WO2012008457A1 - Composition pour application externe - Google Patents

Composition pour application externe Download PDF

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Publication number
WO2012008457A1
WO2012008457A1 PCT/JP2011/065900 JP2011065900W WO2012008457A1 WO 2012008457 A1 WO2012008457 A1 WO 2012008457A1 JP 2011065900 W JP2011065900 W JP 2011065900W WO 2012008457 A1 WO2012008457 A1 WO 2012008457A1
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WIPO (PCT)
Prior art keywords
composition
heparin
vitamin
skin
substance
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PCT/JP2011/065900
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English (en)
Japanese (ja)
Inventor
温子 中田
亮 小紫
文子 石坂
純子 丸川
亜希子 上谷
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ロート製薬株式会社
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Publication of WO2012008457A1 publication Critical patent/WO2012008457A1/fr

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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
    • A61K8/67—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/727—Heparin; Heparan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/23—Sulfur; Selenium; Tellurium; Compounds thereof
    • 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
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • 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
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
    • 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
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • 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 provides rough skin of fingers and the like; elbows, knees, heels, ankle keratosis; cracks and bruises of hands and feet; dry skin; dry skin of children; moistness; scratches and skin lump after burns;
  • a composition for external use which can prevent, treat or ameliorate bruise, swelling after sprain, muscle pain, joint pain and the like;
  • Antioxidants are widely used as additives for pharmaceuticals, quasi drugs, cosmetics, foods and the like. Antioxidants keep each component in the composition stable and contribute to maintaining the composition and dosage form of the composition over a long period of time. Moreover, generation
  • Antioxidants for pharmaceutical, quasi-drug, and cosmetic compositions for external use include dibutylhydroxytoluene (hereinafter sometimes referred to as “BHT”), butylhydroxyanisole, ascorbic acid or a salt thereof, tocopherol or a salt thereof, erythorbine Antioxidants such as acid salts, sulfites, sulfur dioxide, phytic acid, acetylcysteine, cysteine, manganese gluconate, arbutin, and dilauryl thiodipropionate are used. Antioxidants may have skin irritation and cytotoxicity depending on the concentration. For example, Non-Patent Document 1 describes that BHT needs to wear protective gloves to induce skin redness.
  • vitamins A are widely used as active ingredients for external preparations because they have an action of maintaining normal epithelial cells such as skin and mucous membrane to prevent keratinization and an antioxidant action.
  • Patent Document 1 describes that an external preparation for skin containing vitamin A and one or more powders is excellent in prevention and treatment of cutaneous keratosis, prevention of skin aging, and recovery. ing.
  • Heparin-like substances are widely used as active ingredients for external preparations because they have excellent moisturizing action, anti-inflammatory action, blood circulation promoting action and the like.
  • Patent Document 2 an external preparation for skin containing ceramide and a heparin-like substance improves the moisture retention action of the skin and enhances the moisturizing effect, thereby normalizing the moisture retention function or skin barrier function, It describes that it effectively improves dry skin.
  • Patent Document 2 do not describe that an external preparation for skin containing vitamin A and heparin-like substance has an excellent effect of improving rough skin.
  • the first object of the present invention is to provide a composition for external use containing an antioxidant, in which the cytotoxicity of the antioxidant is reduced. Moreover, this invention makes it the 2nd subject to provide the composition for external use excellent in the rough skin improvement effect.
  • the present inventor has conducted research in order to solve the first problem, and by using an antioxidant together with vitamins A and heparin-like substances, the cytotoxicity of the antioxidant is effectively reduced. I found out.
  • the present invention has been completed based on the above findings, and provides the following first external composition.
  • Item 1-1 An external composition containing vitamins A, heparin-like substances, and antioxidants.
  • Item 1-2. Item 1-1 wherein the antioxidant is at least one compound selected from the group consisting of dibutylhydroxytoluene, butylhydroxyanisole, pyrosulfite, bisulfite, and ascorbic acid, a salt thereof, and a glycoside thereof A composition according to 1.
  • Item 1-4. Item 4.
  • Item 5. The composition for external use according to any one of Items 1-1 to 1-4, wherein the content of vitamin A is 0.0001 to 2% by weight based on the total amount of the composition.
  • Item 5. The composition for external use according to any one of Items 1-1 to 1-5, wherein the content of vitamin A with respect to the content of the antioxidant is 1: 0.03 to 50 by weight.
  • Item 8. The composition for external use according to any one of Items 1-1 to 1-7, wherein the content of the heparin-like substance relative to the content of the antioxidant is 1: 0.01 to 50 by weight.
  • Item 11. The composition for external use according to any one of Items 1-1 to 1-8, wherein the content of the heparin-like substance with respect to the content of vitamin A is 1: 0.01 to 10 by weight.
  • Item 1-10 A method for reducing cytotoxicity of an antioxidant, comprising adding a vitamin A and a heparin-like substance to a composition containing an antioxidant.
  • the present inventor repeated researches to solve the second problem and obtained the following knowledge.
  • an external composition containing vitamin A and a heparin-like substance is applied to rough skin, the rough skin is effectively improved.
  • the degree is markedly superior to a composition for external use containing vitamin A or a heparin-like substance alone.
  • an external composition containing vitamin A is applied to rough skin, depending on the concentration of vitamin A, it may have skin irritation.
  • a heparin-like substance is added to this external composition, skin irritation caused by vitamins A is effectively reduced.
  • Item 2-1 An external composition for improving rough skin while suppressing skin irritation, comprising vitamin A and a heparin-like substance.
  • Item 2-2. Item 2. The composition according to Item 2-1, wherein the content of the heparin-like substance relative to the content of vitamin A is 1: 0.01 to 10 by weight.
  • Item 2-3. Item 3. The composition according to Item 2-1 or 2-2, wherein the content of vitamin A is 0.0001 to 2% by weight based on the total amount of the composition.
  • Item 11 The composition according to any one of Items 2-7 to 2-10, wherein the content of the heparin-like substance relative to the content of vitamin A is 1: 0.01 to 10 by weight.
