KR102324181B1 - Skin-whitening cosmetic composition containing Mevalonolactone as a active ingredient - Google Patents
Skin-whitening cosmetic composition containing Mevalonolactone as a active ingredient Download PDFInfo
- Publication number
- KR102324181B1 KR102324181B1 KR1020170046050A KR20170046050A KR102324181B1 KR 102324181 B1 KR102324181 B1 KR 102324181B1 KR 1020170046050 A KR1020170046050 A KR 1020170046050A KR 20170046050 A KR20170046050 A KR 20170046050A KR 102324181 B1 KR102324181 B1 KR 102324181B1
- Authority
- KR
- South Korea
- Prior art keywords
- mevalonolactone
- active ingredient
- skin
- present
- acceptable salt
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Abstract
본 발명은 메발로노락톤을 유효성분으로 포함하는 피부 미백용 조성물에 관한 것으로, 구체적으로 메발로노락톤 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물; 메발로노락톤 또는 이의 허용 가능한 염을 유효성분으로 포함하는, 피부 미백 개선용 피부 외용제; 메발로노락톤 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 미백 개선용 건강기능식품; 또는 메발로노락톤 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 색소 침착의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a skin whitening composition comprising mevalonolactone as an active ingredient, and more particularly, to a skin whitening cosmetic composition comprising mevalonolactone or a cosmetically acceptable salt thereof as an active ingredient; A skin external preparation for improving skin whitening, comprising mevalonolactone or an acceptable salt thereof as an active ingredient; Health functional food for improving skin whitening, comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient; Or it relates to a pharmaceutical composition for preventing or treating skin pigmentation comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
Description
본 발명은 메발로노락톤을 유효성분으로 포함하는 피부 미백용 조성물에 관한 것으로, 구체적으로 메발로노락톤 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물; 메발로노락톤 또는 이의 허용 가능한 염을 유효성분으로 포함하는, 피부 미백 개선용 피부 외용제; 메발로노락톤 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 미백 개선용 건강기능식품; 또는 메발로노락톤 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 색소 침착의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a skin whitening composition comprising mevalonolactone as an active ingredient, and more particularly, to a skin whitening cosmetic composition comprising mevalonolactone or a cosmetically acceptable salt thereof as an active ingredient; A skin external preparation for improving skin whitening, comprising mevalonolactone or an acceptable salt thereof as an active ingredient; Health functional food for improving skin whitening, comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient; Or it relates to a pharmaceutical composition for preventing or treating skin pigmentation comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
사람의 피부색은 피부 내 멜라닌(melanin)의 농도와 분포에 따라 유전적으로 결정되나, 태양 자외선이나 피로, 스트레스 등의 환경적 또는 생리적 조건에 의해서도 영향을 받는다.A person's skin color is genetically determined according to the concentration and distribution of melanin in the skin, but is also affected by environmental or physiological conditions such as solar ultraviolet rays, 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 on the production of melanin, which determines the color of the skin, has been widely reported through various papers so far. After synthesizing melanin having a protective function, the melanin is known to move from melanocytes to keratinocytes, and it is reported that the melanin moved to keratinocytes in this way 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 in the melanin biosynthesis process is an amino acid called tyrosine, which is converted to dihydroxyphenylalanine (DOPA), and then finally converted to melanin through a substance called dopaquinone. is known to be The synthesized melanin makes the skin color dark, and research on a skin whitening method to brighten the skin color by inhibiting the melanin synthesis due to health or cosmetic needs is being actively conducted.
일반적으로 알려진 미백 성분으로서, 코지산(Kojic acid) 또는 알부틴(Arbutin) 등과 같은 티로시나제 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 commonly known whitening ingredient, a substance that inhibits tyrosinase enzyme activity, such as kojic acid or arbutin, hydroquinone, vitamin C (L-Ascorbic acid) or derivatives thereof and various plant extracts There is this. By inhibiting the synthesis of melanin pigment, it is possible not only to realize skin whitening by brightening the skin tone, but also to improve skin hyperpigmentation such as spots or freckles caused by ultraviolet rays, hormones, or heredity. However, when applied to the skin, there is a problem in that the amount of use is limited due to safety issues such as irritation and redness, or the actual effect cannot be expected because the effect is insignificant.
