Topical skin composition

Abstract

Provided is a technique for suppressing a decrease in the content of a steroid in the coexistence of a steroid and panthenol. A composition for external use on the skin, which contains a component (A), i.e., a steroid, a component (B), i.e., panthenol, and a component (C), i.e., a polyhydric alcohol.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202511965732.9 (22) Application Date 2025.12.24 (30) Priority Data 2024-229028 2024.12.25 JP (71) Applicant Daiichi Sankyo Health Business Co., Ltd. Address Japan (72) Inventors Hidehiko Arizumi, Yukiko Namekawa, Masataka Taniguchi, Maiko Otsubo (74) Patent Agency Beijing J&J Intellectual Property Agency Co., Ltd. 11227 Patent Attorney Li Shuhui (51) Int.Cl. A61K 31 / 573 (2006.01) A61K 31 / 58 (2006.01) A61K 9 / 06 (2006.01) A61K 47 / 18 (2017.01) A61K 47 / 10 (2017.01) A61P 17 / 00 (2006.01) A61P 29 / 00 (2006.01) A61P 17 / 04 (2006.01) (54) Invention Title: Topical Skin Composition (57) Abstract: This invention provides a technique for inhibiting the decrease in steroid content when steroids and panthenol coexist. A topical skin composition comprising component (A) a steroid, component (B) panthenol, and component (C) a polyol. Claims 1 page Description 12 pages CN 122272598 A 2026.06.26 CN 1 22 27 25 98 A 1. A topical skin composition comprising the following components (A) to (C): (A) steroid, (B) panthenol, (C) polyol. 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 betamethasone valerate, betamethasone butyrate propionate, prednisolone acetate valerate, and fluocinolone acetonide. 4. The topical skin composition according to claim 1 or 2, wherein component (A) is betamethasone ester. 5. The topical skin composition according to any one of claims 1 to 4, wherein component (C) is glycerin. 6. The topical skin composition according to any one of claims 1 to 5, further comprising component (D), wherein (D) is one or more components selected from benzyloxyethamine, its salts, and their hydrates. 7. The topical skin composition according to any one of claims 1 to 6, which is an anti-inflammatory and antipruritic agent. 8. A method for inhibiting the reduction of the content of said component (A), comprising the steps of: combining the following component (C) in a composition containing the following components (A) and (B): (A) steroid, (B) panthenol, and (C) polyol.Claims 1 / 1 Page 2 CN 122272598 A Skin Topical Composition Technical Field

[0001] The present invention relates to a skin topical composition. Background Art

[0002] As a technique for incorporating desired ingredients into a composition, there are techniques described in Patent Documents 1 to 5.

[0003] Patent Document 1 (Japanese Patent Application Publication No. 2021-11469) describes an ointment containing a water-soluble active ingredient, glycerin, and an oily base (claim 1), indicating that by dissolving a water-soluble active ingredient such as a heparin analog in glycerin, it is possible to mix the ointment in a state where the water-soluble active ingredient is dissolved in an ointment base containing an oily base such as petrolatum, thereby forming a uniform and stable ointment in which the water-soluble active ingredient is contained in the ointment in a dissolved state (paragraph 0010).

[0004] Patent Document 2 (Japanese Patent Application Publication No. 2023-120099) discloses an ointment containing panthenol, a water-soluble solvent, an oily base agent, and a base agent that is solid at room temperature (claim 1), and points out that it can provide an ointment in which panthenol is uniformly dispersed in an oily base agent, and the ointment has excellent storage stability (paragraph 0018).

[0005] Patent Document 3 (Japanese Patent Application Publication No. 2023-145400) discloses a liquid or semi-solid composition containing betamethasone ester; a lower alcohol; one or more selected from local anesthetic ingredients, antihistamine ingredients, terpenes, clomiphene and its salts and their solvates, and one or more selected from panthenol and salicylic acid (claim 1), and points out that it can provide a liquid or semi-solid composition in which crystal precipitation can be suppressed even when containing a lower alcohol agent together with betamethasone ester (paragraph 0012).

