1-(2-(5-(m-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 1-(2-(5 -(4-(hydroxymethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-2-methylbutan-1-one, 1-(isopropylsulfonyl)-2 -(5-(p-Tolyl)-1H-imidazol-2-yl)piperidine, 1-(sec-butylsulfonyl)-2-(5-(p-tolyl)-1H-imidazol-2-yl) Piperidine, 2-methyl-1-(2-(5-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one, 2 -(Methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperazin-1-yl)propan-1-one, 2-(methylthio )-1-(2-(4-(p-tolyl)oxazol-2-yl)piperidin-1-yl)propan-1-one, 2-methyl-1-(2-(4-(p Tolyl)oxazol-2-yl)piperidin-1-yl)butan-1-one or any combination thereof, usually 2-methyl-1-(2-(5-(p-tolyl)-1H -imidazol-2-yl)piperidin-1-yl)butan-1-one, 2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl) )piperidin-1-yl)propan-1-one, 2-methyl-2-(methylthio)-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl) Piperidin-1-yl)propan-1-one, 2,2-dimethyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl) But-3-en-1-one or combinations thereof.

其他合适的凉味剂包括但不限于1-异丙基-3,3,5,7-四甲基八氢苯并[c]异恶唑、5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑(包括(3aR,5R,7S,7aR)-5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑、(3aR,5R,7R,7aR)-5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑、(3aR,5R,7S,7aS)-5-(4-氟苯基)-1,3,3,5,7-五甲基八氢苯并[c]异恶唑，或它们的任何组合。Other suitable cooling agents include, but are not limited to, 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 5-(4-fluorophenyl)-1, 3,3,5,7-Pentamethyloctahydrobenzo[c]isoxazole (including (3aR,5R,7S,7aR)-5-(4-fluorophenyl)-1,3,3,5 ,7-pentamethyloctahydrobenzo[c]isoxazole, (3aR,5R,7R,7aR)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyl Octahydrobenzo[c]isoxazole, (3aR,5R,7S,7aS)-5-(4-fluorophenyl)-1,3,3,5,7-pentamethyloctahydrobenzo[c ]isoxazole, or any combination thereof.

适用于身体护理产品的清凉度修饰组合物Cooling modifying compositions suitable for use in body care products

在任何前述实施方案的一些实施方案中，清凉度修饰组合物包含通常包括在身体护理产品(例如适合施用于人类毛发或皮肤的产品)中的任何化合物、材料或它们的组合。In some embodiments of any of the preceding embodiments, the coolness modifying composition comprises any compound, material, or combination thereof typically included in body care products (eg, products suitable for application to human hair or skin).

在一些实施方案中，组合物包含一种或多种芳香剂(fragrance，香氛)。在一些实施方案中，至少一部分芳香剂可以被包封。合适的芳香剂包括芳香剂化合物的复杂混合物，这些芳香剂化合物经选择以提供任何所需的气味。在本公开的语境中，术语“芳香剂/香氛”与“香料”同义使用。通常用于香料领域并且适合于本公开的目的的芳香剂化合物在S.Arctander的PERFUME FLAVORS AND CHEMICALS,Vols.I and II(1969)以及THE MERCKINDEX,8th edition,Merck&Co.,Inc.Rahway,N.J.中更全面地描述。术语“芳香剂化合物”涵盖天然存在的以及已知用于香料的合成材料，以及动物油。芳香剂化合物还可以是香氛组合物中使用的任何天然油或提取物、或化学化合物。天然油和提取物描述于Guenther的THE ESSENTIAL OILS1949，并且可以包括来自合适植物的任何一下部分的提取物、压榨物、收集渗出物和蒸馏物：根、根茎(rhizomes)、鳞茎(bulbs)、球茎(corms)、茎、树皮、心材、叶、花、种子和水果。此类提取物和蒸馏物的例子包括柑橘类水果油例如橙、橘(mandarin)、葡萄柚、酸橙或柠檬的油，树油例如松树或雪松，草本油例如胡椒薄荷、百里香、薰衣草、罗勒、迷迭香、丁香，或花提取物例如玫瑰、茉莉、铃兰或天竺葵的油。In some embodiments, the compositions include one or more fragrances. In some embodiments, at least a portion of the fragrance may be encapsulated. Suitable fragrances include complex mixtures of fragrance compounds selected to provide any desired odor. In the context of this disclosure, the term "perfume" is used synonymously with "perfume." Fragrance compounds commonly used in the fragrance field and suitable for the purposes of the present disclosure are described in S. Arctander, PERFUME FLAVORS AND CHEMICALS, Vols. I and II (1969) and THE MERCK INDEX, 8th edition, Merck & Co., Inc. Rahway, N.J. Describe more fully. The term "perfume compound" encompasses naturally occurring as well as synthetic materials known for use in fragrances, as well as animal oils. The fragrance compound may also be any natural oil or extract, or chemical compound used in fragrance compositions. Natural oils and extracts are described in Guenther, THE ESSENTIAL OILS 1949, and may include extracts, presses, exudates and distillates from any of the following parts of suitable plants: roots, rhizomes, bulbs, Corms, stems, bark, heartwood, leaves, flowers, seeds and fruits. Examples of such extracts and distillates include citrus fruit oils such as orange, mandarin, grapefruit, lime or lemon, tree oils such as pine or cedar, herbal oils such as peppermint, thyme, lavender, basil , rosemary, clove, or flower extracts such as oils of rose, jasmine, lily of the valley, or geranium.

在一些实施方案中，身体护理组合物可包含一种或多种为头发或皮肤护理提供活性有益效果的成分，例如具有抗氧化活性的化合物。例如，在一些实施方案中，身体护理产品包含抗坏血酸，也称为维生素C，其是具有抗氧化活性的必需营养素。在一些实施方案中，身体护理组合物包含维生素E，其是指表现出自由基清除活性的八种结构相关的抗氧化剂化合物。这些化合物包括四种生育酚化合物和四种生育三烯酚化合物。在一些实施方案中，身体护理组合物包含白藜芦醇，其是天然存在于葡萄皮中的抗氧化剂化合物。在一些实施方案中，身体护理组合物包含某些寡肽，例如乙酰基六肽-8(也称为乙酰基六肽-3)，其是松弛皱纹的合成肽。还可以包括多种其他此类化合物，例如视黄醇、烟酰胺、辅酶Q10和各种多酚，例如类黄酮如儿茶素。这些活性成分的用量可以与其他身体护理产品中的典型用量相同。In some embodiments, body care compositions can include one or more ingredients that provide active benefits for hair or skin care, such as compounds with antioxidant activity. For example, in some embodiments, body care products include ascorbic acid, also known as vitamin C, which is an essential nutrient with antioxidant activity. In some embodiments, the body care composition includes vitamin E, which refers to eight structurally related antioxidant compounds that exhibit free radical scavenging activity. These compounds include four tocopherol compounds and four tocotrienol compounds. In some embodiments, the body care composition includes resveratrol, which is an antioxidant compound naturally found in grape skins. In some embodiments, body care compositions include certain oligopeptides, such as acetyl hexapeptide-8 (also known as acetyl hexapeptide-3), which is a wrinkle-relaxing synthetic peptide. A variety of other such compounds may also be included, such as retinol, nicotinamide, coenzyme Q10, and various polyphenols, such as flavonoids such as catechins. The amounts of these active ingredients can be the same as those typically found in other body care products.

本文公开的身体护理组合物可包括或掺入到任何合适类型的赋形剂(vehicle)和载体中。一般而言，赋形剂或载体将是皮肤病学上可接受的赋形剂或载体。赋形剂或载体的非限制性例子包括水、甘油、醇、油、含硅化合物、有机硅化合物和蜡。变化形式和其他合适的载体对于本领域技术人员来说将是显而易见的并且适合用于本公开的身体护理组合物中。在某些实施方案中，可以选择化合物、成分和试剂的浓度和组合，使得这些组合是化学相容的并且不形成从成品身体护理产品中沉淀的复合物。The body care compositions disclosed herein may include or be incorporated into any suitable type of vehicle and carrier. Generally, the excipient or carrier will be a dermatologically acceptable excipient or carrier. Non-limiting examples of excipients or carriers include water, glycerin, alcohols, oils, silicon-containing compounds, organosilicon compounds and waxes. Variations and other suitable carriers will be apparent to those skilled in the art and are suitable for use in the body care compositions of the present disclosure. In certain embodiments, concentrations and combinations of compounds, ingredients, and agents may be selected such that the combinations are chemically compatible and do not form complexes that precipitate from the finished body care product.

本文公开的身体护理组合物可被构造或配制为多种不同的形式。非限制性例子包括乳液(例如油包水、水包油包水、水包油、水包有机硅、有机硅包水、油包水包油、有机硅包水包油乳液等)、乳霜(creams)、乳剂(lotions)、溶液(例如水性或水醇性)、无水基质(例如口红和粉末)、凝胶、面膜、磨砂膏、身体润肤霜(body butters)、去角质霜和药膏。变化形式和其他结构对于本领域技术人员来说将是显而易见的并且适合用于本公开的身体护理组合物中。The body care compositions disclosed herein can be constructed or formulated in a variety of different forms. Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil-in-water, oil-in-water, silicone-in-water, water-in-silicone, oil-in-water-in-oil, water-in-water-in-silicone oil-in-water emulsions, etc.), creams Creams, lotions, solutions (e.g. aqueous or hydroalcoholic), anhydrous bases (e.g. lipsticks and powders), gels, masks, scrubs, body butters, exfoliants and ointment. Variations and other structures will be apparent to those skilled in the art and are suitable for use in the body care compositions of the present disclosure.

可以使用多种其他成分，例如通常用于美容产品(cosmetics)、皮肤护理产品或头发护理产品的成分。CTFA INTERNATIONAL COSMETIC INGREDIENT DICTIONARY ANDHANDBOOK(2004年和2008年)描述了可用于本发明公开的组合物中的多种非限制性成分。这些成分类别的例子包括：芳香剂(人造的和天然的；例如葡萄糖酸、苯氧基乙醇和三乙醇胺)、染料和色素成分(例如Blue 1、Blue 1Lake、Red 40、二氧化钛、D&C蓝色4号、D&C绿色5号、D&C橙色4号、D&C红色17号、D&C红色33号、D&C紫罗兰2号、D&C黄色10号和D&C黄色11号)、调味剂或香味剂(例如甜叶菊(Stevia rebaudiana)(甜叶)提取物和薄荷醇)、吸附剂、润滑剂、溶剂、保湿剂(包括例如润肤剂、润湿剂、成膜剂、封闭剂和影响皮肤自然保湿机制的试剂)、防泼水剂(water-reppelants)、UV吸收剂(物理和化学吸收剂，例如对氨基苯甲酸(“PABA”)及相应的PABA衍生物、二氧化钛、氧化锌等)、精油、维生素(如B、D、E和K)、微量金属(例如锌、钙和硒)、抗刺激剂(例如类固醇和非类固醇抗炎药)、植物提取物(例如芦荟、洋甘菊、黄瓜提取物、银杏叶、人参和迷迭香)、抗微生物剂、抗氧化剂(例如BHT和生育酚)、螯合剂(例如，EDTA二钠和EDTA四钠)、防腐剂(例如对羟基苯甲酸甲酯和对羟基苯甲酸丙酯)、pH调节剂(例如氢氧化钠和柠檬酸)、吸收剂(例如淀粉辛烯基琥珀酸铝、高岭土、玉米淀粉、燕麦淀粉、环糊精、滑石粉和沸石)、皮肤漂白和增白剂(例如氢醌和烟酰胺乳酸酯)、保湿剂(例如山梨醇、尿素、甲基葡萄糖聚醚20、糖同分异构体(saccharide isomerate)和甘露醇)、去角质剂、防水剂(例如硬脂酸氢氧化镁/氢氧化铝)、皮肤调理剂(例如芦荟提取物、尿囊素、红没药醇、神经酰胺、聚二甲基硅氧烷、透明质酸、生物糖胶-1、乙基己基甘油、戊二醇、氢化聚癸烯、油酸辛基十二烷基酯和甘草酸二钾)。以下小节中提供了这些成分中的一些的进一步非限制性例子。A variety of other ingredients can be used, such as those commonly used in cosmetics, skin care products or hair care products. CTFA INTERNATIONAL COSMETIC INGREDIENT DICTIONARY ANDHANDBOOK (2004 and 2008) describes a variety of non-limiting ingredients that can be used in the compositions disclosed herein. Examples of these ingredient categories include: fragrances (artificial and natural; such as gluconic acid, phenoxyethanol, and triethanolamine), dyes and color ingredients (such as Blue 1, Blue 1Lake, Red 40, Titanium Dioxide, D&C Blue 4 No., D&C Green No. 5, D&C Orange No. 4, D&C Red No. 17, D&C Red No. 33, D&C Violet No. 2, D&C Yellow No. 10 and D&C Yellow No. 11), flavoring or fragrance (such as Stevia rebaudiana) ) (sweet leaf) extract and menthol), adsorbents, lubricants, solvents, humectants (including, for example, emollients, humectants, film-forming agents, occlusive agents and agents that affect the skin's natural moisturizing mechanism), anti- Water-reppelants, UV absorbers (physical and chemical absorbers, such as para-aminobenzoic acid ("PABA") and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, vitamins (such as B, D , E and K), trace metals (e.g. zinc, calcium and selenium), counter-irritants (e.g. steroids and non-steroidal anti-inflammatory drugs), plant extracts (e.g. aloe vera, chamomile, cucumber extract, ginkgo leaf, ginseng and amygdala). rosemary), antimicrobials, antioxidants (such as BHT and tocopherol), chelating agents (such as disodium EDTA and tetrasodium EDTA), preservatives (such as methylparaben and propylparaben) , pH adjusters (such as sodium hydroxide and citric acid), absorbents (such as aluminum starch octenylsuccinate, kaolin, corn starch, oat starch, cyclodextrin, talc and zeolite), skin bleaching and whitening agents (e.g. hydroquinone and nicotinamide lactate), humectants (e.g. sorbitol, urea, methylglucose polyether 20, saccharide isomerate and mannitol), exfoliants, water repellents ( such as magnesium hydroxide stearate/aluminum hydroxide), skin conditioning agents (such as aloe vera extract, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, biosaccharide gum- 1. Ethylhexylglycerol, pentylene glycol, hydrogenated polydecene, octyldodecyl oleate and dipotassium glycyrrhizinate). Further non-limiting examples of some of these ingredients are provided in the following subsections.

在一些实施方案中，身体护理组合物包含一种或多种UV吸收剂或反射剂。合适的UV吸收剂或反射剂包括化学和物理防晒物质。化学防晒物质的非限制性例子包括对氨基苯甲酸(PABA)、PABA酯(PABA甘油酯、PABA戊基二甲酯和PABA辛基二甲酯)、PABA丁酯、PABA乙酯、PABA乙基二羟丙酯、二苯甲酮类(羟苯甲酮、磺异苯甲酮、二苯甲酮和二苯甲酮1至12)、肉桂酸盐/酯(甲氧基肉桂酸辛酯(oxtinoxate)、对甲氧基肉桂酸异戊酯、辛基甲氧基肉桂酸酯、西诺沙酯(cinoxate)、二异丙基肉桂酸甲酯、甲氧基肉桂酸DEA盐、二异丙基肉桂酸乙酯、甘油辛酸酯二甲氧基肉桂酸酯和甲氧基肉桂酸乙酯)、肉桂酸酯类、水杨酸盐/酯(均甲基水杨酸酯、水杨酸苄酯、乙二醇水杨酸酯、水杨酸异丙基苄酯等)、邻氨基苯甲酸盐/酯、尿刊酸乙酯、胡莫柳酯(homosalate)、水杨酸辛酯(octisalate)、二苯甲酰基甲烷衍生物(例如阿伏苯宗)、奥克立林、辛基三嗪酮、二没食子三油酸酯、氨基苯甲酸甘油酯、2-羟基-1,4-萘醌(lawsone)和二羟基丙酮、乙基己基三嗪酮、二辛基丁酰胺三嗪酮、亚苄基丙二酸酯聚硅氧烷、对苯二亚甲基二樟脑磺酸、苯基二苯并咪唑四磺酸二钠、二乙氨基羟基苯甲酰基苯甲酸己酯、双二乙氨基羟基苯甲酰基苯甲酸酯、双苯并恶唑基苯基乙基己基亚氨基三嗪、甲酰曲唑三硅氧烷、亚甲基双苯并三唑基四甲基丁基苯酚，以及双乙基己氧基苯酚甲氧基苯基三嗪，4-甲基亚苄基樟脑和4-甲氧基肉桂酸异戊酯。物理防晒物质的非限制性例子包括高岭土、滑石、凡士林和金属氧化物(例如二氧化钛和氧化锌)。In some embodiments, body care compositions include one or more UV absorbers or reflectors. Suitable UV absorbers or reflectors include chemical and physical sunscreen substances. Non-limiting examples of chemical sunscreen substances include para-aminobenzoic acid (PABA), PABA esters (PABA glyceride, PABA pentyl dimethyl ester, and PABA octyl dimethyl ester), PABA butyl ester, PABA ethyl ester, PABA ethyl Dihydroxypropyl ester, benzophenones (oxybenzophenone, sulfisobenzophenone, benzophenone and benzophenone 1 to 12), cinnamate/ester (oxtinoxate ), isoamyl p-methoxycinnamate, octylmethoxycinnamate, cinoxate, methyl diisopropylcinnamate, DEA salt of methoxycinnamate, diisopropyl Ethyl cinnamate, glyceryl caprylate dimethoxycinnamate and ethyl methoxycinnamate), cinnamic acid esters, salicylates/esters (same methyl salicylate, benzyl salicylate ester, ethylene glycol salicylate, isopropyl benzyl salicylate, etc.), anthranilate/ester, ethyl urocanate, homosalate (homosalate), octyl salicylate (octisalate ), dibenzoylmethane derivatives (e.g. avobenzone), octocrylene, octyltriazone, dipallotrioleate, glyceryl aminobenzoate, 2-hydroxy-1,4-naphthalene Quinone (lawsone) and dihydroxyacetone, ethylhexyltriazone, dioctylbutylamidotriazone, benzylidene malonate polysiloxane, terephthalimethylene dicamphorsulfonic acid, phenyl Disodium dibenzimidazole tetrasulfonate, diethylaminohydroxybenzoylhexyl benzoate, bisdiethylaminohydroxybenzoyl benzoate, bisbenzoxazolylphenylethylhexyl iminotriazine , formyltrisiloxane, methylenebisbenzotriazolyltetramethylbutylphenol, and bisethylhexyloxyphenol methoxyphenyltriazine, 4-methylbenzylidene camphor and isoamyl 4-methoxycinnamate. Non-limiting examples of physical sunscreen materials include kaolin, talc, petrolatum, and metal oxides (eg, titanium dioxide and zinc oxide).

