Composition

Abstract

To provide a liquid or semisolid composition which contains Prednisolone Valerate Acetate in an amount of more than 0.15 mass% based on the total mass of the composition and in which the deposition of crystals is suppressed when the composition is stored under low temperature conditions.SOLUTION: The liquid or semisolid composition comprises the following components (A) and (B): (A) more than 0.15 mass% of Prednisolone Valerate Acetate based on the total mass of the composition; and (B) terpenes.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition and the like. [Background technology]

[0002] Prednisolone valerate acetate, an adrenal corticosteroid, has excellent efficacy in the affected area. While it exhibits anti-inflammatory effects, it is a highly safe prodrug that turns into a less active substance in the body. Such excellent efficacy and high safety characteristics are the key factors in so-called self-medication. Therefore, in Japan, prednisolone valerate ester is Tertetraceate is effective against eczema, dermatitis, rashes, insect bites, itching, heat rash, hives, etc. It is widely used as an active ingredient in OTC drugs with efficacy and effectiveness (e.g., non-patented References 1, 2). [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Package insert: "Eczema and Dermatitis Treatment Drug Livmex Kowa Cream," Kowa Company, Ltd., October 2011 [Non-patent document 2] Package insert: "Eczema and Dermatitis Treatment Drug Livmex Kowa Ointment," Kowa Company, Ltd., October 2012 Summary of the Invention [Problem to be solved by the invention]

[0004] Prednisolone valerate acetate-containing OTC medicines currently on the market Each product contains 1.5g of prednisolone valerate acetate per 1g of composition. mg (i.e., 0.15% by weight based on the total weight of the composition) It is a composition (ointment, cream, etc.). However, the anti-inflammatory effect is basically dose-dependent, so prednisolone valerate If the content of ester acetate exceeds 0.15% by mass, the anti-inflammatory effect is enhanced. It is believed that this will result in a pharmaceutical product with strong and excellent efficacy.

[0005] Therefore, the present inventors have developed a method for producing a prednisolone valerate acetate containing more than 0.15% by mass. In order to develop a liquid or semi-solid composition having the above properties, the storage stability of the composition was examined. The amount of prednisolone valerate acetate was 0.3 mass % based on the total mass of the composition. In the case of a liquid or semi-solid composition containing 100% of the above-mentioned hydroxybenzoates, the crystals were not crystalline after storage at -20°C for 1 week. It was found that precipitation problems occur. In a liquid or semi-solid composition containing 0.15% by mass of an acid ester acetate, Since no crystallization problems were observed during storage under these conditions, it is possible to When prednisolone valerate acetate is present, crystal precipitation occurs. It was found that the problem occurs when the content exceeds 0.15 mass %. Therefore, the present invention provides a composition containing more than 0.15% by weight of prednisolone valerate based on the total weight of the composition. A liquid containing tertiary acetic acid ester that is inhibited from crystallizing when stored at low temperatures. Alternatively, the present invention aims to provide a semi-solid composition. [Means for solving the problem]

[0006] Therefore, the present inventors have further studied to solve the above problems, and as a result, have found that More than 0.15% by mass of prednisolone valerate acetate (hereinafter, A liquid or semi-solid composition containing (sometimes simply referred to as "component (A)" in The product further contains any one of the following components 1 to 7 (hereinafter, in this specification, components 1 to 6 are respectively "Component (B-1)", "Component (B-2)", "Component (B-3)", and "Component (B -4), "Component (B-5)", "Component (B-6)", "Component (B-7)", and "One or more selected from the group consisting of components (B-1) to (B-7)" is referred to as "component (B)." Sometimes referred to as:

[0007] 1. Local anesthetic ingredients, such as lidocaine and lidocaine hydrochloride 2: Crotamitons, represented by crotamiton 3. Antihistamine ingredients, such as diphenhydramine and diphenhydramine hydrochloride 4: Salicylic acids, such as glycol salicylate 5: Therapeutic compounds such as l-menthol, dl-camphor, and isopropylmethylphenol Lupen species 6: Panthenols, typified by panthenol 7: Hydroxycarboxylic acids, such as sodium citrate

[0008] By incorporating component (B), the composition exhibits improved durability under low temperature conditions compared to when component (B) is not incorporated. The inventors have found that crystal precipitation during storage is relatively suppressed, and have completed the present invention.

[0009] That is, the present disclosure provides a composition comprising the following components (A) and (B): (A) Prednisolone valerate acetate ester in an amount exceeding 0.15% by mass relative to the total mass of the composition Le; (B) one or more selected from the group consisting of the following components (B-1) to (B-7): (B-1) Local anesthetic ingredient (B-2) Crotamiton (B-3) Antihistamine ingredients (B-4) Salicylic acids (B-5) Terpenes (B-6) Panthenols (B-7) Hydroxycarboxylic acids The present invention provides a liquid or semi-solid composition comprising: [Effects of the Invention]

[0010] According to the present disclosure, a storage-safe product in which crystal precipitation is relatively suppressed when stored under low-temperature conditions is provided. Prednisolone valerate acetate, which has good quality and excellent efficacy, A liquid or semi-solid composition containing the compound can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0011] <Component (A)> In the present disclosure, "prednisolone valerate acetate" in a liquid or semi-solid composition The content of sterol is more than 0.15% by mass, preferably 0.3% by mass or more. More preferably, it is 0.3 to 0.5 mass %, and particularly preferably, 0.3 mass %. As specifically disclosed in the test examples below, the predators that have been sold so far Nisolone valerate acetate-containing OTC drugs (0.15% by mass) No particular problems occurred after storage at -20°C for one week, while prednisolone valerate acetate For liquid or semi-solid compositions containing more than 0.15% by mass of esters, the storage conditions are the same. However, the presence of the compound causes the problem of crystal precipitation. By including component (B), the composition is relatively more viscous than when component (B) is not included. Crystallization can be suppressed.

[0012] <Component (B-1)> In the present disclosure, the term "local anesthetic component" is not particularly limited as long as it has a local anesthetic effect. Specifically, for example, ethyl aminobenzoate, oxypolyethoxydodeca dibucaine, tetracaine, procaine, bupivacaine, propitocaine, benzocaine mepivacaine, meprylcaine, lidocaine themselves, as well as their pharmaceutically acceptable salts. Salts of ethyl aminobenzoate, oxypolyethoxydodecane, dibucaine, Tetracaine, procaine, bupivacaine, propiocaine, benzocaine, mepivacaine A mixture of lidocaine, meprylcaine, lidocaine itself or their pharmaceutically acceptable salts with water or alcohol. The concept also includes solvates with alcohols, etc. Here, the salts are pharmaceutically acceptable salts. There is no particular limitation on the type of salt, and examples thereof include hydrochlorides, sulfates, nitrates, hydrofluorides, and hydrobromides. Inorganic acid salts such as salts; acetate, tartrate, lactate, citrate, fumarate, maleate, Succinate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluene Examples of organic acid salts include benzophenone sulfonates, naphthalene sulfonates, and camphor sulfonates. can be done. These may be used alone or in appropriate combination of two or more. These local anesthetic ingredients are known ingredients and can be produced by known methods or can be purchased commercially. Commercially available products include lidocaine (manufactured by Delta Co., Ltd.), lidocaine hydrochloride, etc. Examples include acetaminophen (manufactured by Iwaki Pharmaceutical Co., Ltd.).