[0006] Patent Document 4 (Japanese Patent Application Publication No. 2023-120462) addresses the issue of providing a pharmaceutical composition containing betamethasone ester that inhibits discoloration during high-temperature storage (paragraph 0007). This document describes a pharmaceutical composition containing betamethasone ester and a saturated terpene (claim 1).

[0007] Furthermore, Patent Document 5 (Japanese Patent Application Publication No. 2023-44681) describes an ointment containing betamethasone valerate and an ointment base, and containing at least one of clomiphene, menthol, camphor, glycyrrhetinic acid, urea, diphenhydramine and its salts, and tocopheryl acetate (claim 1), and indicates that this provides an ointment containing betamethasone valerate with good formulation stability (paragraph 0014).

[0008] Prior Art Documents

[0009] Patent Documents

[0010] Patent Document 1: Japanese Patent Application Publication No. 2021-11469

[0011] Patent Document 2: Japanese Patent Application Publication No. 2023-120099

[0012] Patent Document 3: Japanese Patent Application Publication No. 2023-145400

[0013] Patent Document 4: Japanese Patent Application Publication No. 2023-120462

[0014] Patent Document 5: Japanese Patent Application Publication No. 2023-44681 Summary of the Invention

[0015] The inventors have recently discovered that when steroids and panthenol are combined in a composition, the stability of the steroids in the composition varies depending on the overall composition, resulting in a decrease in the content of steroids in the composition. (Specification 1 / 12 pages 3 CN 122272598 A)

[0016] Therefore, the present invention provides a technique for inhibiting the decrease in steroid content when steroids and panthenol coexist.

[0017] According to the present invention, the following compositions and methods can be provided.

[0018] [1] A topical skin composition comprising the following components (A) to (C):

[0019] (A) steroid,

[0020] (B) panthenol,

[0021] (C) polyol.

[0022] [2] The topical skin composition according to [1], wherein the dosage form is an ointment.

[0023] [3] The topical skin composition according to [1] or [2], wherein the above component (A) is one or more components selected from betamethasone valerate, betamethasone butyrate propionate, prednisolone acetate valerate, and fluocinolone acetonide.

[0024] [4] The skin composition according to [1] or [2], wherein the above-mentioned component (A) is betamethasone ester.

[0025] [5] The skin composition according to any one of [1] to [4], wherein the above-mentioned component (C) is glycerin.

[0026] [6] The skin composition according to any one of [1] to [5], further comprising the following component (D),

[0027] (D) is selected from one or more of benzyloxyethamine ( ), its salts and their hydrates.

[0028] [7] The skin composition according to any one of [1] to [6] is an anti-inflammatory and antipruritic agent.

[0029] [8] A method for suppressing the decrease in the content of the above-mentioned component (A) includes the following steps: combining the following component (C) with a composition containing the following components (A) and (B),

[0030] (A) steroid,

[0031] (B) panthenol,

[0032] (C) polyol.

[0033] According to the present invention, it is possible to suppress the decrease in the content of steroid when steroid and panthenol coexist. Detailed Embodiments

[0034] Hereinafter, embodiments of the present invention will be described.In this embodiment, the composition may contain two or more of each component individually or in combination.

[0035] In this specification, the "~" indicating a numerical range means above and below a certain value, including both ends of the value.

[0036] (Topical Skin Composition)

[0037] In this embodiment, the topical skin composition contains the following components (A) to (C):

[0038] (A) Steroid,

[0039] (B) Panthenol,

[0040] (C) Polyol.

[0041] In this embodiment, since the topical skin composition contains components (A) to (C), compared with a composition containing components (A) and (B) but not component (C), it is possible to effectively suppress the variation of the content stability of component (A) in the composition according to the overall composition. Therefore, for example, it is also possible to appropriately suppress the decrease in the content of component (A) in the composition. In addition, for example, it is possible to increase the degree of freedom in the overall composition.

[0042] Here, Patent Document 1 described above states that by dissolving the water-soluble active ingredient in glycerin, mixing can be performed in a state where the water-soluble active ingredient is 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 in a dissolved state can be formed (paragraph 0010). Many components containing panthenol as a water-soluble active ingredient are listed (paragraph 0022). In contrast, the inventors have recently discovered that when panthenol and steroids are combined in a composition, the stability of the steroids varies depending on the overall composition of the composition, such as changes in any component. Moreover, according to this embodiment, by combining component (C) with components (A) and (B), the decrease in the content of component (A) in a topical skin composition containing components (A) and (B) can be effectively suppressed. In addition, changes in the stability of component (A) can also be suppressed.

