KR100613266B1 - Keratin exfoliation accelerator and pharmaceuticals or cosmetics containing it as an active ingredient - Google Patents
Keratin exfoliation accelerator and pharmaceuticals or cosmetics containing it as an active ingredient Download PDFInfo
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- KR100613266B1 KR100613266B1 KR1019990040579A KR19990040579A KR100613266B1 KR 100613266 B1 KR100613266 B1 KR 100613266B1 KR 1019990040579 A KR1019990040579 A KR 1019990040579A KR 19990040579 A KR19990040579 A KR 19990040579A KR 100613266 B1 KR100613266 B1 KR 100613266B1
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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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
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- A—HUMAN NECESSITIES
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- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A61K8/9789—Magnoliopsida [dicotyledons]
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
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Abstract
본 발명은 지금까지 알려진 각질 박리 물질인 알파하이드록시산 (AHA), 트리클로로아세틱산 등의 부작용이나 안정성 문제를 극복하여 독성이 없고 안정성이 좋으며, 기존의 물질들보다 각질 박리 효과가 우수한 각질 박리 촉진제로서, 하기 일반식 (I), (II)로 각각 표시되는 5,15-디아세톡시-3-페닐아세톡시-14-옥소라티라디엔-6(17)-에폭사이드(Euphorbia factor L1), 및 5,15-디아세톡시-3,7-디벤조일옥시The present invention overcomes side effects and stability problems such as alpha hydroxy acid (AHA) and trichloroacetic acid, which are known to date, have no toxicity and have good stability, and have excellent exfoliation effect than existing substances. As an accelerator, 5,15-diacetoxy-3-phenylacetoxy-14-oxoratyadiene-6 (17) -epoxide represented by the following general formulas (I) and (II), respectively (Euphorbia factor L1) And 5,15-diacetoxy-3,7-dibenzoyloxy
-14-옥소라티라디엔(Euphorbia factor L2)으로 이루어진 군으로부터 선택된 1종 이상의 화합물을 제공한다.At least one compound selected from the group consisting of -14-oxorathiadiene (Euphorbia factor L2).
[일반식 I][Formula I]
[일반식 II][Formula II]
각질 박리 촉진제, 케라틴, 데스모좀, 각질중층화, 알파하이드록시산, 트리클로로아세틱산, 속수자, 유포비아 팩터 L1, L2 Keratin exfoliation accelerator, keratin, desmosome, keratin stratification, alpha hydroxy acid, trichloroacetic acid, water soluble, euphorbia factor L1, L2
Description
[산업상 이용분야][Industrial use]
본 발명은 각질 박리 촉진제에 관한 것으로서, 더욱 상세하게는 하기 일반식 (I), (II)로 각각 표시되는 5,15-디아세톡시-3-페닐아세톡시-14-옥소라티라디엔-TECHNICAL FIELD The present invention relates to a keratin exfoliation accelerator, and more particularly, 5,15-diacetoxy-3-phenylacetoxy-14-oxoratyadiene- represented by the following general formulas (I) and (II), respectively.
6(17)-에폭사이드(5,15-diacetoxy-3-phenylacetoxy-14-oxolathyradiene-6(17)6 (17) -epoxide (5,15-diacetoxy-3-phenylacetoxy-14-oxolathyradiene-6 (17)
-epoxide), 및 5,15-디아세톡시-3,7-디벤조일옥시-14-옥소라티라디엔(5,15--epoxide), and 5,15-diacetoxy-3,7-dibenzoyloxy-14-oxoratiadiene (5,15-
diacetoxy-3,7-dibenzoyloxy-14-oxolathyradiene)으로부터 선택된 각질 박리 촉진제 및 이를 유효 성분으로 함유하는 의약품 또는 화장료에 관한 것이다.It relates to a keratin exfoliation promoter selected from diacetoxy-3,7-dibenzoyloxy-14-oxolathyradiene) and to pharmaceuticals or cosmetics containing the same as an active ingredient.
[일반식 I][Formula I]
[일반식 II][Formula II]
[종래 기술][Prior art]
일반적으로 피부는 피부 상층으로부터 표피, 진피, 피하 지방층의 세 부분으로 분류된다. 이 중 표피는 다시 각질층, 과립층, 유극층, 기저층으로 세분되며, 기저층의 표피 세포는 피부 상부로 올라오면서 분화되어, 최종적으로 각질층에 도달하게 된다. 각질층에 도달한 표피 세포는 핵이 소실되고 케라틴이라 불리우는 불수용성 단백질로 채워지면서 죽은 세포로 전환된다. 각질층은 분화된 표피 세포 (각질 세포)와 이들 사이를 채워주는 피부 지질(skin lipid)로 구성되며 체내 물질이 외부로 나가는 것을 막아주고 외부의 물리적, 화학적, 생물학적 자극으로부터 인체를 보호하는 방어 기능을 한다. 각질 세포는 데스모좀이라 불리우는 단백질에 의하여 연결되어 있으며, 각질층 상부로 올라갈수록 데스모좀은 분해되어 각질 세포간 응집력이 약화되고 최종적으로 각질 세포는 피부로부터 분리되어 떨어져 나간다. 정상 피부의 경우 각질층은 15 - 20 층으로 구성되고 이들이 완전히 분리되는데는 15 - 20 일이 소요된다(British Journal of Dermatology, 86, 14 - 19, 1974; K. M. Halprin, 향장회지, 12(4), 265 - 271, 1988; M. Takahashi).Generally, the skin is divided into three parts from the upper layer of skin: epidermis, dermis and subcutaneous fat layer. Of these, the epidermis is further subdivided into the stratum corneum, granule layer, polar layer, and basal layer. The epidermal cells of the basal layer are differentiated as they rise to the upper part of the skin and finally reach the stratum corneum. Epidermal cells that reach the stratum corneum lose their nuclei and are converted to dead cells as they are filled with insoluble proteins called keratin. The stratum corneum consists of differentiated epidermal cells (skin cells) and the skin lipids that fill them in. They protect defense against external physical, chemical and biological stimuli and protect the body from external physical, chemical and biological stimuli. do. Keratinocytes are connected by a protein called desmosome, and as they rise up the stratum corneum, desmosomes are broken down, weakening cohesion between keratinocytes and finally keratinocytes are separated from the skin. In normal skin, the stratum corneum consists of 15-20 layers and it takes 15-20 days for them to be completely separated (British Journal of Dermatology, 86, 14-19, 1974; KM Halprin, Fragrance Society, 12 (4), 265-271, 1988; M. Takahashi).