  • Item 13 The composition according to any one of Items 2-7 to 2-12, wherein the content of the heparin-like substance is 0.0001 to 10% by weight based on the total amount of the composition.
  • Item 14 The composition according to any one of Items 2-7 to 2-13, wherein the vitamin A is retinol palmitate.
  • compositions comprising vitamin A and a heparin-like substance for producing a composition for external use for improving rough skin while suppressing skin irritation.
  • Item 2-17 A composition comprising vitamin A and a heparin-like substance, which is externally applied to improve rough skin while suppressing skin irritation.
  • Item 2-18. A method for improving rough skin while suppressing skin irritation, comprising a step of applying a composition containing vitamin A and a heparin-like substance to rough human skin.
  • Item 2-19. Use of a composition comprising vitamin A and a heparin-like substance for the production of an external composition for improving rough skin.
  • Item 2-20 A composition containing vitamin A and a heparin-like substance, which is used externally for improving rough skin.
  • Item 2-21. A method for improving rough skin, comprising a step of applying a composition containing vitamin A and a heparin-like substance to rough human skin.
  • the first external composition of the present invention contains an antioxidant, vitamin A, and heparin-like substance, thereby reducing or eliminating the cytotoxicity of the antioxidant.
  • an antioxidant vitamin A
  • heparin-like substance thereby reducing or eliminating the cytotoxicity of the antioxidant.
  • the addition of heparin-like substances with skin moisturizing action has no effect on reducing cytotoxicity, but heparin-like substances are combined with fat-soluble vitamin A. Together, it synergistically reduces antioxidant cytotoxicity.
  • the first external composition of the present invention can effectively exhibit the original action of the composition containing vitamin A and heparin-like substance, and rough skin such as fingers; elbows, knees Keratinosis of the ankles, ankles, cracks in the limbs, scratches; dry skin; dry skin of children; moistness; lumps and tension in the skin after scratches, burns; bruises, swelling after sprains, muscle pain,
  • the composition is useful for improving joint pain and the like.
  • the second composition for external use of the present invention contains stratum corneum moisture for rough skin such as xeroderma and keratosis by combining vitamin A and a heparin-like substance together. Leads to increased volume, reduced transepidermal water loss (improved barrier function), normalization or improvement of skin texture, improved skin findings (degree of skin dryness and desquamation). Furthermore, such an improvement is far superior to a composition containing vitamin A and a heparin-like substance alone.
  • an external composition containing vitamin A may have skin irritation when the concentration of vitamin A is high.
  • the stratum corneum which constitutes the outermost layer of the epidermis, is composed of stratum corneum, and intercellular lipids and natural moisturizing components are present between these cells. Prevents foreign substances from entering and prevents moisture from evaporating (barrier function).
  • this barrier function is lowered and the keratin is dry, so that the applied composition is easy to enter the inside, and irritation by vitamin A is particularly Easy to feel.
  • the second composition for external use of the present invention is able to improve the barrier function and to improve the barrier function with a healthy skin texture (a state in which keratinocytes are lined up and intercellular lipids and natural moisturizing substances are present between the cells). Since the heparin-like substance suppresses the irritation, it can effectively improve rough skin such as xeroderma and keratosis while suppressing skin irritation.
  • the second composition for external use of the present invention has rough skin such as xeroderma and keratosis, specifically rough skin of fingers and the like; elbows, knees, heels, ankle keratosis; Dry skin of children; moist; skin lump and scratches after scratches, burns; useful for improving bruise, swelling after sprain, muscle pain, joint pain, sebum deficiency, hypertrophic scar, keloid, etc. Composition.
  • the first external composition of the present invention is a composition containing vitamins A, heparin-like substances, and antioxidants.
  • the vitamin A in vitamin A present invention include retinol, retinal, retinoic acid, these dehydro body, these esters and pro-vitamin A.
  • Esters include retinol acetate, retinol propionate, retinol butyrate, retinol octylate, retinol laurate, retinol palmitate, retinol stearate, retinol myristate, retinol oleate, retinol linolenate, retinol linoleate, retinol palmitate, Examples thereof include retinal acetate, retinal propionate, methyl retinoate, ethyl retinoate, retinol retinoic acid, tocopherol retinoic acid (which may be any isomer of ⁇ , ⁇ , ⁇ , and ⁇ ).
  • provitamin A examples include ⁇ -carotene, ⁇ -carotene, ⁇ -carotene, ⁇ -carotene, lycopene, zeaxanthin, ⁇ -cryptoxanthin, and echinenone.
  • retinol or an ester of retinoic acid is preferable, and retinol acetate, retinol palmitate, and ⁇ -retinoic acid tocopherol are more preferable.
  • Vitamin A can be used individually by 1 type or in combination of 2 or more types.
  • the vitamin A may be either isolated from natural products such as animal materials or chemically synthesized. Vitamin A can also be used in the form of vitamin A oil.
  • the vitamin A oil may be a natural oil extracted and purified from an animal, or a vitamin A dissolved in a vegetable oil or the like.
  • a typical example of the latter is vitamin A oil (containing 30000 vitamin A units (IU) or more per gram) described in the Japanese Pharmacopoeia.
  • the content of vitamin A in the first external composition of the present invention is usually 0.0001% by weight or more, preferably 0.001% by weight or more, more preferably 0.01% by weight relative to the total amount of the composition. What is necessary is just to be more than weight%. Further, it is usually 2% by weight or less, preferably 1% by weight or less, more preferably 0.5% by weight or less. If it is the said range, physiological effects, such as a cornification inhibitory action and an antioxidant action which vitamin A has, can be exhibited, and the cytotoxicity of an antioxidant is suppressed effectively. Moreover, if it is the said range, the side effect (inflammation, such as serious erythema, stinging, etc.) by excessive use of vitamin A will not arise.
  • the ratio of the content of vitamin A to the content of antioxidant is preferably about 1: 0.001 to 50 by weight, and about 1: 0.01 to 30 is more preferred, and about 1: 0.1-20 is even more preferred. If it is the said range, physiological effects, such as a cornification inhibitory action and an antioxidant action which vitamin A has, can be exhibited, and the cytotoxicity of an antioxidant is suppressed effectively. Moreover, if it is the said range, the side effect (inflammation, such as serious erythema, stinging, etc.) by excessive use of vitamin A will not arise.
