KR102274599B1 - Novel Cinnamic Acid Derivatives and Antimicrobial Compositions Comprising the Same - Google Patents
Novel Cinnamic Acid Derivatives and Antimicrobial Compositions Comprising the SameDownload PDFInfo
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Abstract
Translated fromKoreanDescription
Translated fromKorean본 발명은 우수한 항균 효과를 가지는 신규 계피산 유도체에 관한 것이다. 더 상세하게는 본 발명은 항균 효과 및 우수한 수용해성을 동시에 갖는 신규 계피산 유도체 및 이를 포함하는 조성물에 관한 것이다.The present invention relates to a novel cinnamic acid derivative having an excellent antibacterial effect. More particularly, the present invention relates to a novel cinnamic acid derivative having both an antibacterial effect and excellent water solubility, and a composition comprising the same.
우리 생활주변에서 널리 이용되는 식품, 의약품, 생활용품, 화장품 등의 많은 제품에는 보습제, 오일, 계면활성제, 무기분말, 유기 수용성 고분자, 향료 등의 다양한 재료들이 함유되어 있어 미생물이 성장하기에 적합한 상태이다. 따라서, 미생물에 의해 제품이 부패하는 것을 방지하고, 미생물을 경시적으로 사멸시켜 제품의 열화를 방지하기 위하여 화학적 방부제를 첨가하는 것이 일반적이다. 이러한 화학적 방부제로서 파라벤, 이미다졸리디닐 우레아, 페녹시 에탄올, 파라옥시안식향산 에스테르 또는 염화벤잘코늄 등이 일반적으로 사용되고 있다.Many products such as foods, medicines, daily products, and cosmetics widely used in our daily life contain various materials such as moisturizers, oils, surfactants, inorganic powders, organic water-soluble polymers, and fragrances, which are suitable for the growth of microorganisms. to be. Therefore, it is common to add a chemical preservative to prevent the product from decaying by microorganisms and to prevent deterioration of the product by killing the microorganisms over time. As such chemical preservatives, parabens, imidazolidinyl urea, phenoxy ethanol, paraoxybenzoic acid esters, or benzalkonium chloride are generally used.
그러나, 최근 단백질, 검, 비타민, 약용 식물 등 새로운 첨가물이 제품에 추가되면서, 미생물의 작용으로 인해 생기는 변화도 다양해지고 화학적 방부제에 의한 방부효과가 약해져, 화학적 방부제의 함량이 증가됨에 따라, 피부에 대한 자극, 알러지 증상 등이 유발되는 등 인체유해성의 문제점이 대두되고 있다.However, as new additives such as proteins, gums, vitamins, and medicinal plants are recently added to products, the changes caused by the action of microorganisms are diversified and the antiseptic effect of chemical preservatives is weakened, and as the content of chemical preservatives increases, skin The problem of harm to the human body, such as irritation and allergy symptoms, is emerging.
따라서, 화학적 방부제를 함유하지 않거나 적은 함량을 함유하여도 미생물에 의해 오염되지 않는 새로운 제품들이 요구되고 있다.Accordingly, there is a demand for new products that do not contain chemical preservatives or are not contaminated by microorganisms even if they contain a small amount.
한편, 천연물인 계피산 및 계피 알데히드는 항균효과가 있다고 알려져 부분적으로 사용되기도 하지만, 첫째로 용해도가 낮고(계피산 0.05%, 4-히드록시 계피산 0.2% 수준), 둘째로 적용 pH가 산성에서 중성으로 변화함에 따라 활성을 잃는 문제점이 있어 화장품 및 인체용품에서의 보존 용도로의 적용이 어려웠다. 이는 일반적인 산 형태의 보존제 특징이기도 하다. 계피산 유도체중 에틸 페룰레이트(Ethyl ferulate)가 산화방지제 및 방부제 용도로 화장품원료로 등재되어 있지만, 물에 거의 녹지 않으며, 제품 보존제로서 사용된 예는 알려진 바 없다.On the other hand, natural products such as cinnamic acid and cinnamon aldehyde are known to have antibacterial effects and are partially used, but firstly, their solubility is low (cinnamic acid 0.05%, 4-hydroxy cinnamic acid level of 0.2%), and secondly, the applied pH changes from acidic to neutral There is a problem in that activity is lost as a result, making it difficult to apply it for preservation purposes in cosmetics and human body products. This is also characteristic of the common acid form of preservatives. Among the cinnamic acid derivatives, Ethyl ferulate is registered as a cosmetic ingredient for use as an antioxidant and preservative, but it is hardly soluble in water, and there is no known example of its use as a product preservative.
본 명세서 전체에 걸쳐 다수의 문헌이 참조되고 그 인용이 표시되어 있다. 인용된 문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.Numerous references are referenced throughout this specification and citations thereof are indicated. The disclosures of the cited documents are incorporated herein by reference in their entirety to more clearly describe the content of the present invention and the level of the art to which the present invention pertains.
본 발명자들은 화장품 및 인체용품 등에 처방이 가능하며 방부제를 대체할 수 있는 천연물질 유래 화합물을 제공하기 위하여 연구 노력한 결과, 신규한 구조의 계피산 아마이드 유도체를 합성하고 이들 화합물이 우수한 항균 효과와 동시에 우수한 수용해성을 가지므로, 보존제로서 화장품 및 인체용품에 적용가능함을 확인해냄으로써, 본 발명을 완성하게 되었다.As a result of research efforts to provide a compound derived from a natural substance that can be prescribed for cosmetics and human body products and can be used as an alternative to preservatives, the present inventors synthesized a cinnamic acid amide derivative having a novel structure, and these compounds have excellent antibacterial effect and excellent water Since it has solubility, the present invention has been completed by confirming that it can be applied to cosmetics and human body products as a preservative.
