KR101832415B1 - Cosmetic composition for skin whitening comprising retinoids derivative as active ingredient - Google Patents
Cosmetic composition for skin whitening comprising retinoids derivative as active ingredient Download PDFInfo
- Publication number
- KR101832415B1 KR101832415B1 KR1020110109760A KR20110109760A KR101832415B1 KR 101832415 B1 KR101832415 B1 KR 101832415B1 KR 1020110109760 A KR1020110109760 A KR 1020110109760A KR 20110109760 A KR20110109760 A KR 20110109760A KR 101832415 B1 KR101832415 B1 KR 101832415B1
- Authority
- KR
- South Korea
- Prior art keywords
- cosmetic composition
- skin
- present
- skin whitening
- melanin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000002537 cosmetic Substances 0.000 title claims abstract description 24
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- 150000004492 retinoid derivatives Chemical class 0.000 claims abstract description 30
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Classifications
-
- 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
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Cosmetics (AREA)
Abstract
본 발명은 레티노이드 유도체를 유효성분으로 함유하는 피부 미백용 화장료 조성물을 제공한다. 본 발명의 레티노이드 유도체는 티로시나제 활성 억제 효과 및 멜라닌 합성 억제 효과가 뛰어나, 피부 미백용 화장료 조성물로 유용하게 이용될 수 있다. The present invention provides a skin whitening cosmetic composition containing a retinoid derivative as an active ingredient. The retinoid derivatives of the present invention are excellent in an effect of suppressing tyrosinase activity and an effect of inhibiting melanin synthesis, and can be usefully used as a cosmetic composition for skin whitening.
Description
본 발명은 레티노이드 유도체를 유효성분으로 함유하는 피부 미백용 화장료 조성물에 관한 것이다. The present invention relates to a cosmetic composition for skin whitening comprising a retinoid derivative as an active ingredient.
피부는 외부 환경과 직접 접하면서 인체를 보호하며 생화학적이고 물리적인 기능이 있는 아주 중요한 조직으로, 크게 3가지 즉, 표피(epidermis), 진피(dermis), 그리고, 피하(hypodermis)로 나누어진다.Skin is a very important tissue with direct contact with the external environment and has a biochemical and physical function. It is divided into three parts: epidermis, dermis, and hypodermis.
멜라닌은 피부의 표피층에 존재하는 색소로서, 표피의 기저층에 존재하는 멜라노사이트(melanocyte)로부터 만들어져 케라티노사이트(keratinocyte)라는 표피 세포로 이동한다. 생체 내에는 멜라닌을 분해하는 효소가 없고, 다만 케라티노사이트가 표피에서 떨어져 나갈 때 같이 피부에서 떨어져 나가는 것으로 제거된다.Melanin is a pigment present in the epidermis of the skin. It is made from melanocytes in the basal layer of the epidermis and migrates to epidermal cells called keratinocytes. In vivo, there is no enzymes that degrade melanin, but keratinocytes are removed from the skin as they fall off the epidermis.
멜라닌 합성 과정을 살펴보면, 멜라노사이트 내의 멜라노좀이라는 소포체에서 먼저 티로시나제(Tyrosinase)라는 효소에 의해 타이로신이 도파(DOPA)를 거쳐 도파퀴논(dopaquinone)으로 전환되고, 도파퀴논으로부터 자동 산화반응과 효소 반응으로 도파크롬(dopachrome)을 거쳐 흑갈색의 공중합체인 멜라닌이 생성된다. 이렇게 생성된 멜라닌은 멜라노좀을 통해 케라티노사이트로 옮겨지고 여기에서 약 28일간의 각화 과정을 거치면서 피부 표면으로 나와 각질과 함께 소실된다. In melanosome synthesis, tyrosine is first converted to dopaquinone via dopase (DOPA) by an enzyme called tyrosinase in the melanosome called ERA in melanocytes, and then by autoxidation and enzymatic reaction from dopaquinone Melanin, which is a dark brown copolymer, is produced through dopachrome. The resulting melanin is transferred to the keratinocyte through melanoma, and after about 28 days of keratinization, it exits the skin surface and disappears with the keratinocytes.
멜라닌은 햇빛 UV의 빛 에너지를 흡수하여 UV에 의한 손상으로부터 진피 이하의 피부 기관을 보호하는 역할을 하며, 피부 생체 내에 생겨난 유해산소 및 프리 라디칼 등을 잡아주는 등 외부 유해인자로부터 피부를 보호해주는 유용한 역할을 수행한다. 또한, 피부 세포 내의 멜라닌 양에 따라 사람의 피부색을 결정된다. Melanin absorbs the light energy of sunlight UV and protects the subcutaneous skin organs from UV damage. It also helps protect the skin from external harmful factors such as harmful oxygen and free radicals generated in the skin. Role. In addition, the skin color of a person is determined according to the amount of melanin in the skin cells.
멜라닌 색소가 많은 사람은 갈색 또는 검은 색 피부를 갖는 반면, 멜라닌 색소가 적은 사람은 흰색의 피부를 갖게 된다. 그러나 멜라닌이 비정상적으로 적게 생산되면 백반증과 같은 피부병변이 유발되고, 반대로 일광, 호르몬변화, 염증, 약제 등에 의해 멜라닌이 과도하게 합성되거나 각화작용이 원활히 이루어지지 않아 멜라닌이 완전히 없어지지 않으면 피부에 손상을 준다. 뿐만 아니라 피부의 색소가 침착되어 기미, 주근깨를 형성하며, 이와 같은 병변으로부터 나아가 피부암의 원인이 되기도 한다. 따라서, 이러한 색소 침착 현상을 방지하기 위해서는 멜라닌 생성 과정의 일부분을 저해하여 멜라닌의 생성을 감소시켜야 한다.People with high melanin pigment have brown or black skin while those with low melanin pigment have white skin. However, abnormal production of melanin causes skin lesions such as vitiligo. On the other hand, when melanin is not completely eliminated due to excessive synthesis of melanin due to sunlight, hormonal changes, inflammation, give. In addition, pigmentation of the skin is deposited, forming spots and freckles, and it also causes skin cancer from such lesions. Therefore, in order to prevent such pigment deposition phenomenon, it is necessary to inhibit a part of the melanin production process to reduce the production of melanin.
