KR101721022B1 - Composition for comprising adipic acid for improving skin wrinkle or enhancing skin elasticity - Google Patents
Composition for comprising adipic acid for improving skin wrinkle or enhancing skin elasticity Download PDFInfo
- Publication number
- KR101721022B1 KR101721022B1 KR1020160017137A KR20160017137A KR101721022B1 KR 101721022 B1 KR101721022 B1 KR 101721022B1 KR 1020160017137 A KR1020160017137 A KR 1020160017137A KR 20160017137 A KR20160017137 A KR 20160017137A KR 101721022 B1 KR101721022 B1 KR 101721022B1
- Authority
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- South Korea
- Prior art keywords
- skin
- adipic acid
- collagen
- composition
- present
- Prior art date
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Abstract
Description
본 발명은 아디프산을 유효성분으로 함유하는 피부주름개선 및 탄력증진용 조성물에 관한 것으로, 보다 상세하게는 아디프산을 유효성분으로 함유하는 주름 개선용 화장료 조성물, 피부 외용제, 식품 조성물 및 약학적 조성물과 아디프산을 유효성분으로 함유하는 탄력 증진용 화장료 조성물, 피부 외용제, 식품 조성물 및 약학적 조성물에 관한 것이다.The present invention relates to a composition for improving skin wrinkles and improving elasticity containing adipic acid as an active ingredient, and more particularly to a cosmetic composition for improving wrinkles containing adipic acid as an active ingredient, an external preparation for skin, a food composition, An external preparation for skin, a food composition, and a pharmaceutical composition containing an adipic acid and adipic acid as an active ingredient.
피부는 크게 표피(epidermis), 진피(dermis), 피하지방(hypodermis)의 세층으로 구성되어 있다, 표피, 특히 표피의 가장 외층인 각질층은 피부장벽의 역할을 함으로서 피부로부터 수분과 전해질 손실되는 것을 억제하는 한편, 진피층은 콜라겐과 엘라스틴 합성을 통하여 피부의 탄력을 유지하고 구조를 지지하는 역할을 한다. 즉, 콜라겐과 엘라스틴은 섬유아세포에서 생성되는 주요 단백질로서 피부의 기계적 견고성, 조직의 결합력 및 탄력성 등에 관여한다. 콜라겐은 형태와 구조적 특징에 따라 다양한 isoform을 구성하며, 사람의 조직에서 총 28가지 콜라겐 isotype이 존재하는데, 이중 피부조직에 존재하는 콜라겐은 타입 1, 3. 4. 6. 7. 13, 14, 17 등이 알려져 있다. 콜라겐 타입 1과 3은 진피층의 세포간질 구성성분을 이루고, 콜라겐 타입 7은 표피와 진피를 연결부위(dermal and epidermal junction)의 주요 구성물질이 된다.The skin consists largely of epidermis, dermis, and hypodermis. The epidermis, especially the stratum corneum, which is the outermost layer of the epidermis, acts as a skin barrier to inhibit the loss of moisture and electrolytes from the skin. While the dermis, through the synthesis of collagen and elastin, maintains the elasticity of the skin and supports the structure. In other words, collagen and elastin are the main proteins produced in fibroblasts, which are involved in the mechanical durability of the skin, the binding force and elasticity of the tissue. Collagen forms a variety of isoforms depending on its morphology and structural characteristics. There are 28 types of collagen isotypes in human tissues, including
피부결합조직에는 세포외기질 단백질 중 타입 1 콜라겐이 가장 많은 양으로 존재하며, 그 밖에 엘라스틴, 피브로넥틴, 인테그린, 피브리린, 프로테로글리칸 등의 단백질들이 존재한다. 새로이 합성된 프로콜라겐은 프롤린 및 라이신 아미노산 잔기에서 hydroxylation이 일어나 세가닥의 나선이 꼬인 형태로 세포외 공간으로 분비된다. 이곳에서 프로콜라겐은 procollagen proteinase에 의해 양 말단이 잘려나가 비로소 콜라겐 단백질을 형성하게 되고, 후자는 다시 삼중나선구조(triple helix configuration)의 마이크로피브릴을 형성하고, 마이크로 피브릴은 leucine-rich small proteoglycans과 결합하여 피브릴을 형성한다. 결과적으로 이렇게 만들어진 피브릴들이 모여 피부의 결합력과 탄력성을 제공하는 콜라겐 섬유를 형성하게 된다. In skin connective tissue,
피부노화는 피부 진피조직의 교원질 중 대부분을 차지하는 단백질인 콜라겐 함량이 감소하기 때문으로 알려져있고, 콜라겐은 피부의 장력과 강도를 부여하기 때문에 콜라겐의 감소는 피부노화 및 주름생성과 매우 깊은 관계를 가지고 있다. 피부노화는 크게 생리학적 노화에 의한 내인성 노화, 그리고 지속적인 자외선(ultraviolet radiation, UV) 노출에 의해 일어나는 광노화로 구분된다. 반복적인 자외선 노출은 콜라겐 분해효소를 증가시키고 콜라겐 섬유의 변성 및 파괴를 유발하여 피부의 탄력을 감소시키고 주름의 생성을 촉진하는 결과를 초래한다.Skin aging is known to be caused by a decrease in collagen content, which is the protein that occupies most of the collagen in skin dermal tissue. Since collagen gives skin tension and strength, collagen reduction has a very deep relationship with skin aging and wrinkle formation have. Skin aging is largely divided into endogenous aging by physiological aging and photoaging caused by continuous exposure to ultraviolet radiation (UV). Repeated exposure to ultraviolet light results in increased collagenase and denaturation and destruction of collagen fibers, reducing skin elasticity and promoting the production of wrinkles.
최근 의료기술의 발달로 평균수명이 연장되고 삶의 질 향상과 건강하고 아름다운 삶에 대한 욕구가 증가함에 따라 피부미용 및 건강에 대한 관심이 확대되고 있다. 이에 건강한 피부를 유지하도록 하는 다양한 미용 기능성 화장품이 개발되었으며, 특히 피부 주름형성 예방, 완화와 개선을 위한 연구가 활발히 진행되고 있다. 아울러 최근 화장품의 성분이 피부진피에 도달하여 영양분을 공급하는데 한계가 있고, 식품으로 섭취하여 피부에 영양분 또는 기능성분을 공급하여 피부미용증진 효과를 나타낼 수 있다는 인식의 변화가 일어남에 따라 이너뷰티 식품소재들을 발굴하는 연구 또한 활발히 진행되고 있다.Recent advances in medical technology have led to increased interest in skin care and health as life expectancy has been extended and quality of life has been improved and the desire for a healthy and beautiful life has increased. Various cosmetic functional cosmetics have been developed to maintain healthy skin. Especially, researches for prevention of skin wrinkle formation, mitigation and improvement have been actively carried out. In addition, recently, cosmetic ingredients reach skin dermis and there is a limitation in supplying nutrients. As a result of the change in perception that ingestion of nutrients or functional ingredients to the skin can provide a skin cosmetic enhancement effect, Research to excavate materials is also being actively pursued.
본 출원인 또한, 부작용이 적은 천연물에서 콜라겐 분해효소의 작용을 억제하고 콜라겐의 합성을 촉진시킴으로써 주름 개선에 효과가 있는 식품 또는 화장품 소재를 개발하는 연구를 진행하였다. 그 결과, 지금까지 산도조절제의 용도로만 사용되던 아디프산이 피부 탄력 증진 및 피부 주름 완화 효과가 있다는 사실을 확인하고 본 발명을 완성하였다.The present applicant has also researched the development of a food or cosmetic material which is effective in reducing wrinkles by inhibiting the action of collagenase in natural products with low side effects and promoting the synthesis of collagen. As a result, it was confirmed that adipic acid, which has been used only for the purpose of an acidity controlling agent, has an effect of improving skin elasticity and reducing skin wrinkles, and completed the present invention.
이에 본 발명자들은 아디프산을 유효성분으로 함유하는 주름 개선용 또는 피부 탄력 증진용 화장료 조성물, 피부 외용제 및 식품 조성물을 개발하여 본 발명을 완성하였다.Accordingly, the present inventors completed the present invention by developing a cosmetic composition for improving wrinkles or skin elasticity, an external preparation for skin and a food composition containing adipic acid as an active ingredient.
따라서, 본 발명의 목적은 아디프산을 유효성분으로 함유하는 주름 개선용 화장료 조성물, 피부 외용제 및 식품 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a cosmetic composition for improving wrinkles, an external preparation for skin and a food composition containing adipic acid as an active ingredient.
본 발명의 또 다른 목적은, 아디프산을 유효성분으로 함유하는 피부 탄력 증진용 화장료 조성물, 피부 외용제 및 식품 조성물을 제공하는 것이다.It is still another object of the present invention to provide a cosmetic composition for enhancing skin elasticity, an external preparation for skin and a food composition containing adipic acid as an active ingredient.
상기의 목적을 달성하기 위해, 본 발명은 아디프산을 유효성분으로 함유하는 주름 개선용 화장료 조성물을 제공한다.In order to achieve the above object, the present invention provides a cosmetic composition for improving wrinkles containing adipic acid as an active ingredient.
본 발명의 바람직한 다른 일실시예에 따르면, 아디프산은 화장료 전체 중량에 대하여 0.0001 내지 20 중량% 포함되는 것일 수 있다.According to another preferred embodiment of the present invention, the adipic acid may be contained in an amount of 0.0001 to 20% by weight based on the total weight of the cosmetic.
본 발명의 바람직한 다른 일실시예에 따르면, 본 발명의 조성물은 프로콜라겐 분비량의 증가, 콜라겐 생합성의 촉진, MMP-1 유전자의 발현 감소 및 피부 각질층 형성 억제로 이루어지는 군에서 선택되는 어느 하나 이상의 효과를 가지는 것 일 수 있다.According to another preferred embodiment of the present invention, the composition of the present invention is effective to any one or more of effects selected from the group consisting of an increase in procollagen secretion amount, promotion of collagen biosynthesis, reduction of expression of MMP-1 gene and inhibition of skin stratum corneum formation It can be something to have.
본 발명의 바람직한 또 다른 일실시예에 따르면, 본 발명의 화장료는 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 맛사지 크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 팩, 마스크팩, 마스크시트, 비누, 샴푸, 클렌징 폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더 및 아이섀도로 구성된 그룹에서 선택된 어느 하나의 제형일 수 있다.According to another preferred embodiment of the present invention, the cosmetic composition of the present invention is used as a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, It can be any one selected from the group consisting of essence, pack, mask pack, mask sheet, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, milky lotion, press powder, loose powder and eye shadow have.
본 발명의 바람직한 다른 일실시예에 따르면, 본 발명의 조성물은 화장품학적으로 허용 가능한 담체를 추가로 포함하는 것일 수 있다.According to another preferred embodiment of the present invention, the composition of the present invention may further comprise a cosmetically acceptable carrier.
본 발명의 바람직한 다른 일실시예에 따르면, 본 발명의 조성물은 피부 주름개선 성분 또는 피부탄력 증진 성분을 추가로 포함하는 것일 수 있다. 피부 주름개선 성분 또는 피부탄력 증진 성분은 구체적으로 비타민 C, 레티노산, TGF, 동물 태반 유래의 단백질, 베튤린산 및 클로렐라 추출물로 구성되는 군으로부터 선택되는 것일 수 있다.According to another preferred embodiment of the present invention, the composition of the present invention may further comprise a skin wrinkle improving component or a skin elasticity improving component. The skin wrinkle improving component or skin elasticity enhancing component may be specifically selected from the group consisting of vitamin C, retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract.
본 발명은 또한, 아디프산을 유효성분으로 함유하는 주름 개선용 피부 외용제 조성물을 제공한다.The present invention also provides a composition for external application for skin for improving wrinkles containing adipic acid as an active ingredient.
본 발명은 또한, 아디프산을 유효성분으로 함유하는 주름 개선용 식품 조성물을 제공한다.The present invention also provides a food composition for improving wrinkles containing adipic acid as an active ingredient.
본 발명의 바람직한 다른 일실시예에 따르면, 본 발명의 식품은 정제, 과립, 분말, 캅셀, 액상의 용액 및 환으로 이루어진 군으로부터 선택된 어느 하나의 제형으로 제조된 것일 수 있다.According to another preferred embodiment of the present invention, the food of the present invention may be made into any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings.
본 발명은 또한, 아디프산을 유효성분으로 함유하는 주름 개선용 약학적 조성물을 제공한다.The present invention also provides a pharmaceutical composition for improving wrinkles containing adipic acid as an active ingredient.
본 발명은 또한, 아디프산을 유효성분으로 함유하는 피부 탄력 증진용 화장료 조성물, 피부 외용제, 식품 조성물 및 약학적 조성물을 제공한다.The present invention also provides a cosmetic composition for enhancing skin elasticity, an external preparation for skin, a food composition and a pharmaceutical composition containing adipic acid as an active ingredient.
