KR20170001314A - Composition for improving skin - Google Patents
Composition for improving skin Download PDFInfo
- Publication number
- KR20170001314A KR20170001314A KR1020150091117A KR20150091117A KR20170001314A KR 20170001314 A KR20170001314 A KR 20170001314A KR 1020150091117 A KR1020150091117 A KR 1020150091117A KR 20150091117 A KR20150091117 A KR 20150091117A KR 20170001314 A KR20170001314 A KR 20170001314A
- Authority
- KR
- South Korea
- Prior art keywords
- substituted
- group
- oligomer
- pentose
- skin
- Prior art date
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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Abstract
Description
본 발명은 피부 주름 개선, 탄력 증진, 미백, 보습 및 항산화 등의 피부 개선용 조성물에 관한 것이다.
The present invention relates to a composition for improving skin such as skin wrinkle improvement, elasticity enhancement, whitening, moisturizing and antioxidation.
피부의 줄기세포는 피부의 건강과 생리학적 및 생화학적인 항상성을 유지하는데 중요한 역할을 수행한다. 피부에 존재하는 줄기세포도 노화로 인하여 기능에 이상이 발생하게 되고, 이에 따라 피부의 항상성이 깨지면서 여러 가지 문제가 발생된다. 따라서 노화된 줄기세포를 다시 활성화시킨다면 피부의 나이를 역으로 돌리는 것과 같은 효과를 가져올 것이다.The skin's stem cells play an important role in maintaining the health and physiological and biochemical homeostasis of the skin. Stem cells present in the skin are also abnormally functioned due to aging, which causes various problems due to the breakdown of the homeostasis of the skin. Thus, reactivation of aging stem cells will have the same effect as turning skin age backwards.
피부는 외부로부터 표피, 진피 및 피하지방층의 3개의 층으로 구성되어 있다. 표피는 3개 층 가운데 가장 얇으며 부위에 따라 두께에 차이가 있다. 표피는 주로 각질 형성 세포로 구성되며, 이외에 멜라닌 색소를 생산하는 멜라닌 세포 및 면역학적 기능을 수행하는 랑게르한스 세포 등으로 구성되어 있다. 진피는 주로 교원질과 탄력섬유로 구성되는 결체조직 및 기질로 이루어지며, 그 속에 신경, 혈관, 림프관, 근육, 모낭, 피지선 및 땀샘선 등을 내포하고 있다.The skin consists of three layers of skin from the outside: the epidermis, the dermis and the subcutaneous fat layer. The epidermis is the thinnest of the three layers and varies in thickness depending on the region. The epidermis consists mainly of keratinocyte cells, melanocytes that produce melanin pigment, and Langerhans cells that perform immunological functions. The dermis consists of connective tissue and matrix composed mainly of collagen and elastic fibers, and it contains nerve, blood vessels, lymphatic vessels, muscles, hair follicles, sebaceous glands and sweat glands.
발생학적으로 사람 피부의 모든 구성성분은 외배엽이나 중배엽에서 유래되는 것으로 알려져 있다. 표피, 모낭, 피지선 및 땀샘선 등은 외배엽에서 기원하며, 멜라닌 세포, 신경 및 특수 감각 수용체는 신경외배엽에서 유래된다. 신경외배엽에서 유래되는 멜라닌 세포는 발생 8 주 후 피부에 도달하며, 발생 4 내지 5 개월이 되면 수지상 돌기가 발달하여 주위 각질형성 세포로 멜라닌 소체를 이동시킨다. 이와 같이 발생학적 시기에 따라 배아의 줄기세포는 분화를 거듭하게 되며 각각 맡은 바 기능에 알맞은 특성을 갖게 된다. 성체가 된 후에도 일정수의 줄기세포는 조직에 남게 되는데 피부에서는 주로 두 곳에 줄기세포들이 존재한다. 첫째는 모낭(hair follicle)에 존재한다. 이곳은 세포분화가 일어나기 전의 세포로 표피의 재생과 관련해 중요한 역할을 담당하는 것으로 알려져 있으며, 털의 재생과 성장에도 중요한 역할을 수행하고 있다. 둘째는 모낭과 모낭 사이의 표피(interfollicular epidermis)라고 불리는 표피의 기저층(the basal cell layer of epidermis)이다. 이곳에 자리하고 있는 줄기세포는 표피는 물론 진피층의 섬유아세포까지 관장하여 피부 건강을 지키는 중요한 역할을 수행하고 있음이 밝혀졌다. 이곳의 줄기세포는 양이 많고 쉽게 얻을 수 있다는 장점이 있어 피부줄기세포 연구에 널리 사용되고 있다. 피부는 지속적으로 재생(renew)되며, 피부의 상피에 존재하는 줄기세포 즉, 피부의 상피줄기세포(epidermal stem cells)는 상처 후 상피의 복구에 관여한다(비특허문헌 1). 상기 피부의 상피줄기세포는 피부줄기세포(skin stem cells)로도 칭해지며, 상기 피부줄기세포를 활성화시킬 경우, 외상 등의 피부상처를 치료하거나 상처치료를 촉진할 수 있으며, 피부의 주름 완화 또한 기대할 수 있다. 피부줄기세포의 지표로는 인테그린β1(integrin β1) 및 인테그린 α6(integrin α6)이 사용되고 있고, 상피 형태 형성 및 분화에 필요한 피부줄기세포의 유지는 p63 단백질에 의해 조절된다고 보고되고 있다.Embryologically, all components of human skin are known to originate from ectoderm or mesodermal lobe. Epidermis, hair follicles, sebaceous glands and glands are originated from ectoderm, and melanocytes, nerves and special sensory receptors are derived from neuroepithelial cells. Melanocytes, which are derived from neuroectodermal cells, reach the skin 8 weeks after development, and at 4 to 5 months after development, dendritic processes are developed to move the melanocytes to surrounding keratinocytes. Thus, embryonic stem cells will undergo differentiation depending on the developmental stage, and will have characteristics appropriate to their function. After becoming adult, a certain number of stem cells remain in the tissues. There are mainly two stem cells in the skin. The first is in the hair follicle. It is known to play an important role in the regeneration of the epidermis into cells before cell differentiation occurs, and plays an important role in hair regeneration and growth. The second is the basal cell layer of the epidermis, called the interfollicular epidermis, between the hair follicle and the hair follicle. The stem cells found here play an important role in maintaining skin health by administering not only the epidermis but also the fibroblasts of the dermal layer. The stem cells here are large in quantity and easy to obtain, making them widely used in the study of skin stem cells. The skin is constantly renewed, and stem cells present in the epithelium of the skin, that is, epidermal stem cells of the skin, are involved in the recovery of the epithelium after injury (Non-Patent Document 1). The skin epithelial stem cells are also referred to as skin stem cells. When the skin stem cells are activated, it is possible to treat skin wounds such as trauma, promote wound healing, . Integrin β1 and integrin α6 are used as indicators of dermal stem cells, and maintenance of skin stem cells necessary for epithelial morphogenesis and differentiation has been reported to be regulated by p63 protein.
세포 외 기질(extracellular matrix)의 주요 구성성분인 콜라겐은 피부의 섬유아세포에서 생성되는 주요 기질 단백질이다. 또한, 생체 단백질 총 중량의 약 30%를 차지하는 중요한 단백질로서 견고한 3중 나선 구조로 되어 있다. 콜라겐은 피부, 건(tendon), 뼈 및 치아의 유기물질의 대부분을 형성하는데, 특히 뼈와 피부(진피)에 그 포함량이 높다. 대부분의 다른 체내 구조물에서는 섬유상 봉입체로서 존재한다.Collagen, a major component of the extracellular matrix, is a major substrate protein produced by the fibroblasts of the skin. In addition, it is an important protein occupying about 30% of the total weight of the bioprotein, and has a solid triple helix structure. Collagen forms most of the organic matter in the skin, tendons, bones and teeth, especially in bone and skin (dermis). In most other body structures, it exists as a fibrous inclusion.
콜라겐은 비교적 약한 면역원인데, 이는 콜라겐의 나선구조에 의한 잠재성 항원 결정인자의 차폐가 그 일부 원인이고, 이 나선구조는 또한 콜라겐이 단백질 분해에 대한 내성을 갖도록 한다. 콜라겐의 주된 기능으로는 피부의 기계적 견고성, 결합조직의 저항력과 조직의 결합력, 세포 접착의 지탱, 세포 분할과 분화(유기체의 성장 혹은 상처 치유시)의 유도 등이 알려져 있다(비특허문헌 2).Collagen is a relatively weak immunogen, partly due to the blocking of the potential antigenic determinant by the helical structure of the collagen, which also causes the collagen to be resistant to proteolysis. The main functions of collagen are known to be mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, induction of cell division and differentiation (when organism grows or healing the wound) (Non-Patent Document 2) .
이러한 콜라겐은 연령 및 자외선 조사에 의한 광노화에 의해 감소하며, 이는 피부의 주름 형성과 밀접한 연관이 있다고 알려져 있다(비특허문헌 3). 또한 콜라겐은 상처치유에 있어서 중요한 역할을 담당하며, 손상된 상피에서 콜라겐의 합성을 촉진시켜서 상처를 신속하고 흉터 없이 회복시킬 수 있다.Such collagen is reduced by aging and photoaging due to ultraviolet irradiation, which is known to be closely related to the formation of wrinkles in the skin (Non-Patent Document 3). Collagen also plays an important role in wound healing and can accelerate the synthesis of collagen in the damaged epithelium, allowing quick, scarless wound healing.
종래에는 콜라겐의 피부 보습 효과 및 상처 치유 효과를 이용하기 위하여 화장품 또는 연고 등과 같은 피부외용제 조성물에 콜라겐을 배합한 제품들이 출시되어 있으나, 이들 제품들은 콜라겐 자체를 피부 표면에 도포하는 것으로서 고분자 물질인 콜라겐의 경피 흡수가 어려워 보습작용 또는 상처치유 효과를 기대할 수 없으므로 본질적인 피부기능 개선 및 상처치유의 기능을 나타낸다고 말할 수 없었다. Conventionally, products using collagen in a composition for external application for skin such as cosmetics or ointment have been marketed in order to utilize the skin moisturizing effect and wound healing effect of collagen. However, these products apply collagen itself to the skin surface, It is impossible to expect a moisturizing action or a wound healing effect, so that it can not be said that it exhibits essential skin function improvement and wound healing function.
이러한 문제를 해결하기 위하여 콜라겐 합성 촉진 물질에 대한 관심이 높아졌으며, 종래에 알려진 콜라겐 합성촉진 물질로는 비타민 C, 레티노익산(retinoic acid), 발암증식인자(비특허문헌 4), 동물 태반 유래의 단백질(특허문헌 1), 베툴린산(betulinic acid)(특허문헌 2), 클로렐라 추출물(특허문헌 3 및 4) 등이 있다. In order to solve this problem, there has been a growing interest in collagen synthesis promoting substances, and known collagen synthesis promoting substances include vitamin C, retinoic acid, carcinostatic factors (non-patent document 4) (Patent Document 1), betulinic acid (Patent Document 2), chlorella extract (Patent Documents 3 and 4), and the like.
