Topical preparation composition

Abstract

The present invention provides a topical formulation that can continuously release the active ingredient into the skin, has good film-forming properties, is highly applicable to the skin, dries quickly, suppresses stickiness and tightness of the formed film, and exhibits excellent appearance and durability of the film. [Solution] An external preparation composition containing (A) a pharmacoactive ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less.

Description

[Technical Field]

[0001] This invention relates to a topical formulation composition. [Background technology]

[0002] Liquid topical skin preparations and patches containing medicinal ingredients such as anti-inflammatory and analgesic components, and antiseptic and disinfectant components are known. However, existing liquid topical skin preparations have problems such as being easily rubbed off by clothing after application to the skin, making it difficult to continuously release the medicinal ingredients to the skin. Similarly, if patches containing medicinal ingredients do not conform well to the skin and peel off easily, it becomes difficult to continuously release the medicinal ingredients to the skin. On the other hand, patches with high adhesiveness to the skin also have the problem of causing a greater burden on the skin when removed. Furthermore, patches have practical use issues such as being prone to causing skin irritation and being aesthetically unappealing when applied to the skin.

[0003] Therefore, film-forming formulations that can continuously release active ingredients into the skin are being investigated. Because film-forming formulations can form a film when applied to the skin, they are less likely to rub off compared to liquid topical skin preparations. They are also preferable because they are not as noticeable as patches when applied to the skin, and they cause less skin irritation when removed.

[0004] For example, Patent Document 1 proposes an adhesive solid formulation for skin delivery of a drug, comprising: a drug; a solvent excipient comprising a volatile solvent system containing a volatile solvent and a non-volatile solvent system containing a non-volatile solvent; and a solidifying agent; having a viscosity suitable for application to and adhesion to a skin surface prior to the evaporation of the volatile solvent system; the formulation, when applied to the skin surface, forms a solidified layer after at least partial evaporation of the volatile solvent system, and the drug is continuously delivered to the skin after at least substantially the evaporation of the volatile solvent system, provided that the formulation contains at least two volatile solvents, two non-volatile solvents, or two solidifying agents. It is stated that the formulation can provide sustained drug delivery over a long period of time, is not susceptible to unintended removal by contact with clothing, other objects, or people during the duration of application, can be applied to a skin area that conforms to stretching and expanding without causing unpleasant or poor contact with the skin, and can be easily removed after application and use.

[0005] Patent Document 2 proposes a composition for transdermal administration of a physiological activator comprising: ethyl acrylate / methyl methacrylate copolymer; ethanol, isopropanol or a mixture thereof; water; and at least one physiological activator. The composition is described as a film-forming composition that rapidly forms a non-sticky, durable, and highly flexible film. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Special Publication No. 2009-519956 [Patent Document 2] Special Publication No. 2014-515365 [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] However, even in the disclosed technologies of Patent Documents 1 and 2, there was room for improvement in the sustained slow release of drugs, physiologically active agents, etc. to the skin. In addition, improvement in the performance in actual use as an external preparation composition, such as quick drying property and appearance after applying the composition to the skin, is also desired. The present invention relates to an external preparation composition that can continuously and slowly release a medicinal ingredient to the skin, has good film-forming properties, high applicability and quick drying property to the skin, has an effect of suppressing stickiness and tight feeling of the formed film, and is excellent in the appearance and durability of the film. [Means for Solving the Problems]

[0008] The present inventors have found that an external preparation composition containing a medicinal ingredient, a water-insoluble polymer, and a predetermined solvent component and having a predetermined viscosity can solve the above problems. That is, the present invention relates to the following. [1] An external preparation composition containing (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and having a viscosity at 25°C of 1.0 mPa·s or more and 10,000 mPa·s or less. [2] A lotion preparation, a gel preparation, an ointment preparation, a cream preparation, or a foamy preparation comprising the external preparation composition according to [1] above. [3] An aerosol preparation or a pump spray type preparation using the external preparation composition according to [1] above. [4] A method for using an external preparation composition, which comprises applying to the skin an external preparation composition containing (A) a medicinal ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water and having a viscosity at 25°C of 1.0 mPa·s or more and 10,000 mPa·s or less, and then drying. [5] A method for producing a film, which comprises a step of directly applying or spraying the external preparation composition according to [1] above onto the skin. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a pharmaceutical composition for external use that can continuously release a pharmaceutically active ingredient onto the skin, has good film-forming properties, high applicability and quick-drying properties on the skin, suppresses the stickiness and tightness of the formed film, has excellent appearance and durability of the film, a preparation using the same, a method for using the pharmaceutical composition for external use, and a method for producing the film.

Embodiments for Carrying Out the Invention

[0010] [Pharmaceutical Composition for External Use] The present invention relates to a pharmaceutical composition for external use containing (A) a pharmaceutically active ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and having a viscosity at 25°C of 1.0 mPa·s or more and 10,000 mPa·s or less. Hereinafter, the composition is also appropriately referred to as "the composition of the present invention".

[0011] [Definition] In the present specification, the "pharmaceutical composition for external use" mainly refers to a composition applied to the skin surface. In the present specification, the "water-insoluble polymer" refers to a polymer having the property that when 1 g of the polymer is immersed in 10 g of ion-exchanged water at 23°C and 1 atm for 24 hours, more than 0.5 g of the immersed polymer does not dissolve. In the present specification, the "non-volatile base" refers to a base that is liquid at 70°C and has a mass reduction rate of less than 1% after spreading 1 g of the base in a glass petri dish with a diameter of 48 mm and leaving it at 25°C and normal pressure for 24 hours. The "volatile solvent" means a component other than water that is liquid at 25°C and has a mass reduction rate of 1% or more after spreading 1 g of the solvent in a glass petri dish with a diameter of 48 mm and leaving it at 25°C and normal pressure for 24 hours. In addition, in the present specification, the resistance of the film to sweat, humidity, etc. (moisture resistance) and the difficulty of the film being rubbed off (abrasion resistance) are collectively referred to as the "durability of the film".

[0012] The composition of the present invention contains component (A): pharmaceutically active ingredient, component (B): water-insoluble polymer, component (C): non-volatile base, component (D): volatile base, and component (E): water. However, component (A) is not included in any of the other components (B), (C), and (D), and component (B) is not included in any of the other components (C) and (D).

[0013] The composition of the present invention, having the above-described structure, can continuously release the active ingredient to the skin, has good film-forming properties, high applicability to the skin, dries quickly, suppresses stickiness and tightness of the formed film, and also exhibits excellent appearance and durability of the film. The reason for this is not entirely clear, but it is thought to be as follows. The composition of the present invention is a film-forming composition containing a water-insoluble polymer (component B) and a non-volatile base (component C) as film-forming components. When the composition of the present invention is applied to the skin and then dried, components (D) and (E) volatilize to form a film containing components (A) to (C). Here, if a highly crystalline component such as felbinac, described later, is used as the active ingredient (A), then if the compatibility between component (A) and the coating is low, component (A) is likely to crystallize in the coating, reducing its sustained release to the skin. However, if the compatibility between component (A) and the coating is too high, it is thought that component (A) will be incorporated into the coating and will not be easily released to the skin. When a water-insoluble polymer, component (B), is used as a film-forming component, the compatibility between the film and component (A) may be excessively high or low, potentially reducing the sustained release properties of component (A). In the composition of the present invention, by using component (C), it is believed that if the compatibility between the film and component (A) is excessively high, the compatibility between the film and component (A) is reduced, or if the compatibility between the film and component (A) is low, the compatibility is improved to suppress the crystallization of component (A), thereby improving the sustained release properties of component (A). Furthermore, since component (B) is water-insoluble, it can form a highly hydrophobic film, so even after application to the skin, the film is less likely to rub off due to sweat, humidity, etc., and the active ingredient can be continuously released to the skin. Moreover, due to the synergistic effect of components (B) and (C), it is believed that a composition can be obtained that has good applicability to the skin, dries quickly, is not sticky or tight, has a good appearance, and forms a durable film that is less likely to rub off after application to the skin. Component (D) is thought to contribute to improving the applicability, quick-drying properties, and storage stability of the composition, while component (E) is thought to contribute to improving the storage stability of the composition. Furthermore, because the composition of the present invention contains components (D) and (E) and has a viscosity within a predetermined range, the composition becomes more easily absorbed by the skin, enabling a balance between film-forming properties and film durability, as well as applicability and quick-drying properties. As a result, component (A) can be effectively released onto the skin.

[0014] <Ingredient (A): Medicinal ingredient> The composition of the present invention contains a pharmacoactive ingredient as component (A). From the viewpoint of use in topical formulations, component (A) is preferably a topical drug ingredient that can be administered transdermally. Specifically, component (A) preferably contains one or more selected from the group consisting of anti-inflammatory and analgesic components, local irritants, blood circulation promoting components, antihistamine components, herbal components, antipruritic components, local anesthetic components, keratolytic components, bactericidal components, and antimicrobial components.

[0015] The anti-inflammatory and analgesic ingredients include glycol salicylate, methyl salicylate, aspirin, sulpyrine hydrate, acetaminophen, diclofenac sodium, fenbufen, ibuprofen, aminoprofen, loxoprofen sodium or its hydrate, naproxen, oxaprofen, ketoprofen, tiaprofenic acid, sulindac, aluminum flufenamate, felbinac, mefenamic acid, indomethacin, indomethacin farnesyl, acemetacin, and progourmet. Examples include tacin maleate, bendazac, piroxicam, ampiroxicam, lornoxicam, tenoxicam, meloxicam, etodolac, tiaramide hydrochloride, bucolome, flurbiprofen, esflurbiprofen, lysozyme hydrochloride, bromelain, diphenhydramine hydrochloride, dibucaine, dimethylisopropylazulene, benzethonium chloride, glycyrrhizic acid, dipotassium glycyrrhizinate, zinc oxide, allantoin, heparinoids, and glycyrrhetinic acid.

[0016] Examples of local irritants include l-menthol, dl-camphor, nonyl vanillylamide, ammonia, and peppermint oil.

[0017] Examples of ingredients that promote blood circulation include benzyl nicotinate, sodium polyethylene sulfonate, and tocopherol acetate.

[0018] Examples of antihistamine components include diphenhydramine, diphenhydramine hydrochloride, diphenhydramine salicylate, and chlorpheniramine maleate.

[0019] Herbal ingredients include chili pepper, eucalyptus oil, Phellodendron bark, arnica tincture, Houttuynia cordata, peony, mugwort, cinnamon, Cnidium officinale, Cyperus rotundus, Atractylodes macrocephala, Star anise, Schisandra chinensis, Citrus unshiu peel, ginseng, Magnolia officinalis, clove, ginger, Gardenia fruit, licorice, fennel, Akebia quinata, safflower, Magnolia bark, spruce, and inch.

[0020] Examples of antipruritic ingredients include crotamiton, cortisone acetate, isotipendyl hydrochloride, benzalkonium chloride, calamine, d-borneol, ammonia water, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, dexamethasone, dexamethasone acetate, prednisolone, prednisolone acetate, prednisolone valerate acetate, and ufenamate.

[0021] Examples of local anesthetic components include lidocaine, mepivacaine, bupivacaine, ropivacaine, levopipivacaine, dibucaine, dibucaine hydrochloride, and ethyl aminobenzoate.

[0022] Examples of keratin-softening ingredients include urea, sulfur, and salicylic acid.