본 발명은 아디프산을 유효성분으로 함유하는 주름 개선용 화장료 조성물, 피부 외용제 및 식품 조성물과 아디프산을 유효성분으로 함유하는 탄력 증진용 화장료 조성물, 피부 외용제 및 식품 조성물을 제공한다. 아디프산을 함유하는 조성물은 프로콜라겐 분비량의 증가, 콜라겐 생합성의 촉진, MMP-1 유전자의 발현 감소 및 피부 표피층 비후 억제효과가 있어, 피부 주름 개선 또는 피부 탄력 증진에 효과적이다.The present invention provides a cosmetic composition for improving wrinkles containing adipic acid as an active ingredient, an external preparation for skin and a food composition, a cosmetic composition for enhancing elasticity containing adipic acid as an active ingredient, an external preparation for skin and a food composition. The composition containing adipic acid has an effect of increasing the amount of procollagen secretion, promoting collagen biosynthesis, decreasing expression of MMP-1 gene, and inhibiting skin skin layer thickening, thereby being effective in improving skin wrinkles or skin elasticity.
도 1은 사람 피부섬유아세포에서 프로콜라겐 분비량을 측정한 그래프이다(-UVB: UVB를 처리하지 않은 대조군, +UVB : UVB를 처리한 대조군, AA : UVB를 조사한 후 아디프산을 처리한 실험군, VitC : UVB를 조사한 후 비타민 C를 처리한 대조군, AA+VitC : UVB를 조사한 후 아디프산과 비타민 C를 함께 처리한 실험군).
도 2는 사람 섬유세포에서 프로콜라겐 및 MMP-1 유전자 발현량을 측정한 전기영동 사진과 그래프이다.
도 3은 실험식이를 섭취한 마우스의 체중증가량(A 및 B) 및 식이섭취량(C 및 D)을 나타낸 그래프이다.
도 4는 실험식이를 섭취한 마우스 피부조직의 수분함유량(A), 수분증발량(B), 탄력성(C) 및 홍반지수(D)를 측정한 그래프이다.
도 5는 실험식이를 섭취한 마우스의 등피부조직 사진이다.
도 6은 실험식이를 섭취한 마우스 등 피부조직의 주름 형성 정도를 나타낸 사진(A)과 그래프(B)이다.
도 7은 실험식이를 섭취한 마우스의 피부 두께를 나타낸 그래프(A)와 사진(B)이다.
도 8은 아디프산을 처리한 마우스 등조직에서 콜라겐 및 MMPs 유전자 발현 변화를 나타낸 전기영동 사진과 그래프이다.FIG. 1 is a graph showing the amount of procollagen secreted from human skin fibroblasts (-UVB: control group not treated with UVB, + UVB: control group treated with UVB, AA: test group treated with adipic acid after UVB irradiation, VitC: Control group treated with vitamin C after UVB irradiation, AA + VitC: Experimental group treated with adipic acid and vitamin C after UVB irradiation).
2 is an electrophoresis photograph and a graph showing the amounts of procollagen and MMP-1 gene expressed in human fibroblasts.
FIG. 3 is a graph showing weight gain (A and B) and dietary intake amounts (C and D) of a mouse consuming an experimental diet.
4 is a graph showing moisture content (A), moisture evaporation amount (B), elasticity (C), and erythema index (D) of mouse skin tissues consumed in the experimental diet.
Fig. 5 is a photograph of the dorsal skin tissue of a mouse ingested with an experimental diet.
FIG. 6 is a photograph (A) and a graph (B) showing the degree of wrinkling of the skin tissue such as a mouse ingested with the experimental diet.
Fig. 7 is a graph (A) and a photograph (B) showing the skin thickness of a mouse ingested with the experimental diet.
8 is an electrophoresis photograph and graph showing changes in collagen and MMPs gene expression in tissues such as mouse treated with adipic acid.
이하, 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
상술한 바와 같이, 아디프산의 산도조절 용도는 공지되어 있었으나, 피부 탄력 증진 및 피부 주름 완화 효과에 대한 연구는 이루어진바 없다.As described above, the use of adipic acid for regulating the acidity has been known, but no research has been conducted on the skin elasticity enhancement and skin wrinkle reduction effect.
본 발명에서 제공하는 아디프산을 함유하는 조성물은 프로콜라겐 분비량의 증가, 콜라겐 생합성의 촉진, MMP-1 유전자의 발현 감소 및 피부 표피층 비후 억제효과가 있어, 피부 주름 개선 또는 피부 탄력 증진에 효과적이다.The composition containing adipic acid provided by the present invention is effective for increasing the amount of procollagen secretion, promoting collagen biosynthesis, decreasing expression of MMP-1 gene, and inhibiting skin skin layer thickening, thereby improving skin wrinkles or skin elasticity .
따라서, 본 발명은 아디프산을 유효성분으로 함유하는 주름 개선용 화장료 조성물을 제공한다. Accordingly, the present invention provides a cosmetic composition for improving wrinkles containing adipic acid as an active ingredient.
아디프산은 사탕무(sugar beet)와 감비르(gambir) 등에 함유되어 있는 카르복실계 화합물로서 아디핀산, 아디픽산, 1,4-butanedicarboxylic acid; 1,6-hexanedioic acid; acifloctin; acinetten; adipinic acid; hexanedioic acid; octafluorohexanedioic acid으로도 불리 운다. 본 발명의 아디프산은 아디프산을 포함하는 다양한 식물로부터 추출, 분리 및 정제하여 얻을 수 있다.Adipic acid is a carboxyl-based compound which is contained in sugar beet and gambir, and includes adipic acid, adipic acid, 1,4-butanedicarboxylic acid; 1,6-hexanedioic acid; acifloctin; acinetten; adipinic acid; hexanedioic acid; It is also called octafluorohexanedioic acid. The adipic acid of the present invention can be obtained by extraction, isolation and purification from various plants including adipic acid.
아디프산의 Cas No.는 124-04-9이고 구조식은 C6H10O4, 그리고 분자량은 146.1 g/mol이다. 그 구체적인 구조는 하기 화학식1과 같다. 아디프산은 가연성 물질이고, 건조한 곳에서는 와류, 공기 수송, 주입 등에 의해 정전기적으로 하전될 수 있다. 열에 분해되어 발레르산 및 기타 물질이 포함된 부식성 화학가스와 독성 물질을 만들어낸다.The Cas No. of adipic acid is 124-04-9, the structural formula is C 6 H 10 O 4 , and the molecular weight is 146.1 g / mol. The specific structure thereof is shown in the following formula (1). Adipic acid is a flammable substance and can be electrostatically charged in a dry place by vortexing, air transport, injection, and the like. It decomposes in heat and produces corrosive chemical gases and toxic substances containing valeric acid and other substances.
[화학식1][Chemical Formula 1]
아디프산은 국내 식품공전에 "산도조절제"의 용도를 가지는 식품첨가물로 등록되어 있으며, 미국 FDA의 Food and Color Additive Database에도 산도 조절제로 등록되어 있다. 아디프산은 베이킹파우더에 효모 산미제로 첨가되며 과일맛 주스 및 병 음료의 농축분말 등에도 산미제로 첨가된다. 또한 가공 치즈 및 치즈 스프레드의 녹는 특성과 질감을 향상시키기 위해서도 사용될 수 있다. 아디프산은 계란 흰자가 들어가는 제품에 거품이 잘 만들어지도록 첨가될 수 있으며 잼 및 젤리에 젤 생성제로 사용될 수 있다. 아디프산은 식품에 완충제 및 중화제로 첨가되어 지고, 의약품의 원료로 사용되며 향수 고정제로도 사용되어져 왔다.Adipic acid is registered as a food additive having the use of an "acidity modifier" in the domestic food cycle, and is also registered as an acidity modifier in the Food and Color Additive Database of the US FDA. Adipic acid is added to baking powder as a yeast acidic additive and is also added to the concentrate powder of fruit flavored juice and bottle drinks. It can also be used to improve the melting characteristics and texture of processed cheese and cheese spreads. Adipic acid can be added to produce a foam in the egg whites and can be used as a gel-forming agent in jams and jellies. Adipic acid has been added to food as a buffer and neutralizing agent, and is used as a raw material for pharmaceuticals and as a perfume fixing agent.
그동안 알려진 아디프산의 생리활성으로는 항-키토제닉 효과와 항-고혈압 효과가 보고되었다. 아디프산은 랫트에서 긴-체인과 짧은-체인 모노카르복시산에 의해 야기된 된 케톤증을 개선하는 효과가 보고되었다. 고혈압 환자를 대상으로 한 임상연구에서 8주 동안 암로디핀 아디페이트염(amlodipine adipate)을 섭취한 결과, 혈압이 개선되었다. 그러나 지금까지 아디프산의 피부 탄력 증진 및 피부 주름 완화 효과에 대해서는 공지된 바 없었다.The known physiological activities of adipic acid have been reported to be anti-chitosanic and anti-hypertensive. Adipic acid has been reported to improve the ketosis induced by long-chain and short-chain monocarboxylic acids in rats. In a clinical study in patients with hypertension, amlodipine adipate intake for 8 weeks improved blood pressure. However, up to now, the effect of improving adipic acid skin elasticity and reducing skin wrinkles has not been known.
여러 실험을 통해, 아디프산의 안전성은 어느 정도 알려져 있다. 다양한 종류의 실험동물에서 흡입, 정맥주사, 경구투여, 복강주사 등의 방법으로 아디프산을 투여하여 얻은 LD50 이 [표 1]에 제시되어 있으며 마우스를 대상으로 경구투여 시 11,000 mg/kg 몸무게로 보고되었다. Through several experiments, the safety of adipic acid is known to some extent. LD 50 values obtained by administration of adipic acid by various methods such as inhalation, intravenous injection, oral administration and intraperitoneal injection are shown in [Table 1], and oral administration of 11,000 mg / kg body weight Respectively.
(Reference: 독성정보제공시스템(Tox-Info), 식품의약품안전평가원)(Reference: Tox-Info System, Food and Drug Safety Evaluation Institute)
교배한 CD-1 알비노 마우스 암컷 20-24마리를 대상으로 임신 후 6일부터 15일까지 아디프산을 매일 투여한 연구에서 배자독성 또는 기형유발 영향은 나타나지 않았다. 또한 암컷 랫드 17-20마리로 구성된 시험군에게 0, 10, 20, 40 mg/kg과 동등한 용량 수준의 아디프산이 포함된 식단을 28일 동안 유지했을 때 성장 유해 반응은 발견되지 않았다. 수컷 랫드 18마리로 구성된 시험군에게 5주 동안 0, 200, 400, 800 mg/일과 동등한 용량 수준의 아디프산이 포함된 식단을 유지했을 때 성장률이 감소한 고용량 그룹을 제외하면 성장률은 정상이었다. In the 20-24 female CD-1 albino mice that were mated, adipic acid was administered daily from 6 to 15 days after pregnancy, and there was no embryotoxic or teratogenic effect in the study. No growth adverse reaction was observed when the test group consisting of 17-20 female rats were kept for 28 days in a diet containing adipic acid at dose levels equivalent to 0, 10, 20, and 40 mg / kg. The test group consisting of 18 male rats had normal growth rates except for the high-dose group in which the growth rate was reduced when the diet containing adipic acid at dose levels equivalent to 0, 200, 400, 800 mg / day for 5 weeks was maintained.
또한, 인간 배자의 폐 배양체(WI - 38)를 아디프산(2, 20, 200 μg/ml)과 양성 대조 및 음성 대조 화합물이 존재하는 조건에서 성장시킨 결과 염색체의 뚜렷한 이상은 없었다. 아급성 연구에서 아디프산을 3.75, 37.5, 375 mg/kg/일 용량으로 5일 연속 투여하여 골수세포 염색체 이상을 평가한 결과, 골수 중기 염색체에 뚜렷한 이상은 나타나지 않았다.In addition, no significant abnormality of the chromosome was observed when the lung cultures of human embryos (WI - 38) were grown in the presence of adipic acid (2, 20, 200 μg / ml) and positive control and negative control compounds. In a subacute study, adipic acid was administered at doses of 3.75, 37.5, and 375 mg / kg / day for 5 consecutive days, and bone marrow cell chromosomal abnormalities were not observed.
아디프산은 인체에서 섭취 후 부분적으로만 대사되고 나머지는 변화되지 않은 채 그대로 소변으로 배설됨이 보고되었다. 예를 들어, 랫드에게 1일 0.75 g의 아디프산을 4주 동안 섭취시키고 섭취를 중단한 지 사흘 뒤 희생시킨 조직에서 아디프산의 잔재는 검출되지 않았다는 보고가 있다. 아디프산은 베타산화를 통해 숙신산과 아세트산으로 대사되고 이어서 정상적 기타 중간 대사산물로 대사되는 것으로 보고된 바 있으며, 공복상태의 실험용 랫드에게 방사성 아디프산을 섭취시킨 후 소변에서 검출된 대사 산물은 요소, 글루탐산, 젖산, 베타 케토아디프산, 시트르산으로 보고되었다.Adipic acid has been reported to be excreted in the urine as it is metabolized only partially after ingestion in the human body and unchanged in the remainder. For example, there is a report that residues of adipic acid were not detected in tissues sacrificed three days after ingesting 0.75 g of adipic acid for 4 weeks and stopping the ingestion of the rats. Adipic acid has been reported to be metabolized to succinic acid and acetic acid via beta oxidation and then to metabolism to other normal intermediate metabolites and metabolites detected in the urine after feeding radioactive adipic acid to fasting experimental rats , Glutamic acid, lactic acid, betacetoadipic acid, and citric acid.