그러나, 이들 물질은 피부적용시 자극, 발적 등의 안전성 문제로 사용량의 제한이 있거나, 효과가 미미하여 실질적으로 피부기능 개선 또는 상처 치유의 효과를 기대할 수 없었다. 따라서, 기존의 피부외용제 조성물보다 생체에 안전하고 효과가 높은 새로운 피부외용제 조성물의 개발이 절실히 요구되고 있다.However, these materials have limited use due to safety problems such as irritation and reddening when applied to the skin, or the effect is insignificant and virtually no effect of skin function improvement or wound healing can be expected. Therefore, there is a desperate need to develop a novel composition for external skin application that is safer and more effective in living body than existing skin external composition compositions.
또한, 엘라스틴(Elastin) 섬유는 콜라겐과 가교 결합을 형성하며 피부 탄력에 관여하고 있는 주름 생성에 중요한 피부 구성성분이다. 엘라스틴 섬유의 결핍과 응집, 엘라스틴 분해 효소인 엘라스타제(Elastase)의 활성도의 현격한 증가는 피부 주름생성 요인 중의 하나로 밝혀지고 있다. 엘라스타제는 엘라스틴을 분해할 수 있는 유일한 효소로서 이에 대한 저해는 피부 주름 개선을 근본적으로 줄여 줄 수 있다고 알려져 있다.In addition, Elastin fiber forms crosslinks with collagen and is a skin constituent important for wrinkle formation involved in skin elasticity. The deficiency and aggregation of elastin fibers and the dramatic increase in the activity of the elastin degrading enzyme Elastase have been found to be one of the causes of skin wrinkles. Elastase is the only enzyme capable of degrading elastin, and inhibition of it is known to be able to radically reduce wrinkles.
한편, 콜라겐 및 엘라스틴 섬유는 진피층 내의 수분 보유에 중요한 역할을 하는 기질 단백질로 이러한 기질 단백질이 수분을 흡착하며, 이들이 이루는 구조 내부에 수분 보유력을 높여 피부가 적정 수분을 함유한 상태를 유지할 수 있도록 해주며, 이를 통해 피부의 탄력을 유지하는데 관여한다고 알려져 있다.On the other hand, collagen and elastin fibers are substrate proteins that play an important role in water retention in the dermal layer. These protein proteins adsorb moisture and increase the water holding capacity inside the structure, thereby allowing the skin to maintain proper moisture content. And it is known to be involved in maintaining the elasticity of the skin.
화장품으로서의 미백제의 연구는 최근 정서적으로 흰 피부를 선호하는 동양권의 생활 수준 향상과 더불어 피부 흑화가 자외선에 의한 피부 노화로 인식되면서 그 필요성이 점차 증대되고 있다. 그에 따라 아스코르빈산(ascorbic acid), 하이드로퀴논(hydroquinone), 글루타치온(glutathione), 알부틴(arbutin) 등의 티로시나아제 저해 활성을 나타내는 물질들이 화장료나 의약품에 배합되어 사용되어 왔으나(특허문헌 5 및 6), 이들 중 대부분의 것은 효과가 불충분하거나 제형 상 불안정한 면이 있어 활용도가 떨어진다. 특히, 하이드로퀴논과 같은 화합물은 강한 탈색 작용을 나타내며 그 자체가 피부 감작성을 가지고 있어 피부 알레르기 등을 유발할 수 있고, 정상적인 피부의 기능을 변화시켜 백반증을 유발하는 등의 부작용을 나타내어 피부에 대한 안전성 측면에서 그 사용이 제한되고 있다. Recently, the study of whitening agents as cosmetics has become increasingly necessary as skin blackness is recognized as skin aging due to ultraviolet rays, along with the improvement of living standards in Asian countries, which prefer emotionally white skin. Accordingly, substances exhibiting tyrosinase inhibitory activity such as ascorbic acid, hydroquinone, glutathione, and arbutin have been used in cosmetics and pharmaceuticals (Patent Documents 5 and 6) 6), and most of them are ineffective or unstable due to poor formulation. In particular, a compound such as hydroquinone exhibits a strong decolorizing action, has a skin sensitization itself, can induce skin allergies and the like, and exhibits adverse effects such as inducing vitiligo by changing normal skin function. Thus, Its use is limited on the side.
또한, 상기와 같이 티로시나아제의 활성을 저해하는 물질이라 하더라도 이러한 물질이 각질 형성 세포인 케라티노사이트에 작용하여 멜라닌의 생합성을 촉진시키는 인자의 생성을 증가시킨다면, 결과적으로 미백 작용은 약화되거나 오히려 악효과를 거둘 수 있기 때문에 단순히 티로시나아제의 활성 저해제가 좋은 미백제라고 볼 수 없으며, 이에 많은 티로시나아제 저해제가 개발되고 있으나 거의 대부분이 우수한 미백 효과를 나타내지 않는 것으로 알려져 있다.In addition, even if the substance inhibits the activity of tyrosinase as described above, if such a substance acts on keratinocytes, which are keratinocytes, to increase the production of factors promoting melanin biosynthesis, the whitening action is consequently weakened The active inhibitor of tyrosinase is not considered to be a good whitening agent because it can cause harmful effects, and many tyrosinase inhibitors have been developed, but most of them are known to show no excellent whitening effect.
한편, 생체 외부로부터 유입되거나, 생체 내에서 발생하는 활성 산소는 생체의 노화를 촉진시키거나, 암을 발생시키는 등 많은 문제의 원인이 된다. 따라서 활성 산소에 의한 산화를 억제하는 항산화 물질에 대한 개발 및 연구가 많이 이루어 지고 있다. 종래에는 수퍼옥사이드 디스뮤테이즈(SOD), 비타민 E 유도체, 아스코르브산 및 그 유도체, 플라보노이드(Flavonoid) 등의 항산화제를 화장료에 배합함으로써 피부노화 방지 효과를 얻어 보려는 노력이 많이 있었으나 피부 안전성 면에서나 화장료 배합 시 안정성 면에서 문제점이 발생하여 그 사용이 제한되고 있다.On the other hand, active oxygen introduced from the outside of the living body or generated in the living body causes many problems such as promoting aging of the living body, cancer, and the like. Therefore, the development and research of antioxidants that inhibit oxidation by active oxygen have been performed. Conventionally, there have been many attempts to obtain an anti-aging effect by adding an antioxidant such as superoxide dismutase (SOD), vitamin E derivative, ascorbic acid and derivatives thereof, and flavonoid to cosmetics. However, The use thereof is limited due to problems in terms of stability in formulation.
따라서, 생체에 안전하고, 유효성분이 안정하며, 무엇보다도 기존의 피부 줄기세포 활성화, 미백, 탄력 증진, 주름 개선, 항산화 및 보습 효과가 있는 물질보다 효과가 우수한 피부 줄기세포 활성화, 미백, 탄력 증진, 주름 개선, 항산화 및 보습 효과를 지닌 성분의 개발이 절실히 요망되고 있다.Accordingly, it is possible to provide a method for producing a stem cell which is safe in the living body, stable in its effectiveness, and more effective than the substance having the existing skin stem cell activation, whitening, elasticity enhancement, wrinkle improvement, antioxidant and moisturizing effect, whitening, The development of a composition having wrinkle-improving, antioxidation and moisturizing effects is desperately in demand.
이에, 본 발명자들은 하기 화학식 1로 표시되는 폴리히드록시스테로이드가 피부의 줄기세포 증식 및 콜라겐 합성을 촉진하며, 엘라스타제 활성을 저해하는 효과를 나타냄으로써 피부 줄기세포를 활성화 하며, 보습, 피부 탄력 및 주름 개선 효과가 있다는 사실을 확인하고 본 발명을 완성하게 되었다. 또한, 하기 화학식 1로 표시되는 폴리히드록시스테로이드는 자유라디칼을 소거하여 항산화 효과, 멜라닌 합성을 억제하여 미백 효과를 나타내는 것을 확인하고 본 발명을 완성하게 되었다.Accordingly, the present inventors have found that a polyhydroxysteroid represented by the following formula (1) promotes stem cell proliferation and collagen synthesis of skin and inhibits elastase activity, thereby activating skin stem cells, And a wrinkle-reducing effect, and completed the present invention. In addition, the polyhydroxysteroid represented by the following formula (1) has been shown to exhibit a whitening effect by inhibiting free radicals to inhibit antioxidative and melanin synthesis, thus completing the present invention.
[화학식 1][Chemical Formula 1]
상기 화학식 1에서,In Formula 1,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다. R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
따라서, 본 발명의 목적은 화학식 1로 표시되는 폴리히드록시스테로이드 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 주름 개선, 탄력 증진, 미백 및 항산화 조성물을 제공하는데 있다.Accordingly, an object of the present invention is to provide a wrinkle-improving, elasticity-enhancing, whitening and antioxidative composition comprising the polyhydroxysteroid represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명의 다른 목적은 화학식 1로 표시되는 폴리히드록시스테로이드 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 줄기세포 활성 촉진용 조성물을 제공하는데 있다.Another object of the present invention is to provide a composition for promoting stem cell activity comprising the polyhydroxy steroid represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Chemical Formula 1]
상기 화학식 1에서,In Formula 1,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
상기 과제를 해결하기 위한 수단으로서, As means for solving the above problems,
본 발명은 화학식 1로 표시되는 폴리히드록시스테로이드 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 피부 주름 개선, 탄력 증진, 미백 및 항산화 조성물을 제공한다:The present invention provides a skin wrinkle-improving, elasticity-enhancing, whitening and antioxidant composition comprising the polyhydroxysteroid represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[화학식 1][Chemical Formula 1]
상기 화학식 1에서,In Formula 1,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
또한, 상기 과제를 해결하기 위한 다른 수단으로서, As another means for solving the above problems,
본 발명은 화학식 1로 표시되는 폴리히드록시스테로이드 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 줄기세포 활성 촉진용 조성물을 제공한다:The present invention provides a composition for promoting stem cell activity comprising the polyhydroxy steroid represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[화학식 1][Chemical Formula 1]
상기 화학식 1에서,In Formula 1,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
본 발명에 따른 화학식 1로 표시되는 폴리히드록시스테로이드가 피부의 줄기세포 증식 및 콜라겐 합성을 촉진하며, 엘라스타제 활성을 저해하고, 피부 줄기세포를 활성화하여 피부 탄력 증진 및 주름 개선 효과를 나타낼 뿐만 아니라, 자유라디칼을 소거하여 항산화 효과, 멜라닌 합성을 억제하여 미백 효과를 나타냄으로써 의약품, 화장료 또는 건강식품에 사용할 수 있다.
The polyhydroxysteroid represented by Formula 1 according to the present invention promotes stem cell proliferation and collagen synthesis in skin, inhibits elastase activity, activates skin stem cells, exhibits skin elasticity improvement and wrinkle improvement But it can be used in medicines, cosmetics or health foods by eliminating free radicals, thereby exhibiting antioxidative effects and inhibiting melanin synthesis, thereby exhibiting a whitening effect.
이하, 본 발명의 구성을 구체적으로 설명한다.Hereinafter, the configuration of the present invention will be described in detail.