현재 피부미용을 위한 미백제의 개발에 있어서, 생성된 멜라닌 색소를 환원시켜 탈색하는 방법과 멜라닌 색소를 형성하는 효소인 티로시나제의 활성을 억제하는 방법이 알려져 있다. 그러나 멜라닌 색소를 환원시키기 위해 사용되는 토코페롤이나 비타민류 등을 사용한 미백제는 멜라닌 색소의 탈색효과가 미미한 것으로 알려져 있다. 따라서 티로시나제의 활성을 저해시킴으로써 멜라닌 색소의 생성을 억제하는 저해제가 주목받고 있다.Currently, in the development of a whitening agent for skin cosmetics, there is known a method of decolorizing by reducing the produced melanin pigment and a method of inhibiting the activity of tyrosinase, an enzyme that forms a melanin pigment. However, it is known that the whitening agent using tocopherol, vitamins and the like, which is used for reducing the melanin pigment, has little discoloration effect of the melanin pigment. Accordingly, inhibitors that inhibit the production of melanin pigment by attenuating the activity of tyrosinase have been attracting attention.
종래의 화장품 분야에서는 미백 성분으로서, 예를 들면, 코지산(Kojic acid), 알부틴(Arbutin) 등과 같은 티로시나제 효소활성을 억제하는 물질, 하이드로퀴논(Hydroquinone), 비타민-C(L-Ascorbic acid) 및 이들의 유도체와 각종 식물 추출물이 사용되어 왔다.In the field of the conventional cosmetics, as a whitening component, for example, substances inhibiting tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, L-ascorbic acid, Derivatives thereof and various plant extracts have been used.
그러나, 안정성이 나빠 분해되어 착색되거나, 이취의 발생, 생체 레벨에서의 효능, 효과의 불분명 및 안전성 문제 등으로 그 사용이 제한되고 있는 실정이다. 코지산은 티로시나제의 활성부위에 존재하는 구리 이온을 흡착시켜 효소활성을 저해하지만, 화장품에 배합 시 불안정성, 피부 부작용의 문제 및 최근 동물실험 결과 간암유발이 밝혀져 화장품 원료로 사용이 중지되었다. 비타민-C 및 그 유도체는 산화가 잘되는 불안정성 때문에 화장품 원료로서 사용이 어려우며, 하이드로퀴논은 피부에 대한 미백효과는 탁월하지만 알레르기를 유발하는 성질, 멜라닌 생성 세포에 대한 독성, 피부에의 영구 탈색화 등 피부에 대한 자극성이 높으며, 최근 발암성 물질로 규정되어 사용이 금지되어 각 나라별로 제한적인 농도만 허가하고 있다.However, the use thereof is limited due to poor stability and coloration, generation of odor, efficacy at a living body level, unclear effect, and safety problem. Kojisan inhibits the enzyme activity by adsorbing copper ions present in the active site of tyrosinase, but when used in cosmetics, instability, problems of skin side effects, and recent animal tests have revealed that liver cancer has been caused and the use of cosmetic ingredients has been discontinued. Vitamin-C and its derivatives are difficult to use as a raw material for cosmetics because of its good oxidative instability. Hydroquinone has excellent whitening effect on skin, but it has allergic properties, toxicity to melanin-producing cells, permanent decolorization to skin It is highly irritating to the skin. It has recently been prescribed as a carcinogenic substance and its use is prohibited.
또한, 알부틴은 하이드로퀴논에 글루코피라노사이드(Glucopyranoside)가 결합된 유도체로 하이드로퀴논 사용 시 나타나는 부작용이 적으면서 인체에 대한 독성은 없이 멜라닌 색소의 합성을 억제하는 작용이 있어, 멜라닌 색소 침착이 증가되는 피부질환의 치료제로서 이용가능성이 제시되었으나, 피부효소에 의해 일부 분해되는 단점이 있다. 따라서 이제까지의 미백제 보다 효능이 뛰어나고 좀 더 안전한 미백제를 개발하는 것이 절실한 실정이다.In addition, arbutin is a derivative in which hydroquinone is conjugated with glucopyranoside. As a result, hydroquinone is less toxic to human body, and inhibits the synthesis of melanin pigment, resulting in an increase in melanin pigmentation However, it is disadvantageous in that it is partially decomposed by skin enzymes. Therefore, it is urgent to develop a whitening agent that is more effective than the whitening agent so far and more safe.
한편, 레티노이드(비타민A)는 피부노화, 피부 주름 개선을 위한 화장료로 잘 알려져 있으며, 주로 사용되는 레티노이드는 레티놀 (Retinol: Vitamin A alcohol), 레티날 (Retinal: Vitamin A aldehyde), 레티닐 에스테르의 일종인 레티닐 아세테이트 (Retinyl acetate), 레티닐 프로피오네이트(Retinyl propionate), 레티닐 리놀리에이트 (Retinyl linoleate) 및 레티닐 팔미테이트 (Retinyl palmitate) 등이 있다. On the other hand, retinoids (vitamin A) are well known as cosmetics for skin aging and skin wrinkle improvement. The main retinoids are retinol (Vitamin A alcohol), retinal (Vitamin A aldehyde), retinyl ester Retinyl acetate, retinyl propionate, retinyl linoleate, and retinyl palmitate, which are one kind, are available.
이러한 레티노이드의 피부 자극, 제형의 불안정성과 같은 문제점을 해결하기 위해 개발된 신규한 레티노이드 유도체에 관한 것으로, 대한민국 특허등록 제10-0556037호는 콜라겐 합성 촉진, 항산화, 티로시나아제 활성 저해, 미백, 피부 주름 개선 효과를 갖는 레티놀 유도체를 제안하고 있다. The present invention relates to a novel retinoid derivative which is developed for solving such problems as skin irritation and instability of a retinoid. Korean Patent Registration No. 10-0556037 discloses a novel retinoid derivative which is effective for promoting collagen synthesis, antioxidation, inhibition of tyrosinase activity, A retinol derivative having a wrinkle-improving effect is proposed.
본 발명자들은 우수한 미백효과를 나타내면서도 부작용이 없는 새로운 미백제를 제공하기 위하여 노력한 결과, 신규한 레티노이드 유도체가 티로시나제의 활성을 저해하고 멜라닌 생성을 효과적으로 억제할 수 있음을 발견하고 본 발명을 완성하게 되었다.The present inventors have made efforts to provide a novel whitening agent exhibiting excellent whitening effect and no side effect, and as a result, found that a novel retinoid derivative can inhibit the activity of tyrosinase and effectively inhibit melanin production, and have completed the present invention.