  • the content and ratio of the above vitamin A were calculated based on the weight of vitamin A oil in which vitamin A was dissolved in vegetable oil or the like when vitamin A was included in the composition in the form of vitamin A oil. Value.
  • Heparin analogs are polysulfated mucopolysaccharides such as chondroitin polysulfate. It is preferable to have an average of 0.5 to 5 molecules, especially an average of 0.6 to 3 molecules of sulfate groups per molecule of monosaccharide constituting the mucopolysaccharide.
  • heparin-like substances include heparin; chondroitin sulfate D, chondroitin sulfate D such as chondroitin sulfate E, and the like. Among them, heparin-like substances that are included in the Japanese Pharmacopoeia Standards for Drugs can be suitably used.
  • Heparin-like substances can be obtained by sulfating mucopolysaccharides. It can also be obtained by extracting and purifying from the viscera including the bronchi of animals such as cows and pigs using an aqueous carrier, and further sulfating if necessary. Since heparin-like substances are commercially available as raw materials for pharmaceuticals and cosmetics, commercially available products can also be used.
  • the content of the heparin-like substance in the first external composition of the present invention is usually 0.005% by weight or more, preferably 0.01% by weight or more, more preferably 0.05% by weight with respect to the total amount of the composition. It may be at least 0.1% by weight, more preferably at least 0.1% by weight. Further, it is usually 10% by weight or less, preferably 5% by weight or less, more preferably 1% by weight or less, and still more preferably 0.5% by weight or less. If it is the said range, physiological effects, such as a moisturizing effect and a blood circulation promotion effect which a heparin analog has, can exhibit the cytotoxicity of an antioxidant effectively.
  • the ratio of the content of the heparin-like substance to the content of the antioxidant is preferably about 1: 0.0001 to 50 by weight, and about 1: 0.001 to 40 is more preferred, and about 1: 0.01 to 35 is even more preferred. If it is the said range, physiological effects, such as a moisturizing effect and a blood circulation promotion effect which a heparin analog has, can exhibit the cytotoxicity of an antioxidant effectively.
  • the ratio of the content of heparin-like substance to the content of vitamin A is preferably about 1: 0.01 to 10, preferably about 1: 0.05 to weight ratio. 5 is more preferred, and about 1: 0.1 to 2 is even more preferred.
  • the content of the heparin-like substance relative to the vitamin A content is in the above range, rough skin on the fingers, etc .; elbows, knees, heels, ankle keratosis; cracks on the hands and feet; dry skin; sexual skin; moist; skin lump and scratching after scratches and burns; can prevent, treat, or ameliorate bruises, swelling after sprain, muscle pain, joint pain, etc., and also has the effect of antioxidant cytotoxicity Can be reduced.
  • Antioxidants include BHT, butylhydroxyanisole (BHA), ascorbic acid, salts thereof (stearate, palmitate, phosphate, etc.) or glycosides thereof (ascorbic acid 2-glucoside, etc.) , Tocopherol or its salt (acetate, nicotinate, succinate), sulfite (sodium salt, potassium salt, etc.), pyrosulfite (sodium salt, potassium salt, etc.), bisulfite (sodium salt, potassium salt) Etc.).
  • the content of the antioxidant in the first external composition of the present invention is usually 0.001% by weight or more, preferably 0.005% by weight or more, more preferably 0.01% by weight with respect to the total amount of the composition.
  • weight% is usually 1% by weight or less, preferably 0.5% by weight or less, more preferably 0.3% by weight or less. If it is in the above-mentioned range, it is possible to effectively suppress the cytotoxicity of the antioxidant with the use amount of vitamin A and heparin-like substance that can sufficiently obtain the antioxidant effect and obtain the original medicinal effect. it can.
  • the first composition for external use of the present invention comprises a vitamin A, a heparin-like substance, and an antioxidant, a base or carrier usually used in pharmaceuticals, quasi drugs, or cosmetics, and as necessary. It can mix with an additive and can be set as the external composition for pharmaceuticals, a quasi-drug, or cosmetics.
  • the form of the composition for external use for pharmaceuticals is not particularly limited, and examples thereof include liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, and poultices. These preparations can be produced according to the method described in the 15th revised Japanese Pharmacopoeia General Rules for Preparations.
  • the form of the composition for external use for quasi-drugs or cosmetics is not particularly limited, and for example, lotion, milky lotion, cream, serum, cosmetic for sunscreen, pack, hand cream, body lotion, body cream, etc. Basic cosmetics; cleansing cosmetics such as facial cleansers, makeup removers, body shampoos; makeup cosmetics such as foundations, makeup bases, lip balms, lipsticks, and cheek colors; bathing agents.
  • Bases or carriers include liquid paraffin, squalane, gelled hydrocarbons (such as plastibase), ozokerite, ⁇ -olefin oligomers, hydrocarbons such as light liquid paraffin; methyl polysiloxane, cross-linked methyl polysiloxane, highly polymerized methyl Polysiloxane, Cyclic silicone, Alkyl-modified silicone, Cross-linked alkyl-modified silicone, Amino-modified silicone, Polyether-modified silicone, Polyglycerin-modified silicone, Cross-linked polyether-modified silicone, Cross-linked alkyl polyether-modified silicone, Silicone / alkyl chain copolymer Modified polyether-modified silicone, silicone / alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, Silicone oils such as phenyl-modified silicones and silicone resins;
  • the base or carrier can be used alone or in combination of two or more.
  • additives that are added to pharmaceuticals, quasi-drugs, or cosmetics within a range that does not impair the effects of the present invention, such as surfactants, thickeners, Preservatives, pH adjusters, chelating agents, stabilizers, irritation reducers, preservatives, colorants, fragrances, pearlescent agents, and the like can be added.
  • surfactant examples include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate.
  • thickener examples include guar gum, locust bean gum, carrageenan, xanthan gum, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl methacrylate methacrylate. Copolymers, polyethylene glycol, bentonite, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, (acryloyldimethyltaurine ammonium / vinylpyrrolidone) copolymer, and the like.
  • Preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, benzyl paraoxybenzoate, paraoxybenzoate
  • examples include methyl benzoate and phenoxyethanol.
  • pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.) ) And organic bases (such as triethanolamine, diisopropanolamine, and triisopropanolamine).
  • examples of the chelating agent include EDTA / disodium salt, EDTA / calcium disodium salt, and the like.
  • Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole and the like.
  • Examples of the irritation reducing agent include licorice extract and sodium alginate.
  • Examples of the preservative include benzoate, sorbate, dehydroacetate, p-hydroxybenzoate, benzethonium chloride, phenoxyethanol, chlorhexidine gluconate and the like.
  • Additives can be used singly or in combination of two or more.
  • the 1st composition for external use of this invention can contain another active ingredient in the range which does not impair the effect of this invention.
  • active ingredients include moisturizing ingredients, anti-inflammatory ingredients, antibacterial ingredients, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cell activation ingredients, anti-aging ingredients, blood circulation promoting ingredients, and the like.
  • polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, diglycerin trehalose; sodium hyaluronate, heparin analogue, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, Macromolecular compounds such as chitosan; amino acids such as glycine, aspartic acid, arginine; natural moisturizing factors such as sodium lactate, urea, sodium pyrrolidonecarboxylate; lipids such as ceramide, cholesterol, phospholipid; chamomile extract, hamamelis Plant extract such as extract, tea extract, perilla extract and the like can be mentioned.
  • anti-inflammatory component examples include a plant-derived component (eg Comfrey), allantoin, glycyrrhizic acid or a derivative thereof, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, salicylic acid or a derivative thereof, and ⁇ -aminocaproic acid.
  • plant-derived component eg Comfrey
  • allantoin glycyrrhizic acid or a derivative thereof
  • zinc oxide pyridoxine hydrochloride
  • tocopherol acetate e.glycyrrhizic acid or a derivative thereof
  • salicylic acid a derivative thereof
  • ⁇ -aminocaproic acid examples include a plant-derived component (eg Comfrey), allantoin, glycyrrhizic acid or a derivative thereof, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, salicylic acid or a derivative thereof, and ⁇ -ami
  • Antibacterial components include chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer No. 101 Photosensitive element 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride and the like.
  • Vitamins such as dl- ⁇ -tocopherol, dl- ⁇ -tocopherol acetate, dl- ⁇ -tocopherol succinate, and dl- ⁇ -tocopherol calcium succinate; riboflavin, flavin mononucleotide, flavin adenine dinucleotide Vitamin B2 such as riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5′-phosphate, riboflavin tetranicotinate; nicotinic acid dl- ⁇ -tocopherol, benzyl nicotinate, methyl nicotinate, ⁇ -nicotinic acid ⁇ - Nicotinic acids such as butoxyethyl and 1- (4-methylphenyl) ethyl nicotinate; ascorbigen-A, ascorbyl stearate, ascorbyl palmitate, dipalmitin Vitamin Cs such as L-as
  • Peptides or derivatives thereof include keratin-degrading peptide, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin-degrading peptide , Conchiolin degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soy proteolytic peptide, hydrolyzed soy protein, wheat protein, wheat proteolytic peptide, hydrolyzed wheat protein, casein degrading peptide Acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.).
  • Amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, ⁇ -alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine Leucine, isoleucine, valine, histidine, taurine, ⁇ -aminobutyric acid, ⁇ -amino- ⁇ -hydroxybutyric acid, carnitine, carnosine, creatine and the like.
  • Cell activation components include amino acids such as ⁇ -aminobutyric acid and ⁇ -aminoproic acid; vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids; ⁇ -hydroxy acids such as glycolic acid and lactic acid; tannins, Examples include flavonoids, saponins, allantoin, and photosensitizer 301.
  • Antiaging components include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like.
  • Examples of the blood circulation promoting component include plants (for example, ginseng, ashitaba, arnica, ginkgo, fennel, enamel, Dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake, hawthorn, sorghum, nematode, Assembly, thyme, clove, chimney, spruce, spruce, spruce, carrot, garlic, butcher bloom, grape, button, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpi, touki, spruce, peach, apricot, walnut , A component derived from corn); and glucosyl hesperidin.
  • plants for example, ginseng, ashitaba, arnica, ginkgo, fennel, enamel, Dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawt
  • the pH of the first external composition of the present invention is preferably about 4 to 9, and more preferably about 5 to 8. If it is the said pH range, a stable formulation can be prepared and the cytotoxicity of an antioxidant can be suppressed effectively.
  • the first composition for external use of the present invention varies depending on the skin condition, age, sex, etc. of the subject of use, but may be the following method, for example. That is, an appropriate amount (for example, about 0.05 to 5 g) may be applied to the skin several times a day (for example, about 1 to 5 times, preferably 1 to 3 times).
  • the composition may be applied so that the daily use amount of vitamin A is preferably about 0.1 to 200 mg, more preferably about 1 to 100 mg, and the daily use amount of the heparin-like substance is preferably
  • the composition may be applied so as to be about 0.01 to 100 mg, more preferably about 0.3 to 75 mg, and the daily use amount of the antioxidant is preferably about 0.01 to 30 mg, more preferably about 0.2 to 20 mg.
  • the composition may be applied as described above.
  • the application period may be, for example, about 1 to 14 days, preferably about 3 to 14 days.
  • the first composition for external use of the present invention comprises rough skin such as fingers; elbows, knees, heels, ankle keratosis; cracks and bruises of hands and feet; dry skin; pediatric dry skin; It can be suitably used for the prevention, treatment, or improvement of bruises and tension of the skin afterwards, bruising, swelling after sprain, muscle pain, joint pain and the like. Therefore, in addition to healthy people, people with these skin symptoms are suitable for use.
  • the present invention includes a method for reducing cytotoxicity of an antioxidant, which comprises adding vitamins A and a heparin-like substance to a composition containing an antioxidant.