따라서, 아디프산은 낮은 농도, 구체적으로 0.001 내지 3000 mg/kg, 더욱 바람직하게는 0.001 내지 1500 mg/kg로 투여하는 것은 독성이 아주 미미하거나 없으므로, 화장료 조성물, 피부 외용제, 식품 조성물 또는 약학적 조성물로 사용될 수 있다.Therefore, administration of adipic acid at a low concentration, specifically 0.001 to 3000 mg / kg, more preferably 0.001 to 1500 mg / kg, is insignificant in toxicity or does not exist, so that the cosmetic composition, external preparation for skin, .
본 발명에서 사용되는 용어, "피부 주름 개선"은 피부의 주름 및 탄력과 관련된 능력을 유지 또는 강화시키는 것을 의미한다. 피부 진피층의 교원섬유인 콜라겐(collagen)과 탄력섬유인 엘라스틴(elastin)이 그러한 역할을 하는 주요 단백질로서 피부 탄력을 주관하는데, 콜라겐의 생합성은 피부의 내, 외적 영향을 받게 된다. 구체적으로, 피부세포는 자연 노화로 인하여 세포 활성이 감소되면 콜라겐 섬유의 감소가 일어나거나, 또는 외적요인으로서 자외선의 과량 조사되거나 스트레스 등에 의해 생성된 활성 산소가 단백질의 티올기(thiol: -SH)와 반응하여 효소 활성을 저해하거나, 콜라겐, 엘라스틴 등의 분해 효소의 발현을 증가시켜 피부의 주름을 증가시키고 탄력을 감소시켜 피부 노화가 진행된다. As used herein, the term "improvement of skin wrinkles" means maintaining or enhancing the ability of skin to be associated with wrinkles and elasticity. Collagen (collagen) and elastin (elastin), which are the collagen fibers of the skin dermis layer, play a key role in maintaining skin elasticity. Collagen biosynthesis is affected by internal and external skin. Specifically, the skin cells are reduced in cellular activity due to natural aging, and collagen fibers are decreased. When extreme ultraviolet rays are irradiated as an external factor, or when active oxygen generated by stress or the like causes thiol (-SH) To increase the expression of collagen and elastase, thereby increasing the wrinkles of the skin and reducing the elasticity, thereby aging the skin.
본 발명에서 기재하는 화장료 조성물에 함유되는 아디프산은 화장료 전체 중량에 대하여 0.0001 내지 20 중량%로 포함되는 것일 수 있다. 화장료 내에 0.0001 중량% 미만의 아디프산은 그 용량이 소량이어서 주름 개선 효과가 없을 수 있으며, 20 중량% 이상의 아디프산은 기존에 알려진 독성을 나타낼 수 있다.The adipic acid contained in the cosmetic composition described in the present invention may be contained in an amount of 0.0001 to 20% by weight based on the total weight of the cosmetic. Less than 0.0001% by weight of adipic acid in cosmetics may be less effective in improving wrinkles due to the small amount of adipic acid, and more than 20% by weight of adipic acid may exhibit the conventionally known toxicity.
본 발명의 조성물은 프로콜라겐 분비량의 증가, 콜라겐 생합성의 촉진, MMP-1 유전자의 발현 감소 및 피부 각질층 형성 억제로 이루어지는 군에서 선택되는 어느 하나 이상의 효과를 가지는 것일 수 있다.The composition of the present invention may be one having at least one effect selected from the group consisting of an increase in procollagen secretion amount, promotion of collagen biosynthesis, reduction of expression of MMP-1 gene, and inhibition of skin stratum corneum formation.
본 발명의 일실시예에 따르면, 사람피부섬유아세포에 자외선 조사와 함께 약물을 처리하여 세포외 기질로 분비된 프로콜라겐, 프로콜라겐 타입I C-펩타이드(PIP) 양을 측정한 결과, 도 1에 나타난 바와 같이, 자외선을 조사받은 대조세포(+UVB)에서는 정상세포(-UVB)에 비해 프로콜라겐 분비량이 현저히 감소하였고, 자외선 조사와 함께 아디프산을 처리한 세포에서는 자외선만 조사받은 대조세포(+UVB)에 비해 콜라겐 양이 18% 유의하게 증가하였다. 한편 아디프산을 비타민C와 함께 처리한 세포에서는 대조세포(+UVB)에 비해 콜라겐 양이 50% 유의하게 증가하였고 이는 비타민C(+27%) 또는 아디프산(+18%) 단독으로 처리한 세포에서 관찰된 콜라겐 양보다 더 높은 수치를 보였다(도1 참조).According to one embodiment of the present invention, the amount of procollagen and procollagen type I C-peptide (PIP) secreted into the extracellular matrix by treating the drug with irradiation of ultraviolet rays to human skin fibroblasts was measured. As a result, As shown, the amount of procollagen secretion was significantly reduced in UV irradiated control cells (+ UVB) compared to normal cells (-UVB). In the cells treated with adipic acid with ultraviolet irradiation, control cells + UVB), the amount of collagen was significantly increased by 18%. On the other hand, in the cells treated with adipic acid with vitamin C, the amount of collagen was significantly increased by 50% as compared with the control cells (+ UVB), which was treated with only vitamin C (+ 27%) or adipic acid Which was higher than the amount of collagen observed in one cell (see Fig. 1).
본 발명의 일실시예에 따르면, 아디프산 섭취군의 경우 +UVB 대조군에 비해 콜라겐 타입 1α1과 α2, 그리고 콜라겐 타입 3α1의 발현은 유의하게 증가하였고, MMP-1a 및 -1b, MMP-3, 그리고 MMP-9 유전자 발현은 유의하게 감소하였다(도8 참조). 따라서 아디프산은 피하조직의 콜라겐 단백질 합성을 증가시키고 콜라겐 섬유의 분해를 저해함으로써 자외선조사에 의한 주름형성을 완화시킬 수 있다.According to one embodiment of the present invention, the expression of collagen type 1α1 and α2 and collagen type 3α1 was significantly increased in the adipic acid-supplemented group compared to the + UVB-treated group, and the expression of MMP-1a and -1b, MMP- And MMP-9 gene expression was significantly decreased (see FIG. 8). Thus, adipic acid can increase collagen protein synthesis in subcutaneous tissues and inhibit degradation of collagen fibers, thereby alleviating wrinkle formation caused by ultraviolet irradiation.
본 발명의 일실시예에 따르면, 사람피부섬유아세포에 약물을 처리한 후 프로콜라겐과 MMP-1 유전자 발현변화를 측정한 결과, 도 2에 나타난 바와 같이, 아디프산은 자외선에 의해 유의하게 감소한 프로콜라겐의 발현을 유의하게 증가시킨 한편, 자외선에 의해 유의하게 증가한 MMP-1 유전자발현은 유의하게 감소시켰다. 이와 같은 아디프산의 유전자발현 조절 효능은 비타민 C와 유사한 수준으로 나타났다(도2 참조).According to one embodiment of the present invention, the change in the expression level of procollagen and MMP-1 gene after treatment of the drug with human skin fibroblasts is shown in FIG. 2. As a result, adipic acid has a significantly reduced pro- The expression of collagen was significantly increased while the expression of MMP-1 gene significantly increased by ultraviolet light was significantly reduced. The gene expression regulating activity of adipic acid was similar to that of vitamin C (see FIG. 2).
본 발명에서 사용되는 용어, "화장료 조성물"은 상기 화합물을 포함하는 조성물로서 그 제형은 어떠한 형태라도 가능하다. 이러한 제형의 예를 들면 상기 조성물을 이용하여 제조된 화장료는 영양크림, 아이크림, 마사지크림, 클렌징크림과 같은 크림류, 팩류, 영양로션과 같은 로션류, 에센스류, 유연화장수, 영양화장수와 같은 화장수류, 파우다류, 파운데이션류 및 메이크업 베이스류 등이고, 본 발명의 목적을 달성하기 위하여 이러한 제형 중 어떠한 형태로도 제조되어 상용화될 수 있으며, 상기 예들에 한정되지 않는다. 또한, 본 발명에 따른 화장료 조성물에는 통상의 화장료 제조 방법으로 제형화할 수 있다. The term "cosmetic composition" used in the present invention is a composition containing the above-mentioned compound, and the formulation can be in any form. Examples of such formulations include cosmetic preparations made using the above composition, such as creams such as nutritional creams, eye creams, massage creams, cleansing creams, lotions such as packs, nutritional lotions, essences, softening longevity, A foundation, a makeup base, and the like, and may be manufactured and commercialized in any form of these formulations in order to achieve the object of the present invention, and the present invention is not limited to these examples. Further, the cosmetic composition according to the present invention can be formulated into a usual cosmetic preparation method.
구체적으로 본 발명의 화장료는 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 맛사지 크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 팩, 마스크팩, 마스크시트, 비누, 샴푸, 클렌징 폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더 및 아이섀도로 구성된 그룹에서 선택된 어느 하나의 제형을 가지는 것일 수 있다.Specifically, the cosmetic composition of the present invention can be used as a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, a hand cream, And may be any one selected from the group consisting of soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, milky lotion, press powder, loose powder and eye shadow.
본 발명의 화장료 조성물은 화장품학적으로 허용 가능한 담체를 추가로 포함할 수 있으며, 일반 피부 화장료에 배합되는 보통의 성분을 필요한 만큼 적용 배합하는 것이 가능하다.The cosmetic composition of the present invention may further comprise a cosmetically acceptable carrier, and it is possible to apply the usual ingredients to be blended with the general skin cosmetic composition as needed.
구체적으로, 본 발명의 화장료 조성물은 경피 침투 강화제를 추가로 포함할 수 있다. 본 발명에서 사용되는 용어, 경피 침투 강화제란 피부의 혈관세포 내로 원하는 성분이 높은 흡수율로 침투할 수 있게 해주는 조성물이다. 바람직하게는 레시틴 화장품에 사용되는 다른 인지질 성분, 리포좀 성분 등이 포함되지만 이에 국한되지는 않는다.Specifically, the cosmetic composition of the present invention may further comprise a transdermal penetration enhancer. As used herein, the term transdermal penetration enhancer is a composition that allows a desired component to penetrate into vascular cells of the skin at a high absorption rate. But are not limited to, other phospholipid components, liposomal components, and the like, preferably used in lecithin cosmetics.
또한, 유상 성분으로서 주로 사용될 수 있는 오일로는 식물성 오일, 광물성 오일, 실리콘유 및 합성유 중에서 선택된 하나 이상을 사용할 수 있다. 보다 구체적으로, 미네랄오일, 사이크로메치콘, 스쿠알란, 옥틸도데실 미리스테이트, 올리브오일, 비티스 비니페라 씨드 오일, 마카다미아너트오일, 글리세릴옥타노에이트, 캐스터오일, 에칠헥실 이소노나노에이트, 디메치콘, 사이크로펜타실록산 및 선플라워씨드 오일 등을 사용할 수 있다.As the oil which can be mainly used as an oil component, at least one selected from vegetable oil, mineral oil, silicone oil and synthetic oil can be used. More specifically, there may be mentioned mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitisviniferase seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, Chicone, cyclopentasiloxane, sunflower seed oil and the like can be used.
또한, 유화 능력을 보강하기 위하여 계면활성제, 고급 알콜 등을 0.1 내지 5 중량% 첨가할 수 있다. 이러한 계면 활성제로는 비이온 계면활성제, 음이온성 계면 활성제, 양이온성 계면 활성제, 양성 계면 활성제, 인지질 등과 같은 통상적인 계면활성제를 사용할 수 있으며, 구체적으로, 소르비탄세스퀴놀리에이트, 폴리솔베이트 60, 글리세릴 스테아레이트, 친유형 글리세릴스테아레이트, 소르비탄 올리에이트, 소르비탄 스테아레이트, 디이에이-세틸포스페이트, 소르비탄스테아레이트/슈크로스코코에이트, 글리세릴스테아레이트/폴리에틸렌글라이콜-100 스테아레이트, 세테아레스-6 올리베이트, 아라키딜알코올/베헤닐알코올/아라키딜 글루코사이드. 폴리프로필렌글라이콜-26-부테스-26/폴리에틸렌글라이콜-40 하이드로제네이티드 캐스터오일 등을 사용할 수 있다. 고급 알콜로는 탄소수가 12 내지 20인 알콜, 예컨대 세틸알코올, 스테아릴 알코올, 옥틸도데칸올, 이소스테아릴 알코올 등을 단독으로 또는 1종 이상 혼합하여 사용할 수 있다. Further, 0.1 to 5% by weight of a surfactant, a higher alcohol and the like may be added to reinforce the emulsifying ability. As such surfactants, conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids and the like can be used. Specific examples thereof include sorbitan sesquiunorate,
수상 성분은 수상의 점도 또는 경도를 조절하기 위하여 카보머, 잔탄검, 벤토나이트, 마그네슘알루미늄실리케이트, 셀룰로오스검, 덱스트린 팔미테이트 등과 같은 1종 이상의 점증제를 0.001 내지 5 중량% 더 첨가할 수 있다. In order to control the viscosity or hardness of the water phase, 0.001 to 5% by weight of at least one thickening agent such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like may be further added.
