Pharmaceutical composition for nails and the area around the nails

Abstract

The present invention provides a pharmaceutical composition with excellent spreadability and other properties for application to nails and the surrounding area. [Solution] (A) Antifungal agent; (B) Cellulosic polymer; and (C) Anti-inflammatory agent, topical anesthetic. One or more compounds selected from the group consisting of intoxicants, disinfectants, and antihistamines. Prepare a pharmaceutical composition for nails and / or nail area containing [the specified ingredient].

Description

[[Technical Field]]

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

[0002] Antifungal agents for inhibiting the growth of fungi are used to treat and prevent various diseases and symptoms caused by fungal infections, and are widely used for prevention and improvement. External preparations for antifungal purposes are particularly used for tinea and skin candidiasis, pityriasis versicolor and other skin infections (Patent Document 1).

[0003] On the other hand, fungal infections can also occur on nails and periungual areas, and appropriate treatment is desired, . [[Prior Art Documents]] [[Patent Documents]]

[0004] [[Patent Document 1]] Japanese Unexamined Patent Application Publication No. 2006-232853 [[Summary of the Invention]] [[Problem to be Solved by the Invention]]

[0005] However, regarding antifungal agents for nails and periungual areas, it cannot be said that sufficient research has been conducted on appropriate pharmaceutical compositions.

[0006] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a pharmaceutical composition for nails and periungual areas containing an antifungal agent. [[Means for Solving the Problem]]

[0007] Nails and periungual areas have unique unevenness among parts of the body, so when infected with fungi, the antifungal It is difficult to adequately deliver the preparation containing the drug to the affected area, such as the nail or the deep tissues surrounding the nail. Further detailed studies are needed on delivery techniques for pharmaceutical compositions containing antifungal agents to the nails and surrounding areas. It is necessary.

[0008] The present invention provides a formulation that improves spreadability on the nail and surrounding area, and reduces dryness of the nail and surrounding area. The present inventors aim to provide (A) an antifungal agent and (B) a cellulose-based polymer. (C) Select from the group consisting of anti-inflammatory agents, local anesthetics, disinfectants, and antihistamines. By incorporating one or more selected compounds, the spreadability to the nail and surrounding area is improved. As a result, we discovered that a pharmaceutical composition capable of preventing drying can be obtained, and thus completed the present invention.

[0009] In other words, the present invention provides the following pharmaceutical compositions. Section 1. (A) Antifungal agents; (B) Cellulose polymers; and (C) Selected from the group consisting of anti-inflammatory agents, local anesthetics, bactericides, and antihistamines A pharmaceutical composition for nails and / or the area around the nails containing one or more compounds. Section 2. The nail and / or the area around the nail is the nail groove and / or the groove near the yellow line, according to the pharmaceutical composition described in item 1. thing. Section 3. The pharmaceutical composition according to item 1 or 2, wherein the antifungal agent (A) is an amine-based antifungal agent. 4. The (A) antifungal agent is selected from the group consisting of terbinafine and its salts, and at least The pharmaceutical composition described in item 3, which is also one type. Section 5. The total content of component (B) is 0.01 to 10% by mass, whichever of items 1 to 4 applies. The pharmaceutical composition described above. Section 6. The total content of component (B) is 0.1 to 20 parts by mass relative to 1 part by mass of the total content of component (A) The pharmaceutical composition according to any one of Items 1 to 5, which is parts by mass. Item 7. The pharmaceutical composition according to any one of Items 1 to 6, further comprising ethanol. Item 8. The pharmaceutical composition according to Item 7, wherein the content of the ethanol is 20% by mass or more relative to the total amount of the composition . Item 9. The pharmaceutical composition according to any one of Items 1 to 8, which is a gel or a liquid preparation. [Advantageous Effects of the Invention]

[0010] According to the present invention, a pharmaceutical composition suitable for use on nails and the area around nails can be provided. [Mode for Carrying Out the Invention]

[0011] The present invention relates to a pharmaceutical composition comprising (A) an antifungal agent, (B) a cellulosic polymer, and a predetermined component (C) . The pharmaceutical composition for perionychium use of the present invention has excellent spreadability on nails and the area around nails . Furthermore, it can treat, improve, and prevent skin whitening due to drying and skin peeling on nails and the area around nails .

[0012] [(A) Antifungal agent (antifungal component)] An antifungal agent is a substance having a function of inhibiting or suppressing the growth of fungi, or killing fungi , and is used for treating, preventing, and improving various diseases and symptoms caused by fungal infection .

[0013] Examples of the type of the antifungal agent in the present invention include allylamine antifungal agents, benzylamine antifungal agents, amine antifungal agents such as thiocarbamate antifungal agents, and imidazole antifungal agents Antifungal agents or azole antifungal agents such as triazole antifungal agents, or morpholin-based antifungal agents Examples include antifungal agents. The type of antifungal agent used in the present invention is one that more clearly demonstrates the effects of the present invention. From the viewpoint of achieving the desired effect, amine-based antifungal agents and azole-based antifungal agents are preferred, and amine-based antifungal agents The agent is more preferable.

