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 the portion around the nail.SOLUTION: A pharmaceutical composition for a nail and / or the portion around the nail is prepared which comprises: (A) an antifungal agent; (B) cellulose polymer; 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 aimed to provide a method for producing a cellulose-based polymer comprising the steps of: (A) an antifungal agent; and (C) an anti-inflammatory agent, a local anesthetic agent, a disinfectant, and an antihistamine. By including one or more compounds selected from the above, the spreadability to the nail and the surrounding area is improved. As a result, the present invention has been completed based on the discovery that a pharmaceutical composition capable of preventing drying can be obtained.

[0009] That is, the present invention provides the pharmaceutical compositions listed below. Section 1. (A) Antifungal agents; (B) a cellulosic polymer; and (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. Any one of items 1 to 4, wherein the total content of the component (B) is 0.01 to 10% by mass. The pharmaceutical composition described in Section 6. The total content of the (B) component per 1 part by mass of the total content of the (A) component is 0.1 to 20 parts by mass. 6. The pharmaceutical composition according to any one of items 1 to 5, Section 7. Item 7. The pharmaceutical composition according to any one of Items 1 to 6, further comprising ethanol. Section 8. Item 8. The pharmaceutical composition according to item 7, wherein the content of ethanol is 20% by mass or more based on the total amount of the composition. Pharmaceutical composition. Section 9. Item 9. The pharmaceutical composition according to any one of items 1 to 8, which is in the form of a gel or liquid. 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, (B) a cellulose-based polymer, and a specific (C) component. The pharmaceutical composition for use around the nail of the present invention has good spreadability on the nail and around the nail, and Furthermore, it is effective in preventing whitening and peeling of the skin around the nails and nails due to dryness. It can be treated, ameliorated, or prevented.

[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. There are.

[0013] The types of the antifungal agent of the present invention include, for example, allylamine antifungal agents, benzylamine antifungal agents, antifungal agents such as thiocarbamine antifungal agents, amine antifungal agents such as imidazole antifungal agents, antifungal agents or azole antifungal agents such as triazole antifungal agents, or morpholine antifungal agents The type of the antifungal agent of the present invention is, for example, an agent that can more prominently exhibit the effect of the present invention. From the viewpoint of achieving the above, amine-based antifungal agents and azole-based antifungal agents are preferred, and amine-based antifungal agents are more preferred. The agent 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 aryl amines such as terbinafine and naftifine. Amine antifungal agents, benzylamine antifungal agents such as butenafine, tolnaftate, Among these, the effect of the present invention is more pronounced with thiocarbamine antibiotics such as naphthate. From the viewpoint of excellent effectiveness, the allylamine-based antifungal agents are preferably used, and among them, the allylamine-based antifungal agents are particularly preferred. Examples thereof include terbinafine and a salt thereof such as terbinafine hydrochloride. can be.

[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 pharmaceutical or physiological properties. Any commercially acceptable azole antifungal agent may be used. Examples of the imidazole ring include 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 preferably used in the following cases: 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 dimethylaminopropane or a salt thereof. Each of these components (A) may be used alone. Any combination of two or more of them may be used.

[0017] In the present invention, antifungal agents include, but are not limited to, terbinafine, butenafine, At least one selected from the group consisting of benzodiazepine, miconazole, isoconazole, and salts thereof. One or a combination of two or more of these 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) Cellulosic polymer] The following substances can be used as the cellulose-based polymer (B) of the present invention. That is, the cellulose-based polymer compound is not particularly limited as long as it is a cellulose-based polymer compound. or cellulose obtained by replacing the hydroxyl groups of cellulose with other functional groups. The present invention uses a compound that is a polymeric compound that can be applied to the skin, nails, and nail surroundings. The functional groups that can be substituted for the hydroxyl groups of cellulose include methoxy groups, ethoxy groups, and methyl groups. hydroxy group, hydroxymethoxy group, hydroxyethoxy group, hydroxypropoxy group, carboxyl group, Examples of cellulose-based polymer compounds include The resulting cellulose is methylcellulose, ethylcellulose, hydroxyethylcellulose, and hydroxy Methylcellulose, Hydroxypropylcellulose, Hydroxypropylmethylcellulose Hydrophobized hydroxypropyl methylcellulose, carboxymethyl cellulose, carbo Examples of the salt include hydroxyethyl cellulose and salts thereof. A pharmacologically acceptable salt is preferred, and among them, an alkali metal salt is more preferred, and sodium Among these, the potassium salt and the like are particularly preferred.

