CN114306095A - A kind of microneedle patch for anti-wrinkle moisturizing and preparation method and application thereof - Google Patents

Abstract

The invention relates to the technical field of cosmetics and cosmetology, and particularly discloses a micro-needle patch for resisting wrinkles and preserving moisture, and a preparation method and application thereof. The invention relates to a micro-needle patch for resisting wrinkles and preserving moisture, which comprises a substrate and a needle point loaded with active ingredients, wherein the active ingredients comprise the following components in parts by weight: 2.5-7.5 parts of sodium hyaluronate, 0.5-1.5 parts of recombinant collagen, 0.5-1.5 parts of hydroxypropyl tetrahydropyrane triol, 0.2-0.8 part of tetrahydro methylpyrimidine carboxylic acid, 80.1-0.3 part of acetyl hexapeptide and 40.1-0.3 part of palmitoyl pentapeptide. The microneedle patch disclosed by the invention consists of a needle point capable of piercing the stratum corneum of the skin and a substrate, the specific active ingredient disclosed by the invention is loaded on the needle point, and when the needle point pierces the stratum corneum and sends the active ingredient to the subcutaneous part, wrinkles can be effectively removed, and the effects of resisting wrinkles and preserving moisture are achieved.

Description

Translated fromChinese

一种用于抗皱保湿的微针贴及其制备方法和应用A kind of microneedle patch for anti-wrinkle moisturizing and preparation method and application thereof

技术领域technical field

本发明涉及化妆品美容技术领域，尤其是涉及一种用于抗皱保湿的微针贴及其制备方法和应用。The invention relates to the technical field of cosmetics and beauty, in particular to a micro-needle patch used for anti-wrinkle and moisturizing, and a preparation method and application thereof.

背景技术Background technique

作为用于适用于人体的多种医药的有效的药物传递的方法，广泛地适用通过皮下注射针以液状形态注入医药的方式。但是，直径为数毫米左右的皮下注射针刺激存在于皮肤的多个痛点，从而给患者带来痛症。与传统的皮下注射针给药相比，微针(MNs)尺寸很小，针的长度通常在1mm以下，由于其微米级尺寸，MNs可以无缝地刺穿皮肤角质层，在皮肤表面形成微通道，并将针尖搭载的活性大分子(包括分子量范围很宽的治疗分子，例如小分子，生物大分子，甚至生物大蛋白)直接送到皮下，美容效果显著。由于皮肤角质层的阻挡，普通的美容面膜无法将活性大分子送到皮下，美容效果有限。As a method for efficient drug delivery of various medicines applied to the human body, a method of injecting medicines in a liquid form through a hypodermic needle is widely used. However, the hypodermic needle with a diameter of several millimeters stimulates many pain points on the skin, thereby causing pain to the patient. Compared with traditional hypodermic needle administration, microneedles (MNs) are small in size, and the length of the needle is usually less than 1 mm. Due to their micron-scale size, MNs can seamlessly penetrate the skin stratum corneum and form microscopic microneedles on the skin surface. channel, and the active macromolecules (including therapeutic molecules with a wide molecular weight range, such as small molecules, biological macromolecules, and even biological large proteins) carried by the needle tip are directly sent to the subcutaneous surface, and the cosmetic effect is remarkable. Due to the blocking of the stratum corneum of the skin, ordinary cosmetic masks cannot deliver active macromolecules to the subcutaneous surface, and the cosmetic effect is limited.

透明质酸钠是人体内一种固有的成分，是一种葡聚糖醛酸，没有种属特异性，它广泛存在于胎盘、羊水、晶状体、关节软骨、皮肤真皮层等组织；器官中它分布在细胞质、细胞间质中，对其中所含的细胞和细胞器官本身起润滑与滋养作用。透明质酸钠同时提供细胞代谢的微环境，保湿作用是透明质酸钠在化妆品中最重要的作用，与其他保湿剂相比，透明质酸钠的保湿效果相对更稳定。Sodium hyaluronate is an inherent component in the human body. It is a glucuronic acid with no species specificity. It is widely found in placenta, amniotic fluid, lens, articular cartilage, skin dermis and other tissues; It is distributed in the cytoplasm and intercellular substance, and plays a role in lubricating and nourishing the cells and cellular organs contained in it. Sodium hyaluronate also provides a microenvironment for cell metabolism, and its moisturizing effect is the most important role of sodium hyaluronate in cosmetics. Compared with other moisturizing agents, the moisturizing effect of sodium hyaluronate is relatively more stable.

胶原蛋白存在于我们的皮肤细胞的外基质中，胶原蛋白约占皮肤外基质的80％。人体每天约需更新10％的胶原蛋白，如果合成速度跟不上代谢速度，人体就会缺乏胶原蛋白，通常表现为皮肤缺乏弹性，严重者出现皱纹，所以向皮肤补充胶原蛋白显得尤为重要。Collagen is found in the outer matrix of our skin cells, and collagen makes up about 80% of the outer matrix of the skin. The human body needs to renew about 10% of collagen every day. If the synthesis rate cannot keep up with the metabolic rate, the human body will lack collagen, which usually manifests as lack of elasticity of the skin, and wrinkles in severe cases. Therefore, it is particularly important to supplement the skin with collagen.

目前化妆品常用的胶原蛋白主要是动物来源，例如从猪皮、牛跟腱、鱼皮等动物组织提取，这种胶原为异种胶原，对人体具有免疫排斥反应，且动物来源胶原蛋白可能会携带病毒风险，例如，猪流感、疯牛病、猪丹毒等。而重组胶原蛋白是通过基因工程技术得到的人源胶原蛋白，对人体无免疫排斥反应，且无携带病毒风险，对人体皮肤十分的友好。At present, the commonly used collagen in cosmetics is mainly derived from animals, for example, it is extracted from animal tissues such as pigskin, bovine Achilles tendon, and fish skin. This collagen is a heterologous collagen, which has an immune rejection reaction to the human body, and animal-derived collagen may carry viruses. Risks, for example, swine flu, mad cow disease, swine erysipelas, etc. Recombinant collagen is a human-derived collagen obtained through genetic engineering technology. It has no immune rejection to the human body, and has no risk of carrying viruses. It is very friendly to human skin.

