WO1998017247A1 - Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether - Google Patents

Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether Download PDF

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Publication number
WO1998017247A1
WO1998017247A1 PCT/US1996/016942 US9616942W WO9817247A1 WO 1998017247 A1 WO1998017247 A1 WO 1998017247A1 US 9616942 W US9616942 W US 9616942W WO 9817247 A1 WO9817247 A1 WO 9817247A1
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Prior art keywords
composition
skin
weight
water
aqueous topical
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PCT/US1996/016942
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French (fr)
Inventor
Takayoshi Sakoda
Kazumi Toyama
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The Procter & Gamble Company
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Application filed by The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to EP96937713A priority Critical patent/EP0939616A1/en
Priority to KR1019990703478A priority patent/KR20000052690A/en
Priority to BR9612753-8A priority patent/BR9612753A/en
Priority to CZ991414A priority patent/CZ141499A3/en
Priority to PCT/US1996/016942 priority patent/WO1998017247A1/en
Priority to JP9534362A priority patent/JPH11510820A/en
Priority to AU75187/96A priority patent/AU7518796A/en
Priority to CA002269290A priority patent/CA2269290A1/en
Publication of WO1998017247A1 publication Critical patent/WO1998017247A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37Esters of carboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/39Derivatives containing from 2 to 10 oxyalkylene groups
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin

Definitions

  • the present invention relates to an aqueous topical compositions such as lotions, toners, and astringents comprising kojic acid, salicylic acid and a water soluble glycol ether which is useful for lightening of mammalian skin.
  • Skin lightening is an important skin care need, especially in the Asian population. This includes overall lightening of basal skin tone and hyperpigmented lesions. It is generally known that conditions which result in defective or missing tyrosinase, an enzyme involved in the formation of melanin, lead to a loss of pigmentation, e.g. albinism. Conversely, it is known that inhibition of tyrosinase leads to skin lightening via inhibition of melanogenesis. See King, R. A. and C. G. Summers, Dermatoloeic Clinics. Vol. 6 pp. 217-227 (1988).
  • Tyrosinase is present within the melanosomes in epidermal melanocytes and catalyzes the formation of melanin from tyrosine. See Goldsmith, L. A., Physiology. Biochemistry, and Molecular Biology of the Skin. Oxford University Press, pp. 873-903 (N.Y. 1991). Binding of an inhibitor to the active site of tyrosinase results in decreased melanin formation. See generally Prota, G. Melanins and Melanogenesis. Academic Press, Inc., (San Diego 1992).
  • any active in any composition especially when used for topical application (whether for pharmaceutical or cosmetic purposes) must be efficacious, bioavailable, stable when exposed to light, air or to the skin. Should the product be unstable, the breakdown products of the active must be innocuous.
  • kojic acid One known tyrosinase inhibitor is kojic acid.
  • Kojic acid has been found to be quite useful for topical skin lightening compositions.
  • kojic acid is quite expensive.
  • kojic acid does not have an exfoliation effect.
  • One solution to add exfoliation effect on kojic acid is the addition of salicylic acid to the topical composition.
  • Salicylic acid is commonly used in topical compositions because of its exfoliation effects. When combined with kojic acid, salicylic acid exfoliates mammalian skin which results in improving removal effect of skin pigmentation.
  • An example of such a topical skin lightening composition is found in Japanese Patent Laid-open (KOKAI) No. 7- 300404.
  • the present invention relates to an aqueous topical composition for skin lightening comprising:
  • composition from about 20% to about 30% by weight of the composition, of a water soluble glycol ether of the general formula: R 1 -0-[(CH2)mO]nH; wherein R 1 is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2; wherein said composition has a pH from about 2.5 to about 4, and is absent of thickeners.
  • R 1 is an alkyl of 1 to 6 carbon atoms
  • m is from about 2 to about 3
  • n is from about 1 to about 2
  • said composition has a pH from about 2.5 to about 4, and is absent of thickeners.
  • the composition of the present invention provides an aqueous topical composition without thickener which is useful for lightening of mammalian skin.
  • the composition enhances the penetration of kojic acid to mammalian skin.
  • the composition has excellent lightening effect for mammalian skin, yet requires lower levels of kojic acid than previously believed necessary.
  • the reduced level of kojic acid results in a significant cost savings.
  • composition of the present invention comprises a safe and effective amount of kojic acid.
  • Kojic acid which is 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one is a well known active component and is described in the Merck Index, eleventh edition, page 838 (1989).
  • the structure of kojic acid is as follows:
  • Kojic acid is used as a skin lightening ingredient to inhibit formation of melanin. If the composition comprises more than about 3% by weight of the composition, of kojic acid, it is not economical, and if it comprises less than about 0.5% by weight of the composition, of kojic acid, enough skin lightening effect is not expected. Typically, the composition of the present invention comprises from about 0.5% to about 3%, preferably from about 1% to about 2% by weight of the composition, of kojic acid.
  • SALICYLIC ACID SALICYLIC ACID
  • composition of the present invention comprises a safe and effective amount of salicylic acid.
  • Salicylic acid which is 2-hydroxybenzoic acid is a well known active component and is described in the Merck Index, eleventh edition, page 1324 (1989).
  • T e structure of salicylic acid is as follows:
  • Salicylic acid is used to exfoliate mammalian skin and to enhance penetration of kojic acid to mammalian skin. If the composition comprises more than about 2% by weight of the composition, of salicylic acid, it will cause irritation, and if it comprises less than about 1% by weight of the composition, of salicylic acid, enough exfoliation effect and enough penetration enhancing effect is not expected. Typically, the composition of the present invention comprises from about 1% to about 2%, preferably from about 1.2% to about 1.5% by weight of the composition, of salicylic acid.
  • C. WATER T e composition of the present invention comprises water. Water is used as a solvent.
