KR102002627B1 - A skin-whitening composition comprising spinosin - Google Patents
A skin-whitening composition comprising spinosin Download PDFInfo
- Publication number
- KR102002627B1 KR102002627B1 KR1020170049884A KR20170049884A KR102002627B1 KR 102002627 B1 KR102002627 B1 KR 102002627B1 KR 1020170049884 A KR1020170049884 A KR 1020170049884A KR 20170049884 A KR20170049884 A KR 20170049884A KR 102002627 B1 KR102002627 B1 KR 102002627B1
- Authority
- KR
- South Korea
- Prior art keywords
- skin
- spinosin
- active ingredient
- present
- acceptable salt
- Prior art date
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
본 발명은 스피노신 (spinosin) 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 조성물에 관한 것으로, 상기 조성물은 세포 독성을 나타내지 않으면서도, 피부 색소 침착과 관련된 티로시나아제의 활성을 저해하며, 특히, 양성 대조군으로 사용된 코지산과 우수한 멜라닌 합성 저해 효과를 나타냈으므로, 스피노신을 유효성분으로 포함하는 조성물은 피부 미백용 화장료 조성물, 피부 미백용 피부 외용제 또는 건강기능식품 등으로 유용하게 사용될 수 있다.The present invention relates to a skin whitening composition comprising spinosin or an acceptable salt thereof as an active ingredient, which composition inhibits tyrosinase activity associated with skin pigmentation without exhibiting cytotoxicity In particular, since it exhibited an excellent melanin synthesis inhibitory effect with koji acid used as a positive control, a composition containing spinosyn as an active ingredient can be usefully used as a skin whitening cosmetic composition, a skin whitening external preparation for skin or a health functional food have.
Description
본 발명은 스피노신 (spinosin) 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물에 관한 것으로, 구체적으로 스피노신 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 피부 외용제; 스피노신 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 건강기능식품; 스피노신 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 치료용 약학적 조성물; 및 스피노신 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 개선용 의약외품 조성물에 관한 것이다.The present invention relates to a skin whitening cosmetic composition comprising spinosin or an acceptable salt thereof as an active ingredient, and more particularly to a skin whitening external preparation for skin whitening comprising spinosyn or an acceptable salt thereof as an active ingredient; A skin whitening health functional food comprising spinosyn or a pharmaceutically acceptable salt thereof as an active ingredient; A pharmaceutical composition for preventing or treating skin pigmentation comprising spinosyn or a pharmaceutically acceptable salt thereof as an active ingredient; And spinosyn or a pharmaceutically acceptable salt thereof as an active ingredient. The present invention relates to a quasi-drug composition for prevention or improvement of skin pigmentation.
사람의 피부색은 피부 내 멜라닌(melanin)의 농도와 분포에 따라 유전적으로 결정되나, 태양 자외선이나 피로, 스트레스 등의 환경적 또는 생리적 조건에 의해서도 영향을 받는다.The skin color of a person is genetically determined by the concentration and distribution of melanin in the skin, but is also influenced by environmental or physiological conditions such as sunlight, fatigue, and stress.
피부의 색을 결정하는 멜라닌 생성에 대한 화학적 작용은 현재까지 여러 논문 등을 통해 많이 보고되고 있는데, 멜라닌 생성세포인 멜라노사이트 (melanocyte)가 멜라노좀(melanosome)이라는 세포내 소기관 내에서 자외선으로부터 세포를 보호하는 기능을 가지는 멜라닌을 합성한 후, 상기 멜라닌은 멜라노사이트에서 각질형성세포(keratinocyte)로 이동하는 것으로 알려져 있으며, 이렇게 각질형성세포로 이동된 멜라닌이 피부색을 결정하는 것으로 보고되고 있다.The chemical action of melanogenesis, which determines the color of skin, has been reported so far in various papers, etc. Melanocytes, which are melanocytes, secrete cells from ultraviolet light in melanosomes called intracellular organelles It is known that the melanin is transferred from melanocytes to keratinocytes. It has been reported that melanin transferred to keratinocytes determines skin color.
상기 멜라닌 생합성 과정에서 필요한 전구물질은 티로신(tyrosine)이라는 아미노산으로, 이 티로신은 디히드록시페닐알라닌(dihydroxyphenylalanine, DOPA)으로 전환되고, 그 후 도파퀴논(dopaquinone)이라는 물질 등을 거쳐 최종적으로 멜라닌으로 전환된다고 알려져 있다. 이렇게 합성된 멜라닌은 피부색을 짙게 만드는데, 건강 또는 미용상의 요구로 인해 상기 멜라닌 합성을 억제하여 피부색을 밝게 하려는 피부 미백 방법에 관한 연구가 활발히 진행 중이다.The precursor required for the melanin biosynthesis process is an amino acid called tyrosine. The tyrosine is converted into dihydroxyphenylalanine (DOPA), and then converted to melanin through a substance called dopaquinone . The synthesized melanin makes the skin darker. Studies on skin whitening method to suppress skin melanin synthesis and brighten skin color due to health or cosmetic demand are actively under way.
일반적으로 알려진 미백 성분으로서, 코지산(Kojic acid) 또는 알부틴(Arbutin) 등과 같은 티로시나아제 효소활성을 억제하는 물질, 하이드로퀴논(Hydroquinone), 비타민 C(L-Ascorbic acid) 또는 이들의 유도체와 각종 식물 추출물이 있다. 이들은 멜라닌 색소의 합성을 저해함으로써, 피부 톤을 밝게 하여 피부 미백을 실현할 수 있을 뿐만 아니라, 자외선, 호르몬 또는 유전에 기인한 기미나 주근깨 등의 피부 과색소 침착증의 개선이 가능하다. 그러나 피부 적용 시, 자극과 발적 등의 안전성의 문제로 사용량의 제한이 있거나, 효과가 미미하여 실질적인 효과를 기대할 수 없는 문제점이 있다.As a generally known whitening ingredient, a substance inhibiting tyrosinase enzyme activity, such as kojic acid or arbutin, hydroquinone, L-ascorbic acid or derivatives thereof, There are plant extracts. By inhibiting the synthesis of melanin pigment, they can brighten the skin tone to realize skin whitening, and it is possible to improve skin hypercholesterolemia such as stain or freckles due to ultraviolet rays, hormones or heredity. However, when applied to skin, there is a problem that the use amount is limited due to safety problems such as irritation and redness, or the effect is insignificant, so that a practical effect can not be expected.