따라서 본 발명의 목적은 항균 활성 및 수용해성을 동시에 가지는 신규한 계피산 유도체 화합물을 제공하는 데 있다.Accordingly, an object of the present invention is to provide a novel cinnamic acid derivative compound having both antibacterial activity and water solubility.
본 발명의 다른 목적은 상기 신규한 계피산 유도체 화합물을 포함하는 조성물을 제공하는데 있다.Another object of the present invention is to provide a composition comprising the novel cinnamic acid derivative compound.
본 발명의 또 다른 목적은 상기 신규한 계피산 유도체 화합물을 포함하는 식품, 의약품, 의약외품, 생활용품 및 화장품 등의 제품을 제공하는데 있다.Another object of the present invention is to provide products such as food, pharmaceuticals, quasi-drugs, household goods and cosmetics containing the novel cinnamic acid derivative compound.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 하나의 관점은 하기 화학식 1로 표시되는 계피산 유도체 화합물을 제공하는 것이다.One aspect of the present invention is to provide a cinnamic acid derivative compound represented by the following formula (1).
<화학식 1><Formula 1>
상기 식에서,In the above formula,
R1은 수소, C1-C2 알킬, OH, OCH3, Cl 또는 Br이고,R1 is hydrogen, C1 -C2 alkyl, OH, OCH3 , Cl or Br,
R2는 수소, C1-C2 알킬, OH, OCH3, Cl 또는 Br이고, R3는 수소, C1-C2 알킬, OH, OCH3, Cl 또는 Br이거나; 또는 R2 및 R3은 서로 연결되어 산소원자를 포함하는 헤테로고리를 형성하고,R2 is hydrogen, C1 -C2 alkyl, OH, OCH3 , Cl or Br, and R3 is hydrogen, C1 -C2 alkyl, OH, OCH3 , Cl or Br; Or R2 and R3 are connected to each other to form a heterocycle containing an oxygen atom,
A는 NHR21,
여기서 R21은 (CH2)mR211이며, m은 1 내지 2의 정수이며, R211은
R22는 수소, C1-C2 알킬, 또는
본 발명의 화합물은 구조적으로 연구가 거의 되어 있지 않은 바, 계피산에 알킬아미드기 혹은 사이클릭 아미드기를 도입함으로써 용해도를 크게 증가시킬 수 있었으며, 산성인 계피산 화합물이 중성 조성물에 첨가되었을 때 그 활성을 잃는 것과는 달리 본 발명의 화합물은 중성 pH 조건에서도 그 활성을 잃지 않아 화장품 및 인체용품의 다양한 pH조건에 처방하여 사용할 수 있음을 확인하였다.Since the compound of the present invention has not been studied structurally, its solubility can be greatly increased by introducing an alkylamide group or a cyclic amide group to cinnamic acid, and when an acidic cinnamic acid compound is added to a neutral composition, its activity is lost. Contrary to this, it was confirmed that the compound of the present invention does not lose its activity even under a neutral pH condition and can be prescribed and used for various pH conditions of cosmetics and human products.
본 발명에 따른 상기 화학식 1의 계피산 유도체의 바람직한 예로는 하기 화학식 2 내지 화학식 3으로부터 선택되는 화합물이다.Preferred examples of the cinnamic acid derivative of Formula 1 according to the present invention are compounds selected from Formulas 2 to 3 below.
<화학식 2><Formula 2>
<화학식 3><Formula 3>
또한, 본 발명에 따른 신규 계피산 유도체는 하기의 화합물로 예시될 수 있으나, 하기의 화합물들이 본 발명을 한정하는 것은 아니다.In addition, the novel cinnamic acid derivative according to the present invention may be exemplified by the following compounds, but the following compounds are not intended to limit the present invention.
(CA-1)
(CA-7)
(CA-9)
(CA-12)
(CA-14)
(CA-16)
(CA-18)
본 발명에 따른 상기 화학식 1의 계피산 유도체 화합물들의 합성 반응의 예시를 아래 반응식 1에 나타내었다.An example of the synthesis reaction of the cinnamic acid derivative compounds of Formula 1 according to the present invention is shown in Scheme 1 below.
<반응식 1><Scheme 1>
상기 반응식 1에 나타낸 바와 같이 화학식 1의 화합물은 계피산 유도체와 1차 또는 2차 아민 유도체의 커플링 반응을 통해 합성될 수 있다.As shown in Scheme 1, the compound of Formula 1 may be synthesized through a coupling reaction between a cinnamic acid derivative and a primary or secondary amine derivative.
