Pharmaceutical composition for nail and portion around nail

Abstract

To provide a pharmaceutical composition excelling in properties such as extensibility, for application to a nail and a portion around the nail.SOLUTION: A pharmaceutical composition for a nail and / or a portion around the nail is prepared which comprises: (A) an antifungal agent; (B) at least one selected from the group consisting of a vinyl polymer, an acrylic polymer, mucopolysaccharide, a starch-based polymer, dextran, a dextrin fatty acid ester, casein, dimethyl distearylammonium hectorite, an (ammonium polyacryloyldimethyl taurate / vinyl pyrrolidone) copolymer, polyethyleneglycol distearate, ethylene glycol tri-isostearate, tri-isostearic polyoxyethylene (20) methyl glucoside, bentonite, hectorite, alginic acid and / or its salt, propylene glycol alginate, and a polyhydric alcohol; and (C) one or more compound selected from the group consisting of an anti-inflammatory agent, a local anesthetic, a bactericide, and an antihistamine.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a pharmaceutical composition for nails and nail periungual areas. More specifically, the present invention relates to a pharmaceutical composition for nails and nail periungual areas containing an antifungal agent. The present invention relates to a pharmaceutical composition for use on nails and around the nails. [Background technology]

[0002] Antifungal agents that inhibit fungal growth are useful for treating and preventing various diseases and symptoms caused by fungal infections. Antifungal topical agents are widely used to prevent and improve tinea, dermatomyositis, and other skin conditions. It is used to treat skin infections such as candidiasis and tinea versicolor (Patent Document 1).

[0003] On the other hand, fungal infections can also occur in the nails and around the nails, so appropriate treatment is needed. do. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2006-232853 A Summary of the Invention [Problem to be solved by the invention]

[0005] However, for antifungal agents for the nails and around the nails, suitable pharmaceutical compositions have not been thoroughly studied. It cannot be said that the issue has been thoroughly investigated.

[0006] The present invention has been made in view of the above, and provides a medical product for nails and around the nails, which contains an antifungal agent. The present invention aims to provide a pharmaceutical composition. [Means for solving the problem]

[0007] The nails and the area around the nails have unique unevenness, so if they become infected with fungus, antifungal However, it is difficult to sufficiently deliver a formulation containing the agent to the affected area, i.e., the nail or deep areas around the nail. The technology for delivering pharmaceutical compositions containing antifungal agents to the nails and surrounding areas needs to be examined in more detail. It is necessary.

[0008] The present invention relates to a preparation that has improved spreadability on nails and around the nails and reduces dryness of the nails and around the nails. The present inventors have provided a method for producing a composition comprising: (A) an antifungal agent; (B) a viscosity-increasing polymer; and and / or polyhydric alcohols, and (C) anti-inflammatory agents, local anesthetics, bactericides, and antihistamines. By incorporating one or more compounds selected from the group consisting of It has been found that a pharmaceutical composition can be obtained that has improved spreadability and prevents drying, and the present invention It has been completed.

[0009] That is, the present invention provides the pharmaceutical compositions listed below. Section 1. (A) Antifungal agents; (B) Vinyl polymers, acrylic polymers, starch polymers, dextran, dextrose Phosphorus fatty acid ester, casein, dimethyl distearyl ammonium hectorite, (a Ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer, distearate Polyethylene glycol stearate, Ethylene glycol triisostearate, Triisostearate Polyoxyethylene (20) methyl glucoside, bentonite, hectorite, Alginic acid and / or its salts, propylene glycol alginate and polyhydric alcohols At least one or two selected from the group consisting of (C) one or more selected from the group consisting of anti-inflammatory agents, local anesthetics, bactericides, and antihistamines; A pharmaceutical composition for nails and / or around the nails, comprising one or more compounds. Section 2. Item 2. The pharmaceutical composition according to Item 1, wherein the nail and / or the area around the nail is the nail groove and / or the groove near the yellow line. thing. Section 3. Item 3. The pharmaceutical composition according to item 1 or 2, wherein the (A) antifungal agent is an amine-based antifungal agent. 4. The (A) antifungal agent is at least one selected from the group consisting of terbinafine and its salts. Item 4. The pharmaceutical composition according to Item 3, wherein the compound is one of the above. Section 5. The component (B) is polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol Coal, glycerin, 1,3-butylene glycol, methyl acrylate, acrylic acid-2 -ethylhexyl copolymers and carboxyvinyl polymers Item 1 to 4, which contains at least one thickening polymer or polyhydric alcohol. A pharmaceutical composition comprising: Section 6. Item 6. The pharmaceutical composition according to any one of Items 1 to 5, further comprising ethanol. Section 7. Item 7. The pharmaceutical composition according to item 6, wherein the content of ethanol is 20% by mass or more based on the total amount of the composition. Pharmaceutical composition. Section 8. Item 8. The pharmaceutical composition according to any one of Items 1 to 7, which is a liquid formulation. Effect of the Invention

[0010] According to the present invention, a pharmaceutical composition suitable for use on nails and around the nails can be provided. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention relates to a composition comprising (A) an antifungal agent and (B) a viscosity-increasing polymer and / or a polyhydric alcohol, The pharmaceutical composition for around the nail of the present invention comprises a nail treatment agent and a specified ingredient (C). It also has good spreadability around the nails. It can treat, improve and prevent whitening and peeling.

[0012] [(A) Antifungal agent (antifungal component)] An antifungal agent is a substance that has the function of inhibiting or suppressing the growth of fungi or killing fungi. It is used to treat, prevent, and improve various diseases and symptoms caused by fungal infections. do.

[0013] The types of the antifungal agent of the present invention include, for example, allylamine-based antifungal agents, benzylamine-based antifungal agents, antifungal agents such as amine-based antifungal agents, thiocarbamine-based antifungal agents, imidazole-based antifungal agents, etc. antifungal agents or azole antifungal agents such as triazole antifungal agents, or morpholine antifungal agents As the type of the antifungal agent of the present invention, From the viewpoint of effectiveness, amine-based antifungal agents and azole-based antifungal agents are preferred, and amine-based antifungal agents is more preferred.

[0014] The amine-based antifungal agent of the present invention includes compounds that are known as antifungal agents having an amine in common. Any amine-based antifungal agent that is pharma- ceutical or physiologically acceptable may be used. Examples of the amine-based antifungal agent include allylamines such as terbinafine and naftifine. benzylamine antifungal agents such as butenafine, tolnaftate, liranafine, etc. Among them, the effect of the present invention is more remarkable. From the viewpoint of the above, the allylamine-based antifungal agent is preferably used, and among them, the particularly preferred For example, terbinafine, or a salt of terbinafine such as terbinafine hydrochloride, butenafine or a salt of butenafine such as butenafine hydrochloride.

[0015] The azole antifungal agent of the present invention is an azole skeleton (a heterocyclic compound containing one or more nitrogen atoms). 5-membered ring compound) are known as antifungal agents having pharmacological or physiological properties. Any commercially acceptable azole antifungal agent may be used. Examples of the imidazole ring include an imidazole ring having an imidazole ring (a five-membered heterocyclic ring containing two nitrogen atoms). A triazole antifungal agent, a triazole having a triazole ring (a five-membered heterocyclic ring containing three nitrogen atoms). More specifically, miconazole, laconazole, etc. azole, luliconazole, isoconazole, ketoconazole, clotrimazole, neticonazole azole, sulconazole, bifonazole, oxiconazole, econazole and their Imidazole antifungal agents such as salts; fluconazole, itraconazole, fosfluconazole voriconazole, efficonazole, butoconazole, fenticonazole, sertazoline Conazole and its salts are preferred examples of the triazole-based antifungal agents of the present invention. The azole antifungal agent of the present invention can be suitably used when the effect of the present invention is enhanced. From the viewpoint of remarkable effectiveness, imidazole antifungal agents are preferred, among which miconazole, Luliconazole, isoconazole, and lanoconazole are preferred.