노화 피부, 건조 피부, 여드름 피부 등은 각질층의 분리가 정상보다 늦어져 각질층이 두꺼워지는(각질중층화) 현상을 보이며, 피부 외관상으로 나타나는 두드러진 특징은 피부 비늘(scale)의 발생이다. 각질중층화는 주로 피부의 보습력 감소, 데스모좀 분해 효소의 생성 및 활성 감소, 세포 활성 저하 등에 기인하며 피부 노화, 자외선 노출, 공해 등이 유발 요인이 된다. 이러한 내,외적인 요인에 의해 두꺼워진 각질층을 외부에서 인위적으로 얇게 해주면 각질층 밑에 있는 살아있는 세포의 활성 혹은 재생이 증가되어 피부 외관에 나타나는 피부 비늘이 감소하고 피부가 부드러워지며, 주름제거, 여드름 발생 억제 및 치료 등의 효과가 있어 자극이 유발되지 않는 범위 내에서 각질중층화를 해소하려는 연구가 많이 진행되고 있다. 각질중층화를 해소하기 위해서는 피부를 물리적으로 문지르거나 화학적 박피술을 이용한다. 특히 화학적 박피는 잔주름 개선, 거친 피부 완화, 잡티 제거 등의 부가적인 효과가 있다. 화학적 박피에 사용되는 물질은 트리클로로아세틱산, 페놀, 알파하이드록시산(AHA) 등이 있다. 화학적 박피에 이용되는 알파하이드록시산의 농도는 적어도 20 - 30% 이상의 고농도가 이용되나, 10% 미만의 저농도에서는 각질층을 서서히 박리시키고(Journal of American Academy of Dermatology, 11, 867 - 879, 1984; Van Scott 등), 피부 보습 증진(Happi, July, 66 - 68, 1994; Tom 등), 잔주름 완화(Cutis, 43, 222 - 228, 1989; Van Scott 등) 등의 효과도 보여 최근 화장품이나 제약업계에서 많은 제품들이 출시되고 있다. 또한 각질 박리 촉진을 통해 얼굴 모낭을 좁히는 각질을 제거 함으로써, 여드름의 치료 및 예방도 가능하 다고 알려져 있으며(피부과학, 1994, 여문각), 미백 제품에 있어서도, 효과 상승을 목적으로 멜라닌 생성 억제 물질과 함께 이미 생성된 멜라닌을 제거하기 위한 각질 박리 촉진 물질을 사용하고 있다. 그러나, 알파하이드록시산은 낮은 pH로 인하여 따가움을 호소하며 자극이 유발되는 단점도 있어 사용 농도와 pH 조절이 피부 부작용을 완화하는데 매우 중요하다. 또한 알파하이드록시산에 단백질, 지질 등을 붙이거나 부작용 완화제의 첨가, 구조 변경 등을 시도하여 피부 부작용을 감소 시킬 수 있으나 각질 박리, 잔주름 개선 등의 효과 역시 감소되어 최소의 부작용과 최대의 효과를 얻기에는 아직 어려운 실정이다.Aging skin, dry skin, acne skin and the like, the separation of the stratum corneum is slower than normal, the stratum corneum is thickened (stratum corneum stratification) phenomenon, the outstanding feature that appears in the appearance of the skin is the scale of the skin (scale). The stratum corneum stratification is mainly due to decreased skin moisturizing ability, decreased production and activity of desmosome degrading enzymes, decreased cell activity, and skin aging, UV exposure, and pollution. Artificially thinning the stratum corneum thickened by these internal and external factors externally increases the activity or regeneration of living cells under the stratum corneum, reducing skin scales appearing on the appearance of the skin, softening the skin, removing wrinkles, suppressing the occurrence of acne, and There is a lot of research to solve the stratum corneum stratification within the range that does not cause irritation due to the effects of treatment. To relieve keratinization, physically rub the skin or use chemical dermabrasion. In particular, chemical peels have additional effects such as fine wrinkles, rough skin relief and blemishes. Substances used for chemical peeling include trichloroacetic acid, phenol, and alpha hydroxy acid (AHA). The concentration of alpha hydroxy acid used for chemical peeling is used at a high concentration of at least 20-30%, but at low concentrations below 10%, the stratum corneum is slowly exfoliated (Journal of American Academy of Dermatology, 11, 867-879, 1984; Van Scott et al.), Enhancing skin moisturization (Happi, July, 66-68, 1994; Tom et al.), And reducing fine lines (Cutis, 43, 222-228, 1989; Van Scott et al.). Many products are on the market. In addition, it is known that it is possible to treat and prevent acne by removing keratin that narrows facial hair follicles by promoting keratin exfoliation (Dermatology, 1994, Yeogak-gak). In addition, a keratin exfoliation promoting substance is used to remove the melanin already produced. However, alpha-hydroxy acid complains of tingling and irritation due to low pH, so the use concentration and pH control are very important to alleviate side effects of the skin. In addition, it is possible to reduce skin side effects by attaching proteins, lipids, etc. to alpha hydroxy acids, or by adding side effect relievers, and by changing the structure, but the effects such as exfoliation and fine wrinkles are also reduced to minimize the side effects and maximum effects. It is still difficult to obtain.