在一些实施方案中，身体护理组合物包含一种或多种保湿剂(moisturizingagents)。可以使用的保湿剂的非限制性例子包括氨基酸、硫酸软骨素、双甘油、赤藓糖醇、果糖、葡萄糖、甘油、甘油聚合物、乙二醇、1,2,6-己三醇、蜂蜜、透明质酸、氢化蜂蜜、氢化淀粉水解物、肌醇、乳糖醇、麦芽糖醇、麦芽糖、甘露醇、天然保湿因子、PEG-15丁二醇、聚甘油山梨醇、吡咯烷酮羧酸的盐、PCA钾、丙二醇、糖同分异构体、葡萄糖醛酸钠、PCA钠、山梨糖醇、蔗糖、海藻糖、尿素和木糖醇。其他非限制性例子包括乙酰化羊毛脂、乙酰化羊毛脂醇、丙氨酸、藻类提取物、库拉索芦荟(Aloe barbadensis)、库拉索芦荟提取物、库拉索芦荟凝胶、药蜀葵(Althaea officinalis)提取物、杏(Prunus armeniaca)仁油、精氨酸、精氨酸天冬氨酸盐/酯、山金车(Arnica montana)提取物、天冬氨酸、鳄梨(Persea gratissima)油、屏障鞘脂(barrier sphingolipids)、丁醇、蜂蜡、山嵛醇、β-谷甾醇、垂枝桦(Betula alba)树皮提取物、琉璃苣(Borago officinalis)提取物、假叶树(Ruscus aculeatus)提取物、丁二醇、金盏花(Calendula officinalis)提取物、金盏花油、小烛树(Euphorbia cerifera)蜡、低芥酸菜籽(canola，卡诺拉)油、辛酸/癸酸甘油三酯、小豆蔻(Elettaria cardamomum)油、巴西棕榈(Copernicia cerifera)蜡、胡萝卜(Daucus carota sativa)油、蓖麻(Ricinus communis)油、神经酰胺、地蜡、鲸蜡硬脂醇聚醚-5、鲸蜡硬脂醇聚醚-12、鲸蜡硬脂醇聚醚-20、鲸蜡硬脂基辛酸酯、鲸蜡醇聚醚-20、鲸蜡醇聚醚-24、乙酸鲸蜡醇酯、辛酸鲸蜡醇酯、棕榈酸鲸蜡醇酯、洋甘菊(Anthemis nobilis)油、胆固醇，胆固醇酯、胆甾醇羟基硬脂酸酯、柠檬酸、快乐鼠尾草(Salvia sclarea)油、可可(Theobroma cacao)脂、可可辛酸酯/癸酸酯、椰子(Cocos nucifera)油、胶原蛋白、胶原蛋白氨基酸、玉米(Zea mays)油、脂肪酸、油酸癸酯、聚二甲基硅氧烷共聚醇、聚二甲基硅氧烷醇、己二酸二辛酯、琥珀酸二辛酯、二季戊四醇六辛酸酯/六癸酸酯、DNA、赤藓糖醇、乙氧基二甘醇、亚油酸乙酯、蓝桉(Eucalyptus globulus)油、月见草(Oenothera biennis)油、脂肪酸、斑点老鹳草(Geranium maculatum)油、葡萄糖胺、葡萄糖谷氨酸酯、谷氨酸、甘油聚醚-26、甘油、丙三醇、二硬脂酸甘油酯、羟基硬脂酸甘油酯、月桂酸甘油酯、亚油酸甘油酯、肉豆蔻酸甘油酯、油酸甘油酯、硬脂酸甘油酯、硬脂酸甘油酯SE、甘氨酸、硬脂酸乙二醇酯、硬脂酸乙二醇酯SE、葡糖氨基葡聚糖、葡萄(Vitis vinifera)种子油、榛子(Corylus americana，美国榛子)坚果油、榛子(Corylus avellana，欧洲榛子)坚果油、己二醇、透明质酸、混合红花(Carthamus tinctorius)油、氢化蓖麻油、氢化椰油甘油酯、氢化椰子油、氢化羊毛脂、氢化卵磷脂、氢化棕榈甘油酯、氢化棕榈仁油、氢化大豆油、氢化牛脂酸甘油酯、氢化植物油、水解胶原蛋白、水解弹性蛋白、水解葡糖氨基葡聚糖、水解角蛋白、水解大豆蛋白、羟基化羊毛脂、羟基脯氨酸、硬脂酸异鲸蜡醇酯、硬脂酰基硬脂酸异鲸蜡醇酯、油酸异癸酯、异硬脂酸异丙酯、羊毛酸异丙酯、肉豆蔻酸异丙酯、棕榈酸异丙酯、硬脂酸异丙酯、异硬脂酰胺DEA、异硬脂酸、乳酸异硬脂酯、新戊酸异硬脂酯、茉莉(Jasminum officinale)油、霍霍巴(Buxuschinensis)油、巨藻(kelp)、石栗(Aleurites moluccana)坚果油、乳酰胺MEA、羊毛脂醇聚醚-16、羊毛脂醇聚醚-10乙酸酯、羊毛脂、羊毛脂酸、羊毛脂醇、羊毛脂油、羊毛脂蜡、薰衣草(Lavandula angustifolia，狭叶薰衣草)油、卵磷脂、柠檬(Citrus medica limonum)油、亚油酸、亚麻酸、澳洲坚果(Macadamia ternifolia)油、麦芽糖醇、母菊(Chamomillarecutita)油、甲基葡萄糖倍半硬脂酸酯、甲基硅烷醇PCA、矿物油、貂油、被孢霉油、乳酸肉豆蔻酯、肉豆蔻酸肉豆蔻酯、丙酸肉豆蔻酯、新戊二醇二辛酸酯/二癸酸酯、辛基十二烷醇、肉豆蔻酸辛基十二烷基酯、硬脂酰基硬脂酸辛基十二烷基酯、羟基硬脂酸辛酯、棕榈酸辛酯、水杨酸辛酯、硬脂酸辛酯、油酸、橄榄(Olea europaea)油、橙(Citrus aurantiumdulcis)油、棕榈(Elaeis guineensis)油、棕榈酸、泛硫乙胺、泛醇、泛醇基乙基醚、石蜡、PCA、桃(Prunus persica)仁油、花生(Arachis hypogaea)油、PEG-8C12-18酯、PEG-15椰油烷基胺、PEG-150二硬脂酸酯、PEG-60异硬脂酸甘油酯、PEG-5硬脂酸甘油酯、PEG-30硬脂酸甘油酯、PEG-7氢化蓖麻油、PEG-40氢化蓖麻油、PEG-60氢化蓖麻油、PEG-20甲基葡萄糖倍半硬脂酸酯、PEG-40失水山梨糖醇全油酸酯、PEG-5大豆甾醇、PEG-10大豆甾醇、PEG-2硬脂酸酯、PEG-8硬脂酸酯、PEG-20硬脂酸酯、PEG-32硬脂酸酯、PEG-40硬脂酸酯、PEG-50硬脂酸酯、PEG-100硬脂酸酯、PEG-150硬脂酸酯、十五内酯、胡椒薄荷(Mentha piperita)油、石蜡脂(Petrolatum)、磷脂、浮游生物提取物、多氨基酸多糖缩合物、聚甘油-3二异硬脂酸酯、聚季铵盐-24、聚山梨醇酯20、聚山梨醇酯40、聚山梨醇酯60、聚山梨醇酯80、聚山梨醇酯85、肉豆蔻酸钾、棕榈酸钾、丙二醇、丙二醇二辛酸酯/二癸酸酯、丙二醇二辛酸酯、丙二醇二壬酸酯、丙二醇月桂酸酯、丙二醇硬脂酸酯、丙二醇硬脂酸酯SE、PVP、吡哆醇二棕榈酸酯、视黄醇、视黄醇棕榈酸酯、米(Oryza sativa)糠油、RNA、迷迭香(Rosmarinus officinalis)油、玫瑰油、红花(Carthamus tinctorius)油、鼠尾草(Salvia officinalis)油、檀香(Santalumalbum)油、丝氨酸、血清蛋白、芝麻(Sesamumindicum)油、乳木果(Butyrospermum parkii)油、蚕丝粉、硫酸软骨素钠、透明质酸钠、乳酸钠、棕榈酸钠、PCA钠、聚谷氨酸钠、可溶性胶原蛋白、失水山梨醇月桂酸酯、失水山梨醇油酸酯、失水山梨醇棕榈酸酯、失水山梨醇倍半油酸酯、失水山梨醇硬脂酸酯、山梨糖醇、大豆(Glycine soja)油、鞘脂、角鲨烷、角鲨烯、硬脂酰胺MEA-硬脂酸酯、硬脂酸、硬脂氧基聚二甲基硅氧烷、硬脂氧基三甲基硅烷、硬脂醇、甘草次酸硬脂醇酯、庚酸硬脂醇酯、硬脂酸硬脂醇酯、向日葵(Helianthus annuus)籽油、甜杏仁(Prunus amygdalus dulcis)油、合成蜂蜡、生育酚乙酸酯、生育酚亚油酸酯、三山嵛酸甘油酯(tribehenin)、新戊酸十三烷基酯、硬脂酸十三烷基酯、三乙醇胺、三硬脂酸甘油酯(tristearin)、尿素、植物油、水、蜡、小麦(Triticum vulgare)胚芽油和依兰(Canangaodorata)油。In some embodiments, body care compositions include one or more moisturizing agents. Non-limiting examples of humectants that can be used include amino acids, chondroitin sulfate, diglycerol, erythritol, fructose, glucose, glycerol, glycerol polymers, ethylene glycol, 1,2,6-hexanetriol, honey , hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolyzate, inositol, lactitol, maltitol, maltose, mannitol, natural moisturizing factor, PEG-15 butylene glycol, polyglycerol sorbitol, salt of pyrrolidone carboxylic acid, PCA Potassium, propylene glycol, sugar isomers, sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose, urea and xylitol. Other non-limiting examples include acetylated lanolin, acetylated lanolin alcohol, alanine, algae extract, Aloe barbadensis, Aloe vera extract, Aloe vera gel, marshmallow (Althaea officinalis) extract, apricot (Prunus armeniaca) kernel oil, arginine, arginine aspartate/ester, arnica (Arnica montana) extract, aspartic acid, avocado (Persea gratissima) ) oil, barrier sphingolipids, butanol, beeswax, behenyl alcohol, beta-sitosterol, Betula alba bark extract, Borago officinalis extract, Ruscus pseudoleaf ( Ruscus aculeatus) extract, butylene glycol, Calendula officinalis extract, calendula oil, Euphorbia cerifera wax, canola (canola) oil, caprylic acid/ Capric triglyceride, cardamom (Elettaria cardamomum) oil, Brazilian palm (Copernicia cerifera) wax, carrot (Daucus carota sativa) oil, castor (Ricinus communis) oil, ceramide, ozokerite, cetearyl alcohol poly Ether-5, Cetearyl-12, Cetearyl-20, Cetearyl Caprylate, Ceteth-20, Cetearyl-24, Acetic Acid Cetyl alcohol ester, cetyl alcohol caprylate, cetyl palmitate, chamomile (Anthemis nobilis) oil, cholesterol, cholesteryl ester, cholesteryl hydroxystearate, citric acid, clary sage (Salvia sclarea) oil , Theobroma cacao butter, cocoa caprylate/caprate, coconut (Cocos nucifera) oil, collagen, collagen amino acids, corn (Zea mays) oil, fatty acids, decyl oleate, polydimethylsilane Oxane copolyol, dimethiconol, dioctyl adipate, dioctyl succinate, dipentaerythritol hexacaprylate/hexadecanoate, DNA, erythritol, ethoxydioic acid Glycol, ethyl linoleate, Eucalyptus globulus oil, Oenothera biennis oil, fatty acids, Geranium maculatum oil, glucosamine, glucose glutamate, glutamic acid , Glyceryl polyether-26, glycerin, glycerin, glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glyceryl myristate, glyceryl oleate, glyceryl oleate, Glyceryl stearate, glyceryl stearate SE, glycine, ethylene glycol stearate, ethylene glycol stearate SE, glycosaminoglucan, grape (Vitis vinifera) seed oil, hazelnut (Corylus americana) , American hazelnut) nut oil, hazelnut (Corylus avellana, European filbert) nut oil, hexylene glycol, hyaluronic acid, mixed safflower (Carthamus tinctorius) oil, hydrogenated castor oil, hydrogenated coconut glycerides, hydrogenated coconut oil, hydrogenated Lanolin, hydrogenated lecithin, hydrogenated palm glyceryl ester, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow glyceryl ester, hydrogenated vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycan, hydrolyzed keratin, Hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, isocetyl stearate, isocetyl stearate, isodecyl oleate, isopropyl isostearate, wool Isopropyl acid, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, isostearic acid, isostearyl lactate, isostearyl pivalate, Jasmine (Jasminum officinale) oil, jojoba (Buxuschinensis) oil, kelp, Aleurites moluccana nut oil, lactamide MEA, lanolin polyether-16, lanolin polyether-10 acetate , lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax, lavender (Lavandula angustifolia) oil, lecithin, lemon (Citrus medica limonum) oil, linoleic acid, linolenic acid, macadamia nut (Macadamia ternifolia) oil, maltitol, Chamomile (Chamomillarecutita) oil, methylglucose sesquistearate, methylsilanol PCA, mineral oil, mink oil, Mortierella oil, myristyl lactate, nutmeg Myristyl acid, myristyl propionate, neopentyl glycol dicaprylate/dicaprate, octyldodecanol, octyldodecyl myristate, stearoyl octyldeca stearate Dialkyl ester, octyl hydroxystearate, octyl palmitate, octyl salicylate, octyl stearate, oleic acid, olive (Olea europaea) oil, orange (Citrus aurantiumdulcis) oil, palm (Elaeis guineensis) oil, palm Acid, pantethine, panthenol, panthenyl ethyl ether, paraffin, PCA, peach (Prunus persica) kernel oil, peanut (Arachis hypogaea) oil, PEG-8C12-18 ester, PEG-15 cocoalkyl Amine, PEG-150 distearate, PEG-60 glyceryl isostearate, PEG-5 glyceryl stearate, PEG-30 glyceryl stearate, PEG-7 hydrogenated castor oil, PEG-40 hydrogenated Castor oil, PEG-60 hydrogenated castor oil, PEG-20 methyl glucose sesquistearate, PEG-40 sorbitan per oleate, PEG-5 soybean sterol, PEG-10 soybean sterol, PEG- 2 stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate, PEG-100 stearate Fatty acid ester, PEG-150 stearate, pentalactone, Mentha piperita oil, Petrolatum, phospholipids, plankton extract, polyamino acid polysaccharide condensate, polyglycerol-3 diiso Stearate, Polyquaternium-24, Polysorbate 20, Polysorbate 40, Polysorbate 60, Polysorbate 80, Polysorbate 85, Potassium Myristate, Potassium Palmitate , propylene glycol, propylene glycol dioctrylate/dicaprate, propylene glycol dioctanoate, propylene glycol dinonanoate, propylene glycol laurate, propylene glycol stearate, propylene glycol stearate SE, PVP, pyridoxine di Palmitate, retinol, retinyl palmitate, rice (Oryza sativa) bran oil, RNA, rosemary (Rosmarinus officinalis) oil, rose oil, safflower (Carthamus tinctorius) oil, sage (Salvia officinalis) ) oil, sandalwood (Santalumalbum) oil, serine, serum protein, sesame (Sesamumindicum) oil, shea butter (Butyrospermum parkii) oil, silk powder, chondroitin sulfate sodium, sodium hyaluronate, sodium lactate, sodium palmitate, PCA Sodium, sodium polyglutamate, soluble collagen, sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate, sorbitan Stearate, sorbitol, soybean (Glycine soja) oil, sphingolipid, squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxy dimethicone Oxane, stearoxytrimethylsilane, stearyl alcohol, stearyl glycyrrhetinate, stearyl enanthate, stearyl stearate, sunflower (Helianthus annuus) seed oil, sweet almond ( Prunus amygdalus dulcis) oil, synthetic beeswax, tocopheryl acetate, tocopherol linoleate, tribehenin, tridecyl pivalate, tridecyl stearate, tridecyl pivalate Ethanolamine, tristearin, urea, vegetable oil, water, wax, wheat (Triticum vulgare) germ oil and ylang ylang (Canangaodorata) oil.

在一些实施方案中，本文所公开的身体护理组合物包含一种或多种抗氧化剂，例如，除了上文所公开的那些之外或与上文所公开的那些抗氧化剂组合。例如，在一些实施方案中，这些另外的抗氧化剂中的一种或多种可以与抗坏血酸、维生素E或它们的组合组合使用。可以使用的抗氧化剂的非限制性例子包括乙酰半胱氨酸、抗坏血酸衍生物如抗坏血酸多肽、抗坏血酸二棕榈酸酯、抗坏血酸甲基硅烷醇果胶酸酯、抗坏血酸棕榈酸酯、抗坏血酸硬脂酸酯，BHA、BHT、叔丁基氢醌、半胱氨酸、半胱氨酸HCl、二戊基氢醌、二叔丁基氢醌、硫代二丙酸二鲸蜡醇酯、二油基生育酚甲基硅烷醇、抗坏血酸硫酸酯二钠、硫代二丙酸二硬脂基酯、硫代二丙酸二(十三烷基)酯、没食子酸十二烷基酯、异抗坏血酸、抗坏血酸酯、阿魏酸乙酯、阿魏酸、没食子酸酯、氢醌、硫代乙醇酸异辛酯、曲酸、抗坏血酸镁、抗坏血酸磷酸酯镁、甲基硅烷醇抗坏血酸酯、天然植物抗氧化剂例如绿茶或葡萄籽提取物，去甲二氢愈创木酸、没食子酸辛酯、苯基硫代乙醇酸、抗坏血酸生育酚磷酸酯钾、亚硫酸钾、没食子酸丙酯、醌、迷迭香酸、抗坏血酸钠、亚硫酸氢钠、异抗坏血酸钠、焦亚硫酸钠、亚硫酸钠、超氧化物歧化酶、硫代乙醇酸钠、山梨糖醇糠醛、硫代二甘醇、硫代二甘醇酰胺、硫代二甘醇酸、硫代乙醇酸、硫代乳酸、硫代水杨酸、生育酚聚醚-5、生育酚聚醚-10、生育酚聚醚-12、生育酚聚醚-18、生育酚聚醚-50、托可索伦(tocophersolan)、乙酸生育酚酯、亚油酸生育酚酯、烟酸生育酚酯、琥珀酸生育酚酯和亚磷酸三(壬基苯基)酯。In some embodiments, body care compositions disclosed herein include one or more antioxidants, for example, in addition to or in combination with those disclosed above. For example, in some embodiments, one or more of these additional antioxidants may be used in combination with ascorbic acid, vitamin E, or combinations thereof. Non-limiting examples of antioxidants that may be used include acetylcysteine, ascorbic acid derivatives such as ascorbic acid polypeptides, ascorbyl dipalmitate, ascorbyl methylsilanol pectate, ascorbyl palmitate, and ascorbyl stearate. , BHA, BHT, tert-butylhydroquinone, cysteine, cysteine HCl, dipentylhydroquinone, di-tert-butylhydroquinone, cetyl thiodipropionate, dioleyl tocopherol methylsilane Alcohol, disodium ascorbyl sulfate, distearyl thiodipropionate, tridecyl thiodipropionate, dodecyl gallate, isoascorbic acid, ascorbyl ester, ferulic acid Ethyl ester, ferulic acid, gallate, hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbate, natural plant antioxidants such as green tea or grape seed extract Ingredients, nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid, potassium ascorbyl tocopherol phosphate, potassium sulfite, propyl gallate, quinone, rosmarinic acid, sodium ascorbate, sulfite Sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycolate, sorbitol furfural, thiodiglycol, thiodiglycolamide, thiodiglycolic acid, sulfur Glycolic acid, thiolactic acid, thiosalicylic acid, tocopherol polyether-5, tocopherol polyether-10, tocopherol polyether-12, tocopherol polyether-18, tocopherol polyether-50, tocopherol polyether-50 Tocophersolan, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate and tris(nonylphenyl) phosphite.

在一些实施方案中，身体护理组合物包含一种或多种结构化剂。在某些实施方案中，结构剂有助于向组合物提供有助于稳定性的流变特性。在一些实施方案中，结构化剂还可以充当乳化剂或表面活性剂。结构化剂的非限制性例子包括硬脂酸、棕榈酸、硬脂醇、鲸蜡醇、山嵛醇、硬脂酸、棕榈酸、具有平均约1至约21个环氧乙烷单元的硬脂醇的聚乙二醇醚、具有平均约1至约5个环氧乙烷单元的鲸蜡醇的聚乙二醇醚，以及它们的混合物。In some embodiments, body care compositions include one or more structuring agents. In certain embodiments, structuring agents help provide rheological properties to the composition that contribute to stability. In some embodiments, structuring agents may also act as emulsifiers or surfactants. Non-limiting examples of structuring agents include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, stearic acid having an average of about 1 to about 21 ethylene oxide units. Polyglycol ethers of fatty alcohols, polyglycol ethers of cetyl alcohol having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof.

在一些实施方案中，身体护理组合物包含一种或多种乳化剂。乳化剂可以降低相间的界面张力，并改善乳液的配方和稳定性。乳化剂可以是非离子的、阳离子的、阴离子的和两性离子的乳化剂。非限制性例子包括甘油的酯、丙二醇的酯、聚乙二醇的脂肪酸酯、聚丙二醇的脂肪酸酯、山梨糖醇的酯、山梨糖醇酐的酯、羧酸共聚物、葡萄糖的酯和醚、乙氧基化的醚、乙氧基化的醇、磷酸烷基酯、聚氧乙烯脂肪醚磷酸酯、脂肪酸酰胺、酰基乳酸酯、皂、TEA硬脂酸酯、DEA油醇聚醚-3磷酸酯、聚乙二醇20失水山梨糖醇单月桂酸酯(聚山梨醇酯20)、聚乙二醇5大豆甾醇、硬脂醇聚醚-2、硬脂醇聚醚-20、硬脂醇聚醚-21、鲸蜡硬脂醇聚醚-20、鲸蜡硬脂基葡糖苷、鲸蜡硬脂醇、C12-13链烷醇聚醚-3、PPG-2甲基葡萄糖醚二硬脂酸酯、PPG-5-鲸蜡醇聚醚-20、双-PEG/PPG-20/20聚二甲基硅氧烷、鲸蜡醇聚醚-10、聚山梨醇酯80、磷酸鲸蜡酯、鲸蜡基磷酸酯钾、鲸蜡基磷酸二乙醇胺、聚山梨醇酯60、硬脂酸甘油酯、PEG-100硬脂酸酯、花生醇、花生基葡糖苷，以及它们的混合物。In some embodiments, body care compositions include one or more emulsifiers. Emulsifiers can reduce the interfacial tension between phases and improve the formulation and stability of emulsions. Emulsifiers may be nonionic, cationic, anionic and zwitterionic emulsifiers. Non-limiting examples include esters of glycerol, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of sorbitol, carboxylic acid copolymers, esters of glucose and ethers, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, TEA stearate, DEA oleyl alcohol poly Ether-3 Phosphate, Polyethylene Glycol 20 Sorbitan Monolaurate (Polysorbate 20), Polyethylene Glycol 5 Soybean Sterol, Stearyl Polyether-2, Stearyl Polyether- 20. Stearyl-21, Cetearyl-20, Cetearyl Glucoside, Cetearyl Alcohol, C12-13 Alkanol-3, PPG-2 Methyl Glucose ether distearate, PPG-5-ceteth-20, bis-PEG/PPG-20/20 dimethicone, ceteth-10, polysorbate 80 , Cetyl Phosphate, Potassium Cetyl Phosphate, Diethanolamine Cetyl Phosphate, Polysorbate 60, Glyceryl Stearate, PEG-100 Stearate, Arachidol, Arachidyl Glucoside, and them mixture.