[0013] As the component (B-1), from the viewpoint of the crystal precipitation suppression effect, ethyl aminobenzoate, oxalate, Polyethoxydodecane, dibucaine, procaine, mepivacaine, meprylcaine, One or more compounds selected from the group consisting of docaine, salts thereof, and solvates thereof are preferred. Ethyl aminobenzoate, oxypolyethoxydodecane, dibucaine, procaine, Mepivacaine, meprylcaine, lidocaine, and their hydrochlorides and solvates More preferably, one or more selected from the group consisting of ethyl aminobenzoate, oxypolyethylene glycol Toxidodecane, dibucaine, dibucaine hydrochloride, procaine, procaine hydrochloride, mepidol selected from the group consisting of bacine, meprylcaine hydrochloride, lidocaine and lidocaine hydrochloride More preferably, one or more of the following are used: ethyl aminobenzoate, dibucaine, dibucaine hydrochloride Particularly preferred is one or more selected from the group consisting of lidocaine and lidocaine hydrochloride.

[0014] The content of component (B-1) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, however, it is preferable to use component (B-1) throughout the composition. The content is preferably 0.01 to 20% by mass, and more preferably 0.1 to 10% by mass. It is more preferable that the content is 0.5 to 2 mass %, and it is particularly preferable that the content is 0.5 to 2 mass %. In addition, the mass content of component (A) and component (B-1) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.01 to 50 parts by mass of component (B-1) per part by mass of component (A). The content is more preferably 0.1 to 30 parts by mass, and particularly preferably 2 to 7 parts by mass. It's nice.

[0015] <Component (B-2)> In the present disclosure, "crotamitons" refers to crotamiton and its salts, as well as their solvents. Here, the salt means one or more selected from the group consisting of pharmaceutically acceptable salts. There are no particular limitations on the salts, and crotamiton and its salts may be in the form of solvates such as hydrates. It's okay to have it. These may be used alone or in appropriate combination of two or more. These crotamiton compounds are known compounds and can be produced by known methods or can be purchased commercially. Commercially available products include, for example, crotamiton (manufactured by Sumitomo Chemical Co., Ltd.). Examples include:

[0016] The content of component (B-2) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, however, it is preferable to use component (B-2) throughout the composition. The content is preferably 0.1 to 30 mass % and more preferably 0.5 to 20 mass %. more preferably, and particularly preferably, 2 to 10 mass %. In addition, the mass content of component (A) and component (B-2) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.1 to 70 parts by mass of component (B-2) per part by mass of component (A). The content is more preferably 1 to 50 parts by mass, and particularly preferably 5 to 35 parts by mass. .

[0017] <Component (B-3)> In the present disclosure, the "antihistamine component" refers to a compound having a histamine H1 receptor antagonistic activity. There is no particular limitation as long as it is a compound having a hydroxybenzoate group. Specific examples include azelastine, alimene, and the like. Mazine, Isothipendyl, Iproheptine, Ebastine, Epinastine, Emedastine, Oxatomide, olopatadine, carbinoxamine, clemastine, chlorpheniramine, Ketotifen, difeterol, diphenylpyraline, diphenhydramine, cyproheptone Tadine, cetirizine, triprolidine, tripelennamine, thonzylamine, fexofen Nadine, fenethazine, promethazine, bepotastine, homochlorcyclizine, mequitazidine methdilazine, mebhydroline and loratadine, and pharmaceutically acceptable salts thereof; The salt may be one or more selected from the group consisting of solvates thereof. There are no particular limitations on the salt as long as it is scientifically acceptable, but inorganic acids, organic acids, inorganic bases, organic bases, etc. and salts thereof, for example, hydrochloride, tartrate, maleate, fumarate, diphenyl Disulfonate, teoclate, salicylate, tannate, besylate, napadisil In addition, the chemical structure of the antihistamine component may contain an asymmetric carbon atom. In the case of a compound, it has various optical isomers, but in the present invention, any of the optical isomers is included. It may be a single optical isomer or a mixture of various optical isomers. Various compounds with histamine H1 receptor antagonistic activity, such as azelastine, and their salts, are used in combination with water and alcohol. Solvates with alcohol and the like are also included in the "antihistamine component." These may be used alone or in appropriate combination of two or more. These antihistamine components are known compounds and can be produced by known methods or by commercially available products. Commercially available products can be used. Examples of commercially available products include diphenhydramine (Kongoka) Examples of such antihistamines include diphenhydramine hydrochloride (manufactured by Kongo Chemical Co., Ltd.), and diphenhydramine hydrochloride (manufactured by Kongo Chemical Co., Ltd.).

[0018] Specific examples of the component (B-3) include azelastine such as azelastine hydrochloride; alimemazine or its salts such as alimemazine tartrate; isothipendyl hydrochloride, etc. isothipendyl or its salt; iproheptine or its salt such as iproheptine hydrochloride; Bastine or its salts; epinastine or its salts such as epinastine hydrochloride; emedastine Emedastine or its salts such as the malate salt; oxatomide or its salts; olopatadine hydrochloride, etc. Olopatadine or its salts; Carbinoxamine diphenyldisulfonate, Carbinoxamine carbinoxamine or its salts such as clemastine maleate; clemastine fumarate d-Chlorpheniramine maleate, dl-Chlorpheniramine maleate chlorpheniramine or its salts such as leic acid salt; ketotifen such as ketotifen fumarate difeterol or its salts; difeterol or difeterol such as difeterol hydrochloride, difeterol phosphate its salts; diphenylpyraline such as diphenylpyraline hydrochloride and diphenylpyraline teoclate; diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine Diphenhydramine or its salts such as diphenhydramine tannate; cyproheptadine hydrochloride Cyproheptadine or its salts, such as its salt hydrate; Cetirizine or its salts, such as cetirizine hydrochloride Triprolidine or its salts such as triprolidine hydrochloride; tripelennamine hydrochloride Perennamin or its salts; thonzylamine or its salts such as thonzylamine hydrochloride; Fexo Phenazine or its salts; fenethazine or its salts such as fenethazine hydrochloride; promethazine Promethazine or its salts such as promethazine hydrochloride, promethazine methylene disalicylate, etc.; Bepotasti bepotastine or its salts such as bepotastine hydrochloride; homochlorcyclidine hydrochloride Cyclizine or its salt; Mequitazine or its salt; Methdilazine or its salt such as methdilazine hydrochloride mebhydroline or its salts such as mebhydroline napadisilate; loratadine or Examples of the hydroxybenzoates include salts thereof. As the component (B-3), from the viewpoint of the crystal precipitation inhibitory effect, isothipendyl, chlorphen From the group consisting of niramin, diphenylpyraline and diphenhydramine and their salts Preferably, one or more selected from the group consisting of isothipendyl hydrochloride, chlorpheniramine, chlorpheniramine Niramine maleate, diphenylpyraline hydrochloride, diphenhydramine, diphenhydramine Preferably, one or more selected from the group consisting of diphenhydramine hydrochloride and diphenhydramine salicylate. More preferred are isothipendyl hydrochloride, chlorpheniramine, and chlorpheniramine maleate. one or more selected from the group consisting of diphenhydramine hydrochloride, diphenhydramine, and diphenhydramine hydrochloride The above is particularly preferred.

