Pharmaceutical composition containing prednisolone valerate acetate

Abstract

A pharmaceutical composition containing prednisolone valerate acetate is provided. [Solution] (A) Prednisolone valerate acetate; (B) Dicarboxylic acid Prepare a pharmaceutical composition containing diester and (C) petrolatum. The substance is, in particular, in the form of a topical skin composition.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition containing prednisolone valerate acetate .

Background Art

[0002] Skin diseases such as atopic dermatitis, senile pruritus, urticaria, eczema, and boils, or the itching of the skin associated with dry skin is very uncomfortable for patients and may interfere with daily life. When unable to bear such itching of the skin and scratching causes stimuli such as scratches on the scratched area, the symptoms may further deteriorate, leading to a vicious cycle of stronger itching. Therefore, in order to improve such diseases or conditions accompanied by itching, it is important to first suppress the itching.

[0003] It is known that a decrease in the skin barrier function is involved as a cause and exacerbating factor of such itching, and skin moisturization is important to prevent this. As a method of moisturization, there is a method of increasing the occlusivity of the skin surface

[0004] by oily agents such as vaseline. In addition, steroid agents are known as drugs for suppressing itching. Steroid agents are widely used in the treatment of atopic dermatitis due to their anti-inflammatory effects, and various steroid-containing preparations have been proposed (Patent Document 1).

Prior Art Documents

[0005]

Patent Document 1

Summary of the Invention

[0006] The present invention provides a stable pharmaceutical composition containing prednisolone valerate acetate. The purpose is to provide. [Means for solving the problem]

[0007] According to the inventors' research, including petrolatum in topical pharmaceutical preparations provides moisturizing properties. While particularly desirable from the above standpoint, prednisolone valerate acetate and petrolatum When preparing a formulation containing [the specified substance], it was found that the physical stability of the formulation becomes a problem.

[0008] The inventors of this invention have conducted extensive research to solve this problem, and as a result, have found that (A) prednisolone valerium (B) Acid ester acetate; (C) Dicarboxylic acid diester; and (C) Petrolatum By doing so, we discovered that a stable pharmaceutical composition could be obtained, and thus completed the present invention.

[0009] In other words, the present invention provides the following pharmaceutical compositions. Section 1. (A) Prednisolone valerate acetate; (B) Dicarboxylic acid diesters; and (C) Vaseline A pharmaceutical composition containing the following: Section 2. (B) Dicarboxylic acid diesters include diethyl sebacate, diisopropyl adipate, and One or more selected from the group consisting of diisopropyl sebacate, as described in item 1. A pharmaceutical composition. Section 3. (B) The concentration of the dicarboxylic acid diester is 0.1 to 20% by mass, as described in item 1 or 2. Pharmaceutical composition. Section 4. (B) component's parts by mass with respect to (A) component's parts by mass is 8 - 90, any one of items 1 - 3 or the pharmaceutical composition described in any one of the items 1 - 3.

[0010] Furthermore, the present invention relates to the following method. Item 5. A pharmaceutical composition containing (A) prednisolone valerate acetate and (C) petrolatum A method for formulating a pharmaceutical composition, characterized in that (B) a dicarboxylic acid diester is allowed to coexist. Stabilization method.

[0011] Furthermore, the present invention relates to the following stabilizer. Item 6. A formulation stabilizer for a pharmaceutical composition containing (A) prednisolone valerate acetate and (C) petrolatum, containing (B) a dicarboxylic acid diester.

Advantages of the Invention

[0012] According to the present invention, a stable pharmaceutical composition can be provided.

Modes for Carrying Out the Invention

[0013] [Pharmaceutical Composition] The pharmaceutical composition of the present invention is a pharmaceutical composition containing (A) prednisolone valerate acetate; (B) a dicarboxylic acid diester; and (C) petrolatum.

[0014] ((A) Prednisolone valerate acetate) The prednisolone valerate acetate used in the present invention is not particularly limited as long as it is used in pharmaceuticals or quasi-drugs.

[0015] In the pharmaceutical composition of the present invention, the content of component (A) with respect to the total amount of the pharmaceutical composition is other The amount is set appropriately depending on the balance with the other components. The amount of component (A) relative to the total amount of the pharmaceutical composition The amount is preferably 0.05% by mass or more, more preferably 0.075% by mass or more. More preferably, it is 0.1% by mass or more. The content of component (A) relative to the total amount of the pharmaceutical composition. The amount is preferably 0.25% by mass or less, and more preferably 0.15% by mass or less. The total content of component (A) relative to the total amount of the pharmaceutical composition is preferably 0.05 to 0.25% by mass, more preferably 0.075 to 0.15% by mass, even more preferably 0 It is between 0.1 and 0.15 mass percent.