在一些实施方案中，身体护理组合物包含一种或多种含有机硅(silicone)化合物。含有机硅化合物的非限制性例子包括分子主链由交替的硅和氧原子以及连接至硅原子的侧基组成的聚合物产品家族的任何成员。通过改变-Si-O-链长、侧基和交联，有机硅可以合成为多种材料。它们的稠度可以从液体变化到凝胶再变化到固体。适用于本文公开的身体护理组合物中的含有机硅的化合物包括但不限于本领域普通技术人员通常已知的那些。非限制性例子包括有机硅油(例如挥发性油和非挥发性油)、凝胶和固体。在某些实施方案中，含硅化合物包括有机硅油，例如聚有机硅氧烷。聚有机硅氧烷的非限制性例子包括聚二甲基硅氧烷、环聚二甲基硅氧烷、聚有机硅氧烷-11、苯基聚三甲基硅氧烷、三甲基甲硅烷基氨基聚二甲基硅氧烷、硬脂氧基三甲基硅烷、或这些材料与其他有机硅氧烷材料以任何给定比例的混合物，以便根据预期应用(例如针对特定区域，如皮肤、毛发或眼睛)实现所需的稠度和应用特性。“挥发性有机硅油”包括具有低汽化热的有机硅油，例如小于约50卡/克有机硅油。挥发性有机硅油的非限制性例子包括环聚二甲基硅氧烷；低粘度聚二甲基硅氧烷，例如粘度为约50cst或更小的聚二甲基硅氧烷。可以在本发明的语境中使用的其他非限制性挥发性有机硅油包括可从诸如Dow Corning、General Electric和SWS Silicones等制造商获得的那些。In some embodiments, body care compositions include one or more silicone-containing compounds. Non-limiting examples of organosilicon-containing compounds include any member of a family of polymeric products whose molecular backbone consists of alternating silicon and oxygen atoms with side groups attached to the silicon atoms. By changing the -Si-O- chain length, side groups and cross-linking, silicones can be synthesized into a variety of materials. Their consistency can vary from liquid to gel to solid. Silicone-containing compounds suitable for use in the body care compositions disclosed herein include, but are not limited to, those generally known to those of ordinary skill in the art. Non-limiting examples include silicone oils (eg, volatile and non-volatile oils), gels, and solids. In certain embodiments, silicon-containing compounds include silicone oils, such as polyorganosiloxanes. Non-limiting examples of polyorganosiloxanes include polydimethylsiloxane, cyclomethicone, polyorganosiloxane-11, phenyltrimethicone, trimethylmethicone Silanylaminodimethicone, stearoxytrimethylsilane, or mixtures of these materials with other organosiloxane materials in any given proportion, so that the , hair or eyes) to achieve the desired consistency and application characteristics. "Volatile silicone oil" includes silicone oils that have a low heat of vaporization, such as less than about 50 calories/gram of silicone oil. Non-limiting examples of volatile silicone oils include cyclomethicone; low viscosity dimethicone, such as dimethicone having a viscosity of about 50 cst or less. Other non-limiting volatile silicone oils that may be used in the context of the present invention include those available from manufacturers such as Dow Corning, General Electric, and SWS Silicones.

在一些实施方案中，身体护理组合物包含一种或多种去角质剂。去角质剂包含去除皮肤外表面死皮细胞的成分。这些试剂可以通过机械、化学或其他方式起作用。机械去角质剂的非限制性例子包括研磨剂，例如浮石、二氧化硅、布、纸、贝壳、珠子、固体晶体、固体聚合物等。化学去角质剂的非限制性例子包括酸和酶去角质剂。可用作去角质剂的酸包括但不限于乙醇酸、乳酸、柠檬酸、α羟基酸、β羟基酸等。本领域技术人员已知的其他去角质剂也可考虑为在本公开的身体护理组合物的语境下使用。In some embodiments, body care compositions include one or more exfoliants. Exfoliants contain ingredients that remove dead skin cells from the outer surface of the skin. These agents may act mechanically, chemically, or otherwise. Non-limiting examples of mechanical exfoliants include abrasives such as pumice, silica, cloth, paper, shells, beads, solid crystals, solid polymers, and the like. Non-limiting examples of chemical exfoliants include acid and enzymatic exfoliants. Acids that can be used as exfoliants include, but are not limited to, glycolic acid, lactic acid, citric acid, alpha hydroxy acids, beta hydroxy acids, and the like. Other exfoliants known to those skilled in the art are also contemplated for use in the context of the body care compositions of the present disclosure.

在一些实施方案中，身体护理组合物包含一种或多种精油。精油包括从草药、花卉、树木和其他植物中提取的油。此类油通常作为植物细胞之间的微小液滴存在，并且可以通过本领域技术人员已知的若干方法(例如，蒸汽蒸馏、花香提取(enfleurage，例如，通过使用脂肪提取)、浸渍、溶剂提取、或机械压榨)提取。当这些类型的油暴露在空气中时，它们往往会蒸发(例如挥发油)。精油一般不溶于水，但溶于乙醇、乙醚、固定油(植物)和其他有机溶剂。精油通常以提取精油的植物来命名。可用于本公开的身体护理组合物的精油的非限制性例子包括芝麻油、澳洲坚果油、茶树油、月见草油、西班牙鼠尾草油、西班牙迷迭香油、芫荽油、百里香油、多香果(pimento)油，玫瑰油、大茴香油、香脂油、佛手柑油、花梨木(rosewood)油、雪松油、洋甘菊油、鼠尾草油、快乐鼠尾草油、丁香油、柏木油、桉树油、茴香油、海茴香油、乳香(frankincense)油、老鹳草油、姜油、葡萄柚油、茉莉油、杜松子油、薰衣草油、柠檬油、柠檬草油、酸橙油、橘油、马郁兰油、没药油、橙花油、橙油、广藿香油、胡椒油、黑胡椒油、苦橙叶油、松油、奥图玫瑰(rose otto)油、迷迭香油、檀香油、留兰香油、甘松油、香根草油、鹿蹄草(wintergreen)油和依兰。本领域技术人员已知的其他精油也被认为可用于本发明的语境。In some embodiments, body care compositions include one or more essential oils. Essential oils include oils extracted from herbs, flowers, trees, and other plants. Such oils usually exist as tiny droplets between plant cells and can be extracted by several methods known to those skilled in the art (e.g. steam distillation, enfleurage (e.g. by using fats)), maceration, solvent extraction , or mechanical pressing) extraction. When these types of oils are exposed to air, they tend to evaporate (e.g. volatile oils). Essential oils are generally insoluble in water, but soluble in ethanol, ether, fixed oils (plants) and other organic solvents. Essential oils are usually named after the plant from which they are extracted. Non-limiting examples of essential oils that may be used in the body care compositions of the present disclosure include sesame oil, macadamia oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, allspice oil Pimento oil, rose oil, anise oil, balsam oil, bergamot oil, rosewood oil, cedar oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, Eucalyptus oil, anise oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, juniper berry oil, lavender oil, lemon oil, lemongrass oil, lime oil, orange Oil, marjoram oil, myrrh oil, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, rose otto oil, rosemary oil, sandalwood oil , spearmint oil, spikenard oil, vetiver oil, wintergreen oil and ylang-ylang. Other essential oils known to those skilled in the art are also considered useful in the context of the present invention.

在一些实施方案中，身体护理组合物包含一种或多种增稠试剂。包括增稠剂(thickener)或胶凝剂在内的增稠试剂包括增加组合物粘度的物质。增稠剂包括增加组合物粘度而基本上不修饰组合物内活性成分的功效的那些。增稠剂还可以增加组合物的稳定性。常用的增稠剂包括氢化聚异丁烯、三羟基硬脂酸甘油酯、丙烯酰二甲基牛磺酸铵/vp共聚物，或它们的组合。可以使用的另外增稠剂的其他非限制性例子包括羧酸聚合物、交联的聚丙烯酸酯聚合物、聚丙烯酰胺聚合物、多糖和胶类。羧酸聚合物的例子包括含有一种或多种衍生自丙烯酸、取代的丙烯酸以及这些丙烯酸和取代的丙烯酸的盐和酯的单体的交联的化合物，其中交联剂含有两个或更多个碳-碳双键并且衍生自多元醇。市售羧酸聚合物的例子包括卡波姆，其是与蔗糖或季戊四醇的烯丙基醚交联的丙烯酸均聚物。交联的聚丙烯酸酯聚合物的非限制性例子包括阳离子和非离子聚合物。非限制性例子描述于美国专利号5,100,660；4,849,484；4,835,206；4,628,078；4,599,379。聚丙烯酰胺聚合物(包括非离子聚丙烯酰胺聚合物，包括取代的支化或非支化聚合物)的非限制性例子包括聚丙烯酰胺、异链烷烃和月桂醇聚醚-7、丙烯酰胺和取代的丙烯酰胺与丙烯酸和取代的丙烯酸的多嵌段共聚物。多糖的非限制性例子包括纤维素、羧甲基羟乙基纤维素、乙酸丙酸羧酸纤维素、羟乙基纤维素、羟乙基乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、甲基羟乙基纤维素、微晶纤维素、纤维素硫酸钠、以及它们的混合物。另一个例子是烷基取代的纤维素，其中纤维素聚合物的羟基被羟烷基化(例如羟乙基化或羟丙基化)以形成羟烷基化纤维素，然后用C₁₀-C₃₀直链或支链烷基通过醚键进一步改性。通常这些聚合物是C₁₀-C₃₀直链或支链醇与羟烷基纤维素的醚。其他有用的多糖包括硬葡聚糖类，其包含(1～3)个连接的葡萄糖单元的直链，其中每三个单元有(1～6)个连接的葡萄糖。可以使用的胶类的非限制性例子包括金合欢胶、琼脂、藻胶、藻酸、藻酸铵、支链淀粉、藻酸钙、角叉菜胶钙、肉碱、角叉菜胶、糊精、明胶、结冷胶、瓜尔胶、瓜尔胶羟丙基三甲基氯化铵、锂蒙脱石、透明质酸、水合二氧化硅、羟丙基壳聚糖、羟丙基瓜尔胶、刺梧桐胶、巨藻、刺槐豆胶、纳豆胶、藻酸钾、角叉菜胶钾、藻酸丙二醇酯、菌核胶、羧甲基葡聚糖钠、角叉菜胶钠、黄芪胶、黄原胶，以及它们的混合物。In some embodiments, body care compositions include one or more thickening agents. Thickening agents, including thickeners or gelling agents, include substances that increase the viscosity of the composition. Thickeners include those that increase the viscosity of the composition without substantially modifying the efficacy of the active ingredients within the composition. Thickeners can also increase the stability of the composition. Commonly used thickeners include hydrogenated polyisobutylene, trihydroxystearin, ammonium acryloyldimethyltaurate/vp copolymer, or combinations thereof. Other non-limiting examples of additional thickeners that may be used include carboxylic acid polymers, cross-linked polyacrylate polymers, polyacrylamide polymers, polysaccharides and gums. Examples of carboxylic acid polymers include cross-linked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of these acrylic acids and substituted acrylic acids, wherein the cross-linking agent contains two or more carbon-carbon double bonds and are derived from polyols. Examples of commercially available carboxylic acid polymers include carbomers, which are acrylic acid homopolymers cross-linked with allyl ethers of sucrose or pentaerythritol. Non-limiting examples of cross-linked polyacrylate polymers include cationic and nonionic polymers. Non-limiting examples are described in U.S. Patent Nos. 5,100,660; 4,849,484; 4,835,206; 4,628,078; 4,599,379. Non-limiting examples of polyacrylamide polymers (including nonionic polyacrylamide polymers, including substituted branched or unbranched polymers) include polyacrylamide, isoparaffin and laureth-7, acrylamide and multi-block copolymers of substituted acrylamide with acrylic acid and substituted acrylic acid. Non-limiting examples of polysaccharides include cellulose, carboxymethylhydroxyethylcellulose, carboxycellulose acetate propionate, hydroxyethylcellulose, hydroxyethylethylcellulose, hydroxypropylcellulose, hydroxypropylcellulose Methylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Another example is alkyl-substituted cellulose, in which the hydroxyl groups of the cellulose polymer are hydroxyalkylated (e.g., hydroxyethylated or hydroxypropylated) to form hydroxyalkylated cellulose, which is then treated with C₁₀ -C₃₀ Linear or branched alkyl groups are further modified via ether linkages. Typically these polymers are ethers of C₁₀ -C₃₀ linear or branched alcohols and hydroxyalkyl cellulose. Other useful polysaccharides include scleroglucans, which contain linear chains of (1-3) linked glucose units, with (1-6) linked glucose for every three units. Non-limiting examples of gums that may be used include acacia gum, agar, algin, alginic acid, ammonium alginate, pullulan, calcium alginate, calcium carrageenan, carnitine, carrageenan, paste Essence, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar Eel gum, karaya gum, macroalgae, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, carboxymethyl dextran sodium, carrageenan sodium , tragacanth gum, xanthan gum, and mixtures thereof.

在一些实施方案中，身体护理组合物包含一种或多种防腐剂。可以在本发明的语境中使用的防腐剂的非限制性例子包括季铵防腐剂，例如聚季铵盐-1和苄烷铵卤化物(例如苯扎氯铵和苯扎溴铵)、对羟基苯甲酸酯类(例如对羟基苯甲酸甲酯和对羟基苯甲酸丙酯)、苯氧基乙醇、苯甲醇、氯丁醇、苯酚、山梨酸、硫柳汞(thimerosal)，或它们的组合。In some embodiments, body care compositions include one or more preservatives. Non-limiting examples of preservatives that may be used in the context of the present invention include quaternary ammonium preservatives, such as polyquaternium-1 and benzalkonium halides (such as benzalkonium chloride and benzalkonium bromide), p- Hydrobenzoates (such as methylparaben and propylparaben), phenoxyethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal, or combinations thereof.

在一些实施方案中，身体护理组合物包含一种或多种润肤剂。合适的润肤剂的非限制性例子包括以下：(a)有机硅油及其改性物，例如直链和环状聚二甲基硅氧烷；氨基、烷基、烷基芳基和芳基有机硅油；(b)脂肪和油，包括天然脂肪和油，例如霍霍巴油、大豆油、向日葵油、米糠油、鳄梨油、杏仁油、橄榄油、芝麻油、波斯(persic)油、蓖麻油、椰子油、貂油；可可脂；牛油、猪油；通过氢化上述油而获得的硬化油；以及合成的单甘油酯、二甘油酯和三甘油酯，例如肉豆蔻酸甘油酯和2-乙基己酸甘油酯；(c)蜡，例如巴西棕榈蜡、鲸蜡、蜂蜡、羊毛脂及其衍生物；(d)疏水性植物提取物；(e)碳氢化合物，例如液体石蜡、凡士林、微晶蜡、地蜡、角鲨烯、pristan和矿物油；(f)高级脂肪酸，例如月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、山嵛酸、油酸、亚油酸、亚麻酸、羊毛脂酸、异硬脂酸、花生四烯酸和多不饱和脂肪酸(PUFA)；(g)高级醇，例如月桂醇、鲸蜡醇、硬脂醇、油醇、山嵛醇、胆固醇和2-己基癸醇；(h)酯类，例如辛酸鲸蜡酯、乳酸肉豆蔻酯、乳酸鲸蜡酯、肉豆蔻酸异丙酯、肉豆蔻酸肉豆蔻酯、棕榈酸异丙酯、己二酸异丙酯、硬脂酸丁酯、油酸癸酯、异硬脂酸胆固醇酯、单硬脂酸甘油酯、二硬脂酸甘油酯、三硬脂酸甘油酯、乳酸烷基酯、柠檬酸烷基酯和酒石酸烷基酯；(i)精油及其提取物，例如薄荷属油、茉莉油、樟脑油、白雪松油、苦橙皮油、黑麦(ryu)油、松节油、肉桂油、佛手柑油、温州蜜柑油、菖蒲油、松油、薰衣草油、月桂油、丁香油、丝柏(hiba)油、桉树油、柠檬油、琉璃苣(starflower)油、百里香油、胡椒薄荷油、玫瑰油、鼠尾草油、芝麻油、姜油、罗勒油、刺柏油、柠檬草油、迷迭香油、花梨木油、鳄梨油、葡萄油、葡萄籽油、没药油、黄瓜油、水芹(watercress)油、金盏花油、接骨木花油、老鹳草油、椴树花油、苋菜油、海藻油、银杏油、人参油、胡萝卜油、瓜拉那油、茶树油、霍霍巴油、紫草(comfrey)油、燕麦片油、可可油、橙花油、香草油、绿茶油、普列薄荷(penny royal)油、芦荟油、薄荷脑、桉树脑、丁香酚、柠檬醛、香茅油、冰片、芳樟醇、香叶醇、月见草油、樟脑油、百里酚、绶草醇(spirantol)油、蒎烯(penene)油、柠檬烯油和萜类油；(j)脂质，例如胆固醇、神经酰胺、蔗糖酯和假神经酰胺；(k)维生素、矿物质和皮肤营养素，例如维生素A、E和K；维生素烷基酯，包括维生素C烷基酯；镁、钙和奶；(l)防晒剂，例如甲氧基肉桂酸辛酯和丁基甲氧基苯甲酰甲烷；(l)磷脂；(m)多羟基醇，例如甘油、丙二醇等；和多元醇，例如聚乙二醇；(n)抗衰老化合物，例如α羟基酸、β羟基酸；以及(o)任何前述组分的混合物等。In some embodiments, body care compositions include one or more emollients. Non-limiting examples of suitable emollients include the following: (a) Silicone oils and modifications thereof, such as linear and cyclic polydimethylsiloxanes; amino, alkyl, alkylaryl and aryl groups; Silicone oil; (b) Fats and oils, including natural fats and oils, such as jojoba oil, soybean oil, sunflower oil, rice bran oil, avocado oil, almond oil, olive oil, sesame oil, Persian oil, castor oil , coconut oil, mink oil; cocoa butter; beef tallow, lard; hardened oils obtained by hydrogenating the above oils; and synthetic mono-, diglycerides and triglycerides, such as glyceryl myristate and 2- Glyceryl ethylhexanoate; (c) waxes, such as carnauba wax, spermaceti, beeswax, lanolin and their derivatives; (d) hydrophobic plant extracts; (e) hydrocarbons, such as liquid paraffin, petrolatum , microcrystalline wax, ozokerite, squalene, pristan and mineral oil; (f) higher fatty acids, such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid Acid, lanolic acid, isostearic acid, arachidonic acid and polyunsaturated fatty acids (PUFA); (g) higher alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, cholesterol and 2-hexyldecanol; (h) esters, such as cetyl caprylate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, hexyl Isopropyl diacetate, butyl stearate, decyl oleate, cholesteryl isostearate, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, alkyl lactate, Alkyl citrate and alkyl tartrate; (i) Essential oils and their extracts, such as peppermint oil, jasmine oil, camphor oil, white cedar oil, bitter orange peel oil, ryu oil, turpentine, cinnamon Oil, bergamot oil, mandarin oil, calamus oil, pine oil, lavender oil, laurel oil, clove oil, hiba oil, eucalyptus oil, lemon oil, borage (starflower) oil, thyme oil, peppermint Oil, rose oil, sage oil, sesame oil, ginger oil, basil oil, juniper oil, lemongrass oil, rosemary oil, rosewood oil, avocado oil, grape oil, grape seed oil, myrrh oil, cucumber oil , watercress oil, calendula oil, elderflower oil, geranium oil, linden flower oil, amaranth oil, seaweed oil, ginkgo oil, ginseng oil, carrot oil, guarana oil, tea tree oil , jojoba oil, comfrey oil, oatmeal oil, cocoa butter, neroli oil, vanilla oil, green tea oil, penny royal oil, aloe vera oil, menthol, cineole, eugenol, Citral, citronella oil, borneol, linalool, geraniol, evening primrose oil, camphor oil, thymol, spirantol oil, penene oil, limonene oil and terpene oils ; (j) Lipids, such as cholesterol, ceramides, sucrose esters, and pseudoceramides; (k) Vitamins, minerals, and skin nutrients, such as vitamins A, E, and K; Vitamin alkyl esters, including vitamin C alkyl esters ; Magnesium, calcium and milk; (l) sunscreens, such as octyl methoxycinnamate and butylmethoxybenzoylmethane; (l) phospholipids; (m) polyhydric alcohols, such as glycerin, propylene glycol, etc.; and polyols , such as polyethylene glycol; (n) anti-aging compounds, such as alpha hydroxy acids, beta hydroxy acids; and (o) mixtures of any of the foregoing components, etc.

在一些实施方案中，身体护理组合物包含一种或多种增粘剂。合适的增粘剂的非限制性例子包括脂族烃树脂、芳族改性的脂族烃树脂、氢化聚环戊二烯树脂、聚环戊二烯树脂、松香、松香酯、木松香、木松香酯、妥尔油松香、妥尔油松香酯、多萜烯、芳香族改性多萜烯、萜烯酚醛树脂、芳香族改性的氢化聚环戊二烯树脂、氢化脂肪族树脂、氢化脂肪族芳香族树脂、氢化萜烯和改性萜烯、氢化松香酸、氢化松香酯、聚异戊二烯、部分或完全氢化聚异戊二烯、聚丁烯二烯、部分或完全氢化聚丁烯二烯等。增粘剂可以是完全或部分氢化的。增粘剂还可以是非极性的，非极性意味着增粘剂基本上不含具有极性基团的单体。在一些实施方案中，不存在极性基团。在一些实施方案中，极性基团以最多约5重量％、优选最多约2重量％、更优选最多约0.5重量％的量存在。In some embodiments, body care compositions include one or more viscosifying agents. Non-limiting examples of suitable tackifiers include aliphatic hydrocarbon resins, aromatic modified aliphatic hydrocarbon resins, hydrogenated polycyclopentadiene resins, polycyclopentadiene resins, rosin, rosin esters, wood rosin, wood rosin, Rosin ester, tall oil rosin, tall oil rosin ester, polyterpene, aromatic modified polyterpene, terpene phenolic resin, aromatic modified hydrogenated polycyclopentadiene resin, hydrogenated aliphatic resin, hydrogenated Aliphatic aromatic resins, hydrogenated terpenes and modified terpenes, hydrogenated rosin acids, hydrogenated rosin esters, polyisoprene, partially or fully hydrogenated polyisoprene, polybutylene diene, partially or fully hydrogenated polyisoprene Butene diene etc. Tackifiers may be fully or partially hydrogenated. The tackifier may also be non-polar, which means that the tackifier is substantially free of monomers having polar groups. In some embodiments, no polar groups are present. In some embodiments, polar groups are present in an amount up to about 5% by weight, preferably up to about 2% by weight, more preferably up to about 0.5% by weight.

在一些实施方案中，身体护理组合物包含一种或多种着色剂，例如颜料或染料。合适的颜料的例子包括但不限于无机颜料、有机颜料、色淀、珠光颜料、虹彩或光学可变颜料，以及它们的混合物。术语“颜料”应理解为是指无机或有机的、白色或有色的颗粒。在本发明的范围内，所述颜料可以视情况进行表面处理，但不限于诸如有机硅、全氟化化合物、卵磷脂和氨基酸的处理。In some embodiments, body care compositions include one or more colorants, such as pigments or dyes. Examples of suitable pigments include, but are not limited to, inorganic pigments, organic pigments, lakes, pearlescent pigments, iridescent or optically variable pigments, and mixtures thereof. The term "pigment" is understood to mean inorganic or organic, white or colored particles. Within the scope of the present invention, the pigments may optionally be surface treated, but are not limited to treatments such as silicones, perfluorinated compounds, lecithin and amino acids.