[0023] Examples of antibacterial ingredients include chlorhexidine gluconate, sodium copper chlorophyllin, isopropylmethylphenol, cetylpyridinium chloride hydrate, benzethonium chloride, benzalkonium chloride, resorcinol, acrinol hydrate, chlorhexidine gluconate, povidone-iodine, iodine / potassium iodide, mercurochrome, hydrogen peroxide, cresol, iodoform, and thymol.

[0024] In addition, the antibacterial components include undecylenic acid, zinc undecylenate, phenyl-11-iodo-10-undecinoate, exalamide, clotrimazole, econazole nitrate, miconazole nitrate, thioconazole, zinc diethyldithiocarbamate, cyclopiroxolamine, siccanicin, trichomycin, pyrrolnitrin, thianthol, 2,4,6-tribromophenylcaproate, trimethylcetylammonium pentachlorophenate, tolcyclate, tolnaftate, haloprozine, hibiscus bark, berberine benzoate, decalinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate solution, decalinium acetate, hinokitiol, rebrucin, benzoic acid, chlorobutanol, acetic acid, phenol, iodine tincture, diphenylpyraline hydrochloride, and diphen salicylate. Examples include hydramine, diphenylimidazole, chlorpheniramine maleate, dibucaine hydrochloride, procaine hydrochloride, lidocaine hydrochloride, aldioxa, glycyrrhizic acid and its salts, Lithospermum erythrorhizon, Angelica acutiloba, Borneol, diethyl phthalate, chlorohydroxyaluminum, penicillins, cephalosporins, carbapenems, monobactams, penems, aminoglycosides, fosfomycins, chloramphenicols, macrolides, glycopeptides, quinolones, fluoroquinolones, sulfonamides, fradiomycin sulfate, gentamicin sulfate, pentamidine isethionate, silver sulfadiazine, oxiconazole nitrate, sulconazole nitrate, bifonazole, neticonazole hydrochloride, lanoconazole, tenafine hydrochloride, amorolfine hydrochloride, terbinafine hydrochloride, etc.

[0025] Component (A) may be one or more of the above-mentioned active ingredients. Among the above, from the viewpoint that component (A) is an external preparation composition used on exposed and curved parts of the skin, it is preferable that it contains one or more selected from the group consisting of anti-inflammatory and analgesic components, local irritants, blood circulation promoting components, antihistamine components, and herbal medicine components, and more preferably that it contains one or more selected from the group consisting of anti-inflammatory and analgesic components and local irritants. Specifically, component (A) is more preferably composed of one or more selected from the group consisting of glycol salicylate, methyl salicylate, diclofenac sodium, loxoprofen sodium, ketoprofen, felbinac, indomethacin, piroxicam, flurbiprofen, glycyrrhizic acid, glycyrrhetinic acid, l-menthol, dl-camphor, nonyl vanillylamide, peppermint oil, benzyl nicotinate, sodium polyethylene sulfonate, tocopherol acetate, diphenhydramine, chlorpheniramine maleate, chili pepper, eucalyptus oil, and Phellodendron bark.

[0026] The solubility parameter (SP value) of component (A) is preferably 15.00 or higher, more preferably 18.00 or higher, even more preferably 19.00 or higher, and even more preferably 19.50 or higher, from the viewpoint of the formed film having a good appearance and suppressing the feeling of tightness in the formed film. Also, from the same viewpoint, it is preferably 35.00 or lower, more preferably 27.00 or lower, even more preferably 24.00 or lower, and even more preferably 22.00 or lower. Furthermore, the SP value of component (A) is preferably 15.00 or higher and 35.00 or lower, more preferably 18.00 or higher and 27.00 or lower, even more preferably 19.00 or higher and 24.00 or lower, and even more preferably 19.50 or higher and 22.00 or lower.

[0027] The above SP value can be calculated using solubility parameter calculation software (Hansen Solubility Parameters in Practice 4th Edition 4.1.03). In this specification, the SP value is calculated based on Hansen's solubility parameters. Hansen's solubility parameters are derived by dividing Hildebrand's solubility parameters into three components: dispersion term δD, polarity term δP, and hydrogen bonding term δH, and representing them in three-dimensional space. Specifically, the SP value δ is calculated using the following formula. δ=(δD 2 +δP 2 +δH 2 ) 1 / 2

[0028] Furthermore, the SP value for a mixture of two or more components can be calculated as follows. For example, let "mixture X" be a mixture of two components, component 1 and component 2. Let the Hansen solubility parameters of component 1 and component 2 be [δD1, δP1, δH1] and [δD2, δP2, δH2], respectively, and let the volume ratio of component 1 to component 2 be V1:V2. Then, the dispersion term δDm, polarity term δPm, and hydrogen bonding term δHm of mixture X are expressed by the following formulas. Note that in the case of polymers, the specific gravity was assumed to be 1.0. δDm=(V1×δD1+V2×δD2) / (V1+V2) δPm=(V1×δP1+V2×δP2) / (V1+V2) δHm=(V1×δH1+V2×δH2) / (V1+V2) The SP value δx of mixture X can be calculated using the following formula. δx=(δDm 2 +δPm 2 +δHm 2 ) 1 / 2

[0029] The composition of the present invention can suppress the crystallization of component (A) in the coating even when a highly crystalline component (A) is used, thereby enhancing sustained release to the skin, and also improving the storage stability of the composition. From the viewpoint of the usefulness of this effect, it is preferable that component (A) is one or more crystalline pharmacoactive ingredients selected from the group consisting of glycol salicylate, loxoprofen sodium, felbinac, l-menthol, and nonylic acid vanillylamide. However, in the composition of the present invention, even when an amorphous component (A) is used, a composition that can similarly form a coating with high sustained release to the skin can be obtained.

[0030] <Component (B): Water-insoluble polymer> The composition of the present invention contains a water-insoluble polymer as component (B). Component (B) is a film-forming component that improves the film-forming and quick-drying properties of the composition, suppresses the stickiness of the film, and, through the aforementioned mechanism of action, enables the formation of a film with high sustained release of component (A) to the skin, appearance, and durability. From the viewpoint of improving film-forming properties, component (B) is preferably a film-forming, water-insoluble polymer. The definition of "water-insoluble" for component (B) is as described above.

[0031] The solubility parameter (SP value) of component (B) is preferably 17.00 or higher, more preferably 18.00 or higher, even more preferably 19.00 or higher, and even more preferably 20.00 or higher, from the viewpoint of suppressing the feeling of tightness in the formed film and improving the sustained release of component (A) to the skin. Furthermore, from the viewpoint of suppressing the stickiness of the formed film, improving the sustained release of component (A) to the skin, and improving the durability of the film, it is preferably 27.00 or lower, more preferably 25.00 or lower, even more preferably 24.00 or lower, and even more preferably 23.00 or lower. The SP value of component (B) is preferably 17.00 or higher and 27.00 or lower, more preferably 18.00 or higher and 25.00 or lower, even more preferably 19.00 or higher and 24.00 or lower, and even more preferably 20.00 or higher and 23.00 or lower. The above SP value can be calculated by the same method as described above.

[0032] The type of component (B) is not particularly limited as long as it is a water-insoluble polymer, but from the viewpoint of suppressing stickiness and tightness of the film, improving skin compatibility, film formation, and durability, component (B) is preferably one or more water-insoluble polymers selected from the group consisting of acrylic polymers, cellulose polymers, and vinyl polymers. More preferably, it is one or more water-insoluble polymers selected from the group consisting of acrylic polymers, cellulose polymers, and vinyl polymers, and the SP value is within the range described above.

[0033] Examples of acrylic polymers used as component (B) include water-insoluble polymers that contain at least one structural unit derived from a monomer having a (meth)acrylic group. In this specification, "(meth)acrylic" means both acrylic and methacrylic. Specific examples of the acrylic polymer include, for example, water-insoluble polymers such as (acrylates / diacetone acrylamide) copolymer, acrylamide / methoxypolyethylene glycol methacrylate copolymer, acrylic acid / octyl acrylate copolymer, acrylic acid ester / vinyl acetate copolymer, 2-ethylhexyl acrylate / methyl acrylate / acrylic acid / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / vinyl acetate / hydroxyethyl acrylate / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / diacetone acrylamide / acetoacetoxyethyl methacrylate / methyl methacrylate copolymer, 2-ethylhexyl acrylate / vinylpyrrolidone copolymer, 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, ethyl acrylate / methyl methacrylate copolymer, ethyl acrylate / methyl methacrylate / methacrylate-derived trimethylammonium ethyl copolymer, methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, etc. Of the above, the (acrylates / diacetone acrylamide) copolymer is labeled as "(alkyl acrylate / diacetone acrylamide) copolymer AMP" in the cosmetic ingredient labeling; the acrylamide / methoxypolyethylene glycol methacrylate copolymer is labeled as "acrylamide / methoxypolyethylene glycol methacrylate copolymer solution" as described in the Pharmaceutical Additives Standards 2018 (Pharmaceuticals and Medical Devices Agency, Ministry of Health, Labour and Welfare); and the 2-ethylhexyl acrylate / vinylpyrrolidone copolymer is labeled as "2-ethylhexyl acrylate / vinylpyrrolidone For the 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, "2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer solution" can be used. For the ethyl acrylate / methyl methacrylate copolymer, "ethyl acrylate / methyl methacrylate copolymer dispersion" can be used. For the methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, "aminoalkyl methacrylate copolymer E" can be used. Furthermore, as the ethyl acrylate / methyl methacrylate / trimethylammonium ethyl methacrylate copolymer, "aminoalkyl methacrylate copolymer RS," which is known as a pharmaceutical additive, can be used.

[0034] Examples of cellulose-based polymers used as component (B) include water-insoluble polymers having a cellulose backbone. Examples of the cellulosic polymer include methylcellulose, ethylcellulose, hypromellose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose phthalate, hydrophobized (C16-18) hydroxypropylmethylcellulose, and others that are water-insoluble.

[0035] Examples of vinyl polymers used as component (B) include water-insoluble polymers that contain at least one structural unit derived from a monomer having a vinyl group and do not belong to the acrylic polymer category. Examples of such vinyl polymers include water-insoluble polyvinyl alcohol and polyvinyl butyral.

[0036] Component (B) may consist of one or more types. Among the above, component (B) is preferably (acrylates / diacetone acrylamide) copolymer, acrylamide / methoxypolyethylene glycol methacrylate copolymer, acrylic acid / octyl acrylate copolymer, acrylic acid ester / vinyl acetate copolymer, 2-ethylhexyl acrylate / methyl acrylate / acrylic acid / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / vinyl acetate / hydroxyethyl acrylate / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / diacetone acrylamide / acetoacetoxyethyl methacrylate / methyl methacrylate copolymer, 2-ethylhexyl acrylate / vinylpyrrolidone copolymer, 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, ethyl acrylate / methyl methacrylate copolymer, acrylic One or more selected from the group consisting of ethyl methacrylate / methyl methacrylate / methacrylate-derived trimethylammonium ethyl copolymer, methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, methylcellulose, ethylcellulose, hypromellose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose phthalate, hydrophobized (C16-18) hydroxypropylmethylcellulose, polyvinyl alcohol, and polyvinyl butyral, more preferably one or more selected from the group consisting of (acrylates / diacetone acrylamide) copolymer, acrylamide / methoxypolyethylene glycol methacrylate copolymer, ethylcellulose, hypromellose phthalate, and polyvinyl butyral, and having an SP value within the aforementioned range.

[0037] <Ingredient (C): Non-volatile base> The composition of the present invention contains a non-volatile base as component (C) (excluding those corresponding to component (A)). Component (C), through a synergistic effect with component (B), is thought to improve the film-forming properties, skin applicability, and quick-drying properties of the composition, as well as the sustained release of component (A) to the skin and the storage stability of the composition. The definition of "non-volatile base" in component (C) is as stated above.