  • composition comprises more than 78.5% by weight of the composition, of water, other ingredients which are required in the present invention cannot be included, and if the composition comprises less than 40% by weight of the composition, of water, it is not economical.
  • the composition of the present invention comprises from about 40% to about 78.5%, preferably from about 45% to about 70% by weight of the composition, of water.
  • the composition of the present invention comprises water soluble glycol ether.
  • Water soluble glycol ether can be characterized by the general formula: Rl-0-[(CH2)mO]nH; wherein R is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2.
  • R* include methyl, ethyl, propyl, butyl and hexyl groups.
  • This glycol ether having a diethylene group as the alkylene group and ethyl group as the alkyl moiety is diethyleneglycol monoethyl ether which has been given the CTFA (The Cosmetic, Toiletry and Fragrance Association) designation ethoxydiglycol.
  • CTFA Cosmetic, Toiletry and Fragrance Association
  • Preferred water soluble glycol ether are diethyleneglycol monoethyl ether which is commercially available by the tradename TRANSCUTOL from Gattefosse, France; diethyleneglycol monomethyl ether; and dipropyleneglycol monomethyl ether and the more preferred water soluble glycol ether is diethyleneglycol monoethyl ether.
  • Water soluble glycol ether is used as a solvent of salicylic acid and to aid enhancing penetration of kojic acid to mammalian skin. If the composition comprises more than about
  • aqueous topical composition of the present invention can optionally comprise one or more components which are commonly used in such topical compositions. Examples of such optional components are discussed in more detail below.
  • thickeners not be present in the composition because it decreases the penetration effect of kojic acid to mammalian skin.
  • Thickeners means ingredients which are commonly used to increase the viscosity of cosmetics.
  • the thickeners include natural, semi-synthetic and synthetic types. Natural thickeners include gum arabic, traganth, carrageenan, xanthan gum, gelatin and sodium chondroitin sulfate.
  • Semi-synthetic thickeners include methyl cellulose, carboxymethyl cellulose, sodium nitro cellulose, ethyl cellulose, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxy propyl cellulose, rice starch, wheat starch, sodium alginate and propylene glycol alginate.
  • Synthetic thickeners include polyvinyl alcohol, polyvinyl pyrrolidone, poly (vinyl acetate), sodium polyacrylate, polyacrylic resin, alkanolamine solution, poly (ethyl methacrylate), carboxyvinyl polymer, poly(ethylene glycol) and copolymer of polyoxyethylene and polyoxypropylene.
  • the composition preferably have a pH from about 2.5 to about 4, preferably a pH from about 3 to about 4. If pH is more than 4, preferred exfoliation effect of salicylic acid and preferred skin lightening effect of kojic acid cannot be expected, and if pH is less than 2.5, it will cause skin damage.
  • Polyhydric alcohol is used as a moisturizer. If the composition comprises more than about 15% of polyhydric alcohol, it is not economical, and causes safety issues, and if it comprises less than about 2%, the moisturizing effect is not expected.
  • Compositions of this invention can optionally comprise from about 2% to about 15%, preferably from about 3% to about 10% by weight of the composition, of polyhydric alcohols such as propylene glycol, hexylene glycol, glycerin, and propane diol. Among the polyhydric alcohol, glycerin is preferred.
  • Lower alcohols having 1 to 3 carbons can be used to impart a refreshing feel or cool sensation to the skin. If the composition comprises more than about 15% of the lower alcohols, it will cause irritation, and if the composition comprises less than about 2% of the lower alcohols, the refreshing feel and cool sensation effect is not expected.
  • compositions of this invention can optionally comprise from about 2% to about 15%, preferably from about 3% to about 10% by weight of the composition, of lower alcohols having 1 to 3 carbons such as ethanol and isopropanol Among the lower alcohols having 1 to 3 carbons, ethanol is preferred.
  • Ethanol is preferably comprised upon making compositions which are designed to impart a refreshing feel or cool sensation to the skin. It is known that ethanol in the composition helps improve solubility of salicylic acid. This level of ethanol is expected to provide the desired refreshing feel to skin without being irritating or excessively drying to the skin. 2.
  • Nonionic surfactant is preferably comprised upon making compositions which are designed to impart a refreshing feel or cool sensation to the skin. It is known that ethanol in the composition helps improve solubility of salicylic acid. This level of ethanol is expected to provide the desired refreshing feel to skin without being irritating or excessively drying to the skin.
  • Nonionic surfactant is used to aid dissolving other ingredients. If the composition comprises more than about 5% of nonionic surfactant, it is not economical and may cause safety issues, and if it comprises less than about 1% of nonionic surfactant, the effect to aid dissolving other ingredients is not expected.
  • Compositions of this invention can optionally comprise from about 1% to about 5%, preferably from about 2% to about 4% by weight of the composition, of a nonionic surfactant.
  • Nonionic surfactant acts as a co-solubilizer of salicylic acid, thereby allowing higher salicylic acid level when using the same solvent.
  • Nonionic surfactants useful herein include any of the well-known nonionic surfactants that have an HLB (hydrophile-lipophile balance) from about 10 to about 18, preferably from about 12 to 16.
  • Non-limiting examples of these nonionic surfactants are ethoxylated or propoxylated, preferably ethoxylated, alcohols and alkyl phenols with alcohol derivatives preferred.
  • these alcohol derivatives contain a straight or branched chain alkyl group having 8-22 carbons, preferably 10-20 carbons, more preferably 12-20 carbons, and generally contain from about 6 to about 30, preferably from about 8 to about 25, ethylene oxide or propylene oxide groups.
  • the ethoxylated derivatives are preferred.
