Topical composition for skin

Abstract

To provide an oil-in-water emulsified topical composition for skin which exhibits excellent stability while containing tranexamic acid and allantoin simultaneously.SOLUTION: An oil-in-water emulsified topical composition for skin comprises: (A) tranexamic acid or a salt thereof, (B) allantoin or a salt thereof, (C) at least one selected from the group consisting of esters of fatty acids having 16 to 18 carbon atoms and glycerin, esters of fatty acids having 16 to 18 carbon atoms and sorbitan, and self-emulsifying glyceryl stearate, (D) an alkyl acrylate / methacrylate copolymer, and (E) a higher alcohol, wherein the content of (A) tranexamic acid or a salt thereof is 0.9 to 2.5 mass% based on the total amount of the topical composition for skin, the content of (B) allantoin or a salt thereof is 0.08 to 0.2 mass% based on the total amount of the topical composition for skin, and the pH is 5.4 or less.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for external use on the skin. [Background technology]

[0002] Tranexamic acid is an ingredient that has whitening and anti-inflammatory effects. Allantoin is an ingredient that has anti-inflammatory effects. Therefore, tranexamic acid and allantoin are widely used as active ingredients in external skin preparations. Summary of the Invention [Problem to be solved by the invention]

[0003] However, since tranexamic acid is a basic component, while allantoin has a stable pH range in an acidic range, a technique for stably blending both components in a skin topical preparation at the same time has been required. The present invention aims to provide an oil-in-water emulsion type skin topical composition that contains tranexamic acid and allantoin at the same time and has excellent stability. [Means for solving the problem]

[0004] The present inventors have unexpectedly discovered that, in an oil-in-water emulsion-type topical skin preparation simultaneously containing tranexamic acid and allantoin, by incorporating a specific glycerol fatty acid ester, sorbitan fatty acid ester, or self-emulsifying glyceryl stearate as a surfactant, it is possible to obtain a stable topical preparation that is free from gelation, precipitation at low temperatures, and separation at high temperatures.

[0005] The present invention provides, for example, the following inventions. [1] (A) tranexamic acid or a salt thereof, (B) allantoin or a salt thereof, (C) at least one selected from the group consisting of esters of fatty acids having 16 to 18 carbon atoms and glycerin, esters of fatty acids having 16 to 18 carbon atoms and sorbitan, and self-emulsifying glyceryl stearate; (D) alkyl-modified carboxyvinyl polymers, and (E) Higher alcohol The composition for topical skin application is an oil-in-water emulsion type composition for topical skin application, comprising: (A) a content of tranexamic acid or a salt thereof of 0.9 to 2.5 mass% based on the total amount of the composition for topical skin application; and (B) a content of allantoin or a salt thereof of 0.08 to 0.2 mass% based on the total amount of the composition for topical skin application; and a pH of 5.4 or less. [2] (E) The topical skin composition described in [1], wherein the higher alcohol is behenyl alcohol. [3] (F) The composition for external use on the skin described in [1] or [2], further containing at least one selected from the group consisting of organic acids (excluding tranexamic acid) and salts thereof. [4] (G) The composition for external use on the skin according to any one of [1] to [3], further comprising polyoxyethylene hydrogenated castor oil. [5] (H) The composition for external use on the skin according to any one of [1] to [4], further comprising a liquid oil, the content of the liquid oil being 6 to 15 mass% based on the total amount of the composition for external use on the skin. Effect of the Invention

[0006] According to the present invention, it is possible to provide an oil-in-water emulsion type composition for external use on the skin which simultaneously contains tranexamic acid and allantoin and has excellent stability. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] Hereinafter, an embodiment of the present invention will be described in detail. However, the present invention is not limited to the following embodiment.

[0008] The topical skin composition according to this embodiment contains (A) tranexamic acid or a salt thereof (also referred to simply as "component (A)"), (B) allantoin or a salt thereof (also referred to simply as "component (B)"), (C) at least one member selected from the group consisting of an ester of a fatty acid having 16 to 18 carbon atoms and glycerin, an ester of a fatty acid having 16 to 18 carbon atoms and sorbitan, and a self-emulsifying glyceryl stearate (also referred to simply as "component (C)"), (D) an alkyl-modified carboxyvinyl polymer (also referred to simply as "component (D)"), and (E) a higher alcohol (also referred to simply as "component (E)").

[0009] [(A) Tranexamic acid or a salt thereof] Tranexamic acid is a known compound also called trans-4-(aminomethyl)cyclohexane-1-carboxylic acid. Examples of salts of tranexamic acid include salts with inorganic acids, salts with organic acids, salts with inorganic bases, salts with organic bases, salts with acidic amino acids, and salts with basic amino acids. Tranexamic acid or its salts may be synthesized by known methods, or may be obtained as a commercial product.