[0016] ((B) Dicarboxylic acid diester) Examples of dicarboxylic acid diesters used in the present invention include diethyl adipate, Diisopropyl adipate, diisobutyl adipate, di-2-heptyl adipate Decyl, diethyl sebacate, di-2-ethylhexyl sebacate, diisopropyl sebacate Examples include ropil, diethoxyethyl succinate, and diethylhexyl succinate. Among them, diethyl adipate, diisopropyl adipate, diisobutyl adipate, and A combination of one or more selected from the group consisting of diethyl sebacate is preferred. It is preferable. In particular, diethyl adipate and / or diethyl sebacate are especially preferred. These are not particularly limited as long as they are used in the field of pharmaceuticals or quasi-drugs. Also, commercially available products can be used as is.

[0017] In the pharmaceutical composition of the present invention, the total content of component (B) relative to the total amount of the pharmaceutical composition is favorable. More preferably 0.1% by mass or more, more preferably 1% by mass or more, and even more preferably 2% by mass It is % or more. The total content of component (B) relative to the total amount of the pharmaceutical composition is preferably 20% It is less than or equal to a certain percentage by mass, more preferably less than or equal to 10% by mass, and even more preferably less than or equal to 5% by mass. The total content of component (B) relative to the total amount of the pharmaceutical composition is preferably 0.1 to 20 by mass. The amount is %, more preferably 1 to 10% by mass, and even more preferably 3 to 8% by mass.

[0018] In the pharmaceutical composition of the present invention, the ratio of the content of component (B) to component (A) is particularly While not limited to the above, the total content of component (B) is preferably such that it is equal to 1 part by mass of component (A). Or 8 to 90 parts by mass, more preferably 16 to 42 parts by mass, even more preferably 25 to 42 This is the mass part.

[0019] ((C) Vaseline) (C) Vaseline used in the present invention is a semi-solid hydrocarbon mixture obtained from petroleum, and is medical It is not particularly limited as long as it is used in the fields of pharmaceuticals, quasi-drugs, or cosmetics. For petrolatum, either white petrolatum or yellow petrolatum can be used, but High-quality white petrolatum is preferred.

[0020] You can also use commercially available petroleum jelly as is.

[0021] In the pharmaceutical composition of the present invention, the total content of component (C) relative to the total amount of the pharmaceutical composition is favorable. More preferably 0.01% by mass or more, more preferably 1% by mass or more, and even more preferably 5% by mass It is % or more. The content of component (C) relative to the total amount of the pharmaceutical composition is preferably 90%. The amount is less than or equal to % by mass, more preferably 75% by mass or less, and even more preferably 50% by mass or less. The content of component (C) relative to the total amount of the pharmaceutical composition is preferably 0.01 to 90% by mass. More preferably, 1 to 75% by mass, and even more preferably 5 to 50% by mass. If the pharmaceutical composition is an ointment, preferably 30-95% by mass, more preferably 40% It is 80% by mass.

[0022] In the pharmaceutical composition of the present invention, the ratio of the content of component (C) to component (A) is not particularly limited. Although not specified, the content of component (C) is preferably such that it is 1 part by mass of component (A). The amount is 0.08 to 750 parts by mass, more preferably 8 to 625 parts by mass, and even more preferably 42 to It is 420 parts by mass.

[0023] (water) The pharmaceutical composition of the present invention may be a liquid composition containing water, but may also be a composition that does not contain water. It is acceptable. The proportion of water to be added is not limited, but is preferable for the pharmaceutical composition. The amount is 20-80% by mass, more preferably 30-70% by mass, and even more preferably 35-65%. This is expressed in mass percent. If the pharmaceutical composition is an ointment, it is preferably 5% by mass relative to the pharmaceutical composition. More preferably, the amount is 1% by mass or less, and even more preferably, 0.1% by mass or less.

[0024] (Other ingredients) The pharmaceutical composition of the present invention further contains, in addition to the above components (A), (B), and (C), various One or more active ingredients can be used in combination. Preferably, an antihistamine Antipruritic agents other than methamines and antihistamines, anti-inflammatory ingredients, antibacterial / antiseptic ingredients, local anesthetics, etc. They can also be combined.

