Topical skin components

Abstract

This invention provides a technology to suppress the decrease in steroid content when steroids and panthenol are present together. [Solution] A topical skin composition containing component (A): steroid, component (B): panthenol, and component (C): polyhydric alcohol.

Description

Technical Field

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

Background Art

[0002] As technologies for blending desired components in a composition, there are those described in Patent Documents 1 to 5. Patent Document 1 (Japanese Unexamined Patent Application Publication No. 2021-11469) describes an ointment containing a water-soluble active ingredient, glycerin, and an oily base (Claim 1). By dissolving a water-soluble active ingredient such as a heparin-like substance in glycerin, the water-soluble active ingredient can be mixed in a state of being dissolved in an ointment base containing a fat-soluble base such as petrolatum, and a uniform and stable ointment containing the water-soluble active ingredient dissolved therein can be formed (Paragraph 0010).

[0003] Patent Document 2 (Japanese Unexamined Patent Application Publication No. 2023-120099) describes an ointment containing panthenol, a water-soluble solvent, an oily base, and a solid base at normal temperature (Claim 1). Thereby, an ointment in which panthenol is uniformly dispersed in the oily base can be provided, and such an ointment is said to have excellent storage stability (Paragraph 0018).

[0004] Patent Document 3 (Japanese Unexamined Patent Application Publication No. 2023-145400) describes a liquid or semi-solid composition containing betamethasone ester; a lower alcohol; one or more selected from the group consisting of a local anesthetic component, an antihistamine component, terpenes, crothamiton and its salts, and their solvates; and one or more selected from the group consisting of panthenols and salicylic acids (Claim 1). Thereby, it is said that a liquid or semi-solid composition in which crystal precipitation is suppressed can be provided while containing a lower alcohol together with betamethasone ester (Paragraph 0012).

[0005] Patent Document 4 (Japanese Patent Publication No. 2023-120462) aims to provide a pharmaceutical composition containing betamethasone ester that suppresses discoloration during high-temperature storage (paragraph 0007), and the same document describes a pharmaceutical composition containing betamethasone ester and saturated terpenes (claim 1).

[0006] Furthermore, Patent Document 5 (Japanese Unexamined Patent Publication No. 2023-44681) describes an ointment containing betamethasone valerate and an ointment base, and containing at least one selected from the group consisting of crotamiton, menthol, camphor, glycyrrhetinic acid, allantoin, diphenhydramine and its salts, and tocopherol acetate (Claim 1), and it is stated that this makes it possible to provide a betamethasone valerate-containing ointment with good formulation stability (Paragraph 0014). [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Japanese Patent Publication No. 2021-11469 [Patent Document 2] Japanese Patent Publication No. 2023-120099 [Patent Document 3] Japanese Patent Publication No. 2023-145400 [Patent Document 4] Japanese Patent Publication No. 2023-120462 [Patent Document 5] Japanese Patent Publication No. 2023-44681 [Overview of the project] [Problems that the invention aims to solve]

[0008] The inventors have newly discovered that when a steroid and panthenol are combined in a composition, the stability of the steroid in the composition may vary depending on the overall composition, and the steroid content in the composition may decrease.

[0009] Therefore, the present invention provides a technique for suppressing the decrease in steroid content when steroids and panthenol are present together. [Means for solving the problem]

[0010] The present invention provides the following compositions and methods. [1] A topical skin composition containing the following ingredients (A) to (C). (A) Steroids (B) Panthenol (C) Polyhydric alcohol [2] The topical skin composition according to [1], wherein the dosage form is an ointment. [3] The topical skin composition according to [1] or [2], wherein component (A) is one or more components selected from the group consisting of betamethasone valerate, betamethasone butyrate propionate, prednisolone valerate acetate, and fluocinolone acetonide. [4] The topical skin composition according to [1] or [2], wherein component (A) is a betamethasone ester. [5] The topical skin composition according to any one of [1] to [4], wherein component (C) is glycerin. [6] A topical skin composition according to any one of [1] to [5], further comprising the following component (D). (D) One or more selected from the group consisting of benzethonium, its salts and their hydrates. [7] A topical skin composition according to any one of [1] to [6], which is an antipruritic and anti-inflammatory agent. [8] A method for suppressing the decrease in the content of component (A), comprising incorporating component (C) below into a composition containing the following components (A) and (B). (A) Steroids (B) Panthenol (C) Polyhydric alcohol [Effects of the Invention]