在一些实施方案中，身体护理组合物包含一种或多种表面活性剂。可用作本文公开的组合物中的表面活性剂组分的表面活性剂包括非离子、阴离子、阳离子和两性(两性离子)表面活性剂并且可以彼此组合使用。In some embodiments, body care compositions include one or more surfactants. Surfactants useful as surfactant components in the compositions disclosed herein include nonionic, anionic, cationic and amphoteric (zwitterionic) surfactants and can be used in combination with one another.

在一些实施方案中，身体护理组合物包含一种或多种pH调节剂。pH调节剂包括无机和有机酸和碱，特别是氨水、柠檬酸、磷酸、乙酸、氢氧化钠、乳酸、乙酰丙酸、乙醇酸、酒石酸、苹果酸、吡咯烷酮甲酸(PCA)、琥珀酸、柠檬酸、谷氨酸、2-氨基-2-甲基-1-丙醇(AMP)和三乙醇胺(TEA)。In some embodiments, body care compositions include one or more pH adjusting agents. pH adjusters include inorganic and organic acids and bases, in particular ammonia, citric acid, phosphoric acid, acetic acid, sodium hydroxide, lactic acid, levulinic acid, glycolic acid, tartaric acid, malic acid, pyrrolidone carboxylic acid (PCA), succinic acid, lemon acid, glutamic acid, 2-amino-2-methyl-1-propanol (AMP) and triethanolamine (TEA).

在一些实施方案中，身体护理组合物包含一种或多种还原剂。合适的还原剂包括但不限于硫脲，硫代硫酸盐、亚硫酸盐、亚硫酸氢盐、偏亚硫酸氢盐、硼氢化物和次磷酸盐的盐(例如钠盐)，抗坏血酸及其盐、酯和衍生物(例如抗坏血酸棕榈酸酯和抗坏血酸多肽)，以及生育酚及其盐、酯和衍生物(例如生育酚乙酸酯)。也可以使用其他众所周知的还原剂，例如INCI手册中列出的那些。In some embodiments, body care compositions include one or more reducing agents. Suitable reducing agents include, but are not limited to, thiourea, salts (such as sodium salts) of thiosulfate, sulfite, bisulfite, metabisulfite, borohydride and hypophosphite, ascorbic acid and salts thereof , esters and derivatives (such as ascorbyl palmitate and ascorbic acid polypeptides), and tocopherol and its salts, esters and derivatives (such as tocopherol acetate). Other well-known reducing agents may also be used, such as those listed in the INCI manual.

在一些实施方案中，身体护理组合物包含一种或多种芳香剂。合适的芳香剂的非限制性例子包括天然油或天然衍生材料，以及合成芳香剂例如烃类、醇类、醛类、酮类、酯类、内酯类、醚类、腈类和多官能化合物。天然油的非限制性例子包括以下：罗勒(Ocimumbasilicum)油、月桂(Pimento acris)油、蜂香(Monarda didyma，美国薄荷)油、佛手柑(Citrus aurantium bergamia)油、小豆蔻(Elettaria cardamomum)油、雪松(Cedrusatlantica)油、洋甘菊(Anthemis nobilis)油、肉桂(Cinnamomum cassia)油、香茅(Cymbopogon nardus)油、快乐鼠尾草(Salvia sclarea)油、丁香(Eugenia caryophyllus)油、丁香叶(Eufenia caryophyllus)油、油莎草(Cyperus esculentus)油、柏木(Cupressussempervirens，地中海柏木)油、柠檬桉叶(Eucalyptus citriodora)油、斑点老鹳草(Geranium maculatum)油、姜(Zingiber officinale)油、葡萄柚(Citrus grandis)油、榛子(Corylus avellana)坚果油、茉莉(Jasminum officinale)油、刺柏(Juniperuscommunis)油、酸刺柏焦油(Juniperus oxycedrus tar)、北美圆柏(Juniperusvirginiana)油、猕猴桃(Actinidia chinensis)水、醒目薰衣草(lavandin)(Lavandulahybrida，杂薰衣草)油、薰衣草(Lavandula angustifolia)油、薰衣草(Lavandulaangustifolia)水、柠檬(Citrus medica limonum)油、柠檬草(Cymbopogon schoenanthus，蔺花香茅)油、酸橙(Citrus aurantifolia)油、菩提树(Tilia cordata，欧洲椴)油、菩提树(Tilia cordata)水、柑橘(Citrus nobilis，广西沙柑)油、肉豆蔻(Myristica fragrans)油、橙(Citrus aurantium dulcis)花油、橙(Citrus aurantium dulcis)油，橙(Citrusaurantium dulcis)水、广藿香(Pogostemon cablin)油、胡椒薄荷(Menthe piperita)油、胡椒薄荷(Menthe peperita)水、迷迭香(Rosmarinus officinalis)油、玫瑰油、玫瑰(Rosadamascena，大马士革玫瑰)提取物、玫瑰(Rosa multiflora，蔷薇)提取物、花梨木(Anibarosaeodora)提取物、鼠尾草(Salvia officinalis)油、檀香木(Santalum album)油、留兰香(Menthe viridis)油、茶树(Melaleuca alternifolia)油和依兰(Cananga odorata)油。合成烃芳香剂的一些非限制性例子包括石竹烯、β-法呢烯、柠檬烯、α-蒎烯和β-蒎烯。合成醇芳香剂的一些非限制性例子包括白檀醇(bacdanol)、香茅醇、芳樟醇、苯乙醇和α-萜品醇(R.dbd.H)。合成醛芳香剂的一些非限制性例子包括2-甲基十一醛、柠檬醛、己基肉桂醛、异环柠檬醛、铃兰醛和10-十一碳烯醛。合成酮芳香剂的一些非限制性例子包括开司米酮(cashmeran)、α-香堇酮(α-紫罗兰酮)、龙涎酮E(isocyclemone E)、koavone、麝香酮和吐纳麝香。合成酯芳香剂的一些非限制性例子包括乙酸苄酯、乙酸4-叔丁基环己酯(顺式和反式)、乙酸柏木酯、乙酸三环癸烯酯(cyclacet)、乙酸异冰片酯和乙酸α-萜品酯(R＝乙酰基)。合成内酯芳香剂的一些非限制性例子包括香豆素、茉莉内酯、麝香内酯和桃醛。合成醚芳香剂的一些非限制性例子包括降龙涎香醚(ambroxan)、花药(anther，香芹醚)和佳乐麝香。合成腈芳香剂的一些非限制性例子包括肉桂腈和香叶腈。最后，合成多官能芳香剂的一些非限制性例子包括水杨酸戊酯、异丁子香酚、二氢茉莉酮酸甲酯(hedione)、洋茉莉醛(heliotropine)、新铃兰醛(Lyral)和香草醛。In some embodiments, body care compositions include one or more fragrances. Non-limiting examples of suitable fragrances include natural oils or naturally derived materials, as well as synthetic fragrances such as hydrocarbons, alcohols, aldehydes, ketones, esters, lactones, ethers, nitriles, and polyfunctional compounds. . Non-limiting examples of natural oils include the following: basil (Ocimumbasilicum) oil, bay (Pimento acris) oil, bee balm (Monarda didyma (American peppermint) oil, bergamot (Citrus aurantium bergamia) oil, cardamom (Elettaria cardamomum) oil , cedarwood (Cedrusatlantica) oil, chamomile (Anthemis nobilis) oil, cinnamon (Cinnamomum cassia) oil, citronella (Cymbopogon nardus) oil, clary sage (Salvia sclarea) oil, clove (Eugenia caryophyllus) oil, clove leaf (Eufenia) caryophyllus) oil, Cyperus esculentus oil, Cupressus sempervirens (Mediterranean cypress) oil, Eucalyptus citriodora oil, Geranium maculatum oil, Zingiber officinale oil, Grapefruit (Citrus grandis) oil, hazelnut (Corylus avellana) nut oil, jasmine (Jasminum officinale) oil, juniper (Juniperus communis) oil, acid juniper tar (Juniperus oxycedrus tar), North American juniper (Juniperus virginiana) oil, kiwi fruit (Actinidia chinensis) ) water, lavandin (Lavandulahybrida) oil, lavender (Lavandula angustifolia) oil, lavender (Lavandulaangustifolia) water, lemon (Citrus medica limonum) oil, lemongrass (Cymbopogon schoenanthus, lemongrass) oil, acid Orange (Citrus aurantifolia) oil, linden (Tilia cordata, European linden) oil, linden (Tilia cordata) water, citrus (Citrus nobilis, Guangxi mandarin) oil, nutmeg (Myristica fragrans) oil, orange (Citrus aurantium dulcis) ) flower oil, orange (Citrus aurantium dulcis) oil, orange (Citrusaurantium dulcis) water, patchouli (Pogostemon cablin) oil, peppermint (Menthe piperita) oil, peppermint (Menthe peperita) water, rosemary (Rosmarinus officinalis) ) oil, rose oil, rose (Rosadamascena, Damask rose) extract, rose (Rosa multiflora, rose) extract, rosewood (Anibarosaeodora) extract, sage (Salvia officinalis) oil, sandalwood (Santalum album) oil , spearmint (Menthe viridis) oil, tea tree (Melaleuca alternifolia) oil and ylang ylang (Cananga odorata) oil. Some non-limiting examples of synthetic hydrocarbon aromatics include caryophyllene, beta-farnesene, limonene, alpha-pinene, and beta-pinene. Some non-limiting examples of synthetic alcohol fragrances include bacdanol, citronellol, linalool, phenethyl alcohol, and alpha-terpineol (R.dbd.H). Some non-limiting examples of synthetic aldehyde fragrances include 2-methylundecanal, citral, hexylcinnamal, isocyclic citral, lyraldehyde, and 10-undecenal. Some non-limiting examples of synthetic ketone fragrances include cashmeran, alpha-ionone, isocyclemone E, koavone, muscone, and tonal musk. Some non-limiting examples of synthetic ester fragrances include benzyl acetate, 4-tert-butylcyclohexyl acetate (cis and trans), cedarwood acetate, cyclodecenyl acetate (cyclacet), isobornyl acetate, and acetic acid α-Terpine ester (R=acetyl). Some non-limiting examples of synthetic lactone fragrances include coumarin, jasplactone, muskolactone, and peach aldehyde. Some non-limiting examples of synthetic ether fragrances include ambroxan, anther, and galaxol. Some non-limiting examples of synthetic nitrile fragrances include cinnamonitrile and geranonitrile. Finally, some non-limiting examples of synthetic multifunctional fragrances include amyl salicylate, isoeugenol, hedione, heliotropine, Lyral and vanillin.

在一些实施方案中，身体护理组合物包含一种或多种发泡剂。发泡剂包括例如十二烷基硫酸钠、月桂酰肌氨酸钠、烷基磺基琥珀酸钠、椰子油脂肪酸单甘油磺酸钠、α-烯烃磺酸钠、N-酰基氨基酸盐如N-酰基谷氨酸盐、2-烷基-N-羧甲基-N-羟乙基咪唑啉甜菜碱、麦芽糖醇脂肪酸酯、蔗糖脂肪酸酯、聚甘油脂肪酸酯、脂肪酸二乙醇酰胺、聚氧乙烯失水山梨糖醇单硬脂酸酯、聚氧乙烯氢化蓖麻油和聚氧乙烯脂肪酸酯。这些发泡剂可以单独使用，也可以组合两种以上使用。In some embodiments, body care compositions include one or more foaming agents. Foaming agents include, for example, sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglyceryl sulfonate, sodium alpha-olefin sulfonate, N-acyl amino acid salts such as N -Acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazoline betaine, maltitol fatty acid ester, sucrose fatty acid ester, polyglycerol fatty acid ester, fatty acid diethanolamide, Polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil and polyoxyethylene fatty acid esters. These foaming agents may be used alone or in combination of two or more.

在一些实施方案中，身体护理组合物包含一种或多种晒黑剂。合适的晒黑剂包括但不限于α-羟基醛和酮、甘油醛和相关的醇醛、各种吲哚、咪唑及其衍生物、以及各种批准的色素沉着剂。其他合适的晒黑剂包括但不限于甲基乙二醛、甘油醛、赤藓酮糖、四氧嘧啶、2,3-二羟基琥珀二醛、2,3-二甲氧基琥珀二醛、2-氨基-3-羟基-琥珀二醛和2-苄氨基-3-羟基琥珀二醛。In some embodiments, body care compositions include one or more tanning agents. Suitable tanning agents include, but are not limited to, alpha-hydroxy aldehydes and ketones, glyceraldehydes and related aldols, various indoles, imidazoles and their derivatives, and various approved pigmentation agents. Other suitable tanning agents include, but are not limited to, methylglyoxal, glyceraldehyde, erythritol, alloxan, 2,3-dihydroxysuccinic dialdehyde, 2,3-dimethoxysuccinic dialdehyde, 2-Amino-3-hydroxy-succinic dialdehyde and 2-benzylamino-3-hydroxysuccinic dialdehyde.

在一些实施方案中，身体护理组合物包含一种或多种收敛剂。合适的收敛剂包括但不限于柠檬酸铝、乳酸铝、桦树提取物、咖啡提取物、月见草提取物、葡萄提取物、指甲花提取物、常春藤提取物、柠檬提取物、金缕梅提取物、铵明矾和钾明矾、三磷酸铝、甘氨酸铝和苯酚硫酸铝、铝克洛沙(alcloxa)、尿囊素铝(aldioxa)、硬脂酸铝、硫酸铝和柠檬酸铝、磷酸铝钠、钠明矾、氯羟基乳酸钠铝、乳酸钙、氯化钙、硫酸钙水合物、乳酸铝钠、乙酸锌、氯化锌、硫酸锌、乳酸锌、沸石锌、苯酚磺酸锌，以及它们的组合。In some embodiments, body care compositions include one or more astringents. Suitable astringents include, but are not limited to, aluminum citrate, aluminum lactate, birch extract, coffee extract, evening primrose extract, grape extract, henna extract, ivy extract, lemon extract, witch hazel Plum extract, ammonium and potassium alum, aluminum triphosphate, aluminum glycinate and aluminum phenolsulfate, aluminum cloxa (alcloxa), aluminum allantoin (aldioxa), aluminum stearate, aluminum sulfate and aluminum citrate, phosphoric acid Sodium aluminum, sodium alum, sodium aluminum chlorohydroxylactate, calcium lactate, calcium chloride, calcium sulfate hydrate, sodium aluminum lactate, zinc acetate, zinc chloride, zinc sulfate, zinc lactate, zeolite zinc, zinc phenolsulfonate, and they The combination.

在一些实施方案中，身体护理组合物包含一种或多种抗菌剂(antiseptics)。合适的抗菌剂包括但不限于对羟基苯甲酸的甲酯、乙酯、丙酯或丁酯，苯氧基乙醇、邻苯基苯酚、脱氢乙酸或其盐、对甲酚、间甲酚、邻氯间二甲苯酚、胡椒薄荷油、紫锥花(Echinacea)、血根草(bloodroot)、卡宴辣椒(cayenne)、茶树油、野生佛手柑、小榭树(chaparral)、刺荨麻(stinging metal)、月桂、没药、藤黄树皮、牙痛树、金盏花、洋甘菊、莫匹罗星、硫酸新霉素、杆菌肽、多粘菌素B、1-氧氟沙星、四环素类(盐酸氯四环素(chlortetracyclinehydrochloride)、盐酸氧四环素(oxytetracycline hydrochloride)和盐酸赤四环素(tetrachcycline hydrochoride))、磷酸克林霉素、硫酸庆大霉素、苯扎氯铵、苄索氯铵、己基间苯二酚、甲基苄索氯铵、苯酚、季铵化合物、三氯卡班(triclocarbon)、三氯生和茶树油。In some embodiments, body care compositions include one or more antiseptics. Suitable antibacterial agents include, but are not limited to, methyl, ethyl, propyl or butyl parahydroxybenzoic acid, phenoxyethanol, o-phenylphenol, dehydroacetic acid or its salts, p-cresol, m-cresol, O-chlorometa-xylenol, peppermint oil, Echinacea, bloodroot, cayenne, tea tree oil, wild bergamot, chaparral, stinging nettle metal), laurel, myrrh, garcinia bark, toothache tree, calendula, chamomile, mupirocin, neomycin sulfate, bacitracin, polymyxin B, 1-ofloxacin, tetracyclines (chlortetracyclinehydrochloride, oxytetracycline hydrochloride and tetrachcycline hydrochoride), clindamycin phosphate, gentamicin sulfate, benzalkonium chloride, benzethonium chloride, hexylisophenyl Diphenols, benzethonium chloride, phenol, quaternary ammonium compounds, triclocarbon, triclosan and tea tree oil.

在一些实施方案中，身体护理组合物包含一种或多种体香剂或止汗剂。合适的止汗剂和体香剂包括但不限于锌盐如硫酸锌和氯化锌、甘氨酸盐如甘氨酸锆铝、水合氯化铝、四氯化水合铝锆、碳酸锌、邻苯基苯酚和季铵化合物如二甲基苄基氯化铵和氯化六甲双铵。In some embodiments, body care compositions include one or more deodorants or antiperspirants. Suitable antiperspirants and deodorants include, but are not limited to, zinc salts such as zinc sulfate and zinc chloride, glycinate salts such as aluminum zirconium glycinate, aluminum chloride hydrate, aluminum zirconium tetrachloride hydrate, zinc carbonate, o-phenylphenol and Quaternary ammonium compounds such as dimethylbenzyl ammonium chloride and hexamethonium chloride.

在一些实施方案中，身体护理组合物包含一种或多种亮白剂(lighteningagent)。亮白剂的例子包括但不限于氢醌、曲酸、甘草或其衍生物、抗坏血酸或其衍生物、熊果苷、熊果提取物、光果甘草(Glycyrrhiza glabra)及其衍生物、小球藻(Chlorellavulgaris)提取物、紫苏提取物、椰果提取物和/或其他脱色剂。In some embodiments, body care compositions include one or more lightening agents. Examples of whitening agents include, but are not limited to, hydroquinone, kojic acid, licorice or its derivatives, ascorbic acid or its derivatives, arbutin, bearberry extract, Glycyrrhiza glabra and its derivatives, pellets Algae (Chlorellavulgaris) extract, perilla extract, coconut extract and/or other depigmenting agents.

在一些实施方案中，身体护理组合物包含一种或多种杀生物剂(biocides)。杀生物剂的例子包括但不限于三氯生、3,4,4'-三氯卡苯胺(三氯卡班)；3,4,4'-三氟甲基-4,4'-二氯卡苯胺(氯氟卡班)；5-氯-2-甲基-4-异噻唑啉-3-酮；碘代丙炔基丁基氨基甲酸酯；8-羟基喹啉；8-羟基喹啉柠檬酸盐；8-羟基喹啉硫酸盐；4-氯-3,5-二甲酚(氯二甲酚)；2-溴-2-硝基丙烷-1,3-二醇；二唑烷基脲；布康唑(butoconazole)；制霉菌素(nystatin)；特康唑(terconazole)；呋喃妥因(nitrofurantoin)；非那吡啶(phenazopyridine)；阿昔洛韦(acyclovir)；克霉唑(clortrimazole)；氯二甲酚(chloroxylenol)；氯己定(chlorhexidine)；咪康唑(miconazole)；特康唑(terconazole)；对羟基苯甲酸丁酯；对羟基苯甲酸乙酯；对羟基苯甲酸甲酯；甲基氯异噻唑啉；甲基异噻唑啉；1,3-双(羟甲基)-5,5-二甲基乙内酰脲和3-碘-2-丙炔基丁基氨基甲酸酯的混合物；羟基喹啉；EDTA(乙二胺四乙酸)；EDTA四钠；对羟基苯甲酸酯；烷基吡啶化合物；椰油磷脂酰PG-氯化二甲铵；葡萄糖酸氯己定；二葡萄糖酸氯己定；乙酸氯己定；羟乙基磺酸氯己定；盐酸氯己定；苯扎氯铵；苄索氯铵；聚六亚甲基双胍；以及它们的混合物。In some embodiments, body care compositions include one or more biocides. Examples of biocides include, but are not limited to, triclosan, 3,4,4'-triclocarnidine (triclocarban); 3,4,4'-trifluoromethyl-4,4'-dichloro Carnidine (chloroflucarban); 5-chloro-2-methyl-4-isothiazolin-3-one; iodopropynylbutylcarbamate; 8-hydroxyquinoline; 8-hydroxyquin Phosphine citrate; 8-hydroxyquinoline sulfate; 4-chloro-3,5-xylenol (chloroxylenol); 2-bromo-2-nitropropane-1,3-diol; oxadiazole Alkylurea; butoconazole; nystatin; terconazole; nitrofurantoin; phenazopyridine; acyclovir; clortrimazole ); chloroxylenol; chlorhexidine; miconazole; terconazole; butylparaben; ethylparaben; methylparaben Esters; methylchloroisothiazoline; methylisothiazoline; 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 3-iodo-2-propynylbutylamino Mixture of formates; hydroxyquinoline; EDTA (ethylenediaminetetraacetic acid); tetrasodium EDTA; parabens; alkylpyridine compounds; coconut phosphatidyl PG-dimethylammonium chloride; gluconate chloride Chlorhexidine digluconate; chlorhexidine acetate; chlorhexidine isethionate; chlorhexidine hydrochloride; benzalkonium chloride; benzethonium chloride; polyhexamethylene biguanide; and mixtures thereof .

还可以包括通常用于身体护理组合物例如皮肤护理或头发护理产品中的其他成分。Other ingredients commonly used in body care compositions such as skin care or hair care products may also be included.