目前市场上，重组胶原蛋白用于美容化妆品领域主要用于面膜、精华液、修护液、保湿液、爽肤水等，很少将重组胶原蛋白应用于美容微针贴中，并且目前市场中的微针贴在抗皱保湿的效果不佳，因此，还有改善的空间。Currently on the market, recombinant collagen is mainly used in the field of beauty and cosmetics for facial masks, essences, repair liquids, moisturizing liquids, toners, etc. Recombinant collagen is rarely used in beauty micro-needle patches, and the micro-needle patches in the current market are Needle stickers are not very effective in anti-wrinkle moisturizing, so there is still room for improvement.

发明内容SUMMARY OF THE INVENTION

本发明的目的在于克服上述现有技术的不足之处而提供一种用于抗皱保湿的微针贴及其制备方法和应用。本发明的微针贴由可刺穿皮肤角质层的针尖以及基底组成，在针尖负载本发明特定的活性成分，当针尖刺穿角质层将活性成分送达皮下时，可有效祛除皱纹，达到抗皱保湿的效果。The purpose of the present invention is to overcome the shortcomings of the above-mentioned prior art and provide a micro-needle patch for anti-wrinkle and moisturizing, and a preparation method and application thereof. The microneedle patch of the present invention is composed of a needle tip that can pierce the stratum corneum of the skin and a base. The needle tip is loaded with the specific active ingredient of the present invention. When the needle tip pierces the stratum corneum to deliver the active ingredient under the skin, it can effectively remove wrinkles and achieve anti-wrinkle. Moisturizing effect.

为实现上述目的，本发明采取的技术方案为：To achieve the above object, the technical scheme adopted in the present invention is:

第一方面，本发明提供了一种用于抗皱保湿的微针贴，包括基底和负载活性成分的针尖，活性成分包括以下重量份数的组分：In a first aspect, the present invention provides a micro-needle patch for anti-wrinkle and moisturizing, comprising a base and a needle tip loaded with an active ingredient, and the active ingredient includes the following components in parts by weight:

透明质酸钠2.5～7.5份、重组胶原蛋白0.5～1.5份、羟丙基四氢吡喃三醇0.5～1.5份、四氢甲基嘧啶羧酸0.2～0.8份、乙酰基六肽-8 0.1～0.3份和棕榈酰五肽-4 0.1～0.3份。2.5-7.5 parts of sodium hyaluronate, 0.5-1.5 parts of recombinant collagen, 0.5-1.5 parts of hydroxypropyl tetrahydropyrantriol, 0.2-0.8 parts of tetrahydromethylpyrimidine carboxylic acid, acetyl hexapeptide-8 0.1 ~0.3 part and palmitoyl pentapeptide-4 0.1-0.3 part.

本发明的活性成分中含有重组胶原蛋白，能够促进肌底胶原再生和抑制黑色素生成，具有优异的抗皱祛黑效果。The active ingredient of the present invention contains recombinant collagen, which can promote the regeneration of muscle base collagen and inhibit the production of melanin, and has excellent anti-wrinkle and blackening effect.

本发明以透明质酸钠为微针贴的主要赋形材料，在微针贴的针尖中负载了重组胶原蛋白、羟丙基四氢吡喃三醇、四氢甲基嘧啶羧酸、乙酰基六肽-8和棕榈酰五肽-4等成分，当针尖穿透角质层至皮肤底层时，对皮肤具有较好的抗皱保湿效果，并且还具有一定的祛黑紧致效果。The invention uses sodium hyaluronate as the main excipient material of the microneedle sticker, and the needle tip of the microneedle sticker is loaded with recombinant collagen, hydroxypropyltetrahydropyrantriol, tetrahydromethylpyrimidine carboxylic acid, acetyl group The ingredients such as hexapeptide-8 and palmitoyl pentapeptide-4, when the needle tip penetrates the stratum corneum to the bottom layer of the skin, have a good anti-wrinkle moisturizing effect on the skin, and also have a certain effect of darkening and firming.

本发明发明人经过大量研究及试验发现，将羟丙基四氢吡喃三醇、四氢甲基嘧啶羧酸、乙酰基六肽-8和棕榈酰五肽-4四种活性大分子复配时，美容微针贴刺穿角质层，在皮肤表面形成微通道，针尖负载的上述活性大分子直接送到皮下，可以显著提高抗皱抗衰效果，美容效果显著。羟丙基四氢吡喃三醇不仅助于刺激胶原I，III，IV和VII的产生，还有助于皮肤的保湿和紧致。The inventors of the present invention have found that four active macromolecules, hydroxypropyltetrahydropyrantriol, tetrahydromethylpyrimidine carboxylic acid, acetyl hexapeptide-8 and palmitoyl pentapeptide-4, are compounded through a lot of research and experiments. When the cosmetic micro-needle sticks through the stratum corneum, micro-channels are formed on the skin surface, and the above-mentioned active macromolecules loaded by the needle tip are directly sent to the subcutaneous, which can significantly improve the anti-wrinkle and anti-aging effect, and the cosmetic effect is remarkable. Hydroxypropyltetrahydropyrantriol not only helps to stimulate collagen I, III, IV and VII production, but also helps in moisturizing and firming of the skin.