[0038] Examples of component (C) include lipophilic bases, hydrophilic bases, and amphiphilic bases. However, from the viewpoint of improving the film-forming properties, skin applicability, and quick-drying properties of the composition, and from the viewpoint of enhancing the sustained release of component (A) to the skin, one or more selected from the group consisting of lipophilic bases and hydrophilic bases are preferred.

[0039] Furthermore, from the viewpoint of film-forming properties and improving the storage stability of the composition, component (C) is preferably a compound that does not contain an unsaturated hydrocarbon chain having 16 or more carbon atoms. From the viewpoint of film-forming properties and improving the storage stability of the composition, the content of a non-volatile base containing an unsaturated hydrocarbon chain having 16 or more carbon atoms in component (C) is preferably 30% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, and even more preferably 0% by mass.

[0040] Examples of lipophilic bases include ester oils and non-polar oils. Specific examples of ester oils include non-volatile synthetic ester oils, and more preferably one or more selected from the group consisting of (i) fatty acid monoesters composed of a fatty acid and a monohydric alcohol, (ii) fatty acid diesters composed of a fatty acid and a dihydric alcohol, (iii) dicarboxylic acid diesters composed of a dicarboxylic acid and a monohydric alcohol, (iv) tricarboxylic acid triesters composed of a tricarboxylic acid and a monohydric alcohol, and (v) glycerol fatty acid triesters.

[0041] (i) Examples of fatty acid monoesters consisting of a fatty acid and a monohydric alcohol include monoesters of saturated fatty acids having 8 to 22 carbon atoms and aliphatic or aromatic ring-containing monohydric alcohols having 1 to 24 carbon atoms. Examples include cetyl octanoate, cetyl 2-ethylhexanoate, ethyl laurate, hexyl laurate, isopropyl myristate, myristyl myristate, hexadecyl myristate, 2-hexyldecyl myristate, octyldodecyl myristate, isopropyl palmitate, ethylhexyl palmitate, hexadecyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, butyl stearate, 2-ethylhexyl stearate, isocetyl stearate, isocetyl isostearate, isononyl isononanoate, isotridecyl isononanoate, etc.

[0042] (ii) Examples of fatty acid diesters consisting of a fatty acid and a dihydric alcohol include diesters of saturated fatty acids having 8 to 22 carbon atoms and aliphatic or aromatic dihydric alcohols having 1 to 12 carbon atoms, such as ethylene glycol di-2-ethylhexanoate, ethylene glycol dilaurate, ethylene glycol distearate, neopentyl glycol dicaprate, neopentyl glycol diethylhexanoate, di(caprylic / capric acid)propanediol, and propanediol diisostearate.

[0043] (iii) Examples of dicarboxylic acid diesters consisting of a dicarboxylic acid and a monohydric alcohol include diesters of an aliphatic or aromatic dicarboxylic acid having 4 to 18 carbon atoms and an aliphatic or aromatic ring-containing monohydric alcohol having 1 to 24 carbon atoms, such as 2-ethylhexyl succinate, dibutyl adipate, diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, diethyl sebacate, diisopropyl sebacate, di-2-ethylhexyl sebacate, and diisononyl phthalate.

[0044] (iv) Examples of tricarboxylic acid triesters comprising a tricarboxylic acid and a monohydric alcohol include triesters of an aliphatic or aromatic tricarboxylic acid having 5 to 12 carbon atoms and an aliphatic or aromatic ring-containing monohydric alcohol having 1 to 24 carbon atoms, such as triisodecyl trimellitic acid.

[0045] Furthermore, (v) Glycerin fatty acid triesters include triesters of glycerin and saturated fatty acids having 8 to 22 carbon atoms, such as glycerin tri-2-ethylhexanoate, glycerin trimyristate, glycerin tri-2-heptylundecanoate, and tristearin.

[0046] In addition to the ester oils listed in (i) to (v) above, alkyl benzoate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, dipentaerythritol fatty acid ester, diisostearyl malate, glyceryl di-2-heptylundecanoate, castor oil fatty acid methyl ester, N-lauroyl-L-glutamate-2-octyldodecyl, 2-hexyldecyl adipic acid, etc. can also be used.

[0047] Among the above, the ester oil is more preferably one or more selected from the group consisting of (i) fatty acid monoesters composed of a fatty acid and a monohydric alcohol, and (iii) dicarboxylic acid diesters composed of a dicarboxylic acid and a monohydric alcohol; even more preferably one or more selected from the group consisting of fatty acid monoesters composed of a fatty acid and a monohydric alcohol having 1 to 24 carbon atoms, and dicarboxylic acid diesters composed of a dicarboxylic acid having 4 to 18 carbon atoms and a monohydric alcohol having 1 to 24 carbon atoms; and even more preferably one or more selected from the group consisting of isopropyl myristate, dibutyl adipate, diethyl sebacate, and diisopropyl sebacate.

[0048] Specific examples of non-polar oils include non-volatile hydrocarbon oils, silicone oils, and fluorinated oils. Examples of hydrocarbon oils include liquid paraffin and squalane; examples of silicone oils include dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, and higher alcohol-modified organopolysiloxane; and examples of fluorinated oils include fluoropolyethers and perfluoroalkyl ether silicones.

[0049] The hydrophilic base is preferably one or more selected from the group consisting of polyols and lower amines. Specific examples of polyols include non-volatile alkylene glycols, polyalkylene glycols, and glycerin compounds. Examples of alkylene glycols include ethylene glycol, propylene glycol, 1,3-propanediol, 1,3-butylene glycol (1,3-butanediol), and 1,2-pentanediol. Examples of polyalkylene glycols include diethylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, and polyoxyethylene-polyoxypropylene glycol. Examples of glycerin compounds include glycerin, diglycerin, and triglycerin. Polyethylene glycol, polypropylene glycol, and polyoxyethylene-polyoxypropylene glycol preferably have a weight-average molecular weight of 10,000 or less.

[0050] In this specification, "lower amine" preferably means an amine having 9 or fewer carbon atoms, more preferably amine having 2 to 9 carbon atoms. From the viewpoint of non-volatility, improving the film-forming properties of the composition, skin applicability and quick-drying properties, and enhancing the sustained release of component (A) to the skin, the lower amine is preferably an alkanolamine. Specific examples of alkanolamines include triethanolamine, diethanolamine, monoethanolamine, triisopropanolamine, diisopropanolamine, monoisopropanolamine, and 2-amino-2-methylpropanol.

[0051] Component (C) may consist of one or more types. Among the above, component (C) is preferably one or more selected from the group consisting of ester oils, nonpolar oils, polyols, and alkanolamines, more preferably one or more selected from the group consisting of isopropyl myristate, dibutyl adipate, diethyl sebacate, diisopropyl sebacate, propylene glycol, 1,3-butylene glycol, 1,2-pentanediol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene / polyoxypropylene glycol, glycerin, diglycerin, triethanolamine, monoethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol, and even more preferably one or more selected from the group consisting of isopropyl myristate, diethyl sebacate, triethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol.

[0052] <Component (D): Volatile solvent> The composition of the present invention contains a volatile solvent as component (D) (excluding those corresponding to component (A)). Component (D) contributes to improving the coatability, quick-drying properties, and storage stability of the composition. The definition of "volatile solvent" in component (D) is as stated above.

[0053] Component (D) may include volatile substances such as alcohols, ketones, esters, hydrocarbons, and silicones. The alcohol used as component (D) is preferably a lower alcohol. A "lower alcohol" is preferably a monohydric alcohol having 4 or fewer carbon atoms, and includes methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, and tert-butyl alcohol. Examples of ketones used as component (D) include acetone, ethyl methyl ketone, and methyl isobutyl ketone; examples of esters include methyl acetate, ethyl acetate, and butyl acetate; examples of hydrocarbons include volatile liquid paraffin; and examples of silicones include linear polydimethylsiloxane and cyclic siloxane.

[0054] Component (D) may consist of one or more types. From the viewpoint of improving the applicability and quick-drying properties of the composition, the solubility or dispersibility of components (A) to (C), and the storage stability of the composition, component (D) is preferably a lower alcohol, and more preferably one or more selected from the group consisting of ethanol and isopropyl alcohol.

[0055] <Ingredients (E): Water> The composition of the present invention contains water as component (E). Component (E) contributes to improving storage stability and other properties. There are no particular restrictions on component (E), and for example, ion-exchanged water, pure water, distilled water, etc. can be used.

[0056] <Other ingredients> In addition to the above-mentioned components, the topical composition of the present invention may appropriately contain other components that are commonly incorporated into topical compositions, as long as they do not impair the purpose of the present invention. Examples of such components include surfactants, water-soluble polymers, antioxidants, ultraviolet absorbers, vitamins, preservatives, pH adjusters, fragrances, plant extracts other than component (A), moisturizers, colorants, cooling agents, antiperspirants, skin activators, and the like.

[0057] <Content> From the viewpoint of obtaining an external preparation composition that can sustainably release the active ingredient into the skin, has good film-forming properties, is highly applicable to the skin, dries quickly, and is excellent in suppressing stickiness and tightness of the formed film, as well as improving appearance and durability, the content of each component in the external preparation composition of the present invention is preferably as follows.

[0058] From the viewpoint of ensuring sufficient efficacy as a pharmacoactive ingredient, the content of component (A) in the composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 1.0% by mass or more. From the viewpoint of improving the storage stability of the composition, it is preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, even more preferably 10% by mass or less, and even more preferably 5.0% by mass or less. Furthermore, the content of component (A) in the composition is preferably 0.001% by mass or more and 30% by mass or less, more preferably 0.005% by mass or more and 20% by mass or less, even more preferably 0.01% by mass or more and 15% by mass or less, even more preferably 0.1% by mass or more and 10% by mass or less, and even more preferably 1.0% by mass or more and 5.0% by mass or less.

[0059] If component (A) contains glycol salicylate, the content of glycol salicylate in the composition is preferably 0.1% by mass or more and 30% by mass or less, more preferably 0.5% by mass or more and 20% by mass or less, even more preferably 1.0% by mass or more and 15% by mass or less, even more preferably 2.0% by mass or more and 12% by mass or less, and even more preferably 2.0% by mass or more and 5.0% by mass or less. If component (A) contains loxoprofen sodium, the content of loxoprofen sodium in the composition is preferably 0.01% by mass or more and 20% by mass or less, more preferably 0.05% by mass or more and 10% by mass or less, and even more preferably 0.1% by mass or more and 5.0% by mass or less. If component (A) contains felbinac, the felbinac content in the composition is preferably 0.01% by mass or more and 30% by mass or less, more preferably 0.1% by mass or more and 20% by mass or less, even more preferably 0.5% by mass or more and 15% by mass or less, even more preferably 1.0% by mass or more and 10% by mass or less, and even more preferably 1.5% by mass or more and 5.0% by mass or less. If component (A) contains l-menthol, the l-menthol content in the composition is preferably 0.01% by mass or more and 30% by mass or less, more preferably 0.1% by mass or more and 20% by mass or less, and even more preferably 0.5% by mass or more and 10% by mass or less. If component (A) contains nonylic acid vanillylamide, the content of nonylic acid vanillylamide in the composition is preferably 0.001% by mass or more and 15% by mass or less, more preferably 0.005% by mass or more and 10% by mass or less, even more preferably 0.01% by mass or more and 5.0% by mass or less, even more preferably 0.01% by mass or more and 1.0% by mass or less, and even more preferably 0.01% by mass or more and 0.1% by mass or less.