따라서 본 발명은 지금까지 알려진 각질 박리 물질인 알파하이드록시산 (AHA), 트리클로로아세틱산 등의 피부 따가움 등의 부작용이나 안정성 문제를 극복하여 독성이 없고 안정성이 좋으며, 기존의 물질들보다 각질 박리 효과가 우수한 각질 박리 촉진제을 제공하는 것을 목적으로한다. Therefore, the present invention overcomes side effects and stability problems such as skin tingling such as alpha hydroxy acid (AHA) and trichloroacetic acid, which are known to date, have no toxicity and have good stability, and exfoliate more than conventional substances. It is an object of the present invention to provide an exfoliating accelerator having excellent effects.
[과제를 해결하기 위한 수단][Means for solving the problem]
상기 목적을 달성하기 위하여, 본 발명은 하기 일반식 (I), (II)로 각각 표시되는 5,15-디아세톡시-3-페닐아세톡시-14-옥소라티라디엔-6(17)-에폭사이드, 및 5,15-디아세톡시-3,7-디벤조일옥시-14-옥소라티라디엔으로부터 선택된 각질 박리 촉진제을 제공한다.In order to achieve the above object, the present invention provides 5,15-diacetoxy-3-phenylacetoxy-14-oxolatiadiene-6 (17)-represented by the following general formulas (I) and (II), respectively. Keratin exfoliation promoter selected from epoxide, and 5,15-diacetoxy-3,7-dibenzoyloxy-14-oxoratiadiene.
[일반식 I][Formula I]
[일반식 II][Formula II]
또한 본 발명은 상기 각질 박리 촉진제을 유효 성분으로 함유하는 의약품 또는 화장료를 제공한다.The present invention also provides a pharmaceutical or cosmetics containing the above keratin exfoliation accelerator as an active ingredient.
상기 의약품 또는 화장료는 각질 박리 촉진제을 건조 중량으로 0.0001 - 10.0 중량% 함유하는 것이 바람직하다.The drug or cosmetic preferably contains 0.0001-10.0% by weight of a keratin exfoliation accelerator in dry weight.
상기 의약품 또는 화장료는 피부 유연제, 여드름 치유 및 예방제, 주름 제거제 또는 미백제를 포함한다.The medicines or cosmetics include skin softeners, acne healing and prevention agents, wrinkle removers or whitening agents.
이하 본 발명을 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
상기 일반식 (I), (II)의 각질 박리 촉진제는 화학적으로 합성하거나, 다양한 동물, 식물, 미생물 등에 존재하는 것을 추출하여 얻을 수 있으며, 대표적으로는 속수자(Euphorbia lathyris L.)로 부터 추출하여 얻을 수 있다. 이와같이 속수자로부터 추출한 일반식 (I), (II)의 화합물은 일반적으로 각각 유포비아 팩터(Euphorbia factor) L1, L2로 알려져 있다.The keratin exfoliation promoter of the general formulas (I) and (II) may be obtained by chemical synthesis or by extracting those present in various animals, plants, and microorganisms, and typically by extracting from Euphorbia lathyris L. You can get it. The compounds of formulas (I) and (II) extracted from the recipients are generally known as Euphorbia factors L1 and L2, respectively.
속수자(Euphorbia lathyris L.)는 2년생 초본으로 본 발명에서는 속수자의 종자를 이용하였다. 속수자의 효능으로는 수종(水腫), 행수소종(行水消腫) 등에 효과가 있다고 동의보감에 언급되어 있으며, 또한 속수자 추출물의 미백 효과에 관한 특허(JP08175954)가 보고되어 있으나, 본 발명과는 확실히 구별된다. 속수자의 기존 성분 연구 문헌에서 인게놀(Ingenol) 및 유포비아 팩터 L1 - L8(Euphorbia factor L1 - L8)의 물질이 확인되어 있다(J. Nat. Prod., 1999, 62, 76 - 79; Tetrahedror. Letters, 1971, 18, 1325 - 1329). 본 발명에 사용된 유포비아 팩터 L1, L2의 구조 분석 자료(NMR, MASS)는 문헌값과 비교하여 확인하였다.Euphorbia lathyris L. is a biennial herb and uses the seed of the deceased in the present invention. It is mentioned in the agreement that it is effective in water species, row hydrogen species, and the like, and a patent (JP08175954) relating to the whitening effect of the water extract is reported, but it is certainly different from the present invention. Are distinguished. Ingenol and Euphorbia factors L1-L8 have been identified in the existing component research literature of the recipients (J. Nat. Prod., 1999, 62, 76-79; Tetrahedror. Letters, 1971, 18, 1325-1329). The structural analysis data (NMR, MASS) of Euphoria factors L1 and L2 used in the present invention were confirmed by comparison with literature values.
본 발명의 유포비아 팩터 L1, L2는 속수자 등의 식물에 함유되어 있는 것을 이용하였으나, 본 발명이 이에 한정되지는 않는다.Euphorbia factors L1 and L2 of the present invention are used in the plant, such as the inner water, but the present invention is not limited thereto.