본 발명의 과제는 피부 흑화 과정에 관여하는 티로시나제를 억제함과 아울러 멜라닌 생성을 억제하여 피부 미백 효과가 뛰어난 피부 미백용 화장료 조성물을 제공하는 것이다. The present invention provides a cosmetic composition for skin whitening which is capable of inhibiting tyrosinase involved in the skin darkening process and inhibiting melanin production and having an excellent skin whitening effect.
이를 위해 본 발명은 하기 화학식 1의 레티노이드 유도체를 유효성분으로 함유하는 피부 미백용 화장료 조성물을 제공한다:To this end, the present invention provides a cosmetic composition for skin whitening comprising a retinoid derivative represented by the following formula (1) as an active ingredient:
[화학식 1][Chemical Formula 1]
(상기 식에서, (Wherein,
R1 및 R2는 서로 같거나 다르며 수소 또는 C1~C6의 직쇄 또는 측쇄형의 알킬기이다.)R 1 and R 2 are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.
본 발명에 따른 레티노이드 유도체는 멜라닌 합성 저해 및 티로시나제 활성을 효과적으로 저해하므로, 이를 유효성분으로 함유하는 화장료는 기미나 주근깨 개선 및 피부미백에 매우 유용하다.Since the retinoid derivative according to the present invention effectively inhibits melanin synthesis inhibition and tyrosinase activity, the cosmetic composition containing the same as an effective ingredient is very useful for improvement of spots, freckles and skin whitening.
도 1은 본원발명의 실시예에 따른 1,5-비스 레틴아미도 2-메틸 펜탄 처리농도에 따른 멜라닌 생성량을 나타낸 그래프이다.
도 2는 본원발명의 실시예에 따른 1,5-비스 레틴아미도 2-메틸 펜탄 처리농도에 따른 티로시나제 활성을 나타낸 그래프이다. 1 is a graph showing the amount of melanin produced according to the concentration of 1,5-bis-retinamido 2-methylpentane treatment according to an embodiment of the present invention.
2 is a graph showing tyrosinase activity according to 1,5-bis-retinamido 2-methylpentane treatment concentration according to an embodiment of the present invention.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명에 따른 피부 미백용 화장료 조성물에 유효 성분으로 함유되는 레티노이드 유도체는 하기 화학식 1의 구조를 가진다.The retinoid derivative contained as an active ingredient in the cosmetic composition for skin whitening according to the present invention has a structure represented by the following formula (1).
[화학식 1][Chemical Formula 1]
(상기 식에서, (Wherein,
R1 및 R2는 서로 같거나 다르며 수소 또는 C1~C6의 직쇄 또는 측쇄형의 알킬기이다.)R 1 and R 2 are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.
더욱 바람직하게는 상기 화학식 1에서 R1은 메틸기이고 R2는 수소이다.
More preferably, R 1 in the general formula ( 1) is a methyl group and R 2 is Hydrogen.
본 발명에 따른 상기 화학식 1의 레티노이드 유도체는 하기 기재된 방법에 따라 제조될 수 있다.The retinoid derivatives of Formula 1 according to the present invention can be prepared according to the methods described below.
첫번째 제조방법으로서, Y가 히드록시인 하기 화학식 2의 화합물을 용매 중에서 축합제 및 유기 아민 촉매의 존재 하에 하기 화학식 3의 화합물과 반응시켜 레티노이드 유도체를 얻을 수 있다.As a first preparation method, a compound of formula (2) wherein Y is hydroxy can be reacted with a compound of formula (3) in the presence of a condensing agent and an organic amine catalyst in a solvent to obtain a retinoid derivative.
[화학식 2](2)
[화학식 3](3)
(상기 식에서,(Wherein,
Y는 히드록시 또는 할로겐이고,Y is hydroxy or halogen,
R1 및 R2는 서로 같거나 다르며 수소 또는 C1~C6의 직쇄 또는 측쇄형의 알킬기이다.)R 1 and R 2 are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.
이때, 축합제로 N,N,N',N'-테트라메틸-(벤조트리아졸-1-일)-우로니움테트라플루오로보레이트(TBTU), N-(3-디메틸아미노프로필)-N'-에틸-카보디이미드(EDC), N,N'-디이소프로필카보디이미드(DIC) 또는 N,N‘-디사이클로헥실카보디이미드(DCC)을 사용할 수 있으나, 이에 한정되는 것은 아니다. N, N ', N'-tetramethyl- (benzotriazol-1-yl) -uronium tetrafluoroborate (TBTU) and N- (3-dimethylaminopropyl) -N' But are not limited to, ethyl-carbodiimide (EDC), N, N'-diisopropylcarbodiimide (DIC) or N, N'-dicyclohexylcarbodiimide (DCC).
또한, 축합반응을 촉진시키는 유기아민 촉매로는 디이소프로필에틸아민(DIPEA) 또는 4-디메틸아미노피리딘(DMAP)을 사용할 수 있으나 이에 한정되는 것은 아니다. 용매로는 무수 유기용매, 예를 들어 디클로로메탄, 벤젠, 톨루엔, 테트라하이드로푸란 및 디에틸에테르 중에서 선택된 1종 이상을 사용할 수 있으나, 이에 한정되는 것은 아니다. 반응은 통상 질소 대기 하에서 빛과 수분이 차단된 상태로 진행되는 것이 바람직하며, 냉각 내지 가온된 상태에서 진행될 수 있다.
As the organic amine catalyst for promoting the condensation reaction, diisopropylethylamine (DIPEA) or 4-dimethylaminopyridine (DMAP) may be used, but the present invention is not limited thereto. As the solvent, at least one selected from anhydrous organic solvents such as dichloromethane, benzene, toluene, tetrahydrofuran and diethyl ether may be used, but the present invention is not limited thereto. The reaction is preferably carried out in a state where light and moisture are blocked under a nitrogen atmosphere, and the reaction may proceed in a cooled or warmed state.
다른 방법으로서, Y가 할로겐인 상기 화학식 2의 화합물을 용매 중에서 유기 아민의 존재 하에 상기 화학식 3의 화합물과 반응시킴으로써 제조할 수 있다.Alternatively, the compound of formula (2) wherein Y is halogen can be prepared by reacting the compound of formula (3) in the presence of an organic amine in a solvent.