  • Dialkylpolvsiloxane-polvoxyalkylene copolvmer Compositions of this invention can optionally comprise a dialkylpolysiloxane- polyoxyalkylene copolymer. Such a copolymer is expected to improve the overall skin feel imparted by the composition and to reduce any irritation which might be caused by a component of the present invention. If the composition comprises more than about 5% of dialkylpolysiloxane-polyoxyalkylene copolymer, it is not economical and may cause safety issues, and if it comprises less than about 1% of dialkylpolysiloxane-polyoxyalkylene copolymer, the effect of improving overall skin is not expected.
  • the composition preferably comprises from about 1% to about 5% of dialkylpolysiloxane - polyoxyalkylene copolymer, most preferably from about 2% to about 4% dialkylpolysiloxane - polyoxyalkylene copolymer.
  • Dialkylpolysiloxane - polyoxyalkylene copolymers useful herein include those which are soluble in water. Dimethylpolysiloxane-polyoxyalkylene copolymers, known as Dimethicone copolyols where the polyoxyalkylene group can be a polyoxyethylene or a polyoxypropylene group or a combination of both, are particularly useful.
  • the dimethylpolysiloxane portion is typically made of from 10 to about 30 units, preferably around 15 to 20 units.
  • the polyalkylene portion is typically made of from 8 to about 12, preferably from 10 to about 12 units. 4. Sunscreens, conditioning agents, vitamins, perfumes, etc.
  • optional components can be included in the aqueous topical compositions of the present invention, depending on the needs of the product.
  • optional components include water-soluble additional surfactants to aid solubility of the composition, water-soluble ultraviolet and infrared screening and absorbing agents to screen and absorb ultraviolet and infrared, water-soluble anti-inflammatory agents to reduce inflammation, water-soluble anti-oxidant radical scavenging agents to control oxidation and scavenge radical, water-soluble chelating agents to chelate metal, water-soluble skin conditioning agents to condition skin, water-soluble perfume for preference, water-soluble color for preference, water-soluble pH adjusters for adjusting pH, water-soluble dyes for preference, water-soluble vitamins to condition skin, water-soluble proteins to condition skin, water-soluble plant extracts to condition skin, and water-soluble nutrients to condition skin.
  • a composition of the present invention can include at least one anti-colouring agent selected from the group consisting of sodium metabisulfite, sodium bisulfite and sodium sulfite.
  • a wide variety of acids, bases, buffers, and sequestrants can be utilized to adjust and or maintain the pH and ionic strength of the compositions useful in the present invention.
  • Materials useful for adjusting and/or maintaining the pH and/or the ionic strength include sodium carbonate, sodium hydroxide, hydrochloric acid, phosphoric acid, sulfuric acid, acetic acid, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium citrate, sodium bicarbonate, triethanolamine, EDTA (ethylenediaminetetraacetic acid), disodium EDTA, tetrasodium EDTA, and the like.
  • compositions of the present invention are typically formulated to have a pH from about 2.5 to about 4, preferably a pH from about 3 to about 4.
  • aqueous topical compositions of the present invention include lotions, toners and astringents.
  • the present invention also relates to methods for skin lightening in mammals comprising topical application of the skin lightening composition of the present invention.
  • the amount of active agent and frequency of application will vary widely depending upon the skin color already in existence in the subject, the rate of further darkening of the skin, and the level of lightening desired.
  • a safe and effective amount of skin lightening agent in a topical composition is applied, generally from about 1 mg to about 10 mg per cm ⁇ skin per application, preferably from about 2 mg to about 8 mg/ cm ⁇ skin per application, more preferably from about 3 mg to about 7 mg/cm ⁇ skin, also preferably from about 4 mg to about 5 mg/cm ⁇ skin.
  • Application preferably ranges from about four times a day to about twice a week, more preferably from about three times a day to about once every other day, more preferably still from about once daily to about twice daily.
  • Application for at least five days is required to see a skin lightening effect in lower animals.
  • Application for at least one month is required to see an effect in humans.
  • the frequency and dosage can be reduced to a maintenance level, as desired.
  • maintenance varies according to the individual, but is preferably from about 1/10 to about 1/2, more preferably from about 1/5 to about 1/3 of the original dosage and/or frequency, as needed.
  • TRANSCUTOL is diethyleneglycol monoethyl ether which is commercially available from
  • compositions shown in Table 1 can be prepared by any conventional method well known in the art.
  • An example of a suitable preparing method which may be used is described as follows:
  • Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
  • glycerin, sodium citrate, citric acid and water are mixed together to obtain water phase-I.
  • Water phase-I is also mixed at about 70-75 °C.
  • the salicylic acid/TRANSCUTOL mixture is then slowly added to water phase-I and mixed at 75 °C for 30 minutes to obtain mixture- 1.
  • Kojic acid, sodium metabisulfite and water are mixed together to obtain water phase-II.
  • Water phase-U is also mixed at 45 °C.
  • water phase-H and D&C yellow #10 are also added to mixture- 1 to obtain a lotion.
  • Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
  • water phase-I sodium citrate, citric acid, Isoceteth 20 and water are mixed together to obtain water phase-I.
  • Water phase-I is also mixed at about 70-75 °C.
  • the salicylic acid TRANSCUTOL mixture is then slowly added to water phase-I and mixed at 75 °C for 30 minutes to obtain a lotion.
  • Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
  • glycerin, sodium citrate, citric acid, Isocetech 20 and water are mixed together to obtain water phase-I.
  • Water phase-I is also mixed at about 70-75 °C.
  • the salicylic acid/TRANSCUTOL mixture is then slowly added to water phase-I and mixed at 75 °C for 30 minutes to obtain mixture- 1.
  • Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to obtain water phase-II.
  • Water phase-II is also mixed at 45 °C.
  • water phase-II and D&C yellow #10 are also added to mixture- 1 to obtain a lotion.
  • Preparing method of Example No. 4 Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
  • water phase-I glycerin, sodium citrate, citric acid, Isoceteth 20 and water are mixed together to obtain water phase-I.