본 발명에서는 유포비아 팩터 L1, L2가 다량 함유되어 있는 속수자 (Euphorbia lathyris L.)의 유기 용매 추출물이나 압착하여 얻은 오일에서 유포비아 팩터 L1을 정제하였다. 유포비아 팩터 L1의 정제에는 정제수, 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올, 아세톤, 에테르, 벤젠, 클로로포름, 헥산, 시클로헥산, 석유에테르 등의 각종 용매를 사용한 액-액 추출, 실리카 겔이나 활성 알 루미나 등의 각종 합성 수지를 충진한 칼럼 크로마토그라피 및 고속 액체 크로마토그라피(HPLC) 등의 정제 방법을 이용하였다. 특히, 위의 정제 방법에 한정된 것은 아니다.In the present invention, Euphorbia factor L1 was purified from an organic solvent extract of Euphorbia lathyris L. containing a large amount of Euphorbia factors L1 and L2, or oil obtained by pressing. Purification of Euphorbia Factor L1 includes liquid-liquid extraction using various solvents such as purified water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, hexane, cyclohexane, petroleum ether, silica gel or active eggs. Purification methods such as column chromatography packed with various synthetic resins such as lumina and high performance liquid chromatography (HPLC) were used. In particular, it is not limited to the above purification method.
상기 정제 방법의 일 예를 좀 더 상세히 설명하면, 먼저 생약재로 시판되는 속수자를 구입하여 잘게 분쇄하고 분쇄물 건조 중량에 대하여 5 - 20 부피의 물이나, 탄소수 1 - 4 개의 무수 또는 함수 저급 알코올, 에틸아세테이트, 헥산 또는 클로로포름으로 환류 냉각기가 달린 추출기에서 50 - 100℃로 1 - 5 시간 가열하여 추출한다. 여과포로 여과한 후 잔사를 같은 방법으로 1 회 이상씩 더 추출한다. 추출액을 합하고 감압 농축하여 건조 추출물을 얻는다. 건조된 속수자 추출물을 물에 현탁한 후 동일 부피의 헥산을 가하고 액-액 추출하여 오일상의 헥산 분획을 얻는다. 또는, 생약재로 시판되는 속수자를 구입하여 잘게 분쇄하고, 상온 - 250℃ 범위의 온도에서 압착, 여과하여 속수자의 오일을 얻는다. 위에서 얻은 헥산 분획이나 압착하여 얻은 오일에 오일과 섞이지 않는 에탄올, 메탄올, 아세토나이트릴, 정제수 등의 용매를 각종 비율로 서로 혼합 또는 단일로 0.2 - 10 배의 양을 가한 다음, 액-액 추출하여 용매 분획을 얻는다. 얻은 용매 분획에 헥산을 가해 침전을 형성시키거나, 용매 분획을 감압 농축한 후 헥산을 가해 녹지않은 헥산 불용성 분획을 얻어 이들 침전 및 불용성 분획을 분획 칼럼 크로마토그라피하여 유포비아 팩터 L1, L2를 분리하고 이를 다시 고속 액체 크로마토그라피하여 순수하게 정제하였다. 분리된 정제물을 질량 분석 및 핵자기 공명 스펙트럼으로 구조를 확인하였다.An example of the refining method will be described in more detail. First, a commercially available fastener is purchased as a herbal medicine, finely pulverized, and 5 to 20 volumes of water or 1 to 4 carbon anhydride or hydrous lower alcohol, Extract with ethyl acetate, hexane or chloroform by heating to 50-100 ° C. for 1-5 hours in an extractor equipped with a reflux condenser. After filtering with a filter cloth, the residue is further extracted one or more times in the same manner. The extracts are combined and concentrated under reduced pressure to give a dry extract. The dried Sucrose extract is suspended in water, and then the same volume of hexane is added, followed by liquid-liquid extraction to obtain an oily hexane fraction. Alternatively, a commercially available fastener is purchased and pulverized finely, and compressed and filtered at a temperature in the range of room temperature-250 ° C to obtain a fastener oil. Solvents such as ethanol, methanol, acetonitrile, purified water, etc., which are not mixed with oil, are mixed with each other in various ratios or added 0.2-10 times to the hexane fraction obtained by pressing or compressed oil, and then liquid-liquid extraction. Obtain the solvent fraction. Hexane was added to the obtained solvent fraction to form a precipitate, or the solvent fraction was concentrated under reduced pressure, and then hexane was added to obtain an insoluble hexane insoluble fraction. These precipitates and insoluble fractions were subjected to fractional column chromatography to separate Euphorbia factors L1 and L2. It was purified again by high performance liquid chromatography. The separated purified was confirmed by mass spectrometry and nuclear magnetic resonance spectra.
