KR102093781B1 - Skin-whitening cosmetic composition containing sodium riboflavin phosphate or phytantriol as a active ingredient - Google Patents
Skin-whitening cosmetic composition containing sodium riboflavin phosphate or phytantriol as a active ingredient Download PDFInfo
- Publication number
- KR102093781B1 KR102093781B1 KR1020170046205A KR20170046205A KR102093781B1 KR 102093781 B1 KR102093781 B1 KR 102093781B1 KR 1020170046205 A KR1020170046205 A KR 1020170046205A KR 20170046205 A KR20170046205 A KR 20170046205A KR 102093781 B1 KR102093781 B1 KR 102093781B1
- Authority
- KR
- South Korea
- Prior art keywords
- phytantriol
- riboflavin phosphate
- skin
- active ingredient
- sodium
- Prior art date
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- OHSHFZJLPYLRIP-BMZHGHOISA-M Riboflavin sodium phosphate Chemical compound [Na+].OP(=O)([O-])OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O OHSHFZJLPYLRIP-BMZHGHOISA-M 0.000 title claims abstract description 63
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- 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
- A61K8/55—Phosphorus compounds
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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- A—HUMAN NECESSITIES
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- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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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
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
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- 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
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- 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
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- 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
Landscapes
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- Emergency Medicine (AREA)
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- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate) 또는 피탄트리올(phytantriol)을 유효성분으로 포함하는 피부 미백용 조성물에 관한 것으로, 구체적으로 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물; 피부 미백 개선용 피부 외용제; 피부 미백 개선용 건강기능식품; 또는 피부 색소 침착의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a composition for skin whitening comprising sodium riboflavin phosphate or phytantriol as an active ingredient, specifically one selected from the group consisting of riboflavin phosphate sodium and phytantriol. A cosmetic composition for skin whitening comprising a compound or an acceptable salt thereof as an active ingredient; External preparations for skin whitening; Health functional food for skin whitening improvement; Or it relates to a pharmaceutical composition for the prevention or treatment of skin pigmentation.
Description
본 발명은 리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate) 또는 피탄트리올(phytantriol)을 유효성분으로 포함하는 피부 미백용 조성물에 관한 것으로, 구체적으로 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백용 화장료 조성물; 피부 미백 개선용 피부 외용제; 피부 미백 개선용 건강기능식품; 또는 피부 색소 침착의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a composition for skin whitening comprising sodium riboflavin phosphate or phytantriol as an active ingredient, specifically one selected from the group consisting of riboflavin phosphate sodium and phytantriol. A cosmetic composition for skin whitening comprising a compound or an acceptable salt thereof as an active ingredient; External preparations for skin whitening; Health functional food for skin whitening improvement; Or it relates to a pharmaceutical composition for the prevention or treatment 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.A person's skin color is genetically determined according to the concentration and distribution of melanin in the skin, but is also influenced by environmental or physiological conditions such as sun UV 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 세포 내 소기관에서 자외선으로부터 세포를 보호하는 기능을 가지는 멜라닌을 합성하고, 합성된 멜라닌은 멜라노사이트에서 각질형성세포(keratinocyte)로 이동하며, 이렇게 각질형성세포로 이동된 멜라닌이 피부색을 결정하는 것으로 알려져 있다.The chemical action of melanin production, which determines the color of the skin, has been reported many times through several papers, and melanocytes, melanocytes, protect cells from ultraviolet rays in the organelles called melanosomes. It is known to synthesize melanin having a function to perform, and the synthesized melanin moves from melanocytes to keratinocytes, and melanin transferred to keratinocytes determines skin color.
상기 멜라닌 생합성 과정에 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, and this tyrosine is converted to dihydroxyphenylalanine (DOPA), after which it is finally converted to melanin through a substance called dopaquinone. It is said to be. The melanin synthesized in this way makes the skin color darker, but studies on the skin whitening method to suppress the melanin synthesis and brighten the skin color due to health or cosmetic needs are actively being conducted.
일반적으로 알려진 미백 성분으로서, 코지산(Kojic acid) 또는 알부틴(Arbutin) 등과 같은 타이로시네이즈(tyrosinase) 활성을 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 component, substances that inhibit tyrosinase activity, such as kojic acid or arbutin, hydroquinone, vitamin C (L-Ascorbic acid), or these There are derivatives and various plant extracts. By inhibiting the synthesis of melanin pigments, they can not only realize skin whitening by brightening the skin tone, but also improve skin hyperpigmentation, such as ultraviolet rays, hormones, or freckles caused by genetics. However, when applying the skin, there is a problem in that there is a limitation in the amount of use due to safety problems such as irritation and redness, or the effect is insignificant, so that a practical effect cannot be expected.