본 발명에서 계피산 유도체는 보존제로서 사용되어, 우수한 항균 및 방부 효과를 발휘할 수 있다. 구체적으로, 본 발명의 항균용 조성물은 바람직하게는 세균, 진균 또는 효모에 대해 항균 활성을 가질 수 있으며, 더욱 바람직하게는 대장균 (Escherichia coli), 녹농균 (Pseudomonas aeruginosa), 칸디다균 (Candida albicans), 흑곰팡이(Aspergillus niger)에 동시에 항균 활성을 가질 수 있으나, 이에 제한되지 않는다.In the present invention, the cinnamic acid derivative is used as a preservative, and can exhibit excellent antibacterial and antiseptic effects. Specifically, the antibacterial composition of the present invention may preferably have antibacterial activity against bacteria, fungi or yeast, and more preferably Escherichia coli, Pseudomonas aeruginosa, Candida albicans, It may have antibacterial activity against black mold (Aspergillus niger) at the same time, but is not limited thereto.
본 발명에서 용어, "항균"은 균에 저항하는 능력을 의미하며, 세균이나 진균, 곰팡이, 효모 등과 같은 미생물의 작용으로부터 방어하기 위해 이루어지는 모든 기작을 의미한다. 본 발명의 계피산 유도체를 포함하는 조성물은 세균, 진균 및 효모를 포함하는 미생물에 대한 항균 활성이 뛰어난 것을 확인하였다.As used herein, the term “antibacterial” refers to the ability to resist bacteria, and refers to all mechanisms made to defend against the action of microorganisms such as bacteria, fungi, mold, yeast, and the like. It was confirmed that the composition containing the cinnamic acid derivative of the present invention has excellent antibacterial activity against microorganisms including bacteria, fungi and yeast.
본 발명에서 용어, "세균"은 박테리아에 속하는 생물로서, 생명체들 중에 가장 많이 번성한 종으로 대부분 병원성 균이며 원핵생물의 특징을 그대로 가지고 있으나, 핵막이나 미토콘드리아, 엽록체와 같은 구조는 가지고 있지 않다. 크기는 0.5 μm 부터 0.5 mm까지 다양하다. 상기 세균으로는 예를 들어, 스타필로코커스 아우레우스 (Staphylococcus aureus ATCC 6538), 세도모나스 애루지노사 (Pseudomonas aeruginosa ATCC 15522) 및 에스케리치아 콜라이 (Escherichia coli ATCC10536) 등을 포함하나 이에 제한되는 것은 아니다.As used herein, the term "bacteria" refers to an organism belonging to bacteria, the most prosperous species among living organisms, and is mostly pathogenic and has the characteristics of prokaryotes as it is, but does not have structures such as nuclear membranes, mitochondria, and chloroplasts. The size varies from 0.5 μm to 0.5 mm. Examples of the bacteria include, but are not limited to, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 15522 and Escherichia coli ATCC10536, etc. no.
본 발명에서 용어, "진균"은 곰팡이, 효모, 버섯을 포함한 72,000종 이상의 균종으로 구성되는 미생물군을 총칭 하며, 핵막이 있는 진핵생물에 속하고, 미토콘드리아, 소포체 등의 세포 소기관이 발달해 있으며, 키틴, 글루칸 등으로 구성된 세포벽이 있다. 대부분은 세포성인 균사를 형성하여 신장, 발육하고 유성생식 및 무성생식을 하는 것이 특징이다. 번식체로 포자를 형성하지만 일부 균종은 단세포성 증식을 한다. 주로 부생균으로서 자연계의 유기분해에 관여하지만, 일부는 동식물에 기생 또는 공생한다. 상기 진균에는 예를 들어, 아스퍼질러스 나이거 (Aspergillus niger ATCC 9642) 및 칸디다 알비칸스 (Candida albicans ATCC 10231) 등이 포함되나 이에 제한되는 것은 아니다.As used herein, the term "fungus" refers to a group of microorganisms composed of more than 72,000 species including mold, yeast, and mushrooms, belongs to eukaryotes with a nuclear membrane, and organelles such as mitochondria and endoplasmic reticulum are developed, There is a cell wall composed of chitin and glucan. Most of them form cellular hyphae, elongate and develop, and are characterized by sexual and asexual reproduction. They form spores as propagules, but some species reproduce unicellularly. It is mainly involved in organic decomposition in nature as saprophytes, but some are parasitic or symbiotic with animals and plants. The fungi include, for example, Aspergillus niger (Aspergillus niger ATCC 9642) and Candida albicans (Candida albicans ATCC 10231), but are not limited thereto.
본 발명에서 계피산 유도체는 보존제로서 사용되어, 우수한 항균 및 방부 효과를 발휘할 수 있으며, 이를 위한 상기 계피산 유도체의 함량은 전체 조성물 총 중량에 대하여 0.1 내지 10 중량%(w/v) 또는 0.5 내지 2 중량%(w/v)로 포함될 수 있다. 상기 함량 범위에서 항균 및 보존 효과가 우수하다. 상기 계피산 유도체의 함량이 0.1 중량% 미만이면 항균 및 방부 효과에 크게 도움이 되지 않으며, 10 중량%를 초과하면 함유량 증가에 따른 뚜렷한 효과의 증가가 나타나지 않기 때문이다.In the present invention, the cinnamic acid derivative is used as a preservative, and can exhibit excellent antibacterial and antiseptic effects, for which the content of the cinnamic acid derivative is 0.1 to 10% by weight (w/v) or 0.5 to 2% by weight based on the total weight of the composition. It can be included as %(w/v). Antibacterial and preservative effects are excellent in the above content range. If the content of the cinnamic acid derivative is less than 0.1% by weight, it does not significantly help antibacterial and antiseptic effects, and if it exceeds 10% by weight, it is because there is no significant increase in the effect according to the increase in the content.