[0019] The content of component (B-3) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, however, it is preferable to use component (B-3) throughout the composition. The content is preferably 0.01 to 10 mass % and more preferably 0.1 to 5 mass %. It is more preferable that the content is 0.2 to 2 mass %. In addition, the mass content of component (A) and component (B-3) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.01 to 30 parts by mass of component (B-3) per part by mass of component (A). The content is more preferably 0.1 to 20 parts by mass, and particularly preferably 0.5 to 10 parts by mass. Preferred.

[0020] <Component (B-4)> In the present disclosure, "salicylic acids" refers to salicylic acid and its derivatives (e.g., salicylic acid, Esters of acids (specifically, for example, methyl salicylate, ethyl salicylate, glycerol salicylate, etc.) It means one or more selected from the group consisting of alkoxide, alkoxide, etc.) and salts thereof. The salt is not particularly limited as long as it is a pharmaceutically acceptable salt, but may be an inorganic acid, an organic acid, an inorganic salt, or the like. Examples of the salts include salts with alkali metals such as potassium salts and sodium salts. Salts; ammonium salts, etc. As component (B-4), salicylic acid, glycerin, salicylic acid, etc. are used from the viewpoint of the crystal precipitation inhibitory effect. one or more selected from the group consisting of chol, sodium salicylate and methyl salicylate Preferably, one or more selected from the group consisting of glycol salicylate and methyl salicylate. is more preferred, with glycol salicylate being particularly preferred. These compounds are all known compounds and can be produced by known methods or are commercially available. Commercially available products include glycol salicylate (Ellison Co., Ltd.) (manufactured by PI Corporation)

[0021] The content of component (B-4) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, however, it is preferable to use component (B-4) throughout the composition. The content is preferably 0.01 to 20% by mass, and more preferably 0.1 to 10% by mass. It is more preferable that the content is 0.4 to 5 mass %, and it is particularly preferable that the content is 0.4 to 5 mass %. In addition, the mass content of component (A) and component (B-4) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.1 to 50 parts by mass of component (B-4) per part by mass of component (A). The content is more preferably 0.5 to 30 parts by mass, and particularly preferably 1 to 20 parts by mass. It's nice.

[0022] <Component (B-5)> In the present disclosure, the term "terpenes" refers to terpene hydrocarbons as well as terpene alcohols, Includes terpene aldehydes, terpene ketones, terpene oxides, terpene lactones, etc. The structure of the terpenoid is not particularly limited, and it can be any monoterpenoid. and the like. The terpenes may be cyclic or chain-chain. . Specific examples of such terpenes include isopropyl methylphenol, isopropyl methylphenol, Borneol, iron, ocimene, carveol, carbotanacetone, carbomentone, Carvone, Karen, Calone, Camphene, Camphor, Geraniol, Sabinene, Safrana ol, cyclocitral, citral, citronellal, citronellic acid, citronellol , cineole, cymene, silvestrene, thymol, isothujole, thujone, terpi Neol, terpinene, terpinolene, tricyclene, nerol, pinene, pinocamphe All, pinol, piperitenone, phellandral, phellandrene, fengchen, Fenchyl alcohol, perillyl alcohol, perillaldehyde, borneol, myrcene Menthol, menthol, menthone, ionol, ionone, linalool, limonene, etc. These terpenes can be used alone or in combination of two or more. In cases where optical isomers exist, both isomers are included unless otherwise specified. That is, in the present invention, unless a specific optical isomer is specified as the component name of a terpene, such Such component notation includes all of the various optical isomers alone and mixtures thereof in any proportion, and It may be a single optical isomer or a mixture of various optical isomers in any proportion (e.g., For example, the term "menthol" includes both dl-menthol and l-menthol. In addition, when terpenes are contained in a liquid or semi-solid composition, Terpenes may be used as they are, or essential oils containing terpenes may be used. These terpenes are known compounds and can be produced by known methods or are commercially available. Commercially available products include isopropyl methylphenol (Sumitomo Chemical Co., Ltd.) Co., Ltd.), dl-camphor (Fujian Seishun Co., Ltd.), l-menthol (Takasago International Corporation) Examples include:

[0023] As the component (B-5), a cyclic terpenoid is preferred from the viewpoint of the crystal precipitation inhibitory effect. Cyclic monoterpenoids are more preferred, and monocyclic or bicyclic monoterpenoids are even more preferred. More preferred are monoterpenoids having a p-menthane skeleton (e.g., cymene, thymol, p-menthane unsaturated olefins such as terpinene, terpinolene, phellandrene, and limonene Derivatives: Monomers with a p-menthane skeleton such as carveol, terpineol, and menthol Monoterpene alcohols with a p-menthane skeleton, such as carvone and menthone Monoterpene aldehydes with a p-menthane skeleton, such as perillaldehyde; monoterpene ethers with a p-menthane skeleton, such as cineole; Monoterpenoids (e.g., 3-methyl-4-isopropyl) that have an isomer of pentane as the skeleton The isomers of p-menthane, such as propylphenol (isopropylmethylphenol), saturated derivatives, etc.) or monoterpenoids with a bornane skeleton (e.g., borneol, etc.) Monoterpene alcohols with a bornane skeleton, such as camphor; Even more preferred are monoterpene ketones such as thymol, menthol, and isopropyl alcohols. More preferably, one or more selected from the group consisting of methylphenol, camphor and borneol. More preferred are thymol, l-menthol, dl-menthol, and isopropyl methyl selected from the group consisting of phenol, d-camphor, dl-camphor and d-borneol More preferably, one or more of the following are used: l-menthol, dl-menthol, isopropyl methyl ... Particularly, one or more selected from the group consisting of methylphenol, d-camphor and dl-camphor are Preferred.

[0024] The content of component (B-5) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, however, it is preferable to use component (B-5) throughout the composition. The content is preferably 0.01 to 30% by mass, more preferably 0.05 to 15% by mass. It is more preferable that the content is 0.1 to 7 mass %, and it is particularly preferable that the content is 0.1 to 7 mass %. In addition, the mass content of component (A) and component (B-5) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.01 to 60 parts by mass of component (B-5) per part by mass of component (A). The content is preferably 0.05 to 40 parts by mass, more preferably 0.2 to 25 parts by mass. Particularly preferred.