한편, 스피노신은 분자식 C28H32O15, 분자량 608.549 g/mol을 가지는 화합물로서, 2''-O-glycosylswertisin, 또는 6-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxychromen-4-one으로도 명명된다. 상기 스피노신의 구체적인 약리활성에 대해서는 아직 연구가 진행 중이나, 직접적으로 피부 미백 효과를 갖는지 여부에 대해서는 밝혀진 바가 없다.On the other hand, spinosyn is a compound having the molecular formula C 28 H 32 O 15 , molecular weight 608.549 g / mol, 2 "-O-glycosylswertisin or 6 - [(2S, 3R, 4S, 5S, 6R) dihydroxy-6- (hydroxymethyl) -3 - [(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2-yl] oxyoxan- -hydroxy-2- (4-hydroxyphenyl) -7-methoxychromen-4-one. Although the specific pharmacological activity of the spinosyne is still under investigation, it has not been elucidated whether it has a skin whitening effect directly.
이러한 배경하에서, 본 발명자들은 피부 미백 효과가 우수한 물질에 관하여 연구를 수행하였으며, 스피노신을 유효성분으로 포함하는 조성물이 티로시나아제 활성 저해, 멜라닌 생성 저해 효과를 나타냄을 규명함으로써, 이를 활용한 피부 미백용 화장료 조성물, 피부 외용제, 건강기능식품 및 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 확인함으로써 본 발명을 완성하였다.Under these circumstances, the inventors of the present invention conducted studies on a substance having excellent skin whitening effect, and found that a composition containing spinosyn as an active ingredient exhibits inhibition of tyrosinase activity and inhibition of melanin formation, The present invention has been accomplished by identifying a pharmaceutical composition for preventing or treating skin pigmentation, a cosmetic composition for external use, a skin external preparation, a health functional food and skin pigmentation.
본 발명의 하나의 목적은, 스피노신 (spinosin) 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물을 제공하는 것이다.One object of the present invention is to provide a skin whitening cosmetic composition comprising spinosin or a cosmetically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은, 스피노신 (spinosin) 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 피부 외용제를 제공하는 것이다.It is still another object of the present invention to provide a skin external preparation for skin whitening comprising spinosin or an acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은, 스피노신 (spinosin) 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 건강기능식품을 제공하는 것이다.It is still another object of the present invention to provide a health functional food for skin whitening comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은, 스피노신 (spinosin) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating skin pigmentation comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은, 스피노신 (spinosin) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 개선용 의약외품 조성물을 제공하는 것이다.It is still another object of the present invention to provide a quasi-drug composition for prevention or improvement of skin pigmentation comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.This will be described in detail as follows. On the other hand, each description and embodiment disclosed in the present invention can be applied to each other description and embodiment. That is, all combinations of various elements disclosed in the present invention fall within the scope of the present invention. Further, the scope of the present invention is not limited by the detailed description described below.
상기 목적을 달성하기 위한 하나의 양태로서, 본 발명은 스피노신 (spinosin) 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물을 제공한다.In one aspect of the present invention, the present invention provides a cosmetic composition for skin whitening comprising spinosin or a cosmetically acceptable salt thereof as an active ingredient.
본 발명에서 "스피노신"은 상기 화학식 1로 표시되고, 분자식 C28H32O15, 분자량 608.549 g/mol을 가지는 화합물로서, 2''-O-glycosylswertisin, 또는 6-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxychromen-4-one 으로도 명명된다. 상기 스피노신의 구체적인 약리활성에 대해서는 아직 연구가 진행 중이나, 직접적으로 피부 미백 효과를 갖는지 여부에 대해서는 밝혀진 바가 없다.In the present invention, "spinosyn" is a compound having the molecular formula C 28 H 32 O 15 and the molecular weight of 608.549 g / mol, represented by the above formula (1), and is 2 " -O- glycosylswertisin or 6 - [(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2 -yloxyoxan-2-yl] -5-hydroxy-2- (4-hydroxyphenyl) -7-methoxychromen-4-one. Although the specific pharmacological activity of the spinosyne is still under investigation, it has not been elucidated whether it has a skin whitening effect directly.
상기 스피노신의 획득 방법은 특별히 한정되지 않으며, 당업계에 공지된 방법을 이용하여 화학적으로 합성하거나, 시판되는 물질을 사용할 수 있다.The method for obtaining the spinosyn is not particularly limited and may be chemically synthesized using a method known in the art, or a commercially available material may be used.
본 발명의 화학식 1로 표시되는 스피노신은 용매화된 형태뿐만 아니라 비-용매화된(unsolvated) 형태로 존재할 수도 있다. 본 발명의 스피노신은 결정형 또는 무정형 형태로 존재할 수 있으며, 이러한 모든 물리적 형태는 본 발명의 범위에 포함된다.The spinosyns represented by Formula 1 of the present invention may exist in solvated as well as unsolvated forms. The spinosyn of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.
본 발명에 있어서, "화장품학적으로 허용 가능한 염"은 스피노신이 다른 물질과 결합한 염의 형태인 것으로, 화장품학적으로 스피노신과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, the term "cosmetically acceptable salt" refers to a substance which is in the form of a salt in which spinosyn is combined with another substance, and which can exhibit an activity similar to spinosyn as a cosmetically.
본 발명에 있어서, “피부 미백”이라 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, " skin whitening " refers to not only brightening the skin tone by inhibiting the synthesis of melanin pigment but also improving skin hypercholesterolemia due to ultraviolet rays, hormones or heredity, such as spots or freckles.