또한, 본 발명의 인체용품 조성물은 계피산 유도체 외에 화학적 방부제를 추가로 포함할 수 있다. 이 경우, 계피산 유도체는 화학적 방부제와 함께 사용되어, 시너지 효과가 발생하여 더욱 뛰어난 항균 및 방부 효과를 발휘할 수 있다. 구체적으로, 상기 계피산 유도체는 우수한 항균 및 방부 효과를 발휘하므로, 미량의 화학적 방부제를 사용하여도 뛰어난 항균 및 방부 효과를 발휘할 수 있다. 따라서, 과량의 화학적 방부제를 사용하는 종래의 화장료 조성물이 피부 자극 및 알러지 등의 피부 부작용을 일으키는 것과 달리, 본 발명의 인체용품 조성물은 피부 자극 및 알러지 등의 피부 부작용을 거의 일으키지 않는다.In addition, the human body composition of the present invention may further include a chemical preservative in addition to the cinnamic acid derivative. In this case, the cinnamic acid derivative can be used together with a chemical preservative to generate a synergistic effect, thereby exhibiting more excellent antibacterial and antiseptic effects. Specifically, since the cinnamic acid derivative exhibits excellent antibacterial and antiseptic effects, it is possible to exhibit excellent antibacterial and antiseptic effects even with a small amount of chemical preservatives. Therefore, unlike conventional cosmetic compositions using an excessive amount of chemical preservatives cause skin side effects such as skin irritation and allergies, the composition for human body products of the present invention hardly causes skin side effects such as skin irritation and allergies.
상기 화학적 방부제로는 예를 들어, 3-헥실옥시-1,2-프로판다이올, 1,2-헥산다이올, 옥탄다이올과 같은 폴리올, 메틸파라벤, 에틸파라벤 또는 프로필파라벤 등의 파라벤, 및 페녹시에탄올 등으로 이루어진 그룹으로부터 선택된 하나, 또는 둘 이상 혼합하여 사용할 수 있다.Examples of the chemical preservative include polyols such as 3-hexyloxy-1,2-propanediol, 1,2-hexanediol, and octanediol, parabens such as methylparaben, ethylparaben or propylparaben; and one selected from the group consisting of phenoxyethanol and the like, or a mixture of two or more may be used.
상기 화학적 방부제의 함량은 전체 조성물 총 중량에 대하여 0.01 내지 30 중량%, 0.1 내지 10 중량% 또는 0.5 내지 5 중량%일 수 있다. 상기 범위에서 계피산 유도체와 시너지 효과가 우수하며, 30 중량%를 초과하면 피부 자극 및 알러지 등의 피부 부작용이 발생할 우려가 있다.The content of the chemical preservative may be 0.01 to 30% by weight, 0.1 to 10% by weight, or 0.5 to 5% by weight based on the total weight of the composition. In the above range, the synergistic effect with the cinnamic acid derivative is excellent, and when it exceeds 30% by weight, there is a risk of skin side effects such as skin irritation and allergies.
또한, 본 발명의 계피산 유도체 화합물은 항균 활성 및 수용해성을 동시에 가질 수 있다. 이 경우 상기 계피산 유도체 화합물의 상온(15~25℃)에서의 수용해도는 1 내지 10%, 바람직하게는 1.5 내지 5%로서, 상온의 물 100g에 화합물 1 내지 10g, 바람직하게는 1.5 내지 5g이 용해될 수 있다.In addition, the cinnamic acid derivative compound of the present invention may have both antibacterial activity and water solubility. In this case, the aqueous solubility of the cinnamic acid derivative compound at room temperature (15 to 25° C.) is 1 to 10%, preferably 1.5 to 5%, and 1 to 10 g, preferably 1.5 to 5 g of the compound in 100 g of water at room temperature is can be dissolved.
본 발명의 다른 관점은 상기 계피산 유도체 화합물, 또는 그의 염, 수화물 또는 용매화물을 포함하는 것을 특징으로 하는 조성물을 제공하는 것이다.Another aspect of the present invention is to provide a composition comprising the cinnamic acid derivative compound, or a salt, hydrate or solvate thereof.
상기 염은 하이드로클로라이드, 하이드로브로마이드 또는 하이드로요오다이드와 같은 무기산, 아세테이트, 아디페이트, 알기네이트, 아스파르테이트, 벤조에이트, 벤젠술포네이트, p-톨루엔설포네이트, 비설페이트, 설파메이트, 설페이트, 나프틸레이트, 부티레이트, 시트레이트, 캄포레이트, 캄포설포네이트, 시클로펜탄프로피오네이트, 디글루코네이트, 도데실설페이트, 에탄설포네이트, 푸마레이트, 글루코헵타노에이트, 글리세로포스페이트, 헤미설페이트, 헵타노에이트, 헥사노에이트, 2-히드록시에탄설페이트, 락테이트, 말리에이트, 메탄설포네이트, 2-나프탈렌설포네이트, 니코티네이트, 옥살레이트, 토실레이트 또는 운데카노에이트와 같은 유기산을 이용하여 형성될 수 있다. The salts include inorganic acids such as hydrochloride, hydrobromide or hydroiodide, acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, p-toluenesulfonate, bisulfate, sulfamate, sulfate, Naphthylate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulphate, hep Formed using organic acids such as tanoate, hexanoate, 2-hydroxyethanesulfate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, tosylate or undecanoate can be
수화물은 상기 화합물에 물이 더해지거나 분자의 구성 물질로 물이 들어간 물질을 말하며, 용매화물은 용질의 분자나 이온과 용매의 분자나 이온 사이에 생긴 고차의 화합물을 의미한다. 상기 수화물 또는 용매화물은 전술한 산을 이용하여 제조될 수도 있다.A hydrate refers to a substance in which water is added to the compound or water is added as a component of a molecule, and a solvate refers to a higher-order compound formed between a molecule or ion of a solute and a molecule or ion of a solvent. The hydrate or solvate may be prepared using the above-described acid.