한편, 리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate)은 분자식 C17H20N4NaO9P, 분자량 478.33을 가지는 화합물로서, NADH 탈수소효소(NADH dehydrogenase)를 포함한 여러 산화 효소의 보조효소로서 작용한다. 치아 미백 용도로 사용될 수 있음이 알려져 있으나, 리보플라빈 포스페이트 나트륨이 직접적으로 피부 미백 효과를 가지는 것에 대해서는 밝혀진 바가 없었다.On the other hand, sodium riboflavin phosphate (sodium riboflavin phosphate) is a compound having the molecular formula C 17 H 2 0N 4 NaO 9 P, molecular weight 478.33, and acts as a coenzyme of several oxidizing enzymes including NADH dehydrogenase. It is known that it can be used for teeth whitening, but it has not been found that riboflavin phosphate sodium has a direct skin whitening effect.
또한, 피탄트리올(phytantriol)은 분자식 C20H42O3, 분자량 330.553을 가지는 화합물로서, 손상된 모발을 보호하고 개선할 수 있음이 알려져 있으나, 피탄트리올이 직접적으로 피부 미백 효과를 가지는 것에 대해서는 밝혀진 바가 없었다.In addition, phytantriol (phytantriol) is a compound having a molecular formula C 20 H 42 O 3 , molecular weight 330.553, it is known that can protect and improve damaged hair, but for phytantriol has a direct skin whitening effect Nothing has been revealed.
이러한 배경하에서, 본 발명자들은 피부 미백 효과가 우수한 물질에 관하여 연구를 수행하였으며, 리보플라빈 포스페이트 나트륨 또는 피탄트리올을 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 these backgrounds, the present inventors have conducted research on substances with excellent skin whitening effects, and by examining that the composition comprising riboflavin phosphate sodium or phytantriol as an active ingredient exhibits an effect of inhibiting melanin synthesis and reducing a total amount of melanin, The cosmetic composition for skin whitening, skin external preparations, health functional foods, and pharmaceutical compositions for preventing or treating skin pigmentation have been completed.
본 발명의 하나의 목적은, 리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate) 및 피탄트리올(phytantriol)로 구성된 군에서 선택되는 1종의 화합물 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 화장료 조성물을 제공하는 것이다.One object of the present invention, a riboflavin phosphate sodium (sodium riboflavin phosphate) and phytantriol (phytantriol) selected from the group consisting of a compound or a cosmetic composition comprising a cosmetically acceptable salt thereof as an active ingredient Is to provide.
구체적으로, 본 발명의 목적은 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 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 one compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or a cosmetically acceptable salt thereof as an active ingredient.
또한 구체적으로, 본 발명의 목적은 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백 개선용 피부 외용제를 제공하는 것이다.In addition, specifically, the object of the present invention is to provide a skin external preparation for improving skin whitening, comprising as an active ingredient one compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or an acceptable salt thereof.
또한 구체적으로, 본 발명의 목적은 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 미백 개선용 건강기능식품을 제공하는 것이다.In addition, specifically, the object of the present invention is to provide a health functional food for improving skin whitening comprising as an active ingredient one kind of compound selected from the group consisting of sodium riboflavin phosphate and phytantriol or a food-pharmaceutically acceptable salt thereof. will be.
또한 구체적으로, 본 발명의 목적은 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In addition, specifically, the object of the present invention is a pharmaceutical composition for the prevention or treatment of skin pigmentation comprising one compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or a pharmaceutically acceptable salt thereof as an active ingredient. It is to provide a composition.
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.Specifically, it is as follows. Meanwhile, each description and embodiment disclosed in the present invention can be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in the present invention fall within the scope of the present invention. In addition, the scope of the present invention is not limited by the specific descriptions described below.
상기 목적을 달성하기 위한 본 발명의 하나의 양태는 리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate) 및 피탄트리올(phytantriol)로 구성된 군에서 선택되는 1종의 화합물 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 화장료 조성물을 제공한다.One aspect of the present invention for achieving the above object is a compound selected from the group consisting of sodium riboflavin phosphate (sodium riboflavin phosphate) and phytantriol (phytantriol) or a cosmetically acceptable salt thereof as an active ingredient It provides a cosmetic composition comprising.