본 발명은 상기와 같이 얻어진 유포비아 팩터 L1, L2를 유연 화장수, 영양 화장수, 영양 크림, 맛사지 크림, 에센스, 펙 등을 포함한 화장료, 비누, 폼 클렌징, 바디 클린저, 샴푸, 린스 등을 포함한 피부 및 모발 세정제, 피부 외용 연고에 첨가하는 것이다. 본 발명을 좀더 상세히 설명하면, 상기 유포비아 팩터 L1, L2를 건조 중량에 대하여 0.0001% - 10% (W/W), 바람직하게는 0.001% - 5% (W/W)를 앞서 언급한 화장료, 피부 및 모발 세정제, 피부 외용 연고에 첨가한다. 상기 농도 이하에서는 실질적인 각질 박리 효과를 기대하기 어렵고, 이상의 농도에서는 더 이상의 각질 박리 효과가 증가되지 않았으며, 또한 제형상 및 제품 안정성에 영향을 미친다. The present invention comprises the skin obtained by the above-mentioned Euphorbia factor L1, L2, including cosmetics, soaps, foam cleansing, body cleanser, shampoo, rinse, etc., including flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, peck and the like. It is added to hair cleansers and skin ointments. DETAILED DESCRIPTION OF THE INVENTION In more detail, the Euphorbia factors L1 and L2 are 0.0001% to 10% (W / W), preferably 0.001% to 5% (W / W), based on the dry weight of the cosmetics mentioned above, It is added to skin and hair cleansers, skin ointments. Below this concentration, it is difficult to expect a substantial exfoliation effect, and at the above concentration no further exfoliation effect is increased, and also affects the formulation and product stability.
본 발명을 다음의 실험 및 실시예로 더욱 상세하게 설명하고자 한다. 그러나 본 발명이 하기의 예에만 국한되지 않음을 밝혀둔다.The present invention will be described in more detail with the following experiments and examples. However, it should be noted that the present invention is not limited to the following examples.
실시예 1Example 1
속수자를 구입하여 분쇄물 100 g을 80% 메탄올 용액 500 ㎖에 넣고, 냉각 콘덴서가 달린 환류 추출기에서 3 시간 끓여 추출한 다음, 300 메쉬 여과포로 여과한 후 잔사를 같은 방법으로 1 회 더 추출하였다. 각각의 추출액을 합하여 상온에서 화트만(Whatman) 2번 여과지로 여과하여 불용성 물질을 제거한 후, 냉각 콘덴서가 달린 증류 장치에서 60℃로 감압 농축하여 정제수 300 ㎖에 현탁한 후 헥산 300 ㎖를 가하고 잘 흔들어 헥산 용해물을 얻었다. 이 헥산 용해물을 실리카 겔 칼럼에서 크로마토그라피하여 유효 성분을 함유하는 분획 650 ㎎을 얻었다. 이를 다시 고속 액체 크로마토그라피로 정제하여 유포비아 팩터 L1, L2를 각각 200 ㎎, 300 ㎎ 분리하였다.Purifier was purchased and 100 g of the pulverized product was put in 500 ml of 80% methanol solution, boiled for 3 hours in a reflux extractor equipped with a cooling condenser, filtered through a 300 mesh filter cloth, and the residue was extracted once more in the same manner. Each extract was combined and filtered using Whatman No. 2 filter paper at room temperature to remove insoluble matters, concentrated under reduced pressure at 60 ° C. in a distillation apparatus equipped with a cooling condenser, suspended in 300 ml of purified water, and then 300 ml of hexane was added. Shake to obtain hexane lysate. This hexane lysate was chromatographed on a silica gel column to give 650 mg of a fraction containing the active ingredient. This was further purified by high performance liquid chromatography to separate 200 mg and 300 mg of Euphorbia factor L1 and L2, respectively.
실시예 2Example 2
속수자를 구입하여 분쇄물 100 g을 상온에서 압착, 여과하여 속수자의 오일 35 ㎖를 얻었다. 위에서 얻은 오일에 에탄올 35 ㎖를 가하여 액-액 추출로 얻은 에탄올 분획을 실리카 겔 칼럼에서 크로마토그라피하여 유효 성분을 함유하는 분획 700 ㎎을 얻었다. 이를 다시 고속 액체 크로마토그라피로 정제하여 유포비아 팩터 L1, L2를 각각 210 ㎎, 350 ㎎ 분리하였다.The water injector was purchased, and 100 g of the pulverized product was pressed at room temperature and filtered to obtain 35 mL of the oil in the inoculator. 35 ml of ethanol was added to the oil obtained above, and the ethanol fraction obtained by liquid-liquid extraction was chromatographed on a silica gel column to obtain 700 mg of a fraction containing the active ingredient. This was further purified by high performance liquid chromatography to separate 210 mg and 350 mg of Euphorbia factor L1 and L2, respectively.
실시예 3Example 3
속수자를 구입하여 분쇄물 100 g을 100% 에탄올 용액 500 ㎖에 넣고, 실시예 1과 동일한 방법으로 실시하여 유포비아 팩터 L1, L2를 각각 200 ㎎, 310 ㎎ 얻었다.100 g of ground product was put in 500 ml of 100% ethanol solution, and it carried out by the same method as Example 1, and obtained 200 mg and 310 mg of Euphorbia factors L1 and L2, respectively.
실시예 4Example 4
속수자 분쇄물 100 g을 클로로포름 용액 500 ㎖에 넣고, 실시예 1과 동일한 방법으로 실시하여 유포비아 팩터 L1, L2를 각각 360 ㎎, 250 ㎎ 얻었다.100 g of the ground water was crushed into 500 ml of chloroform solution, and the same method as in Example 1 was carried out to obtain 360 mg and 250 mg of Euphorbia factors L1 and L2, respectively.