[0043] Here, the reduction in the content of component (A) specifically refers to at least one of the reduction in content during the manufacturing process of the topical skin composition and the reduction in content during storage after the manufacture of the topical skin composition.

[0044] For example, according to this embodiment, it is also possible to suppress the reduction in the amount of component (A) contained in the freshly manufactured topical skin composition relative to the amount of component (A) incorporated during the manufacture of the topical skin composition.

[0045] Furthermore, according to this embodiment, for example, it is also possible to suppress the reduction in the content of component (A) in the topical skin composition over time. More specifically, according to this embodiment, it is also possible to effectively suppress the reduction in the content of component (A) when the topical skin composition is stored at a temperature exceeding room temperature (e.g., 40°C or higher).In addition, it can also effectively inhibit the decrease in the content of component (A) when storing the topical skin composition under more severe temperature conditions, such as at a temperature above 60°C.

[0046] Hereinafter, each component will be described.

[0047] (Component (A))

[0048] Component (A) is a steroid. A steroid is a component that has a steroid hormone or a structure derived therefrom having a steroid core. Steroids can be classified as glucocorticoids, mineralocorticoids, sex hormones, etc., but glucocorticoids are mainly used in topical skin compositions. As glucocorticoids, specifically, one or more of the following can be selected: cortisone, hydrocortisone, fludrocortisone acetate, etc.; prednisolone, methylprednisolone, etc.; dexamethasone; betamethasone; clobetasol; triamcinolone; their derivatives and their salts and their hydrates. In addition, component (A) may also be a glucocorticoid other than the above, such as fluocinolone acetonide.

[0049] Specific examples of the above-mentioned derivatives include phosphate esters, carboxylic acid esters (e.g., valerate, butyrate, propionate, acetate) and mixed esters of two or more thereof; acetone compounds.

[0050] Specific examples of the above-mentioned salts include alkali metal salts such as sodium and potassium.

[0051] Specific examples of component (A) include cortisone, dexamethasone acetate, dexamethasone, hydrocortisone acetate, hydrocortisone, prednisolone acetate, prednisolone, hydrocortisone butyrate, prednisolone acetate valerate, triamcinolone acetone compound, betamethasone valerate, betamethasone dipropionate, betamethasone butyrate propionate (betamethasone butyrate propionate), and sodium betamethasone phosphate. In addition, as a specific example of component (A), fluocinolone acetonide may also be mentioned.

[0052] Component (A) is preferably selected from one or more of betamethasone carboxylic acid esters (e.g., betamethasone valerate, betamethasone dipropionate, betamethasone butyrate propionate, betamethasone sodium phosphate, etc., or salts thereof; and prednisolone acetate, prednisolone valerate, etc., or salts thereof, more preferably selected from one or more of betamethasone valerate, betamethasone butyrate propionate, and prednisolone valerate. This allows for more reliable inhibition of the reduction in the content of component (A) in the topical skin composition. From the same viewpoint, component (A) is also preferably selected from one or more of betamethasone valerate, betamethasone butyrate propionate, prednisolone valerate, and fluocinolone acetonide.

[0053] From the same viewpoint, component (A) is preferably selected from one or more of betamethasone esters or prednisolone esters. (Instruction manual 3 / 12 pages 5 CN) 122272598 A or more, more preferably betamethasone ester, and even more preferably betamethasone carboxylate ester.

[0054] Betamethasone valerate, one of the betamethasone carboxylic acid esters, is specifically a halogenated adrenocortical hormone in which the 17-hydroxyl group is converted to valerate. Betamethasone valerate is listed in the 18th revised edition of the Japanese Pharmacopoeia. Betamethasone valerate is a type of topical adrenocortical hormone with anti-inflammatory effects, showing excellent efficacy against various skin diseases such as eczema, dermatitis, prickly heat, contact dermatitis, pruritus, chilblains, insect bites, and urticaria, and is widely used as a topical medication.