作为本发明所述用于抗皱保湿的微针贴的优选实施方式，所述活性成分包括以下重量份数的组分：As a preferred embodiment of the microneedle patch for anti-wrinkle and moisturizing according to the present invention, the active ingredient includes the following components in parts by weight:

透明质酸钠5.0～7.5份、重组胶原蛋白1.0～1.5份、羟丙基四氢吡喃三醇1.0～1.5份、四氢甲基嘧啶羧酸0.2～0.5份、乙酰基六肽-8 0.1～0.2份和棕榈酰五肽-4 0.1～0.2份。5.0-7.5 parts of sodium hyaluronate, 1.0-1.5 parts of recombinant collagen, 1.0-1.5 parts of hydroxypropyl tetrahydropyrantriol, 0.2-0.5 parts of tetrahydromethylpyrimidine carboxylic acid, acetyl hexapeptide-8 0.1 ~0.2 part and palmitoyl pentapeptide-4 0.1-0.2 part.

作为本发明所述用于抗皱保湿的微针贴的优选实施方式，所述活性成分包括以下重量份数的组分：As a preferred embodiment of the microneedle patch for anti-wrinkle and moisturizing according to the present invention, the active ingredient includes the following components in parts by weight:

透明质酸钠5.0份、重组胶原蛋白1.0份、羟丙基四氢吡喃三醇1.0份、四氢甲基嘧啶羧酸0.5份、乙酰基六肽-8 0.2份和棕榈酰五肽-4 0.2份。5.0 parts of sodium hyaluronate, 1.0 part of recombinant collagen, 1.0 part of hydroxypropyltetrahydropyrantriol, 0.5 part of tetrahydromethylpyrimidine carboxylic acid, 0.2 part of acetyl hexapeptide-8 and palmitoyl pentapeptide-4 0.2 servings.

当微针贴负载上述重量份数的活性成分时，微针贴能够透过角质层将活性组分深层递送，对皮肤起到最佳的抗皱保湿效果。When the micro-needle patch is loaded with the above-mentioned active ingredients in parts by weight, the micro-needle patch can deeply deliver the active ingredient through the stratum corneum, and has the best anti-wrinkle and moisturizing effect on the skin.

第二方面，本发明提供了上述的微针贴的制备方法，包括以下步骤：In a second aspect, the present invention provides a method for preparing the above-mentioned microneedle patch, comprising the following steps:

1)按照配比称取上述组分，使用纯化水溶解组分，均质混匀配置成溶液；1) Weigh the above components according to the proportions, dissolve the components in purified water, and mix them uniformly to form a solution;

2)将步骤1)配置的溶液转移到聚二甲基硅氧烷微针模具中，刮涂处理，然后将聚二甲基硅氧烷微针模具放入真空干燥箱中，抽真空，然后将聚二甲基硅氧烷微针模具置于黑暗条件下干燥，干燥温度为3～5℃，剥离脱模，获得微针贴。2) Transfer the solution configured in step 1) into a polydimethylsiloxane microneedle mold, scrape coating, and then put the polydimethylsiloxane microneedle mold into a vacuum drying box, vacuumize, and then The polydimethylsiloxane microneedle mold is dried in a dark condition, and the drying temperature is 3-5° C., and the mold is peeled off to obtain a microneedle sticker.

作为本发明所述微针贴的制备方法的优选实施方式，所述步骤2)中，抽真空至-80Kpa。As a preferred embodiment of the method for preparing the microneedle patch of the present invention, in the step 2), the vacuum is evacuated to -80Kpa.

作为本发明所述微针贴的制备方法的优选实施方式，所述步骤2)中，干燥温度为4℃。As a preferred embodiment of the method for preparing the microneedle patch of the present invention, in the step 2), the drying temperature is 4°C.

作为本发明所述微针贴的制备方法的优选实施方式，所述步骤2)中，抽真空后，保持真空度持续3小时，直至没有气泡产生。As a preferred embodiment of the method for preparing the microneedle patch of the present invention, in the step 2), after vacuuming, the degree of vacuum is maintained for 3 hours until no bubbles are generated.

第三方面，本发明提供了上述的微针贴在美容产品中的应用。In a third aspect, the present invention provides the application of the above-mentioned microneedle patch in cosmetic products.

与现有技术相比，本发明具有以下有益效果：Compared with the prior art, the present invention has the following beneficial effects:

本发明提供了一种用于抗皱保湿的微针贴及其制备方法，本发明的微针贴中负载重组胶原蛋白、羟丙基四氢吡喃三醇、四氢甲基嘧啶羧酸、乙酰基六肽-8和棕榈酰五肽-4等活性成分，微针贴能够透过角质层形成微通道，同时含有透明质酸钠的针尖能够吸收组织液而溶解，然后将活性组分递送到皮下，停留在皮下的透明质酸钠以及重组胶原蛋白、羟丙基四氢吡喃三醇、四氢甲基嘧啶羧酸、乙酰基六肽-8和棕榈酰五肽-4等成分对皮肤起到较好的抗皱保湿效果。The invention provides a micro-needle patch for anti-wrinkle and moisturizing and a preparation method thereof. The micro-needle patch of the invention is loaded with recombinant collagen, hydroxypropyl tetrahydropyrantriol, tetrahydromethylpyrimidine carboxylic acid, acetyl Active ingredients such as base hexapeptide-8 and palmitoyl pentapeptide-4, the microneedle patch can form microchannels through the stratum corneum, while the needle tip containing sodium hyaluronate can absorb tissue fluid and dissolve, and then deliver the active ingredients subcutaneously , Sodium hyaluronate and ingredients such as recombinant collagen, hydroxypropyl tetrahydropyrantriol, tetrahydromethylpyrimidine carboxylic acid, acetyl hexapeptide-8 and palmitoyl pentapeptide-4 that stay under the skin are effective on the skin. For better anti-wrinkle moisturizing effect.