이때 염기로 작용하는 유기아민으로 피리딘 또는 트리에틸아민을 사용할 수 있으나 이에 한정되는 것은 아니다. 용매로는 무수 유기용매, 예를 들어 디클로로메탄, 벤젠, 톨루엔, 테트라하이드로푸란 및 디에틸에테르 중에서 선택된 1종 이상을 사용할 수 있으나, 이에 한정되는 것은 아니다. 이때, 유기아민은 화학식 3의 화합물을 기준으로 하여 1.0 내지 2.0 당량비로 사용하는 것이 바람직하다. 반응은 통상 질소 대기 하에서 빛과 수분이 차단된 상태로 진행되는 것이 바람직하며, 냉각 내지 가온된 상태에서 진행될 수 있다.In this case, pyridine or triethylamine may be used as the organic amine serving as the base, but the present invention is not limited thereto. As the solvent, at least one selected from anhydrous organic solvents such as dichloromethane, benzene, toluene, tetrahydrofuran and diethyl ether may be used, but the present invention is not limited thereto. At this time, the organic amine is preferably used in an amount of 1.0 to 2.0 equivalents based on the compound of formula (3). The reaction is preferably carried out in a state where light and moisture are blocked under a nitrogen atmosphere, and the reaction may proceed in a cooled or warmed state.
출발물질로 사용되는, Y가 할로겐인 화학식 2의 화합물은 레티노인산을 삼염화인, 티오닐클로라이드 및 옥살릴클로라이드와 같은 할로겐화제와 반응시켜 제조할 수 있다. Compounds of formula (2) wherein Y is a halogen, used as a starting material, can be prepared by reacting retinoic acid with a halogenating agent such as phosphorus trichloride, thionyl chloride and oxalyl chloride.
상기한 방법으로 제조된 화학식 1의 화합물은 통상의 분리, 정제 방법, 예를 들어 재결정이나 칼럼 크로마토그래피법을 사용하여 분리, 정제할 수 있다.
The compound of formula (I) prepared by the above method can be isolated and purified by conventional separation and purification methods, for example, recrystallization or column chromatography.
본 발명의 조성물에서, 상기 레티노이드 유도체의 함량은 화장료 조성물 총 중량에 대하여 0.0001 내지 10 중량%이며, 바람직하게는 0.01 내지 5.0 중량%이다. 최소한의 피부 미백효과를 달성할 수 있도록 추출물의 함량은 상기 최소치 이상인 것이 바람직하며, 과량 첨가에 따른 사용감 저하 및 각종 제형에의 적용 가능성을 고려하여 추출물의 함량은 상기 최대치 이하인 것이 바람직하다. 이때, 레티노이드 유도체의 함량은 제형 또는 화장료 조성물에 함유되는 성분들의 함량에 따라 상기 범위 내에서 적절히 조절하는 것이 바람직하다.In the composition of the present invention, the content of the retinoid derivative is 0.0001 to 10% by weight, preferably 0.01 to 5.0% by weight, based on the total weight of the cosmetic composition. The content of the extract is preferably at least the above-mentioned minimum value so as to achieve a minimum skin whitening effect, and it is preferable that the content of the extract is below the maximum value in consideration of the deterioration of use feeling due to the excessive addition and applicability to various formulations. At this time, it is preferable that the content of the retinoid derivative is appropriately adjusted within the above-described range according to the content of the components contained in the formulation or cosmetic composition.
또한, 본 발명의 피부 미백용 화장료 조성물은 레티노이드 유도체 외에 본 발명이 목적으로 하는 미백 효과를 손상시키지 않는 범위 내에서 바람직하게는 상기 미백 효과에 상승효과를 줄 수 있는 다른 미백 성분 등을 함유하는 것도 무방하다. 이와 같은 미백 성분으로는 알부틴, 아스코빅산 유도체 등을 들 수 있다.In addition, the cosmetic composition for whitening skin of the present invention may contain other whitening components or the like which can give a synergistic effect to the whitening effect within a range that does not impair the desired whitening effect of the present invention in addition to the retinoid derivatives It is acceptable. Examples of such whitening components include arbutin and ascorbic acid derivatives.
본 발명의 화장품 조성물에 포함되는 성분은 유효 성분으로서의 레티노이드 유도체 이외에 화장품 조성물에 통상적으로 이용되는 성분들을 포함하며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함한다.The components included in the cosmetic composition of the present invention include components commonly used in cosmetic compositions in addition to retinoid derivatives as active ingredients and include conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, Carrier.
본 발명의 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들면 유연화장수, 수렴화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 아이크림, 아이에센스, 클렌징크림, 클렌징폼, 클렌징워터, 팩, 젤, 파우더, 보디로션, 보디크림, 보디오일, 보디에센스 등의 화장료로 제형화 될 수 있다.The composition of the present invention can be prepared in any formulations conventionally produced in the art, and can be used in various forms such as softening agents, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, A cleansing foam, a cleansing water, a pack, a gel, a powder, a body lotion, a body cream, a body oil, a body essence and the like.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다. When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다. When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.
When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.
이하 본 발명의 바람직한 실시예를 기재한다. 하기 실시예는 본 발명을 보다 명확히 표현하기 위한 목적으로 기재될 뿐 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.
Hereinafter, preferred embodiments of the present invention will be described. The following examples are provided for the purpose of more clearly illustrating the present invention and are not intended to limit the scope of the present invention.
[실시예] [Example]
실시예Example 1: 1,5- 1: 1,5- 비스Bis 레틴아미도Retinamido 2- 2- 메틸methyl 펜탄의Pentane 합성 synthesis
레틴인산 35 g(0.0116 mol)을 무수 톨루엔 150 ㎖에 용해시킨 후 여기에 삼염화인(PCl3) 16.3 g(0.0116 mol)을 적가하고 상온에서 빛과 수분을 차단한 채 질소 하에서 15 시간 동안 교반하였다. 수득된 레티노인산클로라이드 용액을 2-메틸-1,5-디아미노펜탄 6.77 g(0.058 mol) 및 트리에틸아민 11.8 g(0.117 mol)이 무수 디클로로메탄 100 ㎖에 용해된 용액에 얼음 냉각하에서 30분간 적가해준 후 계속해서 5 시간 동안 상온에서 교반하였다. 반응용액을 포화 염화나트륨 수용액 250 ㎖에 가하고 유기층을 분리하여 물로 세척한 다음, 무수 황산나트륨으로 건조시키고 여과 및 농축시켰다. 잔류물을 컬럼 크로마토그래피로 분리(SiO2, 200~400 메쉬, 에탈아세테이트/헥산=1:3, v/v)하여 표제화합물 56.1 g(수욜 : 71%)를 수득하였다.