상기 조성물은 항균 조성물일 수 있는데, 이 경우 다른 성분들과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 제형화 될 수 있다. 이러한 다른 성분들은 항균 조성물의 제형 또는 사용목적 등에 따라 임의로 선정하여 배합할 수 있다. 예를 들어, 점증제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 및 담체 등을 포함할 수 있다.The composition may be an antibacterial composition, in which case it may be used together with other ingredients, and may be appropriately formulated according to a conventional method. These other components may be arbitrarily selected and formulated according to the formulation or purpose of use of the antimicrobial composition. For example, it may contain conventional adjuvants such as thickeners, stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers and the like.
본 발명의 항균용 조성물은 화장료 조성물, 방부제 조성물, 약학적 조성물 및 의약외품 조성물에 항균을 위하여 첨가할 수 있다. 본 발명의 계피산 유도체를 유효성분으로 함유하는 항균용 조성물은 예를 들면, 액상, 크림상, 페이스트상, 고체상 등 어떠한 제형으로도 응용될 수 있으며, 그 용도는 다양한 분야에 적용될 수 있다. 예를 들면, 전신, 피부, 구강, 모발 등 인체관련 세정제 등 각종 화장료 조성물 등에 적용될 수 있다.The antibacterial composition of the present invention may be added to a cosmetic composition, an antiseptic composition, a pharmaceutical composition, and a quasi-drug composition for antibacterial purposes. The antibacterial composition containing the cinnamic acid derivative of the present invention as an active ingredient can be applied in any formulation, such as liquid, cream, paste, solid, etc., and its use can be applied to various fields. For example, it can be applied to various cosmetic compositions such as body-related detergents for the whole body, skin, oral cavity, and hair.
본 발명의 조성물이 화장료 조성물인 경우 당업계에 공지된 화장품의 형태로 다양하게 제형화될 수 있으며, 그 제형 및 사용목적에 따라 추가의 성분을 임의로 선정하여 적절히 배합할 수 있다. 예를 들어, 점증제, 계면활성제, 보습제, 연마제, 감미제, pH조정제, 방부제, 결합제, 습윤제, 기포제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 성분을 포함할 수 있다.When the composition of the present invention is a cosmetic composition, it may be variously formulated in the form of cosmetics known in the art, and additional ingredients may be arbitrarily selected and appropriately formulated according to the formulation and purpose of use. For example, it may contain conventional ingredients such as thickeners, surfactants, humectants, abrasives, sweeteners, pH adjusters, preservatives, binders, wetting agents, foaming agents, stabilizers, solubilizers, vitamins, pigments and fragrances.
본 발명의 또 다른 관점은 전술한 조성물을 포함하는 제품으로서, 식품, 의약품, 의약외품, 생활용품 및 화장품으로 이루어진 군으로부터 선택되는 제품을 제공하는 것이다.Another aspect of the present invention is to provide a product comprising the above-described composition, a product selected from the group consisting of food, pharmaceuticals, quasi-drugs, household goods and cosmetics.
상기 식품은 일반 식품, 건강보조식품, 건강기능식품, 기능성 식품, 피부미용 식품, 동물 식품 등을 포함하며 이에 제한되는 것은 아니다. 천연식품, 가공식품, 일반적인 식자재 등에 본 발명의 조성물을 첨가한 것도 본 발명의 식품의 범위에 포함된다.The food includes, but is not limited to, general food, health supplement food, health functional food, functional food, skin beauty food, animal food, and the like. Also included in the scope of the food of the present invention is that the composition of the present invention is added to natural food, processed food, general food material, etc.
상기 의약품은 일반의약품, 전문의약품, 한의약품 및 동물의약품을 포함하여 질병을 치료하거나 증상을 완화하는 데 쓰이는 제품을 의미한다.The above medicines refer to products used to treat diseases or alleviate symptoms, including over-the-counter medicines, prescription medicines, oriental medicines, and veterinary medicines.
의약외품은 구강제제, 살충제, 살서제, 살균제, 소독제제, 액취방지제, 짓무름용제, 콘택트렌즈관리용품, 연고제, 외용 소독제, 비타민 및 자양강장제 등의 내복용 제제 등을 포함하며 이에 제한되는 것은 아니다.Quasi-drugs include, but are not limited to, oral preparations, insecticides, rodenticides, disinfectants, disinfectants, odor inhibitors, erosive agents, contact lens care products, ointments, external disinfectants, vitamins, and formulations for internal use such as nourishing tonic.
생활용품은 청소용 제제, 세탁용 세제, 섬유유연제, 주방세제, 방향제, 왁스, 유화제, 윤활제 등을 포함하며 이에 제한되는 것은 아니다.Household products include, but are not limited to, cleaning agents, laundry detergents, fabric softeners, dish detergents, air fresheners, waxes, emulsifiers, lubricants, and the like.