附图说明Description of drawings

图1为本发明用于抗皱保湿的微针贴的制备流程图；Fig. 1 is the preparation flow chart of the microneedle patch used for anti-wrinkle and moisturizing of the present invention;

图2为本发明用于抗皱保湿的微针贴的显微图像；Fig. 2 is the microscopic image of the micro-needle patch used for anti-wrinkle and moisturizing of the present invention;

图3为本发明用于抗皱保湿的微针贴的力学性能检测结果图；Fig. 3 is a graph showing the results of testing the mechanical properties of the micro-needle patch used for anti-wrinkle and moisturizing according to the present invention;

图4为使用实施例1制备的微针贴后受试者的角质层含水量分析结果图；4 is a graph showing the results of analyzing the moisture content of the stratum corneum of the subject after using the microneedle patch prepared in Example 1;

图5为使用实施例1制备的微针贴后受试者的鱼尾纹数量分析结果图；Fig. 5 is the analysis result of the number of crow's feet of subjects after using the microneedle patch prepared in Example 1;

图6为使用实施例1制备的微针贴后受试者的眼下纹数量分析结果图。6 is a graph showing the results of analysis on the number of under-eye wrinkles of subjects after using the microneedle patch prepared in Example 1.

具体实施方式Detailed ways

为更好的说明本发明的目的、技术方案和优点，下面将结合附图和具体实施例对本发明作进一步说明。In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below with reference to the accompanying drawings and specific embodiments.

在以下实施例和对比例中，所使用的实验方法如无特殊说明，均为常规方法，所用的材料、试剂等，如无特殊说明，均可从商业途径得到。In the following examples and comparative examples, the experimental methods used are conventional methods unless otherwise specified, and the materials, reagents, etc. used, unless otherwise specified, can be obtained from commercial sources.

实施例1Example 1

一种用于抗皱保湿的微针贴，包括基底和负载活性成分的针尖，活性成分包括以下重量的组分：A micro-needle patch for anti-wrinkle and moisturizing, comprising a base and a needle tip loaded with an active ingredient, the active ingredient comprises the following components by weight:

透明质酸钠5.0g、重组胶原蛋白1.0g、羟丙基四氢吡喃三醇1.0g、四氢甲基嘧啶羧酸0.5g、乙酰基六肽-8 0.2g和棕榈酰五肽-4 0.2g。Sodium Hyaluronate 5.0g, Recombinant Collagen 1.0g, Hydroxypropyl Tetrahydropyrantriol 1.0g, Tetrahydromethylpyrimidine Carboxylic Acid 0.5g, Acetyl Hexapeptide-8 0.2g and Palmitoyl Pentapeptide-4 0.2g.

上述用于抗皱保湿的微针贴的制备方法，包括以下步骤：The preparation method of the above-mentioned micro-needle patch for anti-wrinkle and moisturizing includes the following steps:

1)按照配比称取上述组分，使用纯化水溶解组分，通过均质搅拌器均质混匀配置成100ml的溶液，并对溶液进行离心消泡，离心速度为1500rpm，离心时间为10min，检测溶液的pH值；1) Weigh the above-mentioned components according to the proportions, dissolve the components with purified water, mix them uniformly with a homogenizer to prepare a solution of 100ml, and centrifuge the solution for defoaming, the centrifugal speed is 1500rpm, and the centrifugation time is 10min , to detect the pH value of the solution;

2)将步骤1)配置的溶液转移到聚二甲基硅氧烷(PDMS)微针模具中，刮涂处理，然后将聚二甲基硅氧烷微针模具放入真空干燥箱中，抽真空至-80KPa，保持真空度持续约3小时，直至没有气泡产生，然后将聚二甲基硅氧烷微针模具置于黑暗条件下干燥，干燥温度为4℃，用镊子小心地将模具上的微针剥离脱模，获得用于抗皱保湿的微针贴。微针贴的制备方法如图1所示。2) Transfer the solution prepared in step 1) into a polydimethylsiloxane (PDMS) microneedle mold, scrape coating, and then put the polydimethylsiloxane microneedle mold into a vacuum drying oven, and pump Vacuum to -80KPa, keep the vacuum for about 3 hours, until no bubbles are generated, then place the polydimethylsiloxane microneedle mold to dry in the dark, the drying temperature is 4 °C, and carefully place the mold on the mold with tweezers. The microneedle is peeled off the mold to obtain a microneedle patch for anti-wrinkle and moisturizing. The preparation method of the microneedle patch is shown in Figure 1.

实施例2Example 2

一种用于抗皱保湿的微针贴，包括基底和负载活性成分的针尖，活性成分包括以下重量的组分：A micro-needle patch for anti-wrinkle and moisturizing, comprising a base and a needle tip loaded with an active ingredient, the active ingredient comprises the following components by weight:

透明质酸钠2.5g、重组胶原蛋白0.5g、羟丙基四氢吡喃三醇0.5g、四氢甲基嘧啶羧酸0.8g、乙酰基六肽-8 0.1g和棕榈酰五肽-4 0.1g。Sodium Hyaluronate 2.5g, Recombinant Collagen 0.5g, Hydroxypropyl Tetrahydropyrantriol 0.5g, Tetrahydromethylpyrimidine Carboxylic Acid 0.8g, Acetyl Hexapeptide-8 0.1g and Palmitoyl Pentapeptide-4 0.1g.

