Topical skin components

Abstract

This invention provides a technology to suppress the decrease in the content of betamethasone valerate. [Solution] A topical skin composition containing the following components: (A) betamethasone valerate, (B) one or more selected from the group consisting of benzethonium, its salts and hydrates, and (C) panthenol.

Description

Technical Field

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

Background Art

[0002] As a technique for blending betamethasone ester in a composition, there are those described in Patent Documents 1 and 2. Patent Document 1 (Japanese Unexamined Patent Application Publication No. 2024-48695) describes a topical skin application for suppressing a decrease in skin barrier function associated with dermatitis, which contains a steroid anti-inflammatory drug and panthenol or a panthenol analog (Claim 1), and a composition containing betamethasone valerate as a steroid anti-inflammatory drug is described (Claim 4). According to this document, by containing a steroid anti-inflammatory drug and panthenol or a panthenol analog, it is possible to provide a drug that can not only treat the symptoms of dermatitis but also suppress a decrease in skin barrier function associated with dermatitis (Paragraph 0009).

[0003] Patent Document 2 (Japanese Unexamined Patent Application Publication No. 2023-145400) describes that when betamethasone ester and a lower alcohol are made into a liquid or semi-solid composition, crystal precipitation occurs and there is a problem with stability (Paragraph 0009). This document describes, as a technique that aims to provide a liquid or semi-solid composition in which crystal precipitation is suppressed while containing a lower alcohol together with betamethasone ester, a composition containing betamethasone ester; a lower alcohol; one or more selected from the group consisting of a local anesthetic component, an antihistamine component, terpenes, chlorotrimeton and its salts and their solvates, and one or more selected from the group consisting of panthenols and salicylic acids (Claim 1). Also, in this document, specific examples of a number of bactericides containing benzethonium chloride are listed as medicinal components that can be blended in the composition as components other than the above (Paragraphs 0048, 0049).

Prior Art Documents

Patent Documents

[0004] [Patent Document 1] Japanese Patent Publication No. 2024-48695 [Patent Document 2] Japanese Patent Publication No. 2023-145400 [Overview of the project] [Problems that the invention aims to solve]

[0005] The inventors investigated the combination of betamethasone valerate and one or more substances selected from the group consisting of benzethonium, its salts, and their hydrates in a composition. It was found that in compositions containing one or more substances selected from the group consisting of benzethonium, its salts, and their hydrates, the content of betamethasone valerate decreased compared to compositions that did not contain these substances.

[0006] Therefore, the present invention provides a technology to suppress the decrease in the content of betamethasone valerate. [Means for solving the problem]

[0007] The inventors have newly discovered that by incorporating panthenol into a composition containing betamethasone valerate and one or more elements selected from the group consisting of betamethasone valerate, benzethonium, its salts, and their hydrates, the decrease in the content of betamethasone valerate can be effectively suppressed.

[0008] The present invention provides the following compositions and methods. [1] A topical skin composition containing the following ingredients (A) to (C). (A) Betamethasone valerate (B) One or more selected from the group consisting of benzethonium, its salts and their hydrates. (C) Panthenol [2] The topical skin composition according to [1], wherein the mass ratio ((A) / (B)) of the content of component (A) to the content of component (B) in the topical skin composition is 1.2 or more and 24 or less. [3] The topical skin composition according to [1] or [2], wherein the mass ratio of the content of component (C) to the total content of components (A) and (B) in the topical skin composition ((C) / ((A)+(B))) is 2.9 or more and 40 or less. [4] A topical skin composition according to any one of [1] to [3], wherein the dosage form is a cream. [5] A topical skin composition according to any one of [1] to [4], further comprising at least one selected from the group consisting of citric acid, citrates, and hydrates thereof. [6] 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) Betamethasone valerate (B) One or more selected from the group consisting of benzethonium, its salts and their hydrates. (C) Panthenol [Effects of the Invention]

[0009] According to the present invention, the decrease in the content of betamethasone valerate can be suppressed. [Brief explanation of the drawing]

[0010] [Figure 1] This figure shows the results of HPLC measurement of the compositions in the examples. [Figure 2] This figure shows the results of HPLC measurement of the compositions in the examples. [Figure 3] This figure shows the results of HPLC measurement of the compositions in the examples. [Figure 4] This figure shows the results of HPLC measurement of the compositions in the examples. [Modes for carrying out the invention]

[0011] Hereinafter, embodiments of the present invention will be described. In this 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 numerical values at both ends.