[0025] <Component (B-6)> In this disclosure, "panthenols" refers to panthenol and its derivatives (pantothenic acid , Pantothenyl ethyl ether, Acetyl pantothenyl ethyl ether, Pantethine, Pan Coenzyme A, etc.) and their salts (sodium salts and other alkali metal salts; calcium salts) In the present disclosure, the term "aluminum salt" refers to one or more selected from the group consisting of: In this case, these may be used alone or in combination of two or more. As component (B-6), panthenol and pantothenic acid are used from the viewpoint of inhibiting crystal precipitation. , acetylpantothenyl ethyl ether and pantothenyl ethyl ether and their Preferably, one or more selected from the group consisting of panthenol and sodium pantothenate. , calcium pantothenate, acetylpantothenyl ethyl ether and pantothenyl ethyl More preferred are at least one selected from the group consisting of panthenol and pantothenic acid ethers. Particularly preferred is one or more selected from the group consisting of methyl ethyl ether. Panthenols are known ingredients and may be produced by known methods. Specific examples of commercially available products include D-Panthenol 50P (BAS F Japan Co., Ltd.), D-Panthenol 75W (BASF Japan Co., Ltd.), D-Panthenol Calcium pantothenate (Kyowa Pharma Chemical Co., Ltd.), Calcium pantothenate (BASF Japan Ltd.), Calcium pantothenate (Alps Pharmaceutical Co., Ltd.), Viewplex VH (DSM Nutrition Japan ( D-Pantothenyl Alcohol (DSM Nutrition Japan Co., Ltd.), D-Pantothenyl Alcohol (DSM Nutrition Japan Co., Ltd.), Pantothenyl alcohol (Alps Pharmaceutical Co., Ltd.), DL-pantothenyl alcohol (Al Pus Pharmaceutical Industry Co., Ltd.), Pantothenyl ethyl ether (Kyowa Pharma Chemical Co., Ltd.), etc. Examples include:

[0026] The content of component (B-6) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, it is preferable to use component (B-6) throughout the composition. The content is preferably 0.01 to 20% by mass, and more preferably 0.1 to 10% by mass. It is more preferable that the content is 1 to 5 mass %, and it is particularly preferable that the content is 1 to 5 mass %. In addition, the mass content of component (A) and component (B-6) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.1 to 50 parts by mass of component (B-6) per part by mass of component (A). The content is more preferably 1 to 30 parts by mass, and particularly preferably 3 to 20 parts by mass. .

[0027] <Component (B-7)> In this disclosure, "hydroxycarboxylic acids" refers to organic compounds that contain a carboxyl group in one molecule. and a hydroxyl group, specifically, for example, citric acid, tartaric acid, lactic acid, fumaric acid and at least one selected from the group consisting of malic acid, salts thereof, and solvates thereof. Here, the salt is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include: Alkali metal salts such as sodium salts and potassium salts; secondary salts such as calcium salts and magnesium salts Examples of the salts include salts with group elements, ammonium salts, etc. Also, hydroxycarboxylic acids and their salts are The compound may be a solvate such as a hydrate. As component (B-7), citric acid and sodium citrate are used from the viewpoint of crystal precipitation inhibitory effect. lactic acid, calcium lactate, sodium lactate, fumaric acid, One or more selected from the group consisting of malic acid is preferred, citric acid and sodium citrate. Particularly preferred is one or more selected from the group consisting of:

[0028] The content of component (B-7) in the liquid or semi-solid composition of the present disclosure is not particularly limited, and may be any suitable amount. From the viewpoint of the crystal precipitation suppression effect, it is preferable to use component (B-7) throughout the composition. The content is preferably 0.01 to 20% by mass, more preferably 0.05 to 10% by mass. It is more preferable that the content is 0.1 to 5 mass %, and it is particularly preferable that the content is 0.1 to 5 mass %. In addition, the mass content of component (A) and component (B-7) in the liquid or semi-solid composition of the present disclosure The ratio is not particularly limited and may be determined by appropriate consideration. However, from the viewpoint of the crystal precipitation suppression effect, It is preferable to contain 0.01 to 50 parts by mass of component (B-7) per part by mass of component (A). The content is more preferably 0.1 to 30 parts by mass, and particularly preferably 0.3 to 20 parts by mass. Preferred.

[0029] <Liquid or semi-solid composition> In the present disclosure, the term "liquid or semi-solid composition" refers to a liquid or semi-solid composition that is in a state where it ... The term "composition" refers to a composition that is liquid or semi-solid at any temperature. The state of the liquid is not particularly limited, and may be a solution, a colloidal solution (sol (suspension or emulsion)), a gel, or the like. The type and properties of the solvent or base are not particularly limited, and the solvent or base may be hydrophilic. It may be hydrophobic, oily, or the like, and may further be a mixture of several different solvents and bases. Specific examples of such solvents and bases include the following: Examples of additives include the components exemplified above.

[0030] In the present disclosure, the liquid or semi-solid composition is a liquid or semi-solid composition from the viewpoint of safety during use and feeling of use. Therefore, it is preferable to use a composition containing water in addition to the components (A) and (B). Here, the content of water in the composition is not particularly limited, but the amount of water may be determined based on the safety during use and the prednisone-containing From the viewpoint of improving the stability of hydroxyvaleric acid ester acetate, 1% by mass based on the total mass of the composition It is preferably 5% by mass or more, more preferably 10 to 90% by mass. It is more preferable that the content is 20 to 80 mass %, and even more preferable that the content is 25 to 70 mass %. It is even more preferable that the content is 30 to 65 mass %, and particularly preferable that the content is 30 to 65 mass %.

[0031] In the present disclosure, the liquid or semi-solid composition is preferably a composition containing a component selected from the viewpoint of usability. It is preferable to use a mixture containing a lower alcohol in addition to (A) and (B). In the present disclosure, the liquid or semi-solid composition may contain both alcohol and From the viewpoint of safety and usability during use, those containing both water and lower alcohol are preferable. Here, the term "lower alcohol" refers to a linear or branched monohydric alcohol having 1 to 6 carbon atoms. Specific examples include ethanol, isopropanol, and n-propanol. Among these, one may be used alone or two or more may be used in combination. However, ethanol, isopropanol and mixtures thereof are preferred. The content of the lower alcohol in the composition is not particularly limited. It is preferably 5% by mass or more, more preferably 10 to 80% by mass, based on the total mass. It is preferably 15 to 75 mass %, more preferably 20 to 70 mass %. It is preferably 25 to 65 mass %, even more preferably 30 to 60 mass %. Particularly preferred.

[0032] In the present invention, the liquid or semi-solid composition may contain, as a pharmaceutical ingredient, a drug other than those mentioned above. Such drugs may include, for example, glycyrrhizic acids, allantoin, , disinfectant, astringent, protective agent, ammonia water, vitamin E, vitamin A, etc. The examples include one or more selected from the group:

[0033] Examples of glycyrrhizic acids include glycyrrhizic acid and its derivatives, and Salts (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.) , glycyrrhetinic acid, etc. Examples of fungicides include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, Propyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyric acid Benzyl parahydroxybenzoate, Isobutyl parahydroxybenzoate, Sodium benzoate , Benzoic acid, Benzyl benzoate, Benzalkonium chloride, Cetylpyridinium chloride, Chloride Benzethonium and the like. Astringent and protective agents include, for example, calamine and zinc oxide. Examples of vitamin E include tocopherol, tocopherol succinate, Examples include tocopherol acetate and tocopherol nicotinate. Examples of vitamin A include vitamin A oil and retinol palmitate. Examples include:

[0034] In addition, in the present disclosure, the liquid or semi-solid composition may be prepared in accordance with the dosage form, administration method, etc. of the composition. If necessary, additives used in the pharmaceutical field may be added. Examples of the additives include gelling agents, polyhydric alcohols, oils and fats, emulsifiers, solubilizers, pH adjusters, antioxidants, etc. Softeners, softeners, thickeners, moisturizers, preservatives, stabilizers, transdermal absorption enhancers, flavoring agents, sweeteners, etc. These may be used singly or in combination of two or more. Good too.