风味化产品及相关用途Flavored products and related uses

在至少另一种形态中，本公开提供了前述形态及其实施方案的清凉度修饰组合物的用途，以增强风味化产品的清凉感觉，例如增强清凉化合物(例如薄荷醇、荜澄茄醇、或上述其他清凉化合物)在风味化产品中的清凉度。在相关形态中，本公开提供了用于增强风味化产品的清凉感觉的方法，该方法包括将前述形态及其实施方案的清凉度修饰组合物引入至风味化产品中。In at least another form, the present disclosure provides the use of the cooling degree modifying compositions of the aforementioned forms and embodiments thereof to enhance the cooling sensation of flavored products, such as enhancing cooling compounds (e.g., menthol, peppermint, solanol, or other cooling compounds mentioned above) in flavored products. In a related form, the present disclosure provides a method for enhancing the cooling sensation of a flavored product, which method includes introducing the cooling degree modifying composition of the aforementioned forms and embodiments thereof into the flavored product.

与这些形态相关，风味化产品可以是根据下文阐述的形态和实施方案的任何风味化产品。在一些实施方案中，风味化产品是饮料产品，例如增强型起泡饮料、可乐、柠檬-酸橙味起泡饮料、橙子味起泡饮料、葡萄味起泡饮料、草莓味起泡饮料、菠萝味起泡饮料、姜汁汽水、根汁啤酒、果汁、水果味果汁、果汁饮料、蜜汁饮料、蔬菜汁、蔬菜味汁、运动饮料、能量饮料、强化水饮料、含维生素强化水、近水饮料、椰子水、茶类饮料、咖啡、可可饮料、含奶成分的饮料、含谷类提取物的饮料和冰沙(smoothie)。在一些其他实施方案中，风味化产品是食物产品，例如包装食品、罐头食品、代餐产品等。在一些实施方案中，风味化产品是口腔护理产品，例如牙膏、漱口水或牙齿美白组合物，例如美国专利申请公开第2019/0167545号中公开的组合物，其通过引用并入本文。Related to these forms, the flavored product may be any flavored product according to the forms and embodiments set forth below. In some embodiments, the flavored product is a beverage product, such as enhanced sparkling beverage, cola, lemon-lime sparkling beverage, orange sparkling beverage, grape sparkling beverage, strawberry sparkling beverage, pineapple Flavored sparkling drinks, ginger ale, root beer, fruit juices, fruit-flavored juices, juice drinks, honey drinks, vegetable juices, vegetable-flavored juices, sports drinks, energy drinks, fortified water drinks, vitamin-fortified water, near water Beverages, coconut water, tea drinks, coffee, cocoa drinks, milk-containing drinks, cereal extract-containing drinks and smoothies. In some other embodiments, the flavored product is a food product, such as packaged foods, canned foods, meal replacement products, and the like. In some embodiments, the flavored product is an oral care product, such as a toothpaste, mouthwash, or a tooth whitening composition, such as the compositions disclosed in U.S. Patent Application Publication No. 2019/0167545, which is incorporated herein by reference.

风味化产品可以是任何合适的物理形式。例如，在一些实施方案中，风味化组合物可以是固体形式，例如粉末。在进一步的此类实施方案中，风味化产品是牙粉，例如用于美白牙齿、去除污渍(例如烟草污渍)等的牙粉。在一些其他实施方案中，风味化产品可以是糊状物或浆状物，例如牙膏。在一些其他实施方案中，风味化产品可以是乳膏或凝胶的形式，例如牙凝胶、护肤霜或牙霜(tooth cream)。在一些其他实施方案中，风味化产品可以是例如具有水性载体的液体悬浮液或溶液。在一些实施方案中，风味化产品可以是乳液的形式，例如微乳液或纳米乳液，其中可以存在表面活性剂、乳化剂等。在一些实施方案中，风味化产品是个人护理产品，例如用于施用于皮肤、面部、嘴唇、牙龈、口腔等的产品。此类个人产品可以用于任何合适的用途，例如皮肤美白、牙齿美白等。The flavored product may be in any suitable physical form. For example, in some embodiments, the flavoring composition can be in solid form, such as a powder. In further such embodiments, the flavored product is a dentifrice, such as for whitening teeth, removing stains (eg, tobacco stains), and the like. In some other embodiments, the flavored product may be a paste or slurry, such as toothpaste. In some other embodiments, the flavored product may be in the form of a cream or gel, such as a tooth gel, skin cream, or tooth cream. In some other embodiments, the flavored product may be, for example, a liquid suspension or solution with an aqueous carrier. In some embodiments, the flavored product may be in the form of an emulsion, such as a microemulsion or nanoemulsion, in which surfactants, emulsifiers, and the like may be present. In some embodiments, the flavored product is a personal care product, such as a product for application to the skin, face, lips, gums, mouth, etc. Such personal products can be used for any suitable purpose, such as skin whitening, teeth whitening, etc.

在某些形态中，本公开提供了包含前述形态或其实施方案的任何组合物的风味产品。在一些实施方案中，风味化产品是饮料产品，例如苏打水、调味水、茶等。在一些其他实施方案中，风味化产品是食物产品，例如酸奶。In certain forms, the present disclosure provides flavor products comprising any composition of the foregoing forms or embodiments thereof. In some embodiments, the flavored product is a beverage product such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt.

在风味化产品是饮料的实施方案中，饮料可以选自增强型起泡饮料、可乐、柠檬-酸橙味起泡饮料、橙子味起泡饮料、葡萄味起泡饮料、草莓味起泡饮料、菠萝味起泡饮料、姜汁汽水、根汁啤酒、果汁、水果味果汁、果汁饮料、蜜汁饮料、蔬菜汁、蔬菜味汁、运动饮料、能量饮料、强化水饮料、含维生素强化水、近水饮料、椰子水、茶类饮料、咖啡、可可饮料、含奶成分的饮料、含谷类提取物的饮料和冰沙。在一些实施方案中，饮料可以是软饮料。In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of enhanced sparkling beverages, cola, lemon-lime flavored sparkling beverages, orange flavored sparkling beverages, grape flavored sparkling beverages, strawberry flavored sparkling beverages, Pineapple-flavored sparkling drinks, ginger ale, root beer, fruit juices, fruit-flavored juices, juice drinks, honey drinks, vegetable juices, vegetable-flavored juices, sports drinks, energy drinks, fortified water drinks, vitamin-fortified water, near Water drinks, coconut water, tea drinks, coffee, cocoa drinks, drinks containing milk ingredients, drinks containing cereal extracts and smoothies. In some embodiments, the beverage may be a soft drink.

在一些实施方案中，风味化产品是口腔护理产品。通过“口腔护理产品”，是指个人护理产品或其他产品，其在正常使用过程中不是为了全身施用特定治疗剂的目的而有意吞服，而是在口腔中保留足够长的时间以接触基本上所有的牙齿表面和/或口腔组织以进行口腔活动。口腔护理组合物可以是多种形式，包括牙膏、洁牙剂、牙胶、龈下凝胶、漱口水、摩丝、泡沫、口腔喷雾剂、锭剂、咀嚼片、口香糖或假牙产品。口腔护理组合物也可掺入到条或膜上以直接施用或附着到口腔表面。In some embodiments, the flavored product is an oral care product. By "oral care product" means a personal care product or other product that is not intentionally swallowed for the purpose of systemic administration of a specific therapeutic agent in the normal course of use, but is retained in the oral cavity long enough to contact substantially All tooth surfaces and/or oral tissues for oral activities. Oral care compositions may be in a variety of forms, including toothpastes, dentifrices, gums, subgingival gels, mouthwashes, mousses, foams, oral sprays, lozenges, chewable tablets, chewing gum, or denture products. Oral care compositions can also be incorporated into strips or films for direct application or attachment to oral surfaces.

在一些实施方案中，风味化产品是药物产品，例如设计用于携带或递送某些活性药物成分(API)的产品。此类API可以是非处方(OTC)药物，例如对乙酰氨基酚，和其他OTC咳嗽和感冒药物。在一些实施方案中，API是基于处方的药物。In some embodiments, the flavored product is a pharmaceutical product, such as a product designed to carry or deliver certain active pharmaceutical ingredients (APIs). Such APIs may be over-the-counter (OTC) medications such as acetaminophen, and other OTC cough and cold medications. In some embodiments, the API is a prescription-based drug.

在本文阐述的涉及风味化产品的任何形态和实施方案的某些实施方案中，风味化产品是非天然存在的产品，例如包装食物或饮料产品。In certain embodiments of any of the forms and embodiments described herein involving flavored products, the flavored product is a non-naturally occurring product, such as a packaged food or beverage product.

食物和饮料产品或制剂的其他非限制性例子包括此类产品的甜味包衣，糖霜或糖衣，或包括于以下的任何实体：汤类，干加工食品类，饮料类，即食食品类，罐装或腌制食品类，冷冻加工食品类，冷藏加工食品类，零食食品类，烘焙食品类，糖果类，乳制品类，冰淇淋类，代餐类，意大利面(pasta)和面条类，以及酱料、调味料、调味品类，婴儿食品类和/或涂抹酱类。Other non-limiting examples of food and beverage products or preparations include sweetened coatings, frostings or icings of such products, or any entity included in the following: soups, dry processed foods, beverages, ready-to-eat foods, cans Preserved or pickled foods, frozen processed foods, refrigerated processed foods, snack foods, baked foods, candies, dairy products, ice cream, meal replacements, pasta (pasta) and noodles, and sauces Seasonings, condiments, condiments, baby foods and/or spreads.

通常，汤类是指罐装/腌制、脱水、速溶、冷藏、UHT和冷冻汤。为了该定义的目的，汤是指由肉、禽、鱼、蔬菜、谷物、水果和其他成分制成的食品，在液体中煮熟，其中可能包含一些或全部这些成分的可见碎片。它可能是清澈的(作为高汤(broth))或浓稠的(作为杂烩浓汤(chowder))，光滑的，泥状的或大块的，即食的，半浓缩的或浓缩的，并且可冷可热，作为第一道菜或主菜或作为进餐之间的点心(啜饮饮料)。汤可用作制备其他膳食成分的原料，范围从高汤(broth)(清炖肉汤(consommé))到酱汁(基于奶油或起司的汤)。Typically, soups refer to canned/cured, dehydrated, instant, refrigerated, UHT and frozen soups. For the purposes of this definition, soup means a food made from meat, poultry, fish, vegetables, grains, fruits, and other ingredients cooked in a liquid that may contain visible fragments of some or all of these ingredients. It may be clear (as broth) or thick (as chowder), smooth, puréed or chunky, ready-to-eat, semi-condensed or concentrated, and available cold Serve hot, as a first or main course or as a snack between meals (with a sip of a drink). Soups can be used as raw materials for the preparation of other meal components, ranging from broth (consommé) to sauces (cream- or cheese-based soups).

脱水和烹饪食品类通常是指：(i)烹饪辅助产品，例如：粉状、颗粒状、糊状、浓缩的液体产品，包括浓缩肉汤(bouillon)、肉汤，以及压制块体、片剂或粉状或颗粒状的类似肉汤的产品，其作为成品或作为产品、调味料和配方混合物中的成分单独出售(与技术无关)；(ii)膳食溶液产品，例如：脱水汤和冻干汤，包括脱水汤混合物，脱水速溶汤，脱水即食汤，现成菜肴、膳食和单份主菜的脱水或自热制剂，包括意大利面、土豆和米饭；(iii)膳食点缀产品，例如：调味品，腌料，沙拉酱，沙拉浇头，蘸料，拌粉，面糊混合物，储藏稳定的酱料，烧烤酱，液体配方混合物，浓缩物，酱料或酱汁混合物，包括沙拉配方混合物，其作为成品或作为产品中的成分出售，无论是脱水、液态还是冷冻的。Dehydrated and cooking foods generally refer to: (i) Cooking auxiliary products, such as: powder, granular, paste, concentrated liquid products, including concentrated broth (bouillon), broth, and pressed blocks and tablets or broth-like products in powdered or granular form, which are sold individually (irrespective of technology) as finished products or as ingredients in products, sauces and recipe mixtures; (ii) dietary solution products such as: dehydrated soups and freeze-dried products Soups, including dehydrated soup mixes, dehydrated instant soups, dehydrated ready-to-eat soups, dehydrated or self-heating preparations of ready-made dishes, meals and single-serve entrees, including pasta, potatoes and rice; (iii) meal garnishing products, such as condiments , marinades, salad dressings, salad toppings, dips, dressings, batter mixes, shelf-stable sauces, barbecue sauces, liquid recipe mixes, concentrates, sauces or sauce mixes, including salad recipe mixes, as finished products or sold as an ingredient in products, whether dehydrated, liquid or frozen.

饮料类通常是指饮料、饮料混合物和浓缩物，包括但不限于碳酸饮料和非碳酸饮料，酒精和非酒精饮料，即饮饮料，用于制备饮料(例如苏打水)的液体浓缩制剂，以及干粉饮料前体混合物。饮料类还包括酒精饮料、软饮料、运动饮料、等渗饮料和热饮料。酒精饮料包括但不限于啤酒、苹果酒/梨酒、FABs、葡萄酒和烈性酒。软饮料包括但不限于碳酸饮料，例如可乐和非可乐碳酸饮料；水果汁，例如果汁、蜜饮、果汁饮料和水果味饮料；瓶装水，包括苏打水、泉水和纯净/餐用水；功能性饮料，可以是碳酸饮料或无气饮料，包括运动饮料、能量饮料或特效药(elixir)饮料；浓缩液，例如可即饮用的液体和粉末浓缩液。无论是热饮还是冷饮，都包括但不限于咖啡或冰咖啡，例如新鲜、速溶和混合咖啡；茶或冰茶，例如红茶、绿茶、白茶、乌龙茶和调味茶；以及其他饮料，包括与牛奶或水混合的调味的、基于麦芽或基于植物的粉末、颗粒、块或片剂。The beverage category generally refers to beverages, beverage mixes and concentrates, including but not limited to carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrate preparations used to prepare beverages (such as soda), and dry powders Beverage precursor mix. The beverage category also includes alcoholic beverages, soft drinks, sports drinks, isotonic beverages and hot beverages. Alcoholic beverages include, but are not limited to, beer, cider/perry, FABs, wine and spirits. Soft drinks include, but are not limited to, carbonated drinks, such as cola and non-cola carbonated drinks; fruit juices, such as fruit juices, honey drinks, juice drinks and fruit-flavored drinks; bottled water, including sparkling water, spring water and pure/table water; functional drinks, These can be carbonated or still drinks, including sports drinks, energy drinks or elixir drinks; concentrates, such as ready-to-drink liquids and powder concentrates. Beverages, whether hot or cold, include, but are not limited to, coffee or iced coffee, such as fresh, instant, and blended coffee; tea or iced tea, such as black, green, white, oolong, and flavored teas; and other beverages, including with milk or water Mixed flavored, malt-based or plant-based powders, granules, chunks or tablets.

零食(小吃)类通常是指简易、非正式膳食的任何食物，包括但不限于甜味和美味(savory，咸味、辣味等非甜味)零食以及零食棒。零食的例子包括但不限于水果点心、薯片/脆片、挤出零食、玉米饼/玉米片、爆米花、椒盐脆饼、坚果和其他甜味和美味零食。零食棒的例子包括但不限于格兰诺拉麦片/麦片棒、早餐棒、能量棒、水果棒和其他零食棒。Snacks (snacks) generally refer to any food in simple, informal meals, including but not limited to sweet and savory (savory, salty, spicy and other non-sweet) snacks and snack bars. Examples of snacks include, but are not limited to, fruit snacks, potato chips/crisps, extruded snacks, tortillas/corn chips, popcorn, pretzels, nuts and other sweet and savory snacks. Examples of snack bars include, but are not limited to, granola/cereal bars, breakfast bars, energy bars, fruit bars, and other snack bars.

烘焙食品类通常是指任何制备过程中涉及暴露于热或过多阳光下的可食用产品。烘焙食品的例子包括但不限于面包、小圆面包(buns)、饼干、松饼、谷类食品(麦片)、烤面包机糕点、糕点、华夫饼、玉米饼、软饼干、派、百吉饼、蛋挞、乳蛋饼、蛋糕、任何烘焙食品及它们的任何组合。The baked goods category generally refers to any edible product whose preparation involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereal, toaster pastries, pastries, waffles, tortillas, soft cookies, pies, bagels , tarts, quiches, cakes, any baked goods and any combination thereof.

冰淇淋类通常是指包含奶油、糖和调味品的冷冻甜品。冰淇淋的例子包括但不限于：即食(impulse)冰淇淋；家庭装冰淇淋；冷冻酸奶和手工冰淇淋；基于大豆、燕麦、豆类(例如红豆和绿豆)和大米的冰淇淋。Ice cream generally refers to frozen desserts containing cream, sugar and condiments. Examples of ice cream include, but are not limited to: impulse ice cream; family size ice cream; frozen yogurt and artisanal ice cream; soy, oat, legume (eg red and mung bean) and rice based ice cream.

糖果类通常是指味道甜的可食用产品。糖果的例子包括但不限于硬糖、明胶、巧克力糖、砂糖食、口香糖等以及任何组合产品。Confectionery generally refers to sweet-tasting edible products. Examples of confectionery include, but are not limited to, hard candies, gelatin, chocolate candies, confectionery, chewing gum, etc., as well as any combination products.

代餐食品类通常是指旨在替代普通膳食的任何食品，特别是对于那些关注健康或健身的人。代餐的例子包括但不限于减肥产品和康复产品。The meal replacement food category generally refers to any food intended to replace a regular meal, especially for those concerned about health or fitness. Examples of meal replacements include, but are not limited to, weight loss products and recovery products.

即食食品类通常是指无需大量准备或加工即可作为膳食食用的任何食品。即食食品包括制造商为其添加了食谱“技能”的产品，因此具有高度的即食性、完备性和便利性。即食食品的例子包括但不限于罐装/腌制、冷冻、干燥、冷藏的即食食品；晚餐混合品；冷冻比萨；冷藏比萨；和预制沙拉。The ready-to-eat food category generally refers to any food that can be consumed as a meal without extensive preparation or processing. Ready-to-eat foods include products to which the manufacturer has added recipe "know-how" and thus offers a high degree of ready-to-eat, completeness and convenience. Examples of ready-to-eat foods include, but are not limited to, canned/pickled, frozen, dried, refrigerated ready-to-eat foods; dinner mixes; frozen pizza; refrigerated pizza; and prepared salads.

意大利面和面条类包括任何意大利面和/或面条，包括但不限于罐装、干燥和冷藏/新鲜的意大利面；以及原味、速食、冷藏、冷冻和零食类面条。The pasta and noodle category includes any pasta and/or noodles, including but not limited to canned, dried, and refrigerated/fresh pasta; and plain, instant, refrigerated, frozen, and snack type noodles.

罐装/腌制食品类包括但不限于罐装/腌制的肉和肉制品、鱼/海鲜、蔬菜、西红柿、豆类、水果、即食食品、汤、意大利面和其他罐装/腌制食品。The canned/preserved foods category includes, but is not limited to, canned/preserved meats and meat products, fish/seafood, vegetables, tomatoes, beans, fruits, ready meals, soups, pasta, and other canned/preserved foods .

冷冻加工食品类包括但不限于冷冻加工的红肉、加工的禽肉、加工的鱼/海鲜、加工的蔬菜、肉替代品、加工的马铃薯、烘焙产品、甜点、即食食品、比萨、汤、面条和其他冷冻食品。The frozen processed food category includes, but is not limited to, frozen processed red meat, processed poultry, processed fish/seafood, processed vegetables, meat substitutes, processed potatoes, baked products, desserts, ready meals, pizza, soups, noodles and other frozen foods.

干加工食品类包括但不限于大米、甜点混合物、干即食食品、脱水汤、速食汤、干意大利面、纯面和速食面。冷藏加工食品类包括但不限于冷藏加工的肉类、加工的鱼/海鲜产品、午餐盒、鲜切水果、即食食品、比萨、预制沙拉、汤、新鲜意大利面和面条。The dry processed food category includes, but is not limited to, rice, dessert mixes, dry ready meals, dehydrated soups, instant soups, dry pasta, plain noodles and instant noodles. The refrigerated processed food category includes, but is not limited to, refrigerated processed meats, processed fish/seafood products, lunch boxes, fresh cut fruit, ready meals, pizza, prepared salads, soups, fresh pasta and noodles.

酱料、调味料和调味品类包括但不限于番茄酱和泥、肉汤/汤块、药草和香料、谷氨酸单钠(MSG)、佐餐酱、大豆类酱、意大利面酱、湿/烹饪酱、干酱/粉末混合物、番茄酱、蛋黄酱、芥末、沙拉酱、香醋沙司、蘸料、腌制品以及其他酱料、调味料和调味品。Sauces, dressings and condiments categories include, but are not limited to, tomato sauces and purees, bouillons/stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy sauces, pasta sauces, wet/cooking Sauces, dry sauce/powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrette, dips, marinades, and other sauces, dressings and condiments.

婴儿食品类包括但不限于基于牛奶或大豆的配方食品；以及准备好的、干燥的和其他婴儿食品。The baby food category includes, but is not limited to, milk- or soy-based formulas; and prepared, dry, and other baby foods.

涂抹酱类包括但不限于果酱和蜜饯、蜂蜜、巧克力酱、坚果类涂抹酱和酵母类涂抹酱。Spreads include, but are not limited to, jams and preserves, honey, chocolate spreads, nut spreads and yeast spreads.

乳制品类通常是指从哺乳动物的奶中产生的可食用产品。乳制品的例子包括但不限于饮用奶制品、奶酪、酸奶和酸乳饮料以及其他乳制品。Dairy products generally refer to edible products produced from the milk of mammals. Examples of dairy products include, but are not limited to, drinking dairy products, cheese, yogurt and yogurt drinks, and other dairy products.