[0012] (Topical composition for skin) In this embodiment, the topical composition for skin contains the following components (A) to (C). (A) Betamethasone valerate (B) One or more selected from the group consisting of benzethonium, its salts and their hydrates (C) Panthenol

[0013] In this embodiment, since the topical composition for skin contains components (A) to (C) in combination, the stability of component (A) is superior to that of a composition containing components (A) and (B) but not containing component (C), and a decrease in the content of component (A) is preferably suppressed. Moreover, according to this 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 this 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) for a long period (for example, 2 months or more). Hereinafter, each component will be described.

[0014] (Component (A)) Component (A) is betamethasone valerate, specifically, a halogenated corticosteroid with the 17 - hydroxyl group esterified with valeric acid. Component (A) is included in the 18th revised Japanese Pharmacopoeia. Betamethasone valerate is one of the topical corticosteroids, has an anti - inflammatory effect, and shows excellent effects on many skin diseases such as eczema, dermatitis, sweat rash, rash, itching, chilblain, insect bites, and urticaria, and is widely used as a topical agent.

[0015] 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. Similarly, the content of component (A) may be, for example, 0.2% by mass or more. 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 total amount of the 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. Similarly, the content of component (A) may be, for example, 0.2% by mass or less or 0.15% by mass or less.

[0016] (Component (B)) Component (B) is one or more selected from the group consisting of benzethonium, its salts, and their hydrates. Component (B) 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.

[0017] The content of component (B) 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. This ensures that the medicinal effects of component (B) are added to those of component (A), thereby more reliably reducing skin inflammation and preventing the worsening of symptoms caused by infection through its bactericidal effect on the skin. Similarly, the content of component (B) may be, for example, 0.04% by mass or more. Furthermore, the content of component (B) 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 allows for more stable suppression of the decrease in the content of component (A) in the topical skin composition. Similarly, the content of component (B) may be, for example, 0.03% by mass or less.

[0018] The mass ratio ((A) / (B)) of the content of component (A) to the content of component (B) in the topical skin composition is, for example, 1.0 or more, preferably 1.2 or more, and more preferably 5 or more. This more reliably suppresses the decrease in the content of component (A). Similarly, the above mass ratio ((A) / (B)) may be, for example, 10 or more or 20 or more. Furthermore, since the amount of component (B) decreases as the amount of component (A) increases, the above mass ratio ((A) / (B)) is preferably 24 or less, more preferably 20 or less, even more preferably 18 or less, even more preferably 15 or less, and even more preferably 13 or less. Similarly, the above mass ratio ((A) / (B)) may be, for example, 10 or less, 5 or less, or 2 or less. On the other hand, the above mass ratio ((A) / (B)) may be, for example, 30 or less or 25 or less.

[0019] (Component (C)) Component (C) is panthenol, which is listed in the Japanese Pharmacopoeia (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. In this embodiment, since component (C) is included in the topical skin preparation, the decrease in the content of component (A) can be suitably suppressed. As component (C), for example, a commercially available product may be used, or it may be manufactured and used by known methods.

[0020] The content of component (C) 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, relative to the total content of the topical skin composition. This allows for more stable suppression of the decrease in the content of component (A). Similarly, the content of component (C) may be, for example, 2% by mass or more, 3% by mass or more, or 4% by mass or more. Furthermore, the content of component (C) 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, relative to the entire topical skin composition. This is expected to soothe skin inflammation, prevent the worsening of symptoms caused by infection through its bactericidal effect on the skin, and also have a skin-repairing effect. Similarly, the content of component (C) may be, for example, 3% by mass or less or 2% by mass or less.