[0035] Examples of gelling agents include acrylic acid polymers such as carboxyvinyl polymers; Hydroxyethyl cellulose, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose Water-soluble or water-swellable cellulose such as cellulose, methyl cellulose, and ethyl cellulose Examples of suitable polymers include polyvinylpyrrolidone. Examples of polyhydric alcohols include glycerin, ethylene glycol, and propylene glycol. Examples include chol, butylene glycol, macrogol, and polypropylene glycol. . Examples of oils and fats include squalane, paraffin, liquid paraffin, and light liquid paraffin. hydrocarbons such as acetone, petrolatum; isopropyl myristate, octyldodecyl myristate Fatty acid esters such as behenyl alcohol, lauryl alcohol, myristyl alcohol Cole, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleic acid higher alcohols such as behenic acid, lauric acid, myristic acid, stearic acid Higher fatty acids such as carboxylic acid, isostearic acid, and oleic acid; carnauba wax, spermaceti, and ceramide Jojoba oil, beeswax, white beeswax, montan wax, lanolin, refined lanolin, reduced Examples include waxes such as original lanolin; silicone oil; and the like.

[0036] Examples of emulsifiers include propylene glycol mono-fatty acid esters, ethylene glycol Glycerol mono fatty acid ester, glycerin mono fatty acid ester, polyglycerin fatty acid ester Sorbitan fatty acid ester, sucrose fatty acid ester, methyl glucoside fatty acid ester polyhydric alcohol fatty acid esters such as alkyl alcohols, alkyl polyglucosides, etc. alkyl ether; polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl Nyl ether, polyoxyethylene phytosterol, polyoxyethylene phytostano polyoxyethylene polyoxypropylene alkyl ethers, etc. Polyoxyethylene mono-fatty acid ester, polyethylene glycol di-fatty acid Ester, Polyoxyethylene Glycerin Fatty Acid Ester, Polyoxyethylene Sorbita sorbitol fatty acid ester, polyoxyethylene sorbitol fatty acid ester, polyoxyethylene methyl glucoside fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene Castor oil, polyoxyethylene vegetable oil, polyoxyethylene alkyl ether fatty acid In addition to nonionic surfactants such as ether esters, sodium lauryl sulfate and ionic surfactants such as sodium cetyl sulfate. Examples of the solubilizer include the nonionic surfactants or ionic surfactants exemplified above as emulsifiers. In addition to ionic surfactants, examples include liquid paraffin and crotamiton.

[0037] Examples of pH adjusters include organic acids or salts thereof such as acetic acid, sodium acetate, and glacial acetic acid; Hydrochloric acid, sulfuric acid, phosphoric acid, sodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate Inorganic acids or their salts such as sodium, sodium carbonate, sodium bicarbonate, etc.; sodium hydroxide Alkali hydroxides such as potassium hydroxide, calcium hydroxide, magnesium hydroxide, etc.; amines such as ethanolamine, diethanolamine, and diisopropanolamine. can be done. Antioxidants include, for example, sodium sulfite, ascorbic acid, sodium hydrogen sulfite, , edetate sodium, erythorbic acid, cysteine ​​hydrochloride, citric acid, tocopherol , tocopherol acetate, soybean lecithin, propyl gallate, etc. Examples of softeners include allantoin, almond oil, olive oil, glycerin, and fluidizing agents. Paraffin, squalane, squalene, refined lanolin, medium chain triglycerides, natto Examples of suitable oils include laurel oil, castor oil, propylene glycol, and polybutene. Examples of thickeners include polyvinylpyrrolidone, carboxymethyl cellulose, and colophony. Iodized aluminum silicate, xanthan gum, locust bean gum, tragacanth gum, Examples include guar gum, gelatin, gum arabic, alginic acid, and albumin. Moisturizing agents include sodium hyaluronate, glycerin, and 1,3-butylene glycol. , propylene glycol, urea, sucrose, erythritol, sorbitol, etc. . Examples of stabilizers include adipic acid, ascorbic acid, sodium sulfite, and sulfite. Examples include sodium hydrogen carbonate, sodium chloride, hydrogenated oil, and cysteine. Examples of the percutaneous absorption enhancer include fatty acid esters such as diisopropyl adipate. Examples include: Flavoring agents and sweeteners include, for example, acesulfame potassium, stevia, thaumatin, Sucralose, panose, trehalose, erythritol, lactitol, reduced palatin sugar, coupling sugar, fructooligosaccharide, galactooligosaccharide, lactoferrin oligosaccharide, Somalto-oligosaccharide, palatinose oligosaccharide, raffinose, aspartame, fructose, xylose Lithol, brown sugar, saccharin or its salt, sorbitol, lactose, white sugar, honey, Examples include glucose, maltitol, maltose, mannitol, and starch syrup.

[0038] In the present disclosure, the pH of the liquid or semi-solid composition is not particularly limited, but the stability of the composition is important. From the viewpoint of quality and usability, the pH at 25°C is preferably 3 to 8, more preferably 4 to 6. It is particularly preferred that

[0039] In the present disclosure, the method for producing a liquid or semi-solid composition is not particularly limited. Depending on the type and amount of ingredients, properties of the composition, dosage form, route of administration, and use, etc., It can be produced by known methods described in the General Rules for Preparations of the Pharmacopoeia, etc.

[0040] In the present disclosure, the method of administration or application of the liquid or semi-solid composition is not particularly limited, and Oral administration; parenteral administration such as transdermal administration and vaginal administration. In the present invention, prednisolone valerate ester is used. Pharmacological action of ester acetate and properties of liquid or semi-solid compositions (location, shape, etc. of the affected area) Parenteral administration is preferred because it allows flexible application of only the required amount depending on the area. Transdermal administration is particularly preferred.

[0041] In the present disclosure, the formulation of a liquid or semi-solid composition refers to a composition in a liquid or semi-solid form. There are no particular limitations as long as the information is accurate, and depending on the purpose of use, for example, Article 18 The dosage forms can be selected appropriately from those listed in the General Provisions for Preparations in the Revised Japanese Pharmacopoeia. Specifically, for example, preparations to be applied to the skin (external liquids, sprays, ointments, creams, etc.) and oral preparations (oral liquids, syrups, oral jellies, etc.). can be done. In the present disclosure, the dosage form of the liquid or semi-solid composition includes external liquid, spray, The dosage form is preferably selected from the group consisting of ointments, creams and gels, and more preferably liniments, Lotions, topical aerosols, pump sprays, ointments, creams and gels More preferred dosage forms are selected from the group consisting of lotions, ointments, creams and gels. More preferred is a dosage form selected from the group consisting of lotions, and particularly preferred is a lotion.