[0025] Examples of antihistamines include diphenhydramine and bromodifenhydramine. Ethanolamine-based antihistamines such as diphenylpyraline, and chlorpheniramine. Propylamine-based antihistamines such as propylamine-based antihistamines, and phenothiazine-based antihistamines such as isotipendyl. Examples include stamina-inducing drugs and their salts.

[0026] Examples of antipruritic agents other than antihistamines include crotamiton.

[0027] Examples of anti-inflammatory components include allantoin and its derivatives (e.g., alcloxa, (e.g., allantoin), glycyrrhizic acid or its derivatives or salts thereof (e.g., glycyrrhizic acid) Dipotassium lycyrrhizinate, monoammonium glycyrrhizate, etc., glycyrrhetin Acids or their derivatives or salts thereof (for example, glycyrrhetinic acid, glycyrrhetinic acid salts) (such as tharyl), zinc oxide, tocopheryl acetate, menthol, camphor, turpentine oil, (A) Steroids other than the component or their derivatives or salts thereof (e.g., hydrocol Examples include thizone and prednisolone.

[0028] Examples of antibacterial and antiseptic ingredients include benzalkonium chloride, acrinol, and ethanol. Benzethonium chloride, cetyltrimethylammonium chloride, cresol, povidone-iodine Potassium iodide, iodine, isopropylmethylphenol, parabens, phenoxyethanol Cetylpyridinium chloride, miconazole or its salt, chlorobutanol or Plants (for example, aloe, Sophora flavescens, rosemary, mulberry, eucalyptus, cinchona, clove, etc.) Examples include components derived from [the subject].

[0029] Examples of local anesthetics include lidocaine, dibucaine, and ethyl aminobenzoate. .

[0030] (Base, carrier, additives, etc.) The pharmaceutical composition of the present invention does not hinder the effects of the present invention from the viewpoint of improving usability, stability, etc. In addition to the above components (A), (B), and (C), a base, carrier, or additives, etc. It may include.

[0031] Examples of bases, carriers, or additives include surfactants, higher fatty acids, and higher alcohols. (C) hydrocarbons other than component (C), oils and fats, waxes, (B) ester oils other than component (B), silico Oil, moisturizing ingredients, polyhydric alcohol, thickener, cooling agent, antioxidant, preservative or antiseptic Examples include pH adjusters and chelating agents. These components can be used individually or in combination. The above ingredients can be combined in any way you like.

[0032] Surfactants can contribute to the stabilization of components. Examples of surfactants include nonionic surfactants. Any of the following may be used: surfactant, cationic surfactant, anionic surfactant, amphoteric surfactant, etc. .

[0033] Here, an anionic surfactant is, for example, fatty acid soap (for example, lauric acid). Sodium palmitate, sodium palmitate, potassium laurate, potassium myristate, Potassium palmitate, potassium stearate, etc.; alkyl sulfate salts (for example, Sodium lauryl sulfate, potassium lauryl sulfate, etc.; alkyl ether sulfate salts (For example, POE-lauryl sulfate triethanolamine, POE-lauryl sulfate sodium (e.g., sodium laureth sulfate); N-acyl sarcosinate (e.g., lauroyl sarcosinate) Synthodium, etc.); higher fatty acid amide sulfonates (e.g., N-myristoyl-N- Sodium methyl taurate, sodium methyl taurate (coconut oil fatty acid), lauryl methyl taurate Sodium urinate, etc.; phosphate ester salt (POE-oleyl ether sodium phosphate) POE-stearyl ether phosphate, sodium lauryl phosphate, polyoxyethylene Sodium lauryl ether phosphate, etc.); sulfosuccinates (e.g., alkyl sulfosuccinates) Sodium succinate, sodium di-2-ethylhexyl sulfosuccinate, polio Sodium xyethylene sulfosuccinate, lauryl polypropylene glycol sulfosuccinate Sodium citrate, etc.; alkylbenzene sulfonates (e.g., linear dodecylbenzene); Sodium sulfonate, linear dodecylbenzenesulfonate triethanolamine, lin Addecylbenzenesulfonic acid, etc.; amino acid-based surfactants (e.g., cocoyl glutamate) Sodium phosphate, N-acyl glutamate, etc.); N-acyl glutamate (for example, Potassium lauroyl glutamate, monosodium N-lauroyl glutamate, N- Disodium thearoyl glutamate, monosodium N-myristoyl-L-glutamate (e.g., um); higher fatty acid ester sulfate salts (e.g., hydrogenated coconut oil fatty acid glycerin sulf) Sodium phosphate, etc.); sulfurized oil (e.g., funnel oil, etc.); ether carboxylate (e.g., polyphosphate). Polyoxyethylene alkyl ether carboxylic acid, polyoxyethylene alkyl allyl ether telcarboxylate salts, sodium polyoxyethylene lauryl ether acetate, etc.; α-ole Fin sulfonates; higher fatty acid ester sulfonates; secondary alcohol sulfates ;Higher fatty acid alkylolamide sulfate salt;Lauroyl monoethanolamide sugar Sodium citrate; N-palmitoyl aspartate ditriethanolamine; casein Examples include thorium.