  • Water phase-I is also mixed at about 70-75 °C.
  • the salicylic acid/TRANSCUTOL mixture is then slowly added to the water phase-I and mixed at 75 °C for 30 minutes to obtain mixture-1.
  • Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to obtain water phase-II.
  • Water phase-II is also mixed at 45 °C. Then water phase-II is also added to mixture-1 to obtain a lotion.
  • compositions of the present invention have improved skin penetration enhancing effect of kojic acid compared versus compositions which comprise thickener and/or comprise more than about 30% by weight of the composition, of water soluble glycol ether.
  • a strong lightening effect of mammalian skin will be obtained by the compositions of the present invention, due to the resulting strong skin penetration enhancing effect of kojic acid.
  • Example No. 5 This example sets forth a method for lightening mammalian skin using a composition of the present invention.
  • the composition of example No. 1 is applied 5 mg / cm ⁇ skin per application three times a day for one month. After one month, a significant skin lightening effect is seen. Once the desired level of the skin lightening is achieved, treatment is reduced to limit a day, to maintain the level of lightening.

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Abstract

Disclosed is an aqueous topical composition for skin lightening comprising: (a) a safe and effective amount of kojic acid, (b) a safe and effective amount of salicylic acid, (c) water, and (d) from about 20 % to about 30 % by weight of the composition, of a water soluble glycol ether of the general formula R1-O-[(CH¿2?)mO]nH; wherein R?1¿ is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2; wherein said composition has a pH from about 2.5 to about 4, and is absent of a thickener. Also disclosed is a method for lightening mammalian skin comprising topically applying to the skin said aqueous topical composition.

Description

AQUEOUS TOPICAL COMPOSITIONS COMPRISING KOJIC ACID, SALICYLIC ACID AND A WATER SOLUBLE GLYCOL ETHER
TECHNICAL FIELD The present invention relates to an aqueous topical compositions such as lotions, toners, and astringents comprising kojic acid, salicylic acid and a water soluble glycol ether which is useful for lightening of mammalian skin. BACKGROUND OF THE INVENTION
Skin lightening is an important skin care need, especially in the Asian population. This includes overall lightening of basal skin tone and hyperpigmented lesions. It is generally known that conditions which result in defective or missing tyrosinase, an enzyme involved in the formation of melanin, lead to a loss of pigmentation, e.g. albinism. Conversely, it is known that inhibition of tyrosinase leads to skin lightening via inhibition of melanogenesis. See King, R. A. and C. G. Summers, Dermatoloeic Clinics. Vol. 6 pp. 217-227 (1988).
Tyrosinase is present within the melanosomes in epidermal melanocytes and catalyzes the formation of melanin from tyrosine. See Goldsmith, L. A., Physiology. Biochemistry, and Molecular Biology of the Skin. Oxford University Press, pp. 873-903 (N.Y. 1991). Binding of an inhibitor to the active site of tyrosinase results in decreased melanin formation. See generally Prota, G. Melanins and Melanogenesis. Academic Press, Inc., (San Diego 1992).
The art has produced certain tyrosinase inhibitors. However, it is well recognized in the art that any active in any composition, especially when used for topical application (whether for pharmaceutical or cosmetic purposes) must be efficacious, bioavailable, stable when exposed to light, air or to the skin. Should the product be unstable, the breakdown products of the active must be innocuous.
One known tyrosinase inhibitor is kojic acid. Kojic acid has been found to be quite useful for topical skin lightening compositions. Unfortunately, kojic acid is quite expensive. In addition, kojic acid does not have an exfoliation effect. One solution to add exfoliation effect on kojic acid is the addition of salicylic acid to the topical composition. Salicylic acid is commonly used in topical compositions because of its exfoliation effects. When combined with kojic acid, salicylic acid exfoliates mammalian skin which results in improving removal effect of skin pigmentation. An example of such a topical skin lightening composition is found in Japanese Patent Laid-open (KOKAI) No. 7- 300404. The costs of such a composition, however, are still quite high due primarily to the amount and costs of kojic acid. Consequently, there is a need for an economical composition comprising kojic acid which efficaciously lightens mammalian skin. SUMMARY
The present invention relates to an aqueous topical composition for skin lightening comprising:
(a) a safe and effective amount of kojic acid,
(b) a safe and effective amount of salicylic acid,
(c) water, and
(d) from about 20% to about 30% by weight of the composition, of a water soluble glycol ether of the general formula: R1-0-[(CH2)mO]nH; wherein R1 is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2; wherein said composition has a pH from about 2.5 to about 4, and is absent of thickeners.
The composition of the present invention provides an aqueous topical composition without thickener which is useful for lightening of mammalian skin. The composition enhances the penetration of kojic acid to mammalian skin. By the excellent penetration effect of kojic acid to mammalian skin, the composition has excellent lightening effect for mammalian skin, yet requires lower levels of kojic acid than previously believed necessary. The reduced level of kojic acid results in a significant cost savings.
DETAIL DESCRIPTION All percentages and ratios are based on weight, and all measurements are conducted at
25 °C, unless otherwise specified. A. KOJIC ACID
The composition of the present invention comprises a safe and effective amount of kojic acid. Kojic acid which is 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one is a well known active component and is described in the Merck Index, eleventh edition, page 838 (1989). The structure of kojic acid is as follows:
Figure imgf000004_0001
Kojic acid is used as a skin lightening ingredient to inhibit formation of melanin. If the composition comprises more than about 3% by weight of the composition, of kojic acid, it is not economical, and if it comprises less than about 0.5% by weight of the composition, of kojic acid, enough skin lightening effect is not expected. Typically, the composition of the present invention comprises from about 0.5% to about 3%, preferably from about 1% to about 2% by weight of the composition, of kojic acid. B. SALICYLIC ACID
The composition of the present invention comprises a safe and effective amount of salicylic acid. Salicylic acid which is 2-hydroxybenzoic acid is a well known active component and is described in the Merck Index, eleventh edition, page 1324 (1989). T e structure of salicylic acid is as follows:
Figure imgf000005_0001
Salicylic acid is used to exfoliate mammalian skin and to enhance penetration of kojic acid to mammalian skin. If the composition comprises more than about 2% by weight of the composition, of salicylic acid, it will cause irritation, and if it comprises less than about 1% by weight of the composition, of salicylic acid, enough exfoliation effect and enough penetration enhancing effect is not expected. Typically, the composition of the present invention comprises from about 1% to about 2%, preferably from about 1.2% to about 1.5% by weight of the composition, of salicylic acid. C. WATER T e composition of the present invention comprises water. Water is used as a solvent.