[0060] The content of component (B) in the 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 0.5% by mass or more, and even more preferably 1.0% by mass or more, from the viewpoint of film-forming properties and durability of the film, and preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less, even more preferably 12% by mass or less, and even more preferably 5.0% by mass or less. Furthermore, the content of component (B) in the composition is preferably 0.01% by mass or more and 30% by mass or less, more preferably 0.05% by mass or more and 25% by mass or less, even more preferably 0.1% by mass or more and 20% by mass or less, even more preferably 0.5% by mass or more and 12% by mass or less, and even more preferably 1.0% by mass or more and 5.0% by mass or less.

[0061] If component (B) contains an (acrylates / diacetone acrylamide) copolymer, the content of the copolymer in the composition is more preferably 0.1% by mass or more and 15% by mass or less, more preferably 0.5% by mass or more and 10% by mass or less, and more preferably 1.5% by mass or more and 5.0% by mass or less, and if component (B) contains an acrylamide / methoxypolyethylene glycol methacrylate copolymer, the content of the copolymer in the composition is more preferably 0.1% by mass or more and 10% by mass or less, and component ( If component (B) contains ethylcellulose, the ethylcellulose content in the composition is more preferably 0.1% by mass or more and 20% by mass or less. If component (B) contains hypromellose phthalate, the hypromellose phthalate content in the composition is more preferably 0.1% by mass or more and 20% by mass or less, more preferably 0.5% by mass or more and 15% by mass or less, more preferably 1.0% by mass or more and 10.0% by mass or less, and more preferably 1.5% by mass or more and 5.0% by mass or less. If component (B) contains polyvinyl butyral, the polyvinyl butyral content in the composition is more preferably 0.1% by mass or more and 20% by mass or less.

[0062] The content of component (C) in the composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 1.0% by mass or more, from the viewpoint of improving the sustained release of component (A) to the skin and suppressing the feeling of tightness of the formed film, and preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 10% by mass or less, even more preferably 8.0% by mass or less, and even more preferably 5.0% by mass or less, from the viewpoint of suppressing the stickiness of the formed film and improving the abrasion resistance. Furthermore, the content of component (C) in the composition is preferably 0.001% by mass or more and 30% by mass or less, more preferably 0.005% by mass or more and 20% by mass or less, even more preferably 0.1% by mass or more and 15% by mass or less, even more preferably 0.01% by mass or more and 10% by mass or less, even more preferably 0.1% by mass or more and 8.0% by mass or less, and even more preferably 1.0% by mass or more and 5.0% by mass or less.

[0063] If component (C) contains isopropyl myristate, the content of isopropyl myristate in the composition is more preferably 0.1% by mass or more and 10% by mass or less, more preferably 0.25% by mass or more and 7.5% by mass or less, and more preferably 0.5% by mass or more and 5.0% by mass or less. If component (C) contains diethyl sebacate, the content of diethyl sebacate in the composition is more preferably 0.1% by mass or more and 10% by mass or less, more preferably 0.25% by mass or more and 7.5% by mass or less, and more preferably 0.5% by mass or more and 5.0% by mass or less. If component (C) contains diisopropanolamine, the content of diisopropanolamine in the composition is more preferably 0.1% by mass or more and 5.0% by mass or less, more preferably 0.5% by mass or more and 4.0% by mass or less, and more preferably 1.0% by mass or more and 3.0% by mass or less; if component (C) contains triethanolamine, the content of triethanolamine in the composition is more preferably 0.1% by mass or more and 5.0% by mass or less, and more preferably 1.0% by mass or more and 3.0% by mass or less; and if component (C) contains 2-amino-2-methylpropanol, the content of 2-amino-2-methylpropanol in the composition is more preferably 0.01% by mass or more and 3.0% by mass or less.

[0064] The content of component (D) in the composition is preferably 10% by mass or more, more preferably 25% by mass or more, even more preferably 45% by mass or more, and even more preferably 65% ​​by mass or more, from the viewpoint of improving the applicability, quick-drying properties, and storage stability of the composition, and preferably 95% by mass or less, more preferably 90% by mass or less, even more preferably 80% by mass or less, and even more preferably 75% by mass or less, from the viewpoint of maintaining the applicability and film-forming properties of the composition. Furthermore, the content of component (D) in the composition is preferably 10% by mass or more and 95% by mass or less, more preferably 25% by mass or more and 90% by mass or less, even more preferably 45% by mass or more and 80% by mass or less, and even more preferably 65% ​​by mass or more and 75% by mass or less. When component (D) contains ethanol, the ethanol content in the composition is more preferably 30% by mass or more and 90% by mass or less, more preferably 30% by mass or more and 75% by mass or less, and more preferably 45% by mass or more and 75% by mass or less. When component (D) contains isopropyl alcohol, the isopropyl alcohol content in the composition is more preferably 30% by mass or more and 90% by mass or less, more preferably 30% by mass or more and 75% by mass or less, and more preferably 45% by mass or more and 75% by mass or less.

[0065] Furthermore, the content of component (E) in the composition is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 5% by mass or more, and even more preferably 13% by mass or more, from the viewpoint of improving the applicability and storage stability of the composition and maintaining film-forming properties. From the viewpoint of the applicability of the composition, maintaining the quick-drying properties of the composition, improving storage stability and maintaining a good appearance during low-temperature storage, it is preferably 70% by mass or less, more preferably 50% by mass or less, even more preferably 30% by mass or less, even more preferably 25% by mass or less, even more preferably 22% by mass or less, even more preferably 21% by mass or less, and even more preferably 20% by mass or less. Furthermore, the content of component (E) in the composition is preferably 0.1% by mass or more and 70% by mass or less, more preferably 0.5% by mass or more and 50% by mass or less, even more preferably 0.5% by mass or more and 30% by mass or less, even more preferably 0.5% by mass or more and 25% by mass or less, even more preferably 0.5% by mass or more and 22% by mass or less, even more preferably 5% by mass or more and 22% by mass or less, even more preferably 5% by mass or more and 21% by mass or less, and even more preferably 13% by mass or more and 20% by mass or less. The content of component (E) in the composition may be greater than 30% by mass and less than or equal to 70% by mass, from the viewpoint of improving the applicability and storage stability of the composition, maintaining film-forming properties, and maintaining a good appearance during low-temperature storage.

[0066] The total content of components (A) to (E) in the composition is preferably 50% by mass or more, more preferably 70% by mass or more, even more preferably 80% by mass or more, and even more preferably 90% by mass or more, and also 100% by mass or less, from the viewpoint of obtaining the effects of the present invention.

[0067] The mass ratio of component (A) to component (B) in the composition [(A) / (B)] is preferably 0.01 or higher, more preferably 0.02 or higher, even more preferably 0.03 or higher, even more preferably 0.05 or higher, even more preferably 0.10 or higher, and even more preferably 0.15 or higher, from the viewpoint of improving the sustained release of component (A) to the skin. From the viewpoint of improving the applicability of the composition, storage stability, film formation, and film durability, it is preferably 50 or lower, more preferably 30 or lower, even more preferably 20 or lower, even more preferably 10 or lower, even more preferably 5.0 or lower, and even more preferably 3.0 or lower. Furthermore, the mass ratio [(A) / (B)] in the composition is preferably 0.01 to 50, more preferably 0.02 to 30, even more preferably 0.03 to 20, even more preferably 0.05 to 10, even more preferably 0.10 to 5.0, and even more preferably 0.15 to 3.0.

[0068] The mass ratio of component (A) to component (C) in the composition [(A) / (C)] is preferably 0.01 or higher, more preferably 0.02 or higher, even more preferably 0.03 or higher, even more preferably 0.05 or higher, even more preferably 0.10 or higher, and even more preferably 0.15 or higher, from the viewpoint of improving the sustained release of component (A) to the skin and improving the storage stability of the composition. From the viewpoint of improving the applicability and storage stability of the composition and the durability of the formed film, it is preferably 10 or lower, more preferably 5.0 or lower, even more preferably 3.0 or lower, even more preferably 2.5 or lower, even more preferably 2.0 or lower, and even more preferably 1.5 or lower. Furthermore, the mass ratio [(A) / (C)] in the composition is preferably 0.01 to 10, more preferably 0.02 to 5.0, even more preferably 0.03 to 3.0, even more preferably 0.05 to 2.5, even more preferably 0.10 to 2.0, and even more preferably 0.15 to 1.5.

[0069] The mass ratio of component (C) to component (B) in the composition [(C) / (B)] is preferably 0.05 or higher, more preferably 0.10 or higher, even more preferably 0.20 or higher, and even more preferably 0.50 or higher, from the viewpoint of improving the sustained release of component (A) to the skin and improving film formation, and from the viewpoint of the durability of the formed film, it is preferably 50 or lower, more preferably 35 or lower, even more preferably 20 or lower, even more preferably 10 or lower, even more preferably 5.0 or lower, and even more preferably 3.5 or lower. Furthermore, the mass ratio [(C) / (B)] in the composition is preferably 0.05 to 50, more preferably 0.10 to 35, even more preferably 0.20 to 20, even more preferably 0.20 to 10, even more preferably 0.20 to 5.0, even more preferably 0.50 to 5.0, and even more preferably 0.50 to 3.5. Alternatively, the mass ratio [(C) / (B)] in the composition is preferably 0.05 to 50, more preferably 0.05 to 35, even more preferably 0.05 to 20, even more preferably 0.05 to 10, even more preferably 0.05 to 5.0, even more preferably 0.05 to 5.0, and even more preferably 0.05 to 3.5.

[0070] The mass ratio of component (E) to component (D) in the composition [(E) / (D)] is preferably 0.005 or higher, more preferably 0.05 or higher, even more preferably 0.10 or higher, even more preferably 0.16 or higher, and even more preferably 0.20 or higher, from the viewpoint of improving the applicability, quick-drying properties, and storage stability of the composition. Similarly, it is preferably 3.0 or lower, more preferably 2.0 or lower, even more preferably 1.0 or lower, even more preferably 0.80 or lower, and even more preferably 0.40 or lower. Furthermore, the mass ratio [(E) / (D)] in the composition is preferably 0.005 to 3.0, more preferably 0.05 to 2.0, even more preferably 0.10 to 1.0, even more preferably 0.16 to 0.80, and even more preferably 0.20 to 0.40.

[0071] The mass ratio of component (B) to the total content of components (D) and (E) in the composition [(B) / {(D)+(E)}] is preferably 0.001 or more, more preferably 0.01 or more, and even more preferably 0.02 or more, from the viewpoint of improving film formation, and preferably 1.0 or less, more preferably 0.50 or less, even more preferably 0.20 or less, even more preferably 0.12 or less, and even more preferably 0.10 or less, from the viewpoint of improving coatability and quick drying. Furthermore, the mass ratio in the composition [(B) / {(D)+(E)}] is preferably 0.001 or more and 1.0 or less, more preferably 0.01 or more and 0.50 or less, even more preferably 0.01 or more and 0.20 or less, even more preferably 0.01 or more and 0.12 or even more preferably 0.02 or more and 0.10 or less.