[0034] Examples of nonionic surfactants include sorbitan fatty acid esters (e.g., sorbitan fatty acid esters). Sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate , sorbitan monostearate, diglycerol penta-2-ethylhexyl sorbita (e.g., diglycerol sorbitan tetra-2-ethylhexylate); propylene glycol) Fatty acid esters (e.g., propylene glycol monostearate); hydrogenated castor oil Oil derivatives (e.g., polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxy Ethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (H CO-60), polyoxyethylene hydrogenated castor oil 80, etc.; polyoxyethylene sorbita Fatty acid esters (for example, polyoxyethylene (20) sorbitan monolaurate) Polysorbate 20), Polyoxyethylene (20) Sorbitan Monostearate (Poly Sorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate (80%), polyoxyethylene (20) sorbitan isostearate, etc.; glycerin Derivatives (e.g., polyoxyethylene monococonut oil fatty acid glyceryl, glycerin alkyl) Ethers); polyoxyalkylene alkyl ethers (e.g., polyoxyethylene ethers) Ethers, etc.; silicone-based surfactants (e.g., polyoxyethylene methylpolysaccharide) Roxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG Examples include polydimethylsiloxyethyl dimethicone, alkyl glucoside, etc. .

[0035] Examples of higher fatty acids include saturated or unsaturated straight-chain or branched-chain fatty acids with 12 to 2 carbon atoms. Two fatty acids can be used, for example, preferably lauric acid, myristic acid, and palladium. Linear saturated fatty acids such as mitic acid, stearic acid, or behenic acid (solid at room temperature); oleic acid Acids, linoleic acid, linolenic acid, palmitoleic acid, eicosapentaenoic acid, paxenic acid or is an unsaturated fatty acid such as docosahexaenoic acid (liquid at room temperature); or isostearic acid or Examples include branched fatty acids such as lanolin fatty acids, or 12-hydroxystearic acid. .

[0036] Examples of higher alcohols include higher alcohols with 12 to 22 carbon atoms and sterols. Examples include lauryl alcohol, myristyl alcohol, and cetanol. L, cetostearyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl Alcohols, such as straight-chain saturated alcohols (solid at room temperature); oleyl alcohol, cerakyl Unsaturated alcohols such as alcohol (liquid at room temperature); or hexyldecanol, iso Stearyl alcohol, octyldodecanol, decyltetradecanol, lanolin alcohol Examples include calls, etc.

[0037] Examples of hydrocarbons other than component (C) include paraffin, ceresin, and isoparaffin. Hard fat, microcrystalline wax, polybutene, polyethylene powder, fluid Paraffin, squalane, gelling hydrocarbons (such as Plastibase), ozokerite, α- Olefin oligomers, light liquid paraffins, and hydrocarbons such as light liquid paraffins It can be listed.

[0038] Oils and fats include avocado oil, linseed oil, camellia oil, macadamia nut oil, and corn oil. Oils: oat oil, olive oil, safflower oil, apricot kernel oil, jojoba oil, grape seed oil, sunflower oil Almond oil, camellia oil, rapeseed oil, sesame oil, castor oil, cocoa butter, coconut oil, hydrogenated oil Japanese oak oil, palm oil, palm kernel oil, Japanese wax kernel oil, Japanese wax, wheat germ oil, rice germ oil, rice bran Oils, cottonseed oil, soybean oil, peanut oil, tea seed oil, evening primrose oil, kukui nut oil, hazelnut oil Examples include oils and fats such as shea butter, orange oil, and chamomile oil.