[화학식 1][Formula 1]
본 발명에서 "리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate)"은 상기 화학식 1로 표시되고, 분자식 C17H20N4NaO9P, 분자량 478.33을 갖는다. NADH 탈수소효소(NADH dehydrogenase)를 포함한 여러 산화 효소의 보조효소로서 작용하며, 치아 미백 용도로 사용될 수 있음이 알려져 있으나, 리보플라빈 포스페이트 나트륨 자체의 피부 미백 효과에 대해서는 밝혀진 바가 없었다.In the present invention, "sodium riboflavin phosphate" is represented by Chemical Formula 1, and has a molecular formula C 17 H 2 0N 4 NaO 9 P, molecular weight 478.33. It is known that it acts as a coenzyme of several oxidizing enzymes, including NADH dehydrogenase, and can be used for tooth whitening, but the skin whitening effect of sodium riboflavin phosphate itself has not been revealed.
이때, 리보플라빈 포스페이트 나트륨의 화장품학적으로 허용 가능한 염의 구체적인 예로서, 리보플라빈-5'-포스페이트 나트륨염 2수화물(Riboflavin-5'-phosphate sodium salt dehydrate), 리보플라빈 나트륨 포스페이트(Riboflavin sodium phosphate), 리보플라빈-5'-포스페이트 나트륨염 수화물(Riboflavin 5'-phosphate sodium salt hydrate) 또는 리보플라빈 5'-1인산염 나트륨염(Riboflavin 5'-monophosphate sodium salt)일 수 있으나, 이에 제한되는 것은 아니다.At this time, as specific examples of cosmetically acceptable salts of sodium riboflavin phosphate, Riboflavin-5'-phosphate sodium salt dehydrate, Riboflavin sodium phosphate, Riboflavin sodium phosphate, Riboflavin-5 It may be '-phosphate sodium salt hydrate (Riboflavin 5'-phosphate sodium salt hydrate) or riboflavin 5'-1 phosphate sodium salt (Riboflavin 5'-monophosphate sodium salt), but is not limited thereto.
[화학식 2][Formula 2]
본 발명에서 "피탄트리올(phytantriol)"은 상기 화학식 2로 표시되고, 분자식 C20H42O3, 분자량 330.553을 가지며, 3,7,11,15-테트라메틸헥사데칸-1,2,3-트리올(3,7,11,15-Tetramethylhexadecane-1,2,3-triol) 또는 1,2,3-트리히드록시-3,7,11,15-테트라메틸헥사데칸( 1,2,3-Trihydroxy-3,7,11,15-tetramethylhexadecane) 등으로도 명명된다. 손상된 모발을 보호하고 개선할 수 있음이 알려져 있으나, 피탄트리올 자체의 피부 미백 효과에 대해서는 밝혀진 바가 없었다.In the present invention, "phytantriol (phytantriol)" is represented by the formula (2), has a molecular formula C 20 H 42 O 3 , molecular weight 330.553, 3,7,11,15-tetramethylhexadecane-1,2,3 -Triol (3,7,11,15-Tetramethylhexadecane-1,2,3-triol) or 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane (1,2, 3-Trihydroxy-3,7,11,15-tetramethylhexadecane). It is known that it can protect and improve damaged hair, but the skin whitening effect of phytantriol itself has not been revealed.
상기 리보플라빈 포스페이트 나트륨 및/또는 피탄트리올의 획득 방법은 특별히 한정되지 않으며, 당업계에 공지된 방법을 이용하여 화학적으로 합성하거나, 시판되는 물질을 사용할 수 있다.The method of obtaining the riboflavin phosphate sodium and / or phytantriol is not particularly limited, and chemically synthesized or commercially available materials may be used using methods known in the art.
본 발명의 화학식 1로 표시되는 리보플라빈 포스페이트 나트륨 및/또는 화학식 2로 표시되는 피탄트리올은 용매화된 형태뿐만 아니라 비-용매화된(unsolvated) 형태로 존재할 수도 있다. 본 발명의 리보플라빈 포스페이트 나트륨 및/또는 피탄트리올은 결정형 또는 무정형 형태로 존재할 수 있으며, 이러한 모든 물리적 형태는 본 발명의 범위에 포함된다.The riboflavin phosphate sodium represented by Chemical Formula 1 of the present invention and / or phytantriol represented by Chemical Formula 2 may exist in unsolvated form as well as solvated form. The riboflavin phosphate sodium and / or phytantriol of the present invention may exist in crystalline or amorphous form, and all such physical forms are included in the scope of the present invention.