[0072] The mass ratio of component (A) to the total amount of components (B) and (C) in the composition [(A) / {(B)+(C)}] is preferably 0.001 or higher, more preferably 0.005 or higher, even more preferably 0.01 or higher, even more preferably 0.05 or higher, and even more preferably 0.10 or higher, from the viewpoint of ensuring sufficient efficacy as a pharmacoactive ingredient and improving the sustained release of component (A) to the skin. From the viewpoint of suppressing crystallization of component (A), the durability of the formed film, and improving the storage stability of the composition, it is preferably 5.00 or lower, more preferably 3.00 or lower, even more preferably 2.50 or lower, even more preferably 2.40 or lower, even more preferably 2.00 or lower, even more preferably 1.60 or lower, even more preferably 1.00 or lower, and even more preferably 0.60 or lower. Furthermore, the mass ratio [(A) / {(B)+(C)}] in the composition is preferably 0.001 to 5.00, more preferably 0.005 to 3.00, even more preferably 0.01 to 2.50, even more preferably 0.05 to 2.50, even more preferably 0.10 to 2.50, even more preferably 0.10 to 1.60, even more preferably 0.10 to 1.00, and even more preferably 0.10 to 0.60. In addition, from the viewpoint of suppressing crystallization of component (A) in particular, it is preferably 0.001 to 2.40, more preferably 0.005 to 2.00, even more preferably 0.01 to 1.60, even more preferably 0.05 to 1.00, and even more preferably 0.05 to 0.60.

[0073] <Viscosity> The viscosity of the external preparation composition of the present invention at 25°C is 1.0 mPa·s or more from the viewpoint of improving the applicability to the skin and the uniformity of the formed film, preferably 3.0 mPa·s or more, more preferably 5.0 mPa·s or more, still more preferably 10.0 mPa·s or more. Further, from the viewpoint of improving the quick-drying property of the composition and the appearance improvement of the formed film, it is 10,000 mPa·s or less, preferably 7,500 mPa·s or less, more preferably 5,000 mPa·s or less, still more preferably 3,000 mPa·s or less, even more preferably 2,000 mPa·s or less, even more preferably 1,000 mPa·s or less, even more preferably 700 mPa·s or less. And the viscosity of the external preparation composition at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less, preferably 3.0 mPa·s or more and 7,500 mPa·s or less, more preferably 3.0 mPa·s or more and 5,000 mPa·s or less, still more preferably 3.0 mPa·s or more and 3,000 mPa·s or less, even more preferably 3.0 mPa·s or more and 2,000 mPa·s or less, even more preferably 5.0 mPa·s or more and 1,000 mPa·s or less, even more preferably 10.0 mPa·s or more and 700 mPa·s or less. The viscosity of the external preparation composition at 25°C is the value measured by a vibration viscometer for a composition of 1,000 mPa·s or less and by a B-type rotational viscometer for a composition exceeding 1,000 mPa·s, and specifically, it can be measured by the method described in the examples.

[0074] <Δ(SP A -SP B+C )> Further, from the viewpoint of improving the sustained release property of component (A) to the skin and the storage stability improvement of the composition, the present invention's composition has an absolute value of the difference [Δ(SP A ) between the SP value (SP B+C ) of component (A) and the SP value (SP A -SP B+C)] is preferably 0.10 or more, more preferably 0.15 or more, even more preferably 0.20 or more, even more preferably 0.30 or more, even more preferably 0.50 or more, and also preferably 10.00 or less, more preferably 8.00 or less, even more preferably 7.00 or less, and even more preferably 5.00 or less. And, [Δ(SP A -SP B+C The ) is preferably 0.10 to 10.00, more preferably 0.15 to 8.00, even more preferably 0.20 to 7.00, even more preferably 0.30 to 5.00, and even more preferably 0.50 to 5.00. [Δ(SP A -SP B+C If the ratio is 0.10 or higher, the compatibility between component (A) and the film will not be excessively high, the stringiness of the formed film will be suppressed, and the sustained release of component (A) to the skin will be well maintained. If the ratio is 10.00 or lower, the compatibility between component (A) and the film will not be excessively low, and the crystallization of crystalline component (A) will also be suppressed, thus maintaining the sustained release of component (A) to the skin. SP value of component (A) (SP A ), and the SP value (SP) of the mixture of component (B) and component (C). B+C ) can be calculated using the same method as described above.

[0075] <Dosage Form, etc.> The topical formulation composition of the present invention is preferably used as a skin topical formulation composition. The dosage form of the topical composition of the present invention may be any form that has a viscosity within the above-mentioned range and is applicable to the skin. Examples include lotion formulations, gel formulations, ointment formulations, cream formulations, or foam formulations comprising the topical composition of the present invention; aerosol formulations or pump-spray formulations using the topical composition of the present invention; and so on. Examples of foam formulations include formulations in which the topical composition of the present invention is filled into a pump foamer or the like and dispensed in a foamy form. Furthermore, the composition of the present invention can also be electrostatically sprayed onto the skin using an electrostatic spraying device. Electrostatic spraying will be described later.

[0076] The aerosol formulation contains the topical composition described above and a propellant. The aerosol formulation using the topical composition of the present invention can provide a cooling sensation, etc., when the composition is sprayed onto the skin. In aerosol formulations, the topical preparation composition used as the aerosol stock solution and its preferred embodiment are the same as described above. That is, the content and viscosity of components (A) to (E) in the aerosol stock solution are preferably within the above range. Examples of propellants used in aerosol formulations include ethane, propane, n-butane, isobutane, isopentane, and mixtures thereof, such as liquefied petroleum gas (LPG); ethers such as dimethyl ether; compressed gases such as nitrogen and carbon dioxide; and one or more of these can be used.

[0077] In aerosol formulations, the ratio of the topical preparation composition, which is the aerosol concentrate, to the propellant is not particularly limited as long as the topical preparation composition can be sprayed onto the skin. However, from the viewpoint of aerosol performance and the stability of component (A), the mass ratio of the topical preparation composition to the propellant is preferably in the range of 1:0.01 to 1:10, and more preferably in the range of 1:0.05 to 1:7.5. When the propellant is LPG, the mass ratio of the topical formulation composition to LPG is more preferably 1:0.5 to 1:5; when the propellant is dimethyl ether, the mass ratio of the topical formulation composition to dimethyl ether is more preferably 1:0.1 to 1:5; and when the propellant is carbon dioxide, the mass ratio of the topical formulation composition to carbon dioxide is more preferably 1:0.1 to 1:0.5.

[0078] Examples of aerosol containers used for aerosol formulations include known pressure-resistant containers made of metal, plastic, etc., and double-walled containers in which an inner bag is housed inside a pressure-resistant container. In double-walled containers, it is preferable to fill the inner bag with the topical preparation composition, which is the aerosol concentrate, and to fill the space between the pressure-resistant container and the inner bag with a propellant.

[0079] The method for preparing the aerosol formulation is not particularly limited. For example, it can be prepared by filling an aerosol container with an external preparation composition, which is the aerosol concentrate, attaching a valve, and then filling it with a propellant through the valve.

[0080] Furthermore, a pump-spray type formulation is a formulation in which the topical composition of the present invention is filled into a pump-spray container for use.

[0081] [How to use] The present invention also provides a method for using a topical preparation composition, comprising the steps of applying the topical preparation composition to the skin and then drying it. According to the method of the present invention, by applying the topical preparation composition to the skin and then drying it, a film containing the active ingredient (A) can be formed on the skin surface. The film has excellent moisture resistance and abrasion resistance, and the sustained release of ingredient (A) to the skin is high, so that ingredient (A) can be continuously released to the skin. Hereinafter, the step of applying the topical preparation composition to the skin and then drying it will also be referred to as the "film formation step".

[0082] The method of applying the topical preparation composition to the skin can be appropriately selected depending on the dosage form of the topical preparation composition, for example, by application, casting, or spraying. Among these, application by application or spraying is preferred. After applying the topical preparation composition, the component (D) volatilizes by drying by natural drying or the like, and a film containing components (A) to (C) is formed on the skin surface.

[0083] In the method of the present invention, when the topical composition is applied directly to the skin, the topical composition can be applied by hand or using an applicator such as a metal roller, plastic roller, sponge-like porous body, or brush. In the method of the present invention, when applying a topical preparation composition to the skin by spraying, methods for spraying the composition include using an aerosol, a pump spray, or an electrostatic spray device. For aerosols and pump sprays, the topical preparation composition can be prepared using the topical preparation composition as a stock solution, and the topical preparation composition can be sprayed onto the skin using the prepared preparation. Specifically, the electrostatic spray device comprises a storage section capable of containing the topical agent composition, a nozzle for dispensing the topical agent composition, a power supply for applying voltage to the nozzle, and means for supplying the topical agent composition from the storage section to the nozzle. One embodiment of this device is a handheld electrostatic spray device having dimensions that allow it to be held in one hand. As an electrostatic spraying device, those exemplified in International Publication No. 2018 / 194140, etc., can be used.

[0084] The application site of the topical composition is not particularly limited, but is preferably the skin surface of a body part, more preferably the skin surface of the hands, arms, feet, legs, or torso.

[0085] There are no particular restrictions on the amount of the topical formulation composition applied to the skin, but from the viewpoint of sufficiently releasing component (A) to the skin, 0.5 μL / cm³ is preferred. 2 More preferably, 1 μL / cm² 2 More preferably 3 μL / cm² 2 That concludes the explanation. Furthermore, from the viewpoint of the appearance (transparency) of the formed film, a concentration of 100 μL / cm² is preferred. 2 More preferably, 50 μL / cm² 2 The following applies:

[0086] [Method for manufacturing the coating] The present invention also provides a method for producing a coating, comprising the step of applying the topical composition directly to the skin by application or spraying. When the topical composition is applied directly to the skin, it can be applied by hand or using an applicator such as a metal roller, as described above. When the topical composition is applied by spraying it directly onto the skin, methods for spraying the composition include using an aerosol, pump spray, or electrostatic spray device.

[0087] An embodiment of a method for producing a coating when applying a topical preparation composition to the skin by electrostatic spraying using a topical preparation composition and an electrostatic spraying device is described below. First, the external agent composition is filled into the housing of the handheld electrostatic spray device. The user, that is, the person who will be forming a film on the skin application area by electrostatic spraying, holds the device in their hand and directs one end of the device, where the nozzle is located, towards the application area to be sprayed. Under these conditions, the electrostatic spraying method can be performed by switching on the electrostatic spraying device. When the device is powered on, an electric field is generated between the nozzle and the skin, a high positive voltage is applied to the nozzle, and the skin becomes the negative electrode. When an electric field is generated between the nozzle and the skin, the topical agent composition at the tip of the nozzle is polarized by electrostatic induction, and the tip becomes cone-shaped. From the tip of the cone, charged droplets of the topical agent composition are ejected into the air along the electric field toward the skin. As the volatile solvent, component (D), evaporates from the charged topical agent composition ejected into the space, the charge density on the surface of the topical agent composition becomes excessive, and it spreads into the space while repeatedly becoming atomized by Coulomb repulsion, reaching the skin. In this case, by appropriately adjusting the viscosity of the topical agent composition, the amount of volatile solvent, the type and amount of polymer, the flow rate and voltage, etc., the sprayed composition can reach the application site in droplet form. Preferably, while being discharged into space, component (D) is allowed to volatilize from the droplet, and component (B), which is the main film-forming component, is allowed to solidify while being stretched and deformed by the potential difference to form fibers, which are then deposited on the application site. As a result, a porous film consisting of fiber deposits is formed on the surface of the application site.