[0011] According to the present invention, it is possible to suppress a decrease in the content of a steroid when the steroid and panthenol coexist.

Embodiments for Carrying out the Invention

[0012] Hereinafter, embodiments of the present invention will be described. In the present embodiment, the composition can contain each component alone or in combination of two or more. In this specification, "~" indicating a numerical range represents "above" and "below", and includes both end values.

[0013] (Topical composition for skin) In the present embodiment, the topical composition for skin contains the following components (A) to (C). (A) Steroid (B) Panthenol (C) Polyhydric alcohol

[0014] In the present embodiment, since the topical composition for skin contains the components (A) to (C) in combination, compared with a composition containing the components (A) and (B) and not containing the component (C), it is possible to effectively suppress the variation in the content stability of the component (A) in the composition depending on the formulation composition of the whole composition. Therefore, for example, it is also possible to preferably suppress a decrease in the content of the component (A) of the composition. Also, for example, the degree of freedom in formulating the whole composition can be increased.

[0015] Here, in the aforementioned Patent Document 1, it is described that by dissolving a water-soluble active ingredient in glycerin, the water-soluble active ingredient can be mixed in a state of being dissolved in an ointment base containing a fat-soluble base such as petrolatum, and a uniform and stable ointment containing the water-soluble active ingredient dissolved therein can be formed (paragraph 0010), and a number of components containing panthenol as the water-soluble active ingredient are listed (paragraph 0022). In contrast, the present inventor newly found that when panthenol is combined and formulated with a steroid in the composition, the stability of the steroid varies depending on the formulation composition of the whole composition such as fluctuations in optional components. And according to the present embodiment, by combining and formulating component (C) together with components (A) and (B), it is possible to effectively suppress a decrease in the content of component (A) in the topical composition for skin containing components (A) and (B) combined. Also, it is possible to suppress fluctuations in the stability of component (A).

[0016] Here, the decrease in the content of component (A) is specifically at least one of the decrease in content during the production process of the topical composition for skin and the decrease in content during storage after the production of the topical composition for skin. For example, according to the present embodiment, it is also possible to suppress a decrease in the amount of component (A) contained in the topical composition for skin immediately after production with respect to the amount of component (A) formulated at the time of production of the topical composition for skin. Also, according to the present embodiment, for example, it is also possible to suppress a decrease in the content of component (A) over time in the topical composition for skin. More specifically, according to the present embodiment, it is also possible to effectively suppress a decrease in the content of component (A) when storing the topical composition for skin at a temperature exceeding room temperature (for example, 40°C or higher). Also, it is possible to effectively suppress a decrease in the content of component (A) when storing the topical composition for skin under more severe temperature conditions, for example, at a temperature of 60°C or higher. Hereinafter, each component will be described.