[0039] Examples of waxes include candelilla wax, rice bran wax, cotton wax, carnauba wax, and lanoli wax. Lanolin fatty acid isopropyl, POE lanolin alcohol ether, POE lanolin Alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin Examples include alcohol ethers, shellac wax, and waxes such as beeswax.

[0040] Other ester oils besides component (B) include isopropyl myristate and butyric myristate. L, Decyl myristate, Myristyl myristate, Cetyl myristate, Palmitic acid Isopropyl, cetyl palmitate, ethyl stearate, butyl stearate, stear Stearyl phosphate, isocetyl stearate, hexyl laurate, ethyl oleate, Ethyl linoleate, isopropyl linoleate, cetyl caprylate, decyl oleate, o Oleyl leate, isodecyl oleate, cetyl octanoate, 2-octyl myristate Ludodecyl, 2-octyldodecyl dimethyloctanoate, hexyl dimethyloctanoate Sil, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, adipic acid 2-Hexyldecyl, Isocetyl Isostearate, Isostearyl Isostearate, Isononyl isononanoate, Isotridecyl isononanoate, 12-hydroxystearyl acid Cholesteryl, cholesteryl stearate, cholesteryl oleate, macadamia nuts Fatty acid phytosteryl, oleate phytosteryl, stearate inulin, di-2-e Ethylene glycol ethylhexylate, cetyl 2-ethylhexanoate, monoisostearin N-alkyl glycol acid, neopentyl glycol dicaprate, di-2-heptyl Glyceryl endodecanoate, tri-2-ethylhexyl trimellitate, tri-tride trimellitate Syl, trimethylolpropane tri-2-ethylhexylate, triisostearate Methylolpropane, pentaerythritol tetra-2-ethylhexanoate, tri-2- Glycerin ethylhexanoate, trimethylolpropane triisostearate, cetyl 2 -Ethylhexanoate, Glyceryl Trimyristate, Caprylic / Capric Tri(Capric Acid) ) Glyceryl, Tri(Caprylic / Capric / Myristic / Stearic) Glycerides Medium-chain triglyceride, castor oil fatty acid methyl ester, lauroyl glutamine Di(phytosteryl / octyldodecyl) acid, di(octyldodecyl) lauroyl glutamate (Syl / Phytosteryl / Behenyl), Cetyl Lactate, Myristyl Lactate, Cyclohexane-1 ,4-Dicarboxylic acid bisethoxydiglycol, lanolin acetate, ethyl acetate, butyl acetate , amyl acetate, triethyl citrate, dimer dilinoleate (phytosteryl / isosteryl) Allyl / Cetyl / Stearyl / Behenyl), Dimer Dilinoleyl Dimer Dilinoleate , dipentaerythrityl tripolyhydroxystearate, tri(behenate / isostearate) Examples include glyceryl phosphate / eicosanedioic acid.

[0041] Examples of silicone oils include methylpolysiloxane, methylphenylpolysiloxane, and decane. Methyltetrasiloxane, methylcyclopentasiloxane, highly polymerized methylpolysiloxane Octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, methyl Hydrogen polysiloxane, methyl trimethicone, dimethiconol, dimethiconol Rospolymers, siloxanes such as caprylyl methicone, alkyl-modified silicones, Amino-modified silicones such as minopropyl dimethicone and amodimethicone, cross-linked methyl polymer Risiloxane, cross-linked alkyl-modified silicone, amino-modified silicone, polyether-modified Silicone, polyglycerin-modified silicone, cross-linked polyether-modified silicone, Bridged alkyl polyether modified silicone, silicone-alkyl chain comodified polyether Modified silicone, silicone-alkyl chain comodified polyglycerin, poly Polyglycerin-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, Examples include silicone-modified silicones and silicone oils such as silicone resins.