[0020] These components (B) may all be used alone or in any combination of two or more. It may also be used in combination.

[0021] These components (B) are not limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, Of these, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose cellulose, hydrophobized hydroxypropyl methylcellulose, hydroxypropyl cellulose cellulose, carboxymethylcellulose, and salts thereof. Hydroxypropyl methylcellulose and hydrophobized hydroxypropyl methylcellulose are preferred. More preferred are cellulose, hydroxyethyl cellulose, and sodium carboxymethyl cellulose. Hydroxypropyl methylcellulose and hydrophobized hydroxypropyl methylcellulose are preferred. More preferred are cellulose and hydroxyethyl cellulose.

[0022] 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, preferably 0.1% by mass or more, more preferably It is preferably 0.5% by mass or more, more preferably 0.8% by mass or more, and particularly preferably 1. The total content of the (B) component is determined from the viewpoint of the feel of the formulation and ease of handling. The amount is usually 10% by mass or less, preferably 5% by mass or less, based on the total amount of the pharmaceutical composition. More preferably, it is 4.5% by mass or less, further preferably, it is 3.5% by mass or less, and particularly preferably The total content of the component (B) relative to the total amount of the pharmaceutical composition is 2.5% by mass or less. From the viewpoint of exhibiting a more prominent brightening effect, the content is usually 0.01 to 10 mass %, preferably 0 0.1 to 5% by mass, more preferably 0.5 to 4.5% by mass, and even more preferably The content is 0.8 to 3.5 mass %, and particularly preferably 1.5 to 2.5 mass %.

[0023] 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, ( The total content of the component (B) is usually 0.1 to 20 parts by mass, preferably 0.5 to 10 parts by mass. 0.625 to 5 parts by mass is more preferable, 0.7 to 3 parts by mass is even more preferable, and 0.8 to It is particularly preferable that the content is 2.7 parts by mass. Also, it is preferable that the content is 1.4 to 2.5 parts by mass, or 1.5 to 2 parts by mass. Parts may also be presented as preferred ratios.

[0024] Furthermore, for example, when the component (B) is hydroxypropyl methylcellulose, In order to achieve a more pronounced effect of illumination, the inclusion of hydroxypropyl methylcellulose The amount is preferably 0.1 to 1.5% by mass, more preferably is preferably 0.2 to 1.3 mass%, more preferably 0.3 to 1.2 mass%, and particularly preferably is 0.4 to 1 mass%. Also, 0.5 to 5 mass%, 0.75 mass% to 2.5 mass%, A preferred blending amount is 1 to 2% by mass. For example, when component (B) is hydrophobized hydroxypropyl methylcellulose, the present invention In order to more significantly exert the effect of the hydrophobicity, The content is preferably 0.1 to 0.9% by mass, more preferably 0.1 to 0.9% by mass, based on the total amount of the pharmaceutical composition. The content is preferably 0.2 to 0.8 mass%, more preferably 0.3 to 0.7 mass%, and particularly preferably Or 0.4 to 0.6 mass%. Also, 0.5 to 5 mass%, 1 to 2.5 mass%, 1. A content of 2 to 2 mass % can also be presented as a preferable blending amount.

[0025] [(C) component] Examples of the component (C) of the present invention include the following. That is, (C) from the group consisting of anti-inflammatory agents, local anesthetics, bactericides, and antihistamines. The compound is selected from one or more compounds.

