Topical composition for skin

Abstract

To provide a topical composition for skin which exhibits excellent stability while containing tranexamic acid and allantoin simultaneously.SOLUTION: A 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 1,3-butylene glycol, dipropylene glycol, 1,3-propanediol, 1,2-pentanediol, and 1,2-hexanediol, and (D) at least one selected from the group consisting of organic acids (excluding tranexamic acid) and salts thereof, 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 ingredient, while allantoin has a stable pH range in an acidic range, a technique for stably blending both ingredients in a skin topical preparation at the same time has been required. The present invention aims to provide a 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 a topical skin preparation simultaneously containing tranexamic acid and allantoin, by adding one or more polyhydric alcohols selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, 1,3-propanediol, 1,2-pentanediol, and 1,2-hexanediol and setting the pH within a predetermined range, it is possible to obtain a stable topical preparation in which coloration of the preparation and decomposition of allantoin are suppressed.

[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 1,3-butylene glycol, dipropylene glycol, 1,3-propanediol, 1,2-pentanediol, and 1,2-hexanediol; and (D) at least one selected from the group consisting of organic acids (excluding tranexamic acid) and salts thereof The composition for external application on the skin contains (A) tranexamic acid or a salt thereof in an amount of 0.9 to 2.5 mass% based on the total amount of the composition for external application on the skin, and (B) allantoin or a salt thereof in an amount of 0.08 to 0.2 mass% based on the total amount of the composition for external application on the skin, and has a pH of 5.4 or less. [2] The topical skin composition described in [1], further comprising (E) at least one selected from the group consisting of alkyl-modified carboxyvinyl polymers and water-soluble polysaccharides. [3] (F) The topical skin composition described in [1] or [2], further containing polyoxyethylene hydrogenated castor oil. [4] The composition for external skin application according to any one of [1] to [3], which has a viscosity at 20°C of 1 to 50,000 mPa·s. [5] The composition for external skin application according to any one of [1] to [3], which has a viscosity at 20°C of 1 to 1000 mPa·s. Effect of the Invention

[0006] According to the present invention, it is possible to provide a composition for external application to 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 of 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 selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, 1,3-propanediol, 1,2-pentanediol, and 1,2-hexanediol (also referred to simply as "component (C)"), and (D) at least one selected from the group consisting of organic acids (excluding tranexamic acid) and salts thereof (also referred to simply as "component (D)").

[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 2.5% 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 / or anti-inflammatory effect of the component (A) can be 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 0.085 to 0.15% by mass, more preferably 0.09 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 1,3-butylene glycol, dipropylene glycol, 1,3-propanediol, 1,2-pentanediol, and 1,2-hexanediol] The component (C) may be used alone or in combination of two types.

[0015] The total content of the component (C) 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 purpose and formulation form of the composition for external use on skin, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the component (C) is preferably 1 to 30% by mass, more preferably 3 to 25% by mass, and even more preferably 5 to 20% by mass, based on the total amount of the composition for external use on skin.

[0016] The content ratio of the (C) 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 effect of the present invention, the content ratio of the (C) component to the (A) component may be, for example, 1 to 25 parts by mass, preferably 1.5 to 20 parts by mass, and more preferably 2.5 to 15 parts by mass, of the total content of the (C) component per 1 part by mass of the (A) component contained in the composition for external use on skin according to this embodiment.

[0017] [(D) At least one selected from the group consisting of organic acids and salts thereof] The organic acid is not particularly limited as long as it is an organic acid other than tranexamic acid. As component (D), a compound that is usually used as a component of an external preparation for skin in the fields of medicines, quasi-drugs, or cosmetics can be used.

[0018] 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.

[0019] 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.

[0020] The component (D) may be used alone or in combination of two kinds, and is preferably an organic acid.