[0010] The content of the component (A) in the composition for external use on skin according to this embodiment is 0.9 to 2.2% by mass based on the total amount of the composition for external use on skin. By setting the content of the component (A) within the above range, the whitening effect and anti-inflammatory effect of the component (A) are effectively exhibited. The content of the component (A) is preferably 0.95 to 2.2% by mass, more preferably 1.0 to 2.2% by mass, and even more preferably 1.8 to 2.2% by mass based on the total amount of the composition for external use on skin.

[0011] [(B) Allantoin or its salt] Allantoin is a known compound, also called (2,5-dioxo-4-imidazolidinyl) urea.The salt of allantoin includes salts with inorganic acid, salts with organic acid, salts with inorganic base, salts with organic base, salts with acidic amino acid, salts with basic amino acid, etc.Allantoin or its salt may be synthesized by known method, or may be obtained as a commercial product.

[0012] The content of the (B) component in the composition for external use on skin according to this embodiment is 0.08 to 0.2% by mass based on the total amount of the composition for external use on skin. By setting the content of the (B) component within the above range, the anti-inflammatory effect of the (B) component is effectively exhibited. The content of the (B) component is preferably 0.09 to 0.15% by mass, more preferably 0.095 to 0.12% by mass, based on the total amount of the composition for external use on skin.

[0013] In the composition for external use on skin according to this embodiment, the content ratio of the (B) component to the (A) component is not particularly limited, and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of further enhancing the effect of the present invention, the content ratio of the (B) component to the (A) component may be, for example, 0.001 to 3 parts by mass, preferably 0.005 to 2.5 parts by mass, and more preferably 0.01 to 2 parts by mass, of the (B) component per 1 part by mass of the (A) component contained in the composition for external use on skin according to this embodiment.

[0014] [(C) at least one selected from the group consisting of esters of fatty acids having 16 to 18 carbon atoms and glycerin, esters of fatty acids having 16 to 18 carbon atoms and sorbitan, and self-emulsifying glyceryl stearate] Esters of fatty acids having 16 to 18 carbon atoms and glycerin, esters of fatty acids having 16 to 18 carbon atoms and sorbitan, and self-emulsifying glyceryl stearate are all nonionic surfactants used in pharmaceuticals, quasi-drugs, and cosmetics for external use in skin preparations.

[0015] In the ester of a fatty acid having 16 to 18 carbon atoms and glycerin, the fatty acid is preferably a saturated fatty acid. In addition, in the ester of a fatty acid having 16 to 18 carbon atoms and glycerin, the number of carbon atoms of the fatty acid is preferably 16. Specific examples include glyceryl stearate, glyceryl isostearate, glyceryl oleate, and glyceryl palmitate. Among them, glyceryl stearate is preferred from the viewpoint of more prominently exhibiting the effects of the present invention.

[0016] In the ester of a fatty acid having 16 to 18 carbon atoms and sorbitan, the fatty acid is preferably a saturated fatty acid. In the ester of a fatty acid having 16 to 18 carbon atoms and sorbitan, the number of carbon atoms of the fatty acid is preferably 16. Specific examples include sorbitan stearate, sorbitan isostearate, sorbitan oleate, and sorbitan palmitate. Among them, sorbitan stearate is preferred from the viewpoint of more prominently exhibiting the effects of the invention.

[0017] Self-emulsifying glyceryl stearate is a component that is made self-emulsifying by blending glyceryl stearate as the main component with sodium stearate, potassium stearate, a hydrophilic nonionic surfactant, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the HLB of the self-emulsifying glyceryl stearate is preferably 6.0 to 12.0, more preferably 7.5 to 11.5, and even more preferably 8.0 to 11.0. One type of component (C) may be used alone, or two types may be used in combination.

[0018] The total content of component (C) in the topical skin composition according to this embodiment is not particularly limited, and is appropriately set according to the type and content of other blended ingredients, the purpose of the topical skin composition, the formulation form, etc. From the viewpoint of more prominently exhibiting the effects of the present invention, the total content of component (C) is preferably 0.1% by mass or more, more preferably 0.3% by mass or more, and even more preferably 0.5% by mass or more, based on the total amount of the topical skin composition. Also, it is preferably 5% by mass or less, more preferably 4% by mass or less, even more preferably 3% by mass or less, and most preferably 2% by mass.

[0019] In the composition for external use on skin according to this embodiment, the content ratio of the component (C) relative to the component (A) is not particularly limited, and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the component (C) relative to the component (A) may be, for example, 0.05 to 3 parts by mass, preferably 0.1 to 2.5 parts by mass, and more preferably 0.15 to 2 parts by mass, of the total content of the component (C) relative to 1 part by mass of the component (A) contained in the composition for external use on skin according to this embodiment.