  • the types of antioxidants, vitamin As, and heparin-like substances, the amounts used (concentrations, ratios), and other components that may be included in the composition are as described for the composition for external use of the present invention.
  • the present invention includes an external composition for improving rough skin containing vitamins A and heparin-like substances. Moreover, this invention includes the external composition for improving rough skin, suppressing the skin irritation containing vitamin A class and a heparin analog.
  • the vitamin A in vitamin A present invention include retinol, retinal, retinoic acid, these dehydro body, these esters and pro-vitamin A.
  • Esters include retinol acetate, retinol propionate, retinol butyrate, retinol octylate, retinol laurate, retinol palmitate, retinol stearate, retinol myristate, retinol oleate, retinol linolenate, retinol linoleate, retinol palmitate, Examples thereof include retinal acetate, retinal propionate, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, tocopherol retinoic acid (which may be any isomer of ⁇ , ⁇ , ⁇ , and ⁇ ).
  • provitamin A examples include ⁇ -carotene, ⁇ -carotene, ⁇ -carotene, ⁇ -carotene, lycopene, zeaxanthin, ⁇ -cryptoxanthin, and echinenone.
  • retinol or an ester of retinoic acid is preferable, and retinol acetate, retinol palmitate, and ⁇ -retinoic acid tocopherol are more preferable.
  • Vitamin A can be used individually by 1 type or in combination of 2 or more types.
  • the vitamin A may be either isolated from natural products such as animal materials or chemically synthesized. Vitamin A can also be used in the form of vitamin A oil.
  • the vitamin A oil may be a natural oil extracted and purified from an animal, or a vitamin A dissolved in a vegetable oil or the like.
  • a typical example of the latter is vitamin A oil (containing 30000 vitamin A units (IU) or more per gram) described in the Japanese Pharmacopoeia.
  • the content of vitamin A in the second external composition of the present invention is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and 0.01% by weight relative to the total amount of the composition. % Or more is even more preferable. Moreover, 2 weight% or less is preferable, 1 weight% or less is more preferable, and 0.5 weight% or less is still more preferable. If it is in the above range, it can exhibit physiological effects such as keratinization inhibiting action and antioxidant action of vitamin A, and side effects (such as inflammation and stinging such as severe erythema) caused by excessive use of vitamin A. Does not occur.
  • the content and ratio of the vitamin A are the weight of vitamin A oil obtained by dissolving the vitamin A in vegetable oil or the like.
  • Heparin analogs are polysulfated mucopolysaccharides such as chondroitin polysulfate. It is preferable to have an average of 0.5 to 5 molecules, especially an average of 0.6 to 3 molecules of sulfate groups per molecule of monosaccharide constituting the mucopolysaccharide.
  • heparin-like substances include heparin; chondroitin sulfate D, chondroitin sulfate D such as chondroitin sulfate E, and the like. Among them, heparin-like substances that are included in the Japanese Pharmacopoeia Standards for Drugs can be suitably used.
  • Heparin-like substances can be obtained by sulfating mucopolysaccharides. It can also be obtained by extracting and purifying from the viscera including the bronchi of animals such as cows and pigs using an aqueous carrier, and further sulfating if necessary. Since heparin-like substances are commercially available as raw materials for pharmaceuticals and cosmetics, commercially available products can also be used.
  • the content of the heparin-like substance in the second external composition of the present invention is usually 0.005% by weight or more, preferably 0.01% by weight or more, based on the total amount of the composition. 0.05% by weight or more is more preferable, and 0.1% by weight or more is even more preferable. Further, it may be usually 10% by weight or less, preferably 5% by weight or less, more preferably 1% by weight or less, and still more preferably 0.5% by weight or less. If it is the said range, physiological effects, such as a moisturizing effect
  • the ratio of the content of heparin-like substance to the content of vitamin A is preferably about 1: 0.01 to 10, preferably about 1: 0.05 to weight ratio. 5 is more preferred, and about 1: 0.1 to 2 is even more preferred. If the content of the heparin-like substance relative to the content of vitamin A is within the above range, the water content of the stratum corneum is increased, the amount of transepidermal water loss is reduced, the skin texture is normalized, and the skin findings (skin dryness and desquamation The degree of improvement in skin roughness such as improvement of the degree) can be fully exhibited. Moreover, the irritation to rough skin by vitamin A can be fully suppressed.
  • the second composition for external use of the present invention is a mixture of vitamins A and heparin-like substances together with bases or carriers usually used in pharmaceuticals, quasi drugs or cosmetics, and, if necessary, additives. And it can be set as the external composition for pharmaceuticals, a quasi-drug, or cosmetics.
  • composition for external use for pharmaceuticals is not particularly limited, and examples thereof include solutions, suspensions, emulsions, creams, ointments, gels, liniments, lotions, and poultices.
  • the pharmaceutical composition for external use is preferably used in the form of an emulsion, cream, ointment, gel, more preferably an emulsion, cream, and even more preferably an emulsion. By setting it as this form, the rough skin improvement effect can fully be exhibited.
  • These preparations can be produced according to the method described in the 15th revised Japanese Pharmacopoeia General Rules for Preparations.
  • the form of the composition for external use for quasi-drugs or cosmetics is not particularly limited, and for example, lotion, milky lotion, cream, serum, cosmetic for sunscreen, pack, hand cream, body lotion, body cream, etc.
  • Basic cosmetics cleansing cosmetics such as facial cleansers, makeup removers, body shampoos
  • makeup cosmetics such as foundations, makeup bases, lip balms, lipsticks, and cheek colors
  • bathing agents The composition for external use for quasi-drugs or cosmetics is preferably used in the form of a milky lotion, cream, cosmetic liquid, more preferably a milky lotion, cream, and even more preferably a milky lotion.
  • Base or carrier examples include those described for the first composition of the present invention.
  • carrier can be used individually by 1 type or in combination of 2 or more types.
  • additives added to pharmaceuticals, quasi drugs, or cosmetics for example, antioxidants, surfactants, Thickeners, preservatives, pH adjusters, chelating agents, stabilizers, irritation reducers, preservatives, colorants, fragrances, pearlescent agents and the like can be added.
  • antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, L-cysteine hydrochloride and the like.
  • An additive can be used individually by 1 type or in combination of 2 or more types.
  • the 2nd external composition of this invention can contain another active ingredient in the range which does not impair the effect of this invention.
  • active ingredients include moisturizing ingredients, anti-inflammatory ingredients, antibacterial ingredients, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cell activation ingredients, anti-aging ingredients, blood circulation promoting ingredients, and the like.
  • active ingredients include those described for the first composition of the present invention.
  • Other active ingredients can be used alone or in combination of two or more.
  • Viscosity of the second external composition of the present invention is preferably about 10,000 to 60,000, more preferably about 20,000 to 45,000. This viscosity is a value measured using a B-type viscometer RB-80L and an M-3 rotor under conditions of 3 rpm, 1 minute, and 25 ° C. If it is the said viscosity range, the rough skin improvement effect can fully be exhibited.
  • the pH of the second external composition of the present invention is preferably about 4 to 9, more preferably about 5 to 8. If it is the said pH range, a stable formulation can be prepared.
  • the second composition for external use of the present invention varies depending on the condition, age, sex, etc. of the skin to be used, but may be the following method, for example. That is, an appropriate amount (for example, about 0.05 to 5 g) may be applied to the skin several times a day (for example, about 1 to 5 times, preferably 1 to 3 times).
  • the composition may be applied so that the daily use amount of vitamin A is preferably about 0.1 to 200 mg, more preferably about 1 to 100 mg, and the daily use amount of the heparin-like substance is preferably
  • the composition may be applied so as to be about 0.01 to 100 mg, more preferably about 0.3 to 75 mg, and the application period may be, for example, about 1 to 14 days, preferably about 3 to 14 days.
  • the second composition for external use of the present invention comprises rough skin such as fingers; elbows, knees, heels, ankle keratosis; cracks and bruises of hands and feet; dry skin; pediatric dry skin; It can be suitably used for prevention, treatment, or improvement of lumps and tension of the skin afterwards, bruise, swelling after sprain, muscle pain, joint pain, sebum deficiency, hypertrophic scar, keloid and the like. Therefore, in addition to healthy people, people with these skin symptoms are suitable for use. That is, the present invention relates to a method for improving rough skin comprising a step of applying a composition containing vitamin A and heparin-like substance, particularly an effective amount thereof to rough human skin, and a composition containing vitamin A and heparin-like substance.
  • the present invention includes a method for improving rough skin while suppressing skin irritation, which comprises the step of applying an effective amount thereof to rough human skin.
  • the present invention includes the following inventions.
  • the number of viable cells was counted after 24 hours of culture.
  • a Cell Counting Kit (Dojindo Laboratories) was used for counting the number of viable cells.
  • heparin indicates a heparin-like substance
  • retinol indicates retinol palmitate
  • BHT dibutylhydroxytoluene.
  • BHT at a concentration of 0.01 w / w% greatly reduced the survival rate of normal human epidermal cells to about 30%. Even when BHT and heparin-like substance were used in combination, the survival rate of normal human epidermal cells was hardly recovered. However, when BHT, heparin-like substance and retinol palmitate were used in combination, the survival rate of normal human epidermis cells was greatly increased. Recovered to about 100%. A synergistic effect of heparin-like substance and retinol palmitate was observed in reducing the cytotoxicity of BHT.
  • Ascorbic acid 2-glucoside Ascorbic acid 2-glucoside as an antioxidant is shown in Table 1-6 below as to the types of components in the test liquid and the final concentrations in the culture liquid. The results are shown in Fig. 1-5.
  • “heparin” indicates a heparin-like substance
  • “retinol” indicates retinol palmitate.
  • Ascorbic acid 2-glucoside at a concentration of 1.2 w / w% reduced the survival rate of normal human epidermal cells to about 30%, but when a heparin analog and retinol palmitate were added thereto, normal human epidermal cells The survival rate was recovered to about 60%.
  • Formulation examples of the first external composition of the present invention are shown in Tables 1-7 and 1-8 below.
  • the unit of numerical values in the formulation examples is “% by weight”.
  • Example 2-1 Second external composition of the present invention (2-1) Evaluation of rough skin improvement effect Preparation of composition for external use
  • the composition for external use of Example 2-1 was produced according to the formulation shown in Table 2-1. Specifically, retinol palmitate, concentrated glycerin, 1,3-butylene glycol, absolute ethanol, isopropyl palmitate, dimethylpolysiloxane, cetanol, polysorbate 60, sorbitan monostearate and ethyl parahydroxybenzoate are added to about 70 ° C. It melt
  • a mixed solution B The mixed solutions A and B were uniformly mixed and then cooled, and triethanolamine was further added to obtain an emulsion composition for external use.
  • the viscosity of the obtained composition was measured at 3 rpm for 1 minute at 25 ° C. using a B-type viscometer RB-80L and an M-3 rotor, and found to be 30000-35000 Pa ⁇ s.
  • Example 1 An appropriate amount of the composition of Example 1 was applied 1 to several times a day for 2 weeks to the forearm of 10 adult women with xeroderma. The following evaluations (2-1-1) to (2-1-4) were performed before coating, 5 days after starting coating, and 14 days after coating.
  • Example 2-1 The stratum corneum moisture content was measured using a Corneometer [registered trademark] CM825 before the application of the stratum corneum moisture content , and 5 days and 14 days after the start of the application. The results are shown in FIG. As is apparent from FIG. 2-1, it was found that the composition of Example 2-1 increased the stratum corneum moisture content.
  • transepidermal water loss was measured using Tewameter (registered trademark) TM300 before application, 5 days and 14 days after the start of application. The results are shown in Fig. 2-2. As is apparent from FIG. 2-2, it was found that the composition of Example 1 reduced the amount of transepidermal water loss.
  • Example 2-1-3 Enlarged image of skin surface Before application and 14 days after the start of application, an enlarged image of the skin surface was taken with a digital microscope (VHX-900: manufactured by Keyence Corporation). The results are shown in Fig. 2-3. As is apparent from FIG. 2-3, it was found that the composition of Example 2-1 prepared skin texture.