[0026] 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.

[0027] From the viewpoint of exhibiting the effects of the present invention more significantly, the total content of (C) is The content is usually 0.01% by mass or more, preferably 0.1% by mass or more, and more preferably Preferably, the content is 0.8% by mass or more, more preferably 1% by mass or more, and particularly preferably 1.2% by mass or more. The total content of (C) is set to 100% by mass spectrometry from the viewpoint of more significantly exhibiting the effects of the present invention. It is usually 5% by mass or less, preferably 4.1% by mass or less, based on the total amount of the substance. Preferably, it is 2.8% by mass or less, more preferably, it is 2.5% by mass or less, and particularly preferably, it is 2.8% by mass or less. The total content of (C) is usually 0.01 to 5 mass % based on the total amount of the pharmaceutical composition. %, preferably 0.1 to 4.1 mass%, more preferably 0.8 to 2.8 mass%, and The content is more preferably 1 to 2.5 mass %, and particularly preferably 1.2 to 2 mass %.

[0028] 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 (C) component to the (A) component is, for example, 1 part by mass of the total content of the (A) component. The total content of the C) component is usually 0.01 to 5 parts by mass, preferably 0.1 to 4.1 parts by mass, More preferably, it is 0.8 to 2.8 parts by mass, even more preferably, it is 1 to 2.5 parts by mass, and particularly preferably The content is usually 1.2 to 2 parts by mass.

[0029] (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; Medicine, Allantoin, Glycyrrhetinic Acid, Glycyrrhetinic Acid, Stearyl Glycyrrhetinate , Aldioxa, Ufenamate, Bufexamac, Ibuprofenpiconol, India Methacin, diclofenac, piroxicam, epsilon-aminocaproic acid, berberine , Lysozyme, Sodium Azulene Sulfonate, Dimethylisopropylazulene, Brome Rhein, serrapeptase, semi-alkaline proteinase, or their pharmacologically tolerable Examples of such drugs include nonsteroidal anti-inflammatory drugs such as salts thereof. From the viewpoint of exhibiting a more pronounced effect, nonsteroidal anti-inflammatory drugs are preferred, and glycyrrhizinic acid is preferred. , glycyrrhetinic acid, salts of glycyrrhetinic acid, salts of glycyrrhizinic acid (e.g., glycyrrhetinic acid, Dipotassium rhizinate, monoammonium glycyrrhizinate), and allantoin are more preferred. One or more of these drugs may be used in appropriate combination.

[0030] (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 local anesthetics having amine and ester structures such as rakaine and their salts ethyl aminobenzoate, oxypolyethoxydodecane, and the like. Among these drugs, there are, but are not limited to, amide-type local anesthetics having amine and amide structures. From the viewpoint of more significantly exhibiting the effects of the present invention, lidocaine is particularly preferred. Examples of these drugs include dibucaine hydrochloride. It can also be used.

[0031] (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 Examples of such drugs include benzoic acid, berberine benzoate, or biguanide compounds. Of these drugs, the present invention is particularly useful. From the viewpoint of exhibiting a more remarkable effect, isopropylmethylphenol is preferred.

[0032] 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, Vastin, diphenylimidazole, diphenhydramine, or salts of these compounds Illustrated.

[0033] 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, diphenhydramine, Preferred examples thereof include chlorpheniramine, chlormaleate, and salts thereof. These drugs are rupheniramine, diphenhydramine, and diphenhydramine hydrochloride. One or more of the agents may be used in appropriate combination.

[0034] These components (C) may all be used alone or in any combination of two or more. It may also be used in combination.