피부 주름 개선, 탄력 증진, 미백 및 항산화 성분이 실제 피부에 적용 시 우수한 효과를 발휘하기 위해서는 저농도에서 고활성의 피부 주름 개선, 탄력 증진, 미백 및 항산화 활성을 나타내고, 피부를 투과하여 흡수되는 능력이 우수하고, 피부 주름 개선, 탄력 증진, 미백 및 항산화 효과를 나타내기에 충분한 시간 동안 머무를 수 있도록 휘발성이 낮고, 조성물이나 피부 상에서 활성 성분이 안정하게 유지되고, 의약이나 화장품으로의 제형화가 용이하며, 또한 피부에 안전한 것이 바람직하다. 그러나, 공지의 성분 중 상기 특성을 모두 만족시키는 성분은 흔치 않다. 예를 들어, 몇몇 피부 주름 개선, 탄력 증진, 미백 및 항산화 성분들은 시험관 내 실험 시 저농도에서도 피부 주름 개선, 탄력 증진, 미백 및 항산화 활성은 우수하나, 피부를 투과하여 흡수되는 능력이 떨어져 실제 피부에 적용하기엔 어렵다. 또 다른 활성 성분들은 친수성이 낮아 의약이나 화장품으로 제형화가 어렵다. 또한, 몇몇 피부 주름 개선, 탄력 증진, 미백 및 항산화 성분들은 열, 광, 또는 산소에 노출되었을 때 상기 활성 성분이 분해되거나 다른 화합물로 변형되어 피부에 적용하기 전에 이미 효과가 사라지는 경우도 있다. To improve skin wrinkles, improve skin elasticity, whitening, and antioxidant properties, it is necessary to improve skin wrinkles, elasticity, whitening and antioxidant activity at low concentrations and to absorb skin penetration Is low in volatility so as to be able to stay for a sufficient time to exhibit skin wrinkle improvement, elasticity enhancement, whitening and antioxidative effect, and the active ingredient is stably maintained on the composition or on the skin and is easy to be formulated into medicines and cosmetics, It is preferable to be skin-safe. However, the components satisfying all of the above-mentioned characteristics among the known components are not common. For example, some skin wrinkle improvement, elasticity enhancement, whitening, and antioxidant components have excellent wrinkle improvement, elasticity enhancement, whitening and antioxidant activity even at low concentration in the in vitro test, It is difficult to apply. Other active ingredients have low hydrophilicity and are difficult to formulate into medicines or cosmetics. In addition, some skin wrinkle improvement, elasticity enhancement, whitening, and antioxidant ingredients may be degraded or transformed into other compounds when exposed to heat, light, or oxygen, and the effect may already be lost before application to the skin.
하기 실시예에서 확인할 수 있는 바와 같이, 화학식 1로 표시되는 폴리히드록시스테로이드는 저농도에서도 콜라겐 합성 촉진 효과, 엘라스타제 활성 저해 효과, 멜라닌 생성 저해 효과, 자유라디칼 소거 효과를 나타내므로 피부 주름 개선, 탄력 증진, 미백 및 항산화를 위한 의약품, 화장료, 건강식품 등의 유효성분으로 사용할 수 있다. As can be seen in the following examples, the polyhydroxysteroid represented by the general formula (1) exhibits collagen synthesis promotion effect, elastase activity inhibition effect, melanin formation inhibition effect and free radical scavenging effect at low concentration, And can be used as an effective ingredient for medicines for promoting elasticity, whitening and antioxidation, cosmetics, and health food.
따라서, 본 발명은 화학식 1로 표시되는 폴리히드록시스테로이드 또는 이의 약학적으로 허영가능한 염을 유효성분으로 포함하는 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 약학적 조성물을 제공한다:Accordingly, the present invention provides a composition for improving skin wrinkles, improving skin elasticity, skin whitening, and antioxidant comprising the polyhydroxy steroid represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[화학식 1] [Chemical Formula 1]
상기 화학식 1에서,In Formula 1,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
상기 화학식 1로 표시되는 화합물은 가능한 모든 이성질체를 포함할 수 있다. 특히, 화학식 1에서 3,4,6,7,8,15,16,24의 탄소 위치에서는 (R) 또는 (S)의 이성질체를 포함할 수 있다.The compound represented by Formula 1 may include all possible isomers. In particular, at the carbon position of 3, 4, 6, 7, 8, 15, 16 and 24 in the general formula (1), it may include an isomer of (R) or (S).
더 바람직하게는 상기 5탄당 내지 6탄당은 글루코오스, 갈락토오스, 자일로오스, 퓨코오스, 퀴노보오스, 아라비노오스 중에서 선택된 1종 이상일 수 있다. 보다 바람직하기로는 상기 메틸기 및 황산기가 치환된 5탄당은 을 포함할 수 있다.More preferably, the pentose to hexose sugar may be at least one selected from the group consisting of glucose, galactose, xylose, fucose, quinobose and arabinose. More preferably, the pentasaccharide substituted with a methyl group and a sulfate group . ≪ / RTI >
상기 화학식 1로 표시되는 폴리히드록시스테로이드는 구체적으로, 하기 화학식 2, 화학식 3 또는 화학식 4로 표시되는 화합물을 포함할 수 있다.The polyhydroxysteroid represented by the formula (1) may specifically include compounds represented by the following formulas (2), (3) or (4).
[화학식 2](2)
[화학식 3](3)
상기 화학식 2 또는 3으로 표시되는 화합물은 각각 5α-콜레스탄-3β,6α, 7α,8,15α,16β,26-헵톨 (화학식 2) 및 5α-콜레스탄-3β,4β,6α,7α,8,15β,16β,26-옥톨 (화학식 3)로 명명된다.The compound represented by Formula 2 or 3 is represented by 5α-cholestan-3β, 6α, 7α, 8,15α, 16β, 26-heptol (Formula 2) and 5α- , 15 [beta], 16 [beta], 26-octol (Formula 3).
[화학식 4][Chemical Formula 4]
상기 화학식 4의 화합물은 분자식 C33H57O12SNa, 분자량 700을 가지며, 아스테로사포닌 P1(Asterosaponin P1)으로 명명된다The compounds of the formula (4) Molecular formula C 33 H 57 O 12 having a SNa, molecular weight 700, is named Aspergillus saponin Tero P 1 (Asterosaponin P 1)
상기 화학식 1로 표시되는 폴리히드록시스테로이드의 합성 방법에 특별히 한정되지 않으며, 당업계에 공지된 방법으로 화학적으로 합성하거나, 천연물로부터 분리하거나 시판되는 물질을 사용할 수 있다.The method for synthesizing the polyhydroxysteroid represented by the formula (1) is not particularly limited, and may be chemically synthesized by a method known in the art, separated from a natural product, or a commercially available substance.
본 발명의 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 약학적 조성물은 상기 화학식 1로 표시되는 폴리히드록시스테로이드의 약제학적으로 허용 가능한 염을 포함할 수 있다.The composition for improving skin wrinkles, improving skin elasticity, skin whitening, and antioxidant composition of the present invention may include a pharmaceutically acceptable salt of the polyhydroxysteroid represented by Formula 1 above.
상기 화학식 1로 표시되는 폴리히드록시스테로이드의 약제학적으로 허용 가능한 염은 유기산 또는 무기산을 이용하여 형성된 산 부가염일 수 있으며, 상기 유기산은, 예를 들면 포름산, 아세트산, 프로피온산, 락트산, 부티르산, 이소부티르산, 트리플루오로아세트산, 말산, 말레산, 말론산, 푸마르산, 숙신산, 숙신산 모노아미드, 글루탐산, 타르타르산, 옥살산, 시트르산, 글리콜산, 글루쿠론산, 아스코르브산, 벤조산, 프탈산, 살리실산, 안트라닐산, 디클로로아세트산, 아미노옥시 아세트산, 벤젠술폰산, p-톨루엔술폰산 및 메탄술폰산계 염을 포함하며 무기산은 예를 들면 염산, 브롬산, 황산, 인산, 질산, 탄산 및 붕산계 염을 포함한다. 바람직하게는 염산염 또는 아세트산염 형태일 수 있으며, 보다 바람직하게는 염산염 형태일 수 있다.The pharmaceutically acceptable salt of the polyhydroxysteroid represented by Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, , Malic acid, maleic acid, malonic acid, fumaric acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloro Acetic acid, aminooxyacetic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and the inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.
상기 언급된 산 부가염은 a) 상기 화학식 1로 표시되는 폴리히드록시스테로이드 및 산을 직접 혼합하거나, b) 이들 중 한 가지를 용매 또는 함수 용매 중에 용해시키고 혼합시키거나, 또는 c) 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 용매 또는 수하 용매 중의 산에 위치시키고 이들을 혼합하는 일반적인 염 제조방법으로 제조된다.The above-mentioned acid addition salts may be prepared by a) directly mixing the polyhydroxysteroid and the acid represented by the above formula (1), or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Is placed in an acid in a solvent or an undercooling solvent and the mixture is mixed with the polyhydroxysteroid.
위와는 별도로 추가적으로 염이 가능한 형태는 가바염, 가바펜틴염, 프레가발린염, 니코틴산염, 아디페이트염, 헤미말론산염, 시스테인염, 아세틸시스테인염, 메티오닌염, 아르기닌염, 라이신염, 오르니틴염, 아스파르트산염 등이 있다. In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.
약학적으로 허용 가능한 염기 부가염은 나트륨, 칼륨, 칼슘, 암모늄, 마그네슘 또는 유기 아미노로 이루어진 염을 포함하나, 이에 한정되는 것은 아니다.Pharmaceutically acceptable base addition salts include, but are not limited to, salts formed with sodium, potassium, calcium, ammonium, magnesium or organic amino.
본 발명의 화학식 1로 표시되는 폴리히드록시스테로이드는 수화물, 에탄올화물 등의 형태를 포함하는 용매화된 형태뿐만 아니라 비-용매화된(unsolvated) 형태로 존재할 수도 있다. 본 발명의 화학식 1로 표시되는 폴리히드록시스테로이드는 결정형 또는 무정형 형태로 존재할 수 있으며, 이러한 모든 물리적 형태는 본 발명의 범위에 포함된다.
The polyhydroxysteroid represented by Formula 1 of the present invention may exist in unsolvated form as well as solvated form including form of hydrate, ethanol, and the like. The polyhydroxysteroid represented by formula (1) of the present invention may exist in a crystalline or amorphous form, and all such physical forms are included in the scope of the present invention.