上述用于抗皱保湿的微针贴的制备方法，包括以下步骤：The preparation method of the above-mentioned micro-needle patch for anti-wrinkle and moisturizing includes the following steps:

1)按照配比称取上述组分，使用纯化水溶解组分，通过均质搅拌器均质混匀配置成100ml的溶液，并对溶液进行离心消泡，离心速度为1500rpm，离心时间为10min，检测溶液的pH值；1) Weigh the above-mentioned components according to the proportions, dissolve the components with purified water, mix them uniformly with a homogenizer to prepare a solution of 100ml, and centrifuge the solution for defoaming, the centrifugal speed is 1500rpm, and the centrifugation time is 10min , to detect the pH value of the solution;

2)将步骤1)配置的溶液转移到聚二甲基硅氧烷(PDMS)微针模具中，刮涂处理，然后将聚二甲基硅氧烷微针模具放入真空干燥箱中，抽真空至-80KPa，保持真空度持续约3小时，直至没有气泡产生，然后将聚二甲基硅氧烷微针模具置于黑暗条件下干燥，干燥温度为3℃，用镊子小心地将模具上的微针剥离脱模，获得用于抗皱保湿的微针贴。2) Transfer the solution prepared in step 1) into a polydimethylsiloxane (PDMS) microneedle mold, scrape coating, and then put the polydimethylsiloxane microneedle mold into a vacuum drying oven, and pump Vacuum to -80KPa, keep the vacuum for about 3 hours, until no bubbles are generated, then place the polydimethylsiloxane microneedle mold to dry in the dark, the drying temperature is 3 °C, and carefully place the mold on the mold with tweezers. The microneedle is peeled off the mold to obtain a microneedle patch for anti-wrinkle and moisturizing.

实施例3Example 3

一种用于抗皱保湿的微针贴，包括基底和负载活性成分的针尖，活性成分包括以下重量的组分：A micro-needle patch for anti-wrinkle and moisturizing, comprising a base and a needle tip loaded with an active ingredient, the active ingredient comprises the following components by weight:

透明质酸钠7.5g、重组胶原蛋白1.5g、羟丙基四氢吡喃三醇1.5g、四氢甲基嘧啶羧酸0.2g、乙酰基六肽-8 0.3g和棕榈酰五肽-4 0.3g。Sodium Hyaluronate 7.5g, Recombinant Collagen 1.5g, Hydroxypropyl Tetrahydropyrantriol 1.5g, Tetrahydromethylpyrimidine Carboxylic Acid 0.2g, Acetyl Hexapeptide-8 0.3g and Palmitoyl Pentapeptide-4 0.3g.

上述用于抗皱保湿的微针贴的制备方法，包括以下步骤：The preparation method of the above-mentioned micro-needle patch for anti-wrinkle and moisturizing includes the following steps:

1)按照配比称取上述组分，使用纯化水溶解组分，通过均质搅拌器均质混匀配置成100ml的溶液，并对溶液进行离心消泡，离心速度为1500rpm，离心时间为10min，检测溶液的pH值；1) Weigh the above-mentioned components according to the proportions, dissolve the components with purified water, mix them uniformly with a homogenizer to prepare a solution of 100ml, and centrifuge the solution for defoaming, the centrifugal speed is 1500rpm, and the centrifugation time is 10min , to detect the pH value of the solution;

2)将步骤1)配置的溶液转移到聚二甲基硅氧烷(PDMS)微针模具中，刮涂处理，然后将聚二甲基硅氧烷微针模具放入真空干燥箱中，抽真空至-80KPa，保持真空度持续约3小时，直至没有气泡产生，然后将聚二甲基硅氧烷微针模具置于黑暗条件下干燥，干燥温度为5℃，用镊子小心地将模具上的微针剥离脱模，获得用于抗皱保湿的微针贴。2) Transfer the solution prepared in step 1) into a polydimethylsiloxane (PDMS) microneedle mold, scrape coating, and then put the polydimethylsiloxane microneedle mold into a vacuum drying oven, and pump Vacuum to -80KPa, keep the vacuum for about 3 hours, until no bubbles are generated, then place the polydimethylsiloxane microneedle mold to dry in the dark, the drying temperature is 5 °C, and carefully place the mold on the mold with tweezers. The microneedle is peeled off the mold to obtain a microneedle patch for anti-wrinkle and moisturizing.

实施例4Example 4

一种用于抗皱保湿的微针贴，包括基底和负载活性成分的针尖，活性成分包括以下重量的组分：A micro-needle patch for anti-wrinkle and moisturizing, comprising a base and a needle tip loaded with an active ingredient, the active ingredient comprises the following components by weight:

透明质酸钠6.0g、重组胶原蛋白1.0g、羟丙基四氢吡喃三醇1.0g、四氢甲基嘧啶羧酸0.6g、乙酰基六肽-8 0.2g和棕榈酰五肽-4 0.2g。Sodium Hyaluronate 6.0g, Recombinant Collagen 1.0g, Hydroxypropyl Tetrahydropyrantriol 1.0g, Tetrahydromethylpyrimidine Carboxylic Acid 0.6g, Acetyl Hexapeptide-8 0.2g and Palmitoyl Pentapeptide-4 0.2g.

上述用于抗皱保湿的微针贴的制备方法，包括以下步骤：The preparation method of the above-mentioned micro-needle patch for anti-wrinkle and moisturizing includes the following steps:

1)按照配比称取上述组分，使用纯化水溶解组分，通过均质搅拌器均质混匀配置成100ml的溶液，并对溶液进行离心消泡，离心速度为1500rpm，离心时间为10min，检测溶液的pH值；1) Weigh the above-mentioned components according to the proportions, dissolve the components with purified water, mix them uniformly with a homogenizer to prepare a solution of 100ml, and centrifuge the solution for defoaming, the centrifugal speed is 1500rpm, and the centrifugation time is 10min , to detect the pH value of the solution;

2)将步骤1)配置的溶液转移到聚二甲基硅氧烷(PDMS)微针模具中，刮涂处理，然后将聚二甲基硅氧烷微针模具放入真空干燥箱中，抽真空至-80KPa，保持真空度持续约3小时，直至没有气泡产生，然后将聚二甲基硅氧烷微针模具置于黑暗条件下干燥，干燥温度为4℃，用镊子小心地将模具上的微针剥离脱模，获得用于抗皱保湿的微针贴。2) Transfer the solution prepared in step 1) into a polydimethylsiloxane (PDMS) microneedle mold, scrape coating, and then put the polydimethylsiloxane microneedle mold into a vacuum drying oven, and pump Vacuum to -80KPa, keep the vacuum for about 3 hours, until no bubbles are generated, then place the polydimethylsiloxane microneedle mold to dry in the dark, the drying temperature is 4 °C, and carefully place the mold on the mold with tweezers. The microneedle is peeled off the mold to obtain a microneedle patch for anti-wrinkle and moisturizing.

