EP1165039A2 - Dermatological topical composition - Google Patents

Dermatological topical composition

Info

Publication number
EP1165039A2
EP1165039A2 EP00925137A EP00925137A EP1165039A2 EP 1165039 A2 EP1165039 A2 EP 1165039A2 EP 00925137 A EP00925137 A EP 00925137A EP 00925137 A EP00925137 A EP 00925137A EP 1165039 A2 EP1165039 A2 EP 1165039A2
Authority
EP
European Patent Office
Prior art keywords
uva
ursi
composition according
ascorbic acid
composition
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.)
Withdrawn
Application number
EP00925137A
Other languages
German (de)
English (en)
French (fr)
Inventor
Hiroki Pentapharm Japan Corporation NAKAYAMA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DSM Nutritional Products AG
Original Assignee
Pentapharm AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Pentapharm AG filed Critical Pentapharm AG
Publication of EP1165039A2 publication Critical patent/EP1165039A2/en
Withdrawn legal-status Critical Current

Links

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
    • A61K8/96—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0212—Face masks
    • 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
    • A61K8/35—Ketones, e.g. benzophenone
    • 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
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
    • 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
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A61K8/466—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfonic acid derivatives; Salts
    • 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
    • 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
    • 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
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • A61K8/96—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
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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

Definitions

  • the present invention refers to dermatological topical compositions which comprise a uva-ursi and L-ascorbic acid and/or a derivative of L-ascorbic acid, or an uva-ursi extract and L-ascorbic acid and/or a derivative of L- ascorbic acid and at least one compound selected from UV absorbers, allantoin or its derivatives, and pantethine-S- sulfonate or a salts thereof.
  • uva- ursi and its extracts can be active ingredients of whitening agents and pigmentation reducing agents.
  • the contents of Tokkaihei 6-166609 is incorporated herein by reference.
  • the purpose of the present invention is to use the whitening and pigmentation reducing effects of uva-ursi and its extracts for the preparation of dermatological topical compositions with effects superior to those of existing products of this category by combining uva-ursi and/or its extracts with ingredients which synergistically supplement or enhance their effects.
  • the present invention refers to a dermatological topical composition characterized in that said composition comprises at least a mixture of uva-ursi and L-ascorbic acid and/or a derivative of L-ascorbic acid, or a mixture of an uva-ursi extract and L-ascorbic acid and/or a derivative of L- ascorbic acid further containing at least one compound selected from UV absorbers, allantoin or its derivatives, and pantethine-S-sulfonate or a salt thereof.
  • the present invention further refers to a method of making a dermatological topical compositions according to the present invention said method comprising providing a composition comprising at least (i) a mixture of uva-ursi and L-ascorbic acid and/or a derivative of L-ascorbic acid, or (ii) a mixture of an uva-ursi extract and L-ascorbic acid and/or a derivative of L-ascorbic acid, and adding thereto at least one compound selected from UV absorbers, allantoin or its derivatives, and pantethine-S-sulfonate or a salt thereof.
  • the present invention further refers to the use of said composition as a whitening and pigmentation reducing agent, especially for the topical treatment of the human skin to effectively reduce skin problems caused by pigmentation such as liver spots, freckles and dark complexion.
  • dermatological topical agents according to this invention may be prepared by adding the components in any desired sequence and as mentioned, preferably by adding at least one of the following compounds to mixtures of uva-ursi and L-ascorbic acid and/or its derivatives, or mixtures of uva-ursi extract and L-ascorbic acid and/or its derivatives: UV absorbents, allantoin or its derivatives, and pantethine- S-sulfonate or at least one of its salts.
  • Uva-ursi or the extract of uva-ursi is preferably made be drying and subsequently milling the leafs of arctostaphylos uva-ursi to any desired size.
  • the obtained milled product is left in an aqueous extraction solvent for about 24 hours at room temperature, preferably under stirring.
  • aqueous extraction solvent is preferably a mixture of an organic solvent with water, for example an alcohol or a polyol and water in a ratio of alcohol to water of 1:10 to 10:1, preferably 1:4 to 4:1.
  • an extraction solvent which is a mixture of acetone and water having a ratio of acetone to water from 1:10 to 10:1, preferably 1:5 to 5:1.
  • the filtrate containing uva-ursi is carefully concentrated to dryness, preferably at a temperature below 50°C.
  • the dry extract is dissolved in an aqueous solvent and submitted to an ultra- filtration.
  • the resulting permeate is concentrated and filtrated and used according to the present invention.
  • L-ascorbic acid added to uva-ursi or its extract in the present invention, is generally known as vitamin C and has been shown to promotes cellular respiration, enzymatic activation and collagen formation and to reduce melanin by its potent reducing effects.
  • L-ascorbic acid examples include L-ascorbate monoalkylesters such as L-ascorbate monostearate, L-ascorbate monopalmitate and L-ascorbate monooleate; L-ascorbate monoester derivatives such as L- ascorbate monophosphate ester and L-ascorbate-2-sulfate; L- ascorbate diester derivatives such as L-ascorbate diphosphate esters, e.g.
  • the ratio of uva-ursi to vitamin C and/or the derivative thereof is preferably within the range of about 20:0.5 to 20:5, preferably about 20:0.5 to 20:2 and preferably about 20:1.
  • Dermatological topical agents according to the present invention containing uva-ursi or its extract as the active ingredient to which L-ascorbic acid or its derivatives is added are further outlined in greater details below.
  • UV absorber Any known conventional UV absorber may be added to the dermatological composition of the present invention.
  • UV-absorbers are Benzoate UV absorbers such as Paraaminobenzoate (PABA) , PABA monoglycerin ester, N,N- dipropoxy PABA ethyl ester, N,N-dietoxy PABA ethyl ester, N,N-dimethyl PABA ethyl ester, N,N-dimethyl PABA butylester, N,N-dimethyl PABA amylester, and N,N-dimetyl PABA octyl ester.
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • PABA Paraaminobenzoate