[0017] (Component (A)) Component (A) is a steroid. A steroid is a steroid hormone having a steroid nucleus or a component having a structure derived therefrom. Steroids are classified into glucocorticoids, mineralocorticoids, sex hormones, etc., but glucocorticoids are mainly used in topical skin compositions. Specific examples of glucocorticoids include cortisones such as cortisone, hydrocortisone, and fludrocortisone acetate; prednisolones such as prednisolone and methylprednisolone; dexamethasone; betamethasone; clobetasol; triamcinolone; and one or more selected derivatives and salts thereof, as well as their hydrates. Component (A) may also be a glucocorticoid other than those listed above, such as fluocinolone. Specific examples of the above derivatives include phosphate esters, carboxylic acid esters (e.g., valerate esters, butyrate esters, propionic acid esters, acetate esters), and esters of two or more of these mixed acids; and acetonides. Specific examples of the salts mentioned above include alkali metal salts such as sodium and allium. Specific examples of component (A) include cortisone, dexamethasone acetate, dexamethasone, hydrocortisone acetate, hydrocortisone, prednisolone acetate, prednisolone, hydrocortisone butyrate, prednisolone valerate acetate, triamcinolone acetonide, betamethasone valerate, betamethasone dipropionate, betamethasone butyrate propionate (betamethasone butyrate propionate), and betamethasone sodium phosphate. Another specific example of component (A) is fluocinolone acetonide.

[0018] Component (A) is preferably one or more selected from betamethasone carboxylic acid esters (e.g., betamethasone valerate, betamethasone dipropionate, betamethasone butyrate propionate), betamethasone sodium phosphate, or a salt thereof; and prednisolone esters or salts thereof (e.g., prednisolone acetate, prednisolone valerate acetate, etc.), and more preferably one or more selected from betamethasone valerate, betamethasone butyrate propionate, and prednisolone valerate acetate. This more reliably suppresses the decrease in the content of component (A) in the topical skin composition. Similarly, it is also preferable that component (A) is one or more selected from the group consisting of betamethasone valerate, betamethasone butyrate propionate, prednisolone valerate acetate, and fluocinolone acetonide. Similarly, component (A) is preferably one or more selected from betamethasone esters or prednisolone esters, more preferably betamethasone esters, and even more preferably betamethasone carboxylic acid esters. Betamethasone valerate, one of the betamethasone carboxylic acid esters, is specifically a halogenated corticosteroid with a valerate ester at the 17th hydroxyl group. Betamethasone valerate is listed in the 18th edition of the Japanese Pharmacopoeia. Betamethasone valerate is a topical corticosteroid with anti-inflammatory properties, showing excellent efficacy against many skin diseases such as eczema, dermatitis, heat rash, contact dermatitis, itching, chilblains, insect bites, and hives, and is widely used as a topical agent.

[0019] The content of component (A) in the topical skin composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 0.12% by mass or more, relative to the total amount of the topical skin composition. This makes it possible to more reliably impart the desired pharmacological effects to the topical skin composition. Furthermore, the content of component (A) in the topical skin composition is preferably 1.0% by mass or less, more preferably 0.5% by mass or less, even more preferably 0.3% by mass or less, and even more preferably 0.25% by mass or less, relative to the entire topical skin composition. This makes it possible to impart the desired pharmacological effects to the topical skin preparation while suppressing the amount of component (A) used. Alternatively, the content of component (A) in the topical skin composition may be, for example, 0.1% by mass or less or 0.05% by mass or less, relative to the entire topical skin composition.

[0020] (Component (B)) Component (B) is panthenol, which is listed in the Japanese Pharmacopoeia Non-Official Drug Standards (2002). Panthenol, also known as pantothenyl alcohol or D-pantothenyl alcohol, is a water-soluble provitamin, also called provitamin B5, which is converted to vitamin B5 (pantothenic acid) in the body. It is known to exhibit moisturizing, tissue repair promoting, and anti-inflammatory effects. For component (B), commercially available products may be used, for example, or it may be manufactured and used by known methods.

[0021] The content of component (B) in the topical skin composition is, for example, 0.1% by mass or more, preferably 0.5% by mass or more, more preferably 0.8% by mass or more, even more preferably 1% by mass or more, and may also be, for example, 3% by mass or more, relative to the total amount of the topical skin composition. This is expected to promote skin metabolism and further repair the skin. Furthermore, the content of component (B) in the topical skin composition is preferably 10% by mass or less, more preferably 8% by mass or less, even more preferably 5% by mass or less, and may also be, for example, 2% by mass or less, relative to the total content of the topical skin composition. This makes it possible to more reliably suppress the decrease in the content of component (A) in the topical skin composition.