如下提供风味化产品，特别是食物和饮料产品或制剂的另外的例子。示例性的可摄取组合物包括一种或多种糖果、巧克力糖、巧克力片、巧克力板(countlines)、袋装巧克力棒(selflines)/软棒(softlines)、盒装花色品种、标准盒装花色品种、扭转包裹的微型巧克力、调味巧克力、带玩具的巧克力、夹心饼、其他巧克力糖果、薄荷糖、标准薄荷糖、强力薄荷糖、硬糖、软锭剂、树胶、果冻和咀嚼物、太妃糖、焦糖和牛轧糖、含药糖果、棒棒糖、甘草、其他糖果、面包、包装/工业面包、散装/手工面包、糕点、蛋糕、包装/工业蛋糕、散装/手工蛋糕、饼干、巧克力涂层饼干、夹心饼干、夹馅饼干、咸饼干和薄脆饼干、面包替代品、早餐麦片、即食麦片、家庭早餐麦片、薄片、麦片、其他麦片、儿童早餐麦片、热麦片、冰淇淋、即食冰淇淋、单份奶制品冰淇淋、单份水冰淇淋、多包装奶制品冰淇淋、多包装水冰淇淋、家庭装冰淇淋、家庭装奶制品冰淇淋、冰淇淋甜点、散装冰淇淋、家庭装水冰淇淋、冷冻酸奶、手工冰淇淋、乳制品、牛奶、新鲜/巴氏灭菌奶、全脂新鲜/巴氏灭菌奶、半脱脂新鲜/巴氏杀菌奶、保存期较长的/超高温奶、全脂保存期较长的/超高温奶、半脱脂保存期较长的/超高温奶、无脂保存期较长的/超高温奶、羊奶、炼乳/淡炼乳、原味炼乳/淡炼乳、调味的、功能性和其他炼乳、调味乳饮料、仅乳制品调味奶饮品、调味带果汁奶饮品、豆浆、酸奶饮料、发酵乳饮料、咖啡用奶精、奶粉、调味奶粉饮品、奶油、干酪、加工干酪、涂抹干酪、不易涂开的加工干酪、未加工干酪、涂抹未加工干酪、硬干酪、包装硬干酪、未包装的硬干酪、酸奶、原味/天然酸奶、调味酸奶、水果酸奶、益生菌酸奶、饮用酸奶、常规饮用酸奶、益生菌饮用酸奶、冷冻和耐储存点心、基于乳品的点心、基于大豆的甜点、冷冻点心、鲜奶酪和夸克奶酪、原味鲜奶酪和夸克奶酪、调味鲜奶酪和夸克奶酪、咸味鲜奶酪和夸克奶酪、甜味和咸味零食、水果零食、薯条/薯片、膨化休闲食品、玉米粉圆饼/玉米片、爆米花、椒盐脆饼、坚果、其他甜味和美味零食、零食棒、格兰诺拉麦片、早餐棒、能量棒、水果棒、其他零食棒、代餐、减肥产品、康复饮料、即食食品、罐头即食食品、冷冻即食食品、干燥即食食品、冷冻即食餐、晚餐混合物、冷冻比萨、冷藏比萨、汤、罐头汤、脱水汤、速溶汤、冷汤、热汤、速冻汤、意大利面、罐装意大利面、干意大利面、冷冻/新鲜的意大利面、面条、原味面条、方便面、杯装/碗装方便面、袋装方便面、冷冻面条、零食面、罐头食品、肉类和肉制品罐头、鱼/海鲜罐头、蔬菜罐头、番茄罐头、豆类罐头、水果罐头、罐装即食食品、罐头汤、罐头意大利面、其他罐头食品、冷冻食品、冷冻加工红肉、冷冻加工家禽、冷冻加工鱼/海鲜、冷冻加工蔬菜、冷冻肉类替代品、冷冻土豆、烤箱烤薯片、其他烤箱烤马铃薯产品、非烤箱冷冻土豆、冷冻烘焙食品、冷冻甜品、冷冻即食食品、冷冻比萨饼、冷冻汤、冷冻面、其他冷冻食品、干制食品、甜点混合物、干燥即食食品、脱水汤、速溶汤、干意大利面、原味面条、方便面、杯装/碗装方便面、袋装方便面、冷藏食品、冷藏加工肉类、冷藏鱼/海鲜产品、冷藏加工鱼、冷藏涂覆鱼、冷藏熏鱼、冷藏午餐包、冷藏即食食品、冷藏比萨、冷藏汤、冷藏/新鲜意大利面、冷藏面条、油和脂肪、橄榄油、植物油和种子油、烹饪脂肪、黄油、人造黄油、涂抹油和脂、功能性涂抹油和脂、酱料、调味料和调味品、番茄糊和泥、肉汤/汤料块、汤料块、肉汁颗粒、液体汤料和原料、药草和香料、发酵酱汁、大豆类酱、意大利面酱、湿酱料、干酱/粉末混合物、番茄酱、蛋黄酱、常规蛋黄酱、芥末、沙拉酱、常规沙拉酱、低脂沙拉酱、香醋沙司、蘸料、腌制品、其他酱料、调味料和调味品、婴儿食品、配方奶粉、标准配方奶粉、成长配方奶粉、幼儿配方奶粉、防过敏奶粉配方、预制婴儿食品、干制婴儿食品、其他婴儿食品、涂抹酱、果酱和蜜饯、蜂蜜、巧克力酱、坚果类涂抹酱和酵母类涂抹酱。示例性的可摄取组合物还包括糖果、烘焙产品、冰淇淋、乳制品、甜味和美味零食、零食棒、代餐产品、即食食品、汤、意大利面、面条、罐头食品、冷冻食品、干食品、冷藏食品、油和脂肪、婴儿食品或涂抹食品或其混合物。示例性的可摄取组合物还包括早餐麦片、甜饮料或用于制备饮料的固体或液体浓缩物组合物，理想地是使得能够降低先前已知的糖类甜味剂或人工甜味剂的浓度。Additional examples of flavored products, particularly food and beverage products or preparations, are provided below. Exemplary ingestible compositions include one or more candies, chocolate candies, chocolate chips, countlines, selflines/softlines, boxed varieties, standard boxed varieties. Variety, twist-wrapped miniature chocolates, flavored chocolates, chocolates with toys, Twinkies, other chocolate candies, mints, standard mints, power mints, hard candies, soft lozenges, gums, jellies and chews, toffees Sugar, caramel and nougat, medicated confectionery, lollipops, licorice, other confectionery, bread, packaged/industrial bread, bulk/artisan bread, pastries, cakes, packaged/industrial cakes, bulk/artisan cakes, biscuits, chocolate Coated biscuits, sandwich biscuits, sandwich biscuits, crackers and crackers, bread substitutes, breakfast cereals, ready-to-eat cereals, family breakfast cereals, flakes, muesli, other cereals, children's breakfast cereals, hot cereals, ice cream, ready-to-eat ice cream, Single serving dairy ice cream, single serving water ice cream, multi-pack dairy ice cream, multi-pack water ice cream, family size ice cream, family size dairy ice cream, ice cream desserts, bulk ice cream, family size water ice cream, frozen yogurt, handmade ice cream, dairy Products, milk, fresh/pasteurized milk, full-fat fresh/pasteurized milk, semi-skimmed fresh/pasteurized milk, long shelf life/UHT milk, full fat long shelf life/Ultra high temperature milk High-temperature milk, semi-skimmed long-life/UHT milk, fat-free long-life/UHT milk, goat milk, condensed milk/evaporated milk, original condensed milk/evaporated milk, flavored, functional and other condensed milk, Flavored milk drinks, dairy-only flavored milk drinks, flavored milk drinks with fruit juice, soy milk, yogurt drinks, fermented milk drinks, coffee creamer, milk powder, flavored milk powder drinks, cream, cheese, processed cheese, spread cheese, non-spreadable cheese Processed cheese, unprocessed cheese, spread unprocessed cheese, hard cheese, packaged hard cheese, unpackaged hard cheese, yogurt, plain/natural yogurt, flavored yogurt, fruit yogurt, probiotic yogurt, drinking yogurt, regular drinking yogurt, Probiotic drinking yogurt, frozen and shelf-stable snacks, dairy-based snacks, soy-based desserts, frozen snacks, fresh cheese and quark cheese, plain fresh cheese and quark cheese, flavored fresh cheese and quark cheese, savory fresh cheese and quark cheese Cheese, sweet and salty snacks, fruit snacks, potato chips/chips, puffed snack foods, tortillas/corn chips, popcorn, pretzels, nuts, other sweet and savory snacks, snack bars, griddles Ranola, breakfast bars, energy bars, fruit bars, other snack bars, meal replacements, weight loss products, recovery drinks, ready meals, canned ready meals, frozen ready meals, dry ready meals, frozen ready meals, dinner mixes, frozen Pizza, refrigerated pizza, soup, canned soup, dehydrated soup, instant soup, cold soup, hot soup, frozen soup, pasta, canned pasta, dried pasta, frozen/fresh pasta, noodles, plain noodles, instant noodles , cup/bowl instant noodles, bagged instant noodles, frozen noodles, snack noodles, canned food, canned meat and meat products, canned fish/seafood, canned vegetables, canned tomatoes, canned beans, canned fruit, canned ready-to-eat food , canned soups, canned pasta, other canned foods, frozen foods, frozen processed red meat, frozen processed poultry, frozen processed fish/seafood, frozen processed vegetables, frozen meat substitutes, frozen potatoes, oven baked potato chips, other oven Baked potato products, non-oven frozen potatoes, frozen baked goods, frozen desserts, frozen ready meals, frozen pizza, frozen soups, frozen noodles, other frozen foods, dried foods, dessert mixes, dry ready to eat foods, dehydrated soups, instant soups, Dried pasta, plain noodles, instant noodles, instant noodles in cups/bowls, instant noodles in bags, refrigerated foods, refrigerated processed meats, refrigerated fish/seafood products, refrigerated processed fish, refrigerated coated fish, refrigerated smoked fish, refrigerated lunch packs , refrigerated ready meals, refrigerated pizza, refrigerated soups, refrigerated/fresh pasta, refrigerated noodles, oils and fats, olive, vegetable and seed oils, cooking fats, butter, margarine, spreading oils and fats, functional spreading oils and Fats, sauces, sauces and condiments, tomato pastes and purées, broth/stock cubes, stock cubes, gravy granules, liquid stocks and stock, herbs and spices, fermented sauces, soy sauces, pasta Sauce, Wet Sauce, Dry Sauce/Powder Mix, Ketchup, Mayonnaise, Regular Mayonnaise, Mustard, Salad Dressing, Regular Salad Dressing, Low-Fat Salad Dressing, Balsamic Sauce, Dips, Marinades, Other Sauces Seasonings, seasonings and condiments, baby food, powdered formula, standard formula, growing up formula, infant formula, hypoallergenic formula, prepared baby food, dry baby food, other baby food, spreads, jams and preserves , honey, chocolate spreads, nut spreads and yeast spreads. Exemplary ingestible compositions also include candies, baked products, ice cream, dairy products, sweet and savory snacks, snack bars, meal replacement products, ready-to-eat meals, soups, pasta, noodles, canned goods, frozen foods, dry foods , refrigerated foods, oils and fats, baby foods or spreads or mixtures thereof. Exemplary ingestible compositions also include breakfast cereals, sweetened beverages, or solid or liquid concentrate compositions for preparing beverages, ideally enabling a reduction in the concentration of previously known sugar sweeteners or artificial sweeteners. .

一些实施方案提供了可吞咽或可不吞咽的可咀嚼组合物。在一些实施方案中，可咀嚼组合物可以是胶糖、口香糖、糖化胶糖、无糖胶糖、功能性胶糖、泡泡糖，其单独地或组合地包含本文公开和描述的化合物。Some embodiments provide chewable compositions that may or may not be swallowed. In some embodiments, the chewable composition may be a gum, chewing gum, saccharified gum, sugarless gum, functional gum, bubble gum, containing compounds disclosed and described herein, alone or in combination.

在一些实施方案中，本文公开和描述的清凉度修饰组合物可以单独或组合地以调味浓缩物制剂的形式提供，例如适合于随后的加工以生产即用型(即，即食型)产品。“调味浓缩物制剂”是指应当用一种或多种稀释介质复原以成为即用型组合物的制剂。术语“即用型组合物”在本文中与“可摄取组合物”互换使用，其表示无论打算用于还是不用于食用，无论是单独还是与另一种物质一起可以通过口服摄取的任何物质。在一种实施方案中，即用型组合物包括可以被人或动物直接食用的组合物。调味浓缩物制剂通常通过与一种或多种稀释介质例如任何可食用或可摄取的成分或产品混合或由其稀释来使用，以将一种或多种调味剂赋予或改变稀释介质。这样的使用过程通常被称为复原。复原可以在家庭环境或工业环境中进行。例如，消费者可以在厨房中用水或其他水性介质将冷冻的果汁浓缩物复原，以获得即用型果汁饮料。在另一个例子中，软饮料糖浆浓缩物可以由制造商以大规模工业规模用水或其他水性介质进行复原，以生产即用型软饮料。由于调味浓缩物制剂具有的调味剂或调味料的浓度高于即用型组合物，因此调味浓缩物制剂通常不适合不经复原而直接食用。使用和生产调味浓缩物制剂有许多好处。例如，一个好处是减少了运输的重量和体积，因为可以在使用时通过添加合适的溶剂、固体或液体来将调味浓缩物制剂复原。In some embodiments, the coolness modifying compositions disclosed and described herein may be provided, alone or in combination, in a flavor concentrate formulation, e.g., suitable for subsequent processing to produce a ready-to-use (i.e., ready-to-eat) product. "Flavour concentrate formulation" means a formulation that should be reconstituted with one or more diluting media to form a ready-to-use composition. The term "ready-to-use composition" is used interchangeably herein with "ingestible composition" to mean any substance that can be ingested orally, whether intended for consumption or not, whether alone or together with another substance . In one embodiment, ready-to-use compositions include compositions that can be consumed directly by humans or animals. Flavor concentrate formulations are typically used by mixing with or diluting from one or more diluting media, such as any edible or ingestible ingredient or product, to impart or modify the diluting medium with one or more flavoring agents. This usage process is often called recovery. Rehabilitation can take place in a domestic setting or an industrial setting. For example, consumers can reconstitute frozen juice concentrate in the kitchen with water or other aqueous medium to obtain a ready-to-use juice drink. In another example, soft drink syrup concentrate can be reconstituted by a manufacturer on a large industrial scale with water or other aqueous media to produce ready-to-use soft drinks. Because flavor concentrate formulations have a higher concentration of flavoring agent or flavoring than ready-to-use compositions, flavor concentrate formulations are generally not suitable for direct consumption without reconstitution. There are many benefits to using and producing flavor concentrate formulations. For example, one benefit is reduced weight and volume for shipping, since flavor concentrate formulations can be reconstituted at the time of use by adding suitable solvents, solids or liquids.

根据前述实施方案中任一项所述的风味化产品在某些实施方案中还包括一种或多种额外的风味修饰化合物，例如增强甜味的化合物(例如橙皮素、柚皮素、葡糖基化甜菊醇糖苷等)、阻断苦味的化合物、增强鲜味的化合物、增强浓厚味的化合物、减少酸味的化合物、增强咸味的化合物、增强清凉效果的化合物，或前述的任何组合。The flavored product according to any of the preceding embodiments further includes, in certain embodiments, one or more additional flavor modifying compounds, such as sweet taste enhancing compounds (e.g., hesperetin, naringenin, glucose Glycosylated steviol glycosides, etc.), bitter taste-blocking compounds, umami-enhancing compounds, kokumi-enhancing compounds, sour-reducing compounds, salty-enhancing compounds, cooling-enhancing compounds, or any combination of the foregoing.

在本文所述的涉及增甜或调味浓缩物的任何形态和实施方案的某些实施方案中，该增甜或调味浓缩物是非天然存在的产品，例如专门为生产风味化产品例如食物或饮料产品而制造的组合物。In certain embodiments of any of the forms and embodiments described herein involving sweetened or flavored concentrates, the sweetened or flavored concentrates are non-naturally occurring products, such as are specifically formulated for the production of flavored products such as food or beverage products. and manufactured compositions.

在一种实施方案中，调味浓缩物制剂包含i)单独或组合形式的本文公开和描述的化合物；ii)载体；和iii)可选地至少一种佐剂。术语“载体”表示通常不活泼的辅助物质，例如溶剂、粘合剂或其他惰性介质，其与本发明化合物和一种或多种可选的佐剂组合使用以形成制剂。例如，水或淀粉可以是调味浓缩物制剂的载体。在一些实施方案中，载体与用于将调味浓缩物制剂复原的稀释介质相同；在其他实施方案中，载体不同于稀释介质。如本文所用，术语“载体”包括但不限于摄取上可接受的载体。In one embodiment, a flavor concentrate formulation includes i) a compound disclosed and described herein, alone or in combination; ii) a carrier; and iii) optionally at least one adjuvant. The term "carrier" refers to a generally inert auxiliary substance, such as a solvent, binder or other inert medium, which is used in combination with a compound of the invention and one or more optional adjuvants to form a formulation. For example, water or starch can be the carrier for flavor concentrate formulations. In some embodiments, the carrier is the same as the diluting medium used to reconstitute the flavor concentrate formulation; in other embodiments, the carrier is different than the diluting medium. As used herein, the term "carrier" includes, but is not limited to, an ingestively acceptable carrier.

术语“佐剂”表示补充、稳定、维持或增强活性成分例如本发明化合物的预期功能或功效的添加剂。在一种实施方案中，至少一种佐剂包含一种或多种调味剂。调味剂可以具有本领域技术人员或消费者已知的任何风味，例如巧克力、咖啡、茶、摩卡、法式香草、花生酱、印度奶茶(chai)，或其组合的风味。在另一种实施方案中，至少一种佐剂包含一种或多种甜味剂。一种或多种甜味剂可以是本申请中描述的任何甜味剂。在另一种实施方案中，该至少一种佐剂包含一种或多种从由如下构成的群组中选出的成分：乳化剂、稳定剂、抗微生物防腐剂、抗氧化剂、维生素、矿物质、脂肪、淀粉、蛋白质浓缩物和分离物、盐、和它们的组合。乳化剂、稳定剂、抗微生物防腐剂、抗氧化剂、维生素、矿物质、脂肪、淀粉、蛋白质浓缩物和分离物以及盐的例子描述于美国专利No.6,468,576，其全部内容通过引用整体并入本文以用于所有目的。The term "adjuvant" means an additive that supplements, stabilizes, maintains or enhances the intended function or efficacy of an active ingredient, such as a compound of the invention. In one embodiment, at least one adjuvant includes one or more flavoring agents. The flavoring may be any flavor known to those skilled in the art or to consumers, such as chocolate, coffee, tea, mocha, French vanilla, peanut butter, chai, or combinations thereof. In another embodiment, at least one adjuvant includes one or more sweeteners. The one or more sweeteners can be any sweetener described in this application. In another embodiment, the at least one adjuvant comprises one or more ingredients selected from the group consisting of: emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals Substances, fats, starches, protein concentrates and isolates, salts, and combinations thereof. Examples of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, and salts are described in U.S. Patent No. 6,468,576, the entire contents of which are incorporated herein by reference in their entirety. for all purposes.

在一种实施方案中，本发明的调味浓缩物制剂可以为选自包括溶液和悬浮液的液体、固体、泡沫材料、糊剂、凝胶、乳剂以及它们的组合的形式，例如含有一定量固体内容物的液体。在一种实施方案中，调味浓缩物制剂为包括水基和非水基的液体形式。在一些实施方案中，本发明的调味浓缩物制剂可以是碳酸化的或非碳酸化的。In one embodiment, the flavor concentrate formulations of the present invention may be in a form selected from the group consisting of liquids, solids, foams, pastes, gels, emulsions, and combinations thereof, including solutions and suspensions, e.g., containing an amount of solids The liquid content. In one embodiment, flavor concentrate formulations are in liquid forms including aqueous and non-aqueous based. In some embodiments, flavor concentrate formulations of the present invention may be carbonated or non-carbonated.

调味浓缩物制剂可以进一步包含凝固点降低剂、成核剂或两者作为该至少一种佐剂。凝固点降低剂是摄取上可接受的化合物或试剂，其可以降低添加了该化合物或试剂的液体或溶剂的凝固点。即，含有凝固点降低剂的液体或溶液的凝固点比没有凝固点降低剂的液体或溶剂的凝固点低。除了降低起始凝固点之外，凝固点降低剂还可以降低调味浓缩物制剂的水活度。凝固点抑制剂的例子包括但不限于碳水化合物、油、乙醇、多元醇例如甘油以及它们的组合。成核剂表示能够促进成核的摄取上可接受的化合物或试剂。调味浓缩物制剂中成核剂的存在可以改善雪泥的口感，并通过增加所需的冰结晶中心的数量来帮助在冷冻温度下保持雪泥的物理性质和性能。成核剂的例子包括但不限于硅酸钙、碳酸钙、二氧化钛以及它们的组合。The flavor concentrate formulation may further comprise a freezing point depressant, a nucleating agent, or both as the at least one adjuvant. Freezing point depressants are ingestively acceptable compounds or agents that lower the freezing point of a liquid or solvent to which the compound or agent is added. That is, a liquid or solution containing a freezing point depressant has a lower freezing point than a liquid or solvent without a freezing point depressant. In addition to lowering the initial freezing point, freezing point depressants can also reduce the water activity of flavor concentrate formulations. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethanols, polyols such as glycerol, and combinations thereof. Nucleating agent means an uptakeably acceptable compound or agent capable of promoting nucleation. The presence of nucleating agents in flavored concentrate formulations can improve the mouthfeel of slushies and help maintain the physical properties and performance of slushies at freezing temperatures by increasing the number of ice crystallization centers required. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide, and combinations thereof.

在一种实施方案中，调味浓缩物制剂被配制为具有低水活度以延长保存期限。水活度是在相同温度下制剂中水的蒸气压与纯水的蒸气压之比。在一种实施方案中，调味浓缩物制剂的水活度小于约0.85。在另一种实施方案中，调味浓缩物制剂的水活度小于约0.80。在另一种实施方案中，调味浓缩物制剂的水活度小于约0.75。In one embodiment, the flavor concentrate formulation is formulated to have low water activity to extend shelf life. Water activity is the ratio of the vapor pressure of water in a formulation to the vapor pressure of pure water at the same temperature. In one embodiment, the flavor concentrate formulation has a water activity of less than about 0.85. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.80. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.75.