If the composition comprises more than 78.5% by weight of the composition, of water, other ingredients which are required in the present invention cannot be included, and if the composition comprises less than 40% by weight of the composition, of water, it is not economical. Typically, the composition of the present invention comprises from about 40% to about 78.5%, preferably from about 45% to about 70% by weight of the composition, of water. P. WATER SOLUBLE GLYCOL ETHER
The composition of the present invention comprises water soluble glycol ether. Water soluble glycol ether can be characterized by the general formula: Rl-0-[(CH2)mO]nH; wherein R is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2. Examples of the alkyl group R* include methyl, ethyl, propyl, butyl and hexyl groups. This glycol ether having a diethylene group as the alkylene group and ethyl group as the alkyl moiety is diethyleneglycol monoethyl ether which has been given the CTFA (The Cosmetic, Toiletry and Fragrance Association) designation ethoxydiglycol. Preferred water soluble glycol ether are diethyleneglycol monoethyl ether which is commercially available by the tradename TRANSCUTOL from Gattefosse, France; diethyleneglycol monomethyl ether; and dipropyleneglycol monomethyl ether and the more preferred water soluble glycol ether is diethyleneglycol monoethyl ether. Water soluble glycol ether is used as a solvent of salicylic acid and to aid enhancing penetration of kojic acid to mammalian skin. If the composition comprises more than about
30% of water soluble glycol ether, enough penetration effect of kojic acid is not expected, it is not mild enough to skin and it is not economical, and if the composition comprises less than 20% of water soluble glycol ether, salicylic acid cannot be dissolved in it.
Typically the water soluble glycol ether is included in the composition in amounts from about 20% to about 30%, preferably from about 23% to about 27% by weight of the composition, of water soluble glycol ether. E. OPTIONAL COMPONENTS The aqueous topical composition of the present invention can optionally comprise one or more components which are commonly used in such topical compositions. Examples of such optional components are discussed in more detail below.
However, it is an important aspect of the invention that thickeners not be present in the composition because it decreases the penetration effect of kojic acid to mammalian skin. Thickeners means ingredients which are commonly used to increase the viscosity of cosmetics. The thickeners include natural, semi-synthetic and synthetic types. Natural thickeners include gum arabic, traganth, carrageenan, xanthan gum, gelatin and sodium chondroitin sulfate. Semi-synthetic thickeners include methyl cellulose, carboxymethyl cellulose, sodium nitro cellulose, ethyl cellulose, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxy propyl cellulose, rice starch, wheat starch, sodium alginate and propylene glycol alginate. Synthetic thickeners include polyvinyl alcohol, polyvinyl pyrrolidone, poly (vinyl acetate), sodium polyacrylate, polyacrylic resin, alkanolamine solution, poly (ethyl methacrylate), carboxyvinyl polymer, poly(ethylene glycol) and copolymer of polyoxyethylene and polyoxypropylene.
It is also an important aspect of the invention that after all of the optional components are added, the composition preferably have a pH from about 2.5 to about 4, preferably a pH from about 3 to about 4. If pH is more than 4, preferred exfoliation effect of salicylic acid and preferred skin lightening effect of kojic acid cannot be expected, and if pH is less than 2.5, it will cause skin damage.
Examples of optional compositions which may be used in the present invention include the following.
1. Polyhydric alcohol and lower alcohols having 1 to 3 carbons
Polyhydric alcohol is used as a moisturizer. If the composition comprises more than about 15% of polyhydric alcohol, it is not economical, and causes safety issues, and if it comprises less than about 2%, the moisturizing effect is not expected. Compositions of this invention can optionally comprise from about 2% to about 15%, preferably from about 3% to about 10% by weight of the composition, of polyhydric alcohols such as propylene glycol, hexylene glycol, glycerin, and propane diol. Among the polyhydric alcohol, glycerin is preferred.
Lower alcohols having 1 to 3 carbons can be used to impart a refreshing feel or cool sensation to the skin. If the composition comprises more than about 15% of the lower alcohols, it will cause irritation, and if the composition comprises less than about 2% of the lower alcohols, the refreshing feel and cool sensation effect is not expected.
Compositions of this invention can optionally comprise from about 2% to about 15%, preferably from about 3% to about 10% by weight of the composition, of lower alcohols having 1 to 3 carbons such as ethanol and isopropanol Among the lower alcohols having 1 to 3 carbons, ethanol is preferred.
Ethanol is preferably comprised upon making compositions which are designed to impart a refreshing feel or cool sensation to the skin. It is known that ethanol in the composition helps improve solubility of salicylic acid. This level of ethanol is expected to provide the desired refreshing feel to skin without being irritating or excessively drying to the skin. 2. Nonionic surfactant
Nonionic surfactant is used to aid dissolving other ingredients. If the composition comprises more than about 5% of nonionic surfactant, it is not economical and may cause safety issues, and if it comprises less than about 1% of nonionic surfactant, the effect to aid dissolving other ingredients is not expected. Compositions of this invention can optionally comprise from about 1% to about 5%, preferably from about 2% to about 4% by weight of the composition, of a nonionic surfactant.