[0035] From the viewpoint of more prominently exhibiting the effects of the present invention, the preferred component (C) is glycyrrhetinic acid, a Amide-type local anesthetics having amine and amide structures, isopropyl methylphenol, diphenyl ether One or more selected from the group consisting of salts of diphenhydramine and diphenhydramine. From the viewpoint of more prominently exhibiting the effects of the present invention, the particularly preferred component (C) is glycyl Retinoic acid, lidocaine, isopropyl methylphenol, diphenhydramine, and dif The compound is one or more selected from the group consisting of diphenhydramine and its salts. As the salt of diphenhydramine, although it is not limited thereto, diphenhydramine hydrochloride is preferable. The most preferred component (C) is glycyrrhetinic acid and / or isopropyl methylphenol. It is.

[0036] Furthermore, for example, the component (C) may be glycyrrhizinic acid and its salts, glycyrrhizinic acid and its salts, When the compound is at least one selected from the group consisting of glycyrrhetinic acid and its salts, The content of glycyrrhizinic acid and its salt is determined from the viewpoint of significantly exhibiting the effects of the present invention. Therefore, the amount is preferably 0.1 to 1% by mass, more preferably 0. The content is preferably 2 to 0.8% by mass, and more preferably 0.25 to 0.5% by mass.

[0037] 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% by weight 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 component (C) is lidocaine or dibucaine or a salt thereof, From the viewpoint of more significantly exhibiting the effects of the present invention, lidocaine, dibucaine, or a salt thereof The content of each of these is preferably 0.25 to 2.5% by mass based on the total amount of the pharmaceutical composition. and more preferably 0.5 to 2 mass %.

[0038] For example, when the component (C) is isopropyl methylphenol, the effect of the present invention is exhibited. From the viewpoint of being particularly effective, 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 %.

[0039] For example, when component (C) is diphenhydramine or a salt thereof, the effect of the present invention is From the viewpoint of exhibiting a remarkable effect, the content of diphenhydramine and its salts is It is preferably 0.1 to 2 mass %, more preferably 0.5 to 1 mass %, based on the total amount of the substance. It is.

[0040] In the present invention, (A) an antifungal agent, (B) a cellulose-based polymer, and (C) a component In addition, it can be used as medicines, quasi-drugs, cosmetics, etc., to the extent that its functions are not impaired. Any known ingredient may be included in the pharmaceutical composition. Preferably, ethanol may be contained.

[0041] [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.

[0042] 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 %.

[0043] 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.

[0044] [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 those 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 Acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid Acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid salts with organic acids such as tin acid, salicylic acid, etc.; or salts with acidic acids such as aspartic acid, glutamic acid, etc. The term "salt" also includes solvates and hydrates of salts. In particular, the form of the salt of component (A) is not particularly limited, but it is preferable that the salt be in the form of a salt that is easily available. From the viewpoint of suitability, the salt is preferably an inorganic acid salt, more preferably a hydrochloride or a nitrate. be.

[0045] [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:

[0046] 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. I wish.

[0047] The shape of the container is not limited, but may be a tube, a drip container, or a squeeze container. preferable.

[0048] [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, suspensions, emulsions, gels, lotions, air It is preferable that the composition is provided in the form of an aqueous pharmaceutical composition such as a sol or mist, and more preferably in the form of a gel. , cream, liquid, suspension, emulsion, lotion, or mist is more preferable. In particular, a gel formulation is preferable. The proportion of water or water-soluble solvent contained in the mixture is 10% by mass or more, preferably 20% by mass or more, and more preferably 20% by mass or more. Preferably, this refers to a dosage form containing 30% by mass or more.

[0049] 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

[0050] [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.

[0051] [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, various polymers, preservatives, chelating agents, p H regulators, stabilizers, solubilizers, suspending agents, isotonicity agents, buffers, fragrances, coloring agents, pigments, etc. These additives can be used alone or in combination of two or more. Can be used together.