[0021] The mass ratio of the content of component (C) to the total content of components (A) and (B) in the topical skin composition ((C) / ((A)+(B))) is, for example, 2.5 or more, preferably 2.9 or more, more preferably 3.5 or more, and even more preferably 4 or more. This allows for more stable suppression of the decrease in the content of component (A). Similarly, the above mass ratio ((C) / ((A)+(B))) may be, for example, 10 or more, 15 or more, 20 or more, or 30 or more. Similarly, the above mass ratio ((C) / ((A)+(B))) is, for example, 40 or less, preferably 38.5 or less, more preferably 30 or less, even more preferably 25 or less, even more preferably 15 or less, and still more preferably 8 or less. Similarly, the above mass ratio ((C) / ((A)+(B))) may be, for example, 7 or less or 5 or less.

[0022] 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.

[0023] 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.

[0024] The above drugs include, for example, steroids other than component (A) such as cortisone acetate, dexamethasone acetate, dexamethasone, hydrocortisone acetate, hydrocortisone, prednisolone acetate, prednisolone, hydrocortisone butyrate, and prednisolone valerate acetate; antihistamines 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; and salicylic acid derivatives such as glycol salicylate and methyl salicylate. Examples include allantoin; disinfectants other than component (B), such as isopropylmethylphenol and benzalkonium chloride; astringents such as calamine and zinc oxide; local anesthetics such as ethyl aminobenzoate, oxypolyethoxide dodecane, dibucaine, dibucaine hydrochloride, lidocaine, and lidocaine hydrochloride; cooling agents 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 (C), 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. The content of glycyrrhetinic acid derivatives in the topical skin composition can be, for example, 0.01 to 2% by mass relative to the total amount of the topical skin composition. The content of salicylic acid derivatives in the topical skin composition can be, for example, 0.05 to 10% by mass relative to the total amount of the topical skin composition. The tannic acid content in the topical skin composition can be, for example, 0.01 to 0.2% by mass relative to the total amount of the topical skin composition. Furthermore, the gamma-oryzanol content in the topical skin composition can be, for example, 0.1 to 5% by mass relative to the total amount of the topical skin composition.

[0025] 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.

[0026] Examples of bases include water; oily bases; partially neutralized polyacrylic acid; polyhydric alcohols such as polyvinyl alcohol (partially saponified), propylene glycol, dipropylene glycol, macrogol, 1,3-butylene glycol, glycerin (e.g., concentrated glycerin), and D-sorbitol.

[0027] When a topical skin composition contains water, the water content may be, for example, the remainder after removing components other than water from the topical skin composition. Furthermore, the water content in the topical skin composition is preferably 20% by mass or more, more preferably 40% by mass or more, and even more preferably 60% by mass or more, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A). Similarly, the water content in the topical skin composition is preferably 85% by mass or less, more preferably 80% by mass or less, and even more preferably 75% by mass or less, relative to the entire topical skin composition.

[0028] 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. The content of the oily base in the topical skin composition is preferably 1% by mass or more, more preferably 5% by mass or more, even more preferably 10% by mass or more, and also preferably 30% by mass or less, more preferably 25% by mass or less, and even more preferably 20% by mass or less, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A).

[0029] The polyhydric alcohol content in the topical skin composition is preferably 1% by mass or more, more preferably 2% by mass or more, even more preferably 3% by mass or more, and also preferably 20% by mass or less, more preferably 15% by mass or less, even more preferably 12% by mass or less, and even more preferably 8% by mass or less, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A).

[0030] Examples of wetting agents include at least one selected from the group consisting of dl-pyrrolidone carboxylate sodium and polysorbate 40 solution.

[0031] Examples of adhesives include at least one selected from the group consisting of dibutylhydroxytoluene and hydrogen rosin glycerol esters.

[0032] 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.

[0033] The topical skin composition preferably further contains at least one selected from the group consisting of citric acid, citrate, and hydrates thereof, and more preferably contains citric acid or its hydrate and sodium citrate or its hydrate. This allows for more stable suppression of the decrease in the content of component (A).