[0021] 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 0.001 to 2 mass%, more preferably 0.005 to 1.5 mass%, even more preferably 0.05 to 1 mass%, even more preferably 0.08 to 0.5 mass%, and particularly preferably 0.15 to 0.3 mass%, based on the total amount of the composition for external use on skin.

[0022] 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 effect of the present invention, the content ratio of the (D) component to the (A) component may be, for example, 0.0005 to 3 parts by mass, preferably 0.01 to 1 part by mass, and more preferably 0.1 to 0.5 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.

[0023] [(E) At least one member selected from the group consisting of alkyl-modified carboxyvinyl polymers and water-soluble polysaccharides] The topical skin composition according to this embodiment may further contain at least one selected from the group consisting of (E) alkyl-modified carboxyvinyl polymers and water-soluble polysaccharides (also referred to simply as "component (E)"). This can further increase the stability of the topical skin composition. As component (E), 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.

[0024] Examples of alkyl-modified carboxyvinyl polymers include acrylic acid alkyl methacrylate copolymers and acrylates copolymers. From the viewpoint of achieving the effects of the invention more remarkably, acrylic acid alkyl methacrylate copolymers are preferred. Alkyl-modified carboxyvinyl polymers are readily available as commercial products. Examples of such commercial products include PEMULEN TR-1, PEMULEN TR-2, PEMULEN EZ-4 Polymeric Emulsifier, Carbopol ETD 2020, Carbopol ULTREZ 20, and Carbopol SC800 (all trade names, Lubrizol Japan Co., Ltd.).

[0025] Examples of water-soluble polysaccharides 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, and tragacanth gum; cellulose polysaccharides such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, and hydrophobized hydroxypropylmethylcellulose; and mucopolysaccharides such as hyaluronic acid or a salt thereof, acetyl hyaluronic acid or a salt thereof, and chondroitin sulfate or a salt thereof. Among these, from the viewpoint of more significantly exerting the effects of the present invention, gum polysaccharides and cellulose polysaccharides are preferred, and xanthan gum and hydroxyethylcellulose are more preferred.

[0026] The component (E) may be used alone or in combination of two types.

[0027] The total content of the component (E) in the composition for external use on 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 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 (E) is preferably 0.01 to 1 mass%, more preferably 0.05 to 0.8 mass%, and even more preferably 0.1 to 0.5 mass%, based on the total amount of the composition for external use on skin.

[0028] 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, 0.005 to 1 part by mass, preferably 0.025 to 1 part by mass, and more preferably 0.05 to 0.5 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.

[0029] [(F) Polyoxyethylene hydrogenated castor oil] The topical skin composition according to this embodiment may further contain (F) polyoxyethylene hydrogenated castor oil (also simply referred to 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.

[0030] 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.

[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 type and content 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 5 mass%, more preferably 0.01 to 2 mass%, even more preferably 0.05 to 1 mass%, and most preferably 0.2 to 0.8 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 according to the type and content of other blended ingredients, 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 (F) component to the (A) component may be, for example, 0.005 to 2 parts by mass, preferably 0.025 to 1.5 parts by mass, and more preferably 0.1 to 1.0 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] The skin topical composition according to this embodiment may contain, in addition to the components (A), (B), (C), and (D), an optional component (E) and / or a component (F), and may further contain one or more of various components such as water, a polyhydric alcohol other than the component (C), a chelating agent, a thickener other than the component (E), a surfactant other than the component (F), an ultraviolet absorbing agent, an ultraviolet scattering agent, a moisturizing component, an antioxidant, a preservative, or an 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.

[0034] The water content is preferably 50 to 95 mass%, more preferably 70 to 95 mass%, even more preferably 72 to 92 mass%, and most preferably 75 to 90 mass%, based on the total amount of the topical skin composition.