  • anthranilate UV absorbers such as monomethyl-N-acetylanthranilate, homomenthyl-N- acetylanthranilate.
  • salicylate UV absorbents such as amylsalicylate, methylsalicylate, homomenthylsalicylate, octylsalicylate, phenylsalicylate, benzylsalicylate, and p-isopropanolphenylsalicylate.
  • cinnamate UV absorbers such as octylcinnamate, ethyl-4-isopropylcinnamate, methyl-2,5- diisopropylcinnamate, ethyl-2, 4-diisopropylcinnamate, methyl-2, 4-diisopropylcinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate) , 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p- methoxycinnamate, ethyl-
  • UV absorbers such as 2,4- dihydroxybenzophenone, 2, 2 ' -dihydroxy-4-methoxybenzophenone, 2,2' -dihydroxy-4 , 4 ' -dimethoxybenzophenone, 2, 2 ' -4 , 4 ' - tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4 ' -methylbenzophenone, 2-hydroxy-4- methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2- ethylhexyl-4 ' -phenylbenzophenone-2-carboxylate, 2-hydroxy-4- n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenone.
  • UV absorbers are 3- (4 ' -methylbenzilidene) - d, 1-camphor, 3-benzilidene-d, 1-camphor, urocanic acid, ethylester urocanate, 2-phenyl-5-methylbenzoxazol, 2,2'- hydroxy-ethylbenzotriazol, 2- (2 ' -hydroxy-5 ' -t-actylphenyl) benzotriazole, 2- (2 ' -hydroxy-5 ' -methylphenyl) benzotriazole, dibenzaladine, dianisoilmethane, 4-methoxy-4 ' -t- butyldibenzoilmethane, 5- (3, 3-dimethyl-2-norbolnilidene) -3- pentane-2-on.
  • UV absorbents in the dermatological topical composition according to the present invention whose active ingredient is uva-ursi to which L-ascorbic acid or its derivatives are added or uva- ursi extract to which L-ascorbic acid or its derivatives are added.
  • their content is 0.05%-10%, and preferably 0.5%-8%, calculated to the total weight of the dermatological topical preparation.
  • UV absorbers do not prevent sunburn if their content is too low, and this offsets the whitening effects of uva-ursi or its extract. However, if contained in an excess amount, UV absorbers may affect the stability of the dermatological topical composition.
  • ingredients of cosmetic and pharmaceutical products may be added as necessary to the dermatological topical preparations according to the present invention.
  • Such ingredients are for example oils, antioxidants, surfactants, moisturizing agents, flavors, water, alcohols, viscosity donors, antiseptics, colorants, powders, and drugs.
  • the dermatological topical preparations according to the present invention may be made available in any dosage form, including solubilized preparations (such as toilet lotions) , emulsified preparations (milky liquid or creamy preparations), ointments, and dispersions.
  • Dermatological topical compositions according to the present invention prepared by adding allantoin derivatives to uva- ursi or its extract containing L-ascorbic acid or its derivatives are outlined below. Allantoin derivatives used for this purpose include dihydroxyalluminum allantoinate and chlorohydroxyalluminum allantoinate. To reduce the present invention into practice, allantoin or 1 or 2 or more of its derivatives are selected as necessary. Their content should be 0.01%-5.0% (preferably 0.1%-3.0%) of the total weight of the dermatological topical preparations.
  • compositions according to the present invention prepared by adding allantoin or its derivatives to uva-ursi or its extract containing L-ascorbic acid or its derivatives: surfactants, oils, moisturizing agents, UV absorbers, antioxidants, antiseptics, flavors, water, alcohol, chelating agents, pH-adjusters, and/or viscosity donors.
  • Dermatological topical preparations according to the present invention are not only useful in the form creams (such as nutrient creams, hand creams, body creams, and massage creams) , nutrient milky lotions, packs, and toilet waters but also as hair treatment compositions, in particular for scalp treatment.
  • creams such as nutrient creams, hand creams, body creams, and massage creams
  • nutrient milky lotions such as nutrient milky lotions, packs, and toilet waters
  • hair treatment compositions in particular for scalp treatment.
  • Dermatological topical preparations prepared by adding pantethine-S-sulfonate (PPS) or its salts to uva-ursi or its extract containing L-ascorbic acid or its derivatives are outlined below.
  • PPS pantethine-S-sulfonate
  • I formula (I)
  • compound of formula (I) is found in carrots and is known as a factor that promotes the growth of Bifidobacterium bifidum. It is also known to exert whitening effects .
  • PSS can be used in the form of the free acid or in its salt form. Although a wide range of organic and inorganic acid salts can be employed, alkali metal salts and alkali earth metal salts thereof are preferred.
  • PPS and/or its salts are used with uva-ursi at weight ratios of PPS and/or its salts to uva-ursi of 1:0.1 or higher, preferably at weight ratios of 1:0.1 to 1:10 and more preferably at 1:0.5 to 1:5. The ratio of less than 1:0.1 is undesirable because a sufficient stabilising effects cannot be obtained.
  • compositions according to the present invention can be added as necessary to the dermatological topical compositions according to the present invention in addition to uva-ursi, PSS or its salts.
  • Such products are aqueous ingredients, powdered ingredients, surfactants, moisturizing agents, viscosity donors, UV absorbers, colorants, drugs, and flavors. These ingredients of course must be added in quantities and quality standards that do not affect the effects of the composition according to the present invention.
  • Dermatological topical preparations under the present invention may be produced in any dosage form, including those commonly used for topical preparations of this type such as ointments, creams, milky lotions and lotions.
  • 100 parts of leafs of arctostaphylos uva-ursi was dried at 75 °C for 24 hours and milled to a fine powder.
  • the obtained powder was mixed with 300 parts of a water/acetone mixture (80 parts of water, 20 parts of acetone) and left at room temperature under stirring for 24 hours.
  • the mixture was then filtered and concentrated under vacuum at a temperature of 45°C to a third of its original volume.
  • the concentrate was then treated in an ultra-centrifuge to separate from any fine components.
  • the concentrate was then further concentrated to a volume of about 50 ml and left at a temperature of 5°C where upon a crystallised product of uvi-ursi was obtained. Both the crystallised product as well as the obtained concentrate were used to prepare the composition of the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Emergency Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP00925137A 1999-03-26 2000-03-24 Dermatological topical composition Withdrawn EP1165039A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP11083961A JP2000281555A (ja) 1999-03-26 1999-03-26 皮膚外用剤
JP8396199 1999-03-26
PCT/EP2000/002629 WO2000057840A2 (en) 1999-03-26 2000-03-24 Dermatological topical composition