  • composition for external use An external composition having the composition shown in Table 2-4 below was prepared. That is, as a base, a composition obtained by mixing white petrolatum, light liquid paraffin, stearyl alcohol, cetanol, polysorbate 60, sorbitan monostearate, polyoxyethylene hydrogenated castor oil 50, and purified water was used. An oil (containing 1 million IU / g retinol palmitate), a heparin-like substance, or a composition containing both of these was prepared. The formulation of the base was designed based on a JP hydrophilic ointment that can be used as an ointment base for a long time.
  • mice HR-1 female mice (7 weeks old) were treated with cotton wool soaked in acetone and diethyl ether mixed on the back, and then cotton wool soaked in water was placed on the back (A). / E treatment). This treatment was performed twice a day for 3 days for each group to prepare a dry skin model. Administration of the test substance was started after the A / E treatment on the third day, and 50 mL was applied twice a day for 2 consecutive days on the back of the mouse.
  • the group composition of mice was 7 mice per group, and 5 groups of no drug application group (normal), base group (control), vitamin A oil group, heparin-like substance group, vitamin A oil + heparin-like substance group .
  • the skin irritation on the second day after application was scored according to Table 2-5 below.
  • Formulation Example A formulation example of the second external composition of the present invention is shown below.
  • the unit of numerical values in the formulation examples is “% by weight”.
  • Example 2-1 (milky lotion) 1st drug heparin analog 0.3 Vitamin A oil (retinol palmitate, 1 million IU / g) 0.5 Sorbitan monostearate 0.6 Polyoxyethylene sorbitan isostearate (20.EO.) 0.8 Carboxyvinyl polymer 0.2 1,3-butylene glycol 3 Dipropylene glycol 3 Sodium edetate 0.05 Behenyl alcohol 0.3 Stearyl alcohol 0.4 Tri (Capryl / Capric Acid) Glyceryl 4 Alpha olefin oligomer 8 Tri (capryl / caprin / myristin / stearic acid) glyceride 0.5 Hyaluronic acid Na 0.01 Dibutylhydroxytoluene 0.1 pH adjuster Appropriate amount of preservative Appropriate amount of purified water The remaining amount was stored in glass containers.
  • Example 2-2 (gel lotion) Heparin analog 0.3 Vitamin A oil ( ⁇ -tocopherol retinoic acid, 1 million IU / g) 0.5 Polyoxyethylene sorbitan isostearate (20. EO.) 0.6 Carboxyvinyl polymer 0.15 Hydroxyethyl cellulose 0.1 Dipropylene glycol 3 Glycerin 5 Sodium edetate 0.05 Tri (capryl / capric) glyceryl 3 Butylhydroxyanisole 0.1 pH adjuster Appropriate amount of preservative Appropriate amount of purified water A residual amount preparation was prepared and stored in a polyethylene container.
  • Example 2-3 (gel serum) Heparin analog 0.3 Vitamin A oil (retinol palmitate, 1 million IU / g) 0.5 Sorbitan monoisostearate0.4 Polyoxyethylene sorbitan isostearate (20. EO.) 0.4 Carboxyvinyl polymer 0.3 Xanthan gum 0.05 Dipropylene glycol 3 Glycerin 5 Sodium edetate 0.05 Acetylated sodium hyaluronate 0.01 Behenyl alcohol 0.2 Methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer 2 Stearyl alcohol 0.3 Tri (capryl / capric) glyceryl 3 Tocopherol acetate 0.05 pH adjuster Appropriate amount of preservative Appropriate amount of purified water A residual amount preparation was prepared and accommodated in a polyethylene terephthalate container.
  • Example 2-4 Heparin analog 0.3 Vitamin A oil (retinol palmitate, 1 million IU / g) 0.5 Dipotassium glycyrrhizinate 0.05 Evening primrose oil 3 Lychee seed extract 0.1 ⁇ -Lipoic acid 0.01 Hydrolyzed soy protein 0.1 Grape seed extract 0.00.5 Chigaya Root Extract 0.001 Artemia extract 0.5 2-Ethylhexyl paramethoxycinnamate 10 Diethylaminohydroxybenzoyl hexyl benzoate 5 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] 1,3,5-triazine 3 Silicone coated zinc oxide 5 Silicone coated titanium oxide 1 Inorganic compound coated zinc oxide 0.05 Glycerin 5 1,3-butylene glycol 2 Lauryl PEG-9 polydimethylsiloxyethyl dimethicone 1 PEG-9 polydimethylsiloxyethyl dimethi
  • Example 2-5 (milky lotion) Heparin analog 0.3 Vitamin A oil (retinol palmitate, 1 million IU / g) 0.5 Sorbitan monostearate0.6 Polyoxyethylene sorbitan isostearate (20.EO.) 0.8 Carboxyvinyl polymer 0.2 1,3-butylene glycol 3 Dipropylene glycol 3 Soy hydrolyzate 0.01 Sodium edetate 0.05 Behenyl alcohol 0.3 Stearyl alcohol 0.4 Tri (Capryl / Capric Acid) Glyceryl 4 Alpha olefin oligomer 8 Tri (capryl / caprin / myristin / stearic acid) glyceride 0.5 Sodium bisulfite 0.1 pH adjuster Appropriate amount of preservative Appropriate amount of purified water A residual amount preparation was prepared and stored in a polypropylene container.