[0042] Examples of moisturizing ingredients include hyaluronic acid (hydrolyzed hyaluronic acid, low molecular weight hyaluronic acid). (Contains acids, etc.); Salts of hyaluronic acid (e.g., sodium hyaluronate, zinc hyaluronate) , low molecular weight zinc hyaluronate, etc.); hyaluronic acid derivatives (acetylated hyaluronic acid or similar) Salt (e.g., sodium acetylated hyaluronate, zinc acetylated hyaluronate, etc.), frame Bridge-type hyaluronic acid derivatives (e.g., sodium hyaluronate crosspolymer), carboxymethyl hyaluronic acid Sodium hyaluronate, unsaturated hyaluronic acid or its salt, hydrolyzed alkyl hyaluronate (C12 -13) Glyceryl, cationized hyaluronic acid derivative (hydroxypropyl hyaluronate) Trimonium, etc.; dimethylsilanol hyaluronate, etc.); chondroitin sulfate or the Salt (chondroitin sulfate sodium, chondroitin sulfate potassium, dermatan sulfate sodium Potassium diuretic, dermatan sulfate, etc.; heparin-like substances, alanine, serine, asparagus Ginic acid, glycine, proline, hydroxyproline, glucosamine, theanine, arginine Amino acids and their derivatives such as ; polyhydric alcohols; PPG-17, buteth-17, PPG -25 Sorbitol, Polyoxyalkylene Alkyl Glucoside, PEG / PPG / Poly Butylene glycol-8 / 5 / 3 glycerin, polyoxyalkylenediglyceryl, etc. Alkylene oxide; glycosyltrehalose, trehalose; ceramide, glucosyl trehalose Lamide, cholesterol, phytosterol, cholesterol derivatives, phytosterol Derivatives; 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer Combined solution, polymethacryloyloxyethyl phosphorylcholine, etc. 2-methacryloyloxy Phosphorylcholine-containing polymer; lactic acid, sodium lactate, sodium pyrrolidone carboxylate , NMF-derived components such as urea; collagen, elastin, keratin, chitin, chitosan, etc. and their hydrolysates; hydroxyethyl urea; plants (e.g., aloe, seaweed, cuttlebone) Corn, chlorella, lemongrass, chamomile, witch hazel, tea, perilla, grapefruit Examples include components derived from plants such as Gynostemma pentaphyllum.

[0043] Examples of polyhydric alcohols include low-molecular-weight substances having two or more hydroxyl groups, for example, Glycerin, diglycerin, triglycerin, propylene glycol, dipropylene glycol 1,3-Butanediol, Ethylene Glycol, Diethylene Glycol, Isopropyl 1,3-butylene glycol, 1,3-propanediol, 1,2- tanediol, 1,2-hexanediol, 1,2-octanediol, decanediol Neopentyl glycol, sorbitol, xylitol, erythritol, mannitol One example is [the character].

[0044] Examples of thickening agents include polyvinyl alcohol, polyvinylpyrrolidone, and polyvinyl Methyl ether, vinyl-based thickeners such as carboxyvinyl polymer, methylcellulose, etc. Hydroxycellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxy hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose Cellulose, carboxyethylcellulose, hydrophobized hydroxypropylmethylcellulose, etc. Lulurose-based thickeners, guar gum, sclerotium gum, tamarind gum, xanthan gum Dextran, pectin, pullulan, gelatin, locust bean gum, carrageenan Agar, biosaccharide gum, alkyl acrylate methacrylate copolymer, polyacrylic acid Sodium acid, bentonite, dextrin fatty acid ester, dimethyl distearyl ammonium compound Monium hectorite, sodium alginate, polyethylene glycol, trimethyl chloride Ammonium hydroxypropyl guar gum, trimethylammonium hydroxypropyl chloride (hydroxyethyl cellulose, (hydroxyethyl acrylate / acryloyl hydrate) (Sodium taurate) copolymer, (ammonium acryloyldimethyltaurate / vinyl Examples include pyrrolidone copolymers.

[0045] Examples of cooling agents include menthol and its derivatives, camphor, and chlorobutanol. , borneol, geraniol, cineole, anethole, limonene, eugenol, etc. Terpenes (these may be d-isomers, l-isomers, or dl-isomers); eucalyptus oil, berga Mot oil, peppermint oil, cool mint oil, spearmint oil, fennel oil, peppermint oil Examples include essential oils such as cinnamon oil, rose oil, and turpentine oil.

[0046] Examples of antioxidants include dibutylhydroxytoluene and butylhydroxyanisodium. Sodium sorbite, sodium sulfite, ascorbic acid, ascorbic acid derivatives, tocopherol Tocopherol, tocopherol derivatives, tocotrienol, bisulfite, sodium hyposulfite Examples include erythorbic acid, sodium erythorbate, and L-cysteine ​​hydrochloride. .

[0047] Examples of preservatives or antimicrobials include benzoic acid, sodium benzoate, dehydroacetic acid, Sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate Pill, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, pro parahydroxybenzoate Pills, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol , benzyl alcohol, methylisothiazoline, iodide propynyl butylcarbamate, 1,3-propanediol, 1,2-pentanediol, 1,2-hexanediol, or Examples include 1,2-octanediol.