[0088] With regard to the embodiments described above, the present invention further discloses the following embodiments. <1> A topical composition comprising (A) a pharmaceutically active ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the viscosity at 25°C is 1.0 mPa·s or more, preferably 3.0 mPa·s or more, more preferably 5.0 mPa·s or more, even more preferably 10.0 mPa·s or more, and 10,000 mPa·s or less, preferably 7,500 mPa·s or less, more preferably 5,000 mPa·s or less, even more preferably 3,000 mPa·s or less, even more preferably 2,000 mPa·s or less, even more preferably 1,000 mPa·s or less, and even more preferably 700 mPa·s or less. <2> A topical preparation composition comprising (A) a pharmacoactive ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of ingredient (E) in the topical preparation composition is 0.1% by mass or more and 30% by mass or less, the mass ratio of ingredient (A) to the total amount of ingredients (B) and (C) [(A) / {(B)+(C)}] is 0.001 or more and 2.40 or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less. <3> A topical preparation composition comprising (A) a pharmacoactive ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of ingredient (E) in the topical preparation composition is greater than 30% by mass and 70% by mass or less, the mass ratio of ingredient (A) to the total amount of ingredients (B) and (C) [(A) / {(B)+(C)}] is 0.001 or more and 2.40 or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less. <4> A topical preparation composition comprising (A) an anti-inflammatory and analgesic component, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of component (B) in the topical preparation composition is 0.1% by mass or more and 15% by mass or less, the mass ratio of component (C) to component (B) in the topical preparation composition [(C) / (B)] is 0.05 or more and 3.5 or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less. <5> A topical preparation composition comprising (A) one or more pharmaceutically active ingredients selected from the group consisting of glycol salicylate, diclofenac sodium, loxoprofen sodium, felbinac, indomethacin, piroxicam, flurbiprofen, methyl salicylate, ketoprofen, and nonylic acid vanillylamide, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of component (C) in the topical preparation composition is 5.0% by mass or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less. <6> The viscosity of the topical composition at 25°C is preferably 3.0 mPa·s or more, more preferably 5.0 mPa·s or more, even more preferably 10.0 mPa·s or more, preferably 7,500 mPa·s or less, more preferably 5,000 mPa·s or less, even more preferably 3,000 mPa·s or less, even more preferably 2,000 mPa·s or less, even more preferably 1,000 mPa·s or less, and even more preferably 700 mPa·s or less. <2> ~ <5> A topical composition according to any one of the following. <7> The SP value of component (B) is preferably 17.00 or higher, more preferably 18.00 or higher, even more preferably 19.00 or higher, even more preferably 20.00 or higher, preferably 27.00 or lower, more preferably 25.00 or lower, even more preferably 24.00 or lower, and even more preferably 23.00 or lower. <1> ~ <6> A topical composition according to any one of the following. <8> SP value of component (A) (SP A ) and the SP value (SP) of the mixture of component (B) and component (C). B+C The absolute value of the difference between ) and [Δ(SP A -SP B+C)] is preferably 0.10 or higher, more preferably 0.15 or higher, even more preferably 0.20 or higher, even more preferably 0.30 or higher, even more preferably 0.50 or higher, and also preferably 10.00 or lower, more preferably 8.00 or lower, even more preferably 7.00 or lower, and even more preferably 5.00 or lower. <1> ~ <7> A topical composition according to any one of the following. <9> Component (A) contains one or more selected from the group consisting of anti-inflammatory and analgesic components, local irritants, blood circulation promoting components, antihistamine components, herbal components, antipruritic components, local anesthetic components, keratolytic components, bactericidal components, and antimicrobial components, preferably one or more selected from the group consisting of anti-inflammatory and analgesic components, local irritants, blood circulation promoting components, antihistamine components, and herbal components, more preferably one or more selected from the group consisting of anti-inflammatory and analgesic components and local irritants. <1> ~ <3> , <6> ~ <8> A topical composition according to any one of the following. <10> Component (A) contains one or more selected from the group consisting of glycol salicylate, methyl salicylate, diclofenac sodium, loxoprofen sodium, ketoprofen, felbinac, indomethacin, piroxicam, flurbiprofen, glycyrrhizic acid, glycyrrhetinic acid, l-menthol, dl-camphor, nonylic acid vanillylamide, peppermint oil, benzyl nicotinate, sodium polyethylene sulfonate, tocopherol acetate, diphenhydramine, chlorpheniramine maleate, chili pepper, eucalyptus oil, and Phellodendron amurense, preferably containing one or more selected from the group consisting of glycol salicylate, loxoprofen sodium, felbinac, l-menthol, and nonylic acid vanillylamide. <1> ~ <3> , <6> ~ <9> A topical composition according to any one of the following. <11> The SP value of component (A) is preferably 15.00 or higher, more preferably 18.00 or higher, even more preferably 19.00 or higher, even more preferably 19.50 or higher, preferably 35.00 or lower, more preferably 27.00 or lower, even more preferably 24.00 or lower, and even more preferably 22.00 or lower. <1> ~ <10> A topical composition according to any one of the following. <12> Component (B) is a film-forming, water-insoluble polymer, preferably one or more water-insoluble polymers selected from the group consisting of acrylic polymers, cellulose polymers, and vinyl polymers. <1> ~ <11> A topical composition according to any one of the following. <13> The acrylic polymer contains at least one structural unit derived from a monomer having a (meth)acrylic group, and includes (acrylates / diacetone acrylamide) copolymer, acrylamide / methoxypolyethylene glycol methacrylate copolymer, acrylic acid / octyl acrylate copolymer, acrylic acid ester / vinyl acetate copolymer, 2-ethylhexyl acrylate / methyl acrylate / acrylic acid / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / vinyl acetate / hydroxyethyl acrylate / glycidyl methacrylate copolymer, and 2-ethylhexyl acrylate One or more selected from the group consisting of ethylhexyl diacetone acrylamide acetoacetoxyethyl methacrylate methyl methacrylate copolymer, 2-ethylhexyl acrylate vinylpyrrolidone copolymer, 2-ethylhexyl acrylate 2-ethylhexyl methacrylate methacrylate dodecyl methacrylate copolymer, ethyl acrylate methyl methacrylate copolymer, ethyl acrylate methyl methacrylate methacrylate acid trimethylammonium ethyl methacrylate copolymer, and methyl methacrylate butyl methacrylate dimethylaminoethyl methacrylate copolymer. <12> The topical composition described above. <14> The aforementioned cellulosic polymer is one or more selected from the group consisting of methylcellulose, ethylcellulose, hypromellose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose phthalate, and hydrophobized (C16-18) hydroxypropylmethylcellulose. <12> The topical composition described above. <15> The vinyl polymer is one or more selected from the group consisting of polyvinyl alcohol and polyvinyl butyral. <12> The topical composition described above. <16> Component (B) is an (acrylates / diacetone acrylamide) copolymer, acrylamide / methoxypolyethylene glycol methacrylate copolymer, acrylic acid / octyl acrylate copolymer, acrylic acid ester / vinyl acetate copolymer, 2-ethylhexyl acrylate / methyl acrylate / acrylic acid / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / vinyl acetate / hydroxyethyl acrylate / glycidyl methacrylate copolymer, 2-ethylhexyl acrylate / diacetone acrylamide / acetoacetoxyethyl methacrylate / methyl methacrylate copolymer, 2-ethylhexyl acrylate / vinylpyrrolidone copolymer, 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, ethyl acrylate / methyl methacrylate copolymer One or more selected from the group consisting of ethyl acrylate / methyl methacrylate / methacrylate-derived trimethylammonium ethyl copolymer, methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, methylcellulose, ethylcellulose, hypromellose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose phthalate, hydrophobized (C16-18) hydroxypropylmethylcellulose, polyvinyl alcohol, and polyvinyl butyral, preferably one or more selected from the group consisting of (acrylates / diacetone acrylamide) copolymer, acrylamide / methoxypolyethylene glycol methacrylate copolymer, ethylcellulose, hypromellose phthalate, and polyvinyl butyral. <1> ~ <15> A topical composition according to any one of the following.

[0089] <17> Component (C) is one or more selected from the group consisting of lipophilic bases, hydrophilic bases, and amphiphilic bases, preferably one or more selected from the group consisting of lipophilic bases and hydrophilic bases. <1> ~ <16> A topical composition according to any one of the following. <18> The content of the non-volatile base containing an unsaturated hydrocarbon chain with 16 or more carbon atoms in component (C) is preferably 30% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, and even more preferably 0% by mass. <1> ~ <17> A topical composition according to any one of the following. <19> Component (C) is one or more selected from the group consisting of ester oils, nonpolar oils, polyols, and alkanolamines. <1> ~ <18> A topical composition according to any one of the following. <20> The ester oil is one or more selected from the group consisting of (i) fatty acid monoesters composed of a fatty acid and a monohydric alcohol, (ii) fatty acid diesters composed of a fatty acid and a dihydric alcohol, (iii) dicarboxylic acid diesters composed of a dicarboxylic acid and a monohydric alcohol, (iv) tricarboxylic acid triesters composed of a tricarboxylic acid and a monohydric alcohol, and (v) glycerin fatty acid triesters; preferably one or more selected from the group consisting of (i) fatty acid monoesters composed of a fatty acid and a monohydric alcohol, and (iii) dicarboxylic acid diesters composed of a dicarboxylic acid and a monohydric alcohol; more preferably one or more selected from the group consisting of fatty acid monoesters composed of a fatty acid and a monohydric alcohol having 1 to 24 carbon atoms, and dicarboxylic acid diesters composed of a dicarboxylic acid having 4 to 18 carbon atoms and a monohydric alcohol having 1 to 24 carbon atoms; even more preferably one or more selected from the group consisting of isopropyl myristate, dibutyl adipate, diethyl sebacate, and diisopropyl sebacate. <19> The topical composition described above. <21> The nonpolar oil is one or more selected from the group consisting of hydrocarbon oils, silicone oils, and fluorinated oils, preferably one or more selected from the group consisting of liquid paraffin, squalane, dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, higher alcohol-modified organopolysiloxane, fluoropolyether, and perfluoroalkyl ether silicone. <19> The topical composition described above. <22> The polyol is one or more selected from the group consisting of alkylene glycols, polyalkylene glycols, and glycerins, preferably one or more selected from the group consisting of ethylene glycol, propylene glycol, 1,3-propanediol, 1,3-butylene glycol (1,3-butanediol), 1,2-pentanediol, diethylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene / polyoxypropylene glycol, glycerin, diglycerin, and triglycerin. <19> The topical composition described above. <23> The alkanolamine is preferably one or more selected from the group consisting of alkanolamines having 9 or fewer carbon atoms, more preferably alkanolamines having 2 to 9 carbon atoms, and more preferably one or more selected from the group consisting of triethanolamine, diethanolamine, monoethanolamine, triisopropanolamine, diisopropanolamine, monoisopropanolamine, and 2-amino-2-methylpropanol. <19> The topical composition described above. <24> Component (C) is one or more selected from the group consisting of isopropyl myristate, dibutyl adipate, diethyl sebacate, diisopropyl sebacate, propylene glycol, 1,3-butylene glycol, 1,2-pentanediol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene / polyoxypropylene glycol, glycerin, diglycerin, triethanolamine, monoethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol, preferably one or more selected from the group consisting of isopropyl myristate, diethyl sebacate, triethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol. <1> ~ <23> A topical composition according to any one of the following. <25> Component (D) is one or more selected from the group consisting of alcohols, ketones, esters, hydrocarbons, and silicones, preferably lower alcohols, more preferably one or more selected from the group consisting of methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, and tert-butyl alcohol, and even more preferably one or more selected from the group consisting of ethanol and isopropyl alcohol. <1> ~ <24> A topical composition according to any one of the following.