[0022] (Component (C)) Component (C) is a polyhydric alcohol. Component (C) can be, for example, an alcohol having two or more hydroxyl groups in its molecular structure that is listed in the 2021 Dictionary of Pharmaceutical Additives.

[0023] Component (C) is more specifically one or more components selected from the group consisting of glycerin, diglycerin, polyglycerin, propylene glycol, dipropylene glycol, polypropylene glycol, 1,3-butylene glycol, macrogol (also called polyethylene glycol), D-sorbitol, 1,2-pentanediol, and 1,2-hexanediol, and is preferably glycerin. This allows for more stable suppression of the decrease in the content of component (A) in the topical skin composition. Similarly, it is also preferable that component (C) is one or more components selected from the group consisting of glycerin, propylene glycol, 1,3-butylene glycol, and polyethylene glycol.

[0024] For example, Japanese Pharmacopoeia glycerin can be used as the glycerin. Japanese Pharmacopoeia glycerin is a liquid containing 84.0-87.0% glycerin (C3H8O3), with the remainder being water.

[0025] The molecular weight of component (C) is preferably 500 or less, more preferably 300 or less, and even more preferably 200 or less, and may also be, for example, 50 or more. This makes it possible to more stably suppress the decrease in the content of component (A) in the topical skin composition.

[0026] The content of component (C) in the topical skin composition is, for example, 3% by mass or more, preferably more than 5% by mass, more preferably 10% by mass or more, more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 25% by mass or more, and even more preferably 30% by mass or more, relative to the total amount of the topical skin composition. This makes it possible to more reliably suppress the decrease in the content of component (A) in the topical skin composition. Furthermore, the content of component (C) in the topical skin composition is preferably less than 50% by mass of the entire topical skin composition, more preferably 45% by mass or less, and even more preferably 40% by mass or less. This allows for a formulation that maintains a more suitable viscosity and is easy to apply. In addition, to further increase the flexibility of the overall formulation of the topical skin composition, the content of component (C) in the topical skin composition may be 35% by mass or less or 30% by mass or less.

[0027] Furthermore, it is preferable to have a glycerin content in the topical skin composition exceed 5% by mass relative to the entire topical skin composition, and a total content of component (C) of 20% by mass or more. This makes it possible to more reliably suppress the decrease in the content of component (A) in the topical skin composition.

[0028] The mass ratio ((C) / (B)) of the content of component (C) to the content of component (B) in the topical skin composition is, for example, 1 or more, preferably greater than 1, more preferably 3 or more, and may also be, for example, 5 or more, 10 or more, 20 or more, or 30 or more. This makes it possible to more reliably suppress the decrease in the content of component (A) in the topical skin composition. Similarly, the above mass ratio ((C) / (B)) may be, for example, 100 or less, more preferably 80 or less, even more preferably 60 or less, even more preferably 35 or less, and may also be 10 or less.

[0029] In this embodiment, the topical skin composition may contain components other than those described above. Other components can be selected, for example, depending on the dosage form of the topical skin composition and the efficacy to be imparted to the topical skin composition.

[0030] (Component (D)) The topical skin composition may further contain one or more substances selected from the group consisting of component (D): benzethonium, its salts, and their hydrates. This may impart further efficacy. Component (D) is preferably a benzethonium salt, and more preferably benzethonium chloride. Benzethonium chloride is listed in the 18th edition of the Japanese Pharmacopoeia. Benzethonium chloride is a quaternary ammonium salt classified as a reverse soap, and has broad antibacterial activity against non-spore-forming bacteria and fungi, showing efficacy against Gram-positive bacteria at lower concentrations than against Gram-negative bacteria.