한편, 메발로노락톤은 분자식 C6H10O3, 분자량 130.14을 가지는 화합물이다. 천연에는 산호나무 등에 존재하는 것으로 알려져 있으며, 부형제, 분석용 시약, 첨가제 등의 용도로 사용될 수 있으나, 메발로노락톤이 직접적으로 피부 미백 효과를 가지는 것에 대해서는 밝혀진 바가 없다.On the other hand, mevalonolactone is a compound having a molecular formula C 6 H 10 O 3 and a molecular weight of 130.14. It is known to exist in coral trees in nature, and can be used as an excipient, an analytical reagent, an additive, etc. However, it has not been revealed that mevalonolactone has a direct skin whitening effect.
이러한 배경하에서, 본 발명자들은 피부 미백 효과가 우수한 물질에 관하여 연구를 수행하였으며, 메발로노락톤을 유효성분으로 포함하는 조성물이 멜라닌 합성 억제 및 멜라닌 총량 감소 효과를 나타냄을 규명함으로써, 이를 활용한 피부 미백용 화장료 조성물, 피부 외용제, 건강기능식품 및 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 완성하기에 이르렀다.Under this background, the present inventors conducted a study on a material having an excellent skin whitening effect, and by identifying that a composition containing mevalonolactone as an active ingredient exhibits the effect of inhibiting melanin synthesis and reducing the total amount of melanin, the skin using this Cosmetic compositions for whitening, external preparations for skin, health functional foods, and pharmaceutical compositions for preventing or treating skin pigmentation have been completed.
본 발명의 하나의 목적은, 메발로노락톤 (Mevalonolactone) 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 화장료 조성물을 제공하는 것이다.One object of the present invention is to provide a cosmetic composition comprising mevalonolactone or a cosmetically acceptable salt thereof as an active ingredient.
구체적으로, 본 발명의 목적은 메발로노락톤 (Mevalonolactone) 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물을 제공하는 것이다.Specifically, an object of the present invention is to provide a cosmetic composition for skin whitening comprising mevalonolactone or a cosmetically acceptable salt thereof as an active ingredient.
또한 구체적으로, 본 발명의 목적은 메발로노락톤 (Mevalonolactone) 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백 개선용 피부 외용제를 제공하는 것이다.Also, specifically, it is an object of the present invention to provide an external preparation for skin whitening comprising mevalonolactone or an acceptable salt thereof as an active ingredient.
또한 구체적으로, 본 발명의 목적은 메발로노락톤 (Mevalonolactone) 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백 개선용 건강기능식품을 제공하는 것이다.In addition, specifically, an object of the present invention is to provide a health functional food for improving skin whitening comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
또한 구체적으로, 본 발명의 목적은 메발로노락톤 (Mevalonolactone) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Also, specifically, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating skin pigmentation comprising mevalonolactone 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. Meanwhile, each description and embodiment disclosed in the present invention may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be considered that the scope of the present invention is limited by the specific descriptions described below.
상기 목적을 달성하기 위한 본 발명의 하나의 양태는 메발로노락톤 (Mevalonolactone) 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 화장료 조성물을 제공한다.One aspect of the present invention for achieving the above object provides a cosmetic composition comprising mevalonolactone or a cosmetically acceptable salt thereof as an active ingredient.
본 발명에서 "메발로노락톤 (Mevalonolactone)"은 상기 화학식 1로 표시되고, 분자식 C6H10O3, 분자량 130.14을 가지며, 만니트 (Mannit) 등으로도 명명된다. 천연에는 산호나무 등에 존재하는 것으로 알려져 있으며, 일반적으로 부형제, 분석용 시약, 첨가제 등으로 사용될 수 있다. 그러나, 메발로노락톤 자체의 피부 미백 효과에 대해서는 밝혀진 바가 없다.In the present invention, "Mevalonolactone" is represented by Chemical Formula 1, has a molecular formula C 6 H 10 O 3 , a molecular weight of 130.14, and is also called Mannit. It is known to exist in coral trees in nature, and can generally be used as an excipient, a reagent for analysis, an additive, and the like. However, the skin whitening effect of mevalonolactone itself has not been revealed.