[0020] [(D) Alkyl-modified carboxyvinyl polymer] Examples of alkyl-modified carboxyvinyl polymers include acrylic acid / alkyl methacrylate copolymers. When the alkyl-modified carboxyvinyl polymer is an acrylic acid / alkyl methacrylate copolymer, from the viewpoint of more prominently exhibiting the effects of the present invention, it is preferable that the viscosity at pH 5 when a 0.5% by mass aqueous dispersion of the acrylic acid / alkyl methacrylate copolymer is neutralized with triethanolamine is 25 to 35 Pa s. As such an acrylic acid / alkyl methacrylate copolymer, for example, commercially available Pemulen (registered trademark) EZ4U (manufactured by Lubrizol) can be used.

[0021] Furthermore, when the alkyl-modified carboxyvinyl polymer is an acrylic acid-alkyl methacrylate copolymer, from the viewpoint of more prominently exhibiting the effects of the present invention, it is preferable that the gradient of the linear approximation of the viscosity value in the pH range of 3 to 8 when a 0.5% by mass aqueous dispersion of the acrylic acid-alkyl methacrylate copolymer is neutralized with triethanolamine is 2 to 10. As such an acrylic acid-alkyl methacrylate copolymer, for example, commercially available Pemulen (registered trademark) EZ4U (manufactured by Lubrizol) can be used.

[0022] The total content of the component (D) in the composition for external use on skin according to this embodiment is not particularly limited and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the component (D) is preferably 0.05 to 1 mass%, more preferably 0.1 to 0.5 mass%, and even more preferably 0.15 to 0.3 mass%, based on the total amount of the composition for external use on skin.

[0023] The content ratio of the (D) component to the (A) component in the composition for external use on skin according to this embodiment is not particularly limited, and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the (D) component to the (A) component may be, for example, 0.01 to 10 parts by mass, preferably 0.05 to 1 part by mass, and more preferably 0.06 to 0.2 parts by mass, of the total content of the (D) component per 1 part by mass of the (A) component contained in the composition for external use on skin according to this embodiment.

[0024] [(E) Higher alcohol] The higher alcohol is not particularly limited as long as it is an alcohol having 12 to 22 carbon atoms, and examples thereof include linear saturated higher alcohols such as lauryl alcohol, myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, arachyl alcohol, and behenyl alcohol; unsaturated higher alcohols such as oleyl alcohol and selachyl alcohol; and branched higher alcohols such as hexyldecanol, isostearyl alcohol, octyldodecanol, decyltetradecanol, and lanolin alcohol. Among these, from the viewpoint of more significantly exhibiting the effects of the present invention, linear saturated higher alcohols are preferred, and cetanol, stearyl alcohol, and behenyl alcohol are more preferred, with behenyl alcohol being even more preferred. The (E) component may be used alone or in combination of two types.

[0025] The total content of the (E) component in the skin topical composition according to this embodiment is not particularly limited, and is appropriately set according to the type and content of other blended components, the purpose of the skin topical composition, the formulation form, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the (E) component is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and even more preferably 0.3% by mass or more based on the total amount of the skin topical composition. Also, it is preferably 3% by mass or less, more preferably 2% by mass or less, and most preferably 1% by mass or less.

[0026] The content ratio of the (E) component to the (A) component in the composition for external use on skin according to this embodiment is not particularly limited, and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the (E) component to the (A) component may be, for example, 0.01 to 20 parts by mass, preferably 0.05 to 5 parts by mass, and more preferably 0.1 to 2 parts by mass, of the total content of the (E) component per 1 part by mass of the (A) component contained in the composition for external use on skin according to this embodiment.

[0027] [(F) At least one selected from the group consisting of organic acids and salts thereof] The topical skin composition according to this embodiment may further contain at least one selected from the group consisting of (F) organic acids (excluding tranexamic acid) and their salts (also referred to simply as "component (F)"). This can further increase the stability of the topical skin composition. As component (F), a compound that is usually used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used.

[0028] Examples of organic acids include carboxylic acids such as citric acid, succinic acid, malic acid, tartaric acid, lactic acid, acetic acid, dehydroacetic acid, sorbic acid, benzoic acid, salicylic acid, gluconic acid, glycolic acid, etc.; and sulfonic acids such as aminoethylsulfonic acid, etc. Among these, from the viewpoint of more significantly exhibiting the effects of the present invention, carboxylic acids are preferred, with citric acid, succinic acid, malic acid, tartaric acid, and lactic acid being more preferred, and citric acid and succinic acid being even more preferred.

[0029] Examples of the salts of organic acids include salts with inorganic bases (e.g., alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; ammonium salts; and aluminum salts), and salts with organic bases (e.g., salts with tertiary amines such as trimethylamine salts, triethylamine salts, monoethanolamine salts, and triethanolamine salts). Among these, from the viewpoint of more significantly exhibiting the effects of the present invention, salts with inorganic bases are preferred, and alkali metal salts are more preferred.