Publications (1)

Publication Number Publication Date
EP1165039A2 true EP1165039A2 (en) 2002-01-02

Family

ID=13817169

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00925137A Withdrawn EP1165039A2 (en) 1999-03-26 2000-03-24 Dermatological topical composition

Country Status (7)

Country Link
EP (1) EP1165039A2 (ko)
JP (1) JP2000281555A (ko)
KR (1) KR20010102468A (ko)
CN (1) CN1345228A (ko)
AU (1) AU4396500A (ko)
CA (1) CA2362388A1 (ko)
WO (1) WO2000057840A2 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10732171B2 (en) 2011-12-20 2020-08-04 The Procter & Gamble Company Human skin sample methods and models for validating hypotheses for mechanisms driving skin pigmentation

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2829696B1 (fr) * 2001-09-17 2004-02-27 Oreal Utilisation de l'acide pantetheine sulfonique et/ou de ses sels en tant qu'agent anti-radicalaire
US7429391B2 (en) 2004-01-30 2008-09-30 Access Business Group International Llc Holistic composition and method for reducing skin pigmentation
CA2896646A1 (en) * 2012-12-27 2014-07-03 Hayashibara Co., Ltd. Skin-exterior anti-ageing composition and production method therefor

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH502821A (fr) * 1969-01-07 1971-02-15 Dso Pharmachim Produit cosmétique de blanchiment de l'hyperpigmentation de la peau
GB1224145A (en) * 1969-01-16 1971-03-03 Dso Farmacim Composition for bleaching hyperpigmentation of the skin
JPS6479103A (en) * 1987-06-09 1989-03-24 Lion Corp External preparation
JP3167148B2 (ja) * 1991-09-11 2001-05-21 第一製薬株式会社 美白剤
US5958437A (en) * 1997-06-06 1999-09-28 Geneda Corporation Dermatological healing kit, components therefor, and process for making

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0057840A2 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10732171B2 (en) 2011-12-20 2020-08-04 The Procter & Gamble Company Human skin sample methods and models for validating hypotheses for mechanisms driving skin pigmentation

Also Published As

Publication number Publication date
JP2000281555A (ja) 2000-10-10
AU4396500A (en) 2000-10-16
KR20010102468A (ko) 2001-11-15
CN1345228A (zh) 2002-04-17
WO2000057840A3 (en) 2001-01-11
WO2000057840A2 (en) 2000-10-05
CA2362388A1 (en) 2000-10-05

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