상기 메발로노락톤의 획득 방법은 특별히 한정되지 않으며, 당업계에 공지된 방법을 이용하여 화학적으로 합성하거나, 시판되는 물질을 사용할 수 있다.The method for obtaining the mevalonolactone is not particularly limited, and it may be chemically synthesized using a method known in the art, or a commercially available material may be used.
본 발명의 화학식 1로 표시되는 메발로노락톤은 용매화된 형태뿐만 아니라 비-용매화된(unsolvated) 형태로 존재할 수도 있다. 본 발명의 메발로노락톤은 결정형 또는 무정형 형태로 존재할 수 있으며, 이러한 모든 물리적 형태는 본 발명의 범위에 포함된다.Mevalonolactone represented by Formula 1 of the present invention may exist in a solvated form as well as a non-solvated form. The mevalonolactone 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.
구체적으로, 본 발명에 따른 조성물에 있어, 상기 메발로노락톤의 함량은 조성물 전체 중량 대비 0.0001 내지 10 중량%일 수 있으며, 보다 구체적으로 조성물 전체 중량 대비 0.0001 내지 5 중량%일 수 있다. 보다 더 구체적으로, 상기 메발로노락톤의 함량은 조성물 전체 중량 대비 0.0001 내지 1 중량%일 수 있으며, 가장 구체적으로 0.002 내지 0.006 중량%일 수 있으나, 이에 한정된 것은 아니다.Specifically, in the composition according to the present invention, the content of mevalonolactone may be 0.0001 to 10% by weight based on the total weight of the composition, and more specifically, 0.0001 to 5% by weight based on the total weight of the composition. More specifically, the content of mevalonolactone may be 0.0001 to 1% by weight based on the total weight of the composition, and most specifically, 0.002 to 0.006% by weight, but is not limited thereto.
본 발명은 메발로노락톤 또는 이의 화장품학적으로 허용 가능한 염을 포함하는 화장료 조성물을 제공한다. The present invention provides a cosmetic composition comprising mevalonolactone or a cosmetically acceptable salt thereof.
또한, 구체적으로, 본 발명은 메발로노락톤 또는 이의 화장품학적으로 허용 가능한 염을 포함하는 피부 미백용 화장료 조성물을 제공할 수 있다.In addition, specifically, the present invention may provide a cosmetic composition for skin whitening comprising mevalonolactone or a cosmetically acceptable salt thereof.
본 발명에 있어서, "메발로노락톤"은 상기에서 설명한 바와 같다.In the present invention, "mevalonolactone" is as described above.
본 발명에 있어서, "화장품학적으로 허용 가능한 염"은 메발로노락톤이 다른 물질과 결합한 염의 형태인 것으로, 화장품학적으로 메발로노락톤과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "cosmetically acceptable salt" refers to a substance in the form of a salt in which mevalonolactone is combined with other substances, and which can cosmetically exhibit similar activity to mevalonolactone.
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 skin tone by inhibiting the synthesis of melanin pigment, but also improving skin hyperpigmentation such as spots or freckles caused by ultraviolet rays, hormones or heredity.
본 발명의 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가한 후 멜라닌 총량을 측정한 결과, 상기 화합물을 첨가한 실험군의 경우 우수한 멜라닌 총량 감소 효과를 나타내어, 화학식 1로 표시되는 화합물을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, as a result of measuring the total amount of melanin after adding the compound represented by Formula 1 to B-16 mouse melanoma cells, excellent total amount of melanin in the experimental group to which the compound was added By showing a reducing effect, it was confirmed that the composition containing the compound represented by Formula 1 can be used as a cosmetic composition for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가하여 세포 수준에서의 타이로시네이즈 활성 저해 효과를 확인한 결과, 상기 화합물은 농도 의존적으로 멜라노마 세포의 타이로시네이즈 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 타이로시네이즈의 활성을 저해함을 확인하여, 상기 화학식 1로 표시되는 화합물은 피부 미백용 화장료 조성물로 사용될 수 있음을 재확인하였다 (표 2).In addition, in another embodiment of the present invention, as a result of confirming the tyrosinase activity inhibitory effect at the cellular level by adding the compound represented by Formula 1 to B-16 mouse melanoma cells, the The compound showed an effect of reducing the tyrosinase activity of melanoma cells in a concentration-dependent manner, and in particular, it was confirmed that it inhibited the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was reconfirmed that the compound to be used can be used as a cosmetic composition for skin whitening (Table 2).