[0034] The pH adjusting agent content 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, even more preferably 0.15% by mass or more, and even more preferably 0.18% by mass or more, relative to the total amount of the topical skin composition. This makes it possible to more stably suppress the decrease in the content of component (A). Similarly, the content of the pH adjusting agent in the topical skin composition is preferably 5% by mass or less, more preferably 3% by mass or less, even more preferably 1% by mass or less, even more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less, relative to the total amount of the topical skin composition.

[0035] 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. The antioxidant content in the topical skin composition is preferably 0.01% by mass or more, more preferably 0.03% by mass or more, even more preferably 0.05% by mass or more, and also preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A).

[0036] Examples of cooling agents include one or more selected from the group consisting of menthol such as l-menthol, terpenes such as camphor, peppermint oil, eucalyptus oil, and the like.

[0037] 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, sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, alkyl polyglucosides, polyethylene glycol fatty acid esters; and polyoxyethylene 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 selected from the group consisting of 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 ether esters such as polyoxyethylene polyoxypropylene glycol. The content of the nonionic surfactant in the topical skin composition is preferably 0.1% by mass or more, more preferably 1% by mass or more, even more preferably 3% by mass or more, and also preferably 15% by mass or less, more preferably 10% by mass or less, and even more preferably 8% by mass or less, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A).

[0038] Furthermore, specific examples of ionic surfactants include anionic surfactants such as sodium lauryl sulfate and sodium cetyl sulfate. The content of the ionic surfactant in the topical skin composition is preferably 0.01% by mass or more, more preferably 0.03% by mass or more, even more preferably 0.05% by mass or more, and also preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A).

[0039] Examples of stabilizers include one or more selected from the group consisting of the aforementioned antioxidants and ionic surfactants. To more stably suppress the decrease in the content of component (A), the topical skin composition preferably contains at least one of sodium edetate and sodium lauryl sulfate, and more preferably contains one of sodium edetate and sodium lauryl sulfate.

[0040] The content of the stabilizer in the topical skin composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, and even more preferably 0.08% by mass or more, 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). Similarly, the content of the stabilizer in the topical skin composition is preferably 5% by mass or less, more preferably 3% by mass or less, even more preferably 1% by mass or less, even more preferably 0.5% by mass or less, and even more preferably 0.2% by mass or less, relative to the total amount of the topical skin composition.

[0041] 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. The preservative content 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 also preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.3% by mass or less, relative to the total amount of the topical skin composition. This makes it possible to more reliably obtain the effect of suppressing the decrease in the content of component (A).

[0042] 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.

[0043] 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.

[0044] The dosage form of the topical skin composition can be selected from the group consisting of, for example, creams, ointments, topical solutions, gels, topical solids, sprays (aerosols or pump sprays), foams, and patches. The topical skin composition is preferably a cream. This allows for a more reliable suppression of the decrease in the content of component (A).

[0045] 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.

[0046] (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), the decrease in the content of component (A) that occurs in a composition containing components (A) and (B) but not component (C) can be effectively suppressed.

[0047] The embodiments of the present invention have been described above, but these are merely examples, and various other configurations can also be adopted. [Examples]

[0048] 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".

[0049] (Examples 1-5, Comparative Examples 1-3, Reference Examples 1 and 2) Each component was prepared according to the composition shown in Table 1 or Table 2, in accordance with the section on "Creams" in the General Provisions of the 18th Revised Japanese Pharmacopoeia, and each example composition (cream) was prepared.

[0050] (Stability of BV content) For the compositions obtained in each example, the BV content immediately after production (n=3) and after storage (n=3) was determined by high-performance liquid chromatography (HPLC). The HPLC charts for Comparative Example 2, Example 1, Comparative Example 3, and Example 2 are shown in Figures 1 to 4, respectively. In Figures 1 to 4, subdivisions (a) and (b) show the charts immediately after production and after storage, respectively.