[0090] <26> The content of component (A) in the topical preparation composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, even more preferably 1.0% by mass or more, preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, even more preferably 10% by mass or less, and even more preferably 5.0% by mass or less. <1> ~ <25> A topical composition according to any one of the following. <27> The content of component (B) in the topical preparation 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 0.5% by mass or more, even more preferably 1.0% by mass or more, preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less, even more preferably 12% by mass or less, and even more preferably 5.0% by mass or less. <1> ~ <3> , <5> ~ <26> A topical composition according to any one of the following. <28> The content of component (C) in the topical preparation composition is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, even more preferably 1.0% by mass or more, preferably 30% by mass or less, more preferably 20% by mass or less, even more preferably 15% by mass or less, even more preferably 10% by mass or less, even more preferably 8.0% by mass or less, and even more preferably 5.0% by mass or less. <1> ~ <4> , <6> ~ <27> A topical composition according to any one of the following. <29> The content of component (D) in the topical composition is preferably 10% by mass or more, more preferably 25% by mass or more, even more preferably 45% by mass or more, even more preferably 65% ​​by mass or more, preferably 95% by mass or less, more preferably 90% by mass or less, even more preferably 80% by mass or less, and even more preferably 75% by mass or less. <1> ~ <28> A topical composition according to any one of the following. <30> The content of component (E) in the topical preparation composition is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, even more preferably 5% by mass or more, even more preferably 13% by mass or more, preferably 70% by mass or less, more preferably 50% by mass or less, even more preferably 30% by mass or less, even more preferably 25% by mass or less, even more preferably 22% by mass or less, even more preferably 21% by mass or less, and even more preferably 20% by mass or less. <1> , <4> ~ <29> A topical composition according to any one of the following. <31> The mass ratio of component (A) to component (B) in the topical preparation composition [(A) / (B)] is preferably 0.01 or more, more preferably 0.02 or more, even more preferably 0.03 or more, even more preferably 0.05 or more, even more preferably 0.10 or more, even more preferably 0.15 or more, preferably 50 or less, more preferably 30 or less, even more preferably 20 or less, even more preferably 10 or less, even more preferably 5.0 or less, and even more preferably 3.0 or less. <1> ~ <30> A topical composition according to any one of the following. <32> The mass ratio of component (A) to component (C) in the topical preparation composition [(A) / (C)] is preferably 0.01 or more, more preferably 0.02 or more, even more preferably 0.03 or more, even more preferably 0.05 or more, even more preferably 0.10 or more, even more preferably 0.15 or more, preferably 10 or less, more preferably 5.0 or less, even more preferably 3.0 or less, even more preferably 2.5 or less, even more preferably 2.0 or less, and even more preferably 1.5 or less. <1> ~ <31> A topical composition according to any one of the following. <33> The mass ratio of component (C) to component (B) in the topical preparation composition [(C) / (B)] is preferably 0.05 or more, more preferably 0.10 or more, even more preferably 0.20 or more, even more preferably 0.50 or more, preferably 50 or less, more preferably 35 or less, even more preferably 20 or less, even more preferably 10 or less, even more preferably 5.0 or less, and even more preferably 3.5 or less. <1> ~ <3> , <5> ~ <32> A topical composition according to any one of the following. <34> The mass ratio of component (E) to component (D) in the topical preparation composition [(E) / (D)] is preferably 0.005 or more, more preferably 0.05 or more, even more preferably 0.10 or more, even more preferably 0.16 or more, even more preferably 0.20 or more, preferably 3.0 or less, more preferably 2.0 or less, even more preferably 1.0 or less, even more preferably 0.80 or less, and even more preferably 0.40 or less. <1> ~ <33> A topical composition according to any one of the following. <35> The mass ratio of component (B) to the total content of component (D) and component (E) in the topical preparation composition [(B) / {(D)+(E)}] is preferably 0.001 or more, more preferably 0.01 or more, even more preferably 0.02 or more, preferably 1.0 or less, more preferably 0.50 or less, even more preferably 0.20 or less, even more preferably 0.12 or less, and even more preferably 0.10 or less. <1> ~ <34> A topical composition according to any one of the following. <36> The mass ratio of component (A) to the total amount of component (B) and component (C) in the topical preparation composition [(A) / {(B)+(C)}] is preferably 0.001 or more, more preferably 0.005 or more, even more preferably 0.01 or more, even more preferably 0.05 or more, even more preferably 0.10 or more, preferably 5.00 or less, more preferably 3.00 or less, even more preferably 2.50 or less, even more preferably 2.40 or less, even more preferably 2.00 or less, even more preferably 1.60 or less, even more preferably 1.00 or less, and even more preferably 0.60 or less. <1> , <4> ~ <35> A topical composition according to any one of the following. <37> <1> ~ <36> A lotion, gel, ointment, cream, or foam formulation comprising the topical composition described in any one of the above. <38> <1> ~ <36> An aerosol formulation or pump-spray formulation using the topical composition described in any one of the above. <39> The external preparation composition and a propellant are contained, and the mass ratio of the external preparation composition to the propellant is preferably in the range of 1:0.01 to 1:10, more preferably in the range of 1:0.05 to 1:7.5. <38> Aerosol formulation.

[0091] <40> A method for using a topical preparation composition comprising the steps of applying the topical preparation composition, which contains (A) a pharmaceutically active ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, and having a viscosity at 25°C of 1.0 mPa·s or more, preferably 3.0 mPa·s or more, more preferably 5.0 mPa·s or more, even more preferably 10.0 mPa·s or more, and 10,000 mPa·s or less, preferably 7,500 mPa·s or less, more preferably 5,000 mPa·s or less, even more preferably 3,000 mPa·s or less, even more preferably 2,000 mPa·s or less, even more preferably 1,000 mPa·s or less, and even more preferably 700 mPa·s or less, to the skin and then drying. <41> A method for using an external preparation composition comprising the steps of applying the external preparation composition to the skin, and then drying it, wherein the external preparation composition contains (A) a pharmacoactive ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of ingredient (E) in the external preparation composition is 0.1% by mass or more and 30% by mass or less, the mass ratio of ingredient (A) to the total amount of ingredient (B) and ingredient (C) [(A) / {(B)+(C)}] is 0.001 or more and 2.40 or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less. <42> A method for using an external preparation composition comprising the steps of applying the external preparation composition, which contains (A) a pharmacoactive ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of component (E) in the external preparation composition is more than 30% by mass and 70% by mass or less, the mass ratio of component (A) to the total amount of component (B) and component (C) [(A) / {(B)+(C)}] is 0.001 or more and 2.40 or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less, to the skin and then drying. <43> A method for using an external preparation composition comprising the steps of applying the external preparation composition to the skin, and then drying it, wherein the external preparation composition contains (A) an anti-inflammatory and analgesic component, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of component (B) in the external preparation composition is 0.1% by mass or more and 15% by mass or less, the mass ratio of component (C) to component (B) in the external preparation composition [(C) / (B)] is 0.05 or more and 3.5 or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less. <44> A method for using an external preparation composition comprising the steps of applying the external preparation composition to the skin, wherein the external preparation composition contains (A) one or more pharmaceutically active ingredients selected from the group consisting of glycol salicylate, diclofenac sodium, loxoprofen sodium, felbinac, indomethacin, piroxicam, flurbiprofen, methyl salicylate, ketoprofen, and nonylic acid vanillylamide, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the content of component (C) in the external preparation composition is 5.0% by mass or less, and the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less, and then drying. <45> The aforementioned topical composition is applied by spraying it onto the skin. <40> ~ <44> A method of using the topical composition described in any one of the following. <46> The method for spraying the aforementioned topical composition is to use an aerosol, pump spray, or electrostatic spray device. <45> Method of using the topical composition described above. <47> The aforementioned topical composition is applied to the skin by spraying it using an electrostatic spray device. <45> or <46> Method of using the topical composition described above. <48> <1> ~ <36> A method for producing a coating, comprising the step of applying or spraying the topical composition described in any one of the above onto the skin. <49> The method for spraying the aforementioned topical composition is to use an aerosol, pump spray, or electrostatic spray device. <48> A method for manufacturing the coating described above. <50> The aforementioned topical composition is applied to the skin by electrostatic spraying using an electrostatic spray device. <48> or <49> A method for manufacturing the coating described above. [Examples]

[0092] The present invention will be described below with reference to examples, but the present invention is not limited to the scope of these examples. In these examples, various measurements and evaluations were performed by the following methods.

[0093] (SP value) The SP values ​​of the components used in each example of topical formulation were calculated using solubility parameter calculation software (Hansen Solubility Parameters in Practice 4th Edition 4.1.03) based on Hansen's solubility parameters. In calculating the SP values, the specific gravity of the polymer components (B) and (B') was assumed to be 1.0.

[0094] (viscosity) The viscosity of each example of topical formulation at 25°C was measured using a vibrating viscometer (VM-10AL, manufactured by Sekonic Corporation). For compositions with a viscosity exceeding 1000 mPa·s, the viscosity was measured using a B-type rotational viscometer (TV-10M, manufactured by Toki Sangyo Co., Ltd., rotor: TM3, rotation speed: 6 rpm).

[0095] (pH) The pH of each example of topical formulation at 25°C was measured without dilution using a pH meter (Horiba, Ltd. "F-51").

[0096] (Feeling of use) Dispense each example of the topical formulation into the medial side of the forearm using the tip of a pipette at a rate of 6 μL / cm². 2 Regarding the user experience after application, ten expert panelists evaluated each of the following six items on a 5-point scale. The average score of the ten panelists (rounded to two decimal places) is shown in the table. A higher score indicates a better evaluation result. (1) Applicability to the skin 5: Very easy to spread, 4: Easy to spread, 3: Average, 2: Somewhat difficult to spread, 1: Very difficult to spread (2) Fast drying when applied to the skin 5: Dries within 30 seconds, 4: Dries within 1 minute, 3: Dries within 2 minutes, 2: Dries within 10 minutes, 1: Does not dry even after 10 minutes. (3) Appearance of the coating 5: Transparent, 4: Slightly whitened but nearly transparent, 3: Slightly whitened but transparent, 2: Semi-transparent, 1: Completely whitened (4) Stickiness of the coating 5: Not sticky at all, 4: Slightly sticky, 3: Slightly sticky, 2: Noticeably sticky, 1: Very sticky (5) feeling of tightness 5: No tightness at all, 4: Slight tightness felt, 3: Some tightness, 2: Noticeable tightness, 1: Very tight (6) Durability of the coating After applying the topical formulation to the inner side of the forearm, expert panelists performed their daily activities. The resulting film was then visually observed after a certain period of time to confirm whether or not the film remained. The longest time the film remained was scored according to the following criteria. 5: 8 hours later, 4: 4 hours later, 3: 1 hour later, 2: 30 minutes later, 1: 10 minutes later

[0097] (Storage stability) Ten g of each example of the topical preparation composition was placed in a No. 4 screw-cap tube (manufactured by Maruemu Co., Ltd.), sealed, and stored in a constant temperature bath at 0°C and 40°C for one week. The changes in appearance, odor, viscosity, and pH over time were then observed and evaluated according to the following criteria. A: No change in appearance, odor, viscosity, or pH. B: There is a slight change in one or more of the following: appearance, odor, viscosity, or pH. C: Changes observed in one of the following: appearance, odor, viscosity, or pH. D: Changes observed in 2 or more of the following: appearance, odor, viscosity, and pH.