[0030] The component (F) may be used alone or in combination of two kinds. The component (F) is preferably an organic acid.

[0031] The total content of the component (F) in the topical composition for skin according to this embodiment is not particularly limited and is appropriately set depending on the types and contents of other blended ingredients, the use of the topical composition for skin and the preparation form, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the component (F) is preferably 0.005 to 10 mass%, more preferably 0.01 to 5 mass%, and even more preferably 0.2 to 0.5 mass%, based on the total amount of the topical composition for skin.

[0032] The content ratio of the (F) component to the (A) component in the composition for external use on skin according to this embodiment is not particularly limited, and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the (F) component to the (A) component may be, for example, 0.01 to 20 parts by mass, preferably 0.04 to 10 parts by mass, and more preferably 0.08 to 7 parts by mass, of the total content of the (F) component per 1 part by mass of the (A) component contained in the composition for external use on skin according to this embodiment.

[0033] [(G) Polyoxyethylene hydrogenated castor oil] The topical skin composition according to this embodiment may further contain (G) polyoxyethylene hydrogenated castor oil (also referred to simply as "component (G)"). This can further increase the stability of the topical skin composition. As component (G), a compound that is usually used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used.

[0034] The degree of polymerization of ethylene oxide in polyoxyethylene hydrogenated castor oil is not particularly limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, it is preferably 40 to 80, and more preferably 40 to 60. Specific examples of polyoxyethylene hydrogenated castor oil include polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene hydrogenated castor oil 80. Among these, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, and polyoxyethylene hydrogenated castor oil 60 are preferred.

[0035] The total content of the (G) component in the skin topical composition according to this embodiment is not particularly limited, and is appropriately set according to the type and content of other blended components, the purpose of the skin topical composition, the formulation form, etc. The total content of the (G) component is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and even more preferably 0.3% by mass or more, based on the total amount of the skin topical composition, from the viewpoint of more prominently exhibiting the effects of the present invention. In addition, if the blended amount of the (G) component is too large, stickiness occurs, so the total amount of the skin topical composition is preferably 5% by mass or less, more preferably 4% by mass or less, more preferably 3% by mass or less, and most preferably 2% by mass or less, based on the total amount of the skin topical composition.

[0036] The content ratio of the (G) component to the (A) component in the composition for external use on skin according to this embodiment is not particularly limited, and is appropriately set according to the type and content of other blended components, the use and formulation form of the composition for external use on skin, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the (G) component to the (A) component may be, for example, 0.001 to 3 parts by mass, preferably 0.005 to 2.5 parts by mass, and more preferably 0.01 to 2 parts by mass, of the total content of the (G) component per 1 part by mass of the content of the (A) component contained in the composition for external use on skin according to this embodiment.

[0037] [(H) Liquid oil] The topical skin composition according to this embodiment may further contain (H) liquid oil (also referred to simply as "component (H)"). This can further improve the sensation of use of the topical skin composition. Here, liquid oil refers to an oil component that is liquid at room temperature and normal pressure (25°C, 1 atm). As component (H), a compound that is normally used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used.