[0055] 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, further preferably 0.1% by mass or more, and even more preferably 0.12% by mass or more, relative to the total topical skin composition. This allows for more reliable application of the desired pharmacological effects to the topical skin composition.

[0056] 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, further preferably 0.3% by mass or less, and even more preferably 0.25% by mass or less, relative to the total amount of the topical skin composition. This allows the desired pharmacological effects to be imparted to the topical skin medication while suppressing the amount of component (A) in the composition. Additionally, the content of component (A) in the topical skin composition may, for example, be 0.1% by mass or less or 0.05% by mass or less, relative to the total amount of the topical skin composition.

[0057] (Component (B))

[0058] Component (B) is panthenol, which is listed in the Japanese Pharmacopoeia Standard for Non-Pharmaceutical Products (2002). Panthenol, also known as panthenol or D-panthenol, is a water-soluble provitamin B5, which can be converted into vitamin B5 (pantothenic acid) in the body and is known to exhibit moisturizing, tissue repair promoting, and anti-inflammatory effects. As component (B), commercially available products may be used, or it may be manufactured and used using known methods.

[0059] 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, and even more preferably 1% by mass or more. It may also be, for example, 3% by mass or more. Therefore, it is expected to promote skin metabolism and thus repair the skin.

[0060] 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, and even more preferably 5% by mass or less. It may also be, for example, 2% by mass or less. Therefore, it is possible to more reliably suppress the decrease in the content of component (A) in the topical skin composition.

[0061] (Component (C))

[0062] Component (C) is a polyol. Component (C) may, for example, be a substance listed in the Dictionary of Pharmaceutical Additives 2021 that has two or more hydroxyl groups in its molecular structure.

[0063] More specifically, component (C) is one or more components selected from glycerin, diglycerin, polyglycerol, propylene glycol, dipropylene glycol, polypropylene glycol, 1,3-butanediol, macrogol (also known as polyethylene glycol), D-sorbitol, 1,2-pentanediol, and 1,2-hexanediol, preferably glycerin. This allows for more stable suppression of the decrease in the content of component (A) in the topical skin composition. From the same viewpoint, component (C) is also preferably selected from one or more components selected from glycerin, propylene glycol, 1,3-butanediol, and polyethylene glycol.

[0064] As glycerin, for example, Japanese Pharmacopoeia glycerin can be used. Japanese Pharmacopoeia glycerin is a liquid containing 84.0% to 87.0% glycerin (C3H8O3), with the balance being water.

[0065] The molecular weight of component (C) is preferably 500 or less, more preferably 300 or less, further preferably 200 or less, and may also be 50 or more, for example. Therefore, the decrease in the content of component (A) in the topical skin composition can be suppressed more stably.

[0066] 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, further preferably 20% by mass or more, even more preferably 25% by mass or more, and even more preferably 30% by mass or more. Therefore, the decrease in the content of component (A) in the topical skin composition can be suppressed more reliably.

[0067] In addition, the content of component (C) in the topical skin composition is preferably less than 50% by mass, more preferably 45% by mass or less, and even more preferably 40% by mass or less, relative to the overall topical skin composition. Therefore, a formulation that maintains a more appropriate viscosity and is easy to apply can be provided. Furthermore, from the perspective of further improving the flexibility of the overall formulation of the topical skin composition, the content of component (C) in the topical skin composition can be made to be 35% by mass or less or 30% by mass or less.

[0068] In addition, it is also preferable that the content of glycerin in the topical skin composition is greater than 5% by mass while the total content of component (C) is 20% by mass or more relative to the overall topical skin composition. As a result, the decrease in the content of component (A) in the topical skin composition can be more reliably suppressed.

[0069] 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 can be, for example, 5 or more, 10 or more, 20 or more, or 30 or more. As a result, the decrease in the content of component (A) in the topical skin composition can be more reliably suppressed.

[0070] From the same point of view, the above-mentioned mass ratio ((C) / (B)) is, for example, 100 or less, more preferably 80 or less, further preferably 60 or less, even more preferably 35 or less, and may also be 10 or less.

[0071] In this embodiment, the topical skin composition may also contain ingredients other than those described above. Other ingredients may be selected, for example, depending on the dosage form of the topical skin composition and the efficacy imparted to the topical skin composition.