본 발명의 일 실시예에서는, 피부 색소 침착과 관련된 티로시나아제의 활성에 대한 스피노신의 억제 효과를 확인한 결과, 상기 화합물은 티로시나아제 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 코지산과 유사한 티로시나아제 활성 감소 효과를 나타내었는바, 스피노신을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 확인하였다(도 2).In one embodiment of the present invention, the inhibitory effect of spinosyne on the activity of tyrosinase associated with skin pigmentation was confirmed. As a result, the compound showed a decrease in tyrosinase activity, and in particular, Showing similar tyrosinase activity reduction effects, it was confirmed that a composition containing spinosyn can be used as a cosmetic composition for skin whitening (FIG. 2).
또한, 본 발명의 다른 일 실시예에서는, 스피노신의 멜라닌 생성 저해 효과를 분석한 결과, 상기 화합물은 농도 의존적으로 멜라닌 합성을 저해하였으며, 특히 양성 대조군으로 사용된 코지산보다 우수한 멜라닌 합성 억제 효과를 나타냄을 확인하여 (도 4), 스피노신을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 재확인하였다.In another embodiment of the present invention, the inhibitory effect on melanin formation of spinosyn was analyzed. As a result, the compound inhibited melanin synthesis in a concentration-dependent manner. In particular, melanin synthesis inhibitory effect was superior to that of kojic acid used as a positive control (FIG. 4), confirming that the composition containing spinosyn can be used as a skin whitening cosmetic composition.
본 발명에 따른 화장료 조성물은 용액, 외용연고, 크림, 폼, 영양화장수, 유연화장수, 팩, 유연수, 유액, 메이크업베이스, 에센스, 비누, 액체 세정료, 입욕제, 선 스크린크림, 선오일, 현탁액, 유탁액, 페이스트, 겔, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 패취 및 스프레이로 구성된 군으로부터 선택되는 제형으로 제조할 수 있으나, 이에 제한되는 것은 아니다.The cosmetic composition according to the present invention can be used as a cosmetic composition in the form of a solution, an ointment for external use, a cream, a foam, a nutritional lotion, a softening water, a pack, a soft water, an emulsion, a makeup base, But are not limited to, emulsions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays It is not.
또한, 본 발명의 화장료 조성물은 일반 피부 화장료에 배합되는 화장품학적으로 허용 가능한 담체를 1 종 이상 추가로 포함할 수 있으며, 통상의 성분으로 예를 들면 유분, 물, 계면활성제, 보습제, 저급 알콜, 증점제, 킬레이트제, 색소, 방부제, 향료 등을 적절히 배합할 수 있으나, 이에 제한되는 것은 아니다.In addition, the cosmetic composition of the present invention may further comprise at least one cosmetically acceptable carrier to be incorporated in a general skin cosmetic composition, and examples thereof include oil, water, a surfactant, a moisturizer, A thickening agent, a chelating agent, a coloring matter, an antiseptic, a perfume, and the like may be appropriately compounded, but the present invention is not limited thereto.
본 발명의 화장료 조성물에 포함되는 화장품학적으로 허용 가능한 담체는 제형에 따라 다양하다.The cosmetically acceptable carrier to be contained in the cosmetic composition of the present invention varies depending on the formulations.
본 발명의 제형이 연고, 페이스트, 크림 또는 젤인 경우에는, 담체 성분으로서 동물성 유, 식물성 유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크, 산화아연 또는 이들의 혼합물이 이용될 수 있다.When the formulation of the present invention is an ointment, a paste, a cream or a gel, the carrier component may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide Mixtures of these may be used.
본 발명의 제형이 파우더 또는 스프레이인 경우에는, 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록사이드, 칼슘 실케이트, 폴리아미드 파우더 또는 이들의 혼합물이 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진제를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or a mixture thereof may be used as the carrier component, Propellants such as fluorohydrocarbons, propane / butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는, 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되며, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알콜, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일이 이용될 수 있으며, 특히, 목화씨 오일, 땅콩 오일, 옥수수 배종 오일, 올리브오일, 피마자 오일 및 참깨 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 이용될 수 있다.When the formulation of the present invention is a solution or emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, 1,3-butyl glycol oil may be used, in particular fatty acid esters of cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol aliphatic esters, polyethylene glycols or sorbitan may be used have.
본 발명의 제형이 현탁액인 경우에는, 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알콜, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
본 발명의 제형이 비누인 경우에는 담체 성분으로서 지방산의 알칼리 금속 염, 지방산 헤미에스테르 염, 지방산 단백질 히드롤리제이트, 이세티오네이트, 라놀린 유도체, 지방족 알콜, 식물성 유, 글리세롤, 당 등이 이용될 수 있다.When the formulation of the present invention is a soap, an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolizate, isethionate, a lanolin derivative, an aliphatic alcohol, a vegetable oil, glycerol, .
본 발명의 다른 하나의 양태는, 스피노신 (spinosin) 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 피부 외용제를 제공한다.Another aspect of the present invention provides a skin external preparation for skin whitening comprising spinosin or an acceptable salt thereof as an active ingredient.
본 발명에 있어서, "스피노신"은 상기에서 설명한 바와 같다.In the present invention, "spinosyn" is as described above.
본 발명에 있어서, "허용 가능한 염"이란, 스피노신이 다른 물질과 결합한 염의 형태인 것으로, 스피노신과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "acceptable salt" means a salt in the form of a salt in which spinosyn is combined with another substance, which means a substance capable of exhibiting an activity similar to spinosyn.