구체적으로, 본 발명에 따른 조성물에 있어, 상기 리보플라빈 포스페이트 나트륨 또는 피탄트리올의 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 리보플라빈 포스페이트 나트륨 또는 피탄트리올의 함량은 조성물 전체 중량 대비 0.0001 내지 0.006 중량%일 수 있으며, 가장 구체적으로 0.002 내지 0.0004 중량%일 수 있으나, 이에 한정된 것은 아니다.Specifically, in the composition according to the present invention, the content of the riboflavin phosphate sodium or phytantriol 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 the riboflavin phosphate sodium or phytantriol may be 0.0001 to 0.006% by weight based on the total weight of the composition, and most specifically, it may be 0.002 to 0.0004% by weight, but is not limited thereto.
본 발명은 리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate) 및 피탄트리올(phytantriol)로 구성된 군에서 선택되는 1종의 화합물 또는 이의 화장품학적으로 허용 가능한 염을 포함하는 화장료 조성물을 제공한다. The present invention provides a cosmetic composition comprising one compound selected from the group consisting of sodium riboflavin phosphate and phytantriol or a cosmetically acceptable salt thereof.
또한, 구체적으로, 본 발명은 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 화장품학적으로 허용 가능한 염을 포함하는 피부 미백용 화장료 조성물을 제공할 수 있다.In addition, specifically, the present invention can provide a cosmetic composition for skin whitening comprising one compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or a cosmetically acceptable salt thereof.
본 발명에 있어서, "리보플라빈 포스페이트 나트륨" 및 "피탄트리올"은 상기에서 설명한 바와 같다.In the present invention, "riboflavin phosphate sodium" and "phytantriol" are as described above.
본 발명에 있어서, "화장품학적으로 허용 가능한 염"은 리보플라빈 포스페이트 나트륨 및/또는 피탄트리올이 다른 물질과 결합한 염의 형태인 것으로, 화장품학적으로 만니톨과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "cosmetically acceptable salt" is a form of a salt in which riboflavin phosphate sodium and / or phytantriol is combined with other substances, and refers to a substance that can exhibit cosmetic activity similar to mannitol.
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, the term "skin whitening" refers to not only brightening the skin tone by inhibiting the synthesis of melanin pigments, but also improving skin hyperpigmentation, such as ultraviolet rays, hormones or oil-induced freckles and freckles.
본 발명의 일 실시예에서는, 화학식 1 또는 2로 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 1 또는 2로 표시되는 화합물을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, after adding the compound represented by Formula 1 or 2 to the melanocytes of mice (B-16 mouse melanoma cells), as a result of measuring the total amount of melanin, excellent in the case of the experimental group to which the compound was added By showing the effect of reducing the total amount of melanin, it was confirmed that the composition comprising the compound represented by Formula 1 or 2 can be used as a cosmetic composition for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1 또는 2로 표시되는 화합물을 쥐의 멜라노마 세포에 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 1 또는 2로 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 inhibitory effect of tyrosinase activity at the cellular level by adding the compound represented by Formula 1 or 2 to the melanoma cells of rats, the compound is melamine in a concentration-dependent manner. It showed the effect of reducing tyrosinase activity of normal cells, and in particular, it was confirmed that it inhibits the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was confirmed that it can be used as a cosmetic composition for 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 is a solution, ointment for ointment, cream, foam, nutrient makeup, softening makeup, pack, softening water, emulsion, makeup base, essence, soap, liquid detergent, bathing agent, sunscreen cream, sun oil, suspension, 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 1종 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 formulated in general skin cosmetics, and for example, oils, water, surfactants, moisturizers, lower alcohols as common ingredients, Thickeners, chelating agents, pigments, preservatives, fragrances, etc. may be appropriately blended, but are 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, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these can 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, especially in the case of a spray, additional chloro And propellants such as fluorohydrocarbon, 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, solubilizing agent or emulsifying agent 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 can be used, in particular cottonseed oil, peanut oil, corn seed oil, olive oil, castor oil and sesame oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan. 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, liquid diluents such as water, ethanol or propylene glycol as carrier components, suspensions such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, micro Crystalline cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can 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 hydrolyzates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars, etc. may be used as carrier components. You can.