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 includes solutions, external ointments, creams, foams, nourishing lotions, softening lotions, packs, soft water, emulsions, makeup bases, essences, soaps, liquid detergents, bathing agents, sunscreen creams, sun oils, suspensions, Emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays can be prepared in a formulation selected from the group consisting of, but not limited to 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 include one or more cosmetically acceptable carriers to be formulated in general skin cosmetics, and conventional ingredients include, for example, oil, water, surfactant, humectant, lower alcohol, A thickener, a chelating agent, a colorant, a preservative, a fragrance, etc. may be appropriately mixed, but the present invention is not limited thereto.
본 발명의 화장료 조성물에 포함되는 화장품학적으로 허용 가능한 담체는 제형에 따라 다양하다.The cosmetically acceptable carrier included in the cosmetic composition of the present invention varies depending on the formulation.
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, paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures thereof 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 a carrier component. In particular, in the case of a spray, additional chlorophyll 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, solubilizer or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil may be used, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol fatty ester, fatty acid ester of polyethylene glycol 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, as a carrier component a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters; Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth 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, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolysates, isethionate, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugar, etc. may be used as carrier components. can
본 발명의 다른 하나의 양태는 메발로노락톤 (Mevalonolactone) 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백 개선용 피부 외용제를 제공한다.Another aspect of the present invention provides an external preparation for skin whitening comprising mevalonolactone or an acceptable salt thereof as an active ingredient.
본 발명에 있어서, "메발로노락톤"은 상기에서 설명한 바와 같다.In the present invention, "mevalonolactone" is as described above.
본 발명에 있어서, "허용 가능한 염"이란, 메발로노락톤이 다른 물질과 결합한 염의 형태인 것으로, 메발로노락톤과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "acceptable salt" refers to a substance in the form of a salt in which mevalonolactone is combined with other substances, and which can exhibit similar activity to mevalonolactone.
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 concept that encompasses all substances generally used for external application to the skin, and non-limiting examples of external preparations for skin include PLASTERS, LOTIONS, and liniment agents. (LINIMENTS), liquids (LIQUIDS AND SOLUTIONS), aerosols (AEROSOLS), extracts (EXTRACTS), ointments (OINTMENTS), fluid extracts (FLUIDEXTRACTS), emulsions (EMULSIONS), suspensions (SUSPESIONS), capsules (CAPSULES) , creams (CREAMS), soft and hard gelatin capsules, patches, or sustained release formulations.
본 발명의 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가한 후 멜라닌 총량을 측정한 결과, 상기 화합물을 첨가한 실험군의 경우 우수한 멜라닌 총량 감소 효과를 나타내어, 화학식 1로 표시되는 화합물을 포함하는 조성물은 피부 미백용 피부 외용제로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, as a result of measuring the total amount of melanin after adding the compound represented by Formula 1 to B-16 mouse melanoma cells, excellent total amount of melanin in the experimental group to which the compound was added By showing a reducing effect, it was confirmed that the composition including the compound represented by Formula 1 can be used as an external preparation for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가하여 세포 수준에서의 타이로시네이즈 활성 저해 효과를 확인한 결과, 상기 화합물은 농도 의존적으로 멜라노마 세포의 타이로시네이즈 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 타이로시네이즈의 활성을 저해함을 확인하여, 상기 화학식 1로 표시되는 화합물은 피부 미백용 피부 외용제로 사용될 수 있음을 재확인하였다 (표 2).In addition, in another embodiment of the present invention, as a result of confirming the tyrosinase activity inhibitory effect at the cellular level by adding the compound represented by Formula 1 to B-16 mouse melanoma cells, the The compound showed an effect of reducing the tyrosinase activity of melanoma cells in a concentration-dependent manner, and in particular, it was confirmed that it inhibited the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was reconfirmed that the compound used can be used as an external preparation for skin whitening (Table 2).