화장품은 인체를 청결·미화하여 매력을 더하고 용모를 밝게 변화시키거나 피부·모발의 건강을 유지 또는 증진하기 위하여 인체에 바르고 문지르거나 뿌리는 등 이와 유사한 방법으로 사용되는 물품으로서 인체에 대한 작용이 경미한 것을 말하며, 영유아용 화장품, 목욕용 제품, 인체 세정용 제품류, 눈 화장용 제품, 방향용 제품, 두발 염색용 제품, 색조 화장 제품, 두발용 제품, 손발톱용 제품, 면도용 제품, 기초화장용 제품, 체취 방지용 제품 등을 포함하며 이에 제한되는 것은 아니다.Cosmetics are products that are used in a similar way, such as rubbing, spraying, etc., on the human body to clean and beautify the human body to add attractiveness, to brighten the appearance, or to maintain or promote the health of the skin and hair. Cosmetics for babies, bath products, human body cleaning products, eye makeup products, fragrance products, hair dye products, color makeup products, hair products, nail products, shaving products, basic makeup products, It includes, but is not limited to, products for preventing body odor.
본 발명의 신규한 계피산 유도체 화합물은 항균력과 함께 우수한 수용해성을 갖기 때문에 물을 기본으로 하는 식품, 의약품, 의약외품, 생활용품 및 화장품을 포함하여 다양한 제품에 널리 처방이 가능하다는 장점이 있다.Since the novel cinnamic acid derivative compound of the present invention has excellent water solubility along with antibacterial activity, it has the advantage that it can be widely prescribed for a variety of products including water-based foods, pharmaceuticals, quasi-drugs, household goods, and cosmetics.
본 발명에 따른 신규 계피산 유도체는 용해도가 향상되어 별도의 유화제 및 가용화제를 사용하지 않아도 쉽게 처방이 가능하며, 다양한 pH조건에서의 안정성과 미생물에 대한 우수한 저항성을 가져 화학적 방부제를 사용하지 않은 화장품 및 인체용품 분야 등에서 다양하게 활용이 가능하다.The novel cinnamic acid derivative according to the present invention has improved solubility, so it can be easily prescribed without the use of a separate emulsifier and solubilizer, and has stability in various pH conditions and excellent resistance to microorganisms. It can be used in various ways in the field of human products.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명 하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art to which the present invention pertains that the scope of the present invention is not limited by these examples.
실시예Example
1. 계피산 유도체의 합성1. Synthesis of cinnamic acid derivatives
본 발명에 따른 [화학식 1]로 표시되는 계피산 유도체 중에서 대표적인 예인 CA-9를 하기와 같이 제조하였다.CA-9, which is a representative example among the cinnamic acid derivatives represented by [Formula 1] according to the present invention, was prepared as follows.
구체적으로 하기 <반응식 2>에 따라서 4-메톡시 시남알데히드(1)(5g, 28 mmol, 1당량)과 염화티오닐 (3 mL, 42 mmol, 1.5 당량)을 디클로메탄 30 mL에 넣고 50도에서 4시간 동안 교반하였다. 반응 종료 후, 감압하여 잔류 염화티오닐과 용제를 제거하여 4-메톡시 시나믹산염화물(2)를 짙은 노란색의 점도 높은 액체상태로 얻었다. 상기 반응에서 수득한 4-메톡시 시나믹산염화물(2)을 디클로로메탄 50 mL에 녹이고, 메틸 피페라진(8.4 g, 84 mmol)을 천천히 떨어뜨리고, 상온에서 12시간 교반한다. 반응종료 후, 생성된 아민염 고체를 셀라이트 필터로 제거한 뒤, 유기층을 정제수로 2번 씻어내었다. 유기층을 모아서 무수황산마그네슘으로 건조하고, 감압하여 용제를 제거하여 옅은 노란색 고체인 CA-9을 얻었다(6.9g, 94.7%). 1H NMR (400 MHz, CDCl3-d3) δ 2.3 (s, 3H), 2.42-2.44 (m, 4H), 3.68-3.71 (m, 4H), 3.78 (s, 3H), 6.73 (d, J = 15.2, 1H), 6.85 (d, J=8.4, 2H) 7.43 (d, J=8.4, 2H), 7.61 (d, J=15.2, 1H).Specifically, according to the following <Reaction Scheme 2>, 4-methoxycinamaldehyde (1) (5 g, 28 mmol, 1 equiv) and thionyl chloride (3 mL, 42 mmol, 1.5 equiv) were added to 30 mL of dichloromethane and 50 The mixture was stirred for 4 hours in FIG. After completion of the reaction, the pressure was reduced to remove residual thionyl chloride and the solvent to obtain 4-methoxycinamic acid chloride (2) as a dark yellow liquid with high viscosity. The 4-methoxycinamic acid chloride (2) obtained in the above reaction was dissolved in 50 mL of dichloromethane, methyl piperazine (8.4 g, 84 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, the resulting amine salt solid was removed with a Celite filter, and the organic layer was washed twice with purified water. The organic layers were collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain CA-9 as a pale yellow solid (6.9 g, 94.7%). 1H NMR (400 MHz, CDCl3-d3) δ 2.3 (s, 3H), 2.42-2.44 (m, 4H), 3.68-3.71 (m, 4H), 3.78 (s, 3H), 6.73 (d, J = 15.2) , 1H), 6.85 (d, J=8.4, 2H) 7.43 (d, J=8.4, 2H), 7.61 (d, J=15.2, 1H).