또한, 본 발명의 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 의약품으로 사용하는 경우, 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다. 예컨대, 공지의 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 성분을 포함할 수 있을 것이다. 추가적인 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 성분을 포함하게 되면 본 발명의 조성물의 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 효과는 더욱 증진될 수 있을 것이다. 상기 성분 추가 시에는 복합 사용에 따른 피부 안전성, 제형화의 용이성, 유효성분들의 안정성을 고려할 수 있다. 본 발명의 한 구체예에서, 상기 조성물은 당업계에 공지된 당업계에 공지된 항산화 성분으로서, 토코페롤, 셀레늄, 비타민 C 및 페놀성 화합물, 당업계에 공지된 미백 성분으로서, 코지산(Kojic acid), 알부틴(Arbutin) 등과 같은 티로시나제 효소활성을 억제하는 물질, 하이드로퀴논(Hydroquinone), 비타민-C(L-Ascorbic acid) 및 이들의 유도체와 각종 식물 추출물로 구성되는 군으로부터 선택되는 1종 또는 2종 이상의 성분을 추가로 포함할 수 있다. 추가의 성분은 전체 조성물 중량에 대하여 0.0001 중량% 내지 10 중량%로 포함될 수 있을 것이며, 상기 함량 범위는 피부 안전성, 상기 화학식 1의 화합물의 제형화 시의 용이성 등의 요건에 따라 조절될 수 있을 것이다.When the polyhydroxysteroid represented by Formula 1 of the present invention is used as a pharmaceutical, it may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known skin wrinkle improvement, elasticity enhancement, skin whitening and antioxidant components. The skin wrinkle improvement, the elasticity enhancement, the skin whitening and the antioxidant effect of the composition of the present invention may be further enhanced if the skin wrinkle improvement, the skin elasticity enhancement, the skin whitening, and the antioxidant component are included. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition comprises an antioxidant component known in the art, such as tocopherol, selenium, vitamin C and a phenolic compound, as well as whitening components known in the art, such as kojic acid ), Arbutin and the like, a substance inhibiting tyrosinase enzyme activity such as arbutin, hydroquinone, vitamin C (L-ascorbic acid), derivatives thereof and various plant extracts. May further comprise more than one species of component. The additional component may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety, ease of formulation of the compound of Formula 1 .
또한, 본 발명의 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 약학적 조성물은 약학적으로 허용 가능한 담체를 더 포함할 수 있다.In addition, the composition for improving skin wrinkles, improving elasticity, skin whitening, and antioxidant pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier.
약학적으로 허용되는 담체는 완충액, 주사용 멸균수, 일반 식염수 또는 인산염 완충 식염수, 슈크로스, 히스티딘, 염 및 폴리솔베이트 등과 같은 여러 성분을 함유할 수 있다.Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates.
본 발명의 약학적 조성물은 경구 또는 비경구로 투여할 수 있으며, 일반 의약품 제제의 형태, 예를 들어, 임상 투여 시 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, , An extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like.
경구 투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 약학적 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose) 또는 락토오스(Lactose), 젤라틴 등을 섞어 조제될 수 있다.Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like.
단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌 글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.
Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명에 있어서, '주름 개선 효과'라 함은 피부에 주름이 생성되는 것을 억제 또는 저해하거나, 이미 생성된 주름을 완화시키는 것을 말한다. In the present invention, the term " wrinkle-reducing effect " refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating already-generated wrinkles.
본 발명에 있어서, '탄력 증진 효과'라 함은 피부에 대한 탄력성이 증가되는 것으로, 피부 탄력의 손실을 억제 또는 저해하거나, 이미 감소된 탄력을 완화시키는 것을 말한다. In the present invention, the 'elasticity-enhancing effect' refers to an increase in elasticity to the skin, which suppresses or inhibits the loss of elasticity of the skin, or alleviates the already-reduced elasticity.
본 발명에 있어서, '미백 효과'라 함은 멜라닌 색소의 합성을 저해함으로써 피부 톤을 밝게 할 뿐만 아니라, 자외선, 호르몬 또는 유전에 기인한 기미나 주근깨 등의 피부 과색소 침착을 개선하는 것을 말한다.In the present invention, the 'whitening effect' refers to not only brightening the skin tone by inhibiting the synthesis of the melanin pigment but also improving skin hypercholesterolemia due to ultraviolet rays, hormones or heredity, such as spots or freckles.
본 발명에 있어서, '항산화 효과'라 함은 세포내 대사 또는 자외선의 영향으로 인한 산화적 스트레스에 따라 반응성이 높은 자유 라디칼(free radical) 또는 활성산소종(reactive oxygen species;ROS)에 의한 세포의 산화를 억제하는 것을 말하며, 자유 라디칼 또는 활성산소종을 제거하여 이로 인한 세포의 손상이 감소되는 것을 포함한다.In the present invention, the term 'antioxidative effect' refers to the action of free radicals or reactive oxygen species (ROS), which are highly reactive according to oxidative stress caused by intracellular metabolism or ultraviolet rays, Refers to inhibition of oxidation, and includes removal of free radical or reactive oxygen species, thereby reducing damage to the cells.
본 발명의 약학적 조성물은 유효량의 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 포함할 때 바람직한 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 효과를 제공할 수 있다. 본 발명에 있어서, '유효량'이라 함은 손상된 피부의 재생을 촉진하거나, 주름을 개선하거나, 탄력을 증진시키거나, 항산화 효과, 미백 효과를 나타낼 수 있는 화합물의 양을 의미한다. 본 발명의 조성물에 포함되는 상기 화학식 1의 화합물의 유효량은 조성물이 제품화되는 형태, 상기 화합물이 피부에 적용되는 방법 및 피부에 머무르는 시간 등에 따라 달라질 것이다. 예컨대, 상기 조성물이 의약품으로 제품화되는 경우에는 일상적으로 피부에 적용하게 되는 화장품으로 제품화되는 경우에 비해 높은 농도로 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 포함할 수 있을 것이다. 따라서, 일일 투여량은 상기 화학식 1로 표시되는 폴리히드록시스테로이드의 양을 기준으로 0.1 내지 100 ㎎/㎏이고, 바람직하게는 30 내지 80 ㎎/㎏이고, 더욱 바람직하게는 50 내지 60 mg/kg이며, 하루 1 ~ 6 회 투여될 수 있다. When the pharmaceutical composition of the present invention contains the effective amount of the polyhydroxysteroid represented by the above formula (1), it can provide desirable skin wrinkles, elasticity enhancement, skin whitening and antioxidative effects. In the present invention, the term "effective amount" means the amount of a compound capable of promoting regeneration of damaged skin, improving wrinkles, improving elasticity, exhibiting antioxidative and whitening effects. An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a medicine, it may contain a polyhydroxysteroid represented by the above formula (1) at a higher concentration than a cosmetic product that is routinely applied to skin. Accordingly, the daily dose is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the polyhydroxysteroid represented by the above formula And can be administered 1 to 6 times a day.
본 발명의 약학적 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응조절제를 사용하는 방법들과 병용하여 사용할 수 있다.
The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
본 발명은 또한 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 유효성분으로 포함하는 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 피부 외용제의 제형으로 제공할 수 있다.The present invention can also be provided as a formulation for improving skin wrinkles, improving elasticity, skin whitening, and an antioxidant skin external preparation containing the polyhydroxysteroid represented by Formula 1 as an active ingredient.
상기 화학식 1로 표시되는 폴리히드록시스테로이드를 피부외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 피부용 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다. When the polyhydroxysteroid represented by the above formula (1) is used as an external preparation for skin, it may further contain at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, , A perfume, a surfactant, water, an ionic or nonionic emulsifier, a filler, a sequestering and chelating agent, a preservative, a vitamin, a barrier, a wetting agent, a essential oil, a dye, a pigment, a hydrophilic or lipophilic active agent, Or any other ingredient conventionally used in external preparations for dermatological purposes. The components can also be introduced in amounts commonly used in the field of dermatology.
상기 화학식 1로 표시되는 폴리히드록시스테로이드가 피부 외용제 제형으로 제공될 경우, 이에 제한되는 것은 아니나, 연고, 패취, 겔, 크림 또는 분무제와 같은 제형을 가질 수 있다.
When the polyhydroxysteroid represented by Formula 1 is provided as an external preparation for skin, it may have a formulation such as, but not limited to, an ointment, a patch, a gel, a cream or a spray.
본 발명은 또한 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 유효성분으로 포함하는 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 화장료의 제형으로 제공할 수 있다.The present invention can also provide a composition for improving skin wrinkles, improving elasticity, skin whitening, and antioxidant cosmetic comprising the polyhydroxysteroid represented by Formula 1 as an active ingredient.
상기 화학식 1로 표시되는 폴리히드록시스테로이드를 화장품으로 사용하는 경우, 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 유효성분으로 함유하여 제조되는 화장품은 일반적인 유화 제형 및 가용화 제형의 형태로 제조할 수 있다. 예컨대, 유연 화장수 또는 영양 화장수 등과 같은 화장수, 훼이셜 로션, 바디로션 등과 같은 유액, 영양 크림, 수분 크림, 아이 크림 등과 같은 크림, 에센스, 화장연고, 스프레이, 젤, 팩, 선 스크린, 메이크업 베이스, 액체 타입, 고체 타입 또는 스프레이 타입 등의 파운데이션, 파우더, 클렌징 크림, 클렌징 로션, 클렌징 오일과 같은 메이크업 제거제, 클렌징 폼, 비누, 바디 워쉬 등과 같은 세정제 등의 제형을 가질 수 있다. When the polyhydroxysteroid represented by Formula 1 is used as a cosmetic product, the cosmetics containing the polyhydroxysteroid represented by Formula 1 as an active ingredient can be prepared in the form of a general emulsified formulation and a solubilized formulation . For example, creams, essences, cosmetic creams, sprays, gels, packs, sunscreens, make-up bases, liquids such as lotions such as lotion, facial lotion, body lotion, A powder, a cleansing lotion, a makeup removing agent such as a cleansing oil, a cleansing foam, a soap, a body wash, and the like.
또한, 상기 화장품은 상기 화학식 1로 표시되는 폴리히드록시스테로이드에 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다.In addition, the cosmetic may further contain, in addition to the polyhydroxysteroid represented by Formula 1, a lipid, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, Surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, lipophilic or lipophilic active agents, lipid vesicles or cosmetics And any other ingredients conventionally used in cosmetics applications.
상기 화학식 1로 표시되는 폴리히드록시스테로이드는 화장품으로 제품화되는 경우에 유효성분이 단기간 내에 피부에 머무르게 되는 메이크업 제거제, 세정제 등과 같은 워쉬-오프(wash-off) 타입의 화장품의 경우에는 비교적 높은 농도의 상기 불가사리 유래의 폴리히드록시스테로이드 또는 화학식 1의 화합물을 포함할 수 있을 것이다. 반면, 유효성분이 장기간 동안 피부에 머무르게 되는 화장수, 유액, 크림, 에센스 등의 리브-온(leave-on) 타입의 화장품의 경우에는 워쉬-오프 타입의 화장품에 비해 낮은 농도의 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 포함해도 무방할 것이다. 이에 제한되는 것은 아니나, 본 발명의 한 구체예에서, 상기 조성물은 상기 불가사리 유래의 폴리히드록시스테로이드 또는 화학식 1의 화합물을 전체 조성물 중량에 대하여 0.00001 중량% 내지 10 중량%(바람직하게는 0.0001 중량% 내지 1 중량%)로 포함할 수 있다. 본 발명의 조성물이 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 0.00001 중량% 미만으로 포함할 경우에는 충분한 피부 주름 개선, 탄력 증진, 미백, 보습 및 항산화 효과를 기대할 수 없고, 10 중량%를 초과하여 포함할 경우에는 알러지 등 원치 않는 반응이 발생하거나 피부 안전성에 문제가 있을 수 있으므로 이를 방지하기 위한 것이다.