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 administration preparation formulated in solid, semi-solid or liquid form by adding commercially available inorganic or organic carriers, excipients and diluents. 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, but is not limited thereto.
상기 외용제에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 올리고당, 솔비톨, 메발로노락톤, 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. Carriers, excipients and diluents that may be included in the external preparation include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mevalonolactone, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, 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, other ingredients other than the composition of the present invention can be appropriately selected and formulated by those skilled in the art without difficulty depending on the formulation or purpose of use of other external preparations for skin, in this case, it is applied simultaneously with other raw materials Doing so may result in a synergistic effect.
본 발명의 또 다른 하나의 양태는 메발로노락톤 (Mevalonolactone) 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 미백 개선용 건강기능식품을 제공한다.Another aspect of the present invention provides a health functional food for improving skin whitening, comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, "메발로노락톤"은 상기에서 설명한 바와 같다.In the present invention, "mevalonolactone" 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, "health functional food" refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients useful for the human body. Here, the term “functionality” refers to obtaining useful effects for health purposes such as regulating nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art. In addition, if the formulation of the health functional food is also recognized as a health functional food, it may be manufactured without limitation. The health functional food of the present invention can be manufactured in various types of dosage forms, and unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time by using food as a raw material, and it is excellent in portability, and the present invention health functional food can be taken as a supplement to enhance the skin whitening effect.
본 발명의 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가한 후 멜라닌 총량을 측정한 결과, 상기 화합물을 첨가한 실험군의 경우 우수한 멜라닌 총량 감소 효과를 나타내어, 화학식 1로 표시되는 화합물을 포함하는 조성물은 피부 미백용 건강기능식품으로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, as a result of measuring the total amount of melanin after adding the compound represented by Formula 1 to B-16 mouse melanoma cells, excellent total amount of melanin in the experimental group to which the compound was added By showing a reducing effect, it was confirmed that the composition containing the compound represented by Formula 1 can be used as a health functional food for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가하여 세포 수준에서의 타이로시네이즈 활성 저해 효과를 확인한 결과, 상기 화합물은 농도 의존적으로 멜라노마 세포의 타이로시네이즈 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 타이로시네이즈의 활성을 저해함을 확인하여, 상기 화학식 1로 표시되는 화합물은 피부 미백용 건강기능식품으로 사용될 수 있음을 재확인하였다 (표 2).In addition, in another embodiment of the present invention, as a result of confirming the tyrosinase activity inhibitory effect at the cellular level by adding the compound represented by Formula 1 to B-16 mouse melanoma cells, the The compound showed an effect of reducing the tyrosinase activity of melanoma cells in a concentration-dependent manner, and in particular, it was confirmed that it inhibited the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was reconfirmed that the compound can be used as a health functional food for skin whitening (Table 2).
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 flavoring agents or natural carbohydrates as additional ingredients. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumartin and stevia extract or synthetic sweeteners such as saccharin and aspartame may be used.
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 includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, Carbonating agents used in carbonated beverages, etc. may be contained. These components may be used independently or in combination. The ratio of these additives is not very important, 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 또 다른 하나의 양태는 메발로노락톤 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 mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서, "메발로노락톤"은 상기에서 설명한 바와 같다.In the present invention, "mevalonolactone" is as described above.
본 발명에 있어서, "약학적으로 허용 가능한 염"이란 메발로노락톤이 다른 물질과 결합한 염의 형태인 것으로, 약학적으로 메발로노락톤과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "pharmaceutically acceptable salt" refers to a substance in the form of a salt in which mevalonolactone is combined with other substances, and which can pharmaceutically exhibit similar activity to mevalonolactone.