身体护理产品及相关用途Body care products and related uses

在至少另一种形态中，本公开提供了上述清凉度修饰组合物用于增强身体护理产品的清凉感觉的用途。在一些实施方案中，身体护理产品包含清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In at least another form, the present disclosure provides use of the above-described cooling degree modifying composition to enhance the cooling sensation of a body care product. In some embodiments, the body care product includes a cooling compound (eg, menthol, peppermint, or combinations thereof). In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在至少另一种形态中，本公开提供了增强身体护理产品的清凉感觉的方法，该方法包括将上述清凉度修饰组合物与清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)组合在身体护理产品中。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In at least another form, the present disclosure provides a method of enhancing the cooling sensation of a body care product, the method comprising combining the above-described cooling degree modifying composition with a cooling compound such as menthol, peppermint, or a combination thereof. in body care products. In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在至少另一种形态中，本公开提供了包含上述清凉度修饰组合物和清凉化合物(例如薄荷醇、荜澄茄醇或它们的组合)的身体护理产品。在一些实施方案中，身体护理产品是洗发液、沐浴液、肥皂、去角质磨砂膏、保湿霜、面部精华液、止汗剂、体香剂、润肤露、润肤油、防晒霜或助晒剂。In at least one other form, the present disclosure provides a body care product comprising the above-described coolness modifying composition and a cooling compound (eg, menthol, peppermint, or combinations thereof). In some embodiments, the body care product is a shampoo, body wash, soap, exfoliating scrub, moisturizer, facial serum, antiperspirant, deodorant, body lotion, body oil, sunscreen, or Sun booster.

在一些实施方案中，身体护理产品是个人护理或美容产品。个人护理和美容产品包括可以施涂在皮肤、毛发和指甲上的产品，可以是免洗型产品，也可以是洗去型产品。在本公开的语境中，“洗去型”是指预期的产品用途包括施涂到皮肤和/或毛发上，然后在施涂步骤的几秒至几分钟内从皮肤或毛发上冲洗掉或擦去产品。个人护理和美容产品包括用于施涂到皮肤(面部、手部、足部等)的粉剂、乳霜(creams)、乳液(emulsions)、乳剂(lotions)、凝胶和油，着色基料(液体和糊剂)和浸渍了液体的纸巾；用于在面部和眼部施加化妆和卸去化妆的产品；头发护理产品，包括染发剂(hair tints)和漂发剂(hairbleaches)；用于烫发、拉直、定型和固定头发的产品；剃须产品，包括乳霜、泡沫摩丝和脱毛产品；日光浴产品和无需阳光即可晒黑的产品；体香剂和止汗剂产品。In some embodiments, the body care product is a personal care or beauty product. Personal care and beauty products include products that can be applied to the skin, hair and nails as leave-on or rinse-off products. In the context of this disclosure, "rinse off" means that the intended use of the product involves application to the skin and/or hair and then rinsing from the skin or hair within seconds to minutes of the application step or Wipe off product. Personal care and beauty products include powders, creams, emulsions, lotions, gels and oils for application to the skin (face, hands, feet, etc.), pigmented bases ( liquids and pastes) and liquid-impregnated tissues; products for applying and removing makeup to the face and eyes; hair care products, including hair tints and hairbleaches; for perming hair , products to straighten, style and hold hair; shaving products, including creams, foam mousses and hair removal products; sunbathing products and products for tanning without sunlight; deodorant and antiperspirant products.

在一些实施方案中，个人护理或美容产品从由如下构成的群组中选出：剃须助剂、洗发液、头发护理产品、免洗型皮肤护理产品、皮肤清洁或洗涤产品(例如洗去型皮肤清洁或洗涤产品)、湿巾和身体喷香(body spray)、体香剂或止汗剂。剃须助剂具体包括泡沫、凝胶、乳霜和皂条(可以参考例如美国专利号7,069,658、美国专利号6,944,952、美国专利号6,594,904、美国专利号6,182,365、美国专利号6,185,822、美国专利号6,298,558和美国专利号5,113,585)。洗发液(香波)和头发护理剂(护发素)具体包括二合一洗发液和专为干性或油性头发配制的洗发液，或含有诸如去头屑剂等添加剂的洗发液。头发护理剂可以是洗去型也可以是免洗型头发护理剂，还包括生发剂(hair tonic)、漂发剂、着色剂、定型(setting)和造型(styling)产品。可以参考例如美国专利号6,162,423、美国专利号5,968,286、美国专利号5,935,561、美国专利号5,932,203、美国专利号5,837,661、美国专利号5,776,443、美国专利号5,756,436、美国专利号5,661,118、美国专利号5,618,523。免洗型皮肤护理产品包括淡香精、淡香水、古龙水、湿巾、身体喷香、体香剂和止汗剂。皮肤洗涤产品具体包括美容和卫生用皂条、沐浴露、液体皂、沐浴液、去角质凝胶和膏剂(可以参考例如美国专利号3,697,644；美国专利号4,065,398；美国专利号4,387,040)。湿巾(擦拭巾)具体包括皮肤清洁擦拭巾、婴儿擦拭巾、卸妆擦拭巾和皮肤清爽擦拭巾(可以参考例如美国专利号4,775,582；WO 02/07701；WO 2007/069214和WO 95/16474)。身体喷香、体香剂和止汗剂具体包括棒状、液体走珠涂抹器和加压喷雾剂。In some embodiments, the personal care or beauty product is selected from the group consisting of: shaving aids, shampoos, hair care products, leave-on skin care products, skin cleansing or cleansing products (e.g., shampoos, (removal skin cleansing or washing products), wipes and body spray, deodorant or antiperspirant. Shaving aids specifically include foams, gels, creams, and bars (see, for example, U.S. Patent No. 7,069,658, U.S. Patent No. 6,944,952, U.S. Patent No. 6,594,904, U.S. Patent No. 6,182,365, U.S. Patent No. 6,185,822, U.S. Patent No. 6,298,558, and U.S. Patent No. 5,113,585). Shampoos (shampoos) and hair treatments (conditioners) specifically include two-in-one shampoos and shampoos specially formulated for dry or oily hair, or shampoos containing additives such as anti-dandruff agents . Hair care agents can be rinse-off or leave-on hair care agents, and also include hair tonics, bleaching agents, colorants, setting and styling products. Reference may be made to, for example, U.S. Patent No. 6,162,423, U.S. Patent No. 5,968,286, U.S. Patent No. 5,935,561, U.S. Patent No. 5,932,203, U.S. Patent No. 5,837,661, U.S. Patent No. 5,776,443, U.S. Patent No. 5,756,436, U.S. Patent No. 5,661,118, and U.S. Patent No. 5,618,523. Leave-on skin care products include eau de parfum, eau de toilette, cologne, wipes, body spray, deodorant and antiperspirant. Skin cleansing products specifically include beauty and hygiene bars, shower gels, liquid soaps, shower gels, exfoliating gels and ointments (see, for example, U.S. Patent No. 3,697,644; U.S. Patent No. 4,065,398; U.S. Patent No. 4,387,040). Wet wipes (wipes) specifically include skin cleansing wipes, baby wipes, makeup remover wipes and skin refreshing wipes (see, for example, US Pat. No. 4,775,582; WO 02/07701; WO 2007/069214 and WO 95/16474). Body sprays, deodorants and antiperspirants specifically include sticks, liquid roll-on applicators and pressurized sprays.

进一步的实施方案Further implementations

实施方案1.清凉度增强化合物用于增强风味化产品的清凉感觉的用途，其中该清凉度增强化合物是从由黄烷酮、二氢查尔酮以及它们的任何组合构成的群组中选出的。Embodiment 1. Use of a cooling-enhancing compound to enhance the cooling sensation of a flavored product, wherein the cooling-enhancing compound is selected from the group consisting of flavanones, dihydrochalcones, and any combination thereof of.

实施方案2.根据实施方案1所述的用途，其中该清凉度增强化合物是黄烷酮，例如柚皮素。Embodiment 2. Use according to embodiment 1, wherein the cooling-enhancing compound is a flavanone, such as naringenin.

实施方案3.根据实施方案1所述的用途，其中该清凉度增强化合物是二氢查耳酮，例如根皮素。Embodiment 3. Use according to embodiment 1, wherein the cooling-enhancing compound is a dihydrochalcone, such as phloretin.

实施方案4.根据实施方案1至3中任一项所述的用途，其中该风味化产品包含清凉物质。Embodiment 4. Use according to any one of embodiments 1 to 3, wherein the flavored product comprises a cooling substance.

实施方案5.根据实施方案4所述的用途，其中该清凉物质为(-)-薄荷醇、N-乙基-对薄荷基-3-甲酰胺、荜澄茄醇、异胡薄荷醇、3-(L-薄荷氧基)丙烷-1,2-二醇、顺式/反式-对薄荷烷-3,8-二醇、3-(L-薄荷氧基)-2-甲基丙烷-1,2-二醇、2-[2-(对薄荷烷-3-基氧基)乙氧基]乙醇、薄荷氧基乙醇、(1R,2R,4R)-1-(2-羟基-4-甲基环己基)乙烯酮、(1R,2R,5R)-N-乙基-5-甲基-2-(丙-1-烯-2-基)-环己烷甲酰胺、N-(3-羟基-4-甲氧基苯基)-2-异丙基-5,5-二甲基-环己烷甲酰胺、N-[4-(氰基甲基)苯基]-2-异丙基-5,5-二甲基-环己烷甲酰胺、N-(2-羟基-2-苯基乙基)-2-异丙基-5,5-二甲基-环己烷-1-甲酰胺、L-薄荷醇乳酸酯、(-)-薄荷基乙二醇碳酸酯、(-)-薄荷酮1,2-甘油缩酮、D/L-薄荷酮1,2-甘油缩酮、(-)-薄荷基1-丙二醇碳酸酯、(-)-薄荷基2-丙二醇碳酸酯、D/L-薄荷基1-丙二醇薄荷酯、D/L-薄荷基2-丙二醇薄荷酯、(1R,2S,5R)-N-(4-甲氧基苯基)-5-甲基-2-(1-甲基乙基)环己烷甲酰胺、薄荷基乙酰胺基草酸酯、(E)-3-苯并[1,3]二氧杂环戊烯-5-基-N,N-二苯基-2-丙烯酰胺、3,4-亚甲基二氧基肉桂酸、N,N-二苯基酰胺、N,N-二甲基(-)-薄荷基琥珀酰亚胺、(1R,2S,5R)-N-(4-(氨基甲酰基甲基)苯基)-薄荷基甲酰胺、(-)-薄荷基吡咯烷酮甲酸酯、L-去氧肾上腺素对薄荷烷甲酰胺、(1R,2S,5R)-N-(4-(氰基甲基)-苯基)薄荷基甲酰胺、(1R,2S,5R)-N-(2-(吡啶-2-基)乙基)薄荷基甲酰胺、6-异丙基-3,9-二甲基-1,4-二氧杂螺[4.5]癸-2-酮、(1R,2R,4S)-二氢伞柳醇、N-乙基-对薄荷烷-3-甲酰胺、2-异丙基-N,2,3-三甲基正丁酰胺、3-(对薄荷烷-3-甲酰氨基)乙酸乙酯、N-乙基-2,2-二异丙基丁酰胺、N-(1,1-二甲基-2-羟基乙基)-2,2-二甲基丁酰胺、N-环丙基-5-甲基-2-异丙基-环己烷碳甲酰胺、乙酰乙酸(-)-薄荷酯、琥珀酸(-)-薄荷酯、(S)-3-羟基丁酸(-)-薄荷酯、戊二酸(-)-薄荷酯、1-[2-羟基苯基]-4-[2-硝基苯基]-1,2,3,6-四氢嘧啶-2-酮、戊二酸二-(-)-薄荷酯、N-(2-羟基乙基)-2,3-二甲基-2-异丙基丁酰胺以及它们的任何组合。Embodiment 5. The use according to Embodiment 4, wherein the cooling substance is (-)-menthol, N-ethyl-p-menthyl-3-carboxamide, peppermint, isopulegol, 3 -(L-menthyloxy)propane-1,2-diol, cis/trans-p-menthane-3,8-diol, 3-(L-menthyloxy)-2-methylpropane- 1,2-diol, 2-[2-(p-menthan-3-yloxy)ethoxy]ethanol, menthoxyethanol, (1R,2R,4R)-1-(2-hydroxy-4 -Methylcyclohexyl)ketene, (1R,2R,5R)-N-ethyl-5-methyl-2-(prop-1-en-2-yl)-cyclohexanecarboxamide, N-( 3-Hydroxy-4-methoxyphenyl)-2-isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-[4-(cyanomethyl)phenyl]-2- Isopropyl-5,5-dimethyl-cyclohexanecarboxamide, N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethyl-cyclohexane -1-Carboxamide, L-menthol lactate, (-)-menthyl glycol carbonate, (-)-menthone 1,2-glycerol ketal, D/L-menthone 1,2- Glycerol ketal, (-)-menthyl 1-propylene glycol carbonate, (-)-menthyl 2-propylene glycol carbonate, D/L-menthyl 1-propylene glycol menthyl ester, D/L-menthyl 2-propylene glycol menthyl ester Esters, (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide, menthyl acetamidooxalic acid Ester, (E)-3-benzo[1,3]dioxol-5-yl-N,N-diphenyl-2-acrylamide, 3,4-methylenedioxycinnamon Acid, N,N-diphenylamide, N,N-dimethyl(-)-menthylsuccinimide, (1R,2S,5R)-N-(4-(carbamoylmethyl)benzene (-)-menthyl pyrrolidone carboxamide, L-phenylephrine p-menthane carboxamide, (1R,2S,5R)-N-(4-(cyanomethyl) -Phenyl)menthylcarboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, 6-isopropyl-3,9-dimethyl -1,4-dioxaspiro[4.5]dec-2-one, (1R,2R,4S)-dihydrocymensulfide, N-ethyl-p-menthane-3-carboxamide, 2-isopropyl -N,2,3-trimethyl-n-butanamide, 3-(p-menthane-3-carboxamido)ethyl acetate, N-ethyl-2,2-diisopropylbutanamide, N- (1,1-Dimethyl-2-hydroxyethyl)-2,2-dimethylbutanamide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexanecarbonamide, Acetoacetate (-)-menthyl, (-)-menthyl succinate, (S)-3-hydroxybutyrate (-)-menthyl, glutarate (-)-menthyl, 1-[2-hydroxy Phenyl]-4-[2-nitrophenyl]-1,2,3,6-tetrahydropyrimidin-2-one, di-(-)-menthyl glutarate, N-(2-hydroxyethyl methyl)-2,3-dimethyl-2-isopropylbutanamide and any combination thereof.

实施方案6.根据实施方案5所述的用途，其中该清凉物质是从由以下构成的群组中选出的：(-)-薄荷醇、N-乙基-对薄荷基-3-甲酰胺、荜澄茄醇、以及它们的任何组合。Embodiment 6. Use according to embodiment 5, wherein the cooling substance is selected from the group consisting of: (-)-menthol, N-ethyl-p-menthyl-3-carboxamide , piperonic acid, and any combination thereof.

实施方案7.根据实施方案1至6中任一项所述的用途，其中该风味化物质还包含高强度甜味剂。Embodiment 7. Use according to any one of embodiments 1 to 6, wherein the flavoring substance further comprises a high intensity sweetener.

实施方案8.根据实施方案7所述的用途，其中该高强度甜味剂是糖精钠、三氯蔗糖或它们的任何组合。Embodiment 8. The use of embodiment 7, wherein the high intensity sweetener is sodium saccharin, sucralose or any combination thereof.

实施方案9.根据实施方案1至8中任一项的用途，其中该风味化产品包含4-氨基-5,6-二甲基-噻吩并[2,3-d]嘧啶-2(1H)-酮、或其盐。Embodiment 9. Use according to any one of embodiments 1 to 8, wherein the flavored product comprises 4-amino-5,6-dimethyl-thieno[2,3-d]pyrimidine-2(1H) -ketone, or its salt.

实施方案10.根据实施方案1至9中任一项所述的用途，其中该风味化产品还包含调味剂，例如薄荷调味剂。Embodiment 10. Use according to any one of embodiments 1 to 9, wherein the flavored product further comprises a flavoring agent, such as mint flavoring.

实施方案11.根据实施方案1至10中任一项所述的用途，其中该风味化产品还包含从由以下构成的群组中选出的化合物：Embodiment 11. Use according to any one of embodiments 1 to 10, wherein the flavored product further comprises a compound selected from the group consisting of:

N-乙基-N-(噻吩-2-基甲基)-2-(对甲苯基氧基)乙酰胺；N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide;

N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)-2-(对甲苯基氧基)乙酰胺；N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide;

2-(4-氟苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)乙酰胺；2-(4-fluorophenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide;

2-(2-羟基-4-甲基苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)-乙酰胺；2-(2-hydroxy-4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide;

2-((2,3-二氢-1H-茚-5-基)氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)-乙酰胺；2-((2,3-Dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide ;

2-((2,3-二氢-1H-茚-5-基)氧基)-N-(1H-吡唑-3-基)-N-(噻唑-5-基甲基)-乙酰胺；2-((2,3-Dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiazol-5-ylmethyl)-acetamide ;

5-甲氧基-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)苯并呋喃-2-甲酰胺；5-Methoxy-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)benzofuran-2-carboxamide;

2-(4-乙基苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)乙酰胺；和2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide; and

它们的任何组合。any combination of them.

实施方案12.根据实施方案11所述的用途，其中该风味化产品包含2-(4-乙基苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)乙酰胺。Embodiment 12. Use according to embodiment 11, wherein the flavored product comprises 2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophene-2 -Methyl)acetamide.

实施方案13.根据实施方案1至12中任一项所述的用途，其中该风味化产品是食物产品、饮料产品、口腔护理产品或药物产品。Embodiment 13. Use according to any one of embodiments 1 to 12, wherein the flavored product is a food product, a beverage product, an oral care product or a pharmaceutical product.

实施例Example

为了进一步说明本发明，包括以下实施例。当然，不应将这些实施例解释为具体限制本发明。权利要求书范围内的这些实施例的变型在本领域技术人员的能力范围内，并且被认为落入本文描述和要求保护的本发明的范围内。读者将认识到，掌握了本公开的熟练技术人员和本领域技术人员能够在没有穷举示例的情况下准备和使用本发明。To further illustrate the present invention, the following examples are included. Of course, these examples should not be construed as specifically limiting the invention. Variations on these embodiments within the scope of the claims are within the ability of those skilled in the art and are considered to be within the scope of the invention described and claimed herein. The reader will recognize that those skilled in the art and skilled in the art will be able to prepare and use the invention without exhaustive examples.

实施例1——牙膏配方Example 1 - Toothpaste Formula

牙膏组合物是根据本公开的某些实施方案制备的。下表1列出了包含在两种对照组合物和两种使用清凉度增强化合物的测试组合物中的成分(重量％)列表。Toothpaste compositions are prepared according to certain embodiments of the present disclosure. Table 1 below provides a list of the ingredients (% by weight) contained in the two control compositions and the two test compositions using the cooling-enhancing compound.

表1Table 1

对照1Control 1对照2Control 2样品1Sample 1不透明牙膏基料Opaque toothpaste base98.50％98.50%98.50％98.50%98.50％98.50%糖精钠Saccharin sodium0.20％0.20%0.20％0.20%0.20％0.20%薄荷醇Menthol0.30％0.30%0.40％0.40%0.30％0.30%柚皮素Naringenin0.00％0.00%0.00％0.00%0.01％0.01%水water1.00％1.00%0.90％0.90%0.99％0.99%

实施例2——感官测试Example 2 - Sensory testing

要求感官测试员(由四位口腔护理调味师组成的小组)进行以下测试：(1)首先用对照样品刷牙1分钟；(2)在如下所述的不同时间间隔对3种关键指标(清凉、苦、灼烧，和任何其他感知到的调性)进行评分；以及(3)使用如下所示的0至5的等级，0表示无冲击(impact，最初时刻的效力)/强度，5表示极高冲击/强度。表2a和表2b示出了结果。Sensory testers (a panel of four oral care flavorists) were asked to perform the following tests: (1) first brush teeth with a control sample for 1 minute; (2) evaluate 3 key indicators (cooling, bitter, burning, and any other perceived tonality); and (3) using a scale of 0 to 5 as shown below, with 0 being no impact (initial potency)/intensity and 5 being extremely High impact/strength. Table 2a and Table 2b show the results.

表2aTable 2a

表2bTable 2b

实施例3——牙膏复合基料Example 3 - Toothpaste composite base

下表3显示了本文公开的某些实施方案的牙膏配方的样品成分。量以重量百分比给出。Table 3 below shows sample ingredients for toothpaste formulations of certain embodiments disclosed herein. Amounts are given in weight percent.

表3table 3

牙膏复合基料Toothpaste compound base样品1ASample 1A聚乙二醇400Polyethylene glycol 4002.00％2.00%黄原胶xanthan gum0.60％0.60%山梨醇70％溶液Sorbitol 70% solution50.00％50.00%氟化钠sodium fluoride0.22％0.22%苯甲酸钠sodium benzoate0.20％0.20%水water15.02％15.02%水合二氧化硅(Tixosil 73)Hydrated Silica (Tixosil 73)22.00％22.00%水合二氧化硅(Tixosil 43)Hydrated Silica (Tixosil 43)7.00％7.00%二氧化钛Ci77891Titanium dioxide Ci778910.50％0.50%月桂基硫酸钠sodium lauryl sulfate1.25％1.25%薄荷风味剂mint flavor1.00％1.00%柚皮素Naringenin0.01％0.01%糖精钠Saccharin sodium0.20％0.20%

实施例4——漱口水复合基料Example 4 - Mouthwash composite base

下表4和表5显示了本文公开的某些实施方案的漱口水配方的样品成分。量以重量百分比给出。Tables 4 and 5 below show sample ingredients for mouthwash formulations of certain embodiments disclosed herein. Amounts are given in weight percent.