[0072] (Ingredient (D))

[0073] The topical skin composition may further contain ingredient (D), which is one or more selected from benzyloxyethamine, its salts and their hydrates. Thus, efficacy can be further imparted.

[0074] Ingredient (D) is preferably a benzyloxyethamine salt, more preferably benzyl chloride. Benzyl chloride is included in the 18th revised edition of the Japanese Pharmacopoeia. Benzyl chloride is a quaternary ammonium salt classified as a positive-positive soap. It has broad-spectrum antibacterial activity against non-spore-forming bacteria and fungi, and shows effectiveness against Gram-positive bacteria at lower concentrations compared to Gram-negative bacteria.

[0075] 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 content of the topical skin composition. Therefore, by increasing the efficacy of component (D) on top of the efficacy of component (A), it is more reliable to expect relief of skin inflammation and to prevent the worsening of symptoms caused by infection through bactericidal action on the skin.

[0076] In addition, 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. Therefore, it is possible to more stably inhibit the decrease in the content of component (A) in the topical skin composition.

[0077] In addition, the topical skin composition may further contain, for example, drugs or pharmaceutical additives other than the above-mentioned ingredients that are commonly used in topical skin medicines for anti-inflammatory and antipruritic purposes.

[0078] Examples of the above-mentioned drugs include, for example, antihistamines selected from azithromycin hydrochloride, chlorpheniramine maleate, diphenhydramine, diphenhydramine hydrochloride, etc.; clomiphene; glycyrrhizic acid and its salts and glycyrrhetinic acid derivatives such as glycyrrhetinic acid; salicylic acid derivatives such as glycol salicylic acid and methyl salicylate; urea extract; bactericidal components other than component (D) such as isopropyl methylphenol and benzalkonium chloride; astringent components such as calamine and zinc oxide; local anesthetic components such as ethyl aminobenzoate, hydroxyl polyethoxylate, debucaine, debucaine hydrochloride, lidocaine, lidocaine hydrochloride, etc.; cooling components such as d-camphor, dl-camphor, peppermint oil, dl-menthol, l-menthol, d-borneol, etc.; ammonia; tannic acid; γ- - Oryzanol; and one or more of the following vitamins other than component (B): tocopherol, tocopheryl acetate, vitamin A oil, retinyl palmitate, etc. Instructions 5 / 12 pages 7 CN 122272598 A

[0079] As glycyrrhizic acid and its salts and glycyrrhetinic acid derivatives such as glycyrrhetinic acid, for example, glycyrrhetinic acid, dipotassium glycyrrhizate, etc.

[0080] In addition, as pharmaceutical additives, for example, substances added as needed to further improve the stability of content over time, appearance stability, user experience, etc. Specific examples of pharmaceutical additives include one or more selected from base agents, wetting agents, binders, pH adjusters, antioxidants, cooling agents, surfactants, stabilizers, preservatives, thickeners, or thickening agents.

[0081] As base agents, for example, oily base agents; and water-based base agents other than component (D), such as water.

[0082] As an oily base agent, examples include one or more of the following: styrene-isoprene-styrene copolymer; petrolatum, paraffin wax, liquid paraffin wax, light isoalkanes, liquid isoalkanes, ceresin wax, pure ceresin wax, stearin, microcrystalline wax, squalane, α-olefin oligomers, polyethylene powder, polyisobutylene, etc.; higher alcohols such as stearyl alcohol, cetyl alcohol, behenyl alcohol, cetearyl alcohol, hexyldecyl alcohol, isostearyl alcohol, octyldodecyl alcohol, oleyl alcohol, decyltetradecyl alcohol, myristyl alcohol, etc.; ester oils such as isopropyl palmitate, isopropyl myristate, octyldodecyl myristate, cetyl palmitate, tri-2-ethylhexanoate, medium-chain fatty acid triglycerides, etc.; polymeric organosilicones such as dimethylpolysiloxane and dimethylsiloxane; and vegetable oils such as olive oil.

[0083] From the viewpoint of being able to more reliably suppress the reduction of the content of component (A) in the topical skin composition, the oily base preferably contains hydrocarbons, more preferably contains one or more selected from liquid paraffin, paraffin, white petrolatum, microcrystalline wax, squalane and α-olefin oligomers, and even more preferably contains one or more selected from liquid paraffin, paraffin and white petrolatum.