[0048] Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.) and organic acids (lactic acid, citric acid, etc.) Tartaric acid, malic acid, succinic acid), organic bases (triethanolamine, diisopropanol) Amines, triisopropanolamine, etc., as well as their salts, inorganic bases (hydroxylated ammonium compounds) Examples include sodium hydroxide, sodium ammonium sulfate, etc.

[0049] Examples of chelating agents include ethylenediaminetetraacetic acid (EDTA), ethylenediaminetetraacetic acid, etc. 4-acetic acid (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.) Examples include potassium salts, phytic acid, gluconic acid, polyphosphate, and metaphosphate. .

[0050] [Manufacturing method] The method for producing the pharmaceutical composition of the present invention is not particularly limited and can be set as appropriate.

[0051] Specifically, each component is heated and dissolved as needed, then mixed, and cooled in a water bath while stirring. One possible method is to leave it undisturbed at room temperature, but this is not the only option.

[0052] [Formulation] The pharmaceutical composition of the present invention uses a base or carrier commonly used in pharmaceuticals, quasi-drugs, or cosmetics. The body, and optionally additives, can be mixed together to form a pharmaceutical composition.

[0053] The form of the pharmaceutical composition of the present invention is not particularly limited, but it is more likely to be in the form of a topical skin composition. Preferred. Such forms include, for example, suspensions, emulsions, creams, ointments, and gels. Drugs, liniments, lotions, patches, solid preparations contained in containers (sticks, spheres) Examples include formulations (such as hemispherical formulations). These formulations are described in the General Provisions of the 17th Revised Japanese Pharmacopoeia. It can be manufactured according to the following methods, etc. Among these, creams, gels, or ointments are preferred. It's nice.

[0054] [pH] The pH of the pharmaceutical composition of the present invention is typically pH 3.0 to 7.5, and at pH 3.0 to 7.0 It is preferable that there be a pH, and more preferably that the pH is 3.0 to 6.5, and more preferably that the pH is 3.5 to 6. It is even more preferable that the pH is 0, and particularly preferable that it is between 3.8 and 5.5. Furthermore, this pH can be adjusted, for example, by using a pH adjusting agent. However, p This does not apply to formulations in which H measurement is impossible or difficult.

[0055] (container) The pharmaceutical composition of the present invention is packaged in a container of a shape and material appropriately selected according to its intended use and application. It can be contained and used. Specific containers include, for example, containers with nozzles and pumps. Containers with caps, jar containers, tube containers, containers with holes in the inner stopper, hinged caps Examples include containers with attached heads, sponge-head containers, roll-on containers, stick-type containers, etc. These containers allow the pharmaceutical composition to be applied directly or indirectly to the desired affected area. It can be applied to a small or large area of ​​the affected area. It is also possible to design it to be tapered or have a large diameter. Apply the pharmaceutical composition according to this embodiment to the affected area. It is also possible to apply the product and then spread it using a non-woven fabric or your fingers.

[0056] Furthermore, the container material is polyethylene terephthalate, polybutylene terephthalate. Polyethylene naphthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, polycarbonate, fluororesin, polyvinyl chloride, polya Microwaves, ethylene vinyl alcohol resin, polystyrene, glass, and metals (aluminum, etc.) Examples can be given. Furthermore, these materials are selected considering factors such as strength, flexibility, weather resistance, and component stability. Considering this, various coating treatments are applied, or these materials are combined, for example, by mixing them. They can be combined or laminated and used as container materials.

[0057] [Stability improvement method] The present invention also relates to a pharmaceutical composition comprising (A) prednisolone valerate acetate. The present invention includes methods for improving stability. According to the present invention, (A) prednisolone valerate acetate A pharmaceutical composition containing (B) dicarboxylic acid diester and (C) petrolatum This improves the stability of the pharmaceutical composition. Here, the content of each component The quantity, ratio, and other conditions regarding ingredients shall conform to those described in [Pharmaceutical Composition].

[0058] [Formulation stabilizers for pharmaceutical compositions] The present invention also relates to (B) dicarboxylic acid diester containing (A) prednisolone valerate This includes a formulation stabilizer for pharmaceutical compositions containing acid esters, acetates, and (C) petrolatum. Here, the content, ratio, and other conditions of each component are as described in [Pharmaceutical Composition]. It depends on the size.