실시예 5Example 5
속수자 분쇄물 100 g을 n-헥산 용액 500 ㎖에 넣고, 냉각 콘덴서가 달린 환류 추출기에서 3 시간 끓여 추출한 다음, 300 메쉬 여과포로 여과한 후 잔사를 같은 방법으로 1 회 더 추출하였다. 각각의 추출액을 합하여 상온에서 화트만100 g of the fastener pulverized product was put into 500 ml of n-hexane solution, boiled for 3 hours in a reflux extractor equipped with a cooling condenser, filtered through a 300 mesh filter cloth, and the residue was extracted once more in the same manner. Combine each extract and use only the white at room temperature
(Whatman) 2번 여과지로 여과하여 불용성 물질을 제거한 후, 냉각 콘덴서가 달린 증류 장치에서 60℃로 감압 농축한 후, 실리카 겔 칼럼에서 크로마토그라피하여 유 효 성분을 함유하는 분획 800 ㎎을 얻었다. 이를 다시 고속 액체 크로마토그라피로 정제하여 유포비아 팩터 L1, L2를 각각 380 ㎎, 280 ㎎ 분리하였다.After filtering by filter paper No. 2, the insoluble substance was removed, concentrated under reduced pressure at 60 ° C. in a distillation apparatus equipped with a cooling condenser, and chromatographed on a silica gel column to obtain 800 mg of the fraction containing the active ingredient. It was purified again by high performance liquid chromatography to separate 380 mg and 280 mg of Euphorbia factor L1 and L2, respectively.
실시예 6Example 6
속수자 분쇄물 100 g을 이용하여 실시예 2와 동일한 방법으로 실시하여 얻은 속수자의 오일 35 ㎖에 80% 에탄올 100 ㎖를 가한 후, 액-액 추출하여 얻은 에탄올 분획을 실리카 겔 칼럼에서 크로마토그라피하여 유효 성분을 함유하는 분획 500 ㎎을 얻었다. 이를 다시 고속 액체 크로마토그라피로 정제하여 유포비아 팩터 L1, L2를 각각 270 ㎎, 180 ㎎을 분리하였다.100 ml of 80% ethanol was added to 35 ml of the oil obtained by the same method as in Example 2 using 100 g of the ground water, and the ethanol fraction obtained by liquid-liquid extraction was purified by chromatography on a silica gel column. 500 mg of the fraction containing the component was obtained. This was further purified by high performance liquid chromatography to separate 270 mg and 180 mg of Euphorbia factor L1 and L2, respectively.
실시예 7Example 7
속수자를 구입하여 분쇄물 100 g을 150℃에서 압착, 여과하여 속수자의 오일 40 ㎖를 얻었다. 위에서 얻은 오일에 90% 아세토나이트릴 200 ㎖를 가하여 액-액 추출로 얻은 아세토나이트릴 분획을 실리카 겔 칼럼에서 크로마토그라피하여 유효 성분을 함유하는 분획 520 ㎎을 얻었다. 이를 다시 고속 액체 크로마토그라피로 정제하여 유포비아 팩터 L1, L2를 각각 280 ㎎, 190 ㎎ 분리하였다.The inner water was purchased, and 100 g of the ground product was pressed at 150 ° C. and filtered to obtain 40 ml of the oil of the ground water. 200 ml of 90% acetonitrile was added to the oil obtained above, and the acetonitrile fraction obtained by liquid-liquid extraction was chromatographed on a silica gel column to obtain 520 mg of the fraction containing the active ingredient. This was further purified by high performance liquid chromatography to separate 280 and 190 mg of Euphorbia factor L1 and L2, respectively.
실시예 8Example 8
속수자를 구입하여 분쇄물 100 g을 150℃에서 압착, 여과하여 속수자의 오일 40 ㎖를 얻었다. 위에서 얻은 오일에 80% 에탄올 용액 10 ㎖를 가한 후, 액-액 추출하여 얻은 에탄올 분획에 헥산을 가하여 침전을 얻고, 침전을 헥산으로 세척하여 헥산 비가용성 분획 450 ㎎을 얻었다. 이를 다시 고속 액체 크로마토그라피로 정제하여 유포비아 팩터 L1, L2를 각각 270 ㎎, 160 ㎎ 분리하였다.The inner water was purchased, and 100 g of the ground product was pressed at 150 ° C. and filtered to obtain 40 ml of the oil of the ground water. 10 ml of 80% ethanol solution was added to the oil obtained above, hexane was added to the ethanol fraction obtained by liquid-liquid extraction, and the precipitate was washed with hexane to obtain 450 mg of hexane insoluble fraction. This was further purified by high performance liquid chromatography to separate Euphorbia Factor L1 and L2 270 mg and 160 mg, respectively.
실험예 1Experimental Example 1
상기 실시예 1 - 8에 따라 얻어진 유포비아 팩터 L1, L2에 대하여 각질 박리 촉진 효과를 측정하였다. 피시험자는 20 세에서 40 세 사이의 건강한 남성 30 명을 대상으로 실시하였다. 시료 도포전 피시험자의 팔 상박부 안쪽 색상을 크로마 미터(CR-200, Minolta, 일본)로 측정한 후 10% 농도의 디하이드록시 아세톤(DHA)을 힐 탑 챔버(The Hill Top사 제조)에 0.4 ㎖ 가량 넣고 팔 상박부 안쪽에 6 시간 동안 부착하였다. 24 시간 경과 후 DHA에 의해 갈색으로 착색된 부위의 색상을 측정하여 시료 도포 전과의 색상 차이를 비교하였다. 이후 1 일 2 회씩 에탄올에 5%로 용해시킨 시료를 도포하면서 매일 탈색되는 정도를 크로마 미터로 측정하여 원래의 피부색으로 돌아오는데 걸리는 시간을 측정하였다. 각질 박리율은 아래의 식으로 계산하였다.The exfoliation promoting effect was measured on the Euphorbia factors L1 and L2 obtained according to Examples 1 to 8 above. The test subjects were 30 healthy men aged 20 to 40 years. Before applying the sample, the color of the inside of the test subject's upper arm was measured with a chromameter (CR-200, Minolta, Japan), and 10% dihydroxy acetone (DHA) was added to the Hill Top chamber (manufactured by The Hill Top). About 0.4 mL was added and attached to the inner arm upper arm for 6 hours. After 24 hours, the color of the brown colored area was measured by DHA to compare the color difference with that before the sample application. Thereafter, while applying a sample dissolved in 5% ethanol twice a day, the degree of discoloration was measured by a chromameter every day to measure the time to return to the original skin color. Keratin peeling rate was calculated by the following formula.