[0051] (How to save) The compositions for each example were filled into aluminum tubes and stored in an airtight condition at 40°C for 2 months.

[0052] (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 10 cm, packed with octadecylsilylated silica gel for liquid chromatography with a particle size of 3 μm. Column temperature: Constant temperature around 40°C Mobile phase: A mixture of acetonitrile and formic acid diluted 1000 times with purified water.

[0053] (Remaining BV content) Based on the measurement results of the BV content of the compositions immediately after manufacturing and after storage, the mass ratio of the BV content after storage to the BV content immediately after manufacturing was calculated for each example and expressed as the residual rate. The results are shown in Tables 1 and 2. In Table 1 and Table 2 described below, if the measured survival rate is greater than 100%, the survival rate can be set to 100%.

[0054] [Table 1]

[0055] [Table 2]

[0056] In Tables 1 and 2, the unit of component amounts is mass%. Furthermore, the details of the components listed in Tables 1 and 2 are shown below. Behenyl alcohol: Manufactured by Japan Surfactant Industry Co., Ltd. Glycerin triisooctanoate: Manufactured by Japan Surfactant Industry Co., Ltd. Cetyl palmitate: Manufactured by Nippon Surfactant Industry Co., Ltd. Liquid paraffin: Manufactured by Kaneda Co., Ltd. Dimethylpolysiloxane: Manufactured by Shin-Etsu Chemical Co., Ltd. Glyceryl monostearate: Manufactured by Japan Surfactant Industry Co., Ltd. Polyoxyethylene behenyl ether: Manufactured by Japan Surfactant Industry Co., Ltd.

[0057] In Table 1, compared to Reference Example 1, which contains only component (A) from components (A) to (C), Comparative Example 1, which also contains component (B), showed a lower BV retention rate after storage compared to immediately after manufacturing. Furthermore, in Reference Example 2, which contains components (A) and (C) from components (A) to (C), the BV retention rate after storage compared to immediately after manufacturing also decreased compared to Reference Example 1. Furthermore, a comparison between Example 1 and Comparative Example 2, and between Example 2 and Comparative Example 3, showed that in each example, because components (A) to (C) were incorporated into the composition, the decrease in the remaining BV after storage compared to immediately after manufacturing was suppressed compared to each comparative example that contained components (A) and (B) but did not contain component (C). Furthermore, as shown in Table 2, in Examples 3 to 5, the combination of components (A) to (C) in the composition effectively suppressed the decrease in the remaining BV after storage compared to immediately after manufacturing.

[0058] (Formulation Examples 1-16) The compositions (creams) shown in each example (Examples 7, 8, 10, 12, 13, 15, and 16 are reference examples) can be prepared by compounding each component in accordance with the composition shown in Table 3 and the section on "Creams" in the General Provisions of the 18th Revised Japanese Pharmacopoeia. The cream composition may be stored in a container (for example, a bottle, tube, jar, etc.).

[0059] [Table 3]

Claims

1. A topical skin composition containing the following ingredients (A) to (C). (A) Betamethasone valerate (B) One or more selected from the group consisting of benzethonium, its salts and their hydrates. (C) Panthenol

2. The topical skin composition according to claim 1, wherein the mass ratio ((A) / (B)) of the content of component (A) to the content of component (B) in the topical skin composition is 1.2 or more and 24 or less.

3. The topical skin composition according to claim 1, wherein the mass ratio of the content of component (C) to the total content of components (A) and (B) in the topical skin composition ((C) / ((A)+(B))) is 2.9 or more and 40 or less.

4. A topical skin composition according to any one of claims 1 to 3, wherein the dosage form is a cream.

5. A topical skin composition according to any one of claims 1 to 3, further comprising at least one selected from the group consisting of citric acid, citrates, and hydrates thereof.

6. A method for suppressing a decrease in the content of component (A), comprising incorporating component (C) below into a composition containing the following components (A) and (B). (A) Betamethasone valerate (B) One or more selected from the group consisting of benzethonium, its salts and their hydrates. (C) Panthenol

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