[0016] The morpholine-based antifungal agent of the present invention includes antifungal agents having morpholine in common. Any morpholine antifungal compound known in the art that is pharma- ceutical or physiologically acceptable may be used. As a morpholine-based antifungal agent, a representative example is amorolfi Examples of the component (A) include amines and salts thereof. Each of these components (A) may be used alone. Two or more kinds may be used in any combination.

[0017] In the present invention, (A) the antifungal agent includes, but is not limited to, terbinafine, butenyl ether, A small amount selected from the group consisting of nafin, miconazole, isoconazole, and salts thereof. A combination of at least one or two or more types is exemplified as a preferred embodiment.

[0018] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the antifungal agent (A) is The content is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, based on the total amount. More preferably, the content is 0.3% by mass or more, and particularly preferably 0.5% by mass or more. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the antifungal agent is On the other hand, the content is preferably 10% by mass or less, more preferably 8% by mass or less, and even more preferably or 5% by mass or less, particularly preferably 2% by mass or less, based on the total amount of the pharmaceutical composition. A) The total content of the antifungal agent is preferably 0.05 to 0.5% by weight, from the viewpoint of exhibiting the effects of the present invention more significantly. 0.1% by mass to 10% by mass, more preferably 0.1% by mass to 8% by mass, and even more preferably The content is preferably 0.3% by mass to 5% by mass, and more preferably 0.5% by mass to 2% by mass. 1% by weight is most preferred.

[0019] [(B) Viscosity-increasing polymer and / or polyhydric alcohol] The following substances are used as the thickening polymer and / or polyhydric alcohol (B) of the present invention: There are no particular limitations on the type of polymer that can be used. starch-based polymers, dextran, dextrin fatty acid esters, casein, Dimethyl distearyl ammonium hectorite, (Acryloyldimethyltaurine ammonium Monomer / vinylpyrrolidone copolymer, polyethylene glycol distearate, Ethylene glycol triisostearate, polyoxyethylene triisostearate (2 0) Methyl glucoside, bentonite, hectorite, alginic acid and / or its salts, alginic acid Propylene glycol ester of phosphate, thickening polysaccharides and other thickening polymers and polyhydric alcohols The at least one selected from the group consisting of:

[0020] The vinyl polymers include polyvinylpyrrolidone (PVP) and polyvinylmethyl ether. Examples of the vinyl ether include carboxyvinyl polymers and polyvinylpyrrolidone. The K value according to the Fikentscher method is usually 15 to 100, preferably 20 to 99, more preferably More preferably, it is about 22 to 98, and further preferably about 28 to 35 (for example, 22 to 35 Polyvinylpyrrolidone K17 or 87~93) can be used. , Polyvinylpyrrolidone K25, Polyvinylpyrrolidone K30, Polyvinylpyrrolidone K 90, etc., and preferably polyvinylpyrrolidone K30, polyvinylpyrrolidone K9 0, and more preferably polyvinylpyrrolidone K30. One or more kinds can be used.

[0021] Acrylic polymers include acrylic acid / alkyl methacrylate copolymers (acrylic acid ester-methyl methacrylate copolymer, etc.), hydroxyethyl acrylate-acryloyl Hydroxyethyl acrylate / Acryloyldimethyltaurate copolymer (especially hydroxyethyl acrylate / acryloyldimethyltaurate copolymer) Methyl taurate sodium copolymer), sodium acrylate · acryloyldimethyl taurate Poly(methacrylate) and poly(methacrylate) Sodium acrylate-alkyl methacrylate copolymer, steareth-10 allyl ether acrylate Polyacrylic acid or its salt (carboxyvinyl polymer), acrylic Ammonium dimethyl taurate copolymer, polyoxyethylene acrylate / methacrylate Ethylene glycol ether copolymer, polyacrylamide, and acrylamide-acrylamide Ammonium acrylate copolymer, methyl acrylate / 2-ethylhexyl acrylate copolymer acrylic acid / octyl acrylate copolymer, acrylic acid / vinyl acetate copolymer Nyl copolymer, acrylic acid silk fibroin copolymer resin, acrylic acid starch, acrylic acid Methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion, acrylic resin Al An example of the solvent is canolamine solution.

[0022] Starch-based polymers include hydroxypropyl starch phosphate (e.g., Natio StructureXL, manufactured by Nal Starch, LLC), modified cornstarch and cornstarch.

[0023] Polyhydric alcohols are used as ingredients in pharmaceuticals, quasi-drugs, and cosmetics. The polyhydric alcohol is not particularly limited as long as it can be used as the alcohol. Phosphorus, diglycerin, dipropylene glycol, propylene glycol, 1,3-butylene glycol, 3-methyl-1,3-butanediol, polyethylene glycol, polyvinyl From the viewpoint of exhibiting the effects of the present invention more significantly, preferred examples include ethyl alcohol and the like. The ingredients are polyethylene glycol, polyvinyl alcohol, glycerin, 1,3-butylene It is glycol.

[0024] In this specification, the thickening polysaccharide is a component of an external preparation in the field of medicines, quasi-drugs, or cosmetics. Among the substances used as antioxidants, specifically carrageenan, xanthan gum, and arabic gum Mucopolysaccharides include chondroitin sulfate (sodium chondroitin sulfate), pectin, and mucopolysaccharides. hyaluronic acid or its salts (sodium salts, etc.), and hyaluronic acid derivatives Examples of the glycosaminoglycans include glycosaminoglycans such as heparin and heparinoids. It is possible.

[0025] These components (B) may all be used alone or in any combination of two or more. It may also be used in combination.

[0026] These components (B) are not limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, Among these, polyhydric alcohols, acrylic polymers, starch polymers, and vinyl polymers are Polyhydric alcohols and vinyl polymers are preferred, and vinyl polymers are even more preferred. Of these, polyvinylpyrrolidone is preferred, and polyvinylpyrrolidone is particularly preferred.

[0027] In the present invention, the component (B) is not limited to, but may be, for example, a vinyl polymer and / or Polyhydric alcohols are preferred. Among them, polyvinylpyrrolidone, polyvinyl alcohol, and glycerin. is exemplified as a preferred embodiment.

[0028] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the component (B) is It is usually 0.01% by mass or more, preferably 0.1% by mass or more, more preferably The content is preferably 0.5% by mass or more, more preferably 0.8% by mass or more, and particularly preferably The total content of the component (B) is 1.5 mass % or more. From the viewpoint of the pharmaceutical composition or the ease of use, it is preferably 20% by weight or less based on the total amount of the pharmaceutical composition. More preferably, it is 15% by weight or less, and even more preferably, it is 10% by weight or less. , even more preferably 5% by mass or less, particularly preferably 4.5% by mass or less; Most preferably, it is 3.5% by mass or less, or 3% by mass or less. A preferable value is also exemplified as being equal to or less than mass %.

[0029] In the pharmaceutical composition of the present invention, from the viewpoint of exhibiting the effects of the present invention more significantly, (A) The ratio of the (B) component to the (A) component is, for example, about 1 part by mass of the total content of the (A) component. It is usually 0.01 parts by weight or more, preferably 0.1 parts by weight or more, and more preferably 0. 5 parts by mass or more, more preferably 0.6 parts by mass or more, and even more preferably 0.7 The total content of the component (B) is preferably 1.5 parts by mass or more, and more preferably 1.5 parts by mass or more. From the viewpoint of more prominently exhibiting the effects of the present invention and from the viewpoint of the feeling of use of the preparation, the total amount of the component (A) is Preferably, the content is 15 parts by mass or less, and 10 parts by mass or less, relative to 1 part by mass of the content. More preferably, it is 5 parts by mass or less, further preferably, it is 2.7 parts by mass or less, and particularly preferably, it is 2 parts by mass or less. In the pharmaceutical composition of the present invention, the ratio of component (B) to component (A) is For example, it can be 0.01 to 15 parts by mass per part by mass of the total content of the (A) component. The amount of the water-soluble polymer may be 0.5 to 15 parts by mass, preferably 0.6 to 10 parts by mass, and more preferably 0.6 to 5 parts by mass is more preferred, 0.7 to 2.7 parts by mass is even more preferred, and 1.5 to 2 parts by mass is even more preferred. is particularly preferred.