본 발명의 용어 "피부 외용제"는 일반적으로 피부 외용에 사용하는 물질 전반을 포함하는 포괄하는 개념으로, 피부 외용제 제형의 비제한적인 예로는 경고제(PLASTERS), 로션제(LOTIONS), 리니멘트제(LINIMENTS), 액제(LIQUIDS AND SOLUTIONS), 에어로솔제(AEROSOLS), 엑스제(EXTRACTS), 연고제(OINTMENTS), 유동엑스제(FLUIDEXTRACTS), 유제(EMULSIONS), 현탁제(SUSPESIONS), 캅셀제(CAPSULES), 크림제(CREAMS), 연질, 경질 젤라틴 캅셀, 첩부제, 또는 서방화제제가 있다.The term "external preparation for skin" of the present invention is a generic concept including the entirety of materials used for external skin application. Non-limiting examples of external preparations for skin include PLASTERS, LOTIONS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXTRACTS, OINTMENTS, FLUIDEXTRACTS, EMULSIONS, SUSPENSIONS, CAPSULES, , Creams (CREAMS), soft, hard gelatin capsules, pastes, or sustained release preparations.
본 발명의 일 실시예에서는, 피부 색소 침착과 관련된 티로시나아제의 활성에 대한 스피노신의 억제 효과를 확인한 결과, 상기 화합물은 티로시나아제 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 코지산과 유사한 티로시나아제 활성 감소 효과를 나타내었는바, 스피노신을 포함하는 조성물은 피부 미백용 피부 외용제로 사용될 수 있음을 확인하였다(도 2).In one embodiment of the present invention, the inhibitory effect of spinosyne on the activity of tyrosinase associated with skin pigmentation was confirmed. As a result, the compound showed a decrease in tyrosinase activity, and in particular, Showing similar tyrosinase activity reduction effects, it was confirmed that a composition containing spinosyn can be used as a skin external preparation for skin whitening (FIG. 2).
또한, 본 발명의 다른 일 실시예에서는, 스피노신의 멜라닌 생성 저해 효과를 분석한 결과, 상기 화합물은 농도 의존적으로 멜라닌 합성을 저해하였으며, 특히 양성 대조군으로 사용된 코지산보다 우수한 멜라닌 합성 억제 효과를 나타냄을 확인하여 (도 4), 스피노신을 포함하는 조성물은 피부 미백용 피부 외용제로 사용될 수 있음을 재확인하였다.In another embodiment of the present invention, the inhibitory effect on melanin formation of spinosyn was analyzed. As a result, the compound inhibited melanin synthesis in a concentration-dependent manner. In particular, melanin synthesis inhibitory effect was superior to that of kojic acid used as a positive control (FIG. 4), confirming that a composition containing spinosyn can be used as a skin external preparation for skin whitening.
본 발명에 따른 피부 외용제는 상용되는 무기 또는 유기의 담체, 부형제 및 희석제를 가하여 고체, 반고체 또는 액상의 형태로 제제화된 비경구 투여제일 수 있다. 상기 비경구 투여를 위한 제재로는 점적제, 연고, 로션, 겔, 크림, 패취, 스프레이, 현탁제 및 유제로 이루어진 군에서 선택되는 경피 투여형 제형일 수 있으나, 이에 제한되지 않는다.The external preparation for skin according to the present invention may be a parenteral dosage form which is formulated in solid, semi-solid or liquid form by adding a compatible inorganic or organic carrier, excipient and diluent. The preparation for parenteral administration may be a transdermal dosage form selected from the group consisting of drops, ointments, lotions, gels, creams, patches, sprays, suspensions, and emulsions.
상기 외용제에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 올리고당, 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. Examples of the carrier, excipient and diluent which can be contained in the external preparation include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
각 제형에 의한 피부 외용제 조성물에 있어서, 상기한 본 발명의 조성물 이외의 다른 성분들을 기타 피부 외용제의 제형 또는 사용 목적 등에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있으며, 이 경우 다른 원료와 동시에 적용할 경우 상승효과가 일어날 수 있다.In the composition for external application for skin according to each formulation, components other than the composition of the present invention may be mixed and selected without difficulty by those skilled in the art depending on the formulation or use purpose of other external preparation for skin, etc. In this case, A synergistic effect can occur.
본 발명의 또 다른 하나의 양태는 스피노신 (spinosin) 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 미백용 건강기능식품을 제공한다.Another aspect of the present invention provides a health functional food for skin whitening comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, "스피노신"은 상기에서 설명한 바와 같다.In the present invention, "spinosyn" is as described above.
본 발명에 있어서, "건강기능식품"이란 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캅셀, 분말, 과립, 액상 및 환 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 “기능성”이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 당업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 상기 제조시에는 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 건강기능식품은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 건강기능식품은 피부 미백 효과를 증진시키기 위한 보조제로 섭취가 가능하다.In the present invention, the term "health functional food" refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and rings using raw materials and components having useful functions in the human body. The term "functional" as used herein means that the structure and function of the human body have a beneficial effect on health uses such as controlling nutrients or physiological actions. The health functional food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients that are conventionally added in the art. In addition, the formulations of the above health functional foods may also be manufactured without limitations as long as they are acceptable as health functional foods. The health functional food of the present invention can be manufactured in various formulations, and unlike general pharmaceuticals, it has advantages in that it does not have side effects that may occur when a food is used as a raw material for a long period of time, and has excellent portability. Can be ingested as an adjunct to improve the skin whitening effect.
본 발명의 일 실시예에서는, 피부 색소 침착과 관련된 티로시나아제의 활성에 대한 스피노신의 억제 효과를 확인한 결과, 상기 화합물은 티로시나아제 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 코지산과 유사한 티로시나아제 활성 감소 효과를 나타내었는바, 스피노신을 포함하는 조성물은 피부 미백용 건강기능식품으로 사용될 수 있음을 확인하였다(도 2).In one embodiment of the present invention, the inhibitory effect of spinosyne on the activity of tyrosinase associated with skin pigmentation was confirmed. As a result, the compound showed a decrease in tyrosinase activity, and in particular, Showing similar tyrosinase activity reduction effects, it was confirmed that a composition containing spinosyn can be used as a health functional food for skin whitening (FIG. 2).