[0084] When the topical skin composition contains an oily base, the content of the oily base may be, for example, the balance obtained by removing components other than the oily base in the topical skin composition.

[0085] Furthermore, relative to the overall topical skin composition, 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 50% by mass or more, further preferably 60% by mass or more, even more preferably 70% by mass or more, and for example, 80% by mass or more. This allows for more reliable suppression of the decrease in the content of component (A) in the topical skin composition.

[0086] Furthermore, relative to the overall topical skin composition, the content of the oily base in the topical skin composition is specifically less than 100% by mass, for example, it may be 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.

[0087] As a wetting agent, for example, at least one selected from dl-pyrrolidone sodium carboxylate and polysorbate 40 solution can be cited.

[0088] As an adhesive, for example, at least one selected from butylated hydroxytoluene and hydrogenated rosin glycerol ester can be cited.

[0089] Specific examples of pH adjusters include one or more selected from inorganic acids such as hydrochloric acid and phosphoric acid and their salts; organic acids such as citric acid, malic acid, tartaric acid, gluconic acid, and lactic acid and their salts; bases such as sodium hydroxide and potassium hydroxide; and organic amines such as triethanolamine and diisopropanolamine. Specific examples of the above-mentioned salts include alkali metal salts such as sodium and potassium; and alkaline earth metal salts such as calcium and magnesium. Additionally, the pH adjuster may also be a hydrate.

[0090] As an antioxidant, for example, one or more selected from ascorbic acid, ascorbate palmitate, sodium bisulfite, sodium metabisulfite, sodium edetate, citric acid hydrate, citric anhydride, butylated hydroxytoluene, butylated hydroxyanisole, benzotriazole, and propyl gallate can be cited. From the perspective of obtaining a more stable inhibitory effect by reducing the content of component (A), the topical skin composition preferably contains at least one of sodium bisulfite and sodium edetate, and more preferably sodium edetate. Specification 6 / 12 pages 8 CN 122272598 A

[0091] As a cooling agent, for example, in addition to the above-mentioned components such as menthol (e.g., l-menthol), terpenes (e.g., camphor), and peppermint oil, eucalyptus oil may also be mentioned.

[0092] As a surfactant, a nonionic surfactant or an ionic surfactant may be used. Furthermore, the surfactant may also be an emulsifier.

[0093] Examples of nonionic surfactants include, for example, propylene glycol monofatty acid esters, ethylene glycol monofatty acid esters, glycerol monofatty acid esters (e.g., glycerol monostearate), glycerol polyfatty acid esters (e.g., glycerol triisooctanoate), polyglycerol fatty acid esters (e.g., diglycerol monooleate), sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, alkyl polyglucosides, polyethylene glycol fatty acid esters, and other polyol fatty acid esters or polyol alkyl ethers; polyoxyethylene alkyl ethers (e.g., polyoxyethylene behenyl ether), polyoxyethylene alkylphenyl ethers, polyoxyethylene phytosterols, polyoxyethylene hydrogenated phytosterols, polyoxyethylene polyoxypropylene alkyl ethers, and other polyoxyethylene ethers; polyoxyethylene monofatty acid esters, polyethylene glycol difatty acid esters, etc. Polyoxyethylene glycerol fatty acid ester, polysorbate ester 20, polysorbate ester 40, polysorbate ester 60, polysorbate ester 65, polysorbate ester 80, etc., polyoxyethylene dehydrated sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene methyl glucoside fatty acid ester, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, etc., polyoxyethylene hydrogenated castor oil, polyoxyethylene vegetable oil, polyoxyethylene alkyl ether fatty acid ester, polyoxyethylene polyoxypropylene glycol, etc., one or more of these ether esters.

[0094] Relative to the overall skin topical composition, the content of nonionic surfactant in the skin topical 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, and even more preferably 2% by mass or more. It is 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. This allows for a more suitable stability of the skin topical composition.

[0095] Specific examples of ionic surfactants include anionic surfactants such as sodium lauryl sulfate and sodium cetyl sulfate.