본 발명의 다른 하나의 양태는 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 미백 개선용 피부 외용제를 제공한다.Another aspect of the present invention provides a skin external preparation for improving skin whitening, comprising as an active ingredient one compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or an acceptable salt thereof.
본 발명에 있어서, "리보플라빈 포스페이트 나트륨" 및 "피탄트리올"은 상기에서 설명한 바와 같다.In the present invention, "riboflavin phosphate sodium" and "phytantriol" are as described above.
본 발명에 있어서, "허용 가능한 염"이란, 리보플라빈 포스페이트 나트륨 및/또는 피탄트리올이 다른 물질과 결합한 염의 형태인 것으로, 리보플라빈 포스페이트 나트륨 및/또는 피탄트리올과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "acceptable salt" means a substance in which riboflavin phosphate sodium and / or phytantriol is in the form of a salt in combination with other substances, and exhibits similar activity to sodium riboflavin phosphate and / or phytantriol. do.
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 skin preparation" of the present invention is a comprehensive concept including generally used substances for external application of skin, non-limiting examples of external preparations for skin include PLASTERS, LOTIONS, and linement agents. (LINIMENTS), LIQUIDS AND SOLUTIONS, Aerosols, AEROSOLS, EXTRACTS, OINTMENTS, FLUIDEXTRACTS, Emulsions, Suspension Agents, Capsules (CAPSULES) , Creams (CREAMS), soft, hard gelatin capsules, patches, or sustained release agents.
본 발명의 일 실시예에서는, 화학식 1 또는 2로 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 1 또는 2로 표시되는 화합물을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, after adding the compound represented by Formula 1 or 2 to the melanocytes of mice (B-16 mouse melanoma cells), as a result of measuring the total amount of melanin, excellent in the case of the experimental group to which the compound was added By showing the effect of reducing the total amount of melanin, it was confirmed that the composition comprising the compound represented by Formula 1 or 2 can be used as a cosmetic composition for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1 또는 2로 표시되는 화합물을 쥐의 멜라노마 세포에 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 1 또는 2로 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 inhibitory effect of tyrosinase activity at the cellular level by adding the compound represented by Formula 1 or 2 to the melanoma cells of rats, the compound is melamine in a concentration-dependent manner. It showed the effect of reducing tyrosinase activity of normal cells, and in particular, it was confirmed that it inhibits the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was confirmed that it can be used as a cosmetic composition for 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 dosage form formulated in a solid, semi-solid or liquid form by adding a commercially available 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, but is not limited thereto.
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. Carriers, excipients and diluents that may be included in the external preparation include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, 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 by each formulation, other ingredients other than the composition of the present invention described above can be appropriately selected and blended without difficulty by those skilled in the art according to the formulation or purpose of use of the external application for skin, in this case, applied simultaneously with other raw materials If you do, a synergistic effect can occur.
본 발명의 또 다른 하나의 양태는 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 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 as an active ingredient one compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or a pharmaceutically acceptable salt thereof. do.
본 발명에 있어서, "리보플라빈 포스페이트 나트륨" 및 "피탄트리올"은 상기에서 설명한 바와 같다.In the present invention, "riboflavin phosphate sodium" and "phytantriol" are 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 food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills, etc. using ingredients or ingredients having useful functionality for the human body. Here, the term "functional" means to obtain a useful effect for health use, such as adjusting nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be manufactured by a method conventionally used in the art, and may be prepared by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as a health functional food. The health functional food of the present invention can be manufactured in various types of dosage forms, and has the advantage of not having side effects that may occur when taking the drug for a long time using food as a raw material, unlike general drugs, and has excellent portability. Can be consumed as a supplement to enhance the skin whitening effect.