또한, 본 발명의 화장료 조성물에는 필요에 따라 고급 지방산, 비타민 등의 약효 성분과 자외선 차단제, 산화 방지제(부틸히드록시아니솔,갈릭산프로필, 엘리소르빈산, 토코페릴아세테이드, 부틸레이티드하이드록시톨루엔 등), 방부제(메칠파라벤, 부틸파라벤, 프로필파라벤, 페녹시에탄올, 이미다졸리디닐우레아, 클로르페네신 등), 착색제, pH 조절제(트리에탄올아민, 씨트릭애씨드, 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등), 보습제(글리세린, 솔비톨, 프로필렌 글라이콜, 부틸렌 글라이콜, 헥실렌 글라이콜, 디글리세린, 베타인, 글리세레스-26, 메칠글루세스-20 등), 윤활제 등의 성분을 더 첨가할 수 있다.In addition, the cosmetic composition of the present invention may contain, if necessary, a medicinal ingredient such as higher fatty acids and vitamins, an ultraviolet screening agent, an antioxidant (butylhydroxyanisole, gallic acid propylate, eicosorbic acid, tocopheryl acetatide, (Triethanolamine, citric acid, citric acid, sodium citrate, malic acid, citric acid, etc.), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinyl urea, chlorphenesin and the like) And the like), a humectant (glycerin, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin, etc.), sodium hydrogen carbonate , Betaine, glycereth-26, methylglucose-20, etc.), lubricant, and the like.
또한, 본 발명의 화장료 조성물은 피부에 필수 영양소를 보조적으로 제공할 수 있는 물질을 추가로 포함하는데, 바람직하게는 천연향, 화장품향, 또는 한약재가 포함되지만 이들에 국한되지 않는 보조제를 함유할 수 있다. In addition, the cosmetic composition of the present invention further comprises a substance capable of supplementally providing an essential nutrient to the skin, and preferably it may contain an auxiliary agent including, but not limited to, a natural flavor, a cosmetic flavor, have.
또한, 본 발명의 화장료 조성물은 피부 주름개선 성분 또는 피부탄력 증진 성분을 추가로 포함할 수 있다. 그 구체적인 피부 주름 개선 성분 또는 피부탄력 증진 성분으로는 비타민 C, 레티노산, TGF, 동물 태반 유래의 단백질, 베튤린산 및 클로렐라 추출물로 구성되는 군으로부터 선택되는 어느 하나 이상인 것일 수 있으며, 가장 바람직하게는 비타민 C일 수 있다.In addition, the cosmetic composition of the present invention may further comprise a skin wrinkle improving component or a skin elasticity improving component. The specific skin wrinkle improving component or skin elasticity enhancing component may be at least one selected from the group consisting of vitamin C, retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, and most preferably, Vitamin C < / RTI >
본 발명의 일실시예에서는 비타민 C와 아디프산을 함께 처리하였을 때 50% 향상된 프로콜라겐 분비량을 보였지만, 비타민 C를 단독으로 처리하였을 때에는 27%, 아디프산을 단독으로 처리하였을 때에는 18%의 프로콜라겐 분비량 향상을 보였다. 이러한 결과를 콜비공식에 대입하여 보면, 아디프산과 비타민 C를 함께 처리할 때 상승효과를 나타낸다는 것을 확인할 수 있다.In one embodiment of the present invention, when vitamin C and adipic acid were treated together, the amount of procollagen was increased by 50%, but when vitamin C was treated alone, it was 27% and when adipic acid alone was treated, it was 18% Showed an increase in procollagen secretion. These results, when assigned to the call informal, show that synergistic effects are exhibited when adipic acid and vitamin C are treated together.
본 발명은 아디프산을 유효성분으로 함유하는 주름 개선용 피부 외용제 조성물을 제공한다.The present invention provides a composition for external application for skin for improving wrinkles containing adipic acid as an active ingredient.
본 발명의 외용제 조성물은 피부의 주름을 개선하고, 주름이 생성되는 것을 방지하며, 지연시킬 목적으로 사용되는 것으로, 그 제형에 있어서 특별히 한정되는 바가 없으며, 예를 들면, 유연화장수, 영양화장수, 마사지크림, 영양크림, 팩, 마스크팩, 마스크시트, 젤 또는 피부 점착타입 화장료의 제형을 갖는 화장료 조성물일 수 있으며, 또한, 로션, 연고, 겔, 크림, 패취 또는 분무제와 같은 경피투여형 제형일 수 있다. The composition for external use of the present invention is used for the purpose of improving the wrinkles of the skin, preventing and delaying the generation of wrinkles, and is not particularly limited in its formulation. Examples thereof include softening longevity, The composition may be a cosmetic composition having a formulation of a cream, a nutritional cream, a pack, a mask pack, a mask sheet, a gel or a skin adhesive type cosmetic composition and may also be a transdermal dosage form such as lotion, ointment, gel, cream, patch, have.
또한, 각 제형의 외용제 조성물에 있어서, 상기한 필수 성분 이외의 다른 성분들은 기타 외용제의 제형 또는 사용목적 등에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있다. Further, in the external preparation for each formulation, components other than the above-mentioned essential components can be mixed and selected without difficulty by those skilled in the art depending on the formulation or purpose of use of the other external preparation.
본 발명은 아디프산을 유효성분으로 함유하는 주름 개선용 식품 조성물을 제공한다.The present invention provides a food composition for improving wrinkles containing adipic acid as an active ingredient.
본 발명의 식품 조성물은 정제, 과립, 분말, 캅셀, 액상의 용액 및 환으로 이루어진 군으로부터 선택된 어느 하나의 제형으로 제조된 것일 수 있다. 본 발명에 따른 식품 조성물은 아디프산을 유효성분으로 포함시켜 분말제, 액제, 정제, 연질캅셀제, 과립제, 티백차, 인스턴트 차 또는 드링크제 등의 형태로 제형화될 수 있다. 유효 성분으로서의 아디프산의 함량은 그 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 조성물 중에 포함되는 아디프산의 양은 전체 식품 중량의 0.1 내지 90 중량%로 가할 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있다. 또한, 본 발명에 따른 식품 조성물은 아디프산 이외에 본 발명이 목적으로 하는 주효과를 손상시키지 않는 범위 내에서 바람직하게는 주효과에 상승효과를 줄 수 있는 다른 성분 예를 들면, 비타민 C와 같은 주름 개선용 화합물 또는 녹차 추출물, 닥나무 추출물, 감초추출물, 상백피 추출물, 빈랑자 추출물, 황금 추출물, 산삼 추출물 등의 천연물을 함유하는 것도 무방하다.The food composition of the present invention may be prepared in any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings. The food composition according to the present invention can be formulated in the form of powders, liquids, tablets, soft capsules, granules, tea bags, instant tea or drinks containing adipic acid as an active ingredient. The content of adipic acid as an active ingredient can be appropriately determined depending on the intended use (for prevention or improvement). Generally, the amount of adipic acid contained in the food composition may be 0.1 to 90% by weight based on the total weight of the food. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range. In addition, the food composition according to the present invention may contain other ingredients which can give a synergistic effect to the main effect, such as vitamin C, such as vitamin C, in addition to adipic acid, to the extent that the main effect of the present invention is not impaired A wrinkle improving compound or a green tea extract, a mulberry extract, a licorice extract, a bark extract, a bamboo extract, a golden extract, and a wild ginseng extract.
상기와 같은 형태로 제형화된 식품 조성물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강기능식품은 모두 포함한다. The food composition formulated in this form can be added directly to the food or used together with other food or food ingredients, and can be suitably used according to conventional methods. Examples of food products include dairy products including drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, soups, , Dairy products and dairy products, and all health functional foods in the ordinary sense are included.
본 발명의 식품 조성물이 드링크제인 경우는 지시된 비율로 필수성분으로서 아디프산을 함유하며, 그 밖의 드링크제 제조를 목적으로 사용되는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제 및 합성 향미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.When the food composition of the present invention is a drink, it contains adipic acid as an essential ingredient in the indicated ratio. There are no particular restrictions on other ingredients used for the purpose of producing other drink products, and various flavoring agents Natural carbohydrates and the like as additional components. Examples of such natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors and synthetic flavors and the like can be used as the flavors other than those described above. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
또한 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에도 본 발명의 본 발명의 식품 조성물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 아디프산 100 중량부 당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition, the food composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the inventive food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the adipic acid of the present invention.
본 발명은 아디프산을 유효성분으로 함유하는 주름 개선용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for improving wrinkles containing adipic acid as an active ingredient.
본 발명의 화합물은 UV에 의한 세포 노화 억제 및 활성 산소종의 생성 억제로 피부 노화 억제 효과가 있으며, 피부세포에서 세포외 기질 단백질의 발현을 촉진함으로써 피부의 주름 개선에 효과가 있으므로, 피부 노화 억제 또는 피부 주름 개선용 약학적 조성물로 사용될 수 있다. The compound of the present invention has an effect of inhibiting aging of cells due to inhibition of cell senescence by UV and formation of reactive oxygen species and promoting the expression of extracellular matrix proteins in skin cells, Or as a pharmaceutical composition for improving skin wrinkles.
본 발명에서 사용되는 주름 개선용 또는 피부 탄력 증진용 약학적 조성물의 처리량은 약학적으로 유효한 양이어야 한다. 본 발명에서 사용되는 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 감염된 바이러스 종류, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 유효량은 당업자에게 인식되어 있듯이 처리의 경로, 부형제의 사용 및 다른 약제와 함께 사용할 수 있는 가능성에 따라 변할 수 있다. The amount of the pharmaceutical composition for improving wrinkles or skin elasticity used in the present invention should be a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and the effective dose level will vary depending on the species and severity, The type of virus being infected, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and rate of release, the duration of the treatment, factors including co-administered drugs and other well known factors in the medical field. Effective amounts may vary depending on the route of treatment, the use of excipients, and the likelihood of use with other agents, as will be appreciated by those skilled in the art.
본 발명의 주름 개선용 또는 피부 탄력 증진용 약학적 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 잘 알려진 방법을 사용하여 약학적 제형으로 제조될 수 있다. 제형의 제조에 있어서, 활성 성분을 담체와 함께 혼합 또는 희석하거나, 용기 형태의 담체 내에 봉입시키는 것이 바람직하다. The pharmaceutical compositions for improving wrinkles or improving skin elasticity of the present invention may be formulated into pharmaceutical formulations using methods well known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal . In the preparation of the formulations, it is preferred that the active ingredient is mixed with or diluted with the carrier, or enclosed in a carrier in the form of a container.
따라서, 본 발명의 주름 개선용 또는 피부 탄력 증진용 약학적 조성물은 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제 및 패치의 형태로 제형화하여 사용될 수 있고, 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. Therefore, the pharmaceutical composition for wrinkle improvement or skin elasticity enhancement of the present invention can be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup or aerosol, May be formulated and used, and may further comprise suitable carriers, excipients or diluents conventionally used in the preparation of the composition.
예를 들어, 본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
또한, 본 발명의 상기 약학 조성물은 피부 노화 억제 또는 피부 주름개선을 목적으로 의약외품 제조시 첨가되어 사용될 수 있다. 본 발명의 상기 약학 조성물을 의약외품 첨가물로 사용할 경우, 상기 화합물을 그대로 첨가하거나 다른 의약외품 또는 의약외품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 바람직하게는, 상기 의약외품은 소독청결제, 샤워폼, 가그린, 물티슈, 세제비누, 핸드워시, 가습기 충진제, 마스크, 연고제, 코팅제 또는 필터충진제일 수 있다. In addition, the pharmaceutical composition of the present invention can be added to the skin during the preparation of quasi-drugs for the purpose of inhibiting skin aging or improving skin wrinkles. When the pharmaceutical composition of the present invention is used as a quasi-drug additive, the compound may be added as it is or may be used together with other quasi-drugs or quasi-drugs, and may be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Preferably, the quasi-drug may be a disinfectant cleaner, a shower foam, a gagrin, a wet tissue, a detergent soap, a hand wash, a humidifier filler, a mask, an ointment agent, a coating agent or a filter filler.
또한, 본 발명은 아디프산을 유효성분으로 함유하는 피부 탄력 증진용 화장료 조성물, 피부 외용제 및 식품 조성물을 제공한다.The present invention also provides a cosmetic composition for enhancing skin elasticity, an external preparation for skin and a food composition containing adipic acid as an active ingredient.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.
사람피부섬유아세포를Human skin fibroblasts 이용한 아디프산의 주름개선 효능 Effect of Adipic Acid on Wrinkles
1-1) 세포배양1-1) Cell culture
사람피부섬유아세포(normal human dermal fibroblasts, neonatal foreskin)를 ATCC사(Manassas, VA, USA)로부터 구매하여 사용하였다. 구입한 세포를 fibroblast growth medium(Promo Cell, Heidelberg)을 이용하여 37℃, 5% CO2 인큐베이터에서 배양하여 실험에 사용하였다.Normal human dermal fibroblasts (neonatal foreskin) were purchased from ATCC (Manassas, VA, USA). The cells were cultured in a 5% CO 2 incubator at 37 ° C using a fibroblast growth medium (Promo Cell, Heidelberg).