In the case of a wash-off type cosmetic such as a make-up remover, a detergent, etc. in which the active ingredient remains on the skin in a short period of time when the product is made into a cosmetic product, the polyhydroxysteroid represented by the above formula (1) Starch-derived polyhydroxysteroid or a compound of formula (1). On the other hand, in the case of leave-on type cosmetics, such as lotion, cream, essence, etc., in which the active ingredient remains on the skin for a long period of time, But may also include polyhydroxy steroids. In one embodiment of the present invention, but not limited thereto, the composition comprises 0.00001 wt% to 10 wt% (preferably 0.0001 wt%) of the starch-derived polyhydroxysteroid or the compound of formula (1) To 1% by weight). When the composition of the present invention contains less than 0.00001% by weight of the polyhydroxysteroid represented by the above formula (1), sufficient skin wrinkle improvement, elasticity enhancement, whitening, moisturizing and antioxidative effects can not be expected, If it is included, it is to prevent it because it may cause an unwanted reaction such as allergy or there may be a problem of skin safety.
본 발명은 또한 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 유효성분으로 포함하는 피부 주름 개선, 탄력 증진, 피부 미백, 보습 및 항산화 건강식품에 관한 것이다.The present invention also relates to a composition for improving skin wrinkles, improving elasticity, skin whitening, moisturizing and antioxidant, which comprises the polyhydroxysteroid represented by Formula 1 as an active ingredient.
본 명세서에서 '건강식품'이란, 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있다.The term "health food" as used herein means a food prepared by adding the polyhydroxysteroid represented by the above formula (1) to food materials such as beverage, tea, spice, gum and confectionery, or by encapsulation, This means that it takes a certain effect on health when consumed, but unlike general medicine, there is an advantage that there is no side effect that may occur when a drug is taken for a long time by using food as a raw material.
이와 같이 하여 얻어지는 본 발명의 건강식품은, 일상적으로 섭취하는 것이 가능하기 때문에 높은 피부 주름 개선, 탄력 증진, 피부 미백 및 항산화 효과를 기대할 수 있어 매우 유용하다.Since the health food of the present invention thus obtained can be taken on a daily basis, it can be expected to have a high skin wrinkle, a skin elasticity, a skin whitening effect, and an antioxidant effect, which is very useful.
상기 화학식 1로 표시되는 폴리히드록시스테로이드를 식품첨가물로 사용하는 경우, 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조 시에 본 발명의 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When the polyhydroxysteroid represented by Formula 1 is used as a food additive, the polyhydroxysteroid represented by Formula 1 may be added as it is or may be used in combination with other food or food ingredients, Can be used. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. 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, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.
본 발명의 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL당 일반적으로 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g 이다.The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명은 또한, 상기 화학식 1로 표시되는 폴리히드록시스테로이드를 유효성분으로 포함하는 줄기세포 활성 촉진용 조성물을 제공한다.The present invention also provides a composition for promoting stem cell activity comprising the polyhydroxysteroid represented by Formula 1 as an active ingredient.
본 발명에서 용어 “줄기세포”는 스스로 세포 분열을 할 수 있고, 매우 다양한 형태의 특이 세포 타입(specific cell type)으로 분화할 수 있는 능력을 갖는 세포이다. 이러한 줄기세포의 종류는 특별히 제한되지 않으며, 한 구체예에서, 상기 줄기세포는 피부줄기세포일 수 있다. 상기 “피부줄기세포”는 피부(표피, 진피 및 피하지방층)를 이루는 세포로 분화될 수 있는 줄기세포를 의미한다. 상기 피부를 이루는 세포는 표피에 존재하는 케라티노사이트(keratinocyte), 멜라노사이트(melanocyte) 및 진피에 존재하는 섬유아세포(콜라겐 및 엘라스틴의 생합성을 주로 담당)를 포함한다. The term " stem cell " in the present invention is a cell capable of cell division by itself and capable of differentiating into a very specific type of specific cell type. The type of such stem cells is not particularly limited, and in one embodiment, the stem cells may be dermal stem cells. The term " dermal stem cell " means a stem cell capable of differentiating into cells constituting the skin (epidermis, dermis and subcutaneous fat layer). The cells that make up the skin include keratinocytes, melanocytes, and fibroblasts (mainly responsible for biosynthesis of collagen and elastin) present in the epidermis.
상기 피부줄기세포의 종류는 특별히 제한되지 않는다. 본 발명에서 사용되는 피부줄기세포는 그것이 어디로부터 유래한 것인지 관계없이 이용될 수 있다. 예를 들어, 피부줄기세포는 공지의 피부줄기세포 공급원, 예를 들어, 모낭 또는 표피의 기저층에서 얻을 수 있으며, 채취 대상인 동물은 포유동물일 수 있다. 한 구체예에서, 포유동물은 인간, 마우스, 랫트, 기니어 피그, 토끼, 원숭이, 돼지, 말, 소, 양, 영양, 개 또는 고양이를 포함할 수 있지만, 이에 한정되는 것은 아니다. 바람직하게 포유동물은 인간일 수 있다. 이러한, 피부줄기세포 공급원으로부터 피부줄기세포를 수득하는 방법에 대해서는 당업계에서 잘 알려져 있다.The kind of the skin stem cell is not particularly limited. The dermal stem cells used in the present invention can be used irrespective of where they originate from. For example, dermal stem cells may be obtained from a known source of dermal stem cells, e. G., From the basal layer of hair follicles or epidermis, and the animal to be harvested may be a mammal. In one embodiment, the mammal may include, but is not limited to, a human, a mouse, a rat, a guinea pig, a rabbit, a monkey, a pig, a horse, a cattle, a sheep, Preferably the mammal can be human. Such methods of obtaining dermal stem cells from dermal stem cell sources are well known in the art.
본 발명에 있어서, '줄기세포 활성 촉진 효과'라 함은 줄기세포 증식 촉진 효과를 포함하는 것을 말한다.In the present invention, the term " stem cell activation promoting effect " refers to a stem cell growth promoting effect.
피부줄기세포는 피부의 건강과 생리학적 및 생화학적인 항상성을 유지하는데 중요한 역할을 수행한다. 피부에 존재하는 줄기세포도 노화의 영향으로 인하여 기능에 이상이 발생하게 되고, 이에 따라 피부의 항상성이 깨지면서 여러 가지 문제가 발생된다. 이러한 줄기세포의 활성을 통하여 피부 노화의 여러 현상을 개선할 수 있으며[비특허문헌 5], 이에 대해 본 발명에서는 피부 재생, 주름 개선, 탄력 증진, 미백 및 피부결 개선 효과를 확인하였다.Dermal stem cells play an important role in maintaining the health and physiological and biochemical homeostasis of the skin. Stem cells present in the skin are also abnormally functioned due to the effect of aging, and thus various problems arise as the homeostasis of the skin is broken. Non-patent document 5]. In the present invention, skin regeneration, wrinkle improvement, elasticity enhancement, whitening and skin texture improving effect are confirmed by the activity of stem cells.
따라서, 본 발명은 상기 줄기세포 활성 촉진용 조성물을 포함하는 약학적 조성물, 피부외용제, 건강식품 및/또는 화장료 조성물을 제공할 수 있다. 이러한 약학적 조성물, 피부 외용제, 건강식품, 화장료 제형에 대해서는 앞서 화학식 1로 표시되는 폴리히드록시스테로이드를 포함하는 약학적 조성물, 피부 외용제, 건강식품, 화장료 제형에 관한 설명에 기재된 내용과 동일하다.
Accordingly, the present invention can provide a pharmaceutical composition, an external preparation for skin, a health food and / or a cosmetic composition containing the stem cell activity promoting composition. Such pharmaceutical composition, external preparation for skin, health food, and cosmetic formulation are the same as those described in the description of the pharmaceutical composition containing the polyhydroxysteroid represented by the formula (1), the external preparation for skin, the health food, and the cosmetic formulation.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.
참조예Reference Example 1: 물질 정보 1: Material information
[화학식 2](2)
물질명 : 5α-콜레스탄-3β,6α, 7α,8,15α,16β,26-헵톨Material name: 5α-cholestan-3β, 6α, 7α, 8,15α, 16β, 26-heptol
CAS No. : 100101-16-4
CAS No. : 100101-16-4
[화학식 3] (3)
물질명 : 5α-콜레스탄-3β,4β,6α,7α,8,15β,16β,26-옥톨Material name: 5α-cholestan-3β, 4β, 6α, 7α, 8,15β, 16β, 26-
CAS No. : 128298-63-5
CAS No. : 128298-63-5
[화학식 4][Chemical Formula 4]
물질명 : Asterosaponin P1 Material name: Asterosaponin P 1
CAS No. : 80764-19-8
CAS No. : 80764-19-8
참조예Reference Example 2: 별 불가사리 추출물 및 2: star starfish extract and 분획물Fraction 제조 Produce
(1) 별 불가사리 추출 및 이의 용매 분획 제조(1) Starfish extraction and preparation of its solvent fraction
별 불가사리 (Asterina pectinifera) 약 4 kg을 세절한 후 15 L의 메탄올을 가하여 실온에서 2회 추출한 후 여과한 여과물을 감압건조하여 메탄올 추출물을 얻었다. 상기 메탄올 추출물을 증류수 1 L에 현탁한 후 디클로로메탄(Dichloromethane) (51.8 g), 에틸아세테이트(Ethyl acetate) (0.19 g), 부탄올(n-Butanol) (10.1 g)로 순차적으로 분획하여 4개의 분획물을 얻었다.Starfish ( Asterina About 4 kg of pectinifera was added and 15 L of methanol was added. The mixture was extracted twice at room temperature. The filtered material was dried under reduced pressure to obtain a methanol extract. The methanol extract was suspended in 1 L of distilled water and then sequentially fractionated with dichloromethane (51.8 g), ethyl acetate (0.19 g), and n- Butanol (10.1 g) ≪ / RTI >
(2) 별 불가사리 추출물의 활성 성분 분리(2) Isolation of starch extract from active ingredients
(1)의 디클로로메탄 분획물을 실리카겔 칼럼을 실시하여 디클로로메탄/메탄올 = 10/1 ~ 0/100 (v/v)의 조성으로 서서히 변화를 주어 용출시켜 10개의 소분획을 얻었다.The dichloromethane fraction of the compound (1) was subjected to a silica gel column and eluted by gradually changing the composition of dichloromethane / methanol = 10/1 to 0/100 (v / v) to obtain 10 small fractions.
소분획 3 (1.7 g)을 70% 메탄올을 용출 용매로 하여 ODS 칼럼을 실시하여 화학식 2의 화합물 및 화학식 3의 화합물을 분리하였다.Small fraction 3 (1.7 g) was subjected to ODS column using 70% methanol as elution solvent to separate the compound of formula (2) and the compound of formula (3).
소분획 4 (3.1 g)를 에틸아세테이트/메탄올 = 5/1 (v/v) 조성으로 실리카겔 칼럼 크로마토그래피를 실시하여 화학식 4의 화합물을 분리하였다.
Small fraction 4 (3.1 g) was subjected to silica gel column chromatography with ethyl acetate / methanol = 5/1 (v / v) to separate the compound of formula (IV).