Retinoic phosphoric acid 35 g (0.0116 mol) was added dropwise here, the (PCl 3) 16.3 g (0.0116 mol) phosphorus trichloride to the was dissolved in
실험예Experimental Example 1: B16 1: B16 멜라노마Melanoma 세포주를 이용한 멜라닌 생성 Production of melanin using cell lines 억제능Inhibition 확인 Confirm
설치류 멜라노마 세포주인 B16 세포주(ATCC CRL-6323)를 10% 우태혈청과 100 U/㎖ 페니실린, 100 ㎍/㎖ 스트렙토마이신이 보충된 DMEM 배지에 첨가하여 37℃, 5% CO2,조건에서 배양하였다.Rodent melanoma cell line, B16 cell line (ATCC CRL-6323) with 10% fetal calf cultured in serum with 100 U / ㎖ penicillin, 100 ㎍ / ㎖ streptomycin is added to the supplemented DMEM medium by 37 ℃, 5% CO 2, conditions Respectively.
상기에서 배양된 B16 세포를 웰 플레이트에, 웰 당 1ⅹ105개를 배지 DMEM (Invitrogen-Gibco-BRL, Grand Island, NY)를 이용하여 접종하고, 멜라닌 자극 호르몬인 α-MSH(Melanocyte stimulating hormone) 각각 100 nM 과 1,5-비스 레틴아미도 2-메틸 펜탄이 0 ㎍/㎖, 1 ㎍/㎖, 5 ㎍/㎖, 10 ㎍/㎖, 20 ㎍/㎖ 이 포함된 시료액 2ml을 동시에 처리하였다. 다음으로, 72시간 처리 후에 인산화 완충용액으로 배지를 씻어준 후 멜라닌 추출용액(1N NaOH+50 % DMSO)을 웰당 100 ㎕씩 첨가하여 80 ℃에서 세포를 용해시킨 후 마이크로플레이트 리더기로 492㎚에서 멜라닌의 흡광도를 측정하였다. 그 결과는 도 1에 나타내었다.B16 cells cultured as described above were inoculated into a well plate at 1 × 10 5 per well using medium DMEM (Invitrogen-Gibco-BRL, Grand Island, NY) and melanocyte stimulating hormone (α-MSH) 2 ml of a sample solution containing 100 nM of 1,5-bis-retinamido 2-methylpentane at 0 / / ml, 1 쨉 g / ml, 5 쨉 g / ml, 10 쨉 g / ml and 20 쨉 g / . Next, after 72 hours of treatment, the medium was washed with phosphorylation buffer solution, and 100 μl of melanin extract solution (1N NaOH + 50% DMSO) was added at a rate of 80 ° C to dissolve the cells at 80 ° C. Was measured. The results are shown in Fig.
도 1은 본원발명의 일실시예에 따른 1,5-비스 레틴아미도 2-메틸 펜탄 처리농도에 따른 멜라닌 생성량을 나타낸 그래프이다. 1 is a graph showing the amount of melanin produced according to the concentration of 1,5-bis-retinamido 2-methylpentane treatment according to an embodiment of the present invention.
도 1을 참조하면, 1,5-비스 레틴아미도 2-메틸 펜탄 1 ㎍/㎖, 5 ㎍/㎖, 10 ㎍/㎖, 20 ㎍/㎖l을 α-MSH와 함께 처리한 모든군에서 1,5-비스 레틴아미도 2-메틸 펜탄을 처리하지 않은 군에 비하여 현저한 멜라닌 생성 억제 효과를 보였다. 또한, 1,5-비스 레틴아미도 2-메틸 펜탄을 1 ㎍/㎖ 처리했을 때부터, 미처리군에 비하여 유의성 있게 세포 내의 멜라닌의 함유 정도가 저하되었으며, 이 결과를 바탕으로 농도 의존적으로 맬라닌 생성이 억제된 것을 확인하였다.
1, in all groups treated with 1-g / ml, 5 μg / ml, 10 μg / ml and 20 μg / ml of 1,5-bis- retinamido 2-methylpentane with α- , 5-bis-retinamido showed a remarkable inhibitory effect on melanin formation as compared with the group not treated with 2-methylpentane. In addition, from 1 μg / ml of 1,5-bis-retinamido 2-methylpentane, the content of melanin in the cells decreased significantly compared to the untreated group. Based on these results, Production was suppressed.
실험예Experimental Example 2: 2: 티로시나제Tyrosinase 저해능Low performance 확인 Confirm
시험관에 0.1 M 인산염완충액(pH 6.5) 220㎕와 B16 세포에서 추출한 타이로시나제 20㎕ 그리고 버섯 타이로시나제 20㎕를 순서대로 넣었다. 이 용액에 1.5 mM 타이로신 액 40 ㎕를 넣고 37 ℃에서 10~15분 동안 반응시키고, 이를 마이크로플레이트 리더기를 이용하여 490㎚에서 흡광도를 측정하였다. 상기 시험예 1의 시료액을 각각 200㎕ 으로 티로신 액을 처리하기 전에 처리하였고, 공시료액으로는 시료액 대신 0.1 M 인산염완충액(pH 6.5)을 넣었다. 그 결과는 도 2에 나타내었다.220 μl of 0.1 M phosphate buffer (pH 6.5), 20 μl of tyrosinase extracted from B16 cells, and 20 μl of mushroom tyrosinase were placed in the test tube in this order. 40 μl of 1.5 mM tyrosine solution was added to this solution, and reacted at 37 ° C for 10 to 15 minutes. The absorbance was measured at 490 nm using a microplate reader. Each sample solution of Test Example 1 was treated with 200 mu l of the solution before treatment with tyrosine, and 0.1 M phosphate buffer (pH 6.5) was added as a blank solution instead of the sample solution. The results are shown in Fig.
도 2는 본원발명의 일실시예에 따른 1,5-비스 레틴아미도 2-메틸 펜탄 처리농도에 따른 티로시나제 활성을 나타낸 그래프이다. 2 is a graph showing tyrosinase activity according to 1,5-bis-retinamido 2-methylpentane treatment concentration according to an embodiment of the present invention.