[0035] Examples of polyhydric alcohols other than component (C) include glycerin, diglycerin, triglycerin, propylene glycol, ethylene glycol, diethylene glycol, isoprene glycol, 1,2-octanediol, decanediol, neopentyl glycol, sorbitol, xylitol, erythritol, and mannitol. The content of polyhydric alcohols other than component (C) is preferably 0.1 to 50% by mass, more preferably 1 to 25% by mass, and even more preferably 3 to 15% by mass, based on the total amount of the composition for external use on skin. It may also be 0.1 to 3% by mass, 0.2 to 5% by mass, or 1 to 10% by mass.

[0036] Examples of the chelating agent include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetate (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, polyphosphoric acid, metaphosphoric acid, etc.

[0037] Examples of thickeners other than component (E) include vinyl thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymer; polyethylene glycol; bentonite; dextrin palmitate; (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer; and (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer.

[0038] The surfactant other than the component (F) may be any of a nonionic surfactant, a cationic surfactant, an anionic surfactant, an amphoteric surfactant, and the like. Examples of nonionic surfactants include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexyl acid, and diglycerol sorbitan tetra-2-ethylhexyl acid; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococoate glyceryl; glycerin alkyl ether; glyceryl stearate, glyceryl myristate, and the like. Glycerol fatty acid esters such as glyceryl lyceryl and glyceryl oleate; polyglyceryl-2 oleate, polyglyceryl-2 stearate, 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 copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. Amphoteric surfactants include phospholipids such as lecithin and hydrogenated lecithin.

[0039] Examples of the ultraviolet absorber include salicylic acid-based ultraviolet absorbers such as 2-ethylhexyl salicylate, homomenthyl salicylate, and ethylene glycol salicylate; cinnamic acid-based ultraviolet absorbers such as di-paramethoxycinnamate mono-2-ethylhexanoate glyceryl, and ethylhexyl paramethoxycinnamate; benzoylmethane-based ultraviolet absorbers such as 4-tert-butyl-4'-methoxydibenzoylmethane; 2-[4-(diethylamino)-2- Benzoic acid ester derivatives such as hydroxybenzoyl]benzoic acid hexyl ester UV absorbers; dimethoxybenzylidene dioxoimidazolidinepropionic acid 2-ethylhexyl; 2,2'-methylenebis[6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol], 2,4-bis-[{4-(2-ethylhexyloxy)-2-hydroxy}-phenyl]-6-(4-methoxyphenyl) benzalmalonate derivative ultraviolet absorbers such as dimethicodiethyl benzalmalonate; octocrylene ultraviolet absorbers such as 2-cyano-3,3-diphenylprop-2-enoic acid 2-ethylhexyl ester; imidazole sulfonic acid derivative ultraviolet absorbers such as 2-phenylbenzimidazole-5-sulfonic acid and phenyldibenzimidazole tetrasulfonic acid disodium; and benzophenone derivative ultraviolet absorbers such as 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and salts thereof, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, or tetrahydroxybenzophenone.

[0040] Examples of ultraviolet scattering agents include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, and hydrous silicic acid; inorganic compounds coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica, and talc, or composited with resin powders such as polyamide, polyethylene, polyester, polystyrene, and nylon; and inorganic compounds treated with silicone oil, aluminum salts of fatty acids, alkyl titanates, and the like.

[0041] Examples of moisturizing components include amino acids such as glycine, aspartic acid, and arginine; natural moisturizing factors such as sodium lactate and sodium pyrrolidone carboxylate; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

[0042] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, and L-cysteine ​​hydrochloride.

[0043] Examples of preservatives or antiseptics include isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol, benzyl alcohol, chlorhexidine gluconate, methylisothiazoline, iodopropynyl butylcarbamate, and sodium benzoate.

[0044] The skin topical composition according to the present embodiment can be prepared by adding and mixing the desired amounts of the (A), (B), (C) and (D) components, and other components as necessary, to a desired concentration. For example, in the case of an emulsion-form preparation, the components are added and mixed into the aqueous phase and the oil phase, and then these phases are mixed to prepare the composition. For example, in the case of a single-phase preparation such as a liquid, the components are added and mixed into the base phase to prepare the composition. In addition, regardless of the dosage form, the composition can be efficiently prepared by setting a pre-dissolved or pre-dispersed phase as necessary.