[0096] As stabilizers, for example, one or more selected from the above-mentioned antioxidants and ionic surfactants can be cited.

[0097] As a preservative, for example, one or more of the following can be selected: benzoic acid, sodium benzoate, methylparaben, ethylparaben, propylparaben, butylparaben, dehydroacetic acid, sodium dehydroacetate, sorbic acid and phenoxyethanol.

[0098] As a thickener or thickening agent, examples include cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and hydroxyethylcellulose; magnesium aluminum silicate; carboxyvinyl polymers; sodium alginate; xanthan gum; carrageenan; guar gum; gelatin; dextrin; cyclodextrin; pectin; sodium carboxymethylcellulose; polyvinyl alcohol; polyvinylpyrrolidone; sodium polyacrylate; and light anhydrous silicate.

[0099] The topical skin composition can be manufactured, for example, by combining components (A) to (C) with suitable other components using known manufacturing methods. For example, the topical skin composition can also be manufactured according to the usual methods described in the 18th revised edition of the Japanese Pharmacopoeia, etc.

[0100] The dosage form of the topical skin composition can be selected from, for example, ointments, creams, topical liquids, gels, topical solid dosage forms, sprays (aerosols or pump sprays), foams, and patches.

[0101] The topical skin composition is preferably an ointment. This allows for more reliable suppression of the decrease in the content of ingredient (A) in the topical skin composition. From the same viewpoint, the topical skin composition is preferably an oil-based composition, and furthermore, it is preferable that it does not contain an aqueous phase.

[0102] When the topical skin composition is an ointment, it is preferable that no water is intentionally added to the composition.

[0103] On the other hand, the water content from the raw materials used to manufacture the topical skin composition, such as the water content of commercially available glycerin, can be included in the topical skin composition.

[0104] Furthermore, since the topical skin composition contains ingredient (A), it is suitable for formulation into topical medications such as anti-inflammatory and antipruritic agents. The topical skin composition can be a pharmaceutical composition.

[0105] The application method of the topical skin composition is based on a typical topical composition; for example, it can be applied to the target area of ​​the skin once or multiple times a day according to the symptoms.

[0106] (Method for suppressing the decrease in the content of component (A))

[0107] In this embodiment, the method for suppressing the decrease in the content of component (A) includes the following steps: combining component (C) with a composition containing the above-mentioned components (A) and (B).

[0108] As described above, in this embodiment, by combining component (C) with a composition containing components (A) and (B), it is possible to effectively suppress the variation in the stability of component (A) depending on the combination composition of the composition and the decrease in the content of component (A) in a composition containing components (A) and (B) but not containing component (C).

[0109] The embodiments of the present invention have been described above, but these are merely examples of the present invention, and various configurations other than those described above may also be used.

[0110] Hereinafter, examples will be given to specifically describe this embodiment, but this embodiment is not limited to these examples.

[0111] It should be noted that, hereinafter, betamethasone valerate will also be referred to as "BV".

[0112] (Example 1, Comparative Example 1, Reference Example 1)

[0113] Compositions (ointments) of each example were prepared according to the composition shown in Table 1, in accordance with the "Ointment" section of the General Rules for Preparations of the 18th Revision of the Japanese Pharmacopoeia.

[0114] In Table 1, the amount of each component is the mass (g) when the total amount is set to 100g, which is equivalent to mass %.

[0115] (Stability of BV content)

[0116] The BV amount of the compositions obtained in each example was determined by high performance liquid chromatography (HPLC) immediately after manufacture and after storage.

[0117] (Storage method)

[0118] The compositions of each example were filled into capped glass bottles and sealed, and stored at 40°C for 1 day or at 60°C for 1 day.

[0119] (Measurement Conditions)

[0120] Detector: UV spectrophotometer, wavelength: 240nm

[0121] Column: A chromatographic column made of core-shell silica gel for liquid chromatography with a particle size of 2.7μm, packed in a stainless steel tube with an inner diameter of 4.6mm and a length of 15cm.

[0122] Column temperature: A constant temperature around 40℃.

[0123] Mobile phase: A mixture of acetonitrile / purified water / phosphoric acid.