[0031] The content of component (D) in the topical skin composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and even more preferably 0.01% by mass or more, relative to the total amount of the topical skin composition. This allows for a more reliable expectation that the medicinal effects of component (D) will be added to the medicinal effects of component (A), thereby soothing skin inflammation and preventing the worsening of symptoms caused by infection through its bactericidal effect on the skin. Furthermore, the content of component (D) in the topical skin composition is preferably 0.5% by mass or less, more preferably 0.3% by mass or less, even more preferably 0.2% by mass or less, and even more preferably 0.1% by mass or less, relative to the total content of the topical skin composition. This makes it possible to more stably suppress the decrease in the content of component (A) in the topical skin composition.

[0032] Furthermore, the topical skin composition may also contain other drugs or pharmaceutical additives, such as those commonly used in topical skin preparations for antipruritic and anti-inflammatory purposes.

[0033] The above drugs include, for example, antihistamine components such as isotipendyl hydrochloride, chlorpheniramine, chlorpheniramine maleate, diphenhydramine, and diphenhydramine hydrochloride; crotamiton; glycyrrhizic acid and its salts, and glycyrrhetinic acid derivatives such as glycyrrhetinic acid; salicylic acid derivatives such as glycol salicylate and methyl salicylate; allantoin; antibacterial components other than component (D), such as isopropylmethylphenol and benzalkonium chloride; astringent components such as calamine and zinc oxide; and amine. Local anesthetic components such as ethyl nobenzoate, oxypolyethoxide decane, dibucaine, dibucaine hydrochloride, lidocaine, and lidocaine hydrochloride; cooling components such as d-camphor, dl-camphor, peppermint oil, dl-menthol, l-menthol, and d-borneol; ammonia water; tannic acid; gamma-oryzanol; and one or more selected from the group consisting of vitamins other than component (B), such as tocopherol, tocopherol acetate, vitamin A oil, and retinol palmitate. Examples of glycyrrhizic acid and its salts, as well as glycyrrhetinic acid derivatives such as glycyrrhetinic acid, include glycyrrhetinic acid, glycyrrhizic acid, and dipotassium glycyrrhizinate.

[0034] Furthermore, pharmaceutical additives may be added as needed to further improve, for example, the stability of content or appearance over time, or the feel of use. Specific examples of pharmaceutical additives include one or more selected from the group consisting of bases, humectants, adhesives, pH adjusters, antioxidants, cooling agents, surfactants, stabilizers, preservatives, viscosities, or thickening agents.

[0035] Examples of base materials include oily base materials and aqueous base materials other than component (D), such as water.

[0036] As an oily base, one or more selected from the group consisting of styrene-isoprene-styrene copolymer; hydrocarbons such as petrolatum, paraffin, liquid paraffin, light isoparaffin, liquid isoparaffin, ozokerite, ceresin, hard fat, microcrystalline wax, squalane, α-olefin oligomer, polyethylene powder, and polyisobutylene; higher alcohols such as stearyl alcohol, cetanol, behenyl alcohol, cetostearyl alcohol, hexyldecanol, isostearyl alcohol, octyldodecanol, oleyl alcohol, decyltetradecanol, and myristyl alcohol; ester oils such as isopropyl palmitate, isopropyl myristate, octyldodecyl myristate, cetyl palmitate, glyceryl tri-2-ethylhexylate, and medium-chain triglyceride; polymerized silicones such as dimethylpolysiloxane and dimethylsiloxane; and vegetable oils such as olive oil. To more reliably suppress the decrease in the content of component (A) in the topical skin composition, the oily base preferably comprises hydrocarbons, more preferably one or more selected from the group consisting of liquid paraffin, paraffin, white petrolatum, microcrystalline wax, squalane, and α-olefin oligomers, and even more preferably one or more selected from the group consisting of liquid paraffin, paraffin, and white petrolatum.