[0052] 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 Examples of silicone oils include methyl methacrylate, methyl methacrylate, and methyl methacrylate. Polysiloxane, crosslinked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic siloxane Silicone, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone Polyether modified silicone, polyglycerin modified silicone, cross-linked polyether modified silicone, crosslinked alkyl polyether modified silicone, silicone alkyl polyether modified silicone Chain-co-modified polyether-modified silicone, silicone / alkyl chain-co-modified polyglycerin silicone, polyether modified branched silicone, polyglycerin modified branched silicone, Examples include acrylic silicone, phenyl-modified silicone, silicone resin, etc., and ester Examples of the myristates include isopropyl myristate, octyldodecyl myristate, and palladium myristate. Isopropyl palmitate, cetyl palmitate, isononyl isononanoate, tetraethyl Examples of the lower alcohols include, for example, isopropyl alcohol. Examples of the polyhydric alcohol include diethylene glycol. Glycol ethers such as diethylene glycol monomethyl ether and diethylene glycol monoethyl ether ter; polyethylene glycol, propylene glycol, 1,3-butylene glycol, Examples include glycerin and isoprene glycol.

[0053] The base or carrier may be used alone or in combination of two or more.

[0054] 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 lauryl alcohol ether, etc. 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.

[0055] Other examples of surfactants include anionic surfactants and amphoteric surfactants. Examples of anionic surfactants include laurates, palmitates, and cocoyl. Glutamate, coconut oil 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.

[0056] 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.

[0057] 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.

[0058] 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.

[0059] 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.

[0060] 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.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] Suitable examples of the antioxidant include sulfites and ascorbic acid.

[0065] 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.

[0066] 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 (mentha oil) containing terpenoids or terpenoids, or pharmacologically acceptable salts thereof These drugs can be used in combination with one or more of them. It is also possible.

[0067] Various types of polymers include vinyl polymers, acrylic polymers, mucopolysaccharides, and starch polymers. Molecules, dextran, dextrin fatty acid esters, pectin, casein, dimethyl disodium Tearyl ammonium hectorite, (ammonium acryloyldimethyltaurate / bis Nylpyrrolidone copolymer, polyethylene glycol distearate, triisostearyl Ethylene glycol phosphate, polyoxyethylene (20) methyl glycol triisostearate Glucoside, bentonite, hectorite, alginic acid and / or its salts, propyl alginate Examples of thickening agents include ethylene glycol esters, polyethylene glycol, and thickening polysaccharides.

[0068] The vinyl polymer may be polyvinylpyrrolidone, polyvinyl alcohol, or polyvinyl Examples of the aryl methyl ether include aryl methyl ether, and one or more of these may be used. It is also possible.

[0069] Acrylic polymers include acrylic acid / alkyl methacrylate copolymers, acrylic acid Hydroxyethyl acryloyldimethyl taurate copolymer (especially acrylic acid hydrochloride) (Sodium acrylate copolymer), sodium acrylate Acryloyldimethyltaurine copolymer, sodium acrylate / methacrylate Sodium acrylate-sodium methacrylate-alkyl methacrylate copolymer, stearyl S-10 Allyl ether-acrylates copolymer, polyacrylic acid or its salt (carboxylate Vinyl polymer), acryloyldimethyltaurate ammonium copolymer, acrylic acid Methacrylic acid polyoxyethylene glycol ether copolymer, polyacrylamide, and acrylamide-ammonium acrylate copolymers.

[0070] Polysaccharide thickeners are used as ingredients in pharmaceuticals, quasi-drugs, and cosmetics for external use. Among the substances used, specifically, carrageenan, xanthan gum, gum arabic, pe Cutin and mucopolysaccharides. Mucopolysaccharides include chondroitin sulfate (sodium salts, hyaluronic acid or its salts (sodium salts, etc.), and hyaluronic acid derivatives or Examples of such glycosaminoglycans include salts thereof, heparin, and heparinoids. can.

[0071] Starch-based polymers include hydroxypropyl starch phosphate (e.g., Natio StructureXL, manufactured by Nal Starch, LLC), modified cornstarch and cornstarch.