[0030] Furthermore, for example, when the component (B) contains a polyhydric alcohol, the effects of the present invention are significantly exhibited. From this viewpoint, the content of the polyhydric alcohol is preferably 0.1 to 1.0% based on the total amount of the pharmaceutical composition. % by mass or more, more preferably 0.5% by mass or more, and even more preferably 0.8% by mass or more. The total content of the component (B) is preferably 1.5 mass % or more, and more preferably 1.5 mass % or more. From the viewpoint of more significantly exhibiting the effect of or from the viewpoint of the feeling of use of the preparation, Preferably, it is 10% by mass or less, more preferably, it is 5% by mass or less, and even more preferably is 4.5% by mass or less, particularly preferably 3.5% by mass or less, and most preferably 3% by mass or less. be.

[0031] Furthermore, for example, when the component (B) is polyvinylpyrrolidone, the effects of the present invention are exhibited. From the viewpoint of being particularly effective, the content of polyvinylpyrrolidone is preferably 100% or less relative to the total amount of the pharmaceutical composition. The content is preferably 0.01 to 5 mass%, more preferably 0.1 to 3 mass%, and further preferably The content is 0.5 to 1 mass %. Furthermore, for example, the component (B) is polyvinylpyrrolidone K30 or When the polyvinylpyrrolidone is polyvinylpyrrolidone K90, the effect of the present invention is significantly exhibited. The content of polyvinylpyrrolidone K30 or polyvinylpyrrolidone K90 is the total amount of the pharmaceutical composition. The content is preferably 0.01 to 5 mass%, more preferably 0.1 to 3 mass%, It is more preferably 0.5 to 1% by mass.

[0032] Furthermore, for example, when component (B) is glycerin or polyvinyl alcohol, In order to achieve the effects of the present invention remarkably, the content of glycerin or polyvinyl alcohol is: Each of them is preferably 0.01 to 10% by mass, more preferably 0.01 to 10% by mass, based on the total amount of the pharmaceutical composition. Preferably, the content is 0.05 to 5 mass%, more preferably 0.1 to 3 mass%, and particularly preferably 0.5 to 10 mass%. ~1% by mass.

[0033] [(C) component] Examples of the component (C) of the present invention include the following. That is, the anti-inflammatory agent, the local anesthetic agent, the bactericide, and the antihistamine agent are selected from the group consisting of: It is one or more compounds that can be used.

[0034] These (C) components include those used in the fields of medicines, quasi-drugs, and cosmetics for topical use. There are no particular limitations as long as the grade is acceptable.

[0035] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the component (C) is Preferably, the content is 0.05% by mass or more, more preferably 0.1% by mass or more, More preferably, it is 0.8% by mass or more, particularly preferably 1% by mass or more, and most preferably 1. The total content of the component (C) is 2% by mass or more from the viewpoint of more significantly exhibiting the effects of the present invention. From the viewpoint of the feeling of use of the preparation, the amount is preferably 12.5% ​​by mass or less based on the total amount of the pharmaceutical composition. More preferably, it is 4.5% by mass or less, and even more preferably, it is 4.1% by mass or less. More preferably, it is 2.8% by mass or less, particularly preferably 2.5% by mass or less, and most preferably The total content of the component (C) relative to the total amount of the pharmaceutical composition is preferably 2% by mass or less. The content is preferably 0.01 to 12.5% ​​by mass, more preferably 0.05 to 4.5% by mass, and even more preferably 0.01 to 12.5% ​​by mass. More preferably, it is 0.1 to 4.1 mass%, further preferably, it is 0.8 to 2.8 mass%, and particularly preferably Preferably, it is 1 to 2.5 mass %, and most preferably, it is 1.2 to 2 mass %.

[0036] In the pharmaceutical composition of the present invention, the ratio of the component (C) to the component (A) is From the viewpoint of more significantly exhibiting the above, for example, (C) The total content of the components is preferably 0.01 to 12.5 parts by mass, more preferably 0.05 to 4.5 parts by mass, more preferably 0.1 to 4.1 parts by mass, and even more preferably 0.8 to 2.8 parts by mass, particularly preferably 1 to 2.5 parts by mass, and most preferably 1.2 to 2 parts by mass. do.

[0037] (C) Anti-inflammatory agents include prednisolone valerate acetate, dexamethasone acetate, and vinegar. steroidal anti-inflammatory drugs such as hydrocortisone acid or pharmacologically acceptable salts thereof; , Allantoin, Glycyrrhetinic acid, Stearyl glycyrrhetinate, Glycyrrhetinic acid, Aldioxa, Ufenamate, Bufexamac, Ibuprofenpiconol, Indometac Tacine, Diclofenac, Piroxicam, Epsilon-Aminocaproic Acid, Berberine, Lysozyme, Sodium Azulene Sulfonate, Dimethylisopropylazulene, Bromella In addition, the present invention relates to an enzyme that is capable of acting as a pharmacokinetic agent, and Among these drugs, the following drugs that exhibit the effects of the present invention are exemplified: nonsteroidal anti-inflammatory drugs such as salts thereof. From the viewpoint of more remarkable effect, nonsteroidal anti-inflammatory drugs are preferred, and glycyrrhizic acid, glycyrrhizic acid, Licyrrhetinic acid, salts of glycyrrhizinic acid (e.g., dipotassium glycyrrhizinate, glycyrrhetinic acid, Monoammonium urethane salt, salts of glycyrrhetinic acid, and allantoin are more preferred. One or more of these drugs may be used in appropriate combination.

[0038] (C) Component local anesthetics include lidocaine, dibucaine, mepivacaine, and bupivacaine. apivacaine, ropivacaine, levobupivacaine, and pharma- ceutical acceptable salts thereof. Amide-type local anesthetics having amine and amide structures, procaine, chloroprocaine, tetrahydrofuran, Ester-type topical agents having amine and ester structures, such as lacaine and their salts anesthetics, ethyl aminobenzoate, oxypolyethoxydodecane, etc. Among these drugs, there are, but are not limited to, amide-type topical agents having amine and amide structures. An anesthetic is preferred, and from the viewpoint of more prominently exhibiting the effects of the present invention, lidocaine is particularly preferred. Examples of these drugs include dibucaine and dibucaine hydrochloride. It can also be used in combination.

[0039] (C) Component bactericides include dequalinium chloride, dequalinium acetate, and benzalkonium chloride. Benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, salt Alkyldiaminoethylglycine acid, cetylpyridinium chloride, sodium benzoate, L-butanol, isopropyl methylphenol, thymol, sorbic acid, potassium sorbate Sodium, Sodium Dehydroacetate, Methyl Parahydroxybenzoate, Ethyl Parahydroxybenzoate propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, Phenethyl alcohol, benzyl alcohol, acrinol, hinokitiol, resorcinol , berberine benzoate, or biguanide compounds. Two or more of these drugs may be used in combination. From the viewpoint of more significantly exhibiting the above, isopropylmethylphenol is preferred.

[0040] The antihistamine of component (C) includes, but is not limited to, chlorpheniramine, isopropyl alcohol, Tipendyl, ketotifen, bepotastine, dimenhydrinate, cyproheptadine, di Phenylpyraline, promethazine, iproheptine, emedastine, clemastine, azepine Levocabastine, hydroxyzine, mequitazine, loratadine, fexofena azin, cetirizine, oxatomide, terfenadine, epinastine, astemizole, Examples include vasopressin, diphenylimidazole, diphenhydramine, or salts of these compounds. As shown.