[0038] Examples of liquid oils include ester oils of straight-chain fatty acids and lower alcohols, such as diethyl sebacate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, butyl stearate, ethyl oleate, ethyl linoleate, and isopropyl linoleate; ester oils of straight-chain fatty acids and higher straight-chain alcohols, such as cetyl caprate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, cetyl palmitate, stearyl stearate, decyl oleate, and oleyl oleate; isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearyl myristate, and octyl myristate. Ester oils of straight-chain fatty acids, such as isocetyl palmitate, 2-ethylhexyl palmitate, isocetyl palmitate, isostearyl palmitate, 2-ethylhexyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, and octyldodecyl ricinoleate, with branched-chain alcohols; ester oils of branched-chain fatty acids, such as ethyl isostearate and isopropyl isostearate, with lower alcohols; ester oils of branched-chain fatty acids, such as cetyl 2-ethylhexanoate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, and 2-hexyldecyl isostearate, with higher straight-chain alcohols;Ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol caprylate, propylene glycol dicaprylate, propylene glycol di(caprylic acid / capric acid), propylene glycol dicaprate, dipropylene glycol dioleate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl tri-2-ethylhexanoate (triethylhexanoin), tri(caprylic acid / capric acid) Glyceryl triisopalmitate, glyceryl triisostearate, glyceryl tri(caprylic acid / capric acid / myristic acid / stearic acid), glyceryl (ethylhexanoate / stearic acid / adipic acid), trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, pentaerythritol tetraisostearate, pentaerythritol tetra-2-ethylhexanoate, etc. Ester oils of fatty acids having branched chains and alcohols having branched chains, such as octyldodecyl neopentanoate, isocetyl octanoate, isostearyl octanoate, 2-ethylhexyl isopelargonate, hexyldecyl dimethyloctanoate, octyldodecyl dimethyloctanoate, 2-ethylhexyl isopalmitate, isocetyl isostearate, isostearyl isostearate, and octyldodecyl isostearate, lauryl lactate, lactic acid Ester oils having a hydroxyl group, such as myristyl, cetyl lactate, octyldodecyl lactate, trioctyl citrate, triisocetyl citrate, trioctyldodecyl citrate, diisostearyl malate, and trimethyl trimellitate; ester oils of dibasic acids, such as diethylhexyl succinate, diethoxyethyl succinate, dioctyl succinate, diisopropyl adipate, diisobutyl adipate, dioctyl adipate, diethyl sebacate, diisopropyl sebacate, and dioctyl sebacate;Canola oil, avocado oil, almond oil, olive oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, rice oil, safflower oil, sunflower oil, soybean oil, evening primrose oil, corn oil, rapeseed oil, persic oil, palm oil, palm kernel oil, castor oil, jojoba oil, grapeseed oil, macadamia nut oil, meadowfoam oil, menjitsu oil, coconut oil, rosehip Vegetable oils such as oil; liquid horse oil, mink oil, liquid lanolin and other animal oils; oil-soluble vitamins such as dl-α-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol nicotinate, dl-α-tocopherol acetate, benzyl nicotinate, ascorbyl tetra-2-hexyldecanoate, retinol acetate, retinol palmitate, retinol propionate, and liquid paraffin. linear or branched hydrocarbon oils such as olefin glycol, light liquid isoparaffin, heavy liquid isoparaffin, liquid isoparaffin, polybutene, polyisobutene, hydrogenated polyisobutene, squalane (including sugar squalane), squalene, α-olefin oligomer, isohexadecane, isododecane, etc.; higher fatty acids such as oleic acid and isostearic acid; alkyl glyceryl ethers such as isostearyl glyceryl ether; silicone oils such as methylpolysiloxane, dimethylpolysiloxane, dimethylcyclopolysiloxane, decamethylcyclopentasiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, higher alcohol-modified silicone oil, etc.; fluoropolyethers, perfluoroalkyl ether silicones, etc. Among these, ester oils of fatty acids and polyhydric alcohols, linear or branched hydrocarbon oils are preferred, and glyceryl tri-2-ethylhexanoate (triethylhexanoin) α-olefin oligomer and squalane are more preferred. The component (H) may be used alone or in combination of two types. From the viewpoint of achieving a remarkable effect of the present invention, a combination of an ester oil of fatty acids and polyhydric alcohols and linear or branched hydrocarbon oils is preferred, and a combination of glyceryl tri-2-ethylhexanoate (triethylhexanoin) and α-olefin oligomer is more preferred.

[0039] The total content of the (H) component in the composition for external use on skin according to this embodiment is 0.5 to 25% by mass based on the total amount of the composition for external use on skin. This can further improve the feeling of use of the composition for external use on skin. From the viewpoint of more prominently exhibiting the effects of the present invention, the total content of the (H) component is preferably 1 to 20% by mass, more preferably 3 to 18% by mass, and even more preferably 6 to 15% by mass based on the total amount of the composition for external use on skin.

[0040] The content ratio of the (H) component to the (A) component in the composition for external use on skin according to this embodiment is not particularly limited, and is appropriately set depending on the type and content of other blended ingredients, the use of the composition for external use on skin, the formulation form, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the (H) component to the (A) component may be, for example, 1 to 200 parts by mass, preferably 1.5 to 130 parts by mass, and more preferably 2 to 15 parts by mass, of the total content of the (H) component per 1 part by mass of the content of the (A) component contained in the composition for external use on skin according to this embodiment.

[0041] [Thickener] The skin topical composition according to this embodiment may further contain a thickener other than the component (D). This can further increase the stability of the skin topical composition. As the thickener other than the component (D), a compound that is usually used as a component of skin topical preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used.

[0042] Examples of thickeners other than component (D) include gum polysaccharides such as gellan gum, xanthan gum, sclerotium gum, locust bean gum, biosaccharide gum, tamarind gum, quince seed, gum arabic, tara gum, guar gum, galactan, gum arabic, and tragacanth gum; cellulose polysaccharides such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, and hydrophobized hydroxypropylmethylcellulose; hyaluronic acid or a salt thereof; acetylated hyaluronic acid or a salt thereof; chondroitin sulfate or a salt thereof; vinyl thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymer; polyethylene glycol; bentonite; dextrin palmitate; (hydroxyethyl acrylate / Na acryloyldimethyltaurate) copolymer; and (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer. Among these, from the viewpoint of more significantly exhibiting the effects of the present invention, gum-type polysaccharides are preferred, and xanthan gum is more preferred. The water-soluble polysaccharides may be used alone or in combination of two types. The content of the thickener other than component (D) is preferably 0.01 to 1.0% by mass, more preferably 0.03 to 0.8% by mass, and even more preferably 0.05 to 0.5% by mass, based on the total amount of the composition for external use on skin.