본 발명의 일 실시예에서는, 화학식 1 또는 2로 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 1 또는 2로 표시되는 화합물을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, after adding the compound represented by Formula 1 or 2 to the melanocytes of mice (B-16 mouse melanoma cells), as a result of measuring the total amount of melanin, excellent in the case of the experimental group to which the compound was added By showing the effect of reducing the total amount of melanin, it was confirmed that the composition comprising the compound represented by Formula 1 or 2 can be used as a cosmetic composition for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1 또는 2로 표시되는 화합물을 쥐의 멜라노마 세포에 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 1 또는 2로 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 inhibitory effect of tyrosinase activity at the cellular level by adding the compound represented by Formula 1 or 2 to the melanoma cells of rats, the compound is melamine in a concentration-dependent manner. It showed the effect of reducing tyrosinase activity of normal cells, and in particular, it was confirmed that it inhibits the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was confirmed that it can be used as a cosmetic composition for 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 components. The aforementioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, synthetic sweeteners such as saccharin and aspartame can 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, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonated agents used in carbonated beverages. These ingredients can be used independently or in combination. The proportion of these additives is not critical, but is generally selected from 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 리보플라빈 포스페이트 나트륨 및 피탄트리올로 구성된 군에서 선택되는 1종의 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는, 피부 색소 침착의 예방 또는 치료용 약학적 조성물을 제공한다.Another aspect of the present invention comprises a compound selected from the group consisting of riboflavin phosphate sodium and phytantriol or a pharmaceutically acceptable salt thereof as an active ingredient, a pharmaceutical for preventing or treating skin pigmentation Provides a composition.
본 발명에 있어서, "리보플라빈 포스페이트 나트륨" 및 "피탄트리올"은 상기에서 설명한 바와 같다.In the present invention, "riboflavin phosphate sodium" and "phytantriol" are as described above.
본 발명에 있어서, "약학적으로 허용 가능한 염"이란 리보플라빈 포스페이트 나트륨 및/또는 피탄트리올이 다른 물질과 결합한 염의 형태인 것으로, 약학적으로 만니톨과 비슷한 활성을 나타낼 수 있는 물질을 의미한다.In the present invention, "a pharmaceutically acceptable salt" is a form of a salt in which riboflavin phosphate sodium and / or phytantriol is combined with other substances, and refers to a substance capable of exhibiting pharmacologically similar activity to mannitol.
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 hyperpigmentation macules caused by increased melanin in the skin, nails, mucous membranes surrounding the oral cavity or nasal cavity, and is also referred to as hyperpigmentation.
본 발명의 일 실시예에서는, 화학식 1 또는 2로 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 1 또는 2로 표시되는 화합물을 포함하는 조성물은 피부 미백용 화장료 조성물로 사용될 수 있음을 확인하였다(표 1).In one embodiment of the present invention, after adding the compound represented by Formula 1 or 2 to the melanocytes of mice (B-16 mouse melanoma cells), as a result of measuring the total amount of melanin, excellent in the case of the experimental group to which the compound was added By showing the effect of reducing the total amount of melanin, it was confirmed that the composition comprising the compound represented by Formula 1 or 2 can be used as a cosmetic composition for skin whitening (Table 1).
또한, 본 발명의 다른 일 실시예에서는, 화학식 1 또는 2로 표시되는 화합물을 쥐의 멜라노마 세포에 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 1 또는 2로 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 inhibitory effect of tyrosinase activity at the cellular level by adding the compound represented by Formula 1 or 2 to the melanoma cells of rats, the compound is melamine in a concentration-dependent manner. It showed the effect of reducing tyrosinase activity of normal cells, and in particular, it was confirmed that it inhibits the activity of tyrosinase even at a concentration lower than that of arbutin used as a positive control. It was confirmed that it can be used as a cosmetic composition for whitening (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, intravenous solutions, emulsions, syrups, aerosols, sterile injectable solutions, etc. in accordance with conventional methods for preventing and treating skin pigmentation Formulation is possible.
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. These solid preparations are prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. Can be. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used diluents, various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc. 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 solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like. Vegetable oils such as propylene glycol, polyethylene glycol, olive oil, and injectable esters such as ethyl oleate may be used as the non-aqueous solvent and suspension solvent.
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 include a carrier, excipient or diluent. As carrier, excipient or diluent, lactose, textrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxy Mineral oils such as propyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, flopilhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, silicon dioxide, etc. 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, the degree of the disease, the type of drug, the route and duration of administration, the rate of excretion, and the response sensitivity It can 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 through various routes to mammals such as rats, mice, livestock, and humans. Any mode of administration can be envisaged and can be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.