[0045] The pH of the skin external composition according to this 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 effect 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 this embodiment is preferably 3.5 or more, more preferably 4.0 or more.

[0046] 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 medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable range. The viscosity of the composition according to the present embodiment is preferably 1 to 50,000 mPa·s, more preferably 1 to 40,000 mPa·s, even more preferably 1 to 10,000 mPa·s, even more preferably 1 to 1000 mPa·s, particularly preferably 1 to 500 mPa·s, particularly more preferably 5 to 200 mPa·s, and most preferably 10 to 100 mPa·s, as measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34'×R24; TV-10 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: M4, M3, etc.).

[0047] The skin topical composition according to this embodiment is not particularly limited as long as it is in a form known as a pharmaceutical, quasi-drug, or cosmetic. For example, it can be formulated by a known method in the form of a liquid, suspension, emulsion (milky liquid), cream, ointment, gel, liniment, lotion, aerosol, powder, or a sheet of nonwoven fabric or the like impregnated with the components of the present invention. From the viewpoint of more prominently exerting the effects of the present invention, liquid, gel, and lotion are preferred, and liquid and lotion are particularly preferred. By formulating in such a form, the effect can be fully exerted. In addition, when the skin topical composition according to this embodiment is formulated in an emulsion form, it may be an oil-in-water type or a water-in-oil type.

[0048] When the skin topical composition according to the present embodiment is formulated in a liquid or semi-solid form in the form of a solution, suspension, emulsion (milky lotion), cream, ointment, gel, lotion, etc., the skin topical composition can be directly or indirectly applied to a desired site by storing it in 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., but is not limited thereto. The nozzle or sponge can also 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 be spread by nonwoven fabric, fingers, etc. for use. In another embodiment, when the skin topical composition is formulated in a liquid form in the form of a solution, suspension, emulsion (milky lotion), cream, gel, lotion, etc., the skin topical composition can also be directly sprayed onto a desired site by storing it in a spray container, but is not limited thereto.

[0049] 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.

[0050] 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 (PET), 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).

[0051] 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.

[0052] The skin topical composition according to this embodiment can be used for the purpose of anti-inflammation, whitening, improving dullness, preventing acne, 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

[0053] The present invention will be specifically described below based on test examples, but the present invention is not limited to these.

[0054] [Test Example 1: Coloration of the formulation and stability of allantoin (1)] The preparations (lotions) of each test example having the compositions shown in Tables 1-1 and 1-2 were prepared in a conventional manner. The units of each component are mass %. Regarding color stability, the formulation was stored in a 50 mL glass screw vial, and one trained evaluator visually evaluated the color of the formulation after storage at 60°C for 3 weeks. Colorless to slightly yellowish color was evaluated as "○", and yellow to yellowish brown color was evaluated as "×". Regarding the stability of allantoin, the formulation was stored in a 20-50 mL glass screw vial, and the allantoin content in the formulation after storage at 60°C for 3 weeks was measured using HPLC, and the remaining rate (%) of allantoin was calculated according to the following formula. The measurement conditions and evaluation criteria for HPLC are as follows. (Calculation formula for residual rate (%) of allantoin) (Allantoin content / initial allantoin content) x 100 (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 83%: △ Survival rate 83% or more: 〇 The evaluation results of the coloration of the formulation and the stability of allantoin are shown in Tables 1-1 and 1-2.