[0043] The skin topical composition according to this embodiment may optionally contain at least one component selected from the group consisting of components (F), (G) and (H) in addition to components (A), (B), (C), (D) and (E), and may further contain one or more of various components such as water, polyhydric alcohol, chelating agent, surfactant other than component (C), moisturizing component, antioxidant, preservative or antiseptic. These components are not particularly limited as long as they are used as components of skin topical preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics.

[0044] The content of water is preferably 40 to 95 mass %, more preferably 45 to 90 mass %, and even more preferably 50 to 85 mass %, based on the total amount of the composition for external use on skin.

[0045] Examples of polyhydric alcohols include glycerin, diglycerin, triglycerin, propylene glycol, 1,3-butylene glycol, dipropylene glycol, tripropylene glycol, ethylene glycol, diethylene glycol, isoprene glycol, 1,3-propanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, decanediol, neopentyl glycol, sorbitol, xylitol, erythritol, mannitol, and polyethylene glycol. The content of the polyhydric alcohol is preferably 1 to 30% by mass, more preferably 5 to 25% by mass, and even more preferably 8 to 20% by mass, based on the total amount of the composition for external use on skin.

[0046] Examples of chelating agents include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetate salts (sodium salts (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salts, etc.), phytic acid, gluconic acid, polyphosphoric acid, metaphosphoric acid, caprylhydroxamic acid, etc.

[0047] The surfactant other than the component (C) may be any of nonionic surfactants, cationic surfactants, anionic surfactants, amphoteric surfactants, etc. Examples of the nonionic surfactant include sorbitan fatty acid esters such as diglycerol sorbitan penta-2-ethylhexyl acid and diglycerol sorbitan tetra-2-ethylhexyl acid; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococonut oil fatty acid esters; glycerin alkyl ethers; polyglyceryl-2 oleate, poly stearate, etc. Examples of the surfactants include polyglycerin fatty acid esters such as glyceryl-2, polyglyceryl-10 oleate, polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 distearate, polyglyceryl-10 trioleate, polyglyceryl-10 pentaoleate, and polyglyceryl-10 pentastearate; polysaccharide alkyl fatty acid esters such as sucrose fatty acid esters; polyoxyalkylene alkyl ethers such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, and polyoxyethylene stearyl ether; silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymers, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. Examples of the amphoteric surfactants include phospholipids such as lecithin and hydrogenated lecithin.

[0048] Examples of moisturizing components include amino acids such as glycine, aspartic acid, and arginine; natural moisturizing factors such as sodium lactate, sodium pyrrolidone carboxylate, and sodium hyaluronate; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

[0049] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, and L-cysteine ​​hydrochloride.

[0050] Examples of preservatives or antiseptics include isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, sodium benzoate, phenoxyethanol, benzyl alcohol, chlorhexidine gluconate, methylisothiazoline, and iodopropynyl butylcarbamate.

[0051] The composition for external use on skin according to this embodiment can be produced, for example, by the following method. (1) Component (C), component (E), and, if necessary, other oil components are added and mixed to obtain the desired concentrations to prepare an oil phase. (2) Water, component (A), component (B), component (D), and other aqueous components are added and mixed to obtain the desired concentrations to prepare an aqueous phase. (3) The oil phase and the aqueous phase prepared above are mixed.

[0052] The pH of the skin external composition according to the present embodiment is 5.4 or less. By making the pH within this range, coloration and decomposition of allantoin are significantly suppressed. In order to more significantly achieve the effects of the present invention, the pH is preferably 5.3 or less, more preferably 5.2 or less. In addition, the pH of the skin external composition according to the present embodiment is preferably 3.8 or more, more preferably 4.0 or more.

[0053] The viscosity of the composition for external use on skin according to the present embodiment is not particularly limited as long as it is within a medicamentously, pharmacologically (pharmaceutical) or physiologically acceptable range. The viscosity of the composition according to the present embodiment is preferably 2 to 20 Pa·s, more preferably 3 to 18 Pa·s, and even more preferably 5 to 17 Pa·s, as measured at 25°C with a rotational viscometer (TV-10 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor; M3, etc.).

[0054] The composition for external use on the skin according to this embodiment is an oil-in-water emulsion type, and is used, for example, in the form of an emulsion (milk).