1-2) 프로콜라겐 타입 I C-펩타이드(PIP) 농도 측정1-2) Measurement of procollagen type I C-peptide (PIP) concentration
콜라겐 생합성능을 알아보기 위하여 사람섬유아세포를 12 웰-플레이트에 1.0 × 106 cells/well 씩 분주하여 아디프산과 비타민 C를 각각 100 μM의 농도로 첨가하여 24시간동안 CO2 배양기에서 배양하였다. 각 웰의 배지를 제거한 후 PBS로 1회 세척하고 다시 1 ml의 PBS를 넣은 후 20 mJ/cm2 조건으로 자외선 B(UVB)를 조사하였다. 각 웰의 PBS를 다시 배지로 교체하여 24시간동안 배양한 후, 프로콜라겐 타입Ⅰ C-펩타이드 EIA 키트(Takara bio, Japan)를 이용하여 배지로 분비된 프로콜라겐 양을 측정하였다. 콜라겐 측정 키트에 포함된 표준용액을 농도별로 희석하고 450 nm에서 흡광도를 측정하여 표준농도 곡선을 작성하고 콜라겐 생성량을 산정하였다.To investigate the collagen biosynthesis performance, human fibroblasts were added to 12 well plates at a density of 1.0 × 10 6 cells / well. Adipic acid and vitamin C were added at a concentration of 100 μM, respectively, and cultured in a CO 2 incubator for 24 hours. After removing the medium from each well, the plate was washed once with PBS, and 1 ml of PBS was added thereto. Then, ultraviolet B (UVB) was irradiated at 20 mJ / cm 2 . The PBS of each well was again replaced with the medium and cultured for 24 hours. The amount of procollagen secreted in the medium was measured using a procollagen type I C-peptide EIA kit (Takara Bio, Japan). The standard solution contained in the collagen measurement kit was diluted by concentration, absorbance was measured at 450 nm to prepare a standard concentration curve and the amount of collagen production was calculated.
1-3) 트리졸 방법을 이용한 RNA 분리 및 RT-PCR(reverse transcription-polymerase chain reaction)1-3) RNA isolation and RT-PCR using the triazole method (reverse transcription-polymerase chain reaction)
사람피부섬유아세포 1 × 107 cells 당 트리졸 용액 334 ㎕을 첨가하여 갈아준 후, 4℃, 12,000×g에서 10분간 원심분리하였다. 상층액을 새 튜브로 옮긴 후 클로로포름 67 ㎕을 첨가하고, 볼텍스(vortex)하였다. 다시 상층액을 새 튜브로 옮기고 상층액과 아이소프로페놀의 비율이 1:1이 되도록 아이소프로판올을 첨가하였다. 10회 세게 흔든 다음 실온에서 15분 동안 방치하고, 12,000×g, 4℃에서 10분간 원심분리 시킨 후 상층액을 제거하고, 남은 침전물에 70% 에탄올 1 ml을 가한 후 7,500×g, 4℃에서 5분 동안 원심분리 하였다. 에탄올을 제거한 후 RNA 침전물이 담긴 튜브를 실온에서 15분 동안 건조시키고, 핵산분해효소가 포함되지 않은 물을 사용하여 RNA 펠렛을 용해시켰다. UV/VIS 분광 광도계(Beckman coulter, DU730)를 이용하여 260 nm 및 280 nm 파장에서 추출된 RNA 시료의 농도를 측정하고, 아가로오스 겔 전기영동을 실시하여 RNA 시료에 이상이 없음(integrity)을 확인하였다.After adding 334 μl of trizol solution per 1 × 10 7 cells of human skin fibroblasts, they were changed and centrifuged at 12,000 × g for 10 minutes at 4 ° C. The supernatant was transferred to a new tube, and 67 μl of chloroform was added and vortexed. The supernatant was again transferred to a new tube and isopropanol was added so that the ratio of supernatant to isopropanol was 1: 1. After 10 h of shaking, the mixture was allowed to stand at room temperature for 15 minutes, centrifuged at 12,000 × g for 10 minutes at 4 ° C., and then the supernatant was removed. 1 ml of 70% ethanol was added to the remaining precipitate, And centrifuged for 5 minutes. After removing the ethanol, the tube containing the RNA precipitate was dried at room temperature for 15 minutes, and the RNA pellet was dissolved using water containing no nucleic acid degrading enzyme. The concentration of RNA samples extracted at 260 nm and 280 nm wavelengths was measured using a UV / VIS spectrophotometer (Beckman coulter, DU730) and agarose gel electrophoresis was performed to confirm the integrity of the RNA samples Respectively.
사람피부섬유아세포에서 추출된 RNA시료를 대상으로 올리고 dT 프라이머와 슈퍼스크립트 역전사효소(GIBCO BRL, Gaithersburg, MD, USA)를 이용하여 전역사를 수행함으로써 cDNA를 합성하였다. 역전사를 통해 얻은 cDNA를 template로 하고 증폭하고자 하는 유전자 cDNA의 5‘과 3’측면 염기서열(flanking sequence)을 프라이머로 사용하여 PCR을 수행하였으며, 이때 사용된 프라이머 염기서열은 [표 2]에 제시된 바와 같다. 증폭된 PCR 산물 1 ㎕를 1% 아가로오스 겔에 전기영동하여 DNA band를 확인하였다. CDNAs were synthesized by using oligo dT primers and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA) as a template for RNA samples extracted from human skin fibroblasts. PCR was carried out using the cDNA obtained from the reverse transcription as a template and the 5 'and 3' flanking sequences of the gene cDNAs to be amplified as primers. The primer sequences used herein were as shown in [Table 2] Same as. 1 μl of the amplified PCR product was electrophoresed on 1% agarose gel to confirm the DNA band.
(℃)(° C)
산물 product
(bp)(bp)
1-4) 프로콜라겐 분비량 변화 측정 결과1-4) Results of measurement of changes in the amount of procollagen secretion
피부를 구성하는 주 단백질인 콜라겐은 피부진피에 존재하는 섬유아세포에서 프로콜라겐의 형태로 합성된 후 세포외 기질로 분비된다. 세포외 기질로 분비된 프로콜라겐은 세포표면에 존재하는 프로콜라겐 펩티다아제에 의해 C-말단이 분해되고 활성형 콜라겐으로 형성되므로 C-펩타이드 함량을 측정하면 활성화된 콜라겐 함량을 측정할 수 있다. 사람피부섬유아세포에 자외선 조사와 함께 약물을 처리하여 세포외 기질로 분비된 프로콜라겐, 프로콜라겐 타입I C-펩타이드(PIP) 양을 측정한 결과, 도 1에 나타난 바와 같이, 자외선을 조사받은 대조세포(+UVB)에서는 정상세포(-UVB)에 비해 프로콜라겐 분비량이 현저히 감소하였고, 자외선 조사와 함께 아디프산을 처리한 세포에서는 자외선만 조사받은 대조세포(+UVB)에 비해 콜라겐 양이 18% 유의하게 증가하였다. 한편 아디프산을 비타민C와 함께 처리한 세포에서는 대조세포(+UVB)에 비해 콜라겐 양이 50% 유의하게 증가하였고 이는 비타민 C(+27%) 또는 아디프산(+18%) 단독으로 처리한 세포에서 관찰된 콜라겐 양보다 더 높은 수치이다(도1 참조). 따라서 아디프산은 사람피부섬유아세포에서 콜라겐 양을 증가시키고 이러한 콜라겐 증가효과는 비타민C와 함께 사용 시 더 효과적으로 나타남을 알 수 있다. Collagen, the main protein that makes up the skin, is synthesized in the form of procollagen in fibroblasts in the skin dermis and then secreted into the extracellular matrix. Procollagen secreted into the extracellular matrix is broken down by the pro-collagen peptidase present on the cell surface and is formed into active collagen. Therefore, the activated collagen content can be measured by measuring the C-peptide content. As shown in FIG. 1, the amounts of procollagen and procollagen type I C-peptide (PIP) secreted into the extracellular matrix were measured by irradiating ultraviolet light to human skin fibroblasts, (+ UVB), the amount of procollagen secretion was significantly reduced compared to normal cells (-UVB). In the cells treated with adipic acid with ultraviolet irradiation, the amount of collagen was 18 %. On the other hand, in the cells treated with adipic acid with vitamin C, the amount of collagen was significantly increased by 50% as compared with the control cells (+ UVB), which was treated with only vitamin C (+ 27%) or adipic acid Which is higher than the amount of collagen observed in one cell (see FIG. 1). Thus, adipic acid increases the amount of collagen in human dermal fibroblasts, and this collagen-increasing effect is more effective when used with vitamin C.
1-5) 프로콜라겐 및 MMP-1 유전자 발현변화 측정 결과1-5) Measurement results of pro-collagen and MMP-1 gene expression changes
사람피부섬유아세포에 약물을 처리한 후 프로콜라겐과 MMP-1 유전자 발현변화를 측정한 결과, 도 2에 나타난 바와 같이, 아디프산은 자외선에 의해 유의하게 감소한 프로콜라겐의 발현을 유의하게 증가시킨 한편, 자외선에 의해 유의하게 증가한 MMP-1 유전자발현은 유의하게 감소시켰다. 이와 같은 아디프산의 유전자발현 조절 효능은 비타민 C와 유사한 수준으로 나타났다(도2 참조). 따라서 아디프산은 자외선을 조사받은 사람피부섬유아세포에서 프로콜라겐 합성을 증가시킬 뿐 아니라 MMP-1 발현을 억제함으로서 궁극적으로 피부주름과 밀접한 연관이 있는 콜라겐 함량을 증가시키는데 관여하였을 것으로 사료된다. As shown in FIG. 2, adipic acid significantly increased the expression of procollagen significantly decreased by ultraviolet rays, as shown in Fig. 2, when the changes of procollagen and MMP-1 gene expression were measured after treatment with human skin fibroblasts , Significantly decreased MMP-1 gene expression significantly increased by ultraviolet light. The gene expression regulating activity of adipic acid was similar to that of vitamin C (see FIG. 2). Thus, adipic acid may be involved in increasing collagen content, which is ultimately related to skin wrinkling, by inhibiting MMP-1 expression as well as increasing pro-collagen synthesis in ultraviolet irradiated human dermal fibroblasts.
마우스를 이용한 아디프산의 피부주름 개선, 보습 및 탄력증진 효능평가Evaluation of adipic acid skin wrinkle, moisturizing and elasticity enhancement efficacy using mouse
2-1) 실험식이 제조, 실험동물의 사육 및 자외선 조사2-1) Preparation of empirical formula, breeding of experimental animals and ultraviolet irradiation
본 실험에 사용한 5주령 암컷 알비노 무모 생쥐(SKH-1)는 오리엔트바이오(Gyeonggi-do , Korea)에서 구입하여 고형사료로 1주일간 적응기간을 거쳤다. 실험동물은 4개 군으로 분류하여 군별로 4 마리씩 배정하여 실험에 사용하였다. 모든 실험군은 자외선을 조사하지 않은 정상 대조군(-UVB), 자외선 조사군(+UVB), 자외선조사와 함께 아디프산(AA) 또는 비타민 C(VitC)을 섭취시킨 군으로 나누었다. 사육 기간 동안 사료와 물을 자유로이 섭취하도록 하였으며, 온도는 22±1℃, 습도는 60±5%로 유지하고 매일 광주기와 암주기가 12시간이 되도록 조절하였다. The 5-week-old female albino hairless mouse (SKH-1) used in this experiment was purchased from Orient Bio (Korea) and subjected to a week of adaptation period with solid feed. The experimental animals were divided into 4 groups and 4 mice were assigned to each group. All experimental groups were divided into two groups: normal control group (UVB), ultraviolet irradiation group (UVB), adipic acid (AA) or vitamin C (VitC). During the breeding period, feed and water were freely consumed. The temperature was maintained at 22 ± 1 ° C, the humidity was maintained at 60 ± 5%, and the light period and the dark cycle were adjusted to 12 hours each day.
-UVB군과 +UVB군은 AIN-93 실험쥐 식이 구성(Reeves, PG et al., J Nutr, 123:1939-1951, 1993)에 준하여 조제된 정제식이를 섭취시켰고, AA군은 AIN-93 정제식이에 0.2% 아디프산(Sigma-Aldrich)을, 그리고 VitC군은 AIN-93 정제식이에 0.2% 비타민 C (Sigma-Aldrich)를 첨가하여 제조된 식이를 13주간 공급하였다. 자세한 실험식이의 조성은 [표 3]과 같다. 식이는 매일 오전 10~11시 사이에 물과 함께 공급하였으며, 식이 섭취량은 매일 측정하였다. -UVB group and + UVB group received the purified diet prepared according to AIN-93 mouse diet composition (Reeves, PG et al., J Nutr, 123: 1939-1951, 1993) 0.2% adipic acid (Sigma-Aldrich) was added to the purified diet, and 0.2% vitamin C (Sigma-Aldrich) was added to the VitC group for AIN-93. The composition of the experimental diet is shown in [Table 3]. Diets were supplied daily with water between 10 am and 11 am, and the dietary intake was measured daily.