对比例1Comparative Example 1

与实施例1相同，区别仅在于，用于抗皱保湿的微针贴不含有棕榈酰五肽-4，乙酰基六肽-8的重量为0.4g，其余组分及制备方法与实施例1相同。The same as Example 1, the only difference is that the microneedle patch used for anti-wrinkle and moisturizing does not contain palmitoyl pentapeptide-4, the weight of acetyl hexapeptide-8 is 0.4g, and the rest components and preparation methods are the same as those in Example 1. .

对比例2Comparative Example 2

与实施例1相同，区别仅在于，用于抗皱保湿的微针贴不含有乙酰基六肽-8，四氢甲基嘧啶羧酸的重量为1.5g，其余组分及制备方法与实施例1相同。The same as Example 1, the only difference is that the microneedle patch used for anti-wrinkle and moisturizing does not contain acetyl hexapeptide-8, the weight of tetrahydromethylpyrimidine carboxylic acid is 1.5g, and the remaining components and preparation methods are the same as those in Example 1. same.

对比例3Comparative Example 3

与实施例1相同，区别仅在于，用于抗皱保湿的微针贴中不含有重组胶原蛋白，其余组分及制备方法与实施例1相同。The same as Example 1, the only difference is that the microneedle patch used for anti-wrinkle and moisturizing does not contain recombinant collagen, and the other components and preparation methods are the same as those in Example 1.

对比例4Comparative Example 4

与实施例1相同，区别仅在于，用于抗皱保湿的微针贴中不含有四氢甲基嘧啶羧酸，其余组分及制备方法与实施例1相同。The same as Example 1, the only difference is that the microneedle patch used for anti-wrinkle and moisturizing does not contain tetrahydromethylpyrimidine carboxylic acid, and other components and preparation methods are the same as those in Example 1.

试验例一、用于抗皱保湿的微针贴的形貌观察Test Example 1. Morphology observation of microneedle patch used for anti-wrinkle and moisturizing

1、用于抗皱保湿的微针贴的宏观形貌观察1. Macroscopic observation of the micro-needle patch used for anti-wrinkle and moisturizing

将实施例1-4制备的用于抗皱保湿的微针贴放置于白色背景上，通过光学摄像头拍摄微针眼贴膜的宏观图像。结果表明，已成功制备出负载有重组胶原蛋白等有效组分的微针贴，其制备的微针贴为圆弧形，且只有在中间部位分布有微针。The microneedle patch for anti-wrinkle and moisturizing prepared in Examples 1-4 was placed on a white background, and a macro image of the microneedle eye patch was captured by an optical camera. The results show that the microneedle patch loaded with effective components such as recombinant collagen has been successfully prepared. The prepared microneedle patch is arc-shaped, and only the microneedle is distributed in the middle part.

2、用于抗皱保湿的微针贴的微观形貌观察2. Observation of the microscopic morphology of the micro-needle patch used for anti-wrinkle and moisturizing

将实施例1制备的微针贴放置于生物显微镜载物台上，调整显微镜放大倍数为40倍，通过显微镜拍摄软件获取微针贴的微观图像。如图2所示，为微针贴的针尖显微图像，从图中可以看出，制备的眼贴膜针尖为尖锐的圆锥形，且针尖结构较为完整，能赋予微针贴的针尖较好的性能去刺穿角质层，实现有效组分的皮下输送，发挥眼贴膜较好的美容效果。实施例2-4制备的微针贴其微观形貌与实施例1相似。The microneedle patch prepared in Example 1 was placed on the stage of a biological microscope, the magnification of the microscope was adjusted to 40 times, and the microscopic image of the microneedle patch was obtained through the microscope shooting software. As shown in Figure 2, it is the microscopic image of the needle tip of the microneedle patch. It can be seen from the figure that the needle tip of the prepared eye patch is sharp and conical, and the needle tip structure is relatively complete, which can give the needle tip of the microneedle patch better quality It can pierce the stratum corneum, realize the subcutaneous delivery of effective components, and exert the better cosmetic effect of the eye patch. The microscopic morphology of the microneedle patches prepared in Examples 2-4 is similar to that in Example 1.

试验例二、用于抗皱保湿的微针贴的力学性能测试Test example 2. Mechanical properties test of micro-needle patch used for anti-wrinkle and moisturizing

将制备好的微针贴放置于万能测力机的测试台上，微针贴面朝上，微针长200μm，设置压缩距离为微针长一半(100μm)，并记录压缩过程中的力学性能的变化。Place the prepared microneedle patch on the test table of the universal force measuring machine, with the microneedle patch facing up, the length of the microneedle is 200 μm, set the compression distance to half the length of the microneedle (100 μm), and record the mechanical properties during the compression process. The change.

参考图3，每根微针的最大屈折力学性能达到约0.6N，大于刺穿角质层所需最小力(0.045N)，说明准备的美容微针具有足够的力学性能刺穿角质层，能有效实现活性成分的皮下输送。实施例2-4制备的微针贴其力学性能也符合上述要求。Referring to Figure 3, the maximum inflection mechanical properties of each microneedle reaches about 0.6N, which is greater than the minimum force required to pierce the stratum corneum (0.045N), indicating that the prepared cosmetic microneedles have sufficient mechanical properties to pierce the stratum corneum and can effectively pierce the stratum corneum. Subcutaneous delivery of active ingredients is achieved. The mechanical properties of the microneedle patches prepared in Examples 2-4 also meet the above requirements.