도 2에 나타낸 바와 같이, 1,5-비스 레틴아미도 2-메틸 펜탄 1 ㎍/㎖, 5 ㎍/㎖, 10 ㎍/㎖, 20 ㎍/㎖를 α-MSH와 함께 처리한 군은 1,5-비스 레틴아미도 2-메틸 펜탄를 처리하지 않은 군에 비하여 현저한 티로시나제 활성 저해 효과를 보였다.
As shown in FIG. 2, the group treated with 1-g / ml, 5 μg / ml, 10 μg / ml and 20 μg / ml of 1,5-bis- retinamido 2-methylpentane with α- 5-bis-retinamido showed remarkable inhibitory effect on tyrosinase activity as compared with the group not treated with 2-methylpentane.
실험예Experimental Example 3: 3: 알러지allergy 시험 exam
본 발명에 따른 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 알러지 시험은 에탄올을 운반매개체로 사용하여 안전성 시험을 통해 확인하였다 [참고문헌: J. Appl. Toxicol., 1990, 10(3), 173~180]. 대조물질로서 레티닐 팔미테이트, 레티노인산, 에틸 레티노에이트 및 PEG-레틴아미드, 그리고 1,5-비스 레틴아미도 2-메틸 펜탄를 각각 0.3% 및 1% 농도의 아세톤/올리브오일 (4/1, v/v) 용액으로 제조하였다. 쥐 (Balb/c)의 양쪽 귀에 30 ㎕씩 3 일간 발라준 후 쥐로부터 이개임파절(Auricular lymph node)을 분리하였다. 임파절을 분쇄하여 단일세포 상태로 만든 후 방사성동위원소 (3H-티미딘)를 첨가하여 24 시간 동안 배양한 다음, 세포의 증폭도 (CPM)를 측정한 결과를 하기 표 1에 나타내었다. The allergy test of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention was confirmed by a safety test using ethanol as a carrier medium [Reference: J. Appl. Toxicol., 1990, 10 (3), 173-180). Retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide and 1,5-bis-retinamido 2-methylpentane as control substances were dissolved in acetone / olive oil (4/1, v / v) solution. Auricular lymph nodes were isolated from rats after 3 days of 30 μl of rats (Balb / c) on both ears. The lymph nodes were pulverized into single cells, and radioactive isotopes ( 3 H-thymidine) were added to the cells for 24 hours. Cellular amplification (CPM) was measured and the results are shown in Table 1 below.
표 1에서 대조물질인 레티닐 팔미테이트와 레티노인산은 5배 이상의 높은 알러지 유발성을 보인 반면, 1,5-비스 레틴아미도 2-메틸 펜탄은 0.3% 및 1% 용액에서 각각 1.2배 및 1.6배로 에탄올에 비해 3배 이하의 유발성을 보인 에틸 레티노에이트와 PEG-레틴아미드 보다도 낮은 유발성을 보였다. In Table 1, retinoyl palmitate and retinoic acid as control substances showed higher allergy induction than 5 times, while 1,5-bis-retinamido 2-methylpentane showed 1.2 and 1.6 times in 0.3% and 1% solutions, respectively Than that of ethyl retinoate and PEG-retinamide, which were three times less inducible than ethanol.
(107 세포/ml)Lymph node cell
(10 < 7 > cells / ml)
(0.3%)Retinyl palmitate
(0.3%)
(1%)Retinyl palmitate
(One%)
(0.3%)Retinoic acid
(0.3%)
(1%)Retinoic acid
(One%)
(0.3%)Ethyl retinoate
(0.3%)
(1%)Ethyl retinoate
(One%)
(0.3%)PEG-retinamide
(0.3%)
(1%)PEG-retinamide
(One%)
(0.3%)1,5-Bis Retinamido 2-Methylpentane
(0.3%)
(1%)1,5-Bis Retinamido 2-Methylpentane
(One%)
실험예Experimental Example 4: 피부자극도 시험 4: Skin irritation test
본 발명에 따른 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 피부자극도를 확인하기 위하여, 기니픽 (Guinea Pig)을 이용한 패치시험을 하였다 [참고 문헌: Assoc. Food and Drug officials US., 1959, 46-59; Method of testing primary irritant substances, 1973, 38(187), 1500-1541]. In order to confirm the skin irritation degree of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention, a patch test was conducted using Guinea Pig (Reference: Assoc. Food and Drug officials US, 1959, 46-59; Method of testing primary irritant substances, 1973, 38 (187), 1500-1541].
물과 프로필렌글리콜의 O/W 유화를 운반매개로 하여 0.3% 농도의 시료용액을 제조하였다. 도포할 부위 (등)의 털을 제거하고, 정확한 측정을 위해 주위환경에 24 시간 동안 적응시켰다. 도포부위(1.5 cm×1.5 cm)에 시료를 적신 가아제를 처리한 다음 고형재질의 박지로 밀봉하여 시료의 증발 및 손실을 방지하고 탄력붕대로 48 시간 동안 고정시켰다. 폐쇄 첩포를 제거한 후 24 시간(첩포 후 72 시간)째에 자극의 정도를 판정하여 하기 표 2에 결과를 나타내었다. A 0.3% concentration of sample solution was prepared by transferring O / W emulsions of water and propylene glycol. The hair of the area (s) to be applied was removed and adapted to the surrounding environment for precise measurement for 24 hours. The coated area (1.5 cm x 1.5 cm) was treated with a gauze soaked with a specimen and sealed with a solid material sheet to prevent evaporation and loss of the specimen, and fixed with a resilient bandage for 48 hours. The degree of irritation was determined 24 hours after the closed pellet was removed (72 hours after the patch), and the results are shown in Table 2 below.
상기 표 2에 나타낸 바와 같이, 1,5-비스 레틴아미도 2-메틸 펜탄은 레티닐 팔미테이트 및 레티노인산과 비교하여 자극 정도가 현저히 낮게 나타났다.
As shown in Table 2 above, 1,5-bisretinamido 2-methylpentane showed significantly less irritation than retinyl palmitate and retinoic acid.