<반응식 2><Scheme 2>
CA-9의 제조예와 동일한 반응 원리에 의하여 본 발명에 따른 [화학식 1]로 표시되는 상이한 치환기를 포함하는 계피산 유도체들을 제조하고 핵자기공명분석법에 의하여 합성된 화합물들을 확인하였다. 이와 같이 제조한 본원발명의 계피산 유도체들 및 이들의 NMR 데이터를 하기 표 1에 정리하였다.According to the same reaction principle as in the preparation example of CA-9, cinnamic acid derivatives containing different substituents represented by [Formula 1] according to the present invention were prepared, and the synthesized compounds were confirmed by nuclear magnetic resonance analysis. The cinnamic acid derivatives of the present invention prepared as described above and their NMR data are summarized in Table 1 below.
2. 미생물 최소 억제 농도(2. Microbial Minimum Inhibitory Concentration (MICMIC) 평가) evaluation
계피산 유도체의 최소저해농도(Minimum Inhibition Concentration: MIC)를 측정하였다. 액상배지에 전 배양한 스타필로코커스 아우레우스 (Staphylococcus aureus), 에스케리치아 콜라이(Escherichia coli), 세도모나스 애루지노사(Pseudomonas aeruginosa)는 뇌 심장 인퓨전 브로스 5 ml에 37℃, 24시간 배양하고, Candida albicans, Aspergillus niger는 감자 덱스트로스 브로스 5 ml에 30℃, 48시간 배양하여 준비하였다. 발효배양물의 MIC를 측정하기 위해서 2배 희석법을 사용하였다. 최소저해농도를 측정한 결과를 하기 표 2에 나타내었다.The minimum inhibitory concentration (MIC) of the cinnamic acid derivative was measured. Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, pre-cultured in liquid medium, were cultured in 5 ml of brain heart infusion broth at 37° C. for 24 hours. , Candida albicans and Aspergillus niger were prepared by culturing in 5 ml of potato dextrose broth at 30°C for 48 hours. To measure the MIC of the fermentation culture, a 2-fold dilution method was used. The results of measuring the minimum inhibitory concentration are shown in Table 2 below.
실험결과 본 발명의 계피산 유도체 화합물들은 우수한 항균 효과를 갖는 것으로 확인되었다.3. 수용해도 테스트As a result of the experiment, it was confirmed that the cinnamic acid derivative compounds of the present invention had an excellent antibacterial effect.3. water solubility test
(1) logP값 분석(1) logP value analysis
logP (옥탄올과 물 사이의 분배계수) 값은 신약개발에서 많이 사용되는 물성으로서 값이 낮을수록 극성이 높으며 수용해성이 높다고 통용되는 물성이다. 여러 종류의 계피산 유도체 화합물들에 대하여 logP값 분석하고 그 결과를 하기 표 3에 나타내었다.The logP (partition coefficient between octanol and water) value is a commonly used physical property in drug development. The lower the value, the higher the polarity and the higher the water solubility. LogP values were analyzed for several types of cinnamic acid derivative compounds, and the results are shown in Table 3 below.
상기 화합물들에 대하여 수용해성과 관련이 큰 물성이 logP 값에 대하여 평가해본 결과, 11~14번 화합물(CA-2, CA-14, CA-9 및 CA-17 화합물)은 logP값이 1.4 이하로서 물을 주성분으로 포함되는 화장품 및 생활용품에 용이하게 처방할 수 있는 특성을 갖는 것으로 확인되었다. 5번 화합물은 logP값이 1.35로 평가되었지만 실제로 수용해성이 좋지 않아서 MIC 측정 불가했으며, 수용해도는 0.005%로서, 수용해도가 2%인 CA-9에 비해서 수용해성이 현저히 낮은 것으로 확인되었다. (2) 수용해도 측정As a result of evaluating the logP values of physical properties related to water solubility for the above compounds, compounds 11 to 14 (CA-2, CA-14, CA-9 and CA-17 compounds) have a logP value of 1.4 or less As a result, it was confirmed to have properties that can be easily prescribed for cosmetics and household products containing water as a main ingredient. Compound 5 had a logP value of 1.35, but it was not possible to measure the MIC due to poor water solubility, and it was confirmed that the water solubility was significantly lower than CA-9, which had a water solubility of 2%, with a water solubility of 0.005%. (2) Water solubility measurement
계피산 및 계피산 유도체의 수용해도를 측정하여 하기 표 4에 비교하였다. 본 발명에서 개발한 CA-9 은 상온에서 2% 수용해를 가지며, 40도로 가온시에는 5%까지 용해가 잘 되는 우수한 결과를 보였다.The aqueous solubility of cinnamic acid and cinnamic acid derivatives was measured and compared in Table 4 below. CA-9 developed in the present invention has a 2% aqueous solubility at room temperature, and shows excellent results in that it dissolves well up to 5% when heated to 40 degrees.