본 발명의 리보플라빈 포스페이트 나트륨 또는 피탄트리올을 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, 리보플라빈 포스페이트 나트륨 또는 피탄트리올을 유효성분으로 포함하는 조성물은 피부 미백용 화장료 조성물, 피부 미백용 피부 외용제 또는 건강기능식품 등으로 유용하게 사용될 수 있다.The composition comprising the riboflavin phosphate sodium or phytantriol of the present invention as an active ingredient was confirmed to have an effect of reducing the total amount of melanin in the cell by inhibiting melanin synthesis, in particular, melanin even at a lower concentration than arbutin used as a positive control Since it can inhibit the synthesis, a composition comprising riboflavin phosphate sodium or phytantriol as an active ingredient may be useful 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
리보플라빈 포스페이트 나트륨(sodium riboflavin phosphate) 또는 피탄트리올(phytantriol)을 마우스의 B-16 멜라노마 세포(B-16 mouse melanoma cell)의 배양액에 첨가하여 세포 수준에서의 미백 효과를 실험하고자 하였다.It was intended to test the whitening effect at the cell level by adding sodium riboflavin phosphate or phytantriol to the culture medium of mouse B-16 mouse melanoma cells.
구체적으로, 배양액을 기준으로 리보플라빈 포스페이트 나트륨 또는 피탄트리올의 최종농도가 10 ㎍/㎖, 20 ㎍/㎖이 되도록 배지에 첨가하였으며, 양성 대조군인 알부틴은 100 ㎍/㎖의 농도로 배지에 첨가하였다. 음성 대조군은 배지에 추가적인 시료를 첨가하지 않았다. Specifically, based on the culture medium, riboflavin phosphate sodium or phytantriol was added to the medium so that the final concentrations were 10 µg / ml and 20 µg / ml, and the positive control arbutin was added to the media at a concentration of 100 µg / ml. . The negative control did not add additional samples to the medium.
상기 각각의 배지에서 B-16 멜라노마 세포를 3일간 배양한 후, 배양된 세포에 트립신(trypsin)을 처리하여 배양용기로부터 분리하여 원심분리하였다. 원심분리한 세포로부터 멜라닌을 추출하였으며, 구체적으로, 분리된 세포에 수산화 나트륨 용액(1N 농도) 1 ㎖를 첨가하고 10분간 가열하여 멜라닌을 녹이고, 분광 광도계를 이용하여 400 나노미터(nm)에서 흡광도를 측정하여 생성된 멜라닌의 양을 측정하였다. After incubating B-16 melanoma cells in each medium for 3 days, the cultured cells were treated with trypsin to separate from the culture vessel and centrifuged. Melanin was extracted from the centrifuged cells, 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 표 1에 정리하였다.The amount of melanin was measured to show the unit cell allowance (10 6 cell) absorbance, and the results of calculating the relative inhibition rate (%) of the total amount of melanin in the negative control group are summarized in Table 1 below.
(10 ㎍/㎖)Riboflavin phosphate sodium
(10 μg / ml)
(20 ㎍/㎖)Riboflavin phosphate sodium
(20 μg / ml)
그 결과, 상기 표 1에서 볼 수 있듯이, 리보플라빈 포스페이트 나트륨 및 피탄트리올은 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 shown in Table 1, it was confirmed that riboflavin phosphate sodium and phytantriol have an effect of inhibiting melanin synthesis by reducing the melanin total amount of melanoma cells in a concentration-dependent manner, in particular, as a positive control. It was confirmed that it has the effect of inhibiting the synthesis of melanin even at a lower concentration than the obtained arbutin, thereby reducing the total amount of melanin.
따라서, 리보플라빈 포스페이트 나트륨 및 피탄트리올은 멜라닌 합성을 저해하여 멜라닌 총량을 감소시켜, 피부 미백 용도로 사용될 수 있음을 알 수 있었다.Therefore, it was found that riboflavin phosphate sodium and phytantriol inhibit melanin synthesis, thereby reducing the total amount of melanin, and thus can be used for skin whitening applications.
실시예Example 2: 2: 타이로시네이즈Tyrosinase (( tyrosinasetyrosinase ) 활성 감소 확인) Check for reduced activity
만니톨을 마우스의 B-16 멜라노마 세포(B-16 mouse melanoma cell)의 배양액에 첨가하여 세포 수준에서의 타이로시네이즈 활성 저해 효과를 실험하고자 하였다.The mannitol was added to the culture medium of B-16 mouse melanoma cells to test the inhibitory effect of tyrosinase activity at the cell level.
구체적으로, 배양액을 기준으로 만니톨의 최종농도가 10 ㎍/㎖, 20 ㎍/㎖이 되도록 배지에 첨가하였으며, 양성 대조군인 알부틴은 100 ㎍/㎖의 농도로 배지에 첨가하였다. 음성 대조군은 배지에 추가적인 시료를 첨가하지 않았다.Specifically, based on the culture medium, the final concentration of mannitol was added to the medium such that 10 µg / ml and 20 µg / ml, and the positive control arbutin was added to the medium at a concentration of 100 µg / ml. The negative control did not add additional samples to the medium.