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 hyperpigmented macules caused by an increase in melanin on the skin, nails, mucous membranes surrounding the oral cavity or nasal cavity, and the like, and is also referred to as hyperpigmentation.
본 발명의 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가한 후 멜라닌 총량을 측정한 결과, 상기 화합물을 첨가한 실험군의 경우 우수한 멜라닌 총량 감소 효과를 나타내어, 화학식 1로 표시되는 화합물을 포함하는 조성물은 피부 색소 침착의 예방 또는 치료용 약학적 조성물로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, as a result of measuring the total amount of melanin after adding the compound represented by Formula 1 to B-16 mouse melanoma cells, excellent total amount of melanin in the experimental group to which the compound was added By showing a reducing effect, it was confirmed that the composition containing the compound represented by Formula 1 can be used as a pharmaceutical composition for preventing or treating skin pigmentation (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1로 표시되는 화합물을 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에 첨가하여 세포 수준에서의 타이로시네이즈 활성 저해 효과를 확인한 결과, 상기 화합물은 농도 의존적으로 멜라노마 세포의 타이로시네이즈 활성 감소 효과를 나타내었으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 타이로시네이즈의 활성을 현저히 저해함을 확인하여, 상기 화학식 1로 표시되는 화합물은 피부 색소 침착의 예방 또는 치료용 약학적 조성물로 사용될 수 있음을 재확인하였다 (표 2).In addition, in another embodiment of the present invention, as a result of confirming the tyrosinase activity inhibitory effect at the cellular level by adding the compound represented by Formula 1 to B-16 mouse melanoma cells, the The compound showed an effect of reducing the tyrosinase activity of melanoma cells in a concentration-dependent manner, and in particular, it was confirmed that the activity of tyrosinase was significantly inhibited even at a concentration lower than that of arbutin used as a positive control. It was reconfirmed that the indicated compound can be used as a pharmaceutical composition for preventing or treating skin pigmentation (Table 2).
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 is in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, aerosols, sterile injection solutions, etc. according to conventional methods for preventing and treating skin pigmentation. can be formulated as
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 preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. can be In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. in addition to commonly used simple diluents such as water and liquid paraffin. 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 sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Vegetable oils such as propylene glycol, polyethylene glycol, and olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions.
또한, 본 발명의 약학적 조성물은 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 담체, 부형제 또는 희석제로는 락토즈, 텍스트로즈, 수크로스, 솔비톨, 메발로노락톤, 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 include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mevalonolactone, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose , hydroxypropyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, propyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, mineral oils such as silicon dioxide, etc. this can be used
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 weight, the patient's sex, age, degree of disease, drug form, administration route and period, excretion rate, reaction sensitivity, etc. It can be variously selected by those skilled in the art, and the dosage and frequency 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 may be administered to mammals such as rats, mice, livestock, and humans through various routes. Any mode of administration may be contemplated and may be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.
본 발명의 메발로노락톤을 유효성분으로 포함하는 조성물은 멜라닌 합성을 억제하여 세포 내 멜라닌 총량을 감소시키는 효과가 있음을 확인하였으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 멜라닌 합성을 저해할 수 있으므로, 메발로노락톤을 유효성분으로 포함하는 조성물은 피부 미백용 화장료 조성물, 피부 미백용 피부 외용제 또는 건강기능식품 등으로 유용하게 사용될 수 있다.It was confirmed that the composition comprising mevalonolactone of the present invention as an active ingredient inhibits melanin synthesis to reduce the total amount of melanin in cells. In particular, it inhibits melanin synthesis even at a lower concentration than arbutin used as a positive control Therefore, the composition containing mevalonolactone as an active ingredient can be usefully used as a cosmetic composition for skin whitening, an external preparation for skin whitening, or a health functional food.
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 through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예Example 1: 멜라닌 총량 감소 확인 1: Confirmation of a decrease in the total amount of melanin
메발로노락톤을 마우스의 B-16 멜라노마 세포(B-16 mouse melanoma cell)의 배양액에 첨가하여 세포 수준에서의 미백 효과를 실험하고자 하였다.It was attempted to test the whitening effect at the cellular level by adding mevalonolactone to the culture medium of B-16 mouse melanoma cells of mice.