[0042] The liquid or semi-solid composition of the present disclosure may be contained in a container. Examples of containers include bottles and tubes. The material of the container is not particularly limited, and may be selected appropriately from the viewpoint of ease of use, etc. Specific examples of materials that can be used include aluminum foil, glass, and plastic (polyethylene Polyesters such as polyethylene terephthalate; polyethylenes such as LDPE and HDPE; Examples of the material include polyolefins such as propylene, but aluminum foil is preferred. In the present invention, the means for storing the liquid or semi-solid composition in a container is not particularly limited. The container can be filled in a conventional manner according to the shape of the container and the properties of the composition. The packaged composition of the present invention can be prepared.

[0043] The liquid or semi-solid composition of the present disclosure contains prednisolone valerian, which has excellent anti-inflammatory activity. Since it contains acetic acid esters, it can be used as a pharmaceutical or quasi-drug. For example, as an antipruritic and anti-inflammatory agent, more specifically, for example, eczema, dermatitis, sores, and heat rash , rash, itching, chilblains, insect bites and hives. It can be suitably used as an antipruritic and anti-inflammatory drug.

[0044] The present disclosure provides a composition comprising the following component (A): (A) Prednisolone valerate acetate ester in an amount exceeding 0.15% by mass relative to the total mass of the composition Le; A liquid or semi-solid composition containing the following component (B): (B) one or more selected from the group consisting of the following components (B-1) to (B-7): (B-1) Local anesthetic ingredient (B-2) Crotamiton (B-3) Antihistamine ingredients (B-4) Salicylic acids (B-5) Terpenes (B-6) Panthenols (B-7) Hydroxycarboxylic acids The present invention also relates to a method for inhibiting crystal precipitation, which comprises a step of incorporating " refers to storage conditions at low temperatures (temperatures below 0°C, preferably below 0°C, particularly preferably -20°C). When stored for the same period under the same temperature, the difference was visually confirmed compared to when the product did not contain component (B). This means that no visible crystal precipitation is observed or the amount of crystal precipitation is small. The "method for inhibiting crystal precipitation" refers to a method for inhibiting crystal precipitation by adding components (A) and (B) to a liquid or semi-solid composition. By having the above-mentioned "suppression of crystal precipitation" can be achieved (for example, when the material is stored at a low temperature). If the sample was stored under the conditions described above, the above-mentioned "suppression of crystal precipitation" would occur. It means to do.

[0045] In such an embodiment, the order of the step of blending component (A) and the step of blending component (B) is The order is not particularly limited, and the liquid or semi-solid composition containing components (A) and (B) can be directly The gene may be produced directly or indirectly. In this embodiment, the meanings of various terms, the amounts of each component, etc. are all based on the "liquid or semi-solid" This is the same as that explained for the "composition having the shape of a particle."

[0046] This specification discloses the invention exemplified below in relation to the above embodiments. It is not limited to these in any way. <a1>The following components (A) and (B): (A) Prednisolone valerate acetate ester in an amount exceeding 0.15% by mass relative to the total mass of the composition Le; (B) one or more selected from the group consisting of the following components (B-1) to (B-7): (B-1) Local anesthetic ingredient (B-2) Crotamiton (B-3) Antihistamine ingredients (B-4) Salicylic acids (B-5) Terpenes (B-6) Panthenols (B-7) Hydroxycarboxylic acids A liquid or semi-solid composition comprising:

[0047] <a2>Component (A) is prednisolone valerate ester in an amount of 0.3% by mass based on the total mass of the composition. It is an ester acetate. <a1>The composition described.

[0048] <a3>Component (B-1) is ethyl aminobenzoate, oxypolyethoxydodecane, Dibucaine, procaine, mepivacaine, meprylcaine, lidocaine and their salts and solvates thereof, <a1>or <a2>Note The composition described above. <a4>The component (B-2) is a compound consisting of crotamiton, its salts, and solvates thereof. and one or more selected from the group consisting of <a1> ~ <a3>The composition described in any one of the above. <a5>Ingredient (B-3) is isothipendyl, chlorpheniramine, diphenylpyridine one or more selected from the group consisting of phosphate and diphenhydramine and salts thereof; <a1> ~ <a4>The composition described in any one of the above.

[0049] <a6>Ingredient (B-4) is salicylic acid, glycol salicylate, sodium salicylate and methyl salicylate, <a1> ~ <a5> The composition described in any one of the above. <a7>Ingredient (B-5) is cymene, thymol, terpinene, terpinolene, ferulic acid, Endrene, limonene, carveol, terpineol, menthol, carvone, menthone , perillaldehyde, cineole, monoterpene ether, 3-methyl-4-isopropyl Composed of phenol (isopropylmethylphenol), borneol, and camphor One or more selected from the group <a1> ~ <a6>The composition described in any one of the above. <a8>Ingredient (B-6) is panthenol, pantothenic acid, acetylpantothenyl ester pantothenyl ethyl ether and pantothenyl ethyl ether, and salts thereof. One or more species, <a1> ~ <a7>The composition described in any one of the above. <a9>Ingredient (B-7) is citric acid, sodium citrate, tartaric acid, sodium tartrate lactic acid, calcium lactate, sodium lactate, fumaric acid, and malic acid. There is more than one type that can be identified. <a1> ~ <a8>The composition described in any one of the above.

[0050] <a10>No crystal precipitation occurs when stored at -20°C for one week. 1>~ <a9>The composition described in any one of the above. <a11>A drug selected from the group consisting of lotions, ointments, creams, and gels It is a shape, <a1> ~ <a10>The composition described in any one of the above.

[0051] <b1>The following component (A): (A) Prednisolone valerate acetate ester in an amount exceeding 0.15% by mass relative to the total mass of the composition Le; A liquid or semi-solid composition containing the following component (B): (B) antihistamine components; A method for inhibiting crystal precipitation, comprising the step of incorporating:

[0052] <b2>Component (A) is prednisolone valerate ester in an amount of 0.3% by mass based on the total mass of the composition. It is an ester acetate. <b1>The method described.

[0053] <b3>Component (B-1) is ethyl aminobenzoate, oxypolyethoxydodecane, Dibucaine, procaine, mepivacaine, meprylcaine, lidocaine and their salts and solvates thereof, <b1>or <b2>Note How to post. <b4>The component (B-2) is a compound consisting of crotamiton, its salts, and solvates thereof. and one or more selected from the group consisting of <b1> ~ <b3>Any of the methods described above. <b5>Ingredient (B-3) is isothipendyl, chlorpheniramine, diphenylpyridine one or more selected from the group consisting of phosphate and diphenhydramine and salts thereof; <b1> ~ <b4>Any of the methods described above.