[0041] From the viewpoint of more prominently exhibiting the effects of the present invention, preferred examples of the antihistamine include dihydrotestosterone. Phenhydramine, diphenylpyraline, chlorpheniramine, diphenylimidazole or a salt thereof, more preferred examples of which are chlorpheniramine and diphenhydramine. or salts thereof, more preferred examples of which are chlorpheniramine, chlorpheniramine maleate, These drugs include phenylalanine, diphenhydramine, and diphenhydramine hydrochloride. One or more types may be used in appropriate combination.

[0042] These components (C) may all be used alone or in any combination of two or more. It may also be used in combination.

[0043] From the viewpoint of more significantly exhibiting the effects of the present invention, preferred components (C) are glycyrrhizic acid, glycerol, Lycyrrhetinic acid, an amide-type local anesthetic having an amine and amide structure, isopropyl methyl phenol, diphenhydramine, and salts of diphenhydramine. In view of exhibiting the effects of the present invention more remarkably, it is particularly preferable to use one or more of the above-mentioned (C The ingredients are glycyrrhizinic acid, glycyrrhetinic acid, lidocaine, isopropyl methylphenoxyethanol. one selected from the group consisting of benzoyl peroxidase, diphenhydramine, and salts of diphenhydramine; The salt of diphenhydramine may be, but is not limited to, diphenhydramine hydrochloride. Furthermore, particularly preferred (C) components are glycyrrhetinic acid and and / or isopropyl methylphenol.

[0044] Furthermore, for example, the component (C) may be glycyrrhizinic acid and its salts, glycyrrhizinic acid and and salts thereof, the effects of the present invention can be obtained. From the viewpoint of more remarkable effect, glycyrrhizinic acid and its salts, glycyrrhizinic acid and its The content of each salt is preferably 0.1 to 1% by mass based on the total amount of the pharmaceutical composition. More preferably, the content is 0.2 to 0.8% by mass, and further preferably, the content is 0.25 to 0.5% by mass. be.

[0045] For example, when component (C) is an amide-type local anesthetic having an amine and an amide structure, The content of such an amide type local anesthetic is preferably about 100% based on the total amount of the pharmaceutical composition. The content is preferably 0.25 to 2.5% by mass, and more preferably 0.5 to 2% by mass. For example, when the component (C) is lidocaine or dibucaine or a salt thereof, In order to more significantly exhibit the effects of the present invention, lidocaine, dibucaine, or a salt thereof is The content is preferably 0.25 to 2.5% by mass, based on the total amount of the pharmaceutical composition. It is more preferably 0.5 to 2 mass %.

[0046] For example, when the component (C) is isopropyl methylphenol, the effect of the present invention is enhanced. From the viewpoint of achieving a more remarkable effect, the content of isopropyl methylphenol in the total amount of the pharmaceutical composition is The content is preferably 0.3 to 3 mass %, and more preferably 0.5 to 1 mass %.

[0047] For example, when component (C) is diphenhydramine and / or a salt thereof, In order to more significantly exhibit the effects of the present invention, The content is preferably 0.1 to 2% by mass, more preferably 0.1 to 2% by mass, based on the total amount of the pharmaceutical composition. is 0.5 to 1 mass %.

[0048] In the present invention, (A) an antifungal agent, (B) a viscosity-increasing polymer and / or a polyhydric alcohol, In addition to the (C) component, pharmaceuticals, quasi-drugs, cosmetics, etc., to the extent that their functions are not impaired. Any known ingredient that can be used as a therapeutic agent may be included in the pharmaceutical composition. As a component, ethanol can be particularly preferably contained.

[0049] [ethanol] The ethanol used in the pharmaceutical composition of the present invention is used in medicines, quasi-drugs, cosmetics, etc. There are no particular limitations as long as the grade and quality are as specified in the regulations. Ethanol is preferably 95% ethanol, 99% ethanol (absolute ethanol), etc. It can be used as appropriate.

[0050] From the viewpoint of usability, the content of ethanol is 20% by mass or more based on the total amount of the pharmaceutical composition. It is preferable that the content of the stoichiometric amount ... The content of ethanol is preferably at least 10% by mass of the total pharmaceutical composition from the viewpoint of ease of handling of the formulation. The amount is preferably 90% by mass or less, more preferably 80% by mass or less, and even more preferably 90% by mass or less. The content of ethanol in the pharmaceutical composition is preferably 70% by mass or less. The content is preferably 20 to 90% by mass, more preferably 30 to 80% by mass, and further preferably is 40 to 70 mass %.

[0051] In the pharmaceutical composition of the present invention, the ratio of ethanol to the component (A) is determined from the viewpoint of usability. For example, the content of ethanol is 15 to 1 part by mass per part by mass of the total content of the (A) component. The amount of the water-soluble polymer may be 80 parts by mass, preferably 25 to 140 parts by mass, and more preferably 35 to 80 parts by mass. The content is preferably 100 parts by mass, more preferably 45 to 90 parts by mass, and particularly preferably 60 parts by mass.

[0052] [salt] The term "salt" as used herein includes, for example, organic salts and inorganic salts. Examples of organic salts include: Ammonium, diethanolamine, triethanolamine, ethylenediamine, etc. Examples of inorganic salts include salts with sodium, potassium, calcium, magnesium, etc. Also, examples of the salts include salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; Methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid , tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid , mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotine salts with organic acids such as carboxylic acid, salicylic acid, etc.; or salts with acidic amines such as aspartic acid, glutamic acid, etc. In addition, the term "salt" includes solvates and hydrates of salts. In particular, the form of the salt of component (A) is not particularly limited, but it is preferable to use a salt of the above-mentioned formula (A) because of its availability. From this viewpoint, preferred are salts of inorganic acids, more preferred are hydrochlorides or nitrates.

[0053] [container] The container in which the pharmaceutical composition of the present invention is filled is not particularly limited. Any material that can be used as a cosmetic container may be used. Examples of such container materials include A part or the whole, preferably the whole, of the surface that comes into contact with the pharmaceutical composition is made of polyolefin resin, acrylic resin, etc. Acrylic resin, polyester, polycarbonate, fluororesin, polyvinyl chloride, polyamide ABS resin, AS resin, polyacetal, modified polyphenylene ether, polyaryl Polyimide, cellulose acetate, aluminum, and glass. Examples of the container include a container made of at least one material selected from the group consisting of:

[0054] From the viewpoint of ease of handling of the formulation, the material of the container in which the pharmaceutical composition of the present invention is filled is polyethylene. Polyethylene (PE) (High density polyethylene (HDPE), low density polyethylene (LDPE), ultra Low density polyethylene, linear low density polyethylene (LLDPE), ultra-high molecular weight polyethylene Polypropylene (PP) (isotactic polypropylene, syndiotactic polypropylene, etc.) tactic polypropylene, atactic polypropylene, etc.), and ethylene Propylene copolymer, polymethylpentene, polybutene-1, 1,2-polybutadiene Polyolefin resins such as polyethylene terephthalate and polybutylene terephthalate Polyethylene naphthalate is preferred, and polyethylene or polypropylene is more preferred. It is nice.

[0055] The shape of the container is not limited, but may be a tube, a drip container, or a squeeze container. preferable.

[0056] [Dosage form] The pharmaceutical composition of the present invention may be provided in any form that can be widely used as a drug, quasi-drug, etc. The pharmaceutical composition of the present invention is preferably provided as a preparation that can be used as an external preparation for skin. The pharmaceutical composition is not particularly limited as long as it is in a known form, but it is preferable that the pharmaceutical composition be in a form that can more significantly exhibit the effects of the present invention. From the viewpoint of the above, for example, creams, liquids (including gel compositions), suspensions, emulsions, lotions, etc. It is preferable that the composition be provided in the form of an aqueous pharmaceutical composition such as a poultice, aerosol, or mist. It is more preferable that the composition is a cream, a liquid, a suspension, an emulsion, a lotion, or a mist. It is particularly preferable that the composition is a liquid formulation. This refers to a dosage form in which the proportion of water or water-soluble solvent in the formulation is 10% by mass or more, and is considered to be a dosage form that is stable or usable. From the viewpoint of sensory sensation, the dosage form is preferably 20% by mass or more, more preferably 30% by mass or more. Point.