또한, 본 발명의 다른 일 실시예에서는, 스피노신의 멜라닌 생성 저해 효과를 분석한 결과, 상기 화합물은 농도 의존적으로 멜라닌 합성을 저해하였으며, 특히 양성 대조군으로 사용된 코지산보다 우수한 멜라닌 합성 억제 효과를 나타냄을 확인하여 (도 4), 스피노신을 포함하는 조성물은 피부 미백용 건강기능식품으로 사용될 수 있음을 재확인하였다.In another embodiment of the present invention, the inhibitory effect on melanin formation of spinosyn was analyzed. As a result, the compound inhibited melanin synthesis in a concentration-dependent manner. In particular, melanin synthesis inhibitory effect was superior to that of kojic acid used as a positive control (Fig. 4), confirming that the composition containing spinosyn can be used as a skin-whitening health functional food.
본 발명의 건강기능식품은 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 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.The health functional food of the present invention may contain various flavors or natural carbohydrates as an additional ingredient. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as 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.
상기 외에 본 발명의 건강기능식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 건강식품 100 중량부 당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health functional food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, protective colloid thickener, pH adjuster, stabilizer, preservative, glycerin, A carbonating agent used in a carbonated beverage, and the like. 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 health food of the present invention.
본 발명의 다른 하나의 양태는 스피노신 (spinosin) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 제공한다.Another aspect of the present invention provides a pharmaceutical composition for preventing or treating skin pigmentation comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 하나의 양태는 스피노신 (spinosin) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 개선용 의약외품 조성물을 제공한다.Another aspect of the present invention provides a quasi-drug composition for prevention or improvement of skin pigmentation comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, "스피노신"은 상기에서 설명한 바와 같다.In the present invention, "spinosyn" is as described above.
본 발명에 있어서, "약학적으로 허용 가능한 염"이란 스피노신이 다른 물질과 결합한 염의 형태인 것으로, 약학적으로 스피노신과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, the term "pharmaceutically acceptable salt" means a salt in which spinosyn is combined with another substance, and means a substance that can exhibit a similar activity to spinosyn as a pharmaceutical.
본 발명에 있어서, "피부 색소 침착"은 피부, 손발톱, 구강이나 비강을 둘러싸고 있는 점막 등에 멜라닌 증가에 의해 발생한 과다 색소 침착 반(macule)을 의미하며, 과색소침착이라고도 한다.In the present invention, "skin pigmentation" refers to a hyperpigmentation macule caused by an increase of melanin in skin, nail, mucous membrane surrounding oral cavity or nasal cavity, and is also called hyperpigmentation.
본 발명의 일 실시예에서는, 피부 색소 침착과 관련된 티로시나아제의 활성에 대한 스피노신의 억제 효과를 확인한 결과, 상기 화합물은 티로시나아제 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 코지산과 유사한 티로시나아제 활성 감소 효과를 나타내었는바, 스피노신을 포함하는 조성물은 피부 색소 침착의 예방 또는 치료용 약학적 조성물로 사용될 수 있음을 확인하였다 (도 2).In one embodiment of the present invention, the inhibitory effect of spinosyne on the activity of tyrosinase associated with skin pigmentation was confirmed. As a result, the compound showed a decrease in tyrosinase activity, and in particular, Showing similar tyrosinase activity reduction effects, it was confirmed that a composition containing spinosyn can be used as a pharmaceutical composition for preventing or treating skin pigmentation (FIG. 2).
또한, 본 발명의 다른 일 실시예에서는, 스피노신의 멜라닌 생성 저해 효과를 분석한 결과, 상기 화합물은 농도 의존적으로 멜라닌 합성을 저해하였으며, 특히 양성 대조군으로 사용된 코지산보다 우수한 멜라닌 합성 억제 효과를 나타냄을 확인하여 (도 4), 스피노신을 포함하는 조성물은 피부 색소 침착의 예방 또는 치료용 약학적 조성물로 사용될 수 있음을 재확인하였다.In another embodiment of the present invention, the inhibitory effect on melanin formation of spinosyn was analyzed. As a result, the compound inhibited melanin synthesis in a concentration-dependent manner. In particular, melanin synthesis inhibitory effect was superior to that of kojic acid used as a positive control (FIG. 4), confirming that a composition comprising spinosyn can be used as a pharmaceutical composition for preventing or treating skin pigmentation.
본 발명의 약학적 조성물은 피부 색소 침착을 예방하고 치료하기 위한 통상의 방법에 따라 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 에어로졸, 멸균 주사용액 등의 형태로 제형화가 가능하다.The pharmaceutical composition of the present invention may be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aerosols, sterilized injection solutions etc. according to a conventional method for preventing and treating skin pigmentation . ≪ / RTI >
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제도 사용될 수 있다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 포함되며, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제, 감미제, 방향제, 보존제 등이 사용될 수 있다.Solid formulations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, . In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, Can be used.
비경구투여를 위한 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제 등을 포함할 수 있다. 비수성용제와 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일 등과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the non-aqueous solvent and the suspending agent include vegetable oils such as propylene glycol, polyethylene glycol and olive oil, injectable esters such as ethyl oleate, and the like.
또한, 본 발명의 약학적 조성물은 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 담체, 부형제 또는 희석제로는 락토즈, 텍스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오즈, 메틸 셀루로오즈, 하이드록시 프로필 메틸 셀룰로오즈, 미정질 셀룰로오즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 플로필히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 이산화규소 등의 광물유 등이 사용될 수 있다.In addition, the pharmaceutical composition of the present invention may further comprise a carrier, an excipient or a diluent. Examples of the carrier, excipient or diluent include lactose, textol, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Mineral oil such as propyl methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and silicon dioxide can be used have.