[0072] Preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, and sodium dehydroacetate. Isobutyl parahydroxybenzoate, Isopropyl parahydroxybenzoate, Butyl parahydroxybenzoate, Ethyl parahydroxybenzoate, Propyl parahydroxybenzoate, benzyl benzoate, methyl paraoxybenzoate, phenoxyethanol, etc.

[0073] Chelating agents include EDTA·disodium salt, EDTA·calcium·disodium salt, Examples include salt.

[0074] 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.

[0075] Stabilizers include sodium polyacrylate and dibutyl hydroxytoluene (BHT ), butylated hydroxyanisole (BHA), etc.

[0076] Examples of solubilizing agents include polyethylene glycol, propylene glycol, D-macroglycerin, and the like. Trisaminomethane, Cholesterol, Triethanolamine, Benzyl Benzoate, Examples include amines, sodium carbonate, and sodium citrate.

[0077] Suspending agents include, for example, stearyl triethanolamine and sodium lauryl sulfate. , lauryl aminopropionic acid, lecithin, glycerin monostearate, and other surfactants Examples of such agents include:

[0078] Examples of isotonicity agents include sodium chloride, glycerin, and D-mannitol. can be done.

[0079] Examples of buffering agents include buffer solutions such as phosphate, acetate, carbonate, and citrate. Can be obtained.

[0080] The coloring agent includes inorganic pigments and natural dyes.

[0081] 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.

[0082] Examples of antipruritic ingredients include crotamiton.

[0083] Examples of moisturizing ingredients include hyaluronic acid or its salts (such as sodium salts), and hyaluronic acid. uronic acid derivatives or their salts, trehalose, xylitol, sugars such as oligosaccharides; Phosphorus analogues, polymers such as collagen, elastin, keratin, chitin, and chitosan compounds; amino acids such as glycine, aspartic acid, and arginine; sodium lactate, pyridine Natural moisturizing factors such as sodium lysine carboxylate; ceramides, cholesterol, phospholipids Lipids such as chamomile extract, witch hazel extract, tea extract, and perilla extract Plant extracts and the like.

[0084] 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.

[0085] Astringent ingredients include zinc sulfate, aluminum chlorohydrate, aluminum chloride, and sulfur. Examples include zinc carbonate and tannic acid.

[0086] 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.

[0087] 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.

[0088] 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.

[0089] Vitamin supplements include vitamin B, vitamin C, vitamin D, vitamin E, Cotinic acid, vitamin K, and other vitamins can all be used. The B vitamins include vitamin B1, vitamin B2, vitamin B6, and vitamin B12. , nicotinic acid, pantothenic acid, folic acid, biotin, etc. For example, dl-α-tocopherol, dl-α-tocopherol acetate, dl-succinate -α-tocopherol, dl-α-tocopherol calcium succinate, etc.; Vitamin B2 Examples of the flavin derivatives include riboflavin, flavin mononucleotide, and flavin adenine dinucleotide. Creotide, Riboflavin Butyrate, Riboflavin Tetrabutyrate, Riboflavin 5'-phosphate sodium ester, riboflavin tetranicotinate, etc.; Examples of nicotinic acids include dl-α-tocopherol nicotinate, benzyl nicotinate, Methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methylphenyl) nicotinate Ascorbic acid ethyl, etc.; ascorbic acid group C, for example, ascorbigen A, ascorbic acid sulfate, etc. Thearic acid ester, ascorbyl palmitate, L-ascorbyl dipalmitate Ascorbic Acid, Sodium Ascorbate, Dehydroascorbic Acid, Ascorbic Acid Sodium ascorbic acid phosphate, sodium ascorbyl phosphate, ascorbic acid magnesium phosphate; vitamin D, for example, methyl hesperidin , ergocalciferol, cholecalciferol, etc.; as vitamin K, for example, Phylloquinone, falnoquinone, etc.; Vitamin B1, for example, dibenzoylthiazolinone, Thiamine, Dibenzoyl Thiamine Hydrochloride, Thiamine Hydrochloride, Thiamine Cetyl Hydrochloride, Thiamine Thiamine ocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine Monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, amine triphosphate, thiamine triphosphate monophosphate, etc.; vitamin B6 Examples of pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5' -pyridoxal phosphate, pyridoxamine hydrochloride, etc.; Vitamin B12, for example, Cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, etc.; Nicotine Examples of acids include nicotinic acid and nicotinamide; examples of pantothenic acids include For example, pantothenic acid, calcium pantothenate, pantothenyl alcohol (D-panthenoyl ol), D-pantethin, D-pantethin, coenzyme A, pantothenyl ethyl ether, etc. Vitamin-like factors such as biotin, folic acid, and their pharmacologically acceptable salts. Can be obtained.