실험예Experimental Example 5: 세포독성 시험 5: Cytotoxicity test
본 발명에 따른 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 의약 또는 화장품용 활성소재로서의 1차 안전성을 검증하기 위해, 차이니스햄스터 폐조직 섬유아세포의 연속 세포주 (V79-4)를 배양하여 MTT 실험 [참고문헌: Journal of Immunological Methods, 1983, 65, 55~63]으로 세포독성을 확인하여, 도 3에 결과를 나타내었다. In order to verify the primary safety of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention as an active ingredient for medicines or cosmetics, a continuous cell line of Chinese Hamster lung fibroblasts (V79 -4) was cultured and the cytotoxicity was confirmed by an MTT experiment (Reference: Journal of Immunological Methods, 1983, 65, 55 ~ 63), and the results are shown in FIG.
도 3을 참조하면, 1,5-비스 레틴아미도 2-메틸 펜탄는 대조물질로 사용된 에틸 레티노에이트와 유사한 시험 농도에서 독성을 나타내지 않았다. 그러나, 레티닐 팔미테이트 및 레티노인산은 10 μM 이상에서 독성을 나타내었고, PEG-레틴아미드는 고농도 (25 μM 이상의 농도)에서 급격한 독성을 나타내었다.
3, 1,5-bis Retinamido 2-methyl pentane showed no toxicity at a test concentration similar to that of ethyl retinoate used as a control. However, retinyl palmitate and retinoic acid were toxic at> 10 μM, and PEG-retinamide showed rapid toxicity at high concentrations (> 25 μM).
실험예Experimental Example 6: 6: 광안정성Light stability 시험 exam
본 발명에 따른 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 광안정성을 알아보기 위하여, 실온에서 시료 10 mg에 스펙트롤라인 (Spectroline Model CM-10; Fluorescence analysis cabinet; Spectronics Corporation, Westbury, New York, USA)을 사용하여 UV-A광 (파장 356 nm)을 시간 별로 조사한 후 NMR로 정성 확인하여 하기 표 3에 나타내었다. In order to examine the light stability of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention, Spectroline Model CM-10 (Fluorescence analysis cabinet; UV-A light (wavelength: 356 nm) was irradiated with time using Spectronics Corporation, Westbury, New York, USA and then qualitatively confirmed by NMR.
표 3에서 1,5-비스 레틴아미도 2-메틸 펜탄은 기존의 레티노이드 유도체와 비교하여 광안정하게 나타나고, PEG-레틴아미드에 비교하여서도 유사한 안정성을 나타낸다.
In Table 3, 1,5-bis-retinamido 2-methylpentane appears photostable as compared to conventional retinoid derivatives and exhibits similar stability compared to PEG-retinamide.
실험예Experimental Example 7: 7: 열안정성Thermal stability 시험 exam
본 발명에 따른 상기 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 열안정성을 알아보기 위하여, 실온, 0 ℃, 37 ℃ 및 50 ℃의 항온 항습조 (습도 56%)에서 1 개월간의 상안정성을 비교하여 하기 조건하에 HPLC 정량 분석을 실시하고, 그 결과를 하기 표 4에 나타내었다.To examine the thermal stability of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention, a constant temperature and humidity chamber (at a humidity of 56%) at room temperature, 0 ° C, 37 ° C and 50 ° C, , And the results are shown in Table 4 below. ≪ tb > < TABLE >
표 4에서 확인할 수 있듯이 1,5-비스 레틴아미도 2-메틸 펜탄은 37 ℃ 와 50 ℃에서 열안정성이 우수하게 나타났다.
As shown in Table 4, 1,5-bis-retinamido 2-methylpentane showed excellent thermal stability at 37 ° C and 50 ° C.
실험예Experimental Example 8: 8: 경피흡수Percutaneous absorption 시험 exam
본 발명에 따른 상기 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 경피흡수 시험을 위해, 레티놀, 레티닐 팔미테이트, 레티노인산, 에틸 레티노에이트 및 PEG-레틴아미드를 대조물질로 사용하고, 오일 (카프릴릭카프릭 트리글리세라이드)과 에탄올의 1:1 혼합용매를 매개체로 사용하였다 [참고문헌: J. Invest Dermatol., 1998, 91; 56-61]. Retinol, retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide were used as a control substance for the percutaneous absorption test of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention , And a 1: 1 mixed solvent of oil (caprylic capric triglyceride) and ethanol was used as a medium (Reference: J. Invest Dermatol., 1998, 91; 56-61].
먼저, 7주령의 암컷 무모 마우스의 피부 (등 부위)를 절취하고 1.7 cm2의 피부에 50 mM의 시료용액을 150 ㎕씩 적용하였다. 24시간 후 2% Volpo 20™ (Oleth-20)을 포함하는 50 mM PBS 완충용액 (pH 7.4)인 수용기 용액과 피부에 흡수된 물질을 경피흡수측정기 (Frnaz cell)를 이용하여 추출하고, 고성능 액체 크로마토그래피 (HPLC)로 정량 분석하여 하기 표 5에 결과를 나타내었다.First, the skin (back region) of a 7-week-old female hairless mouse was cut and 150 μl of 50 mM sample solution was applied to the skin of 1.7 cm 2 . After 24 hours, the receptor solution, which is a 50 mM PBS buffer (pH 7.4) containing 2% Volpo 20 ™ (Oleth-20), and the substance absorbed into the skin were extracted using a transdermal absorption detector (Frnaz cell) Chromatography (HPLC) quantitative analysis showed the results in Table 5 below.
상기 표 5를 참조하면, 1,5-비스 레틴아미도 2-메틸 펜탄은 레티놀의 3배, 레티닐 팔미테이트의 5.4배, 레티노인산의 2.4배로 경피흡수가 가능함을 확인하였으며, 특히 용해도가 개선된 것으로 알려진 PEG-레틴아미드와 비교하여 거의 유사한 경피흡수율을 나타내는 것을 확인할 수 있었다.
Referring to Table 5, it was confirmed that 1,5-bis-retinamido 2-methylpentane can be percutaneously absorbed at three times of retinol, 5.4 times of retinyl palmitate, and 2.4 times of retinoic acid, It was confirmed that it exhibited almost the same percutaneous absorption rate as that of PEG-retinamide known to be known.