본 발명에 따른 약학적 조성물의 구체적인 투여량은 제제화 방법, 환자의 상태 및 체중, 환자의 성별, 연령, 질병의 정도, 약물형태, 투여경로 및 기간, 배설 속도, 반응 감응성 등과 같은 요인들에 따라 당업자에 의해 다양하게 선택될 수 있으며, 투여량 및 횟수는 어떠한 면에서든 본 발명의 범위를 제한하는 것은 아니다.The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as the formulation method, the patient's condition and body weight, the patient's sex, age, degree of disease, drug type, administration route and period, excretion rate, May be variously selected by those skilled in the art, and the dosage and the number of times do not limit the scope of the present invention in any way.
본 발명의 약학적 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로를 통해 투여될 수 있다. 투여의 모든 방식은 예상될 수 있으며, 예를 들어 경구, 정맥, 근육 또는 피하 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like through various routes. All modes of administration may be expected and may be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.
본 발명의 스피노신을 유효성분으로 포함하는 조성물은 세포 독성을 나타내지 않으면서도, 피부 색소 침착과 관련된 티로시나아제의 활성을 저해하며, 특히, 양성 대조군으로 사용된 코지산과 우수한 멜라닌 합성 저해 효과를 나타냈으므로, 스피노신을 유효성분으로 포함하는 조성물은 피부 미백용 화장료 조성물, 피부 미백용 피부 외용제 또는 건강기능식품 등으로 유용하게 사용될 수 있다.The composition containing the spinosyn of the present invention as an active ingredient inhibited the activity of tyrosinase associated with skin pigmentation without exhibiting cytotoxicity and exhibited excellent inhibition of melanin synthesis with koji acid used as a positive control Therefore, a composition containing spinosyn as an active ingredient can be usefully used as a cosmetic composition for skin whitening, a skin external preparation for skin whitening, a health functional food, and the like.
도 1은, B16F10 세포에 대한 스피노신의 세포독성 여부를 확인한 그래프이다.
도 2는, 스피노신의 티로시나아제 (tyrosinase) 저해 효과를 확인한 그래프이다.
도 3은, 스피노신의 티로시나아제에 대한 결합력 및 결합 가능 부위를 확인한 것이다.
도 4는, 스피노신의 멜라닌 생성 저해 효과를 확인한 것으로, a)는 αMSH (멜라닌 세포 자극 호르몬, Melanocyte-Stimulating Hormone, 500nM)을 처리한 경우, b)는 UVB (8mJ)를 조사한 경우이며, c)는 멜라닌 생성 정도에 따른 세포의 색깔을 나타낸 것이다.1 is a graph showing the cytotoxicity of spinosyn to B16F10 cells.
FIG. 2 is a graph showing inhibitory effect of tyrosinase of spinosyn. FIG.
Fig. 3 shows the binding force and binding site of spinosyn to tyrosinase.
Fig. 4 shows the effect of inhibiting melanin formation of spinosyn. Fig. 4 (a) shows a case where αMSH (melanocyte-stimulating hormone, 500 nM) Shows the color of cells according to the degree of melanin production.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예Example 1: One: 스피노신의Spinosyne 세포독성 여부 확인 Check cytotoxicity
스피노신이 피부 관련 세포에 독성을 나타내는지 확인하기 위하여, 한국 세포주 은행에서 구입한 B16F10 세포를 96-well microplate에 배양하고, 스피노신을 2, 5, 10, 20μM 농도로 48시간 동안 처리한 후, EZ-Cytox cell viability assay를 실시했다. B16F10 cells purchased from Korean Cell Line Bank were cultured in 96-well microplates and treated with spinosyne at concentrations of 2, 5, 10, and 20 μM for 48 hours. EZ -Cytox cell viability assay.
그 결과, 스피노신은 처리된 농도에 관계 없이 B16F10 세포에 대한 세포 독성을 나타내지 않음을 확인하여, 화장료 조성물 또는 피부 외용제 등으로 안전하게 사용될 수 있음을 알 수 있었다 (도 1).As a result, it was confirmed that spinosyn was not cytotoxic to B16F10 cells regardless of the treated concentration, and thus it could be safely used as a cosmetic composition or external preparation for skin (Fig. 1).
실시예Example 2: 2: 스피노신의Spinosyne 미백 효과 확인 Confirm whitening effect
2-1. 2-1. 스피노신의Spinosyne 티로시나아제 ( Tyrosinase ( tyrosinasetyrosinase ) 저해 효과 확인) Identification of inhibitory effect
스피노신의 티로시나아제 저해효과를 확인하기 위해, 버섯 유래 티로시나아제를 본 실험의 효소원으로 사용하였으며, 종래 알려진 방법 (Life Sci., 1999, 65, 241-246)을 일부 변형하여 분석하였다. In order to confirm the inhibitory effect of tyrosinase of spinosyn, mushroom-derived tyrosinase was used as an enzyme source of this experiment, and a known method (Life Sci., 1999, 65, 241-246) was partially modified and analyzed.
구체적으로, 96-well microplate에 DMSO (control), 양성대조군 코지산 (kojic acid) 및 스피노신을 10μl씩 처리한 후, 1mM L-티로신 용액과 50mM 인산 완충액 (pH 6.5)을 함유하는 버퍼를 170μl를 넣고 버섯 유래 티로시나아제 (330 units) 수용액 20μl를 처리 후 37에서 20분 동안 배양하였다. Specifically, DMSO (control), positive control kojic acid and spinosyn were treated in a 96-well microplate in an amount of 10 μl each, and 170 μl of a buffer containing 1 mM L-tyrosine and 50 mM phosphate buffer (pH 6.5) And 20 μl of a mushroom-derived tyrosinase (330 units) aqueous solution was treated and cultured at 37 for 20 minutes.