[0055] The skin topical composition according to the present embodiment can be directly or indirectly applied to a desired site by storing it in, for example, a container with a nozzle, a container with a pump, a jar container, a tube container, a container with a hole in the inner plug, a container with a hinge cap, a sponge head container, a roll-on container, etc. The nozzle or sponge can be designed to have a tapered or large diameter so that it can be applied to a narrow or wide area of ​​the application site. After applying the skin topical composition according to the present embodiment to the application site, it can also be used by spreading it with a nonwoven fabric, fingers, etc.

[0056] The material of the container that fills the skin external composition according to the present embodiment is not particularly limited, and can be used as a container for pharmaceutical external preparations.As such container material, for example, the container that the surface that contacts with the skin external composition is partially or entirely, preferably entirely, is made of at least one material selected from the group consisting of polyolefin resin, acrylic resin, polyester, polycarbonate, fluororesin, polyvinyl chloride, polyamide, ABS resin, AS resin, polyacetal, modified polyphenylene ether, polyarylate, polysulfone, polyimide, cellulose acetate, aluminum, and glass.

[0057] From the viewpoint of ease of handling the preparation and ease of molding, the material of the container in which the skin topical composition according to the present embodiment is filled is preferably, for example, aluminum, polyethylene (PE) (including high density polyethylene (HDPE), low density polyethylene (LDPE), very low density polyethylene, linear low density polyethylene (LLDPE), ultra-high molecular weight polyethylene, etc.), polypropylene (PP) (including isotactic polypropylene, syndiotactic polypropylene, atactic polypropylene, etc.), ethylene-propylene copolymer, polymethylpentene, polybutene-1, 1,2-polybutadiene and other polyolefin resins, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate and other polyester resins, and more preferably, polyethylene, polypropylene, and polyethylene terephthalate. In addition, the material of the innermost layer of the container in which the skin topical composition according to the present embodiment is preferably, for example, polyethylene (PE) (high density polyethylene (HDPE), low density polyethylene (LDPE), very low density polyethylene, linear low density polyethylene (LLDPE), polypropylene, and polyethylene terephthalate (PET).

[0058] When the topical skin composition according to this embodiment is filled into a container having a lid or cap, it is preferable that the material of the lid or cap is made of one of the materials exemplified above as the container material.

[0059] The skin topical composition according to this embodiment can be used for the purpose of anti-inflammatory, whitening, etc. In addition, application sites include the skin of the hands (palms and fingers), face, feet, head, neck, chest, armpits, back, waist, back of elbows, and back of knees. In addition, it is preferable to apply an appropriate amount of the skin topical composition according to this embodiment to the skin once or several times a day. EXAMPLES

[0060] The present invention will be specifically described below based on test examples, but the present invention is not limited to these.

[0061] [Test Example 1: Stability of the formulation (1)] The formulations (emulsions) of the test examples having the compositions shown in Table 1 were prepared by the following method. The units for each component are % by mass. (1) Components (C), (E), (G), and (H) were added and mixed to give desired concentrations to prepare an oil phase. (2) Components (A), (B), (D), (F), purified water and other aqueous components were added and mixed to obtain the desired concentrations to prepare an aqueous phase. (3) The oil phase and the aqueous phase prepared above were mixed. The above-prepared preparations were evaluated for gelation, precipitation during low-temperature storage, and separation during high-temperature storage by the following methods. Regarding gelation, the formulation was stored in a 50 mL glass screw vial and visually inspected after storage at room temperature for one day, with a rating of ◎ indicating no gelation at all, ○ indicating slight gelation but no quality problem, and × indicating clear gelation. Gelling refers to the lack of fluidity of the formulation when the glass screw vial is placed upside down. Regarding precipitation during low-temperature storage, the formulation was stored in a 50 mL glass screw vial and the condition of the formulation after storage at 0°C for one month was visually inspected. If no precipitation was observed, it was marked with an ◎; if slight precipitation was observed but did not pose a quality problem, it was marked with an ○; and if precipitation was clearly observed, it was marked with an ×. Regarding separation during high-temperature storage, the formulation was stored in a 50 mL glass screw vial and the condition of the formulation after storage at 60°C for 2 weeks was visually inspected. If no separation was observed, it was marked with an ◎; if slight separation was observed but did not pose a quality problem, it was marked with an ○; and if separation was clearly observed, it was marked with an ×. The viscosity was measured at 25° C. using a rotational viscometer (TV-10 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: M3). The evaluation results are shown in Table 1.

[0062] [Table 1]

[0063] The formulations of the examples, which used glyceryl stearate, self-emulsifying glyceryl stearate, or sorbitan stearate as the nonionic surfactant, performed well in terms of all the evaluation items of gelation, low-temperature precipitation, and high-temperature separation, whereas the formulations of the comparative examples, which used polyglyceryl pentastearate or polyglyceryl myristate, showed clear separation when stored at high temperatures.