表4Table 4

漱口水组合物Mouthwash composition样品2ASample 2A溶剂(Dissolvant)PGSolvent(Dissolvant)PG10.00％10.00%氟化钠sodium fluoride0.02％0.02%去离子水/纯化水Deionized water/purified water76.36％76.36%Poloxamer 407NFPoloxamer 407NF0.25％0.25%山梨醇70％溶液Sorbitol 70% solution8.00％8.00%糖精钠Saccharin sodium0.02％0.02%苯甲酸钠sodium benzoate0.06％0.06%薄荷风味剂mint flavor0.20％0.20%柚皮素Naringenin0.01％0.01%甘油NATGlycerin NAT5.00％5.00%三氯蔗糖Sucralose0.01％0.01%苯甲酸benzoic acid0.07％0.07%

表5table 5

漱口水组合物Mouthwash composition样品3ASample 3A乙醇190ProofEthanol 190Proof15.00％15.00%薄荷风味剂mint flavor0.20％0.20%柚皮素Naringenin0.01％0.01%去离子水/纯化水Deionized water/purified water71.31％71.31%Poloxamer 407NFPoloxamer 407NF0.24％0.24%月桂基硫酸钠sodium lauryl sulfate0.04％0.04%山梨醇70％溶液Sorbitol 70% solution10.00％10.00%糖精钠Saccharin sodium0.03％0.03%甘油glycerin3.00％3.00%苯甲酸钠sodium benzoate0.10％0.10%三氯蔗糖Sucralose0.02％0.02%苯甲酸benzoic acid0.05％0.05%

实施例5——牙膏配方Example 5 - Toothpaste Formula

牙膏组合物是根据本公开的某些实施方案制备的。下表6列出了包含在两种对照组合物(对照1和对照2)和一种使用清凉度增强化合物的测试组合物(原型1)中的成分(重量％)列表。Toothpaste compositions are prepared according to certain embodiments of the present disclosure. Table 6 below provides a list of ingredients (% by weight) contained in two control compositions (Control 1 and Control 2) and one test composition using a cooling enhancement compound (Prototype 1).

表6.Table 6.

成分Element对照1Control 1对照2Control 2原型1Prototype 1内部不透明二氧化硅基料Internal opaque silica base99.4％99.4%99.4％99.4%99.4％99.4%糖精saccharin0.2％0.2%0.2％0.2%0.2％0.2%薄荷醇Menthol0.4％0.4%0.3％0.3%0.3％0.3%柚皮素Naringenin0％0%0％0%0.005％0.005%水water0％0%0.1％0.1%0.0995％0.0995%

实施例6——感官测试Example 6 - Sensory testing

在感官测试中评价实施例5的组合物。要求感官测试员(由30名经过培训的口腔护理调味师组成的小组)执行以下操作：(a)在牙刷上涂抹约1～2克样品，(b)在流水下冲洗牙刷5秒以润湿糊膏并软化刷毛，(c)围绕牙齿刷1分钟，尽量减少刷到牙龈，(d)使用0至9的强度等级(0表示无冲击/强度，9表示极高冲击/强度)评价刷牙时以及1、2、3、5、7、10、15、20和30分钟后的清凉强度，并且(e)吐出并用50毫升水冲洗，使用原味牛奶和米粉(rice puffs)进行调味板(pallete)清洁。在每次品尝样品之间保持20分钟的间隔。结果如图1所示。The composition of Example 5 was evaluated in sensory testing. Sensory testers (a panel of 30 trained oral care flavorists) were asked to do the following: (a) apply approximately 1 to 2 grams of sample to the toothbrush, (b) rinse the toothbrush under running water for 5 seconds to moisten it paste and soften the bristles, (c) brush around the teeth for 1 minute, minimizing brushing of the gums, (d) rate brushing using an intensity scale of 0 to 9 (0 being no impact/intensity and 9 being very high impact/intensity) and cooling intensity after 1, 2, 3, 5, 7, 10, 15, 20 and 30 minutes, and (e) spit out and rinse with 50 ml of water, use plain milk and rice puffs for the pallete clean. Maintain a 20-minute interval between each sample tasting. The results are shown in Figure 1.

实施例7——不含酒精的漱口水配方Example 7 – Alcohol-Free Mouthwash Formula

根据本公开的某些实施方案制备不含酒精的漱口水组合物。下表7列出了包含在一种对照组合物(对照3)和一种使用清凉度增强化合物的测试组合物(原型2)中的成分(重量％)列表。Alcohol-free mouthwash compositions are prepared according to certain embodiments of the present disclosure. Table 7 below provides a list of ingredients (% by weight) contained in a control composition (Control 3) and a test composition using a cooling enhancement compound (Prototype 2).

表7.Table 7.

成分Element对照3Control 3原型2Prototype 2薄荷醇Menthol0.0400％0.0400%0.0400％0.0400%柚皮素Naringenin0.0000％0.0000%0.0005％0.0005%去离子水/纯化水Deionized water/purified water80.4200％80.4200%80.4195％80.4195%Poloxamer 407NFPoloxamer 407NF0.3500％0.3500%0.3500％0.3500%山梨醇70％溶液Sorbitol 70% solution10.0000％10.0000%10.0000％10.0000%糖精钠Saccharin sodium0.0200％0.0200%0.0200％0.0200%丙二醇propylene glycol9.0000％9.0000%9.0000％9.0000%苯甲酸钠sodium benzoate0.0800％0.0800%0.0800％0.0800%苯甲酸benzoic acid0.0900％0.0900%0.0900％0.0900%总计total100.0000％100.0000%100.0000％100.0000%

实施例8——感官测试Example 8 - Sensory testing

在感官测试中评价实施例7的组合物。要求感官测试员(由30名经过培训的口腔护理调味师组成的小组)执行以下操作：(a)取样品并漱口30秒然后吐出，(b)使用0至9的强度等级(0表示无冲击/强度，9表示极高冲击/强度)评价漱口时以及1、2、3、5、7、10、15、20和30分钟后的清凉强度，(c)使用原味牛奶和米粉进行调味板清洁。在每次品尝样品之间保持30分钟的间隔。结果如图2所示。The composition of Example 7 was evaluated in sensory testing. Sensory testers (a panel of 30 trained oral care flavorists) were asked to: (a) take a sample and swish it around for 30 seconds before spitting it out, (b) use an intensity scale from 0 to 9 (0 being none Impact/strength, 9 indicates very high impact/strength) Evaluate cooling intensity while gargling and after 1, 2, 3, 5, 7, 10, 15, 20 and 30 minutes, (c) Flavored with plain milk and rice flour Board clean. Maintain a 30-minute interval between each sample tasting. The results are shown in Figure 2.

实施例9——不含酒精的漱口水配方Example 9 – Alcohol-free Mouthwash Formula

根据本公开的某些实施方案制备另外的不含酒精的漱口水组合物。下表8列出了包含在一种对照组合物(对照4)和两种使用清凉度增强化合物的测试组合物(原型3和原型4)中的成分(重量％)列表。Additional alcohol-free mouthwash compositions are prepared according to certain embodiments of the present disclosure. Table 8 below provides a list of the ingredients (% by weight) contained in one control composition (Control 4) and two test compositions using a cooling enhancement compound (Prototype 3 and Prototype 4).

表8.Table 8.

成分Element对照4Control 4原型3Prototype 3原型4Prototype 4甘油NATGlycerin NAT12.0000％12.0000%12.0000％12.0000%12.0000％12.0000%CPC 10％溶液CPC 10% solution0.2500％0.2500%0.2500％0.2500%0.2500％0.2500%糖精钠Saccharin sodium0.0100％0.0100%0.0100％0.0100%0.0100％0.0100%薄荷醇Menthol0.0200％0.0200%0.0200％0.0200%0.0200％0.0200%CL19*CL19*0.0000％0.0000%0.0003％0.0003%0.0003％0.0003%柚皮素Naringenin0.0000％0.0000%0.0015％0.0015%0.0030％0.0030%Cremophor RH40CremophorRH400.8000％0.8000%0.8000％0.8000%0.8000％0.8000%纯化水purified water86.9200％86.9200%86.9182％86.9182%86.9167％86.9167%

*2-(4-乙基苯氧基)-N-(1H-吡唑-3-基)-N-(噻吩-2-基甲基)乙酰胺*2-(4-ethylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide

实施例10——感官评价Example 10 - Sensory evaluation

在感官测试中评价实施例9的组合物。要求感官测试员(由3名专家组成的小组)执行以下操作：(a)取样品并漱口30秒然后吐出，(b)使用0至9的强度等级(0表示无冲击/强度，9表示极高冲击/强度)评价漱口5、10、15、20、25、30秒时以及30秒、1、2、5、10、15、20、25、30分钟后的清凉强度，(c)使用原味牛奶和米粉进行调味板清洁。在每次品尝样品之间保持30分钟的间隔。结果如下表9所示。The composition of Example 9 was evaluated in sensory testing. Sensory testers (a panel of 3 experts) were asked to do the following: (a) take a sample and gargle it for 30 seconds then spit it out, (b) use an intensity scale from 0 to 9 (0 being no impact/intensity and 9 being Extremely high impact/intensity) evaluates the cooling intensity when gargling for 5, 10, 15, 20, 25, 30 seconds and after 30 seconds, 1, 2, 5, 10, 15, 20, 25, 30 minutes, (c) Use plain milk and rice flour for seasoning plate cleaning. Maintain a 30-minute interval between each sample tasting. The results are shown in Table 9 below.

表9.Table 9.

实施例11——沐浴露Example 11 - Shower Gel

在感官测试中评价下表10中的沐浴露组合物。“参考”是指对比例，而“原型5”是指还含有柚皮素的本发明实施例。The shower gel compositions in Table 10 below were evaluated in sensory testing. "Reference" refers to the comparative example, and "Prototype 5" refers to the example of the invention also containing naringenin.

表10.Table 10.

成分Element参考refer to原型5Prototype 5薄荷醇Menthol0.30％0.30%0.30％0.30%柚皮素Naringenin--0.01％0.01%芳香剂Fragrance0.80％0.80%0.80％0.80%沐浴露基料shower gel base余量至100％Balance to 100%余量至100％Balance to 100%

要求感官测试员(由22名经验丰富的测试员组成的小组)执行以下操作：(a)走进淋浴间；用流动的水淋湿全身，(b)将沐浴露涂在湿手上，(c)将沐浴露涂在全身上，打圈并产生良好的泡沫，(d)关闭水流或从水流走出(此时评价“起泡强度”)，(e)彻底冲洗身体，然后走出淋浴间并擦干。要求小组成员在每一步中指出发现特别清凉的任何区域。还要求小组成员指出干燥后5分钟、15分钟、30分钟和1小时的清凉感觉。结果如图3和图4所示。Sensory testers (a panel of 22 experienced testers) were asked to do the following: (a) step into the shower; wet themselves with running water, (b) apply body wash to wet hands, ( c) Apply the shower gel all over the body, using circular motions to create a good lather, (d) Turn off the water flow or step out of the water (evaluate the "foaming intensity" at this time), (e) Rinse the body thoroughly, then step out of the shower and Dry. Ask group members to point out any areas they find particularly cool at each step. Panelists were also asked to indicate the feeling of cooling at 5 minutes, 15 minutes, 30 minutes and 1 hour after drying. The results are shown in Figures 3 and 4.

如图3所示，在起泡步骤中，与参考组合物相比，本发明的组合物在手臂上显示出增强的清凉感觉。此外，如图4所示，干燥后1小时，与参考组合物相比，本发明的组合物继续在手臂和腋下引发清凉感觉。As shown in Figure 3, during the lathering step, the composition of the present invention showed an enhanced cooling sensation on the arms compared to the reference composition. Furthermore, as shown in Figure 4, one hour after drying, the composition of the present invention continued to induce a cooling sensation on the arms and underarms compared to the reference composition.

Claims (19)

1. A cooling modifying composition comprising a cooling enhancing compound, wherein the cooling enhancing compound is selected from the group consisting of flavanones, dihydrochalcones, and any combination thereof.

2. A composition according to claim 1, wherein the cooling enhancing compound is a flavanone, such as naringin.

3. A composition according to claim 1, wherein the cooling enhancing compound is dihydrochalcones, such as phloretin.

4. A composition according to any one of claims 1 to 3 further comprising a cooling compound.

5. The composition according to claim 4, wherein the cooling compound is selected from the group consisting of: (-) -menthol, N-ethyl-p-menthyl-3-carboxamide, piperlongum, isopulegol, 3- (L-menthoxy) propane-1, 2-diol, cis/trans-p-menthane-3, 8-diol, 3- (L-menthoxy) -2-methylpropane-1, 2-diol, 2- [2- (p-menthan-3-yloxy) ethoxy ] ethanol, menthoxyethanol, (1R, 2R, 4R) -1- (2-hydroxy-4-methylcyclohexyl) ketene, (1R, 2R, 5R) -N-ethyl-5-methyl-2- (prop-1-en-2-yl) -cyclohexanecarboxamide, N- (3-hydroxy-4-methoxyphenyl) -2-isopropyl-5, 5-dimethyl-cyclohexanecarboxamide, N- [4- (cyanomethyl) phenyl ] -2-isopropyl-5, 5-dimethyl-cyclohexanecarboxamide, N- (2-hydroxy-2-phenylethyl) -2-isopropyl-5, 5-dimethyl-cyclohexanecarboxamide, L-menthyl-1, L-menthyl carbonate, (-) -glycerol ketal 1, L-menthyl-carbonate, (-) -menthyl-1-menthyl-L-carbonate, (-) -menthyl-L-menthyl-1, 2-glycollate, (-) -menthyl 1-propanediol carbonate, (-) -menthyl 2-propanediol carbonate, D/L-menthyl 1-propanediol menthyl ester, D/L-menthyl 2-propanediol menthyl ester, (1R, 2S, 5R) -N- (4-methoxyphenyl) -5-methyl-2- (1-methylethyl) cyclohexanecarboxamide, menthylacetamidoaxalate, (E) -3-benzo [1,3] dioxol-5-yl-N, N-diphenyl-2-acrylamide, 3, 4-methylenedioxycinnamic acid, N-diphenylamide, N-dimethyl (-) -menthylsuccinimide, (1R, 2S, 5R) -N- (4- (carbamoylmethyl) phenyl) -menthyl carboxamide, (-) -menthylpyrrolidone formate, L-phenylephrine p-menthanecarboxamide, (1R, 2S, 5R) -N- (4- (cyanomethyl) -phenyl) menthanecarboxamide, (1R, 5R) -N- (2S, 2- (2-diphenyl) butanamide, (4-dimethyl (-) -menthanecarboxamide, (4-N, 4-methylenedioxy-2S, 5R) -N- (2-ethyl) phenyl) -menthanecarboxamide, (4-R, 4-dimethyl (-) -menthanecarboxamide, (-) -menthanecarboxamide 2-isopropyl-N, 2, 3-trimethyl N-butyramide, ethyl 3- (p-menthane-3-carboxamido) acetate, N-ethyl-2, 2-diisopropylbutyramide, N- (1, 1-dimethyl-2-hydroxyethyl) -2, 2-dimethylbutyramide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexanecarboxamide, acetoacetate (-) -menthyl succinate (-) -menthyl, (S) -3-hydroxybutyrate (-) -menthyl, glutaric acid (-) -menthyl, 1- [ 2-hydroxyphenyl ] -4- [ 2-nitrophenyl ] -1,2,3, 6-tetrahydropyrimidin-2-one, glutaric acid di- (-) -menthyl, N- (2-hydroxyethyl) -2, 3-dimethyl-2-isopropylbutyramide, and any combination thereof.

6. The composition according to claim 5, wherein the cooling compound is selected from the group consisting of: (-) -menthol, N-ethyl-p-menthyl-3-carboxamide, piperlongum, and any combination thereof.

7. A flavoured product comprising a cooling modifying composition according to any one of claims 1 to 6.

8. The flavored product of claim 7, further comprising a high intensity sweetener.

9. The flavored product of claim 8, wherein the high intensity sweetener is sodium saccharin, sucralose, or any combination thereof.

10. The flavored product of any of claims 7 to 9, further comprising 4-amino-5, 6-dimethyl-thieno [2,3-d ] pyrimidin-2 (1H) -one, or a salt thereof.

11. The flavoured product according to any one of claims 7 to 10, further comprising a flavouring agent, such as peppermint flavouring.

12. The flavoured product of any of claims 7-11, further comprising one or more cooling enhancing compounds selected from the group consisting of:

N-ethyl-N- (thiophen-2-ylmethyl) -2- (p-tolyloxy) acetamide;

n- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) -2- (p-tolyloxy) acetamide;

2- (4-fluorophenoxy) -N- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) acetamide;

2- (2-hydroxy-4-methylphenoxy) -N- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) -acetamide;

2- ((2, 3-dihydro-1H-inden-5-yl) oxy) -N- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) -acetamide;

2- ((2, 3-dihydro-1H-inden-5-yl) oxy) -N- (1H-pyrazol-3-yl) -N- (thiazol-5-ylmethyl) -acetamide;

5-methoxy-N- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) benzofuran-2-carboxamide;

2- (4-ethylphenoxy) -N- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) acetamide;

(E/Z) -2-methyl-2-butenal;

(E/Z) -2-isopropyl-5-methyl-2-hexenal; and

any combination thereof.

13. The flavored product of any of claims 7 to 12, further comprising 2- (4-ethylphenoxy) -N- (1H-pyrazol-3-yl) -N- (thiophen-2-ylmethyl) acetamide.

14. The flavoured product according to any one of claims 7 to 13, wherein the flavoured product is a food product, a beverage product, an oral care product or a pharmaceutical product.

15. A body care product comprising the cooling sensation modification composition of any one of claims 1 to 6.

16. The body care product according to claim 15, wherein the body care product is a cosmetic product, a skin care product or a hair care product.

17. A method for enhancing the cooling sensation of a cooling compound in a flavored product or body care product, the method comprising combining the cooling compound in the flavored product or body care product with a cooling enhancing compound selected from the group consisting of flavanones, dihydrochalcones, and any combination thereof.

18. The method of claim 17, wherein the cooling compound is selected from the group consisting of: (-) -menthol, N-ethyl-p-menthyl-3-carboxamide, piperlongum, isopulegol, 3- (L-menthoxy) propane-1, 2-diol, cis/trans-p-menthane-3, 8-diol, 3- (L-menthoxy) -2-methylpropane-1, 2-diol, 2- [2- (p-menthan-3-yloxy) ethoxy ] ethanol, menthoxyethanol, (1R, 2R, 4R) -1- (2-hydroxy-4-methylcyclohexyl) ketene, (1R, 2R, 5R) -N-ethyl-5-methyl-2- (prop-1-en-2-yl) -cyclohexanecarboxamide, N- (3-hydroxy-4-methoxyphenyl) -2-isopropyl-5, 5-dimethyl-cyclohexanecarboxamide, N- [4- (cyanomethyl) phenyl ] -2-isopropyl-5, 5-dimethyl-cyclohexanecarboxamide, N- (2-hydroxy-2-phenylethyl) -2-isopropyl-5, 5-dimethyl-cyclohexanecarboxamide, L-menthyl-1, L-menthyl carbonate, (-) -glycerol ketal 1, L-menthyl-carbonate, (-) -menthyl-1-menthyl-L-carbonate, (-) -menthyl-L-menthyl-1, 2-glycollate, (-) -menthyl 1-propanediol carbonate, (-) -menthyl 2-propanediol carbonate, D/L-menthyl 1-propanediol menthyl ester, D/L-menthyl 2-propanediol menthyl ester, (1R, 2S, 5R) -N- (4-methoxyphenyl) -5-methyl-2- (1-methylethyl) cyclohexanecarboxamide, menthylacetamidoaxalate, (E) -3-benzo [1,3] dioxol-5-yl-N, N-diphenyl-2-acrylamide, 3, 4-methylenedioxycinnamic acid, N-diphenylamide, N-dimethyl (-) -menthylsuccinimide, (1R, 2S, 5R) -N- (4- (carbamoylmethyl) phenyl) -menthyl carboxamide, (-) -menthylpyrrolidone formate, L-phenylephrine p-menthanecarboxamide, (1R, 2S, 5R) -N- (4- (cyanomethyl) -phenyl) menthanecarboxamide, (1R, 5R) -N- (2S, 2- (2-diphenyl) butanamide, (4-dimethyl (-) -menthanecarboxamide, (4-N, 4-methylenedioxy-2S, 5R) -N- (2-ethyl) phenyl) -menthanecarboxamide, (4-R, 4-dimethyl (-) -menthanecarboxamide, (-) -menthanecarboxamide 2-isopropyl-N, 2, 3-trimethyl N-butyramide, ethyl 3- (p-menthane-3-carboxamido) acetate, N-ethyl-2, 2-diisopropylbutyramide, N- (1, 1-dimethyl-2-hydroxyethyl) -2, 2-dimethylbutyramide, N-cyclopropyl-5-methyl-2-isopropyl-cyclohexanecarboxamide, acetoacetate (-) -menthyl succinate (-) -menthyl, (S) -3-hydroxybutyrate (-) -menthyl, glutaric acid (-) -menthyl, 1- [ 2-hydroxyphenyl ] -4- [ 2-nitrophenyl ] -1,2,3, 6-tetrahydropyrimidin-2-one, glutaric acid di- (-) -menthyl, N- (2-hydroxyethyl) -2, 3-dimethyl-2-isopropylbutyramide, and any combination thereof; typically selected from the group consisting of: (-) -menthol, N-ethyl-p-menthyl-3-carboxamide, piperlongum, and any combination thereof.

19. Use of a cooling enhancing compound for enhancing the cooling sensation of a flavoured or body-care product, wherein the cooling enhancing compound is selected from the group consisting of flavanones, dihydrochalcones and any combination thereof.