The nonionic surfactant acts as a co-solubilizer of salicylic acid, thereby allowing higher salicylic acid level when using the same solvent. Nonionic surfactants useful herein include any of the well-known nonionic surfactants that have an HLB (hydrophile-lipophile balance) from about 10 to about 18, preferably from about 12 to 16.
Non-limiting examples of these nonionic surfactants are ethoxylated or propoxylated, preferably ethoxylated, alcohols and alkyl phenols with alcohol derivatives preferred. In general, these alcohol derivatives contain a straight or branched chain alkyl group having 8-22 carbons, preferably 10-20 carbons, more preferably 12-20 carbons, and generally contain from about 6 to about 30, preferably from about 8 to about 25, ethylene oxide or propylene oxide groups. Among these ethoxylated and propoxylated alcohols, the ethoxylated derivatives are preferred.
Preferred for use herein are polyethylene oxide ethers derived from lauryl alcohol, cetyl alcohol, oleyl alcohol, stearyl alcohol, isocetyl or isostearyl alcohol and mixtures thereof. Most preferred for use herein is isocetyl ether condensed with an average of 20 moles of ethylene oxide, known by CTFA designation as Isoceteth 20 (hereinafter called Isocetech 20).
3. Dialkylpolvsiloxane-polvoxyalkylene copolvmer Compositions of this invention can optionally comprise a dialkylpolysiloxane- polyoxyalkylene copolymer. Such a copolymer is expected to improve the overall skin feel imparted by the composition and to reduce any irritation which might be caused by a component of the present invention. If the composition comprises more than about 5% of dialkylpolysiloxane-polyoxyalkylene copolymer, it is not economical and may cause safety issues, and if it comprises less than about 1% of dialkylpolysiloxane-polyoxyalkylene copolymer, the effect of improving overall skin is not expected. The composition preferably comprises from about 1% to about 5% of dialkylpolysiloxane - polyoxyalkylene copolymer, most preferably from about 2% to about 4% dialkylpolysiloxane - polyoxyalkylene copolymer. Dialkylpolysiloxane - polyoxyalkylene copolymers useful herein include those which are soluble in water. Dimethylpolysiloxane-polyoxyalkylene copolymers, known as Dimethicone copolyols where the polyoxyalkylene group can be a polyoxyethylene or a polyoxypropylene group or a combination of both, are particularly useful. The dimethylpolysiloxane portion is typically made of from 10 to about 30 units, preferably around 15 to 20 units. The polyalkylene portion is typically made of from 8 to about 12, preferably from 10 to about 12 units. 4. Sunscreens, conditioning agents, vitamins, perfumes, etc.
Other optional components can be included in the aqueous topical compositions of the present invention, depending on the needs of the product. Non-limiting examples of such optional components include water-soluble additional surfactants to aid solubility of the composition, water-soluble ultraviolet and infrared screening and absorbing agents to screen and absorb ultraviolet and infrared, water-soluble anti-inflammatory agents to reduce inflammation, water-soluble anti-oxidant radical scavenging agents to control oxidation and scavenge radical, water-soluble chelating agents to chelate metal, water-soluble skin conditioning agents to condition skin, water-soluble perfume for preference, water-soluble color for preference, water-soluble pH adjusters for adjusting pH, water-soluble dyes for preference, water-soluble vitamins to condition skin, water-soluble proteins to condition skin, water-soluble plant extracts to condition skin, and water-soluble nutrients to condition skin.
For the sake of preventing the composition comprising kojic acid from colouring, a composition of the present invention can include at least one anti-colouring agent selected from the group consisting of sodium metabisulfite, sodium bisulfite and sodium sulfite.
A wide variety of acids, bases, buffers, and sequestrants can be utilized to adjust and or maintain the pH and ionic strength of the compositions useful in the present invention. Materials useful for adjusting and/or maintaining the pH and/or the ionic strength include sodium carbonate, sodium hydroxide, hydrochloric acid, phosphoric acid, sulfuric acid, acetic acid, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium citrate, sodium bicarbonate, triethanolamine, EDTA (ethylenediaminetetraacetic acid), disodium EDTA, tetrasodium EDTA, and the like.
The compositions of the present invention are typically formulated to have a pH from about 2.5 to about 4, preferably a pH from about 3 to about 4. The aqueous topical compositions of the present invention include lotions, toners and astringents.
F. METHODS FOR LIGHTENING SKIN IN MAMMALS
The present invention also relates to methods for skin lightening in mammals comprising topical application of the skin lightening composition of the present invention. The amount of active agent and frequency of application will vary widely depending upon the skin color already in existence in the subject, the rate of further darkening of the skin, and the level of lightening desired.
A safe and effective amount of skin lightening agent in a topical composition is applied, generally from about 1 mg to about 10 mg per cm^ skin per application, preferably from about 2 mg to about 8 mg/ cm^ skin per application, more preferably from about 3 mg to about 7 mg/cm^ skin, also preferably from about 4 mg to about 5 mg/cm^ skin. Application preferably ranges from about four times a day to about twice a week, more preferably from about three times a day to about once every other day, more preferably still from about once daily to about twice daily. Application for at least five days is required to see a skin lightening effect in lower animals. Application for at least one month is required to see an effect in humans. After lightening is achieved, the frequency and dosage can be reduced to a maintenance level, as desired. Such maintenance varies according to the individual, but is preferably from about 1/10 to about 1/2, more preferably from about 1/5 to about 1/3 of the original dosage and/or frequency, as needed. The following examples further describe and demonstrate the preferred embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration, and are not to be construed as limitations of the present invention since many variations thereof are possible without departing from its spirit and scope.