[0057] The preparation is prepared by mixing each ingredient in accordance with or in accordance with the General Provisions of the 17th Edition of the Japanese Pharmacopoeia. It can be produced by

[0058] [Manufacturing method] The pharmaceutical composition of the present invention can be produced by a known method. If necessary, it may be sterilized. A step or a filtration step may be included.

[0059] [Base, carrier, or other ingredient] The pharmaceutical composition of the present invention may be used in the form of medicines, quasi-drugs, cosmetics, etc., as long as the effects of the present invention are not impaired. The composition can be formulated by mixing with a known base or carrier that can be used as a pharmaceutical preparation, etc. In addition, the pharmaceutical composition of the present invention may contain, for example, surfactants, oils, alcohols, higher fats, etc. Fatty acids, preservatives, antioxidants, antioxidants, cooling agents, preservatives, chelating agents, pH adjusters, Additives such as stabilizers, solubilizers, suspending agents, isotonicity agents, buffers, flavors, coloring agents, and dyes are included. These additives may be used alone or in combination of two or more. can.

[0060] Examples of the base or carrier include hydrocarbons, silicone oils, esters, lower alcohols, and the like. Examples of the hydrocarbon include liquid paraffin, squalane, Gelling hydrocarbons (such as Plastibase), ozokerite, α-olefin oligomers, light Examples of silicone oils include methylpolysiloxane. , crosslinked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl alkyl-modified silicone, crosslinked alkyl-modified silicone, amino-modified silicone, polyether modified silicone, polyglycerin modified silicone, crosslinked polyether modified silicone , crosslinked alkyl polyether modified silicone, silicone / alkyl chain co-modified polyether Modified silicone, silicone / alkyl chain co-modified polyglycerin modified silicone, Polyether modified branched silicone, polyglycerin modified branched silicone, acrylic silicone Examples of the esters include, for example, For example, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate Pill, Cetyl Palmitate, Isononyl Isononanoate, Tetra 2-Ethylhexanoate Pentaerythritol Examples of the lower alcohols include isopropanol. Examples include:

[0061] The base or carrier may be used alone or in combination of two or more.

[0062] The surfactant may be, for example, a nonionic surfactant. Examples of the functionalizing agent include sorbitan fatty acid esters and propylene glycol fatty acid esters. esters, castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene Alkylene alkyl ethers, amines, silicone surfactants, polyoxyethylene Examples of sorbitan fatty acid esters include: For example, sorbitan monoisostearate, sorbitan monolaurate, sorbitan mono Palmitate, Sorbitan Monostearate, Diglycerol Penta-2-ethylhexyl diglycerol sorbitan, tetra-2-ethylhexyl diglycerol sorbitan, etc. Examples of propylene glycol fatty acid esters include propylene monostearate. Examples include propylene glycol fatty acid esters such as propylene glycol, and castor oil. Derivatives include polyoxyethylene hydrogenated castor oil and polyoxyethylene castor oil. Examples of polyoxyethylene sorbitan fatty acid esters include monolauryl ether. Polyoxyethylene (20) Sorbitan (Polysorbate 20), Monostearate Polyoxyethylene (20) sorbitan (polysorbate 60), polyoxyethylene monooleate Polyoxyethylene (20) sorbitan (polysorbate 80), polyoxyethylene isostearate Ethylene (20) sorbitan, etc., and polyoxyalkylene alkyl ethers include Examples of the fatty acids include polyoxyethylene monococoate glyceryl; glycerin alkyl esters; ether; alkyl glucoside; polyoxyethylene cetyl ether, etc., and amines Examples of the silicone-based compounds include stearylamine and oleylamine. Examples of surfactants include polyoxyethylene-methylpolysiloxane copolymers, lauryl siloxane, and lauric acid. Dimethicone, PEG-9 Polydimethylsiloxyethyl Dimethicone Examples include diethyl dimethicone.

[0063] Other examples of surfactants include anionic surfactants and amphoteric surfactants. Examples of anionic surfactants include laurates, palmitates, and cocoyl. Glutamate, coconut methylalanine salt, acyl methyl taurine salt, polyoxyethylene Examples of amphoteric surfactants include lauryl diaminoethylene sulfate and the like. Examples include tylglycine salt, coconut oil fatty acid betaine salt, etc.

[0064] The oils are natural animal and vegetable oils, hydrocarbon oils, ester oils, silicone oils, and higher alkoxides. These include choline, higher fatty acids, and essential oils from plants, animals, and synthetic sources.

[0065] Examples of natural animal and vegetable oils include avocado oil, linseed oil, almond oil, and olive oil. Oil, cocoa oil, beef tallow, tung oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, safflower oil, Soybean oil, evening primrose oil, camellia oil, corn oil, rapeseed oil, horse fat, persic oil, palm Oil, palm kernel oil, castor oil, sunflower oil, lard, grape oil, jojoba oil, macadamia nuts Oil, mink oil, cottonseed oil, japan wax, beeswax, bleached beeswax, coconut oil, hardened coconut oil, ointment Examples include rosehip oil, lanolin, egg yolk oil, and rosehip oil.

[0066] As the hydrocarbon oil, paraffin-based hydrocarbons and olefin-based hydrocarbons are used. For example, For example, squalane, squalene, ceresin, paraffin, pristane, microcrystalline Examples of suitable waxes include paraffin wax, liquid paraffin, and petrolatum.

[0067] Ester oils include synthetic esters and esters of higher alcohols and higher fatty acids. For example, diisobutyl adipate, 2-hexyldecyl adipate, adipic acid Di-2-heptylundecyl acid, isostearyl isostearate, triisostearin Trimethylolpropane, Cetyl 2-ethylhexanoate, Di-2-ethylhexanoate Opentyl glycol, trimethylolpropane tri-2-ethylhexanoate, tetra- 2-Ethylhexanoate, Pentaerythritol, Cetyl Octanoate, Oleyl Oleate, Octyldodecyl oleate, decyl oleate, neopentyl glycol dicaprate , 2-ethylhexyl succinate, isocetyl stearate, butyl stearate, sebacillus acid Diisopropyl lactate, cetyl lactate, tetradecyl lactate, isopropyl myristate, myristate Octyldodecyl myristate, cetyl myristate, myristyl myristate, palmitic acid Octyl Palmitate, 2-Ethylhexyl Palmitate, 2-Hexyldecyl Palmitate, 2-Heptylundecyl Mitic Acid, Cholesteryl 12-Hydroxystearate, Oleic Acid Phytosteryl phosphate, diisostearyl malate, paramethoxycinnamate, tetraethylhexyl ester pentaerythritol larosinate, etc.

[0068] Examples of silicone oils include dimethylpolysiloxane and highly polymerized methylpolysiloxane. Methylphenylpolysiloxane, Methylhydrogenpolysiloxane, Octamethion Dicyclotetrasiloxane, Octamethylcyclopentasiloxane, Decamethylcyclohexylsiloxane Higher alkoxy-modified silicones such as oxasiloxane and stearoxy silicone, alkyl Examples of the silicone modified material include modified silicone and higher fatty acid ester modified silicone.

[0069] Examples of the alcohol include lower alcohols and higher alcohols. Examples of the alcohol include isopropanol, and examples of the higher alcohol include For example, octyldodecanol, isostearyl alcohol, oleyl alcohol, Examples include tearyl alcohol, cetanol, and behenyl alcohol.

[0070] Higher fatty acids include saturated or unsaturated straight-chain or branched-chain fatty acids having 12 to 22 carbon atoms. Acids can be used, for example, isostearic acid, oxystearic acid, oleic acid, Stearic acid, palmitic acid, behenic acid, myristic acid, lauric acid, lanolinic acid, Examples of such acids include oleic acid and linoleic acid.