실험예Experimental Example 9: 쥐 혈청 중 가수분해 시험 9: Hydrolysis test in rat serum
쥐 (Rat) 혈청 중 에스테르 형태의 에틸 레티노에이트와 아미드 형태의 PEG-레틴아미드 및 본 발명에 따른 상기 실시예 1에서 제조된 1,5-비스 레틴아미도 2-메틸 펜탄의 가수분해 속도를 체내에 보다 근접하게 모델링하는 조건 (37℃)하에서 산출하였다.The rate of hydrolysis of ethyl retinoate in the form of an ester in the rat serum and PEG-retinamide in the amide form and the 1,5-bis-retinamido 2-methyl pentane prepared in Example 1 according to the present invention, (37 < 0 > C).
상기 시료 80 mg을 각각 5 ml의 쥐 혈청 중에 용해시키고, 생성된 용액을 37 ℃에서 인큐베이션하였다. 시간 간격을 두고 0.7 ml의 혈청 혼합물을 취하여, 2 ml의 디클로로메탄으로 2 회 추출하였다. 디클로로메탄 추출물을 Na2SO4로 건조하고, 여과하여 감압 하에 증발, 건조시켰다. 건조 잔류물에 물을 첨가하고, 여과하였다. 여과액을 역상 HPLC (Betasil C18, 100 ×2) 분석법에 의해 그 결과를 도 4에 나타내었다.80 mg of the sample was dissolved in 5 ml of rat serum each, and the resulting solution was incubated at 37 ° C. At time intervals, 0.7 ml of the serum mixture was taken and extracted twice with 2 ml of dichloromethane. The dichloromethane extract was dried over Na 2 SO 4 , filtered and evaporated to dryness under reduced pressure. Water was added to the dry residue and filtered. The filtrate was analyzed by reverse phase HPLC (Betasil C18, 100 x 2) analysis and the results are shown in Fig.
도 4로부터 가수분해의 반감기 (t1 /2)는 에틸 에스테르 형태의 경우 8.7 시간이었고, 1,5-비스 레틴아미도 2-메틸 펜탄의 아미드 형태의 경우 32 시간인 것을 확인하였다. 한편 PEG-레틴아미드의 아미드 형태의 경우는 48 시간 이상이 지나도 60% 정도 유지함을 확인하였다.
Half-life (t 1/2) of hydrolysis of from 4 was confirmed to be 32 hours for the amide form of the ethyl ester was 8.7 hours for the form, 1,5-bis retinoic amido-2-methyl pentane. On the other hand, it was confirmed that the amide form of PEG-retinamide maintained about 60% even after 48 hours or more.
이하, 본 발명의 제형예로서 유연 화장수, 수렴 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스 및 팩을 예시하고 있으나, 본 발명의 화장료 조성물의 제형은 이에 제한되는 것은 아니다.
Hereinafter, the formulations of the present invention are exemplified as a soft lotion, a convergent lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence and a pack, but the formulation of the cosmetic composition of the present invention is not limited thereto.
제형예Formulation Example 1: 유연화장수 ( 1: Softening longevity ( 스킨skin ))
하기의 표 6과 같이 실시예 1의 레티노이드 유도체를 함유하는 유연화장수를 통상의 방법에 따라 제조하였다.The number of softening times containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 6 below.
제형예Formulation Example 2: 영양화장수 (로션) 2: Nourishing lotion (lotion)
하기의 표 7과 같이 실시예 1의 레티노이드 유도체를 함유하는 영양화장수를 통상의 방법에 따라 제조하였다.A nutritional lotion containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 7 below.
제형예Formulation Example 3: 영양크림 3: Nourishing cream
하기의 표 8과 같이 실시예 1의 레티노이드 유도체를 함유하는 영양크림을 통상의 방법에 따라 제조하였다.A nutritional cream containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 8 below.
제형예Formulation Example 4 : 4 : 맛사지Massage 크림 cream
하기의 표 9와 같이 실시예 1의 레티노이드 유도체를 함유하는 맛사지 크림을 통상의 방법에 따라 제조하였다.A massage cream containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 9 below.
제형예Formulation Example 5 : 에센스 5: essence
하기의 표 10과 같이 실시예 1의 레티노이드 유도체를 함유하는 에센스를 통상의 방법에 따라 제조하였다.Essences containing retinoid derivatives of Example 1 were prepared according to the conventional method as shown in Table 10 below.
제형예Formulation Example 6: 팩 6: Pack
하기의 표 11과 같이 실시예 1의 레티노이드 유도체를 함유하는 팩을 통상의 방법에 따라 제조하였다.A pack containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 11 below.
Claims (4)
[화학식 1]
(상기 식에서,
R1 및 R2는 서로 같거나 다르며 수소 또는 C1~C6의 직쇄 또는 측쇄형의 알킬기이다.)A cosmetic composition for skin whitening comprising a retinoid derivative represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]
(Wherein,
R 1 and R 2 are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.
상기 R1은 메틸기이고 R2는 수소인 것을 특징으로 하는 피부 미백용 화장료 조성물. The method according to claim 1,
Wherein R 1 is a methyl group and R 2 is Wherein the composition is hydrogen.
상기 레티노이드 유도체의 함량은 전체 화장료 조성물 총 중량에 대하여 0.001 내지 10 중량%로 함유되는 것을 특징으로 하는 피부 미백용 화장료 조성물.The method according to claim 1,
Wherein the content of the retinoid derivative is 0.001 to 10% by weight based on the total weight of the total cosmetic composition.
상기 피부 미백용 화장료 조성물은 유연화장수, 수렴화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 아이크림, 아이에센스, 클렌징크림, 클렌징폼, 클렌징워터, 팩, 젤, 파우더, 보디로션, 보디크림, 보디오일, 및 보디에센스로 이루어진 군으로부터 선택된 어느 하나의 제형으로 이루어지는 것을 특징으로 하는 피부 미백용 화장료 조성물.The method according to claim 1,
The cosmetic composition for skin whitening may be selected from the group consisting of softening longevity, astringent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, gel, powder, body lotion, , A body oil, and a body essence. The cosmetic composition for skin whitening according to claim 1,
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| KR100371028B1 (en) | 2000-10-06 | 2003-02-06 | 주식회사 엘지생활건강 | Cosmetic composition containing Salvia militiorrhira Bge. extracts and polyethoxylated retinamide |
| KR100478033B1 (en) | 2003-01-14 | 2005-03-22 | 주식회사 엘지생활건강 | Composition having inhibitory effect on formation of skin wrinkle |
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| KR100478033B1 (en) | 2003-01-14 | 2005-03-22 | 주식회사 엘지생활건강 | Composition having inhibitory effect on formation of skin wrinkle |
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