试验例三、用于抗皱保湿的微针贴的角质层含水量、皱纹测试Test Example 3. Test on stratum corneum water content and wrinkle of microneedle patch used for anti-wrinkle and moisturizing

1、角质层含水量分析1. Analysis of water content in the stratum corneum

皮肤角质层含水量是衡量产品保湿性能的一大指标，由Corneomete，CM825测得，其数值越大，表示皮肤角质层水分含水量越高，皮肤角质层含水量在不同时间点与基线值(D0)相比上升越多，提示微针贴的保湿效果越好。The moisture content of the stratum corneum of the skin is a major indicator to measure the moisturizing performance of the product. It is measured by Corneomete, CM825. The larger the value, the higher the moisture content of the stratum corneum of the skin. Compared with D0), the higher the increase, the better the moisturizing effect of the microneedle patch.

选取10名受试者，男女各半，年龄为30～60，无皮肤病过敏史，符合受试者志愿入选标准。受试者使用实施例1制备的微针贴后，面颊皮肤角质层含水量的试验结果如图4所示：与基线值(D0)相比，面颊皮肤角质层含水量在D14(第14天)、D28(第28天)分别上升了20.74％、42.98％。表明本发明制备的用于抗皱保湿的微针贴对皮肤具有一定的保湿效果。Selected 10 subjects, half male and half, aged 30-60, no history of skin allergies, in line with the volunteer selection criteria of the subjects. After the subjects used the microneedle patch prepared in Example 1, the test results of the water content of the stratum corneum of the cheek skin were shown in Figure 4: compared with the baseline value (D0), the water content of the stratum corneum of the cheek skin was at ), D28 (28th day) increased by 20.74% and 42.98%, respectively. It shows that the micro-needle patch for anti-wrinkle and moisturizing prepared by the present invention has a certain moisturizing effect on the skin.

2、鱼尾纹数量分析2. Analysis of the number of crow's feet

选取10名受试者，男女各半，年龄为30～60，无皮肤病过敏史，符合受试者志愿入选标准。鱼尾纹数量是衡量产品抗皱性能的一大指标，鱼尾纹数量是用Primos CR拍摄受试者的眼角局部皮肤3D图像，再通过分析得到，鱼尾纹数量是能够较好反映鱼尾纹程度的参数。鱼尾纹数量越小，则表示鱼尾纹状况越好。Selected 10 subjects, half male and half, aged 30-60, no history of skin allergies, in line with the volunteer selection criteria of the subjects. The number of crow's feet is a major indicator to measure the anti-wrinkle performance of the product. The number of crow's feet is a 3D image of the subject's skin around the corner of the eye taken with Primos CR, and then analyzed. The number of crow's feet is a parameter that can better reflect the degree of crow's feet. The smaller the number of crow's feet, the better the condition of the crow's feet.

受试者使用实施例1制备的微针贴后，鱼尾纹数量的试验结果如图5所示：与基线值(D0)相比,鱼尾纹数量在D14(第14天)、D28(第28天)时分别下降了30.04％、40.08％。表明本发明制备的用于抗皱保湿的微针贴具有一定的抗皱效果，能够延缓鱼尾纹状况。After the subjects used the microneedle patch prepared in Example 1, the test results of the number of crow's feet are shown in Figure 5: compared with the baseline value (D0), the number of crow's feet was in D14 (day 14), D28 (day 28) decreased by 30.04% and 40.08% respectively. It shows that the micro-needle patch for anti-wrinkle and moisturizing prepared by the present invention has a certain anti-wrinkle effect and can delay the condition of crow's feet.

3、眼下纹数量分析3. Analysis of the number of wrinkles under the eyes

眼下纹数量是衡量产品抗皱性能的一大指标，是用Primos CR拍摄受试者的眼下局部皮肤3D图像，再通过分析得到，眼下纹数量是能够较好反映眼下纹程度的参数。眼下纹数量数值越小，则表示眼下纹状况越好。The number of under-eye wrinkles is a major indicator for measuring the anti-wrinkle performance of the product. Primos CR is used to take a 3D image of the subject's under-eye skin, and then through analysis, the number of under-eye wrinkles is a parameter that can better reflect the degree of under-eye wrinkles. The smaller the number of wrinkles, the better the wrinkles are.

选取10名受试者，男女各半，年龄为30～60，无皮肤病过敏史，符合受试者志愿入选标准。受试者使用实施例1制备的微针贴后，鱼尾纹数量的试验结果如图6所示：与基线值(D0)相比,鱼尾纹数量在D14(第14天)、D28(第28天)时分别下降了29.24％、35.12％。表明本发明制备的用于抗皱保湿的微针贴具有一定的抗皱效果，能够延缓眼下纹状况。Selected 10 subjects, half male and half, aged 30-60, no history of skin allergies, in line with the volunteer selection criteria of the subjects. After the subjects used the microneedle patch prepared in Example 1, the test results of the number of crow's feet are shown in Figure 6: compared with the baseline value (D0), the number of crow's feet was in D14 (day 14), D28 (day 28) decreased by 29.24% and 35.12% respectively. It shows that the micro-needle patch for anti-wrinkle and moisturizing prepared by the present invention has a certain anti-wrinkle effect and can delay the condition of wrinkles under the eyes.