분리된 화합학식 2 내지 4의 화합물은 NMR, MS 등의 분광학적 방법을 통하여 구조를 규명하였으며, 기존에 보고된 논문과 비교하여 구조를 결정하였다. Separated compounds The compounds of Schemes 2 to 4 were identified by NMR and MS spectroscopic methods, and their structure was determined by comparison with the previously reported articles.
5α-콜레스탄-3β,6α, 7α,8,15α,16β,26-헵톨 (화학식 2)5α-cholestan-3β, 6α, 7α, 8,15α, 16β, 26-
백색무정형분말; 1H-NMR (600 MHz, methanol-d 4) δ: 0.93 (3H, d, J = 6.6 Hz, H-21), 0.95 (3H, d, J = 6.6 Hz, H-27), 1.02 (3H, s, H-19), 1.14 (3H, s, H-18), 3.44 (1H, dd, J = 10.5, 6 Hz, H-26), 3.51 (1H, m, H-3), 3.78 (2H, overlapped, H-6,7), 4.01 (1H, dd, J = 7.2, 1.8 Hz, H-16), 4.15 (1H, dd, J = 11.1, 1.8 Hz, H-15); 13C-NMR (150 MHz, methanol-d 4) δ:14.0 (C-19), 17.0 (C-18), 17.5 (C-27), 18.4 (C-21), 19.4 (C-11), 25.0 (C-23), 30.7 (C-20), 31.6 (C-2), 32.4 (C-4), 35.1 (C-24), 37.2 (C-22), 37.2 (C-25), 37.9 (C-10), 39.5 (C-1), 43.2 (C-12), 44.6 (C-5), 45.6 (C-13), 51.3 (C-9), 59.8 (C-14), 61.5 (C-17), 68.6 (C-26), 69.0 (C-6), 72.4 (C-3), 76.5 (C-7), 77.8 (C-8), 79.9 (C-15), 82.7 (C-16); EIMS m/z (rel. int., %): 484 [M]+ (1.1), 466 [M - H2O]+ (7.6).White amorphous powder; 1 H-NMR (600 MHz, methanol- d 4) δ: 0.93 (3H, d, J = 6.6 Hz, H-21), 0.95 (3H, d, J = 6.6 Hz, H-27), 1.02 (3H , 3.71 (1H, d, J = 10.5, 6 Hz, H-26), 3.51 (1H, m, H-3), 3.78 2H, overlapped, H-6,7), 4.01 (1H, dd, J = 7.2, 1.8 Hz, H-16), 4.15 (1H, dd, J = 11.1, 1.8 Hz, H-15); 13 C-NMR (150 MHz, methanol- d 4) δ: 14.0 (C-19), 17.0 (C-18), 17.5 (C-27), 18.4 (C-21), 19.4 (C-11), 25.0 (C-23), 30.7 (C-20), 31.6 (C-2), 32.4 (C-10), 39.5 (C-1), 43.2 (C-12), 44.6 (C-5), 45.6 (C-13), 51.3 C-17), 68.6 (C-26), 69.0 (C-6), 72.4 (C-3), 76.5 -16); EIMS m / z (rel. Int.,%): 484 [M] + (1.1), 466 [M - H 2 O] + (7.6).
Tetrahedron, 38, 3615-3622 (1982)
Tetrahedron, 38 , 3615-3622 (1982)
5α-콜레스탄-3β,4β,6α,7α,8,15β,16β,26-옥톨 (화학식 3)5α-cholestan-3β, 4β, 6α, 7α, 8,15β, 16β, 26-
백색무정형분말; 1H-NMR (600 MHz, methanol-d 4) δ: 0.93 (3H, d, J = 6.6 Hz, H-27), 0.97 (3H, d, J = 6.6 Hz, H-21), 1.18 (3H, s, H-19), 1.26 (3H, s, H-18), 3.45 (1H, dd, J = 10.2, 5.4 Hz, H-26), 3.47 (1H, m, H-3), 3.96 (1H, d, J = 3 Hz, H-7), 4.21 (1H, m, H-4), 4.24 (1H, t, J = 7.2 Hz, H-16), 4.30 (1H, dd, J = 11.7, 3 Hz, H-6), 4.50 (1H, t-like, J = 5.4 Hz, H-15); 13C-NMR (150 MHz, methanol-d 4) δ:17.0 (C-19), 17.5 (C-27), 17.9 (C-18), 18.6 (C-21), 18.8 (C-11), 25.0 (C-23), 26.4 (C-2), 31.1 (C-20), 35.1 (C-24), 37.2 (C-25), 37.9 (C-10), 39.8 (C-1), 43.2 (C-12), 44.5 (C-13), 47.9 (C-5), 51.4 (C-9), 55.4 (C-14), 63.2 (C-17), 66.8 (C-6), 68.6 (C-26), 69.7 (C-4), 71.2 (C-15), 72.9 (C-16), 73.9 (C-3), 77.2 (C-7), 79.2 (C-8); EIMS m/z (rel. int., %): 500 [M]+ (0.8), 482 [M - H2O]+ (6.9).White amorphous powder; 1 H-NMR (600 MHz, methanol- d 4) δ: 0.93 (3H, d, J = 6.6 Hz, H-27), 0.97 (3H, d, J = 6.6 Hz, H-21), 1.18 (3H H-19), 1.26 (3H, s, H-18), 3.45 (1H, dd, J = 10.2, 5.4 Hz, H-26), 3.47 1H, d, J = 3 Hz , H-7), 4.21 (1H, m, H-4), 4.24 (1H, t, J = 7.2 Hz, H-16), 4.30 (1H, dd, J = 11.7 , 3 Hz, H-6), 4.50 (1H, t-like, J = 5.4 Hz, H-15); 13 C-NMR (150 MHz, methanol- d 4) δ: 17.0 (C-19), 17.5 (C-27), 17.9 (C-18), 18.6 (C-21), 18.8 (C-11), 25.0 (C-23), 26.4 (C-2), 31.1 (C-20), 35.1 (C-24), 37.2 (C-12), 44.5 (C-13), 47.9 (C-5), 51.4 (C-9), 55.4 C-26), 69.7 (C-4), 71.2 (C-15), 72.9 (C-16), 73.9 (C-3), 77.2 (C-7), 79.2 (C-8); EIMS m / z (rel. Int.,%): 500 [M] + (0.8), 482 [M - H 2 O] + (6.9).
Liebigs Ann. Chem., 12, 1185-1189 (1988)Liebigs Ann. Chem., 12 , 1185-1189 (1988)
Nat. Prod. Res., 27, 1816-1822 (2013)
Nat. Prod. Res., 27 , 1816-1822 (2013)
아스테로사포닌 P1 (Asterosaponin P1)Aspergillus saponin Tero P 1 (Asterosaponin P 1)
백색무정형분말; 1H-NMR (600 MHz, methanol-d 4) δ:0.90 (9H, d, J = 6.6 Hz, H-21, 26, 27), 0.97 (3H, s, H-18), 1.02 (3H, s, H-19), 2.39 (1H, dd, J = 13.5, 3.6 Hz, H-7), 3.44 (3H, s, OCH3), 3.49 (1H, m, H-3), 3.58 (1H, m, H-3′), 3.63 (1H, m, H-6), 4.04 (1H, d, J = 2.4 Hz, H-2′), 4.19 (1H, overlapped, H-4′), 4.21 (1H, overlapped, H-15), 4.94 (1H, s, H-1′); 13C-NMR (150 MHz, methanol-d 4) δ:14.4 (C-19), 15.6 (C-18), 18.3 (C-27), 18.6 (C-26), 19.1 (C-21), 19.8 (C-11), 28.9 (C-23), 31.6 (C-25), 32.0 (C-22), 32.5 (C-2), 33.2 (C-4), 36.5 (C-20), 38.0 (C-10), 39.7 (C-1), 41.9 (C-16), 43.0 (C-12), 45.6 (C-13), 50.4 (C-7), 53.7 (C-5), 56.2 (C-17), 57.4 (C-9), 58.6 (OCH3), 67.1 (C-6), 67.8 (C-14), 69.0 (C-5′), 70.0 (C-15), 72.3 (C-3), 76.1 (C-8), 81.8 (C-2′), 81.9 (C-4′), 84.7 (C-24), 89.5 (C-3′), 109.7 (C-1′); (-)-FAB-MS m/z: 677 [M - Na]-.White amorphous powder; 1 H-NMR (600 MHz, methanol- d 4 ) ?: 0.90 (9H, d, J = 6.6 Hz, H-21,26,27) s, H-19), 2.39 (1H, dd, J = 13.5, 3.6 Hz, H-7), 3.44 (3H, s, OCH 3), 3.49 (1H, m, H-3), 3.58 (1H, m, H-3 '), 3.63 (1H, m, H-6), 4.04 (1H, d, J = 2.4 Hz, H-2'), 4.19 1H, overlapped, H-15), 4.94 (1H, s, H-1 '); 13 C-NMR (150 MHz, methanol- d 4) δ: 14.4 (C-19), 15.6 (C-18), 18.3 (C-27), 18.6 (C-26), 19.1 (C-21), 32.9 (C-11), 28.9 (C-23), 31.6 (C-25), 32.0 (C-10), 39.7 (C-1), 41.9 (C-16), 43.0 (C-12), 45.6 C-17), 57.4 (C -9), 58.6 (OCH 3), 67.1 (C-6), 67.8 (C-14), 69.0 (C-5 '), 70.0 (C-15), 72.3 (C -3), 76.1 (C-8), 81.8 (C-2 '), 81.9 (C-4'), 84.7 (C-24), 89.5 (C-3 '), 109.7 (C-1'); (-) - FAB-MS m / z: 677 [M-Na] <"& gt ; .
J. Nat. Prod., 48, 751-755 (1985)J. Nat. Prod., 48 , 751-755 (1985)
Nat. Prod. Res., 27, 1816-1822 (2013)
Nat. Prod. Res., 27 , 1816-1822 (2013)
참조예Reference Example 3: 피부줄기세포의 배양 3: Culture of dermal stem cells
Cellntec 사에서 구입한 인간 피부줄기세포(Human epidermal stem cell)를 48-웰 플레이트(6×103 cells/well)에, 소태아혈청(fetal bovine serum)과 유사한 BPE(Bovine pituitary extract)가 첨가된 CNT-57 배지(Cellntec사)를 이용하여 24 시간 동안 5% CO2 및 37℃ 조건에서 배양하였다. 그 후, 배양액을 흡입관을 통하여 제거한 다음, BPE가 제거된 CNT-57 배지에 화학식 2 내지 4의 화합물 각각을 2 ppm 처리하여 5% CO2 및 37℃ 조건에서 72 시간 동안 배양하였다.
Human epidermal stem cells purchased from Cellntec were added to 48-well plates (6 × 10 3 cells / well), supplemented with BPE (bovine pituitary extract) similar to fetal bovine serum And cultured for 24 hours at 5% CO 2 and 37 ° C using CNT-57 medium (Cellntec). Thereafter, the culture medium was removed through a suction tube, and CNT-57 medium in which BPE was removed was treated with 2 ppm of each of the compounds of the formulas (2) to (4) and cultured at 5% CO 2 and 37 ° C for 72 hours.