실험사육기간 동안 무모생쥐의 등 부분에 주 3회 자외선 B (UVB)를 조사하였으며 자외선 조사량은 처음 1주간은 73 mJ/cm2, 2주째는 146 mJ/cm2, 3주부터 13주까지는 219 mJ/cm2로 조사하였다. 사육하는 동안 매주 체중 및 피부두께 측정, 등 피부 사진촬영을 실시하였다. 피부두께는 디지털 마이크로 캘리퍼(Marathon Watch Company Ltd, Ontario, Canada)를 이용하여 무모생쥐의 엉덩이 부분을 측정하였다. 측정할 때 사용된 캘리퍼는 0.01 mm 까지 측정가능하며 두께에 일정한 힘을 가할 수 있는 조절기능을 갖추고 있어 같은 힘을 준 상태에서 피부의 두께 측정이 가능하였다.During the experimental period, UV rays were irradiated three times a week on the dorsal part of dull mice. The UV dose was 73 mJ / cm 2 for the first week, 146 mJ / cm 2 for the second week, 219 mJ / cm < 2 & gt ;. During the breeding, weekly skin weight measurements and skin thickness measurements were taken. The skin thickness was measured using a digital micro caliper (Marathon Watch Company Ltd, Ontario, Canada) at the buttocks of the hairless mice. The calipers used in the measurement were able to measure up to 0.01 mm and had a control function to apply constant force to the thickness, and it was possible to measure the skin thickness under the same force.
실험이 종료된 후 실험동물을 마취한 후 혈액을 채취한 후 혈액학적 분석에 사용하였고, 등 쪽 피부조직을 절취하여 일부는 냉동고에 보관한 후 분자생물학적 검사에 사용하였고, 일부는 10% 포르말린 용액에 고정하여 면역조직화학적 염색에 사용하였다.After the end of the experiment, the animals were anesthetized and blood was collected and used for hematological analysis. The dorsal skin tissues were cut, some were stored in the freezer and used for molecular biology, and some were stored in 10% formalin solution Were used for immunohistochemical staining.
(g/kg diet)(g / kg diet)
(g/kg diet)(g / kg diet)
(g/kg diet)(g / kg diet)
2-2) 피부 보습, 탄력성 및 홍반지수 측정2-2) Skin moisturizing, elasticity and erythema index measurement
실험동물의 피부 수분함유량, 수분증발량, 탄력성 및 홍반지수 측정은 각각 Corneometer®, Tewameter®, Cutometer®, Mexameter®(CK Electronics GmbH)을 이용하여 실험 종료일에 1회 측정하였다. 측정 시 실험동물 등의 일정한 부분을 가볍게 눌러서 나타나는 수치를 기록하였다.The skin moisture content, water evaporation, elasticity and erythema index of the experimental animals were measured once at the end of the experiment using Corneometer ® , Tewameter ® , Cutometer ® , and Mexameter ® (CK Electronics GmbH). In the measurement, the numerical value obtained by lightly pressing a certain portion of the test animal or the like was recorded.
2-3) 등피부조직의 주름 측정2-3) Measurement of wrinkles of skin tissue
13주 동안 자외선 조사를 실시한 무모 생쥐의 피부를 실리콘 고무로 모사판을 제작하여 주름의 형성 정도를 측정하였다. 무모 생쥐의 등 부분에 지름이 1 cm가 되는 원모양의 구멍이 있는 디스크를 부착하고 모사판 제작용 시약을 혼합하여 무모 생쥐의 등 부분에 얇게 펴 바르고 완전히 말린 다음 디스크를 조심스럽게 떼어내어 모사판을 제작하였다. 모사판의 제작 온도는 20 ~ 23 ℃, 습도 45 ~ 50%의 항온항습 상태에서 실시하였으며, 모사판 제작용 실리판 고무 인상재(Epigem, Seoul, Korea)를 사용하였다. 제작한 모사판의 분석은 컴퓨터 영상분석기(Visioline VL650, CK electronic GmbH, Germany)을 사용하여 주름의 총면적(total wrinkle area), 최대 주름깊이(max wrinkle depth), 주름 평균깊이(mean depth) 및 평균길이(mean length) 등의 4가지 주름지표 항목을 분석하였다.The skin of hairless mice exposed to ultraviolet rays for 13 weeks was simulated with silicone rubber to measure the degree of wrinkle formation. A disk with a circular hole with a diameter of 1 cm was attached to the back part of the hairless mouse, and the mixture of the reagent for preparing the simulated plate was mixed and thinly spread on the back part of the hairless mouse, completely dried and then carefully peeled off the disk, Respectively. The temperature of the simulated plate was 20 ~ 23 ℃ and the humidity was 45 ~ 50%. The impression material (Epigem, Seoul, Korea) was used for simulating plate. Using the computerized image analyzer (Visioline VL650, CK electronic GmbH, Germany), the total wrinkle area, max wrinkle depth, mean depth and mean And length (mean length).
2-4) 피부조직의 면역조직화학적 염색2-4) Immunohistochemical staining of skin tissue
무모생쥐의 등 피부 조직을 적출하고 10% 포르말린에 고정한 다음 헤마톡실린과 에오신(H&E) 염색을 실시하였다. 형광현미경 (ECLIPSE E600, Nikon, Japan)을 이용하여 관찰하였고, 디지털 카메라(DXM 1200F, Nickon, Japan)를 이용하여 사진촬영을 하였다.The dorsal skin tissues of hairless mice were fixed and fixed in 10% formalin, followed by hematoxylin and eosin (H & E) staining. (ECLIPSE E600, Nikon, Japan) and photographed using a digital camera (DXM 1200F, Nickon, Japan).
2-5) RT-PCR 분석2-5) RT-PCR analysis
등 피부조직 0.1 g 당 트리졸 용액 1 ml을 첨가하여 조직을 분쇄한 후, 4℃, 12,000×g에서 10분간 원심분리 하였다. 상층액을 새 튜브로 옮긴 후 클로로포름 200 ㎕을 첨가하고, 볼텍싱하였다. 이 과정을 두 번 반복한 다음, 상층액을 새 튜브로 옮긴 후 아이소프로판올과 상층액을 1:1 비율로 첨가하였다. 10회 세게 흔든 다음 실온에서 15분 동안 방치한 후, 12,000×g, 4℃에서 10분간 원심분리 시킨 후 상층액을 제거하고, 남은 침전물에 70% 에탄올 1 ml을 가한 후 7,500×4℃에서 5분 동안 원심분리 하였다. 에탄올을 제거한 후 RNA 침전물이 담긴 튜브를 실온에서 15분 동안 건조시키고, 핵산분해효소가 없는 물을 사용하여 RNA 펠렛을 용해시켰다. UV/VIS 분광 광도계(Beckman coulter, DU730)를 이용하여 260 nm 및 280 nm 파장에서 추출된 RNA 시료의 농도를 측정하고, 아가로스 겔 전기영동을 실시하여 RNA 시료에 이상이 없음(integrity)을 확인하였다.The tissue was pulverized by adding 1 ml of the tripozol solution per 0.1 g of skin tissue, and centrifuged at 12,000 x g for 10 minutes at 4 ° C. The supernatant was transferred to a new tube, and then 200 μl of chloroform was added and vortexed. This process was repeated twice, then the supernatant was transferred to a new tube and isopropanol and supernatant were added at a ratio of 1: 1. After 10 h of shaking, the mixture was allowed to stand at room temperature for 15 minutes, and centrifuged at 12,000 × g for 10 minutes at 4 ° C. The supernatant was removed, 1 ml of 70% ethanol was added to the remaining precipitate, Gt; min. ≪ / RTI > After removing the ethanol, the tube containing the RNA precipitate was dried at room temperature for 15 minutes, and the RNA pellet was dissolved using nucleic acid-free water. The concentrations of RNA samples extracted at 260 nm and 280 nm wavelengths were measured using a UV / VIS spectrophotometer (Beckman coulter, DU730) and agarose gel electrophoresis was performed to confirm the integrity of the RNA samples Respectively.
등 피부조직에서 추출된 RNA시료를 대상으로 올리고 dT 프라이머와 슈퍼스크립트 역전사효소(GIBCO BRL, Gaithersburg, MD, USA)를 이용하여 역전사를 수행함으로써 cDNA를 합성하였다. 역전사를 통해 얻은 cDNA를 주형으로 하고 증폭하고자 하는 유전자 cDNA의 5‘과 3’측면 염기서열(flanking sequence)을 프라이머로 사용하여 PCR을 수행하였으며, 이때 사용된 프라이머 염기서열은 [표 4]에 제시된 바와 같다. 증폭된 PCR 산물 1 ㎕를 1% 아가로스 겔에 전기영동 하여 DNA 밴드를 확인하였다.(GIBCO BRL, Gaithersburg, Md., USA), and cDNA was synthesized by reverse transcription using the dT primer and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA). PCR was carried out using 5 'and 3' flanking sequences of the gene cDNA to be amplified with the cDNA obtained through reverse transcription as a template as the primers. The primer sequences used in this case were as shown in [Table 4] Same as. 1 μl of the amplified PCR product was electrophoresed on 1% agarose gel to confirm the DNA band.
(℃)(° C)
산물 product
(bp)(bp)
2-6) 무모 생쥐의 체중 및 식이섭취량 측정 결과2-6) Measurement of body weight and dietary intake of reckless mice
도 3에 나타난 바와 같이, 자외선조사, 아디프산 및 비타민C 섭취는 무모 생쥐 마우스의 체중 및 식이섭취량에 유의한 영향을 미치지 않았다(도3 참조).As shown in FIG. 3, ultraviolet irradiation, adipic acid and vitamin C intake did not significantly affect body weight and dietary intake of reared mice (see FIG. 3).
2-7) 자외선 조사 무모 생쥐 피부조직의 수분량, 탄력성 및 홍반지수 변화 측정 결과2-7) Measurement of moisture content, elasticity and erythema index of ultraviolet irradiated mouse skin
도4에 나타난 바와 같이, 13주 동안 자외선을 조사받은 +UVB 대조군은 자외선을 조사받지 않은 정상군(-UVB)에 비해 피부조직의 수분함유랑 및 탄력성은 유의하게 감소한 한편, 수분증발량 및 홍반지수는 유의하게 증가하였다(도4 참조). 아디프산을 섭취시킨 군(AA)의 경우 같은 세기의 UV가 조사되었음에도 불구하고 +UVB 대조군에 비해 수분함유랑 및 탄력성은 각기 88% 및 83% 유의하게 증가하였고, 수분증발량 및 홍반지수는 각각 56% 및 28% 유의하게 감소하였음을 확인하였다. 이와 같은 아디프산이 피부조직 수분량, 탄력성 및 홍반지수에 미치는 효과는 비타민 C에 의한 효과와 유사하였다(도5 참조).As shown in FIG. 4, in the + UVB control group irradiated with ultraviolet rays for 13 weeks, the moisture content and elasticity of the skin tissue were decreased significantly compared to the UV group (-UVB), while the moisture evaporation and erythema index (See FIG. 4). In the case of adipic acid-supplemented group (AA), moisture content and elasticity were significantly increased by 88% and 83%, respectively, compared with the + UVB control group, 56% and 28%, respectively. The effect of adipic acid on skin tissue moisture, elasticity and erythema index was similar to that of vitamin C (see FIG. 5).
2-8) 자외선 조사 무모 생쥐의 피부주름 생성변화 측정 결과2-8) Changes in skin wrinkle formation in ultraviolet irradiated mice
아디프산의 섭취가 피부주름의 형성정도에 미치는 영향을 평가하기 위하여 무모 생쥐에 13주 동안 UVB를 조사하면서 아디프산을 섭취시킨 군(AA)의 주름생성 억제효능을 자외선만 조사받은 대조군군(+UVB)의 등피부를 촬영하여 비교하였다. 도6에 나타난 바와 같이, +UVB 대조군은 자외선을 조사받지 않은 정상군(-UVB)에 비해 다수의 굵고 깊게 패인 주름과 함께 잔주름이 형성된 것을 육안상으로 관찰할 수 있었으며, 아디프산 섭취군의 경우 +UVB 대조군에 비해 주름의 굵기와 깊이가 현저히 감소하여 자외선을 조사받지 않은 -UVB군에서 관찰된 피부상태와 유사하게 개선된 것을 확인하였다(도5 참조).To evaluate the effects of adipic acid intake on the degree of skin wrinkle formation, the wrinkle formation inhibitory effect of adipic acid-supplemented group (AA) irradiated with UVB for 13 weeks in hairless mice was compared with the control group (+ UVB) were photographed and compared. As shown in FIG. 6, the + UVB control group was visually observed to have fine wrinkles with a large number of coarse and deep wrinkles, compared with the normal UV group (-UVB), and the adipic acid- , The thickness and depth of the wrinkles were significantly decreased compared to the UVB control group, and it was confirmed that the wrinkles were improved in a similar manner to the skin conditions observed in the UV-unexposed UVB group (see FIG. 5).