G. EXAMPLES The following examples further describe and demonstrate embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention. All percentages are based on weight. Example compositions numbers 1-4 are shown in Table 1, below. Table 1
Examples
(Amount in weight %)
Component No.l No.2 No.3 No.4 Kojic acid 1 1 1.5 2
Salicylic acid 1.5 1.2 1.5 1.5
TRANSCUTOL* 25 23 25 27
Sodium citrate 4.5 3 4.5 4.5
Citric acid 6 4 6 6 Glycerin 3 0 3 5
Sodium metabisulfite 0.25 0.25 0.25 0.25
0.01% D&C yellow #10 0.3 0 0.03 0
Isoceteth 20 0 1 3 4
Dimethicone copolyol 0 1 3 4 water ϊ-s. to 100 q.s. to 100 q.s. to 100 q.s. to 100 pH 3.4 3-4 3-4 3-4
* TRANSCUTOL is diethyleneglycol monoethyl ether which is commercially available from
Gattefosse, France.
The compositions shown in Table 1 can be prepared by any conventional method well known in the art. An example of a suitable preparing method which may be used is described as follows:
Preparing method of Example No. 1
Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
Separately, glycerin, sodium citrate, citric acid and water are mixed together to obtain water phase-I. Water phase-I is also mixed at about 70-75 °C. The salicylic acid/TRANSCUTOL mixture is then slowly added to water phase-I and mixed at 75 °C for 30 minutes to obtain mixture- 1. Kojic acid, sodium metabisulfite and water are mixed together to obtain water phase-II. Water phase-U is also mixed at 45 °C. Then water phase-H and D&C yellow #10 are also added to mixture- 1 to obtain a lotion. Preparing method of Example No. 2
Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
Separately, sodium citrate, citric acid, Isoceteth 20 and water are mixed together to obtain water phase-I. Water phase-I is also mixed at about 70-75 °C. The salicylic acid TRANSCUTOL mixture is then slowly added to water phase-I and mixed at 75 °C for 30 minutes to obtain a lotion.
Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to obtain water phase-II. Water phase-II is also mixed at 45 °C. Then water phase-II is also added to mixture- 1 to obtain a lotion. Preparing method of Example No. 3
Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C. Separately, glycerin, sodium citrate, citric acid, Isocetech 20 and water are mixed together to obtain water phase-I. Water phase-I is also mixed at about 70-75 °C. The salicylic acid/TRANSCUTOL mixture is then slowly added to water phase-I and mixed at 75 °C for 30 minutes to obtain mixture- 1. Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to obtain water phase-II. Water phase-II is also mixed at 45 °C. Then water phase-II and D&C yellow #10 are also added to mixture- 1 to obtain a lotion. Preparing method of Example No. 4 Salicylic acid and TRANSCUTOL are combined and heated to about 70-75 °C.
Separately, glycerin, sodium citrate, citric acid, Isoceteth 20 and water are mixed together to obtain water phase-I. Water phase-I is also mixed at about 70-75 °C. The salicylic acid/TRANSCUTOL mixture is then slowly added to the water phase-I and mixed at 75 °C for 30 minutes to obtain mixture-1. Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to obtain water phase-II. Water phase-II is also mixed at 45 °C. Then water phase-II is also added to mixture-1 to obtain a lotion.
The compositions of the present invention have improved skin penetration enhancing effect of kojic acid compared versus compositions which comprise thickener and/or comprise more than about 30% by weight of the composition, of water soluble glycol ether. A strong lightening effect of mammalian skin will be obtained by the compositions of the present invention, due to the resulting strong skin penetration enhancing effect of kojic acid.
Example No. 5 This example sets forth a method for lightening mammalian skin using a composition of the present invention. The composition of example No. 1 is applied 5 mg / cm^ skin per application three times a day for one month. After one month, a significant skin lightening effect is seen. Once the desired level of the skin lightening is achieved, treatment is reduced to limit a day, to maintain the level of lightening.
It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to one skilled in the art and are to be included in the spirit and purview of this application and scope of the appended claims.

Claims

What is claimed is:
1. An aqueous topical composition for skin lightening comprising:
(a) a safe and effective amount of kojic acid,
(b) a safe and effective amount of salicylic acid,
(c) water, and (d) from about 20% to about 30% by weight of the composition, of a water soluble glycol ether of general formula: Rl-0-[(CH2)mO]nH; wherein R* is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2; wherein said composition has a pH from about 2.5 to about 4, and is absent of a thickener.
2. The aqueous topical composition according to claim 1 comprising from about 0.5% to about 3% by weight of the composition, of kojic acid; from about 1% to about 2% by weight of the composition, of salicylic acid; and from about 40% to about 78.5% by weight of the composition, of water.
3. The aqueous topical composition according to claim 1 comprising from about 1% to about 2% by weight of the composition, of kojic acid; from about 1.2% to about 1.5% by weight of the composition, of salicylic acid; and from about 40% to about 78.5% by weight of the composition, of water.
4. The aqueous topical composition according to claim 1 comprising:
(a) from about 1% to about 2% by weight of the composition, of kojic acid;
(b) from about 1.2% to about 1.5% by weight of the composition, of salicylic acid;
(c) from about 40% to about 78.5% by weight of the composition, of water; and (d) from about 23% to about 27% by weight of the composition, of water soluble glycol ether wherein said composition has a pH from about 3 to about 4.
5. The aqueous topical composition according to claim 4 wherein said water soluble glycol ether is diethylene glycol monoethyl ether.
6. The aqueous topical composition according to claim 4 wherein said aqueous topical composition is a lotion.
7. The aqueous topical composition according to claim 4 further comprising at least one anti-colouring agent selcted from the group consisting of sodium metabisulfite, sodium bisulfite and sodium sulfite.
8. A method for lightening mammalian skin comprising topically applying to the skin said aqueous topical composiiton of claim 1.