[0071] Suitable examples of preservatives include benzoic acid, acetic acid, phenol, tincture of iodine, and phenanthrene. Hydroxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol chol, dehydroacetic acid, etc.

[0072] Suitable examples of the antioxidant include sulfites and ascorbic acid.

[0073] Antioxidants include dibutyl hydroxytoluene (BHT), butyl hydroxyaniline, Sole (BHA), sodium sulfite, erythorbic acid, L-cysteine ​​hydrochloride, vitamin Vitamin C, vitamin E, etc. Examples of vitamin C include ascorbic acid, Ascorbyl stearate, Ascorbyl palmitate, L-Ascorbyl Dipalmitate, Ascorbic Acid, Sodium Ascorbate, Dehyd. Ascorbic acid, sodium ascorbyl phosphate, sodium ascorbyl phosphate Examples include thorium salts, magnesium ascorbyl phosphate, etc. Vitamin E Examples of the tocopherol include dl-α-tocopherol, dl-α-tocopherol acetate, and succinate. Examples include dl-α-tocopherol succinate and calcium dl-α-tocopherol succinate. can be.

[0074] Cooling agents include, but are not limited to, menthol (l-menthol, dl-menthol, terpenes such as camphor (d-camphor, dl-camphor, etc.), borneol, etc. essential oils containing terpenoids (mentha oil), or pharmacologically acceptable salts thereof, etc. Examples of these drugs include the following. One or more of these drugs may be used in combination as appropriate. Cut.

[0075] Preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, and sodium dehydroacetate. Isobutyl parahydroxybenzoate, Isopropyl parahydroxybenzoate, Butyl parahydroxybenzoate, Ethyl parahydroxybenzoate, Propyl parahydroxybenzoate, Examples of such an acidic anhydride include benzyl benzoate, methyl paraoxybenzoate, and phenoxyethanol.

[0076] Chelating agents include EDTA·disodium salt, EDTA·calcium·disodium salt, Examples include salt.

[0077] pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, Citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (hydroxides potassium, sodium hydroxide, etc.), organic bases (triethanolamine, diisopropanol amine, triisopropanolamine, etc.

[0078] Stabilizers include sodium polyacrylate and dibutyl hydroxytoluene (BHT ), butylated hydroxyanisole (BHA), etc.

[0079] The solubilizing agents include D-mannitol, benzyl benzoate, trisaminomethane, cobalt. These include cholesterol, triethanolamine, sodium carbonate, and sodium citrate. can be done.

[0080] Suspending agents include, for example, stearyl triethanolamine and sodium lauryl sulfate. , lauryl aminopropionic acid, lecithin, glycerin monostearate, and other surfactants agents; for example, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, Examples of the hydrophilic polymer include dipropyl methylcellulose.

[0081] Examples of isotonicity agents include sodium chloride, glycerin, and D-mannitol. can be done.

[0082] Examples of buffering agents include buffer solutions such as phosphate, acetate, carbonate, and citrate. Can be obtained.

[0083] Examples of colorants include inorganic pigments and natural dyes.

[0084] The pharmaceutical composition of the present invention may further contain other active ingredients within the range not impairing the effects of the present invention. Specific examples of such ingredients include antipruritic ingredients, moisturizing ingredients, Blood circulation promoting ingredients, astringent ingredients, peptides or their derivatives, amino acids or their derivatives, cell activation Examples of such ingredients include synthetic ingredients and vitamin supplements.

[0085] An example of an antipruritic ingredient is crotamiton.

[0086] Moisturizing ingredients include sugars such as trehalose, xylitol, and oligosaccharides; collagen. , elastin, keratin, chitin, chitosan and other polymeric compounds; glycine, asparagus Amino acids such as glycerin, arginine; sodium lactate, sodium pyrrolidone carboxylate Natural moisturizing factors such as cellulose; lipids such as ceramides, cholesterol, and phospholipids; chamomile Examples include plant extracts such as Hamamelis extract, tea extract, and perilla extract. can be done.

[0087] Examples of blood circulation promoters include acetylcholine, caffeine, capsaicin, and cantharine. Stinkweed tincture, gamma oryzanol, rhododendron tincture, zingerone, cepharanthine , Swertia japonica extract, tannic acid, capsicum tincture, tolazoline, nicotinic acid tocopherol Examples of nicotinic acid include nicotinic acid benzyl ester and nicotinic acid amide.

[0088] Astringent ingredients include zinc sulfate, aluminum chlorohydrate, aluminum chloride, and sulfur. Examples include zinc carbonate and tannic acid.

[0089] Examples of peptides or derivatives thereof include keratin decomposition peptides, hydrolyzed keratin, collagen Gen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin hydrolyzate Peptide, collagen decomposition peptide, hydrolyzed collagen, hydroxypropyl ammonium chloride Hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed Decomposed conchiolin, silk protein hydrolyzed peptide, hydrolyzed silk, lauroyl hydrolyzed sil sodium citrate, soybean proteolytic peptide, hydrolyzed soybean protein, wheat protein, wheat proteolytic peptide tide, hydrolyzed wheat protein, casein hydrolyzed peptides, acylated peptides (palmitoyl oligosaccharides) palmitoyl pentapeptide, palmitoyl tetrapeptide, etc. can be done.

[0090] Amino acids or their derivatives include betaine (trimethylglycine), proline, hydroxypropyl esters, Roxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine , β-alanine, threonine, glutamic acid, glutamine, asparagine, asparagine Acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine , taurine, gamma-aminobutyric acid, gamma-amino-β-hydroxybutyric acid, carnitine, carnosine Examples of such supplements include creatine and creatine.

[0091] Cell activation components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid, Vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acid α-hydroxy acids such as glycolic acid and lactic acid, tannins, flavonoids, saponins, Examples include Photosensitive element No. 301.

[0092] Vitamin supplements include vitamin B, vitamin C, vitamin D, vitamin E, Cotinic acids, vitamin K, and other vitamins can be used. The B vitamins include vitamin B1, vitamin B2, vitamin B6, and vitamin B12. Vitamin E includes vitamins such as niacin, nicotinic acid, pantothenic acid, folic acid, and biotin. Examples of such tocopherols include dl-α-tocopherol, dl-α-tocopherol acetate, and dl-α-tocopherol succinate. l-α-tocopherol, dl-α-tocopherol calcium succinate, etc.; Vitamin B Class 2 includes, for example, riboflavin, flavin mononucleotide, and flavin adenine dinucleotide. Nucleotides, Riboflavin butyrate, Riboflavin tetrabutyrate, Riboflavin Sodium 5'-vinyl phosphate, riboflavin tetranicotinate, etc.; Nicotinamide Examples of nicotinic acids include dl-α-tocopherol nicotinate and benzyl nicotinate. , methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methylphenyl) nicotinate (nyl)ethyl, etc.; Vitamin C, for example, ascorbigen-A, ascorbic acid Stearic acid ester, ascorbyl palmitate, L-ascorbyl dipalmitate Colby, Ascorbic Acid, Sodium Ascorbate, Dehydroascorbic Acid, Ascorbic Acid Sodium corbic acid phosphate, sodium ascorbyl phosphate, ascorbic acid magnesium phosphate esters, etc.; vitamin D group, for example, methyl hesperidin vitamin K, e.g., , phylloquinone, falnoquinone, etc.; vitamin B1, for example, dibenzoyl thio Amine, Dibenzoylthiamine hydrochloride, Thiamine hydrochloride, Thiamine cetyl hydrochloride, Thiamine Thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, amine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, Thiamine triphosphate, thiamine triphosphate monophosphate, etc.; Vitamin B Class 6 includes, for example, pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, '-Pyridoxal phosphate, pyridoxamine hydrochloride, etc.; Vitamin B12, e.g. , cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, etc.; Examples of the carboxylic acids include nicotinic acid and nicotinamide; examples of the pantothenic acids include For example, pantothenic acid, calcium pantothenate, pantothenyl alcohol (D-pantothenate), Nol), D-pantethein, D-pantethin, coenzyme A, pantothenyl ethyl ether etc.; vitamin-like factors such as biotin, folic acid, etc.; and pharmacologically acceptable salts thereof. Some examples include:

[0093] [pH] The pH of the pharmaceutical composition of the present invention depends on the type of component (A), the types and contents of other blended components, the preparation The dosage form and method of use should be appropriately determined, and the dosage should be within the physiologically or pharma- ceutical acceptable range. From the viewpoint of safety, the pH may be, for example, 2 to 9, but is not limited thereto. can be about 3 to 8, more preferably about 5 to 7.