[0064] [Test Example 2: Stability of the formulation (2)] The formulations (emulsions) of each test example having the compositions shown in Table 2 were prepared according to the method described in Test Example 1. The units of each component are mass %. The gelling, precipitation during low-temperature storage, separation during high-temperature storage, and viscosity of each of the above-prepared formulations were evaluated in the same manner as in Test Example 1. The evaluation results are shown in Table 2.

[0065] [Table 2]

[0066] The formulations of the examples, which used acrylic acid / alkyl methacrylate copolymer as a thickener, performed well in all evaluation items of gelation, low-temperature precipitation, and high-temperature separation, whereas the formulations of the comparative examples, which used hydroxyethyl cellulose or gellan gum, showed clear separation when stored at high temperatures.

[0067] [Test Example 3: Stability of the formulation (3)] The formulations (lotions) of each test example having the composition shown in Table 3 were prepared according to the method described in Test Example 1. The units of each component are mass %. Regarding the stability of allantoin in each of the above-prepared formulations, the formulations were stored in glass screw vials with a capacity of 20 to 30 mL, and the content of allantoin in the formulations after storage at 60°C for 3 weeks was measured using HPLC, and the remaining rate (%) of allantoin was calculated. The measurement conditions and evaluation criteria for HPLC are as follows. (HPLC measurement conditions) Detector: UV spectrophotometer (detection wavelength: 220 nm) Column: ODP2 HP-4E (4.6 x 250 mm, particle size 5 μm) Column temperature: 40℃ Mobile phase: 10 mM potassium dihydrogen phosphate buffer (pH 3.0) (Evaluation Criteria) Residual rate less than 80%: × Residual rate: 80% or more but less than 85%: △ Survival rate 85% or more: 〇 The evaluation results of the stability of allantoin are shown in Table 3.

[0068] [Table 3]

[0069] The stability of allantoin in the formulation of Example 3-1, in which the pH was set at 5.2, was evaluated as good, with an ◯ rating, whereas the stability of allantoin in the formulation of Comparative Example 3-1, in which the pH was set at 5.5, was evaluated as △, and the stability of allantoin in the formulation of Comparative Example 3-2, in which the pH was set at 5.8, was evaluated as ×, and both were poor.

[0070] [Formulation Example 1] Emulsion Tranexamic acid 2% by mass Allantoin 0.1% by mass Acrylic acid / alkyl methacrylate copolymer 0.25% by mass Xanthan gum 0.1% by mass Self-emulsifying glyceryl stearate 1% by mass Polyoxyethylene hydrogenated castor oil 40 1% by mass Behenyl alcohol 0.5% by mass Squalane 5% by mass Triethylhexanoin 5% by mass Glycerin 5% by mass Pentanediol 1.5% by mass Succinic acid 0.3% by mass Sodium hyaluronate 0.01% by mass Hydrolyzed hyaluronic acid 0.01% by weight Magnesium ascorbate 0.01% by mass Ascorbic acid 0.001% by mass Tocopherol 0.001% by mass Job's tears fermented liquid 0.1% by mass Coix seed extract 0.1% by mass 2-Methacryloyloxyethyl phosphorylcholine-butyl methacrylate copolymer liquid 0.5% by mass Water Residual pH 5.2

Claims

1. (A) tranexamic acid or a salt thereof, (B) allantoin or a salt thereof, (C) at least one selected from the group consisting of an ester of a fatty acid having 16 to 18 carbon atoms and glycerin, an ester of a fatty acid having 16 to 18 carbon atoms and sorbitan, and a self-emulsifying glyceryl stearate; (D) alkyl-modified carboxyvinyl polymers, and (E) Higher alcohol The composition for topical skin application is an oil-in-water emulsion type composition for topical skin application, comprising: (A) a content of tranexamic acid or a salt thereof of 0.9 to 2.5 mass% based on the total amount of the composition for topical skin application; and (B) a content of allantoin or a salt thereof of 0.08 to 0.2 mass% based on the total amount of the composition for topical skin application; and a pH of 5.4 or less.

2. The topical skin composition according to claim 1 , wherein (E) the higher alcohol is behenyl alcohol.

3. The composition for external use on the skin according to claim 1 or 2, further comprising (F) at least one selected from the group consisting of organic acids (excluding tranexamic acid) and salts thereof.

4. The composition for external use on the skin according to claim 1 or 2, further comprising (G) polyoxyethylene hydrogenated castor oil.

5. The composition for external use on the skin according to claim 1 or 2, further comprising (H) a liquid oil, the content of which is 6 to 15 mass% based on the total amount of the composition for external use on the skin.

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