13주 동안 자외선 조사를 실시한 무모 생쥐의 등피부를 실리콘 고무로 모사판을 제작하여 주름의 형성 정도를 측정한 결과, +UVB 대조군은 자외선을 조사받지 않은 정상군(-UVB)에 비해 굵고 깊게 패인 주름과 함께 잔주름이 형성된 것을 관찰할 수 있었으며, 아디프산 섭취군은 같은 세기의 UV가 조사되었음에도 불구하고 +UVB 대조군에 비해 깊은 주름이 거의 사라지는 등, 주름의 굵기와 깊이가 현저히 개선된 것을 확인하였다(도6 참조). 컴퓨터 영상분석기를 이용하여 모사판에서 주름형성 정도를 수치화 한 결과에서도 AA군의 경우 +UVB군에 비해 총주름면적이 38%, 최대 주름깊이가 45%, 평균 주름깊이가 18%, 그리고 평균 주름길이가 37% 유의하게 감소하였고, 이와 같은 아디프산의 주름개선 효능은 비타민 C에서 관찰된 주름개선효능과 유사하였다(도7B 참조). 따라서 아디프산의 섭취는 자외선조사에 의한 주름생성을 현저히 억제하는 효과가 있음을 알 수 있다.As a result of the measurement of the degree of wrinkle formation by using a silicone rubber foil made of the squamous epithelium of the hairless mice subjected to UV irradiation for 13 weeks, the + UVB control group was found to have thicker and deeper wrinkles than the normal UV- , And the adipic acid-supplemented group showed remarkable improvement in the thickness and depth of the wrinkles, such that the deep wrinkles almost disappeared compared with the + UVB control group even though the same UV intensity was irradiated to the adipic acid group (See FIG. 6). The results of numerical analysis of the degree of wrinkle formation in the simulated plate using a computerized image analyzer showed that the total wrinkle area was 38%, the maximum wrinkle depth was 45%, the average wrinkle depth was 18%, and the average wrinkle area was 38% The length was significantly reduced by 37%, and the wrinkle-reducing effect of such adipic acid was similar to the wrinkle-reducing effect observed in vitamin C (see FIG. 7B). Therefore, it can be seen that the ingestion of adipic acid has an effect of remarkably suppressing the generation of wrinkles by ultraviolet irradiation.
2-9) 자외선 조사 무모 생쥐의 피부두께 변화 측정 결과2-9) Measurement of change in skin thickness of ultraviolet irradiated mice
자외선 등에 의한 광노화가 진행되면 피부의 진피층 보호를 위해 각질층의 형성이 증가하여 피부의 두께는 두꺼워지고, 자외선 조사에 의해 피부의 두께가 두꺼워졌다는 것은 그만큼 광노화에 의한 피부손상이 크다는 것을 의미한다(Gail J Molecular mechanism of skin ageing Mech Ageing Dev 123: 801-810, 2002)As the photoaging due to ultraviolet light progresses, the formation of the stratum corneum increases to increase the thickness of the skin to increase the thickness of the skin to protect the dermal layer of the skin, and the thickening of the skin due to ultraviolet irradiation means that the skin damage due to photoaging is large J Molecular mechanism of skin aging Mech Ageing Dev 123: 801-810, 2002)
실험사육 마지막 날 디지털 마이크로 캘리퍼를 이용하여 등피부의 두께를 측정한 결과, 도 7에 나타난 바와 같이, 아디프산을 섭취시킨 군은 +UVB 대조군에 비해 피부두께가 24% 유의하게 감소하였음을 확인하였다(도7A 참조). 피부조직의 H&E 염색을 통해 무모생쥐의 피부 표피층 두께를 관찰한 결과에서도 +UVB 대조군은 자외선을 조사받지 않은 정상군(-UVB)에 비해 피부 표피층의 비후현상이 관찰되었고, AA군의 경우 +UVB 대조군에 비해 비후해진 표피층의 두께가 현저히 감소된 것이 확인되었다(도7B 참조). As a result of measuring the thickness of the back skin using a digital micro caliper on the last day of the experiment, it was confirmed that the skin thickness of the group supplemented with adipic acid was significantly reduced by 24% (See FIG. 7A). As a result of the H & E staining of skin tissues, skin thickening of skin was observed in + UVB control group compared with normal UV group (-UVB), and + UVB It was confirmed that the thickness of the thickened epidermal layer was significantly reduced as compared with the control group (see Fig. 7B).
2-10) 자외선 조사 무모 생쥐 피부조직의 유전자발현 변화2-10) Gene expression of ultraviolet irradiated mouse skin
콜라겐 타입 1과 3은 진피층의 세포간질 구성성분을 이루는 단백질이고, 특히 타입 1 콜라겐은 피부결합조직에 존재하는 세포외기질 단백질 중 가장 많은 양으로 존재한다. 한편, 콜라겐 분해를 촉매하는 MMPs는 포유류에서 23개의 타입이 존재하며 이중 자외선에 의해 증가하는 MMP 타입은 1, 3, 9번으로 알려져 있고 이들 세가지 타입의 MMP는 콜라겐 타입 1과 3을 분해하는 효소로 알려져 있다. MMP-1이 콜라겐섬유의 중간을 절단하는 한편, MMP-3, MMP-9는 절단된 콜라겐섬유를 세분해서 절단하는 역할을 하는 것으로 알려져 있다.
+UVB 대조군은 자외선을 조사받지 않은 정상군(-UVB)에 비해 피부조직의 콜라겐 타입 1α1과 α2, 그리고 콜라겐 타입 3α1의 발현은 유의하게 감소하였고, MMP-1a 및 -1b, MMP-3, 그리고 MMP-9 유전자 발현은 유의하게 증가하였다. 아디프산 섭취군의 경우 +UVB 대조군에 비해 콜라겐 타입 1α1과 α2, 그리고 콜라겐 타입 3α1의 발현은 유의하게 증가하였고, MMP-1a 및 -1b, MMP-3, 그리고 MMP-9 유전자 발현은 유의하게 감소하였다(도8 참조). 따라서 아디프산은 피하조직의 콜라겐 단백질 합성을 증가시키고 콜라겐 섬유의 분해를 저해함으로써 자외선조사에 의한 주름형성을 완화한 것으로 생각된다. + UVB-treated group showed significantly decreased expression of collagen type 1α1 and α2, and collagen type 3α1 in skin tissue compared with normal UV-untreated group (-UVB), and MMP-1a and -1b, MMP-3 and MMP-9 gene expression was significantly increased. In the adipic acid-supplemented group, expression of collagen type 1α1 and α2 and collagen type 3α1 was significantly increased compared to the + UVB control, and expression of MMP-1a and -1b, MMP-3, and MMP-9 gene was significantly (See FIG. 8). Therefore, it is considered that adipic acid increases collagen protein synthesis in subcutaneous tissues and inhibits degradation of collagen fibers, thereby alleviating wrinkle formation caused by ultraviolet irradiation.
피부의 주름개선효과 및 피부자극 관능시험Skin wrinkle improvement effect and skin irritation sensory test
3-1) 제형 실시예 및 비교예3-1) Formulation Examples and Comparative Examples
아디프산을 함유한 영양크림의 성분구성을 하기 표 5와 같이 구성하여 제조하였다. 이때, 성분함량의 단위는 중량%이다. The composition of the nutritional cream containing adipic acid was prepared as shown in Table 5 below. Here, the unit of the component content is% by weight.
한편, 상기 표5의 각 성분번호로 구별된 성분 중에서, 먼저 성분 1 내지 8을 70℃의 온도에서 가열 용해시킨 다음, 성분 9 내지 13을 성분 14에 용해 분산시켜 70℃로 가열한 것에 유화한다. 이후, 상기 유화한 것을 56℃의 온도로 냉각한 후, 분취된 성분 9에 용해시킨 성분 15를 가하여 교반하고 실온에서 냉각하여 제조하였다.On the other hand, among the components identified by the respective component numbers in Table 5, the
상기 제형 실시예에 대한 그 비교예는 성분 15인 아디프산을 제외한 나머지 성분구성이나 제조방법은 동일하게 진행하여 제조한 것을 설정하였다.The comparative example of the above-mentioned formulation examples was set to be prepared by proceeding in the same manner as the other components except for adipic acid of
3-2) 주름개선효과 및 피부자극 관능시험3-2) Wrinkle improvement effect and skin irritation sensory test
본 발명에 따른 피부 주름개선용 화장료 조성물의 피부 주름개선효과 및 피부자극을 평가하기 위하여, 상기 제형 실시예와 제형 비교예에서 제조된 영양크림을 이용하여 관능시험을 실시하였다.In order to evaluate the skin wrinkle improving effect and the skin irritation of the cosmetic composition for improving skin wrinkles according to the present invention, a sensory test was performed using the nutritional cream prepared in the above-mentioned Formulation Examples and Comparative Examples.
구체적으로, 제형 실시예와 제형 비교예의 영양크림을 피부에 각각 도포했을 때 피부의 주름개선효과를 측정하기 위하여 20세 이상의 여성 20명에게 안면 왼쪽 부분에는 제형 실시예의 영양크림(시험군)을, 안면 오른쪽 부분에는 제형 비교예의 영양크림(대조군)을 1일 1회 12주간 지속적으로 사용하게 하였다. Specifically, in order to measure the effect of improving the wrinkles of the skin when each of the nutritional creams of the formulating and comparative examples was applied to the skin, the nutritional cream (test group) of the formulation example was applied to 20 women over 20 years old on the left side of the face, On the right side of the face, the nutritional cream (control group) of the comparative example was continuously used for 12 weeks once a day.
관능시험에서 피부의 주름개선효과 항목에 대하여는 제형 비교예의 영양크림을 기준으로 제형 실시예의 영양크림이 나타내는 주름개선효과를 상대적으로 평가하게 하였고, 피부자극에 대한 관능평가는 피부의 가려움, 따가움 및 홍반 등의 현상을 평가하게 하였다. 평가는 매우 우수(5점), 우수(4점), 보통(3점), 나쁨(2점), 매우 나쁨(1점)의 오점법 기준에 의거하여 수행하였으며, 그 결과를 하기 표 6에 나타내었다. 표 6에서 피부자극은 피부자극이 없는 정도를 나타낸다.In the sensory test, the effect of improving wrinkles on the skin was relatively evaluated based on the nutritional cream of the comparative example, and the sensory evaluation on the skin irritation was caused by the itching, And so on. The evaluation was carried out according to the blotting law standards of excellent (5 points), excellent (4 points), normal (3 points), poor (2 points) and very poor (1 point) Respectively. In Table 6, skin irritation represents the degree of no skin irritation.
상기 표 6에 나타난 바와 같이, 본 발명에 따른 제형 실시예의 화장료 조성물에 대한 피부자극 평가점수는 4.40점으로 매우 양호하게 평가되어, 제형 비교예4와 마찬가지로 피부자극 정도가 낮아 피부 안전성이 우수함을 확인할 수 있었다.As shown in Table 6, the skin irritation evaluation score of the cosmetic composition of the formulation example according to the present invention was extremely good evaluated as 4.40, and it was confirmed that skin safety was excellent due to the low degree of skin irritation I could.
또한, 제형 비교예 대비 제형 실시예의 화장료 조성물이 가진 상대적인 피부의 주름개선효과는 평가점수 4.55점으로 개선 정도가 매우 우수함을 알 수 있었다.In addition, it was found that the effect of improving the wrinkles of the skin of the cosmetic composition of the formulation example was 4.55, which is much better than the comparative example.
이상에서 설명한 바와 같이, 본 발명은 아디프산을 유효성분으로 함유하는 화장료 조성물을 제공한다. 본 발명에 따른 화장료 조성물은 피부 부작용이 없으며, 피부의 주름개선효과, 콜라겐합성효과 및 콜라겐을 분해하는 효소인 콜라게나아제의 발현 저해효과가 우수하여 피부의 주름을 개선하는데 매우 유용하다. 본 발명의 아디프산을 함유하는 조성물은 향후 기능성화장품 또는 건강기능식품의 소재로 활용될 수 있을 것으로 생각된다.INDUSTRIAL APPLICABILITY As described above, the present invention provides a cosmetic composition comprising adipic acid as an active ingredient. The cosmetic composition according to the present invention has no skin side effects and is excellent in improving wrinkles of skin, collagen synthesis effect and collagenase-degrading enzyme, and thus is very useful for improving wrinkles of skin. It is believed that the composition containing adipic acid of the present invention can be utilized as a material for functional cosmetics or health functional foods in the future.
[제조예 1][Production Example 1]
화장료의 제조Manufacture of cosmetics
1-1) 유연 화장수의 제조1-1) Manufacture of flexible lotion
아디프산을 유효성분으로 포함하는 유연 화장수를 통상의 방법에 따라 제조하였다.A flexible lotion containing adipic acid as an active ingredient was prepared according to a conventional method.
성분함량(중량%) 아디프산 0.1, 글리세린3.0, 부틸렌 글리콜 2.0, 프로필렌 글리콜 2.0, 카복시비닐폴리머 0.1, 에탄올 10.0, 트리에탄올아민 0.1, 방부제, 미량색소, 미량향료 및 미량정제수잔량 총계100.0Component Content (% by weight) Adipic acid 0.1, glycerin 3.0, butylene glycol 2.0, propylene glycol 2.0, carboxyvinyl polymer 0.1, ethanol 10.0, triethanolamine 0.1, preservative, trace pigment, trace flavor and trace amount of purified water Total 100.0
1-2) 영양 크림의 제조1-2) Manufacture of nutritional cream
아디프산을 유효 성분으로 포함하는 영양 크림을 통상의 방법에 따라 제조하였다. 성분함량은 중량%로 기재하였다.A nutritional cream containing adipic acid as an active ingredient was prepared according to a conventional method. The component content is expressed as% by weight.