구체적으로, 배양액을 기준으로 메발로노락톤의 최종농도가 10 μg/ml, 20 μg/ml이 되도록 배지에 첨가하였으며, 양성 대조군인 알부틴은 100 μg/ml의 농도로 배지에 첨가하였다. 음성 대조군은 배지에 추가적인 시료를 첨가하지 않았다. Specifically, it was added to the medium so that final concentrations of mevalonolactone were 10 μg/ml and 20 μg/ml based on the culture medium, and arbutin, a positive control, was added to the medium at a concentration of 100 μg/ml. The negative control did not add any additional samples to the medium.
상기 각각의 배지에서 B-16 멜라노마 세포를 3일간 배양한 후, 배양된 세포에 트립신 (trypsin)을 처리하여 배양용기로부터 분리하여 원심분리 하였다. 원심분리한 세포로부터 멜라닌을 추출하였으며, 구체적으로, 분리된 세포에 수산화 나트륨 용액 (1N 농도) 1 ml를 첨가하고 10 분간 가열하여 멜라닌을 녹이고, 분광 광도계를 이용하여 400 나노미터(nm)에서 흡광도를 측정하여 생성된 멜라닌의 양을 측정하였다. After culturing B-16 melanoma cells in each medium for 3 days, the cultured cells were treated with trypsin, separated from the culture vessel, and centrifuged. Melanin was extracted from the centrifuged cells, and specifically, 1 ml of sodium hydroxide solution (1N concentration) was added to the separated cells and heated for 10 minutes to dissolve melanin, and absorbance at 400 nanometers (nm) using a spectrophotometer was measured to measure the amount of melanin produced.
상기 멜라닌 양은 단위 세포수당 (106 cell) 흡광도로 나타나도록 측정하였으며, 음성 대조군의 멜라닌 총량에 대한 상대적인 저해율(%)을 계산한 결과를 하기 표에 정리하였다.The amount of melanin was measured to appear as absorbance per unit cell number (10 6 cells), and the results of calculating the relative inhibition (%) with respect to the total amount of melanin in the negative control group are summarized in the table below.
그 결과, 상기 표 1에서 볼 수 있듯이, 메발로노락톤은 농도 의존적으로 멜라노마 세포의 멜라닌 총량을 감소시켜, 멜라닌 합성을 억제하는 효과가 있음을 확인하였으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 멜라닌 합성을 저해하여, 멜라닌 총량을 감소시키는 효능을 가짐을 확인하였다.As a result, as can be seen in Table 1, mevalonolactone reduced the total amount of melanin in melanoma cells in a concentration-dependent manner, confirming that there was an effect of inhibiting melanin synthesis, in particular, than arbutin used as a positive control. By inhibiting melanin synthesis even at a low concentration, it was confirmed that it had the effect of reducing the total amount of melanin.
따라서, 메발로노락톤은 멜라닌 합성을 저해하여 멜라닌 총량을 감소시켜, 피부 미백 용도로 사용될 수 있음을 알 수 있었다.Therefore, it was found that mevalonolactone inhibits melanin synthesis to reduce the total amount of melanin, and can be used for skin whitening purposes.
실시예Example 2: 2: 타이로시네이즈Tyrosinase (( tyrosinasetyrosinase ) 활성 감소 확인) check for decreased activity
메발로노락톤을 마우스의 B-16 멜라노마 세포(B-16 mouse melanoma cell)의 배양액에 첨가하여 세포 수준에서의 타이로시네이즈 활성 저해 효과를 실험하고자 하였다.To test the inhibitory effect of tyrosinase activity at the cellular level by adding mevalonolactone to the culture medium of B-16 mouse melanoma cells of mice.
구체적으로, 배양액을 기준으로 메발로노락톤의 최종농도가 10 μg/ml, 20 μg/ml이 되도록 배지에 첨가하였으며, 양성 대조군인 알부틴은 100 μg/ml의 농도로 배지에 첨가하였다. 음성 대조군은 배지에 추가적인 시료를 첨가하지 않았다.Specifically, it was added to the medium so that final concentrations of mevalonolactone were 10 μg/ml and 20 μg/ml based on the culture medium, and arbutin, a positive control, was added to the medium at a concentration of 100 μg/ml. The negative control did not add any additional samples to the medium.