* 각질 박리율(%) = (블랭크의 TT - 시료 도포시 TT)/블랭크의 TT x 100* Keratin exfoliation rate (%) = (TT of blank-TT at sample application) / TT x 100 of blank
TT(Turnover Time): 기존의 각질층이 새로운 각질층으로 대체되는데 걸리는 시간(본 실험에서는 DHA에 의해 착색된 피부가 완전히 원상 복귀되는데 걸리는 시간)TT (Turnover Time): The time it takes for the old stratum corneum to be replaced by the new stratum corneum (in this experiment, the time it takes for the skin colored by DHA to fully revert).
[표 1] TABLE 1
기존의 알파하이드록시산과 유포비아 팩터 L1, L2의 각질 박리 효과 비교Comparison of exfoliation effect between conventional alpha hydroxy acid and Euphorbia factor L1, L2
블랭크*: DHA로 착색후 아무 시료도 바르지 않은 군Blank *: No sample applied after staining with DHA
[표 1]에서 우수한 각질 박리제로 알려진 글리콜릭산(Glycolic acid)과 젖산(Lactic acid)은 5% 농도 사용시 약 20% 정도의 각질 박리 효과를 보인 반면, 같은 농도의 유포비아 팩터 L1, L2는 상기 두 알파하이드록시산에 비해 약 2 배 가까운 38.2%, 40.3%의 각질 박리 효과를 보였다.In Table 1, glycolic acid and lactic acid, which are known as excellent exfoliants, showed about 20% exfoliation effect when the 5% concentration was used, whereas the euphoria factors L1 and L2 of the same concentration were mentioned above. Compared to the two alpha hydroxy acids, the exfoliation effect was about 2 times 38.2% and 40.3%.
[표 2] 농도에 따른 유포비아 팩터 L1, L2의 각질 박리 효과[Table 2] The exfoliation effect of Euphorbia factor L1, L2 according to the concentration
상기 결과에서 유포비아 팩터 L1, L2의 농도가 10%일 경우 48.3%, 53.6%의 각질 박리 효과를 보였으며 0.01% 농도에서는 10% 미만의 효과를 보였다.In the above results, when the concentration of Euphorbia factor L1 and L2 was 10%, the exfoliation effect was 48.3%, 53.6%, and less than 10% at 0.01% concentration.
실험예 2Experimental Example 2
이와같이 각질 박리 효과가 우수한 유포비아 팩터 L1, L2로 다음과 같이 피 부 따가움 유발 정도(sting test)를 측정하였다.As described above, the skin test for stinging was measured with the Euphorbia factors L1 and L2 having excellent exfoliation effect as follows.
피시험자는 20 세에서 35 세 사이의 건강한 여성 30 명을 대상으로 실시하였다. 먼저 세안을 하여 기존에 분비된 피지 및 먼지 등을 제거한 후, 항온항습실 (27℃, 70% 상대습도)에서 15 분간 적응시켰다. 부직포에 에탄올에 용해시킨 시료를 0.4 ㎖ 가량 적신후 코 주변 및 뺨에 부직포를 붙인 후 20 초 경과 뒤에 제거하였다. 부직포 제거후 경과시간 10 초, 150 초, 300 초, 480 초의 시간대 별로 아래의 기준에 의해 피시험자의 주관적 판정으로 따가움 정도를 측정하였다.The test subjects were 30 healthy women aged 20 to 35 years. First of all, after washing the face to remove previously secreted sebum and dust, it was adapted for 15 minutes in a constant temperature and humidity room (27 ℃, 70% relative humidity). 0.4 mL of the sample dissolved in ethanol was soaked in the nonwoven fabric and removed after 20 seconds after attaching the nonwoven fabric around the nose and cheeks. After removing the nonwoven fabric, the degree of tingling was measured by subjective judgment according to the following criteria for each time interval of 10 seconds, 150 seconds, 300 seconds, and 480 seconds.
* 따가움 정도 점수(sting score) 기준* Based on sting score
0: 아무런 느낌이 없다. 1: 미미하게 따끔거린다.0: There is no feeling. 1: I sting slightly.
2: 확연히 따끔거린다. 3: 심하게 따끔거린다.2: I am quite stinging. 3: I feel badly tingling.
[표 3] 따가움 정도 판단 기준[Table 3] criteria for stinging degree
[표 4] 시료 적용에 따른 따가움 정도 점수[Table 4] Score of degree of stinging according to sample application
[표 4]에서 유포비아 팩터 L1, L2 는 같은 농도의 글리콜릭산과 젖산에 비해 낮은 따가움 정도를 보였다.In Table 4, Euphorbia factors L1 and L2 showed a low degree of stinging compared to glycolic acid and lactic acid at the same concentration.