상기 각각의 배지에서 B-16 멜라노마 세포를 3일간 배양한 후, 배양된 세포에 트립신(trypsin)을 처리하여 배양용기로부터 분리하여 원심분리하였다. 원심분리한 세포를 세포 용해액(1% triton-100 및 0.1% PMSF가 포함된 0.1M phosphate buffer)에 용해시켰고, 1mM의 도파(DOPA, dihydroxyphenylalanine)를 섞어 1시간 동안 37℃에서 반응시켰다. 이후 분광 광도계를 이용하여 475 나노미터(nm)에서 흡광도를 측정하여 타이로시네이즈의 활성 정도를 측정하였다. After incubating B-16 melanoma cells in each medium for 3 days, the cultured cells were treated with trypsin to separate from the culture vessel and centrifuged. The centrifuged cells were lysed in a cell lysate (0.1M phosphate buffer containing 1% triton-100 and 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 표 2에 정리하였다.The activity level of the tyrosinase was measured to be expressed in unit cell allowance (10 6 cell) absorbance, and the results of calculating the relative inhibition rate (%) for the activity of the tyrosinase in the negative control group are summarized in Table 2 below. Did.
(10 ㎍/㎖)Riboflavin phosphate sodium
(10 μg / ml)
(20 ㎍/㎖)Riboflavin phosphate sodium
(20 μg / ml)
그 결과, 상기 표 2에서 볼 수 있듯이, 리보플라빈 포스페이트 나트륨 및 피탄트리올은 농도 의존적으로 멜라노마 세포의 타이로시네이즈의 활성을 감소시키는 효과가 있음을 확인하였으며, 특히, 양성 대조군으로 사용된 알부틴보다 낮은 농도에서도 타이로시네이즈의 활성을 저해하여, 결과적으로 멜라닌 총량을 감소시키는 효능을 가짐을 확인하였다.As a result, as shown in Table 2, it was confirmed that riboflavin phosphate sodium and phytantriol have an effect of reducing the activity of tyrosinase of melanoma cells in a concentration-dependent manner, in particular, arbutin used as a positive control. Even at a lower concentration, it inhibited the activity of tyrosinase, and as a result, it was confirmed that it has an effect of reducing the total amount of melanin.
따라서, 리보플라빈 포스페이트 나트륨 및 피탄트리올은 멜라노마 세포의 멜라닌 총량을 감소시킬 뿐만 아니라, 멜라닌 합성과 관련된 효소인 타이로시네이즈의 활성을 저해함을 확인함으로써, 리보플라빈 포스페이트 나트륨 및 피탄트리올의 우수한 피부 미백 용도를 재확인하였다.Thus, by confirming that riboflavin phosphate sodium and phytantriol not only reduce the total amount of melanin in melanoma cells, but also inhibit the activity of tyrosinase, an enzyme involved in melanin synthesis, excellent riboflavin phosphate sodium and phytantriol The skin whitening use 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 implemented in other specific forms without changing its technical spirit or essential characteristics. 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 including all changes or modifications derived from the meaning and scope of the following claims rather than the above detailed description and equivalent concepts thereof.
Claims (7)
Cosmetic composition for skin whitening comprising one compound selected from the group consisting of sodium riboflavin phosphate and phytantriol or a cosmetically acceptable salt thereof as an active ingredient.
According to claim 1, The composition is to inhibit the synthesis of melanin, to reduce the total amount of melanin, or to inhibit the activity of tyrosinase (tyrosinase), cosmetic composition.
The composition according to any one of claims 1 to 3, wherein the composition is a solution, cream, foam, nutrient makeup, softening makeup, pack, softening water, makeup base, essence, liquid cleaning agent, bathing agent, sunscreen cream, sun oil , Suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, having a formulation selected from the group consisting of patch and spray Cosmetic composition.
A skin external preparation for improving skin whitening, comprising one compound selected from the group consisting of sodium riboflavin phosphate and phytantriol or a pharmaceutically acceptable salt thereof as an active ingredient.
A health functional food for improving skin whitening, comprising as an active ingredient one compound selected from the group consisting of sodium riboflavin phosphate and phytantriol or a food-pharmaceutically acceptable salt thereof.
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