[0124] Injection volume: 10μL

[0125] (Residual BV content)

[0126] Based on the determination results of the BV content of the compositions immediately after manufacture and after storage at various temperatures, the mass ratio of the BV content after storage to the BV content immediately after manufacture for each example was calculated as the residual rate. The results are shown in Table 1.

[0127] [Table 1] Instruction manual 8 / 12 pages 10 CN 122272598 A

[0128]

[0129] The following shows the details of the ingredients listed in Table 1.

[0130] Glycerin: Manufactured by Kosakai Pharmaceutical Co., Ltd.

[0131] Liquid paraffin: Manufactured by KANEDA Co., Ltd.

[0132] Paraffin: Manufactured by Nippon Reiwa Co., Ltd.

[0133] Glyceryl fatty acid ester: Manufactured by Nikko Chemical Co., Ltd.

[0134] White petrolatum: Manufactured by Kosakai Pharmaceutical Co., Ltd.

[0135] In addition, in Table 1 and Table 2 described below, if the measured value of the residual rate is greater than 100%, it can be recorded as a residual rate of 100%.

[0136] According to Table 1, in Comparative Example 1, which contains components (A) and (B) but not component (C), compared to Reference Example 1, which contains component (A) but not components (B) and (C), the content of component (A) decreased immediately after manufacturing, and the content decreased further during storage.

[0137] On the other hand, in Example 1, which contains components (A) to (C), compared to Comparative Example 1, the decrease in content from the manufacturing process to storage was comprehensively suppressed.That is, 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) caused by storage was also suppressed.

[0138] (Examples 2-13)

[0139] The compositions (ointments) of each example were prepared according to Example 1 according to the composition shown in Table 2.

[0140] For the compositions obtained in each example, the amount of steroids immediately after manufacturing and after storage at 60°C for 1 day was determined by HPLC. The HPLC determination was performed according to Example 1 except that the injection volume of fluocinolone acetonide was 20 μL. The results are shown in Table 2.

[0141] [Table 2] Specification 9 / 12 pages 11 CN 122272598 A

[0142]

[0143] According to Table 2, in each example, compared with Comparative Example 1, the decrease in the content of component (A) immediately after manufacturing was suppressed, and the decrease in the content of component (A) caused by high-temperature storage at 60°C was also suppressed. Instructions for Use, Pages 10 / 12, CN 122272598 A

[0144] (Formulation Examples 1-12)

[0145] The compositions of each example (Formulation Examples 10 and 11 are reference examples) can be prepared by combining the ingredients according to the "Ointment" section of the General Rules for Formulations of the 18th Revision of the Japanese Pharmacopoeia, based on the composition shown in Table 3. In addition, the ointment composition can be contained in a container (e.g., a bottle-shaped container, a tube-shaped container, a jar-shaped container, etc.).

[0146] [Table 3]

[0147] Instructions for Use, Pages 11 / 12, CN 122272598 A

[0148] This application claims priority based on Japanese Patent Application No. 2024-229028 filed on December 25, 2024, the entire contents of which are incorporated herein by reference. Specification 12 / 12 Page 14 CN 122272598 A Abstract The present invention provides a technique for inhibiting a decrease in steroid content when a steroid and panthenol coexist. Provided is a topical skin composition comprising component (A) being a steroid, component (B) being panthenol, and component (C) being a polyhydric alcohol..

Claims

1. A topical skin composition comprising the following ingredients (A) to (C): (A) Steroids (B) Panthenol, (C) Polyols.

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, The ingredient (A) is selected from one or more of betamethasone valerate, betamethasone butyrate propionate, prednisolone acetate valerate, and fluocinolone acetonide.

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

5. The topical skin composition according to any one of claims 1 to 4, wherein, The ingredient (C) is glycerin.

6. The topical skin composition according to any one of claims 1 to 5, wherein, It further contains the following component (D). (D) Selected from one or more of benzyloxyethamine, its salts and their hydrates.

7. The topical skin composition according to any one of claims 1 to 6, wherein it is an anti-inflammatory and antipruritic agent.

8. A method for inhibiting the decrease in the content of said component (A), comprising the steps of: combining component (C) in a composition containing components (A) and (B). (A) Steroids (B) Panthenol, (C) Polyols.