9. A method for lightening mammalian skin comprising topically applying to the skin said aqueous topical composition of claim 4.
10. A method for enhancing penetration of kojic acid to mammalian skin comprising topically applying to the skin said aqueous topical composition of claim 4.
PCT/US1996/016942 1996-10-23 1996-10-23 Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether WO1998017247A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP96937713A EP0939616A1 (en) 1996-10-23 1996-10-23 Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether
KR1019990703478A KR20000052690A (en) 1996-10-23 1996-10-23 Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether
BR9612753-8A BR9612753A (en) 1996-10-23 1996-10-23 Aqueous topical composition to lighten the skin and processes to lighten the skin of mammals and increase the penetrating effect of cojic acid
CZ991414A CZ141499A3 (en) 1996-10-23 1996-10-23 Aqueous preparation containing kojic acid, salicylic acid and water-soluble glycol ether
PCT/US1996/016942 WO1998017247A1 (en) 1996-10-23 1996-10-23 Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether
JP9534362A JPH11510820A (en) 1996-10-23 1996-10-23 Aqueous topical composition
AU75187/96A AU7518796A (en) 1996-10-23 1996-10-23 Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether
CA002269290A CA2269290A1 (en) 1996-10-23 1996-10-23 Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6417223B1 (en) 1998-09-23 2002-07-09 Research Development Foundation Tocopherols, tocotrienols, other chroman and side chain derivatives and uses therof
EP1450771A2 (en) * 2001-10-03 2004-09-01 Innovative Pharmaceutical Concepts (IPC) Inc. Pharmaceutical preparations useful for treating tumors and lesions of the skin and the mucous membranes and methods and kits using same
FR2866563A1 (en) * 2004-02-19 2005-08-26 Oreal Use of 8-hexadecane-1,16-dicarboxylic acid for superficial peeling of skin to attenuate the visible and tactile irregularities e.g. wrinkles, ridules, pigmenting blemishes and scars
WO2007118605A1 (en) * 2006-04-18 2007-10-25 Dsm Ip Assets B.V. Cosmetic compositions comprising salicylic acid and ascorbic acid

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3290043B1 (en) 2015-06-01 2023-03-15 Saisei Pharma Co., Ltd. Enzyme-treated milk product, method for producing same, composition, and product

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59157009A (en) * 1983-02-25 1984-09-06 Yakurigaku Chuo Kenkyusho:Kk External skin drug for suppressing formation of melanin
JPH02200622A (en) * 1989-01-28 1990-08-08 Sansho Seiyaku Co Ltd External agent for suppressing melanogenesis
EP0661035A1 (en) * 1993-12-30 1995-07-05 L'oreal Cosmetic composition for the simultaneous treatment of the superficial skinlayers and the deep skinlayers
EP0661038A1 (en) * 1993-12-30 1995-07-05 L'oreal Depigmentation composition for the simultaneous treatment of the superficial skinlayers and the deep skinlayers
EP0680748A1 (en) * 1994-05-05 1995-11-08 L'oreal, S.A. Cosmetic and/or dermatological composition containing a cationic polymeric gelling agent and its uses especially for skin depigmentation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59157009A (en) * 1983-02-25 1984-09-06 Yakurigaku Chuo Kenkyusho:Kk External skin drug for suppressing formation of melanin
JPH02200622A (en) * 1989-01-28 1990-08-08 Sansho Seiyaku Co Ltd External agent for suppressing melanogenesis
EP0661035A1 (en) * 1993-12-30 1995-07-05 L'oreal Cosmetic composition for the simultaneous treatment of the superficial skinlayers and the deep skinlayers
EP0661038A1 (en) * 1993-12-30 1995-07-05 L'oreal Depigmentation composition for the simultaneous treatment of the superficial skinlayers and the deep skinlayers
EP0680748A1 (en) * 1994-05-05 1995-11-08 L'oreal, S.A. Cosmetic and/or dermatological composition containing a cationic polymeric gelling agent and its uses especially for skin depigmentation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 8442, Derwent World Patents Index; AN 84-259497, XP002031918, "Melanism ihnibitor ointment or cream prepn. for skin - contains e.g. urea, hydroquinone, non-enzyme oxidative polymerisation inhibitor etc." *
DATABASE WPI Week 9038, Derwent World Patents Index; AN 90-286007, XP002031919, "External agent to control melanin formation - contains kojic acid or deriv. uv absorbing material of p-aminobenzoic aid cpds. etc" *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6417223B1 (en) 1998-09-23 2002-07-09 Research Development Foundation Tocopherols, tocotrienols, other chroman and side chain derivatives and uses therof
EP1450771A2 (en) * 2001-10-03 2004-09-01 Innovative Pharmaceutical Concepts (IPC) Inc. Pharmaceutical preparations useful for treating tumors and lesions of the skin and the mucous membranes and methods and kits using same
EP1450771A4 (en) * 2001-10-03 2005-04-27 Innovative Pharmaceutical Conc Pharmaceutical preparations useful for treating tumors and lesions of the skin and the mucous membranes and methods and kits using same
US8658185B2 (en) 2001-10-03 2014-02-25 Innovative Pharmaceutical Concepts (Ipc) Inc. Kit useful for treating tumors and lesions of the skin and the mucous membranes
FR2866563A1 (en) * 2004-02-19 2005-08-26 Oreal Use of 8-hexadecane-1,16-dicarboxylic acid for superficial peeling of skin to attenuate the visible and tactile irregularities e.g. wrinkles, ridules, pigmenting blemishes and scars
WO2007118605A1 (en) * 2006-04-18 2007-10-25 Dsm Ip Assets B.V. Cosmetic compositions comprising salicylic acid and ascorbic acid

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JPH11510820A (en) 1999-09-21
AU7518796A (en) 1998-05-15
CA2269290A1 (en) 1998-04-30

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