[0094] [viscosity] The viscosity of the pharmaceutical composition of the present invention is preferably about 100 μg / g based on the total amount of the pharmaceutical composition from the viewpoint of ease of handling of the formulation. , preferably 1 mPa·s to 10 Pa·s, and more preferably 2 mPa·s to 8 Pa·s. The viscosity in this specification is preferably from 3 Pa·s to 4 Pa·s. The measurements were taken using a RB80 viscometer manufactured by Toki Sangyo Co., Ltd. and an M3 rotor at a rotation speed of 12 rpm. The results are those obtained when the measurement was performed at 1 minute.

[0095] [Application] The pharmaceutical composition of the present invention is preferably used for, but not limited to, athlete's foot or ringworm, candidiasis, etc. The pharmaceutical composition of the present invention is used for the treatment of nails and nail periphery, particularly nail grooves and / or In addition to the groove near the yellow line, the nail matrix, nail root, lunula, nail plate, nail tip, yellow line, posterior nail fold, cuticle, and lateral nail fold It can be used on the nails and around the nails, including the nail bed and subungual skin, and is effective in treating athlete's foot or ringworm. In order to more significantly exhibit the effects of the present invention, it is particularly preferable to use a groove and / or It can be applied to areas of athlete's foot that are difficult to reach with the active ingredient, such as near the yellow line.

[0096] Athlete's foot is a skin condition caused by the fungus Trichophyton. The symptoms and characteristics of the nails and the area around the nails are as follows: , itching, small bumps, peeling skin, dryness of the nails and around the nails, hardening, flaking, roughness, etc. Trichophyton fungi are especially prevalent in the thick areas of the nails and around the nails, where keratin, a component of the keratin, is present. It is easy to develop and symptoms may be particularly noticeable on the nails and around the nails.

[0097] Ringworm is a skin condition caused by the fungus Trichophyton. Small red rings appear on the skin and gradually The symptoms are similar to athlete's foot and include itching, but ringworm occurs in areas with thin skin. Easy to wear.

[0098] Candidiasis is caused by the Candida fungus and causes dry skin on the surface of the hands and peeling skin between the fingers. Symptoms include a white discoloration of the base of the nail.

[0099] The pharmaceutical composition of the present invention can be used to treat, but is not limited to, symptoms caused by tinea fungus, tinea versicolor, candidiasis, digitorrhea, and other conditions. It can be used to treat intertrigo, intertrigo, etc.

[0100] The pharmaceutical composition of the present invention is not limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, It is preferable that the composition be provided as a liquid agent for treating athlete's foot, for application to the nails and around the nails.

[0101] In addition, the method of using the pharmaceutical composition of the present invention can be applied to various conditions such as nails and the skin around the nails, age, and sex. Although the method varies depending on factors such as the above, the following method may be used, for example. 5 times, preferably 1 to 3 times, more preferably 1 time) and administer an appropriate amount (e.g., about 0.5 to 2 g) It may be applied to the nail and around the nail (e.g., the nail groove and / or the groove near the yellow line). The daily dose of the antibacterial agent (e.g., terbinafine or its salt) is, for example, about 5 to 20 mg. The composition can be applied to the nail and around the nail (e.g., in the nail groove and / or groove near the yellow line) in this manner. The application method is selected according to the dosage form, and preferably by application. The application period is, for example, about 3 It is preferable to set the period to 0 days or more.

[0102] [Promotion of spread of pharmaceutical composition] In the present invention, (A) an antifungal agent, (B) a viscosity-increasing polymer and / or a polyhydric alcohol, and (C) a viscosity-increasing agent, C) By making the ingredients coexist, the pharmaceutical composition containing them is particularly effective for nails and The spread of the composition around the nail can be promoted. Here, the promotion of spread of the composition around the nail can be particularly achieved by the following method. In the present invention, the "extendability" of a pharmaceutical composition refers to the ability of the pharmaceutical composition to be applied to nails and The nail groove and / or the groove near the yellow line, as well as the nail matrix, nail root, nail lunula, nail plate, nail Spreads to the nail and surrounding areas, including the tip, yellow line, posterior nail fold, cuticle, lateral nail fold, nail bed, and subungual skin In order to promote such spreading, each component of the pharmaceutical composition of the present invention is The same conditions as those for concentration, pH, viscosity, formulation conditions, etc., are used.

[0103] [Glossy or moisturizing feeling of pharmaceutical composition] In the present invention, the pharmaceutical composition contains (A) an antifungal agent, (B) a viscosity-increasing polymer and / or a polyhydric alcohol. The coexistence of kohl and component (C) provides gloss and / or shine to the nails and around the nails. In the present invention, the composition that exerts such a glossy or moisturizing feeling can impart a moisturizing feeling. In order to achieve this, the conditions of the pharmaceutical composition of the present invention, such as the concentration of each component, pH, viscosity, and formulation, The same conditions are adopted. EXAMPLES

[0104] Next, the present invention will be described in detail with reference to examples and test examples. The present invention is not limited to the above examples.

[0105] [Test Example 1. Surface tension measurement test] Pharmaceutical compositions (liquids) having the compositions of the Examples and Comparative Examples shown in Tables 1 to 5 were prepared according to conventional methods. Next, the surface tension of the compositions of the examples and comparative examples was measured. Take an appropriate amount of each and measure it with a capillary rise type surface tensiometer (capillary size φ6×160mm, Measured using a Pirari inner diameter of φ0.5mm (manufactured by AS ONE, model number 2380-05-10) The surface tension reduction rate of each Example relative to a given Comparative Example was calculated according to Equation 1. The efficacy figure was two digits. The results are shown in Tables 1 to 5. The lower the surface tension, the more the composition spreads. This allows the drug to be delivered to the fungus more effectively after application to the affected area. Equation 1: Surface tension reduction rate = (surface tension of comparative example - example or reference example corresponding to each comparative example) surface tension of the comparative example) / surface tension of the comparative example × 100 (%)

[0106] [Table 1]

[0107] [Table 2]

[0108] [Table 3]

[0109] [Table 4]

[0110] [Table 5]

[0111] It was confirmed that the composition of the example had a lower surface tension than the composition of the comparative example. Therefore, terbinafine hydrochloride is mixed with (B) a thickening polymer or a polyhydric alcohol, and (C ) Isopropyl methylphenol, glycyrrhetinic acid, lidocaine or diphenhydramine The composition has improved extensibility by adding methacrylate hydrochloride. This allows the composition to be more effectively delivered to fungi that reside deep within the tissue.

[0112] (B) Components: polyvinyl alcohol, polyethylene glycol, 1,3-butylene Glycol, methyl acrylate-2-ethylhexyl acrylate copolymer or carbo When a vinyl polymer is used, a similar decrease in surface tension is observed.

[0113] [Test Example 2. Surface tension measurement test] Pharmaceutical compositions (liquids) having the compositions of the Examples and Comparative Examples shown in Table 6 were prepared according to conventional methods. Next, the surface tension of the compositions of the examples and comparative examples was measured in the same manner as in Test Example 1. In the examples, the surface tension reduction rate of each example relative to each comparative example was calculated according to formula 1. The numbers were two digits. The results are also shown in Table 6. The lower the surface tension, the more the composition spreads. Therefore, by applying it to the affected area, the drug can be delivered appropriately to the fungus.