[0037] When a topical skin composition contains an oily base, the amount of the oily base can be, for example, the remainder after removing components other than the oily base in the topical skin composition. Furthermore, the content of the oily base in the topical skin composition is, for example, 20% by mass or more, preferably 40% by mass or more, more preferably more than 50% by mass, even more preferably 60% by mass or more, and even more preferably 70% by mass or more, and may be, for example, 80% by mass or more, based on the total amount of the topical skin composition. This makes it possible to more reliably suppress the decrease in the content of component (A) in the topical skin composition. Furthermore, the content of the oily base in the topical skin composition is specifically less than 100% by mass of the entire topical skin composition, and may be, for example, 99% by mass or less, 95% by mass or less, 90% by mass or less, 80% by mass or less, or 70% by mass or less.

[0038] Examples of wetting agents include at least one selected from the group consisting of dl-pyrrolidone carboxylate sodium and polysorbate 40 solution.

[0039] Examples of adhesives include at least one selected from the group consisting of dibutylhydroxytoluene and hydrogen rosin glycerol esters.

[0040] Specific examples of pH adjusters include one or more selected from the group consisting of inorganic acids and their salts, such as hydrochloric acid and phosphoric acid; organic acids and their salts, such as citric acid, malic acid, tartaric acid, gluconic acid, and lactic acid; bases, such as sodium hydroxide and potassium hydroxide; and organic amines, such as triethanolamine and diisopropanolamine. Specific examples of the salts include alkali metal salts such as sodium and potassium, and alkaline earth metal salts such as calcium and magnesium. Furthermore, pH adjusters may be in hydrate form.

[0041] Examples of antioxidants include one or more selected from the group consisting of ascorbic acid, ascorbic palmitate, sodium bisulfite, sodium pyrosulfite, sodium edetate, citric acid hydrate, anhydrous citric acid, dibutylhydroxytoluene, butylhydroxyanisole, benzotriazole, and propyl gallate. To obtain a more stable effect in suppressing the decrease in the content of component (A), the topical skin composition preferably contains at least one of sodium bisulfite and sodium edetate, and more preferably contains sodium edetate.

[0042] Examples of cooling agents include menthol such as l-menthol, terpenes such as camphor, the aforementioned components such as peppermint oil, and eucalyptus oil.

[0043] As the surfactant, a nonionic surfactant or an ionic surfactant may be used. Furthermore, the surfactant may also be an emulsifier. Nonionic surfactants include, for example, polyhydric alcohol fatty acid esters or polyhydric alcohol alkyl ethers such as propylene glycol monofatty acid esters, ethylene glycol monofatty acid esters, glycerin monofatty acid esters (e.g., glyceryl monostearate), glycerin polyfatty acid esters (e.g., glyceryl triisooctanoate), polyglycerin fatty acid esters (e.g., diglyceryl monooleate), sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, alkyl polyglucosides, polyethylene glycol fatty acid esters; and polyoxyethylene alkyl ethers such as polyoxyethylene alkyl ethers (e.g., polyoxyethylene behenyl ether), polyoxyethylene alkylphenyl ether, polyoxyethylene phytosterol, polyoxyethylene phytostanol, polyoxyethylene polyoxypropylene alkyl ether. One or more ether esters selected from the group consisting of polyoxyethylene ethers, polyoxyethylene mono fatty acid esters, polyethylene glycol di fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80, polyoxyethylene sorbitol fatty acid esters, polyoxyethylene methyl glucoside fatty acid esters, polyoxyethylene hydrogenated castor oil such as polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, and polyoxyethylene hydrogenated castor oil 60, polyoxyethylene castor oil, polyoxyethylene vegetable oil, polyoxyethylene alkyl ether fatty acid esters, and polyoxyethylene polyoxypropylene glycol are included.

[0044] The content of nonionic surfactant in the topical skin composition is preferably 0.1% by mass or more, more preferably 0.8% by mass or more, even more preferably 1.5% by mass or more, even more preferably 2% by mass or more, and also preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, and even more preferably 2.8% by mass or less, relative to the total amount of the topical skin composition. This makes the stability of the topical skin composition more favorable.