[0054] <b6>Ingredient (B-4) is salicylic acid, glycol salicylate, sodium salicylate and methyl salicylate, <b1> ~ <b5> Any of the methods described above. <b7>Ingredient (B-5) is cymene, thymol, terpinene, terpinolene, ferulic acid, Endrene, limonene, carveol, terpineol, menthol, carvone, menthone , perillaldehyde, cineole, monoterpene ether, 3-methyl-4-isopropyl Composed of phenol (isopropylmethylphenol), borneol, and camphor One or more selected from the group <b1> ~ <b6>Any of the methods described above. <b8>Ingredient (B-6) is panthenol, pantothenic acid, acetylpantothenyl ester pantothenyl ethyl ether and pantothenyl ethyl ether, and salts thereof. One or more species, <b1> ~ <b7>Any of the methods described above. <b9>Ingredient (B-7) is citric acid, sodium citrate, tartaric acid, sodium tartrate lactic acid, calcium lactate, sodium lactate, fumaric acid, and malic acid. There is more than one type that can be identified. <b1> ~ <b8>Any of the methods described above. <b10>The dosage form of the composition is selected from the group consisting of lotion, ointment, cream and gel. A dosage form selected from the group consisting of: <b1> ~ <b9>Any of the methods described above. [Example]

[0055] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. It is not something that can be done.

[0056] [Test Example 1] Preservation test Part 1 Various liquid compositions containing the ingredients and amounts (g) per 100 g shown in Table 1 below were prepared. This was prepared by the method and placed in a glass bottle (2K standard bottle). The resulting compositions were stored at -20°C for one week. The absence was confirmed visually, and if no crystal precipitation was observed, it was marked with an O; if crystal precipitation was observed, it was marked with an O. was evaluated as ×. The content (mass%) of prednisolone valerate acetate in various compositions was also The results are shown in Table 1.

[0057] [Table 1]

[0058] From the results shown in Table 1, the amount of prednisolone valerate acetate relative to the total mass of the composition was In the composition of Reference Example 1 containing 0.15% by mass of PEG, no crystal precipitation occurred even after storage at -20°C for 1 week. However, crystal precipitation was observed in the composition of Comparative Example 1 containing 0.3 mass % of cellulose. Since this was observed, it is believed that the crystallization occurred when prednisolone valerate acetate was 0. It was found that the problem occurs when the content exceeds 0.15 mass%. However, in addition to 0.3% by mass of prednisolone valerate acetate, The composition of Example 1 further containing lidocaine, and the composition of Example 2 further containing lidocaine hydrochloride In the composition of Example 2, no crystal precipitation occurs even after storage at -20°C for 1 week. It became clear that:

[0059] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate The liquid or semi-solid composition further contains lidocaine, lidocaine hydrochloride, or By incorporating a local anesthetic ingredient, the effect is improved compared to when such an ingredient is not incorporated. It was revealed that crystal precipitation was relatively suppressed.

[0060] [Test Example 2] Preservation test No. 2 Various liquid compositions containing the ingredients and amounts (g) per 100 g shown in Table 2 below were prepared. The test was carried out in the same manner as in Test Example 1. The results are shown in Table 2.

[0061] [Table 2]

[0062] From the test results shown in Table 2, 0.3% by mass of prednisolone valerate acetate ester In the composition of Example 3, which further contains crotamiton in addition to methicillin, the same results were obtained as in Examples 1 and 2. It was revealed that, similar to the composition of (1), no crystal precipitation occurred even after storage at -20°C for one week.

[0063] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate The liquid or semi-solid composition further contains a crotamiton compound represented by crotamiton. By including these compounds, the crystallization rate is relatively low compared to when these compounds are not included. It was found that the release was suppressed.

[0064] [Test Example 3] Preservation test No. 3 Various liquid compositions containing the ingredients and amounts (g) per 100 g shown in Table 3 below were prepared. The test was carried out in the same manner as in Test Example 1. The results are shown in Table 3.

[0065] [Table 3]

[0066] From the test results shown in Table 3, 0.3% by mass of prednisolone valerate acetate ester The composition of Example 4 further contains diphenhydramine in addition to diphenhydramine. In the composition of Example 5 containing amine hydrochloride, the same as in the compositions of Examples 1 and 2, the concentration of α-tocopherol was −20 It was revealed that no crystal precipitation occurred even after storage at ℃ for one week.

[0067] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate A liquid or semi-solid composition containing, further comprising, diphenhydramine, diphenhydramine By incorporating an antihistamine component, such as imipenem hydrochloride, It was found that crystal precipitation was relatively suppressed compared to when no treatment was performed.

[0068] [Test Example 4] Preservation test No. 4 Various liquid compositions containing the ingredients and amounts (g) shown in Table 4 below per 100 g were prepared. The test was carried out in the same manner as in Test Example 1. The results are shown in Table 4.

[0069] [Table 4]

[0070] From the test results shown in Table 4, 0.3% by mass of prednisolone valerate acetate ester The same experiment was also carried out in the composition of Example 6, which further contained glycol salicylate in addition to the hydroxybenzoate. As with the compositions of Examples 1 and 2, it was found that no crystal precipitation occurred even after storage at -20°C for one week. It was.

[0071] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate A liquid or semi-solid composition containing the above, further comprising a salicylic acid represented by glycol salicylate. By including licylic acids, the effect is relatively improved compared to when such components are not included. It was revealed that crystal precipitation was suppressed.

[0072] [Test Example 5] Preservation test No. 5 Various liquid compositions containing the ingredients and amounts (g) per 100g shown in Table 5 below were prepared. The test was carried out in the same manner as in Test Example 1. The results are shown in Table 5.

[0073] [Table 5]

[0074] From the test results shown in Table 5, 0.3% by mass of prednisolone valerate acetate ester The composition of Example 7 further contains l-menthol in addition to camphor; The composition of Example 8 containing isopropyl methylphenol and the composition of Example 9 containing isopropyl methyl phenol were In this case, similar to the compositions of Examples 1 and 2, no crystal precipitation occurred even after storage at -20°C for one week. It became clear that:

[0075] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate A liquid or semi-solid composition containing the compound, further containing l-menthol, dl-camphor, iodopropanol, methylparaben ... By incorporating terpenes such as isopropylmethylphenol, It was found that crystal precipitation was relatively suppressed compared to when the component was not contained.

[0076] [Test Example 6] Preservation test No. 6 Various liquid compositions containing the ingredients and amounts (g) per 100 g shown in Table 6 below were prepared. The test was carried out in the same manner as in Test Example 1. The results are shown in Table 6.

[0077] [Table 6]

[0078] From the test results shown in Table 6, 0.3% by mass of prednisolone valerate acetate ester In the composition of Example 10, which further contains panthenol in addition to the hydroxybenzoate, As with composition 2, it was revealed that no crystal precipitation occurred even after storage at -20°C for one week.

[0079] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate The liquid or semi-solid composition further contains a panthenol-based compound represented by panthenol. By including these compounds, the crystallization rate is relatively low compared to when these compounds are not included. It was found that the release was suppressed.

[0080] [Test Example 7] Preservation test No. 7 Various liquid compositions containing the ingredients and amounts (g) per 100 g shown in Table 7 below were prepared. The test was carried out in the same manner as in Test Example 1. The results are shown in Table 7.

[0081] [Table 7]

[0082] From the test results shown in Table 7, 0.3% by mass of prednisolone valerate acetate ester The same was also carried out in the composition of Example 11, which further contained sodium citrate in addition to the ethanol. As with the compositions of Examples 1 and 2, it was found that no crystal precipitation occurred even after storage at -20°C for one week. It was.