아디프산 0.1, 밀납 10.0, 폴리소르베이트60 1.5, 소르비탄세스퀴올레이트 0.5, 유동파라핀 10.0, 스쿠알란 5.0, 카프릴릭/카프릭 트리글리세라이드 5.0, 글리세린 5.0, 부틸렌 글리콜 3.0, 프로필렌 글리콜 3.0, 트리에탄올아민 0.2, 방부제, 미량색소, 미량향료 및 미량정제수Propylene glycol 3.0, propylene glycol 3.0, propylene glycol 2.5, glycerin 5.0, glycerin 5.0, glycerin 5.0, sorbitan sesquioleate 0.5, liquid paraffin 10.0, squalane 5.0, caprylic / capric triglyceride 5.0, glycerin 5.0, Triethanolamine 0.2, preservative, trace pigment, trace flavor and trace amount of purified water
1-3) 마스크팩용 조성물 및 마스크팩의 제조1-3) Preparation of mask pack composition and mask pack
아디프산을 유효 성분으로 포함하는 마스크팩용 조성물을 통상의 방법에 따라 제조하였다. 성분함량은 중량%로 기재하였다.A composition for a mask pack containing adipic acid as an active ingredient was prepared by a conventional method. The component content is expressed as% by weight.
아디프산 0.1, 시토스테롤 13.0, 폴리 글리세릴 2-올레이트 0.2, 세라마이드 0.1, 세테아레스-4 5.0, 콜레스테롤 0.3, 디세틸포스페이트 0.4, 농글리세린 2.0, 마카데미아 오일 10.0, 카르복시비닐폴리머 0.4, 산탄검 0.1, 방부제 0.2, 향료 0.15. 정제수 68.05 총계 100.00.1, cetearate -4 5.0, cholesterol 0.3, dicetylphosphate 0.4, concentrated glycerin 2.0, macadamia oil 10.0, carboxyvinyl polymer 0.4, carboxyvinyl polymer 0.4, polyvinylpyrrolidone 0.1, Gum 0.1, preservative 0.2, perfume 0.15. Purified water 68.05 Total 100.0
상기 제조된 마스크팩 조성물을 부직포(가로x세로, 10x10cm)에 함침시켜 마스크팩(Mask Pack) 제품을 제조하였다.The mask pack composition thus prepared was impregnated into a nonwoven fabric (width x length, 10 x 10 cm) to prepare a mask pack product.
[제조예 2][Production Example 2]
약학적 제제의 제조Production of pharmaceutical preparations
2-1) 산제의 제조2-1) Manufacture of powder
본 발명의 아디프산 2 g2 g of the adipic acid of the present invention
유당 1 gLactose 1 g
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above components were mixed and packed in airtight bags to prepare powders.
2-2) 정제의 제조2-2) Preparation of tablets
본 발명의 아디프산 100 ㎎100 mg of the adipic acid of the present invention
옥수수전분 100 ㎎Corn starch 100 mg
유 당 100 ㎎100 mg of milk
스테아린산 마그네슘 2 ㎎2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
2-3) 캡슐제의 제조2-3) Preparation of capsules
본 발명의 아디프산 100 ㎎100 mg of the adipic acid of the present invention
옥수수전분 100 ㎎Corn starch 100 mg
유 당 100 ㎎100 mg of milk
스테아린산 마그네슘 2 ㎎2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.
2-4) 환의 제조2-4) Preparation of rings
본 발명의 아디프산 1 g1 g of the adipic acid of the present invention
유당 1.5 gLactose 1.5 g
글리세린 1 gGlycerin 1 g
자일리톨 0.5 g0.5 g of xylitol
상기의 성분을 혼합한 후, 통상의 방법에 따라 1환 당 4 g이 되도록 제조하였다.After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.
2-5) 과립의 제조2-5) Preparation of granules
본 발명의 아디프산 150 ㎎150 mg of the adipic acid of the present invention
대두추출물 50 ㎎Soybean extract 50 mg
포도당 200 ㎎200 mg of glucose
전분 600 ㎎600 mg of starch
상기의 성분을 혼합한 후, 30% 에탄올 100 ㎎을 첨가하여 섭씨 60 ℃에서 건조하여 과립을 형성한 후 포에 충진하였다.After mixing the above components, 100 mg of 30% ethanol was added and the mixture was dried at 60 캜 to form granules, which were then filled in a capsule.
[제조예 3][Production Example 3]
식품의 제조Manufacturing of food products
아디프산을 함유한 기능식품 조성물은 다음 각각의 제제예와 같은 조성으로 통상의 액제 제조방법으로 제조하였다. 최종 부피는 각 액제에 100 ml이다. 본 제제예는 액제 뿐만 아니라 정제, 산제, 과립제 등으로 통상의 제조방법으로 제조가 가능하다. The functional food composition containing adipic acid was prepared by a conventional liquid preparation method with the same composition as each of the following formulation examples. The final volume is 100 ml for each liquid. This preparation example can be prepared not only as a liquid preparation but also tablets, powders, granules and the like by a usual production method.
성분함량 (중량%) 아디프산 100mg, 벌꿀 1500mg, 비타민C 50mg, 비타민B6 10mg, 니코틴산아미드10mg, 로얄젤리 80mg, 방부제, 향, 미량정제수잔량합계100mgIngredient Amount (wt%) Adipic acid 100 mg, honey 1500 mg,
<110> Industry-Academic Cooperation Foundation, Yonsei University <120> Composition for comprising adipic acid for improving skin wrinkle or enhancing skin elasticity <130> PB15-12968 <160> 22 <170> KopatentIn 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Procollagen forward primer <400> 1 tcttcaagcc atcctgtgtg 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Procollagen reverse primer <400> 2 gcgagtctgt gtttttgcag 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Metalloproteinase 1 forward primer <400> 3 atgacatgag tccggagcaa 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Metalloproteinase 1 reverse primer <400> 4 tcatctcctg ggtccctttc 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase forward primer <400> 5 gtgatggcat ggactgtggt 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase reverse primer <400> 6 ggagccaaaa gggtcatcat 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 1 forward primer <400> 7 ggcaacagtc gcttcaccta 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 1 reverse primer <400> 8 agtccgaatt cctggtctgg 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 2 forward primer <400> 9 cggttctgtt ggtcctgttg 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 2 reverse primer <400> 10 acccctgtgc cctttatcac 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 3 alpha 1 forward primer <400> 11 taaccaaggc tgcaagatgg 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 3 alpha 1 reverse primer <400> 12 accagtgctt acgtgggaca 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1a forward primer <400> 13 ccctgtgttt cacaacggag 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1a reverse primer <400> 14 cctcagcttt tcagccatca 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1b forward primer <400> 15 tttgctcatg cttttctgcc 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1b reverse primer <400> 16 gaatgggaga gtccaaggga 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 3 forward primer <400> 17 tgctggtatg gagcttctgc 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 3 reverse primer <400> 18 catctccaac ccgaggaact 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 9 forward primer <400> 19 gtggaccatg aggtgaacca 20 <210> 20 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 9 reverse primer <400> 20 actgcacggt tgaagcaaag 20 <210> 21 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase forward primer <400> 21 ggagattgtt gccatcaacg 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase reverse primer <400> 22 tgacaagctt cccattctcg 20 <110> Industry-Academic Cooperation Foundation, Yonsei University <120> Composition for comprising adipic acid for improving skin wrinkle or enhancing skin elasticity <130> PB15-12968 <160> 22 <170> Kopatentin 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Procollagen forward primer <400> 1 tcttcaagcc atcctgtgtg 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Procollagen reverse primer <400> 2 gcgagtctgt gtttttgcag 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Metalloproteinase 1 forward primer <400> 3 atgacatgag tccggagcaa 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Metalloproteinase 1 reverse primer <400> 4 tcatctcctg ggtccctttc 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase forward primer <400> 5 gtgatggcat ggactgtggt 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase reverse primer <400> 6 ggagccaaaa gggtcatcat 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 1 forward primer <400> 7 ggcaacagtc gcttcaccta 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 1 reverse primer <400> 8 agtccgaatt cctggtctgg 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 2 forward primer <400> 9 cggttctgtt ggtcctgttg 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 2 reverse primer <400> 10 acccctgtgc cctttatcac 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 3 alpha 1 forward primer <400> 11 taaccaaggc tgcaagatgg 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 3 alpha 1 reverse primer <400> 12 accagtgctt acgtgggaca 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1a forward primer <400> 13 ccctgtgttt cacaacggag 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1a reverse primer <400> 14 cctcagcttt tcagccatca 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1b forward primer <400> 15 tttgctcatg cttttctgcc 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 1b reverse primer <400> 16 gaatgggaga gtccaaggga 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 3 forward primer <400> 17 tgctggtatg gagcttctgc 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 3 reverse primer <400> 18 catctccaac ccgaggaact 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 9 forward primer <400> 19 gtggaccatg aggtgaacca 20 <210> 20 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Matrix metallopeptidase 9 reverse primer <400> 20 actgcacggt tgaagcaaag 20 <210> 21 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase forward primer <400> 21 ggagattgtt gccatcaacg 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Glyceraldehyde 3-phosphate dehydrogenase reverse primer <400> 22 tgacaagctt cccattctcg 20
Claims (19)
Which has adipic acid as an active ingredient and has at least one effect selected from the group consisting of an increase in procollagen secretion amount, promotion of collagen biosynthesis, reduction of expression of MMP-1 gene, and inhibition of skin skin layer thickening A food composition for improving elasticity.
상기 식품은 정제, 과립, 분말, 캅셀, 액상의 용액 및 환으로 이루어진 군으로부터 선택된 어느 하나의 제형으로 제조된 것을 특징으로 하는 피부 탄력 증진용 식품 조성물.18. The method of claim 17,
Wherein the food is prepared from any one selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings.
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KR1020160017137A KR101721022B1 (en) | 2016-02-15 | 2016-02-15 | Composition for comprising adipic acid for improving skin wrinkle or enhancing skin elasticity |
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KR (1) | KR101721022B1 (en) |
WO (1) | WO2017142265A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20200069693A (en) * | 2018-12-07 | 2020-06-17 | 조선대학교산학협력단 | Composition for protecting skin against ultraviolet ray comprising malonic acid from pine needle as effective component |
KR20230065584A (en) | 2021-11-05 | 2023-05-12 | 재단법인대구경북과학기술원 | Composition for improving skin elasticity during wound healing regeneration comprising RGD-containing Elastin-Like Polypeptide and stem cell |
Families Citing this family (1)
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CN114432284A (en) * | 2022-03-16 | 2022-05-06 | 中国农业大学 | Application of adipic acid in preparation of product for resisting skin photodamage |
Citations (3)
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US20130116189A1 (en) * | 2010-06-15 | 2013-05-09 | Sunstar Inc. of Osaka, Japan | Retinol-modified collagen, method for producing same, and external composition for skin containing same |
KR101318084B1 (en) * | 2011-12-26 | 2013-10-14 | 한국콜마주식회사 | Water Dispersion Cosmetic Composition Comprising POLYQUATERNUM-51 and ADIPIC ACID/NEOPENTYL GLYCOL CROSSPOLYMER Suspension Solution |
CN104187702A (en) * | 2014-09-30 | 2014-12-10 | 青岛金佳慧食品有限公司 | Health-care food for delaying skin aging |
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US8568751B1 (en) * | 2011-02-17 | 2013-10-29 | Beachbody, LLC | Anti-aging cosmeceutical composition |
KR101101808B1 (en) * | 2011-06-01 | 2012-01-05 | 연세대학교 산학협력단 | Novel uses of adipic acid |
JP2014125432A (en) * | 2012-12-25 | 2014-07-07 | Lion Corp | Skin patch composition |
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2016
- 2016-02-15 KR KR1020160017137A patent/KR101721022B1/en active IP Right Grant
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- 2017-02-13 WO PCT/KR2017/001528 patent/WO2017142265A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US20130116189A1 (en) * | 2010-06-15 | 2013-05-09 | Sunstar Inc. of Osaka, Japan | Retinol-modified collagen, method for producing same, and external composition for skin containing same |
KR101318084B1 (en) * | 2011-12-26 | 2013-10-14 | 한국콜마주식회사 | Water Dispersion Cosmetic Composition Comprising POLYQUATERNUM-51 and ADIPIC ACID/NEOPENTYL GLYCOL CROSSPOLYMER Suspension Solution |
CN104187702A (en) * | 2014-09-30 | 2014-12-10 | 青岛金佳慧食品有限公司 | Health-care food for delaying skin aging |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20200069693A (en) * | 2018-12-07 | 2020-06-17 | 조선대학교산학협력단 | Composition for protecting skin against ultraviolet ray comprising malonic acid from pine needle as effective component |
KR102132817B1 (en) | 2018-12-07 | 2020-07-10 | 조선대학교산학협력단 | Composition for protecting skin against ultraviolet ray comprising malonic acid from pine needle as effective component |
KR20230065584A (en) | 2021-11-05 | 2023-05-12 | 재단법인대구경북과학기술원 | Composition for improving skin elasticity during wound healing regeneration comprising RGD-containing Elastin-Like Polypeptide and stem cell |
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