배양 후 반응 혼합물에서 생성된 Dopa/Dopaquinone의 양을 405nm (OD405)에서 마이크로플레이트리더 (Molecular Devices, Spectramax i3)를 이용하여 측정하였다. 스피노신이 가지는 고유의 색을 보정하기 위해서 blank군은 양성대조군 및 샘플을 10μl 처리한 후, 1mM L-티로신 용액과 50mM 인산 완충액 (pH 6.5)을 함유하는 버퍼를 190μl 처리 후, 티로시나아제 수용액은 처리하지 않았다. The amount of Dopa / Dopaquinone produced in the reaction mixture after incubation was measured at 405 nm (OD405) using a microplate reader (Molecular Devices, Spectramax i3). In order to correct the intrinsic color of spinosyn, the positive control group and the sample were treated with 10 μl of the blank group, and then treated with 190 μl of a buffer containing 1 mM L-tyrosine solution and 50 mM phosphate buffer (pH 6.5), and the tyrosinase aqueous solution Not processed.
티로시나아제 활성 저해효과의 계산은 샘플군의 흡광도에서 blank군의 흡광도를 빼준 후, DMSO (control) 처리 군을 100으로 설정하여 양성대조군 및 스피노신 처리군의 티로시나아제 활성 저해효과를 %로 나타내었다. 농도별로 처리된 스피노신 및 코지산의 티로시나아제 저해 효과를 측정하여 IC50 (효소 활성을 50% 저해하는 물질의 농도)를 계산하였다. The tyrosinase inhibitory effect was calculated by subtracting the absorbance of the blank group from the absorbance of the sample group and then setting the DMSO (control) -treated group to 100 and the inhibitory effect of the tyrosinase activity of the positive control group and the spinosyn treatment group in% Respectively. The inhibitory effect of tyrosinase of spinosyn and kojic acid treated by concentration was measured to calculate IC 50 (concentration of substance inhibiting 50% of enzyme activity).
실험 결과, 도 2에서 확인할 수 있는 바와 같이, 스피노신은 미백 화장품 원료로서 효과가 우수한 것으로 알려진 코지산의 IC50 (42.1μM)과 유사한 IC50 (47.0μM) 수치를 나타내었음을 확인하였다 (도 2). The experimental results were also confirmed Empty, spinosyns shows the IC 50 (42.1μM) IC 50 ( 47.0μM) similar to the levels of kojic acid known to have an excellent effect as a skin-whitening cosmetic material as can be found in the second (Fig. 2 ).
따라서, 스피노신은 강력한 티로시나아제 저해 효과를 나타내어, 피부 미백 효과가 우수함을 확인하였다.Therefore, spinosyn exhibited a strong tyrosinase inhibitory effect, confirming excellent skin whitening effect.
2-2. 2-2. 스피노신의Spinosyne 티로시나아제에 대한 결합력 및 결합 가능 부위 확인 Identification of binding and binding sites for tyrosinase
스피노신이 티로시나아제 저해 효과를 통해 미백효과를 나타내는 분자생물학적 기전을 밝히기 위해서 스피노신이 티로시나아제에 직접적으로 결합할 수 있는지 여부를 도킹 시뮬레이션 (docking simulation)을 이용해서 확인하였다.In order to elucidate the molecular biological mechanism of spinosynthesis showing the whitening effect by tyrosinase inhibition effect, it was confirmed by docking simulation whether spinosyne can bind directly to tyrosinase.
구체적으로, 도킹 시뮬레이션을 위해서 Autodock vina라는 프로그램을 이용했고, 티로시나아제의 3D 구조는 Agaricus bisporus (PDB ID:2Y9X)를 이용하였다.Specifically, a program called Autodock vina was used for docking simulation, and the 3D structure of tyrosinase was Agaricus bisporus (PDB ID: 2Y9X).
Docking pocket으로 이미 알려진 티로시나아제의 결합 부위 (binding site)를 사용했고, 코지산를 양성대조군으로 하여 스피노신이 티로시나아제에 결합할 수 있는지, 결합력은 얼마인지를 예측했다. 티로시나아제와 코지산 또는 스피노신 간의 수소결합 부위와 pharmacophore generation은 LigandScout 3.0 프로그램을 이용하여 분석하였다. We used tyrosinase binding site known as docking pocket and used kojic acid as a positive control to predict if spinosyne could bind to tyrosinase and how much binding force would be. The hydrogen bonding sites and pharmacophore generation between tyrosinase and kojic acid or spinocyne were analyzed using the LigandScout 3.0 program.
실험 결과, 도 3에서 확인할 수 있는 바와 같이, 코지산 (-5.4kcal/mol)에 비해서 스피노신 (-6.8kcal/mol)의 티로시나아제에 대한 결합력이 더 뛰어남을 확인하였다 (도 3). 이는 티로시나아제의 ASN260A 또는 GLY281A 잔기와 수소결합으로 결합력을 형성할 수 있는 코지산에 비해서 스피노신은 MET280A, GLY281A, ASN260A 잔기와 수소결합을 형성할 뿐만 아니라 PHE192A 잔기와 소수성 결합을 형성할 수 있기 때문인 것으로 분석되었다.As shown in FIG. 3, it was confirmed that spinosyne (-6.8 kcal / mol) had better binding capacity to tyrosinase than koji (-5.4 kcal / mol) (FIG. 3). This is because spinosyn can not only form hydrogen bonds with the residues MET280A, GLY281A and ASN260A but also form hydrophobic bonds with PHE192A residues, as compared to kojic acid, which can form bonds with a hydrogen bond with ASN260A or GLY281A residues of tyrosinase Respectively.
따라서, 상기와 같은 분자 단계에서의 분석을 통해, 스피노신이 코지산에 비해 티로시나아제에 대한 결합력이 더욱 강하므로, 티로시나아제를 더 효과적으로 억제하여 우수한 피부 미백 효과를 발휘할 수 있음을 알 수 있다.Therefore, through the analysis at the molecular stage as described above, spinosyn is more strongly bound to tyrosinase than kojic acid, so that it is possible to more effectively inhibit tyrosinase and exert an excellent skin whitening effect .
2-3. 2-3. 스피노신의Spinosyne 멜라닌 생성 저해 효과 확인 Confirmation of inhibition of melanin formation
스피노신의 멜라닌 생성 저해 효과를 분석하여, 미백 효과를 보다 구체적으로 확인하고자 하였다. The inhibitory effect of spinosyne on melanin formation was analyzed to confirm the whitening effect more specifically.