4、用于抗皱保湿的微针贴使用效果对比4. Comparison of the use effect of micro-needle stickers for anti-wrinkle and moisturizing

选取80名受试者，男女各半，年龄为30～60，无皮肤病过敏史，符合受试者志愿入选标准，将受试者平均随机分为8组，每组10人。以实施例1-4以及对比例1-4制备的微针贴作为受试产品，分别作用于8组受试者。使用方法：将微针贴贴于眼周皱纹处，每天晚上贴覆1次，30分钟后揭下，试用28天。疗效标准如下：效果显著：皱纹消失；有效：皱纹变浅；无效：皮肤无明显变化。A total of 80 subjects, half male and female, aged 30-60, with no history of skin allergies, and meeting the volunteer selection criteria, were randomly divided into 8 groups, with 10 people in each group. The microneedle patches prepared in Examples 1-4 and Comparative Examples 1-4 were used as test products, and acted on 8 groups of subjects respectively. How to use: Apply the microneedle patch to the wrinkles around the eyes, apply it once every night, remove it after 30 minutes, and try it out for 28 days. The curative effect criteria are as follows: significant effect: wrinkles disappear; effective: wrinkles become lighter; ineffective: no obvious changes in skin.

表1：受试者使用28天后的结果Table 1: Subject results after 28 days of use

组别group效果显著人数Significant effect有效人数Effective number of people无效人数Invalid number总有效率total efficiency实施例1Example 177221190％90%实施例2Example 266222280％80%实施例3Example 366331190％90%实施例4Example 455332280％80%对比例1Comparative Example 100446640％40%对比例2Comparative Example 200555550％50%对比例3Comparative Example 300337730％30%对比例4Comparative Example 400446640％40%

28天后统计受试者的反馈情况，结果如表1所示。从表中可以看出，实施例1-4制备的微针贴效果远好于对比例1-4的效果。After 28 days, the feedback of the subjects was counted, and the results are shown in Table 1. It can be seen from the table that the effects of the microneedle patches prepared in Examples 1-4 are much better than those of Comparative Examples 1-4.

本发明提供了一种用于抗皱保湿的微针贴及其制备方法，本发明的微针贴中负载重组胶原蛋白、羟丙基四氢吡喃三醇、四氢甲基嘧啶羧酸、乙酰基六肽-8和棕榈酰五肽-4等活性成分，微针贴能够透过角质层形成微通道，同时含有透明质酸钠的针尖能够吸收组织液而溶解，然后将活性组分递送到皮下，停留在皮下的透明质酸钠以及重组胶原蛋白、羟丙基四氢吡喃三醇、四氢甲基嘧啶羧酸、乙酰基六肽-8和棕榈酰五肽-4等成分对皮肤起到较好的抗皱保湿效果以及一定的祛黑紧致效果。The invention provides a micro-needle patch for anti-wrinkle and moisturizing and a preparation method thereof. The micro-needle patch of the invention is loaded with recombinant collagen, hydroxypropyl tetrahydropyrantriol, tetrahydromethylpyrimidine carboxylic acid, acetyl Active ingredients such as base hexapeptide-8 and palmitoyl pentapeptide-4, the microneedle patch can penetrate the stratum corneum to form microchannels, and the needle tip containing sodium hyaluronate can absorb tissue fluid and dissolve, and then deliver the active ingredients subcutaneously , Sodium hyaluronate and ingredients such as recombinant collagen, hydroxypropyl tetrahydropyrantriol, tetrahydromethylpyrimidine carboxylic acid, acetyl hexapeptide-8 and palmitoyl pentapeptide-4 that stay under the skin have a good effect on the skin. To a better anti-wrinkle moisturizing effect and a certain darkening firming effect.

最后所应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的实质和范围。Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the protection scope of the present invention. Although the present invention is described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that, The technical solutions of the present invention may be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention.

Claims (8)

1. The microneedle patch for resisting wrinkles and preserving moisture is characterized by comprising a substrate and a needle point loaded with active ingredients, wherein the active ingredients comprise the following components in parts by weight:

2.5-7.5 parts of sodium hyaluronate, 0.5-1.5 parts of recombinant collagen, 0.5-1.5 parts of hydroxypropyl tetrahydropyrane triol, 0.2-0.8 part of tetrahydro methylpyrimidine carboxylic acid, 80.1-0.3 part of acetyl hexapeptide and 40.1-0.3 part of palmitoyl pentapeptide.

2. The microneedle patch according to claim 1, wherein the active ingredient comprises the following components in parts by weight:

5.0-7.5 parts of sodium hyaluronate, 1.0-1.5 parts of recombinant collagen, 1.0-1.5 parts of hydroxypropyl tetrahydropyrane triol, 0.2-0.5 part of tetrahydro methylpyrimidine carboxylic acid, 80.1-0.2 parts of acetyl hexapeptide and 40.1-0.2 parts of palmitoyl pentapeptide.

3. The microneedle patch according to claim 1, wherein the active ingredient comprises the following components in parts by weight:

5.0 parts of sodium hyaluronate, 1.0 part of recombinant collagen, 1.0 part of hydroxypropyl tetrahydropyrane triol, 0.5 part of tetrahydro methylpyrimidine carboxylic acid, 80.2 parts of acetyl hexapeptide and 40.2 parts of palmitoyl pentapeptide.

4. A method for preparing a microneedle patch according to any one of claims 1 to 3, comprising the steps of:

1) weighing the components according to the proportion, dissolving the components by using purified water, homogenizing and mixing uniformly to prepare a solution;

2) transferring the solution prepared in the step 1) into a polydimethylsiloxane microneedle mould, carrying out blade coating treatment, then putting the polydimethylsiloxane microneedle mould into a vacuum drying oven, vacuumizing, then drying the polydimethylsiloxane microneedle mould in the dark at the drying temperature of 3-5 ℃, stripping and demoulding to obtain the microneedle patch.

5. The method for preparing a microneedle patch according to claim 4, wherein in the step 2), a vacuum is applied to-80 Kpa.

6. The method for preparing a microneedle patch according to claim 4, wherein the drying temperature in the step 2) is 4 ℃.

7. A method for preparing a microneedle patch according to claim 5, wherein after the vacuum pumping, the vacuum degree is maintained for 3 hours until no air bubbles are generated.

8. Use of the microneedle patch according to any one of claims 1 to 3 in a cosmetic product.

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