실시예Example 1: One: CCKCCK -8 평가법을 통한 피부줄기세포 증식 촉진 효과Promoting the proliferation of skin stem cells through the -8 evaluation method
상기 참조예 3에서 배양된 피부줄기세포에 CCK-8(Cell counting kit-8) 평가를 실시하였다. CCK-8 평가는 세포 내 전자전달계 내의 탈수소효소(Dehydrogenase)가 테트라졸리움 염(Tetrazolium Salt)를 분해하여 생성하는 포르마잔(Formazan)의 흡광도를 측정하여 살아있는 세포의 밀도를 간접적으로 나타내는 분석방법이다. The skin stem cells cultured in Reference Example 3 were evaluated for CCK-8 (Cell counting kit-8). The CCK-8 assay is an indirect method of measuring the density of living cells by measuring the absorbance of Formazan, a dehydrogenase in the intracellular electron transport system, produced by the decomposition of tetrazolium salt.
세포에 CCK-8 용액(배지 부피의 1/10을 처리)을 37℃에서 2 시간 동안 처리한 후, 파장 450 nm에서의 흡광도를 측정함으로써 분광학적으로 측정하였다. 화학식 2 내지 4의 화합물 각각의 피부줄기세포의 증식 촉진 효과는 측정된 흡광도 값으로부터 대조군(BPE 첨가한 CNT-57 배지) 대비 하기 수학식 1에 따라 증식율(%)을 구하고, 그 값을 하기 표 1에 나타냈다.Cells were spectrophotometrically measured by treating CCK-8 solution (treated with 1/10 of the medium volume) at 37 ° C for 2 hours and then measuring the absorbance at 450 nm. The proliferation rate (%) of each of the compounds of Formulas (2) to (4) was determined from the absorbance value measured in the control group (CNT-57 medium supplemented with BPE) according to the following formula 1.
[수학식 1][Equation 1]
증식율(%) = (시료처리군의 흡광도/대조군의 흡광도) × 100Growth rate (%) = (absorbance of sample-treated group / absorbance of control group) x 100
상기 표 1의 결과에서 볼 수 있듯이, 본 발명의 화학식 2 내지 4의 화합물 각각을 처리한 배지조건에서의 피부줄기세포는 우수한 증식 촉진 효과를 나타내었다.
As can be seen from the results of Table 1, the dermal stem cells in the media conditions treated with each of the compounds of Formulas 2 to 4 of the present invention showed an excellent proliferation promoting effect.
실시예Example 2: 2: 엘라스타제Elastase 활성 저해 효과 Active inhibitory effect
엘라스틴(Elastin)을 분해하는 효소인 엘라스타제(Elastase)의 활성 저해 효과를 다음과 같이 확인하였다. The inhibitory effect of the enzyme Elastase, which degrades elastin, was confirmed as follows.
엘라스타제 (Elastase)는 사람의 백혈구 세포로부터 유래한 엘라스테이즈를 사용하였고, 엘라스타제의 기질로 합성 기질인 MeOSuc-Ala-Ala-Pro-Val-pNA를 사용하였다. 완충용액은 100 mM의 Tris(pH 7.5) 용액을 사용하였다. 엘라스타제는 완충용액을 이용하여 최종적으로 0.2 mU을 사용하였다. 또한, 엘라스타제의 합성 기질은 DMSO를 이용하여 100 mM 용액을 만든 후 최종 농도가 0.5 mM이 되도록 완충용액을 이용하여 희석하였다. 이 때, 양성 대조군은 엘라스타제 저해 물질로 알려진 퀘르세틴(Quercetin)을 10 ppm 농도로 넣은 것으로 설정하였다. 화학식 2 내지 4의 화합물 각각을 최종 농도가 10 ppm이 되도록 첨가하였다. 반응은 96-웰 플레이트에서 진행하였으며, 상온에서 20분간 반응시켰다. 분광 광도계를 이용하여 1분 간격으로 405 nm에서 흡광도를 측정하여 시간 대비 흡광도의 기울기를 구하여 효소의 활성도로 정하였다 엘라스타제 저해율은 다음 수학식 2와 같이 계산하였다. Elastase used Elastase from human leukocyte cells and MeOSuc-Ala-Ala-Pro-Val-pNA as synthetic substrate for elastase. The buffer solution used was 100 mM Tris (pH 7.5) solution. Elastase was finally used at 0.2 mU using a buffer solution. In addition, the synthesis substrate of elastase was diluted with a buffer solution to make a final concentration of 0.5 mM after making a 100 mM solution using DMSO. At this time, the positive control group was set to contain 10 ppm of quercetin, which is known as an elastase inhibitor. Each of the compounds of formulas 2 to 4 was added to a final concentration of 10 ppm. The reaction was carried out in a 96-well plate and allowed to react at room temperature for 20 minutes. Absorbance was measured at 405 nm using a spectrophotometer at intervals of 1 minute, and the slope of the absorbance versus time was determined to determine the activity of the enzyme. The inhibition rate of elastase was calculated by the following formula (2).
[수학식 2]&Quot; (2) "
엘라스타제 저해율(%) = ((대조군 기울기 - 시료의 기울기)/대조군 기울기)x100Elastase inhibition rate (%) = ((slope of control - slope of sample) / slope of control) x100
상기 표 2의 결과에서 볼 수 있듯이, 화학식 2 내지 4의 화합물 각각을 처리한 경우, 양성대조군 보다 효과는 적으나, 우수한 엘라스타제 활성 저해 효과가 나타남을 알 수 있다.
As can be seen from the results shown in Table 2, when each of the compounds of formulas (2) to (4) was treated, it was found that the effect was less than that of the positive control but the effect of inhibiting elastase activity was excellent.
실시예Example 3: 콜라겐 합성 촉진 효과 3: Promoting collagen synthesis
화학식 2 내지 4의 화합물 각각을 인간 유래 섬유아세포의 배양액에 첨가하여 세포수준에서 콜라겐 합성 촉진 효과를 실험하였다. Each of the compounds of formulas (2) to (4) was added to culture medium of human-derived fibroblasts to examine the promoting effect of collagen synthesis at the cellular level.
증가된 콜라겐 총량의 측정은 PICP EIA kit(Procollagen Type I C-Peptide Enzyme ImmunoAssay KIT)를 이용하여 정량하였다. 실험 전 인간 유래 섬유아세포를 대상으로 화학식 2 내지 4의 화합물 각각의 농도(ppm)를 달리하여 세포독성을 평가(섬유아세포를 배양하여 MTT 시험을 하는 방법[참고문헌: Mossman T. (1983). Rapid Colorimetric Assay for Cellular Growth & SurvVIal: application to proliferation & cytotoxicity assays. Journal of Immunological Methods 65, 55-63]) 하였으며, 세포독성이 없는 농도를 선정(10 ppm 이하)하여 콜라겐 총량의 증가 정도를 평가하였다.The total amount of collagen was measured using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit). The method of evaluating cytotoxicity (culturing fibroblasts and performing MTT test (Mossman T. (1983)) was carried out by subjecting human-derived fibroblasts to various concentrations (ppm) of each of the compounds of Formulas 2 to 4 before the experiment. To evaluate the extent of increase in the total amount of collagen by selecting a concentration without cytotoxicity (10 ppm or less) .
시료를 인간 섬유아세포의 배양 배지에 첨가하여 1일간 배양한 후, 배양액을 취하여 PICP EIA 키트로 각 농도에서의 콜라겐의 총량 증가 정도를 분광광도계를 이용하여 450 nm에서 측정하였다. 효과의 비교를 위하여 아무것도 첨가하지 않은 섬유아세포의 배양 배지(대조군)와 비타민 C를 최종 농도 52.8 ppm이 되도록 첨가한 시료에 대하여 동일한 방법으로 콜라겐 총량의 증가 정도를 측정하였다. 콜라겐의 총량은 UV 흡광도로서 측정하였으며, 콜라겐 총량의 증가율은 대조군에 대한 상대적인 콜라겐 총량의 비율로 계산하고, 콜라겐 총량 증가 효과(반복수=3)를 하기 표 3에 정리하였다.Samples were added to the culture medium of human fibroblasts and cultured for 1 day. Then, the culture solution was taken and the degree of increase in total amount of collagen at each concentration was measured at 450 nm using a PICP EIA kit using a spectrophotometer. For the comparison of the effects, the increase of the total amount of collagen was measured by the same method for the culture medium of fibroblasts to which nothing was added (control group) and the sample added with vitamin C to a final concentration of 52.8 ppm. The total amount of collagen was measured as UV absorbance. The increase rate of the total amount of collagen was calculated by the ratio of the total amount of collagen relative to the control, and the effect of increasing the total amount of collagen (number of repeats = 3) is summarized in Table 3 below.
상기 표 3의 결과에서 볼 수 있듯이, 화학식 2 내지 4의 화합물 각각은 콜라겐 합성을 촉진하여 콜라겐의 총량을 증가시키는 효능이 나타났다.
As can be seen from the results of Table 3, each of the compounds of Formulas 2 to 4 exhibited the effect of promoting collagen synthesis and increasing the total amount of collagen.
실시예 4: 미백 효과-멜라닌 생성 저해 효과 확인 Example 4: Whitening effect - Confirmation of melanin formation inhibitory effect
화학식 2 내지 4의 화합물 각각을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)의 배양액에 첨가하여 세포 수준에서의 멜라닌 총량을 측정함으로써 미백 효과를 확인하였다 (Lotan R., Lotan D. Cancer Res. 40:3345-3350, 1980).Each of the compounds of Formulas 2 to 4 was added to the culture solution of mouse melanoma cells (B-16 mouse) to determine the whitening effect by measuring the total amount of melanin at the cellular level (Lotan R., Lotan D. Cancer Res 40: 3345-3350, 1980).
실험 전 쥐의 멜라노마 세포에 대하여 독성을 평가하여 독성이 없는 농도를 선정하여 미백 평가를 수행하였다.To evaluate the toxicity of melanoma cells in rats before the experiment, whitening evaluation was performed by selecting a concentration that is not toxic.
화학식 2 내지 4의 화합물 각각을 배양액에 최종 농도가 10 ppm이 되도록 하였으며, 대조군인 알부틴은 100 ppm이 되도록 배지에 첨가하여 각각 B-16 멜라노마 세포에 처리하여 3일간 배양하였다. Each of the compounds of Formulas 2 to 4 was added to the culture medium to a final concentration of 10 ppm, and the control group, arbutin, was added to the medium to a concentration of 100 ppm, and treated with B-16 melanoma cells for 3 days.
이후, 세포들을 트립신(trypsin) 처리하여 배양용기로부터 떼어내 원심분리 한 후 멜라닌을 추출하였다. 떼어 낸 세포는 수산화 나트륨 용액(1N) 1ml를 가하여 10분간 끓여 멜라닌을 녹이고 분광 광도계를 이용하여, 400 nm에서 흡광도를 측정하여 생성된 멜라닌의 양을 측정하였다. Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were incubated with 1 ml of sodium hydroxide solution (1N), boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to determine the amount of melanin produced.
상기 멜라닌 양은 단위 세포수당(1×106 cell)의 흡광도로 나타내는 방법으로 측정하였으며, 대조군에 대한 상대적인 멜라닌 생성 총량을 저해율(%)로 계산하고 결과를 하기 표 4에 정리하였다.The amount of melanin was measured by an absorbance of 1 × 10 6 cells per unit cell, and the total amount of melanin production relative to the control group was calculated as the inhibition rate (%). The results are summarized in Table 4 below.