4. 계피산 유도체를 포함하는 샴푸제조 및 항균효과 확인4. Preparation of shampoo containing cinnamic acid derivative and confirmation of antibacterial effect
하기 표 5에 나타낸 조성 성분과 함량을 사용하여 통상적인 방법으로 에멀전 타입의 샴푸를 제조하였다. 본 발명의 CA-9 및 CA-12 화합물은 물을 주성분으로 하는 에멀전 타입의 샴푸를 제조할 수 있을 정도로 수용해도가 높은 것으로 확인되었기에 이 두 화합물을 사용하여 제조하였다.An emulsion-type shampoo was prepared in a conventional manner using the composition components and contents shown in Table 5 below. CA-9 and CA-12 compounds of the present invention were prepared using these two compounds because it was confirmed that the water solubility was high enough to prepare an emulsion type shampoo containing water as a main component.
상기 제조한 실시예 1 내지 4의 조성물의 항균 및 방부 효과를 실험하기 위하여 세균 또는 진균을 시료에 첨가하고 접종균 수의 변화를 체크하였으며, 진균 또는 세균의 수가 20 CFU/g 이하가 되기 시작한 날을 기록하여 하기 표 6에 나타내었다. 측정은 최대 28일까지 이루어졌으며, 시험과정을 구체적으로 나타내면 다음과 같다.In order to test the antibacterial and antiseptic effects of the compositions of Examples 1 to 4 prepared above, bacteria or fungi were added to the sample and the change in the number of inoculum was checked, and the number of fungi or bacteria started to become 20 CFU/g or less. was recorded and shown in Table 6 below. Measurements were made up to 28 days, and the detailed test process is as follows.
먼저, 화장료 조성물을 40 g씩 담은 후, 세균, 즉, 스타필로코커스 아우레우스(Staphylococcus aureus ATCC 6538), 세도모나스 애루지노사(Pseudomonas aeruginosa ATCC 15522) 및 에스케리치아 콜라이(Escherichia coli ATCC10536) 등의 혼합균액을 시료 1 g당 106 마리 수가 되도록 시료에 첨가, 혼합한 후 4 주간 보관하였다. 그 다음, 접종한 날로부터 1일, 7일 14일, 21일, 28일이 경과할 때마다 접종균 수의 변화를 체크하였다.First, after 40 g of the cosmetic composition is loaded, bacteria, that is, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 15522, Escherichia coli ATCC10536, etc. was added to the sample so that the number of 106 cells per 1 g of the sample was mixed, mixed, and stored for 4 weeks. Then, each time 1, 7, 14, 21, and 28 days elapsed from the inoculation day, the change in the number of inoculated bacteria was checked.
진균을 이용한 시험 과정은 세균을 이용한 시험과정과 종일하며, 진균으로 아스퍼질러스 나이거(Aspergillus niger ATCC 9642) 및 칸디다 알비칸스(Candida albicans ATCC 10231)를 사용하였다.The test process using fungi was the same as the test process using bacteria, and Aspergillus niger ATCC 9642 and Candida albicans ATCC 10231 were used as fungi.
실험결과, 본 발명의 실시예 1은 화학적 방부제를 사용하지 않았음에도 불구하고 14일 차부터 20 CFU/g 이하의 진균 또는 세균의 수를 나타내어 우수한 항균 및 방부 효과가 있음을 알 수 있었다. 특히 계피산 유도체를 2 중량% 이상 함유한 실시예 3의 경우 진균과 세균의 수가 급격하게 줄어들어 7일 차부터 20 CFU/g 이하의 진균 또는 세균의 수를 나타내어 훨씬 우수한 항균 및 방부 효과를 나타냈음을 확인할 수 있다.As a result of the experiment, Example 1 of the present invention showed an excellent antibacterial and antiseptic effect by showing the number of fungi or bacteria of 20 CFU/g or less from the 14th day, despite not using a chemical preservative. In particular, in the case of Example 3 containing 2% by weight or more of the cinnamic acid derivative, the number of fungi and bacteria was rapidly reduced, and the number of fungi or bacteria of 20 CFU/g or less from the 7th day was shown, indicating that much better antibacterial and antiseptic effects can
Claims (10)
Translated fromKorean<화학식 1>
상기 식에서,
R1은 수소, C1-C2 알킬, OH, OCH3, Cl 또는 Br이고,
R2는 수소, C1-C2 알킬, OH, OCH3, Cl 또는 Br이고, R3는 수소, C1-C2 알킬, OH, OCH3, Cl 또는 Br이거나; 또는 R2 및 R3은 서로 연결되어 산소원자를 포함하는 헤테로고리를 형성하고,
A는 NHR21, 또는
여기서 R21은 (CH2)mR211이며, m은 1 내지 2의 정수이며, R211은
R22는 수소, C1-C2 알킬, 또는
<Formula 1>
In the above formula,
R1 is hydrogen, C1 -C2 alkyl, OH, OCH3 , Cl or Br,
R2 is hydrogen, C1 -C2 alkyl, OH, OCH3 , Cl or Br, and R3 is hydrogen, C1 -C2 alkyl, OH, OCH3 , Cl or Br; Or R2 and R3 are connected to each other to form a heterocycle containing an oxygen atom,
A is NHR21 , or
wherein R21 is (CH2 )m R211 , m is an integer of 1 to 2, and R211 is
R22 is hydrogen, C1 -C2 alkyl, or
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| Title |
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| ARKIVOC 2008 (v) pp. 55-64* |
| Bioorganic & Medicinal Chemistry 2014, Vol. 22, pp. 4285-4292* |
| J. Chemometrics 2015, Vol. 29, pp. 13-20* |
| Med Chem Res 2017, Vol. 26, pp. 603-614* |
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