[0090] [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.

[0091] [Viscosity] The viscosity of the pharmaceutical composition of the present invention is determined based on the total amount of the pharmaceutical composition from the viewpoint of ease of handling the formulation. is preferably 1 to 10 Pa·s, more preferably 2 to 8 Pa·s, and further The viscosity in this specification is preferably 4 to 6 Pa·s. Measured using an RB80 type viscometer and M3 rotor at a rotation speed of 12 rpm for a measurement time of 1 minute. The results obtained at the time are used as the results.

[0092] [Application] The pharmaceutical composition of the present invention is preferably, but not limited to, athlete's foot or ringworm, candida The pharmaceutical composition of the present invention is used for the treatment of nails and nail periphery, particularly nail grooves and / or nail periphery. Or in the groove near the yellow line, the nail matrix, nail root, lunula, nail plate, nail tip, yellow line, posterior nail fold, cuticle, lateral nail It can be used on the nails and around the nails, including the nail bed, nail base, and subungual skin, and is effective in treating athlete's foot and ringworm. From the viewpoint of more prominently exhibiting the effects of the present invention, it is particularly preferable to use a groove and / or It can also be applied to areas of athlete's foot that are difficult to reach with the active ingredient, such as near the yellow line area.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] 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 is provided as a gel or liquid for treating athlete's foot for application to the nails and around the nails. .

[0098] 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 antibacterial agent (e.g., terbinafine or its salt) is, for example, about 5 to 20 mg. By applying the composition to the nail and the area around the nail (e.g., the nail groove and / or the groove near the yellow line) as shown in FIG. The application method is selected according to the dosage form, and preferably involves application by painting. The application period is, for example, about It is preferable to set the period to 30 days or more.

[0099] [Promotion of spread of pharmaceutical composition] In the present invention, (A) an antifungal agent, (B) a cellulose-based polymer, and (C) a component are present together. By this, the pharmaceutical composition containing them is particularly promoted to spread to the nails and around the nails. Here, the promotion of spreading in particular is also referred to as "extensibility" in this specification. In the present invention, the "extendability" of the pharmaceutical composition refers to the ease with which the pharmaceutical composition can be applied to nails and around nails, particularly In addition to the nail groove and / or groove near the yellow line, the nail matrix, nail root, lunula, nail plate, nail tip, yellow line, posterior nail fold, This refers to the spread of the nail and the surrounding area, including the cuticle, lateral nail fold, nail bed, and subungual skin. In order to promote spreading, the concentration, pH, viscosity and other properties of each component in the pharmaceutical composition of the present invention may be adjusted. Conditions similar to those for the formulation are adopted.

[0100] [Glossy or moisturizing feeling of pharmaceutical composition] In the present invention, the pharmaceutical composition comprises (A) an antifungal agent, (B) a cellulosic polymer, and (C) By combining these ingredients, it is possible to impart a glossy and / or moisturizing feel to the nails and the areas around the nails. In the present invention, in order to achieve such glossy or moisturizing feeling, Adopt conditions similar to those of the concentration, pH, viscosity, formulation, etc. of each component in the pharmaceutical composition of the invention. do. EXAMPLES

[0101] 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.