[0083] From the above test results, it was found that more than 0.15% by mass of prednisolone valerate acetate The liquid or semi-solid composition containing the above-mentioned compound further contains an oxybenzone such as sodium citrate. By incorporating carboxylic acids, the relative It was revealed that crystal precipitation was effectively suppressed.

[0084] [Manufacturing Example 1] A liquid composition containing the following ingredients and amounts per 100g was prepared by a conventional method and placed in a container ( Cap: Polypropylene, Inner stopper: Polyethylene, Bottle: Polyethylene or Polypropylene pyrene) to obtain a lotion preparation of Production Example 1. Prednisolone valerate acetate 0.3g Diphenhydramine hydrochloride 2.0g Allantoin 0.2g Isopropylmethylphenol 0.1g Additives: edetate sodium hydrate, citric acid hydrate, benzyl alcohol, ethanol and purified water

[0085] [Manufacturing Example 2] A liquid composition containing the following ingredients and amounts per 100g was prepared by a conventional method and placed in a container ( Cap: Polypropylene, Inner stopper: Polyethylene, Bottle: Polyethylene or Polypropylene pyrene) to obtain a lotion preparation of Production Example 2. Prednisolone valerate acetate 0.3g Diphenhydramine hydrochloride 2.0g Allantoin 0.2g Tocopherol acetate 0.5g Additives: edetate sodium hydrate, citric acid hydrate, benzyl alcohol, ethanol and purified water

[0086] [Manufacturing Example 3] A liquid composition containing the following ingredients and amounts per 100g was prepared by a conventional method and placed in a container ( Cap: Polypropylene, Inner stopper: Polyethylene, Bottle: Polyethylene or Polypropylene pyrene) to obtain a lotion preparation of Production Example 3. Prednisolone valerate acetate 0.3g Lidocaine 1.0g Isopropylmethylphenol 0.1g l-menthol 5.0g Additives: edetate sodium hydrate, citric acid hydrate, benzyl alcohol, ethanol and purified water

[0087] [Manufacturing Example 4] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. The ointment of Example 4 was obtained. Prednisolone valerate acetate 0.3g Diphenhydramine hydrochloride 2.0g Allantoin 0.2g Tocopherol acetate 0.5g Additives: methyl parahydroxybenzoate, propyl parahydroxybenzoate, white petrolatum and Animal Paraffin

[0088] [Manufacturing Example 5] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. The ointment of Example 5 was obtained. Prednisolone valerate acetate 0.3g dl-Camphor 1.0g l-menthol 5.0g Tocopherol acetate 0.5g Additives: methyl parahydroxybenzoate, propyl parahydroxybenzoate, white petrolatum and Animal Paraffin

[0089] [Manufacturing Example 6] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. The ointment of Example 6 was obtained. Prednisolone valerate acetate 0.3g Crotamiton 5.0g Allantoin 0.2g Tocopherol acetate 0.5g Additives: methyl parahydroxybenzoate, propyl parahydroxybenzoate, white petrolatum and Animal Paraffin

[0090] [Manufacturing Example 7] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. The cream of Example 7 was obtained. Prednisolone valerate acetate 0.3g Crotamiton 5.0g Glycol salicylate 1.0g Tocopherol acetate 0.5g Additives: Medium chain triglyceride, diisopropyl adipate, dimethylpolysiloxane , concentrated glycerin, behenyl alcohol, polyoxyethylene arachidyl ether, stearic acid Alcohol mixture, xanthan gum, sodium alginate, methylparaben Citric acid hydrate, sodium citrate hydrate and refined water production

[0091] [Manufacturing Example 8] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. The cream of Example 8 was obtained. Prednisolone valerate acetate 0.3g Glycol salicylate 1.0g dl-Camphor 1.0g l-menthol 5.0g Additives: Medium chain triglyceride, diisopropyl adipate, dimethylpolysiloxane , concentrated glycerin, behenyl alcohol, polyoxyethylene arachidyl ether, stearic acid Alcohol mixture, xanthan gum, sodium alginate, methylparaben Citric acid hydrate, sodium citrate hydrate and refined water production

[0092] [Manufacturing Example 9] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. The cream of Example 9 was obtained. Prednisolone valerate acetate 0.3g Diphenhydramine hydrochloride 2.0g Allantoin 0.2g Tocopherol acetate 0.5g Additives: Medium chain triglyceride, diisopropyl adipate, dimethylpolysiloxane , concentrated glycerin, behenyl alcohol, polyoxyethylene arachidyl ether, stearic acid Alcohol mixture, xanthan gum, sodium alginate, methylparaben Citric acid hydrate, sodium citrate hydrate and refined water production

[0093] [Manufacturing Example 10] A semi-solid composition containing the following ingredients and amounts per 100 g was prepared by a conventional method, and the volume was The container (cap: polypropylene, tube: metal or polyethylene) is used for manufacturing. A gel of Example 10 was obtained. Prednisolone valerate acetate 0.3g Diphenhydramine hydrochloride 2.0g Glycyrrhetinic acid 1.0g Tocopherol acetate 0.5g Additives: benzyl alcohol, hypromellose, citric acid hydrate, sodium edetate water hydrate, ethanol, purified water [Industrial Applicability]

[0094] According to the present invention, a storage-safe product in which crystal precipitation is relatively suppressed when stored under low-temperature conditions is obtained. Prednisolone valerate acetate, which has good quality and excellent efficacy, It is possible to provide a liquid or semi-solid composition containing the compound, which can be suitably used in the pharmaceutical industry, etc. . < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / a1> ​ < / a1> < / a1> < / a1> < / a1> < / a1> < / a1>

Claims

1. The following components (A) and (B): (A) Prednisolone valerate acetate ester in an amount of more than 0.15% by weight based on the total weight of the composition Lu; (B) terpenes; A liquid or semi-solid composition comprising:

2. Component (A) is 0.3% by mass of prednisolone valerate acetate based on the total mass of the composition. The composition of claim 1 which is an ester.

3. Component (B) is isopropylmethylphenol, isoborneol, irone, ocimene , Carveol, Carbotanacetone, Carbomentone, Carvone, Karen, Karon, Kan Fen, camphor, geraniol, sabinene, safranal, cyclocitral, citra ol, citronellal, citronellic acid, citronellol, cineole, cymene, silvestris Tren, thymol, isothujol, thujone, terpineol, terpinene, terpinol Rene, tricyclene, nerol, pinene, pinocampheol, pinol, piperitenone , Phellandral, Phellandrene, Fenchyl, Fenchyl alcohol, Perillyl Alcohol, perillaldehyde, borneol, myrcene, menthol, menthone, yono 10. The compound according to claim 9, wherein the compound is one or more selected from the group consisting of ethanol, ionone, linalool, and limonene.

1. The composition described in 1.

4. The composition according to claim 1, which does not cause crystal precipitation when stored at -20°C for one week. Finished product.

5. The dosage form is selected from the group consisting of lotions, ointments, creams and gels. The composition according to any one of claims 1 to 4.

6. The following component (A): (A) Prednisolone valerate acetate ester in an amount of more than 0.15% by weight based on the total weight of the composition Lu; A liquid or semi-solid composition containing the following component (B): (B) terpenes; A method for inhibiting crystal precipitation, comprising the step of incorporating:

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