[0098] (Film forming property) Apply 6 μL / cm³ of each example of topical formulation to the surface of artificial leather ("Sapure" manufactured by Ideatex Japan Co., Ltd.). 2 The mixture was applied and dried for 1 hour on a hot plate (AS ONE Corporation's "Ceramic Hot Plate") set to 32°C. The applied portion of the topical composition was visually inspected, and its film-forming ability was judged according to the following criteria. A score of 3 or higher was considered acceptable. 5: A uniform and sufficiently thick coating is formed; 4: A uniform and thick coating is formed; 3: A thin but uniform coating is formed; 2: A coating is present but non-uniform; 1: The presence of a coating cannot be confirmed.

[0099] (Amount of active ingredient permeated through the skin) Each example of the topical formulation was applied at a rate of 6 μL / cm² to the surface (one side) of the stratum corneum of a pig ear set in a Franz diffusion cell (manufactured by PermeGear). 2 After application, the cumulative amount of the active ingredient absorbed into the skin (μg / cm³) after 8 hours is measured. 2 The following was measured: A higher value indicates greater permeability of the active ingredient into the skin.

[0100] (Crystallization of medicinal components) Dispense each example of the topical composition onto a glass slide at a rate of 5 μL / cm². 2 The coating was applied and dried for 1 hour on a hot plate (AS ONE Corporation's "Ceramic Hot Plate") set to 32°C. The presence or absence of crystals in the formed film was evaluated by observation with a polarizing microscope, and the results were judged according to the following criteria. A higher score indicates that precipitation of crystalline active ingredients is less likely to occur and that the release of active ingredients to the skin is better. 5: No crystals observed, 4: Crystals less than approximately 10 μm are observed, 3: Crystals between approximately 10 μm and 50 μm are observed, 2: Crystals between approximately 50 μm and 100 μm are observed, 1: Crystals larger than approximately 100 μm are observed

[0101] (Stringiness of the coating) Dispense each example of the topical composition onto a glass slide at a rate of 5 μL / cm². 2 The sample was applied and dried for 1 hour on a hot plate (AS ONE Corporation's "Ceramic Hot Plate") set to 32°C. The stringiness of the formed film surface was evaluated by touching it with a finger, and the result was judged according to the following criteria. A higher score indicates that the affinity of the active ingredient to the film is not excessively high, resulting in low stringiness and good release of the active ingredient to the skin. 5: No stringing properties at all, 4: Almost no stringing properties, 3: Slightly stringing properties, 2: Significant stringing properties, 1: Very high stringing properties

[0102] (Changes in appearance when stored at -5°C) 10 g of each composition shown in Table 7 was measured out and placed in a clear vial, and stored at -5°C for 6 hours. After storage, the vials were left to stand at 20°C for 20 minutes, and the appearance of the compositions in the vials was observed according to the following criteria. The background color of the vials during observation was black. • Clear: The composition is transparent, allowing the black background color to be clearly visible without any blurring. • Slightly cloudy: The composition appears slightly hazy, and the black background color looks slightly blurred. • Cloudiness: A haze forms in the composition, causing the black background color to appear blurred.

[0103] Examples 1-42, Comparative Examples 1-10 (Preparation and Evaluation of Topical Compositions) The components (B) or (B') listed in the table, as well as other components, were mixed with components (C), (D), and (E), uniformly dissolved at 30°C, and then component (A) was mixed in and dissolved to prepare the topical formulation. The obtained topical formulations were evaluated using the method described above. The results are shown in Tables 1 to 7. Note that the amounts listed in each table represent the amount of active ingredient (parts by mass) for each component unless otherwise stated as "mass%", and the amount of active ingredient (mass%) for each component where "mass%" is stated. In addition, in the tables, water-soluble polymers that do not fall under component (B) are indicated as "Component (B')".

[0104] [Table 1]

[0105] [Table 2]

[0106] [Table 3]

[0107] [Table 4]

[0108] [Table 5]

[0109] [Table 6]

[0110] [Table 7]

[0111] The ingredients and notes listed in the table are as follows. *1 Felbinac: Manufactured by Fujifilm Wako Pure Chemical Corporation *2 Glycol salicylate: Manufactured by Tokyo Chemical Industry Co., Ltd. *3 Loxoprofen sodium: Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. *4 l-menthol: Manufactured by Takasago International Corporation *5 Nonyl vanillylamide: Manufactured by Tokyo Chemical Industry Co., Ltd. *6 (Acrylates / Diacetone Acrylamide) Copolymer: "Plus Size L-53" manufactured by Go-o Chemical Industry Co., Ltd. *7 Hypromellose phthalate: "HPMCP HP-55" manufactured by Shin-Etsu Chemical Co., Ltd. *8 Acrylamide / methoxypolyethylene glycol methacrylate copolymer: "RP-77T" manufactured by Kao Corporation *9 Ethylcellulose: "Etocell 100P" manufactured by Nisshin Chemical Co., Ltd. *10 Polyvinyl butyral: "S-Rec BM-1" manufactured by Sekisui Chemical Co., Ltd. *11 Methyl vinyl ether / maleic anhydride: "Gantlets AN" manufactured by ISP Japan Co., Ltd. *12 Isopropyl myristate: Kao Corporation's "Excepearl IPM", specific gravity 0.80 *13 Diethyl sebacate: "Diethyl sebacate SP-1" manufactured by NOF Corporation, specific gravity 0.94 *14 Oleyl alcohol: Manufactured by Tokyo Chemical Industry Co., Ltd., specific gravity 0.85 *15 Squalane: Manufactured by Fujifilm Wako Pure Chemical Corporation, specific gravity 0.81 *16 Diisopropanolamine: Specific gravity 0.99 *17 Triethanolamine: Specific gravity 1.13 *18 2-amino-2-methylpropanol: Specific gravity 0.93 *19 Xylitol: Manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., specific gravity 1.52 *20 Example 39 [Δ(SP A -SP B+C )] was calculated for each type of component (A). Δ(SP) in the table. A -SP B+C ) is, in order from top to bottom, Δ(SP) when component (A) is felbinac, l-menthol, and nonyl vanillylamide. A -SP B+C )

[0112] Tables 1-6 show that the topical formulations of these embodiments yield excellent results in terms of sustained release of the active ingredient, film formation, skin application, quick drying, suppression of stickiness and tightness of the formed film, and appearance and durability of the film. Furthermore, the compositions exhibit good storage stability. Furthermore, as can be seen from Table 7, in the topical preparation composition of this embodiment, if the content of component (E) is more preferably 50% by mass or less, even more preferably 30% by mass or less, even more preferably 25% by mass or less, even more preferably 22% by mass or less, even more preferably 21% by mass or less, and even more preferably 20% by mass or less, then clouding is less likely to occur even when stored at a low temperature of -5°C, and a good appearance can be maintained. In contrast, Comparative Examples 1, 6, and 7, which do not contain component (B); Comparative Examples 2 and 8, which do not contain component (C); Comparative Example 3, which do not contain component (D); Comparative Example 4, which do not contain component (E); Comparative Example 5, which do not contain components (D) and (E); and Comparative Examples 9 and 10, whose viscosity is outside the specified range of the present invention, were inferior to the effects of the present invention in at least one of the following aspects.

[0113] Prescription Example 1 (Preparation of Aerosol Formulation) Following the formulation below, component (B) was mixed with components (C), (D), and (E) and uniformly dissolved at 30°C. Then, component (A) was mixed and dissolved to prepare an external preparation composition that would become the aerosol concentrate. After filling this into an aerosol container (manufactured by Toyo Seikan Co., Ltd.), nitrogen was sealed in so that the aerosol concentrate:nitrogen ratio was 1:0.1 by mass to prepare the aerosol formulation. (component) (mass%) (A) Peppermint oil 3.0 (B) Polyvinyl alcohol 3.0 (C) Diglycerin 3.4 (D) Ethanol 65.0 (E) Purified water balance Total 100.0 [Industrial applicability]

[0114] According to the present invention, it is possible to provide an external preparation composition that can continuously release the active ingredient into the skin, has good film-forming properties, is highly applicable to the skin, dries quickly, suppresses stickiness and tightness of the formed film, and is also excellent in the appearance and durability of the film, as well as a formulation using the same, a method of using the external preparation composition, and a method of producing the film.

Claims

1. A film-forming topical preparation composition comprising (A) a pharmaceutically active ingredient, (B) a water-insoluble polymer, (C) a non-volatile base, (D) a volatile solvent, and (E) water, wherein the viscosity at 25°C is 1.0 mPa·s or more and 10,000 mPa·s or less, Ingredient (A) contains one or more selected from the group consisting of glycol salicylate, methyl salicylate, diclofenac sodium, loxoprofen sodium, ketoprofen, felbinac, indomethacin, piroxicam, flurbiprofen, glycyrrhizic acid, glycyrrhetinic acid, l-menthol, dl-camphor, nonyl vanillylamide, peppermint oil, benzyl nicotinate, sodium polyethylene sulfonate, tocopherol acetate, diphenhydramine, chlorpheniramine maleate, chili pepper, eucalyptus oil, and Phellodendron amurense. Component (B) is a polymer that, when immersed in 10 g of deionized water at 23°C and 1 atm, has the property that more than 0.5 g of the immersed polymer does not dissolve after 24 hours, and is an acrylates / diacetone acrylamide copolymer. Component (C) is one or more non-volatile bases selected from the group consisting of ester oils, non-polar oils, polyols, and alkanolamines. The mass ratio of component (C) to component (B) [(C) / (B)] is 0.2 or greater. The mass ratio of component (E) to component (D) [(E) / (D)] is 0.005 or more and 2.0 or less. A film-forming topical preparation composition.

2. The film-forming topical composition according to Claim 1, wherein component (A) comprises one or more selected from the group consisting of glycol salicylate, loxoprofen sodium, felbinac, l-menthol, and nonyl vanillylamide.

3. The film-forming topical composition according to claim 1 or 2, wherein component (C) is one or more selected from the group consisting of isopropyl myristate, dibutyl adipate, diethyl sebacate, diisopropyl sebacate, propylene glycol, 1,3-butylene glycol, 1,2-pentanediol, dipropylene glycol, polyethylene glycol, polypropylene glycol, polyoxyethylene / polyoxypropylene glycol, glycerin, diglycerin, triethanolamine, monoethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol.

4. The film-forming topical composition according to any one of claims 1 to 3, wherein component (C) is one or more selected from the group consisting of isopropyl myristate, diethyl sebacate, triethanolamine, diisopropanolamine, and 2-amino-2-methylpropanol.

5. The film-forming topical composition according to any one of claims 1 to 4, wherein the mass ratio of component (C) to component (B) [(C) / (B)] is 0.2 or more.

6. The film-forming topical composition according to any one of claims 1 to 5, wherein component (D) is a lower alcohol.

7. The film-forming topical agent composition according to any one of claims 1 to 6, wherein the content of component (A) in the film-forming topical agent composition is 0.001% by mass or more and 30% by mass or less.

8. The film-forming topical agent composition according to any one of claims 1 to 7, wherein the content of component (B) in the film-forming topical agent composition is 0.01% by mass or more and 30% by mass or less.

9. The film-forming topical agent composition according to any one of claims 1 to 8, wherein the content of component (C) in the film-forming topical agent composition is 0.001% by mass or more and 30% by mass or less.

10. The film-forming topical agent composition according to any one of claims 1 to 9, wherein the content of component (D) in the film-forming topical agent composition is 10% by mass or more and 95% by mass or less.

11. The film-forming topical agent composition according to any one of claims 1 to 10, wherein the content of component (E) in the film-forming topical agent composition is 0.1% by mass or more and 70% by mass or less.