[0045] Furthermore, specific examples of ionic surfactants include anionic surfactants such as sodium lauryl sulfate and sodium cetyl sulfate.

[0046] Examples of stabilizers include one or more selected from the group consisting of the aforementioned antioxidants and ionic surfactants.

[0047] Examples of preservatives include one or more selected from the group consisting of benzoic acid, sodium benzoate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, dehydroacetic acid, sodium dehydroacetate, sorbic acid, and phenoxyethanol.

[0048] Examples of thickening agents include one or more selected from the group consisting of cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and hydroxyethylcellulose; thickening polysaccharides such as magnesium aluminum silicate, carboxyvinyl polymer, sodium alginate, xanthan gum, carrageenan, guar gum, gelatin, dextrin, cyclodextrin, and pectin; and carboxylate sodium, polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, and light anhydrous silicic acid.

[0049] The topical skin composition can be manufactured, for example, by combining components (A) to (C) and other components as appropriate using known manufacturing methods. For example, the topical skin composition can also be manufactured according to the usual methods described in the 18th edition of the Japanese Pharmacopoeia, etc.

[0050] The dosage form of the topical skin composition can be selected from the group consisting of, for example, ointments, creams, topical solutions, gels, topical solids, sprays (aerosols or pump sprays), foams, and patches. The topical skin composition is preferably an ointment. This more reliably suppresses the decrease in the content of component (A) in the topical skin composition. Similarly, the topical skin composition is preferably an oily composition and preferably does not contain an aqueous phase.

[0051] When the topical skin preparation composition is an ointment, it is preferable that water is not intentionally added to the composition. On the other hand, the skin topical preparation composition may contain moisture or other substances derived from the raw materials for manufacturing the skin topical preparation, such as the moisture contained in commercially available glycerin among the raw materials of component (C).

[0052] Furthermore, since the topical skin composition contains component (A), it is suitable as a topical agent such as an antipruritic and anti-inflammatory agent. The topical skin composition may be a pharmaceutical composition. The method of applying the topical skin composition is the same as for ordinary topical compositions; for example, an appropriate amount can be applied to the target area of ​​skin once to several times a day, according to the symptoms.

[0053] (Method for suppressing the decrease in the content of component (A)) In this embodiment, a method for suppressing the decrease in the content of component (A) includes incorporating component (C) into a composition containing components (A) and (B). As described above, in this embodiment, by incorporating component (C) into a composition containing components (A) and (B), it is possible to effectively suppress fluctuations in the stability of component (A) and a decrease in the content of component (A), which depend on the composition of the composition, in a composition containing components (A) and (B) but not component (C).

[0054] The embodiments of the present invention have been described above, but these are merely examples, and various other configurations can also be adopted.

[0055] The embodiment will be described in detail below with reference to examples, but this embodiment is not limited to these examples. In the following, betamethasone valerate will also be referred to as "BV".

[0056] (Example 1, Comparative Example 1, Reference Example 1) Each component was prepared according to the composition shown in Table 1, in accordance with the section on "Ointments" in the General Provisions of the 18th Revised Japanese Pharmacopoeia, and each example composition (ointment) was prepared. In Table 1, the amounts of each component are given as mass (g) when the total amount is 100g, and correspond to mass %.

[0057] (Stability of BV content) For each example, the BV content was determined by high-performance liquid chromatography (HPLC) measurement immediately after production and after storage of the obtained compositions.

[0058] (How to save) The compositions for each example were filled into glass bottles with lids, sealed, and stored at 40°C for one day or at 60°C for one day.