상기 표 4의 결과에서 볼 수 있듯이, 화학식 2 내지 4의 화합물 각각은 양성대조군인 알부틴보다 낮은 농도에서도 우수한 미백 효능을 나타내었다.
As can be seen from the results in Table 4, each of the compounds of Formulas 2 to 4 exhibited excellent whitening efficacy even at lower concentrations than arbutin, which is a positive control.
실시예Example 5: 항산화 효과- 5: Antioxidant effect - 자유라디칼Free radical 소거율 Erasure rate
화학식 2 내지 4의 화합물 각각의 항산화 작용을 확인하기 위해 자유라디칼 소거 활성을 측정하였다. 자유라디칼 소거 활성은 DPPH를 이용하여 측정하였다. DPPH는 비교적 안정한 자유라디칼로서 라디칼 상태로 존재 시 517 ㎚에서 최대 흡광을 보이며 라디칼이 소거되면 흡광성을 잃는다. DPPH는 시그마(Sigma Co., Ltd, 미국)사의 것을 사용하였으며, 0.15 mM의 농도로 메탄올에 녹여 사용하였다.Free radical scavenging activity was measured to confirm the antioxidant activity of each of the compounds of formulas 2 to 4. [ Free radical scavenging activity was measured using DPPH. DPPH is a relatively stable free radical, which shows maximum absorption at 517 ㎚ in the presence of radicals and loses its absorbance when radicals are eliminated. DPPH was purchased from Sigma Co., Ltd. (USA) and dissolved in methanol at a concentration of 0.15 mM.
먼저, 상기 화학식 2 내지 4의 화합물 각각 및 아스코르브산을 96-well 플레이트 각 웰에 100 ㎕씩 넣었다. 여기에 DPPH 용액을 100 ㎕씩 첨가한 다음 상온에서 30분간 방치한 후 Micro plate reader(BioTek EL-340)를 이용하여 517 ㎚에서의 흡광도를 측정하였다. 이때, 상기 시료 대신 메탄올을 첨가한 것을 대조군으로 하였다. First, 100 μl of each of the compounds of Formulas 2 to 4 and ascorbic acid was added to each well of a 96-well plate. 100 μl of DPPH solution was added thereto, and the mixture was allowed to stand at room temperature for 30 minutes. Then, the absorbance at 517 nm was measured using a Microplate reader (BioTek EL-340). At this time, methanol was added instead of the sample to give a control group.
자유라디칼 소거능은 half maximal inhibitory concentration(억제 중간 값)인 IC50을 구하여 그 결과를 하기 표 5에 나타내었다. IC50은 무첨가 대조군의 자유라디칼을 50% 제거하는데 필요한 아스코르빈산 및 화학식 2 내지 4의 화합물 각각의 농도로서 자유라디칼 소거능을 표현하는 일반적인 방법이다.Free radical scavenging activity and the results are obtained for the IC 50 half maximal inhibitory concentration (median inhibition) shown in Table 5. IC 50 is a common method of expressing the free radical scavenging ability as a concentration of each of the compounds of formulas 2 to 4 and ascorbic acid required to remove 50% of the free radicals of the no-added control group.
상기 표 5에 나타낸 바와 같이, 본 발명의 화학식 2 내지 4의 화합물 각각은 아스코르브산 보다 낮으나, 우수한 자유라디칼 소거 능력이 있음을 알 수 있었다.
As shown in Table 5, each of the compounds of Formulas (2) to (4) of the present invention had lower free radical scavenging ability than ascorbic acid.
제제예Formulation example 1: 약학적 제제의 제조 1: Preparation of pharmaceutical preparations
1. 정제의 제조1. Preparation of tablets
화학식 2, 3 또는 4의 화합물 0.2㎎0.2 mg of the compound of formula (2), (3) or
옥수수전분 100㎎100 mg of corn starch
유 당 100㎎100 mg of milk
스테아린산Stearic acid 마그네슘 2㎎ Magnesium 2 mg
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.
제제예Formulation example 2: 화장품의 제조 2: Manufacture of cosmetics
1. 영양크림의 제조1. Manufacture of nutritional cream
하기 조성과 같이, 화학식 2, 3 또는 4의 화합물을 유효성분으로 포함하는 영양크림을 통상의 방법에 따라 제조하였다.A nutritional cream containing the compound of formula (2), (3) or (4) as an active ingredient was prepared according to a conventional method, as shown below.
화학식 2, 3 또는 4의 화합물 0.2중량%0.2% by weight of a compound of formula (2), (3) or (4)
베타-1,3-글루칸 5.0 중량%Beta-1,3-glucan 5.0 wt%
밀납 10.0 중량%Wax 10.0 wt%
폴리솔베이트60 1.5 중량%Polysorbate 60 1.5 wt%
피이지 60 경화피마자유 2.0 중량%≪ tb > < tb > < tb >
솔비탄세스퀴올레이트 0.5 중량%0.5% by weight of sorbitan sesquioleate
유동파라핀 10.0 중량%Liquid paraffin 10.0 wt%
스쿠알란 5.0 중량%Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량%Caprylic / capric triglyceride 5.0 wt%
글리세린 5.0 중량%Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량%3.0% by weight of butylene glycol
프로필렌글리콜 3.0 중량%3.0% by weight of propylene glycol
트리에탄올아민 0.2 중량%0.2% by weight triethanolamine
방부제 0.05 중량%Preservative 0.05 wt%
색소 0.05 중량%0.05% by weight of pigment
향료 0.05 중량%0.05% by weight fragrance
정제수 to 100 중량%
Purified water to 100%
제제예Formulation example 3: 3: 피부외용제의Topical 제조 Produce
1. 연고의 제조1. Manufacture of ointment
하기 조성과 같이, 화학식 2, 3 또는 4의 화합물을 유효성분으로 포함하는 연고를 통상의 방법에 따라 제조하였다.An ointment containing the compound of formula (2), (3) or (4) as an active ingredient was prepared according to a conventional method, as follows.
화학식 2, 3 또는 4의 화합물 0.5 중량%0.5% by weight of a compound of formula (2), (3) or (4)
베타-1,3-글루칸 10.0 중량%Beta-1,3-glucan 10.0 wt%
밀납 10.0 중량%Wax 10.0 wt%
폴리솔베이트60 5.0 중량%Polysorbate 60 5.0 wt%
피이지 60 경화피마자유 2.0 중량%≪ tb > < tb > < tb >
솔비탄세스퀴올레이트 0.5 중량%0.5% by weight of sorbitan sesquioleate
바셀린 5.0 중량%Vaseline 5.0 wt%
유동파라핀 10.0 중량%Liquid paraffin 10.0 wt%
스쿠알란 5.0 중량%Squalane 5.0 wt%
쉐어버터 3.0 중량%SHARE BUTTER 3.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량%Caprylic / capric triglyceride 5.0 wt%
글리세린 10.0 중량%Glycerin 10.0 wt%
프로필렌글리콜 10.2 중량%Propylene glycol 10.2 wt%
트리에탄올아민 0.2 중량%0.2% by weight triethanolamine
방부제 0.05 중량%Preservative 0.05 wt%
색소 0.05 중량%0.05% by weight of pigment
향료 0.05 중량%0.05% by weight fragrance
정제수 to 100 중량%Purified water to 100%
Claims (11)
[화학식 1]
상기 화학식 1에서,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
A composition for enhancing skin elasticity or improving wrinkles comprising a polyhydroxysteroid represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]
In Formula 1,
R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
상기 폴리히드록시스테로이드는 불가사리로부터 추출된 피부 탄력 증진 또는 주름 개선용 조성물.
The method according to claim 1,
Wherein the polyhydroxysteroid is a composition for enhancing skin elasticity or wrinkles extracted from starfish.
[화학식 1]
상기 화학식 1에서,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
A skin whitening composition comprising a polyhydroxysteroid represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]
In Formula 1,
R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
상기 폴리히드록시스테로이드는 불가사리로부터 추출된 피부 미백용 조성물.
The method of claim 3,
Wherein the polyhydroxysteroid is extracted from a starfish.
[화학식 1]
상기 화학식 1에서,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
1. An antioxidative composition comprising a polyhydroxysteroid represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]
In Formula 1,
R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
상기 폴리히드록시스테로이드는 불가사리로부터 추출된 항산화 조성물.
6. The method of claim 5,
Wherein said polyhydroxysteroid is extracted from a starfish.
[화학식 1]
상기 화학식 1에서,
R2, R4 및 R5는 각각 같거나 다르며, 수소 또는 히드록시기를 나타내고,
R1 및 R3는 각각 같거나 다르며, 수소, 히드록시기 또는 황산기를 나타내며,
R6 및 R7은 각각 같거나 다르며, 수소, 히드록시기 또는 OR8으로 나타내고, 상기 R8은 5탄당 내지 6탄당, 메틸기가 치환된 5탄당 내지 6탄당, 황산기가 치환된 5탄당 내지 6탄당, 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당, 5탄당 내지 6탄당의 올리고머, 메틸기가 치환된 5탄당 내지 6탄당의 올리고머, 황산기가 치환된 5탄당 내지 6탄당의 올리고머, 또는 메틸기 및 황산기가 각각 치환된 5탄당 내지 6탄당의 올리고머를 나타낸다.
A composition for stimulating stem cell activity comprising a polyhydroxysteroid represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:
[Chemical Formula 1]
In Formula 1,
R 2 , R 4 and R 5 are each the same or different and represent hydrogen or a hydroxyl group,
R 1 and R 3 are each the same or different and represent a hydrogen, a hydroxyl group or a sulfuric acid group,
R 6 and R 7 are the same or different and each is hydrogen, a hydroxyl group or OR 8 , and R 8 is a hydrogen atom or a monovalent hydrocarbon group having 5 to 6 carbon atoms, a pentacyan to hexacyano group substituted with a methyl group, An oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexose substituted with a methyl group, an oligomer of pentose to hexane substituted with a methyl group, an oligomer of pentose to hexane substituted with a sulfate group, Each represent a substituted pentad to hexadecyl oligomer.
상기 폴리히드록시스테로이드는 불가사리로부터 추출된 줄기세포 활성 촉진용 조성물.
8. The method of claim 7,
Wherein the polyhydroxysteroid is extracted from a starfish.
상기 줄기세포 활성은 줄기세포 증식 촉진인 조성물.
8. The method of claim 7,
Wherein said stem cell activity promotes stem cell proliferation.
상기 조성물은 화장료 조성물, 약학 조성물 또는 건강식품으로 이용되는 것을 특징으로 하는 조성물.
10. The method according to any one of claims 1 to 9,
Wherein the composition is used as a cosmetic composition, a pharmaceutical composition or a health food.
상기 유효성분은 전체 조성물의 총 중량 대비 0.00001 내지 10 중량% 포함되는 것을 특징으로 하는 조성물.10. The method according to any one of claims 1 to 9,
Wherein the active ingredient is present in an amount of 0.00001 to 10% by weight relative to the total weight of the total composition.
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