상기와 같이 기존의 알파하이드록시산에 비해 각질 박리 효과가 우수하고 낮은 따가움 정도를 가지는 유포비아 팩터 L1, L2로 다음과 같이 제조예를 실시하였다. 그러나 본 발명이 하기의 제조예에만 국한되지 않음을 거듭 밝혀둔다.As described above, the preparation example was carried out with the Euphorbia factors L1 and L2 having excellent keratin exfoliation effect and low stinging compared with the conventional alpha hydroxy acid. However, it should be noted that the present invention is not limited only to the following preparation examples.
제조예 1 - 2 및 비교예 1Preparation Example 1-2 and Comparative Example 1
유포비아 팩터 L1, L2를 함유하는 피부 외용 연고 처방예는 다음과 같다.Examples of prescription ointments for external skin containing Euphorbia factors L1 and L2 are as follows.
제조예 3 - 4 및 비교예 2Preparation Example 3-4 and Comparative Example 2
유포비아 팩터 L1, L2를 함유하는 화장료 중 크림의 처방예는 다음과 같다.Prescription examples of creams in the cosmetics containing Euphoria factors L1 and L2 are as follows.
제조예 5 - 6 및 비교예 3Preparation Examples 5-6 and Comparative Example 3
유포비아 팩터 L1, L2를 함유하는 화장료중 유연 화장수의 처방예는 다음과 같다.Prescription examples of flexible lotion in cosmetics containing Euphoria factors L1 and L2 are as follows.
제조예 7 - 8 및 비교예 4Preparation Examples 7-8 and Comparative Example 4
유포비아 팩터 L1, L2를 함유하는 화장료 중 영양 화장수의 처방예는 다음과 같다.Prescription examples of nutritional lotion among cosmetics containing Euphoria factors L1 and L2 are as follows.
제조예 9 - 10 및 비교예 5Preparation Example 9-10 and Comparative Example 5
유포비아 팩터 L1, L2를 함유하는 화장료 중 팩의 처방예는 다음과 같다.Prescription examples of packs among cosmetics containing Euphoria factors L1 and L2 are as follows.
제조예 11 - 12 및 비교예 6Preparation Examples 11-12 and Comparative Example 6
유포비아 팩터 L1, L2를 함유하는 화장료 중 에센스의 처방예는 다음과 같다.Prescription examples of essences in the cosmetics containing Euphorbia factors L1 and L2 are as follows.
실험예 3Experimental Example 3
상기 제조예에 대하여 각질 박리 효과 및 따가움 테스트를 실시하여 그 결과를 [표 5]에 나타내었다.Keratin peeling effect and stinging test were carried out for the above production example and the results are shown in [Table 5].
[표 5] 유포비아 팩터 L1, L2 함유 제형의 각질 박리 및 따가움 측정Table 5 Determination of keratin exfoliation and stinging of Euphoria factor L1 and L2 containing formulations
[표 5]에서 볼수 있듯이 본 발명에 의한 제조예들은 유포비아 팩터 L1, L2가 함유되어 있는 모두의 경우에서 각질 박리 효과를 보여주고 있으며, 따가움 정도도 낮게 나타났다.As can be seen in Table 5, the preparation examples according to the present invention show the exfoliation effect in all cases containing Euphorbia factor L1 and L2, and the degree of stinging was also low.
본 발명의 각질 박리 촉진제인 5,15-디아세톡시-3-페닐아세톡시-14-옥소라티라디엔-6(17)-에폭사이드(유포비아 팩터 L1), 및 5,15-디아세톡시-3,7-디벤조일옥시-14-옥소라티라디엔(유포비아 팩터 L2)은 사람을 대상으로 하는 각질 박리 효과 및 피부 따가움 측정 실험에서 기존의 알파하이드록시산에 비해 매우 우수한 효과가 입증된 안정성과 안전성이 뛰어난 동시에 각질 박리 효과가 탁월한 물질이다.
5,15-Diacetoxy-3-phenylacetoxy-14-oxoratyadiene-6 (17) -epoxide (Eupovia factor L1), and 5,15-diacetoxy, which are keratin exfoliation promoters of the present invention -3,7-dibenzoyloxy-14-oxoratyadiene (Eupovia factor L2) has been demonstrated to be superior to conventional alpha hydroxy acids in human exfoliation and skin tingling experiments. It is a material with excellent stability and safety and excellent exfoliation effect.
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JPH08176003A (en) * | 1994-12-27 | 1996-07-09 | Kao Corp | Arachidonic acid metabolism inhibitor |
JPH0971527A (en) * | 1995-07-06 | 1997-03-18 | Kao Corp | External preparation for skin |
JPH09249521A (en) * | 1996-03-13 | 1997-09-22 | Kao Corp | External preparation for skin |
KR20010009623A (en) * | 1999-07-12 | 2001-02-05 | 서경배 | Euphorbia Lathyris extract inhibiting the activity of 5a-reductase, and the cosmetic or skincare-pharmaceutical composition thereof for suppressing pimple or sebum |
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JPH08176003A (en) * | 1994-12-27 | 1996-07-09 | Kao Corp | Arachidonic acid metabolism inhibitor |
JPH0971527A (en) * | 1995-07-06 | 1997-03-18 | Kao Corp | External preparation for skin |
JPH09249521A (en) * | 1996-03-13 | 1997-09-22 | Kao Corp | External preparation for skin |
KR20010009623A (en) * | 1999-07-12 | 2001-02-05 | 서경배 | Euphorbia Lathyris extract inhibiting the activity of 5a-reductase, and the cosmetic or skincare-pharmaceutical composition thereof for suppressing pimple or sebum |
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KR101089314B1 (en) | 2010-06-07 | 2011-12-02 | 한국식품연구원 | Composition for the prevention, treatment or improvement of obesity containing Euphorbia steroid as an active ingredient |
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