[0059] (Measurement conditions) Detector: UV absorbance spectrophotometer, Wavelength: 240 nm Column: A stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm, packed with core-shell type silica gel for liquid chromatography with a particle size of 2.7 μm. Column temperature: Constant temperature around 40°C Mobile phase: A mixture of acetonitrile, purified water, and phosphoric acid. Sample injection volume: 10 μL

[0060] (Remaining BV content) Based on the measurement results of the BV content of the compositions immediately after manufacturing and after storage at various temperatures, the mass ratio of the BV content after storage to the BV content immediately after manufacturing was calculated for each example and defined as the residual rate. The results are shown in Table 1.

[0061] [Table 1]

[0062] Details of the ingredients listed in Table 1 are shown below. Glycerin: Manufactured by Kosakai Pharmaceutical Co., Ltd. Liquid paraffin: Manufactured by Kaneda Co., Ltd. Paraffin: Manufactured by Nippon Seiro Co., Ltd. Glycerin fatty acid ester: Manufactured by Nikko Chemicals Co., Ltd. White petrolatum: Manufactured by Kosakai Pharmaceutical Co., Ltd. Furthermore, in Table 1 and Table 2 described below, if the measured value of the survival rate exceeds 100%, the survival rate can be set to 100%.

[0063] Table 1 shows that in Comparative Example 1, which contains components (A) and (B) but does not contain component (C), the content of component (A) decreased immediately after manufacturing compared to Reference Example 1, which contains component (A) but does not contain components (B) and (C), and the content decreased further during storage. On the other hand, in Example 1, which contained components (A) to (C), the overall decrease in content from the manufacturing process to storage was suppressed compared to Comparative Example 1. In other words, in Example 1, the decrease in the content of component (A) immediately after manufacturing was suppressed, and the decrease in the content of component (A) that occurred during storage was also suppressed.

[0064] (Examples 2-13) According to the compositions shown in Table 2, each example composition (ointment) was prepared in accordance with Example 1. For each example, the amount of steroids in the composition obtained was determined by HPLC measurement immediately after preparation and after storage at 60°C for 1 day. The HPLC measurement was performed in the same manner as in Example 1, except that the sample injection volume for fluocinolone acetonide was 20 μL. The results are shown in Table 2.

[0065] [Table 2]

[0066] As shown in Table 2, in each example, the decrease in the content of component (A) immediately after manufacturing was suppressed compared to Comparative Example 1, and the decrease in the content of component (A) caused by high-temperature storage at 60°C was also suppressed.

[0067] (Formulation Examples 1-12) The compositions shown in Table 3 can be prepared by compounding each component in accordance with the section on "Ointments" in the General Provisions of the 18th Revised Japanese Pharmacopoeia, and each example (Formulation Examples 10 and 11 are for reference only) can be prepared. The ointment compositions may also be stored in containers (for example, bottle-type containers, tube-type containers, jar-type containers, etc.).

[0068] [Table 3]

[0069] This application claims priority based on Japanese Patent Application No. 2024-229028, filed on 25 December 2024, and incorporates all of its disclosures herein.

Claims

1. A topical skin composition containing the following ingredients (A) to (C). (A) Steroids (B) Panthenol (C) Polyhydric alcohols

2. The topical skin composition according to claim 1, wherein the dosage form is an ointment.

3. The topical skin composition according to claim 1 or 2, wherein component (A) is one or more components selected from the group consisting of betamethasone valerate, betamethasone butyrate propionate, prednisolone valerate acetate, and fluocinolone acetonide.

4. The topical skin composition according to claim 1 or 2, wherein component (A) is a betamethasone ester.

5. The topical skin composition according to claim 1 or 2, wherein the component (C) is glycerin.

6. The topical skin composition according to claim 1 or 2, further comprising the following component (D). (D) One or more selected from the group consisting of benzethonium, its salts and their hydrates.

7. A topical skin composition according to claim 1 or 2, which is an antipruritic and anti-inflammatory agent.

8. A method for suppressing the decrease in the content of component (A), comprising incorporating component (C) below into a composition containing the following components (A) and (B). (A) Steroids (B) Panthenol (C) Polyhydric alcohols

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