[0059] [Application] The pharmaceutical composition of the present invention is particularly effective as an antipruritic or antipruritic anti-inflammatory agent, for example, Atopic dermatitis, senile skin pruritus, eczema (skin eczema including scalp eczema and hand eczema), skin Inflammation, itching, rash, hives, sores, heat rash, chilblains, insect bites, or dryness, etc. It has an effect on itching and other symptoms caused by [the substance]. Furthermore, it can also have a skin repair function. .

[0060] Due to its effects on the skin, the present invention is applicable to products used as topical skin preparations (formulations for the skin). It is preferable to use it. Suitable skin application areas include hands (palms, fingers), face, feet, Examples of areas of skin include the head, neck, chest, armpits, back, waist, back of the elbows, and back of the knees. The composition is administered once to several times a day, depending on the intended use, using known or commonly used methods. It can be used according to the prescribed dosage and administration. The appropriate amount varies depending on the user, but Pred Nisolone valerate acetate is administered at a dose of 1 FTU (finger tip) per application. It is preferable to apply it in such a way that it becomes a unit. [Examples]

[0061] Next, the present invention will be specifically described with reference to examples, but the present invention is limited to the following examples. It is not. Furthermore, unless otherwise specified, the units for each component amount in the table are in mass percent. .

[0062] The compositions of the examples and comparative examples shown in Table 1 were prepared according to the following steps. That is, each The mixture was heated and dissolved at 80°C, then mixed and stirred for 5 to 10 minutes while cooling in a water bath. The samples were left standing at warm temperatures. Unless otherwise specified in the table, the values ​​represent mass percentages.

[0063] [Stability Testing] After preparing the compositions for the examples and comparative examples, allow them to reach room temperature and test them using an ST-1 (stability tester): Measurements were taken at 30°C for 3 days using Eiko Seiki. ST-1 irradiates the sample with light, and the transmitted light This is a device that evaluates the physical stability of a pharmaceutical product by examining its intensity and backscattered light intensity. If the strength is changing, the physical stability of the formulation, i.e., the emulsified state, dispersion state, and solubility state may be affected. It can be inferred that the state is changing. This is due to emulsified / dispersed particles or dissolved components. The surface condition of the formulation when irradiated with light is due to aggregation, coalescence, creaming, or precipitation of fractions. It is based on fluctuation.

[0064] The measurement conditions are as follows: The obtained backscattered light intensity is plotted on the vertical axis, and the sample cell height is plotted on the vertical axis. By performing linear regression on the change in peak area when the horizontal axis is used, the 3-day rate of change (mm%) can be calculated. The variability ( / d) was calculated. The smaller the absolute value of the variability, the smaller the variation in the dispersion state of the formulation. This indicates high physical stability as a pharmaceutical product. • Starting position: 0mm • End position: 56.5mm • Scan resolution: 0.055mm • Scanning speed: 12.5 mm / s • Number of scans: 289 • Sample height range used for analysis: 0mm to 40mm

[0065] Table 1 shows the evaluation results of the pharmaceutical compositions of the examples and comparative examples. The evaluation results for Comparative Example 1 are as follows: The variation rate of the backscattered light was used as the reference, and the variation rate improvement rate was calculated and expressed using the following formula. Percentage improvement in the rate of variation of each composition (%) = [(Rate of variation of Comparative Example 1 - Rate of variation of each composition) / Comparative Example] [Rate of change of 1] × 100

[0066] [Table 1] From the results in Table 1, the composition of the example showed no change in backscattered light intensity over time. It was found that the physical stability had improved significantly, with less stress on the body.

[0067] [Example prescription] Tables 2-4 below show examples of prescriptions. All units are in mass percent.

[0068] Table 2

[0069] Table 3

[0070] Table 4

Claims

1. (A) Prednisolone valerate acetate; (B) Dicarboxylic acid diesters; (C) Vaseline; and Water 30-70% by mass A pharmaceutical composition containing the following:

2. (B) The pharmaceutical composition according to claim 1, wherein the dicarboxylic acid diester is one or more selected from the group consisting of diethyl sebacate, diisopropyl adipate, and diisopropyl sebacate.

3. (B) The pharmaceutical composition according to claim 1 or 2, wherein the concentration of the dicarboxylic acid diester is 0.1 to 20% by mass.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the ratio of parts by mass of component (B) to 1 part by mass of component (A) is 8 to 90.