[0055] [Table 1-1]

[0056] [Table 1-2]

[0057] The formulations of Examples 1-1 and 1-2, which use 1,3-butylene glycol as polyhydric alcohol, do not show yellowing, whereas the formulations of Comparative Examples 1-3, 1-4 and 1-5, which use propylene glycol, show significant yellowing.In addition, the formulations of Examples 1-1 and 1-2, which are set to pH 5.2, show good stability of allantoin with ◯, whereas the formulations of Comparative Examples 1-1 and 1-6, which are set to pH 5.5, show △, and the formulations of Comparative Examples 1-2 and 1-7, which are set to pH 5.8, show poor stability with ×. In the preparations of Examples 1-3 to 1-14, which used 1,3-propanediol, 1,2-pentanediol, dipropylene glycol and 1,2-hexanediol as polyhydric alcohols and had a pH in the range of 4.9 to 5.3, no yellowing was observed in the preparations, and the stability of allantoin was also good.

[0058] [Test Example 2: Coloration of the formulation and stability of allantoin (2)] Preparations (lotions) of each test example having the compositions shown in Tables 2-1 and 2-2 were prepared in a conventional manner. Regarding color stability, the formulation was stored in a 50 mL glass screw vial and visually evaluated for color after storage at 40°C for 7 days. Colorless to pale yellow was evaluated as ◯, and yellow to yellowish brown was evaluated as ×. Regarding the stability of allantoin, the preparation was stored in a 50 mL glass screw vial, and the content of allantoin in the preparation after storage at 60° C. for 3 weeks was measured by HPLC, and the remaining rate (%) of allantoin was calculated. The measurement conditions and evaluation criteria by HPLC were the same as those in Test Example 1. The evaluation results of the coloration of the formulation and the stability of allantoin are shown in Tables 2-1 and 2-2.

[0059] [Table 2-1]

[0060] [Table 2-2]

[0061] No yellowing was observed in any of the preparations of the examples, and the stability of allantoin was also good.

[0062] [Test Example 3: Coloration of the formulation and stability of allantoin (3)] Test preparations (lotions) having the compositions shown in Tables 3-1 and 3-2 were prepared in a conventional manner. Regarding color stability, the formulation was stored in a 50 mL glass screw vial and visually evaluated for color after storage at 60°C for 7 days. Colorless to pale yellow was evaluated as ◯, and yellow to yellowish brown was evaluated as ×. Regarding the stability of allantoin, the preparation was stored in a 50 mL glass screw vial, and the content of allantoin in the preparation after storage at 60° C. for 3 weeks was measured by HPLC, and the remaining rate (%) of allantoin was calculated. The measurement conditions and evaluation criteria by HPLC were the same as those in Test Example 1. The evaluation results of the coloration of the formulation and the stability of allantoin are shown in Tables 3-1 and 3-2.

[0063] [Table 3-1]

[0064] [Table 3-2]

[0065] No yellowing was observed in the preparations of Examples 3-1 to 3-5, and the stability of allantoin was good. Furthermore, no precipitation was observed in the preparations of Examples 3-1 to 3-5.

[0066] [Formulation example] A skin external composition of the present invention was prepared based on the formulation shown in the following Table 4. The values ​​in the table indicate mass %.

[0067] [Table 4]

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 1,3-butylene glycol, dipropylene glycol, 1,3-propanediol, 1,2-pentanediol, and 1,2-hexanediol; and (D) at least one selected from the group consisting of organic acids (excluding tranexamic acid) and salts thereof The composition for external use on the skin contains (A) tranexamic acid or a salt thereof in an amount of 0.9 to 2.5% by mass based on the total amount of the composition for external use on the skin, and (B) allantoin or a salt thereof in an amount of 0.08 to 0.2% by mass based on the total amount of the composition for external use on the skin, and has a pH of 5.4 or less.

2. The topical skin composition according to claim 1, further comprising (E) at least one member selected from the group consisting of alkyl-modified carboxyvinyl polymers and water-soluble polysaccharides.

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

4. 3. The composition for external use on skin according to claim 1 or 2, having a viscosity at 20° C. of 1 to 50,000 mPa·s.

5. 3. The composition for external use on skin according to claim 1 or 2, having a viscosity at 20° C. of 1 to 1000 mPa·s.

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