구체적으로, B16F10 세포를 5% fetal bovine serum (FBS)과 1% penicillin/streptomycin이 포함된 Dulbecco’s modified Eagle’s medium (DMEM)이 있는 6-well plate에서 배양하였다 (37°C, a humidified 95% air/5% CO2). 세포를 5 x 104 의 농도로 seeding 한 후 24시간이 경과했을 때, kojic acid (10μM) 또는 스피노신 (2μM, 5μM, 또는 10μM)을 1시간 동안 전처리 하였다. 전처리 후, 멜라닌 생성을 유도하기 위해서 (a) αMSH (멜라닌 세포 자극 호르몬, Melanocyte-Stimulating Hormone, 500nM)를 처리하거나 (b) UVB (8mJ)를 조사하였다.B16F10 cells were cultured in a 6-well plate containing Dulbecco's modified Eagle's medium (DMEM) containing 5% fetal bovine serum (FBS) and 1% penicillin / streptomycin (37 ° C, a humidified 95% air / 5% CO2). Cells were seeded at a concentration of 5 × 10 4 , and kojic acid (10 μM) or spinosyn (2 μM, 5 μM, or 10 μM) was pretreated for 24 hours after 24 hours. After pretreatment, (a) treatment with αMSH (melanocyte-stimulating hormone, 500 nM) or (b) irradiation with UVB (8 mJ) was conducted to induce melanin production.
48시간 동안 배양한 후, 멜라닌이 생성된 정도를 측정하기 위해서 세포를 phosphate buffered saline에 두 번 세척한 후, 5% DMSO가 포함된 1 N sodium hydroxide (NaOH) solution (80 μL)에 용해시켰다 (60°C에서 1시간 배양). 가용화 (Solubilized)된 멜라닌이 포함된 수용액을 흡광도계 (405nm)를 통해서 측정했다. 그리고 BCA protein assay를 통해서 각 샘플의 단백질 농도를 구한 후, 멜라닌이 포함된 수용액의 흡광도 값을 보정해 주었다. After 48 h of incubation, the cells were washed twice with phosphate buffered saline and dissolved in 80 μL of 1 N sodium hydroxide (NaOH) solution containing 5% DMSO to determine the extent of melanin production Gt; 60 C < / RTI > for 1 hour). An aqueous solution containing solubilized melanin was measured through an absorbance meter (405 nm). The protein concentration of each sample was determined by BCA protein assay and the absorbance value of the aqueous solution containing melanin was corrected.
실험 결과, 도 4의 a와 같이, αMSH (500nM)의 처리에 의해 B16F10의 멜라닌 생성이 현저하게 증가되었다. 하지만 스피노신은 처리 농도에 비례해서 αMSH에 의해서 유도된 멜라닌 생성을 감소시켰으며, 특히, 10μM 농도에서는 미백 화장품 소재로 사용되고 있는 코지산보다 우수한 멜라닌 활성 억제 효과를 나타내었다 (도 4의 a).As a result of the experiment, the production of melanin of B16F10 was remarkably increased by treatment with? MSH (500 nM) as shown in FIG. 4A. However, spinosyne decreased the production of melanin induced by? MSH in proportion to the treatment concentration. Especially, at the concentration of 10 μM, melanin inhibitory effect was superior to that of kojic acid, which is used as a whitening cosmetic material (FIG.
마찬가지로, 도 4의 b에서 확인할 수 있는 바와 같이, UVB (8mJ)에 의해서 멜라닌 생성이 유도되었으나, 스피노신의 처리 농도에 비례하여 멜라닌 생성이 뚜렷하게 억제되었음을 확인하였다 (도 4의 b).Similarly, as can be seen from Fig. 4 (b), melanin production was induced by UVB (8 mJ), but melanin production was remarkably inhibited in proportion to the treatment concentration of spinosyn (Fig.
특히, 도 4의 c의 세포사진에 따르면, αMSH에 의해서 세포의 색소침착 정도가 증가했지만, 스피노신 (10μM)이 처리된 세포는 αMSH를 처리하지 않은 대조군과 비슷하게 세포의 색깔이 유지되었다 (도 4의 c). In particular, according to the cell photograph of FIG. 4C, the degree of pigmentation of the cells was increased by? MSH, but the cells treated with spinosyn (10 μM) maintained the cell color similar to the control without? MSH 4 c).
따라서, 스피노신은 미백 화장품 소재로 사용되고 있는 코지산보다도 멜라닌 생성을 더욱 효과적으로 억제할 수 있음을 확인하여, 미백 소재로서 더 유용하게 사용될 수 있음을 알 수 있다.Therefore, it has been confirmed that spinosyn can more effectively inhibit melanin formation than koji, which is used as a whitening cosmetic material, so that it can be used more effectively as a whitening material.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all aspects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.
Claims (8)
A cosmetic composition for skin whitening comprising spinosin or a cosmetically acceptable salt thereof as an active ingredient.
The cosmetic composition according to claim 1, wherein the composition inhibits melanin synthesis inhibition or tyrosinase activity.
3. The cosmetic composition according to claim 2, wherein the inhibition of melanin synthesis inhibits increased melanin synthesis due to Melanocyte-Stimulating Hormone (? MSH) or UVB (ultraviolet B).
The composition according to any one of claims 1 to 3, wherein the composition is selected from the group consisting of a solution, a cream, a foam, a nutritional lotion, a softening water, a pack, a soft water, a makeup base, an essence, a liquid cleanser, , A formulation selected from the group consisting of suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays Cosmetic composition.
An external skin preparation for skin whitening comprising spinosin or an acceptable salt thereof as an active ingredient.
A health functional food for skin whitening comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
A pharmaceutical composition for preventing or treating skin pigmentation comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
A quasi-drug composition for preventing or improving skin pigmentation comprising spinosin or a pharmaceutically acceptable salt thereof as an active ingredient.
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