  • Example 2-6 (cream) Heparin analog 0.3 Vitamin A oil (retinol acetate, 1 million IU / g) 0.5 Sorbitan monostearate1.2 Polyoxyethylene sorbitan isostearate (20. EO.) 1.2 Acrylic acid / alkyl methacrylate copolymer 0.4 Pullulan 0.2 Hydrolyzed collagen 0.05 Hydroxyethyl cellulose 0.05 1,3-butylene glycol 10 Glycerin 10 Sodium edetate 0.05 Behenyl alcohol 2 Tri (Capryl / Capric Acid) Glyceryl 8 Polymethacryloyloxyethyl phosphorylcholine 5 Jojoba oil 5 Tri (capryl / caprin / myristin / stearic acid) glyceride 3 Ascorbic acid 0.1 pH adjuster appropriate amount preservative appropriate amount purified water remaining
  • Example 2-7 (cream) Heparin analog 0.3 Vitamin A oil (retinol palmitate, 1 million IU / g) 0.5 Acrylic acid / alkyl methacrylate copolymer 0.1 Xanthan gum 0.05 Polyglyceryl monostearate 1.5 Glycerol monostearate2.1 1,3-butylene glycol 3 Glycerin 5 Dipropylene glycol 2 Sodium edetate 0.05 Behenyl alcohol 1.5 Cetanol 1.5 Squalane 5 Glyceryl tri-2-ethylhexanoate 5 Shea fat 2 pH adjuster appropriate amount preservative appropriate amount purified water remaining
  • Example 2-8 (cream) Heparin analog 0.3 Vitamin A oil (retinol palmitate, 1 million IU / g) 0.5 Ascorbic acid 2-glucoside 0.5 Glycerol monostearate1.6 Polyglyceryl monostearate2.0 Xanthan gum 0.1 1,3-butylene glycol 5 Glycerin 5 Dipropylene glycol 2 Sodium edetate 0.05 Behenyl alcohol 2 Squalane 5 Glyceryl tri-2-ethylhexanoate 5 Tri (capryl / caprin / myristin / stearic acid) glyceride 3 pH adjuster appropriate amount preservative appropriate amount purified water remaining
  • the first and second compositions for external use of the present invention include rough skin such as fingers; elbows, knees, heels, ankle keratosis; cracks and bruises of hands and feet; dry skin; pediatric dry skin; It can be suitably used as an agent for preventing, treating, or improving skin lump and tension after burn, bruise, swelling after sprain, muscle pain, joint pain, sebum deficiency, hypertrophic scar, keloid and the like.

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Abstract

La présente invention concerne une composition pour application externe, qui contient une vitamine A, un analogue d'héparine et un antioxydant. La présente invention concerne également une composition pour application externe pour l'amélioration d'une peau rugueuse et une composition pour application externe pour l'amélioration d'une peau rugueuse tout en réprimant l'irritation cutanée, chacune desdites compositions contenant une vitamine A et un analogue d'héparine.
PCT/JP2011/065900 2010-07-12 2011-07-12 Composition pour application externe WO2012008457A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018016596A (ja) * 2016-07-29 2018-02-01 小林製薬株式会社 α−ＳＭＡ産生抑制剤
JP2019156772A (ja) * 2018-03-14 2019-09-19 ロート製薬株式会社 外用組成物
US10933010B2 (en) 2015-05-11 2021-03-02 Hayashibara Co., Ltd. External dermal agent

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04169512A (ja) * 1990-11-01 1992-06-17 Shiseido Co Ltd 皮膚外用剤
JPH08157337A (ja) * 1994-12-05 1996-06-18 Shiseido Co Ltd 頭髪化粧料
JPH0952848A (ja) * 1995-08-07 1997-02-25 Pola Chem Ind Inc 皮膚外用剤
JP2000204020A (ja) * 1999-01-13 2000-07-25 Pola Chem Ind Inc 唇用の化粧料
JP2003292414A (ja) * 2002-04-01 2003-10-15 Pias Arise Kk 油溶性成分安定化組成物及びその組成物を配合した化粧料、並びに油溶性成分の安定化方法
JP2004307491A (ja) * 2004-03-24 2004-11-04 Taisho Pharm Ind Ltd ヘパリン類似物質を含有する皮膚外用剤
JP2005263689A (ja) * 2004-03-18 2005-09-29 Shiseido Co Ltd コラーゲン産生促進剤
JP2006290787A (ja) * 2005-04-11 2006-10-26 Nippon Fine Chem Co Ltd 化粧料用油剤又は皮膚外用剤用油剤、並びに化粧料又は皮膚外用剤
JP2006312603A (ja) * 2005-05-09 2006-11-16 Shiseido Co Ltd シート状皮膚外用剤及びその製造方法
JP2007153773A (ja) * 2005-12-02 2007-06-21 Shiseido Co Ltd キサントン誘導体並びにそれを含む皮膚外用剤及び医薬組成物

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04169512A (ja) * 1990-11-01 1992-06-17 Shiseido Co Ltd 皮膚外用剤
JPH08157337A (ja) * 1994-12-05 1996-06-18 Shiseido Co Ltd 頭髪化粧料
JPH0952848A (ja) * 1995-08-07 1997-02-25 Pola Chem Ind Inc 皮膚外用剤
JP2000204020A (ja) * 1999-01-13 2000-07-25 Pola Chem Ind Inc 唇用の化粧料
JP2003292414A (ja) * 2002-04-01 2003-10-15 Pias Arise Kk 油溶性成分安定化組成物及びその組成物を配合した化粧料、並びに油溶性成分の安定化方法
JP2005263689A (ja) * 2004-03-18 2005-09-29 Shiseido Co Ltd コラーゲン産生促進剤
JP2004307491A (ja) * 2004-03-24 2004-11-04 Taisho Pharm Ind Ltd ヘパリン類似物質を含有する皮膚外用剤
JP2006290787A (ja) * 2005-04-11 2006-10-26 Nippon Fine Chem Co Ltd 化粧料用油剤又は皮膚外用剤用油剤、並びに化粧料又は皮膚外用剤
JP2006312603A (ja) * 2005-05-09 2006-11-16 Shiseido Co Ltd シート状皮膚外用剤及びその製造方法
JP2007153773A (ja) * 2005-12-02 2007-06-21 Shiseido Co Ltd キサントン誘導体並びにそれを含む皮膚外用剤及び医薬組成物

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* Cited by examiner, † Cited by third party
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US10933010B2 (en) 2015-05-11 2021-03-02 Hayashibara Co., Ltd. External dermal agent
JP2018016596A (ja) * 2016-07-29 2018-02-01 小林製薬株式会社 α−ＳＭＡ産生抑制剤
JP2019156772A (ja) * 2018-03-14 2019-09-19 ロート製薬株式会社 外用組成物

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