[0102] [Test Example 1. Surface tension measurement test] Pharmaceutical compositions having the compositions shown in Tables 1 to 5 in the Examples and Comparative Examples were prepared according to conventional methods. The surface tension of the compositions of the examples and the comparative examples was measured. Tube rising type surface tensiometer (capillary size φ6×160mm, capillary inner diameter φ 0.5mm; AS ONE, model number 2380-05-10) was used for measurement. The surface tension reduction rate of each Example relative to the Comparative Example was calculated according to Equation 1. The results are shown in Table 1. The lower the surface tension, the more the composition spreads, allowing the drug to be more effectively applied to the fungus after application to the affected area. It can be delivered. Formula 1: Surface tension reduction rate = (surface tension of comparative example - surface tension of example) / surface tension of comparative example x 10 0(%)

[0103] [Table 1]

[0104] [Table 2]

[0105] [Table 3]

[0106] [Table 4]

[0107] [Table 5]

[0108] It was confirmed that the composition of the example had a lower surface tension than the composition of the comparative example. Therefore, terbinafine hydrochloride, cellulosic polymer, and isopropyl methylphenanthroline were added to the In the presence of glycyrrhetic acid, lidocaine or diphenhydramine hydrochloride, The composition has improved spreadability. Such a composition is effective against fungi present deep in the nails and around the nails. The composition can be delivered more appropriately to the target area.

[0109] [Test Example 2. Sensory Evaluation] The pharmaceutical compositions of the Examples and Comparative Examples shown in Table 6 were applied to the nails and around the nails of five subjects. The gloss, spreadability, and moisturizing sensation were evaluated at the time of application or 30 minutes after application. 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. Regarding the feeling of shine, the condition of the nails and the area around the nails 30 minutes after application was "No" was chosen as the answer with 0 mm (the left end of the line), and "It feels so strong that it looks like it is shining" was chosen as the answer with 1 The answer was defined as 0 mm (the right end of the line), and the degree of glossiness of each composition was evaluated. Regarding the ease of application of the formulation on the nails and around the nails, " is 0 mm (the left end of the line) and "it stretched well to every corner" is 10 mm (the right end of the line) The answer was defined as the ultimate value, and the degree of extensibility of each composition was evaluated. Regarding the condition of the nails and the area around the nails after 30 minutes, "I can't feel anything at all" is set at 0 mm (the left end of the line). The answer of "very strong feeling" was defined as 10 mm (the right end of the line), and each composition The subjects were blinded to the composition of each composition and evaluated the moisturizing effect of each composition.

[0110] [Table 6]

[0111] Terbinafine hydrochloride, cellulose polymers and isopropyl methylphenol The coexistence of glycyrrhetinic acid improves the gloss, extensibility, and moisturizing effect of the nails and the area around the nails. It was confirmed that.

[0112] The following are examples of the formulation of the present invention. A pharmaceutical composition was prepared by a conventional method according to the formulation shown in Table 7. These formulations are gels that are effectively used on the nails and around the nails. It is also possible to use the product by storing it in a PE container.

[0113] [Table 7]

Claims

1. (A) an antifungal agent; (B) a cellulosic polymer; and (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. The medicine according to claim 1, wherein the nail and / or the area around the nail is the nail groove and / or the groove near the yellow line. composition.

3. The pharmaceutical composition according to claim 1 or 2, wherein the antifungal agent (A) 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. The pharmaceutical composition according to claim 3 , wherein the compound is selected from the group consisting of phenylalanine, ...

5. 5. Any one of claims 1 to 4, wherein the total content of the component (B) is 0.01 to 10 mass %.

2. The pharmaceutical composition according to claim 1.

6. The total content of the (B) component per 1 part by mass of the total content of the (A) component is 0.1 to 20 parts by mass. Item 6. The pharmaceutical composition according to any one of Items 1 to 5,

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

8. 8. The composition according to claim 7, wherein the content of the ethanol is 20% by mass or more based on the total amount of the composition. A pharmaceutical composition comprising:

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

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