상기 각각의 배지에서 B-16 멜라노마 세포를 3일간 배양한 후, 배양된 세포에 트립신 (trypsin)을 처리하여 배양용기로부터 분리하여 원심분리 하였다. 원심분리한 세포를 세포 용해액 (1% triton-100, 0.1% PMSF 가 포함된 0.1M phosphate buffer)에 용해시키고, 1mM의 도파 (DOPA, dihydroxyphenylalanine)를 섞어 1시간 동안 37도에서 반응을 시킨다. 이후 분광 광도계를 이용하여 475 나노미터(nm)에서 흡광도를 측정하여 타이로시네이즈의 활성 정도를 측정하였다. After culturing B-16 melanoma cells in each medium for 3 days, the cultured cells were treated with trypsin, separated from the culture vessel, and centrifuged. The centrifuged cells are dissolved in a cell lysate (0.1M phosphate buffer containing 1% triton-100, 0.1% PMSF), mixed with 1 mM dopa (DOPA, dihydroxyphenylalanine), and reacted at 37°C for 1 hour. Thereafter, the absorbance was measured at 475 nanometers (nm) using a spectrophotometer to measure the activity level of tyrosinase.
상기 타이로시네이즈의 활성 정도는 단위 세포수당 (106 cell) 흡광도로 나타나도록 측정하였으며, 음성 대조군의 타이로시네이즈의 활성에 대한 상대적인 저해율(%)을 계산한 결과를 하기 표에 정리하였다.The degree of activity of tyrosinase was measured to be expressed as absorbance per unit cell number (10 6 cells), and the results of calculating the relative inhibition (%) of the activity of tyrosinase in the negative control group are summarized in the table below. .
그 결과, 상기 표 2에서 볼 수 있듯이, 메발로노락톤은 농도 의존적으로 멜라노마 세포의 타이로시네이즈의 활성을 감소시키는 효과가 있음을 확인하였으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 타이로시네이즈의 활성을 더욱 현저히 저해하여, 결과적으로 멜라닌 총량을 감소시키는 효능을 가짐을 확인하였다.As a result, as can be seen in Table 2, it was confirmed that mevalonolactone had the effect of reducing the tyrosinase activity of melanoma cells in a concentration-dependent manner. Also, it was confirmed that the activity of tyrosinase was significantly inhibited, and as a result, it had the effect of reducing the total amount of melanin.
따라서, 메발로노락톤은 멜라노마세포의 멜라닌 총량을 감소시킬 뿐만 아니라, 멜라닌 합성과 관련된 효소인 타이로시네이즈의 활성을 저해함을 확인함으로써, 메발로노락톤의 우수한 피부 미백 용도를 재확인 하였다.Therefore, by confirming that mevalonolactone not only reduces the total amount of melanin in melanoma cells, but also inhibits the activity of tyrosinase, an enzyme related to melanin synthesis, the excellent use of mevalonolactone for skin whitening was reconfirmed. .
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, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention, rather than the above detailed description, all changes or modifications derived from the meaning and scope of the claims described below and their equivalents.
Claims (7)
A cosmetic composition for skin whitening comprising mevalonolactone or a cosmetically acceptable salt thereof as an active ingredient.
The cosmetic composition of claim 1, wherein the composition inhibits melanin synthesis, decreases the total amount of melanin, or inhibits the activity of tyrosinase.
The composition according to claim 1 or 3, wherein the composition is a solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, soft water, emulsion, makeup base, essence, soap, liquid detergent, bath agent, sunscreen cream , sun oil, suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, patch and spray having a formulation selected from the group consisting of A cosmetic composition, characterized in that
A skin external preparation for preventing or improving skin pigmentation, comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
A health functional food for improving skin whitening, comprising mevalonolactone or a pharmaceutically acceptable salt thereof as an active ingredient.
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