[0114] [Table 6]

[0115] In Test Example 2-1, the composition of the embodiment had a lower surface tension than the composition of the comparative example. Therefore, it was confirmed that butenafine hydrochloride was The extensibility of the composition was improved by the coexistence of K30 and (C) glycyrrhetinic acid. It can be understood that such a composition is more suitable for fungi present deep within the nail and around the nail. The composition can be delivered.

[0116] In Test Example 2-2, the composition of the embodiment had a lower surface tension than the composition of the comparative example. Therefore, it was confirmed that miconazole nitrate was combined with (B) polyvinylpyrrolidone. It was found that the extensibility of the composition was improved by the coexistence of K30 and (C) lidocaine. Such a composition is more suitable for fungi present deep within the nail and around the nail. can be delivered.

[0117] In Test Example 2-3, the composition of the embodiment had a lower surface tension than the composition of the comparative example. It was therefore confirmed that isoconazole nitrate was The extensibility of the composition was improved by the coexistence of (C) glycyrrhetinic acid and (D) glycyrrhetinic acid. It can be understood that such a composition is more suitable for fungi present deep within the nail and around the nail. The composition can be delivered to.

[0118] In Test Examples 2-1 to 2-3, glycerin and polyvinyl alcohol were used as component (B). Polyethylene glycol, 1,3-butylene glycol, methyl acrylate, In the case of using 2-ethylhexyl carboxylate copolymer or carboxyvinyl polymer, Similarly, a decrease in surface tension is observed.

[0119] [Test Example 3. Sensory Evaluation] For five subjects, the pharmaceutical compositions (liquids) of the Examples and Comparative Examples shown in Table 7 were administered to the nails and Apply an appropriate amount to the area around the area and measure the gloss, spreadability, and moisturizing effect immediately after application or 30 minutes after application using the VA. The evaluation was performed using the Visual Analogue Scale (S) method. For each question, measure the length from the left end of a 100mm long line to the diagonal line position you answered. In the case of gloss, the condition of the nails 30 minutes after application was scored 0 as "no feeling at all" and 1 as "no feeling at all." The answer in mm (left end of the line segment), "It feels so strong that it looks bright" is 100mm ( The answer was defined as the answer as the right end of the line, and the degree of glossiness of each composition was evaluated. In the case of the condition of the preparation around the nail immediately after application, "no spreading at all" was defined as 0 mm (left of the line). "extended to every corner" was defined as the answer for 100 mm (the right end of the line segment) In order to evaluate the spreadability of each composition, the degree of moisturizing feeling was evaluated. Regarding the state of the skin, "not felt at all" was answered as 0 mm (the left end of the line), and "very strong" was answered as The answer was defined as 100 mm (the right end of the line), and the extent to which each composition felt moisturizing was measured. The subjects were blinded to the composition of each composition. The results are shown in Table 7. .

[0120] [Table 7]

[0121] Terbinafine hydrochloride alone had low gloss, extensibility, and moisturizing effect on the nails and around the nails (comparison Example 5) On the other hand, (B) a thickening polymer or a polyhydric alcohol, and (C) isopropyl methyl By adding phenylphenol and glycyrrhetinic acid, all subjects reported that the skin had a glossy feel, good spreadability, and It was confirmed that the subjects felt an improvement in the moisturizing sensation on and around the nails.

[0122] (B) Components: polyvinyl alcohol, polyethylene glycol, 1,3-butylene Glycol, methyl acrylate-2-ethylhexyl acrylate copolymer or carbo (C) lidocaine or diphenhydramine hydrochloride is used as the component The composition shown in Table 8 was prepared using the above ingredients, and when Test Example 3 was carried out, the gloss, spreadability, nail and Improved moisturizing effect around nails is confirmed.

[0123] [Table 8]

[0124] [Test Example 4. Surface tension measurement test] Pharmaceutical compositions (liquids) having the compositions of the Examples and Comparative Examples shown in Table 9 were prepared according to conventional methods. Next, the surface tension of the compositions of the examples and comparative examples was measured in the same manner as in Test Example 1. In the examples, the surface tension reduction rate of each example relative to each comparative example was calculated according to formula 1. The numbers were two digits. The results are also shown in Table 8. The lower the surface tension, the more the composition spreads. Therefore, by applying it to the affected area, the drug can be delivered appropriately to the fungus.

[0125] In Test Example 4, the composition of the embodiment had a lower surface tension than the composition of the comparative example. Therefore, it was confirmed that terbitenafine hydrochloride was combined with (B) polyvinyl alcohol. and (C) isopropyl methylphenol is added to improve the extensibility of the composition. It can be understood that such a composition is effective for the nail, around the nail, and especially around the nail groove and / or yellow area. This allows the composition to be more effectively delivered to fungi present deep in the grooves near the lines.

[0126] [Table 9]

[0127] [Test Example 5. Surface tension measurement test] A pharmaceutical composition that is a liquid preparation (gel composition) having the composition of the examples and comparative examples shown in Table 10, The compositions were prepared according to a conventional method. Next, the surface tensions of the compositions of the examples and comparative examples were measured in the same manner as in Test Example 1. In each test example, the surface tension reduction rate of each example relative to each comparative example was calculated using the formula 1. The calculation was performed according to the following formula. The significant figures were two digits. The results are shown in Table 10. The composition spreads so much that it can be applied to the affected area to deliver the drug to the fungus properly. Cut.

[0128] In Test Example 5, the composition of the embodiment had a lower surface tension than the composition of the comparative example. Therefore, it was confirmed that terbitenafine hydrochloride was combined with (B) glycerin and / or Polyvinylpyrrolidone K30, (C) glycyrrhetinic acid, and lidocaine are present together It can be understood that the spreadability of the composition is improved by this. Such a composition is suitable for application to nails, around nails, and nails. It is more effective against fungi present in the deep areas of the nail groove and / or the groove near the yellow line. Can deliver the product.

[0129] [Table 10]

[0130] Formulation examples (medicinal compositions for nails and / or around the nails) of the present invention are shown below. Meanwhile, pharmaceutical compositions were prepared by conventional methods. All preparations were packed in PE containers. It is also possible.

[0131] [Table 11]

Claims

1. (A) an antifungal agent; (B) Vinyl polymers, acrylic polymers, starch polymers, dextran, dextrin Phosphorus fatty acid ester, casein, dimethyl distearyl ammonium hectorite, (a Ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer, distearate Polyethylene glycol stearate, Ethylene glycol triisostearate, Triisostearate Polyoxyethylene (20) methyl glucoside, bentonite, hectorite, Alginic acid and / or its salts, propylene glycol alginate and polyhydric alcohols At least one or two selected from the group consisting of (C) one or more selected from the group consisting of anti-inflammatory agents, local anesthetics, bactericides, and antihistamines; A pharmaceutical composition for nails and / or around the nails, comprising one or more compounds.

2. 2. The pharmaceutical composition according to claim 1, wherein the nail and / or the area around the nail is a nail groove and / or a groove near the yellow line. Composition.

3. The pharmaceutical composition according to claim 1 or 2, wherein the (A) antifungal agent is an amine antifungal agent.

4. The (A) antifungal agent is at least one selected from the group consisting of terbinafine and salts thereof. The pharmaceutical composition according to claim 3 , wherein the compound is one of:

5. The component (B) is polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, glycerin, 1,3-butylene glycol, methyl acrylate, 2-acrylic acid At least one selected from the group consisting of ethylhexyl copolymers and carboxyvinyl polymers. The composition according to any one of claims 1 to 4, further comprising at least one thickening polymer or polyhydric alcohol. The pharmaceutical composition described above.

6. The pharmaceutical composition according to any one of claims 1 to 5, further comprising ethanol.

7. The composition according to claim 6, wherein the content of the ethanol is 20% by mass or more based on the total amount of the composition. Pharmaceutical compositions.

8. The pharmaceutical composition according to any one of claims 1 to 7, which is in the form of a liquid formulation.

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