[0014] The amine-based antifungal agent of the present invention is a compound that is well known as an antifungal agent having an amine in common. Therefore, any pharmaceutically or physiologically acceptable amine antifungal agent may be used. It can be used. For example, allyl amines such as terbinafine or naphthifine can be used as antifungal agents. Amine antifungal agents, benzylamine antifungal agents such as butenafine, tolnaftate, lilac Examples include thiocarbamine antibiotics such as naftate. Among these, those that more clearly demonstrate the effects of the present invention From the perspective of achieving the desired effect, allylamine antifungal agents are preferred, and among them, the most preferred Other examples include terbinafine, or terbinafine salts such as terbinafine hydrochloride. It can be done.

[0015] The azole antifungal agent of the present invention is an azole skeleton (a complex skeleton containing one or more nitrogen atoms) Compounds that are well known as antifungal agents having a common 5-membered ring compound, and which are pharmaceutically or physiologically Any moderately acceptable azole antifungal agent can be used. For example, an imidazole ring (a heterogeneous 5-membered ring containing two nitrogen atoms) Zole-type antifungal agents, triazole rings (heterogeneous 5-membered rings containing 3 nitrogen atoms) Examples include zole antifungal agents. More specifically, miconazole and lanoconazole. Luliconazole, Isoconazole, Ketoconazole, Clotrimazole, Neticonazole Zole, sulconazole, bifonazole, oxiconazole, econazole and these Imidazole antifungal agents such as salts; fluconazole, itraconazole, fosfluconazole Voriconazole, efficonazole, butoconazole, fenticonazole, ceruta Examples of triazole antifungal agents such as conazole and its salts are suitable for the present invention. It can be used appropriately. The azole antifungal agent of the present invention provides the effect of the present invention more effectively. From the standpoint of demonstrating remarkable efficacy, imidazole antifungal agents are preferred, and among them, miconazole, Luliconazole, isoconazole, and lanoconazole are preferred.

[0016] The morpholin-based antifungal agent of the present invention is an antifungal agent that commonly contains morpholin. A well-known compound, any pharmaceutically or physiologically acceptable morpholine antifungal agent. Amorolphy can be used. A typical example of a morpholin antifungal agent is amorolphy. Examples include 'n' or its salts. All of these (A) components may be used individually. You may use two or more types in any combination.

[0017] In the present invention, the antifungal agent is not limited to terbinafine, but includes but also but also but also but also but including terbinafine, butenafine, and terbinafine. At least one selected from the group consisting of , miconazole, isoconazole, and salts thereof. One or a combination of two or more types is also exemplified as a preferred embodiment.

[0018] (A) The total content of the antifungal agent shall be determined from the viewpoint of achieving the effects of the present invention more significantly in the pharmaceutical composition Preferably, it is 0.01% by mass or more, and more preferably 0.1% by mass or less, relative to the total amount. More preferably, it is 0.3% by mass or more, and particularly preferably 0.5% by mass or more. (A The total amount of the antifungal agent is determined from the viewpoint of achieving the effects of the present invention to be in the total amount of the pharmaceutical composition. In contrast, preferably it is 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. ( A) The total content of the antifungal agent is preferably 0. It is 0.1% to 10% by mass, more preferably 0.1% to 8% by mass, even more preferably The amount is 0.3% to 5% by mass, and particularly preferably 0.5% to 2% by mass. Among these, 1% by mass is most preferred.

[0019] [(B) Cellulose polymers] The following substances can be used as the (B) cellulose polymer of the present invention, If so, there are no particular restrictions. That is, as a cellulose polymer compound, cellulose Cellulose obtained by replacing the hydroxyl groups of cellulose or other functional groups A polymer compound is used that is applicable to the skin, nails, and the area around the nails. This is possible. Functional groups that can substitute for the hydroxyl group of cellulose include methoxy groups and ethyl groups. Xy group, hydroxymethoxy group, hydroxyethoxy group, hydroxypropoxy group, cal Examples include boxymethoxy groups and carboxyethoxy groups. Cellulose polymer compounds are given as examples. Then, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxy Methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose S, hydrophobized hydroxypropyl methylcellulose, carboxymethylcellulose, carbo Examples include oxyethylcellulose or salts thereof. Here, the salt is Pharmacologically acceptable salts are preferred, and alkali metal salts are even more preferred, sodium Salts such as potassium salts are particularly preferred.

[0020] All of these (B) components may be used individually or in any combination of two or more. It may be used in combination.

[0021] These (B) components are not limited to those that more significantly enhance the effects of the present invention. Of these, methylcellulose, hydroxyethylcellulose, and hydroxypropylmethylcellulose are Cellulose, hydrophobized hydroxypropyl methylcellulose, hydroxypropyl cellulose One or more selected from the group consisting of cellulose, carboxymethylcellulose, and salts thereof Preferably, hydroxypropyl methylcellulose, hydrophobized hydroxypropyl methylcellulose Rose, hydroxyethylcellulose, and sodium carboxymethylcellulose are preferred. Hydroxypropyl methylcellulose, hydrophobized hydroxypropyl methylcellulose Hydroxyethylcellulose is even more preferred.

[0022] (B) The total content of component (B) is the total amount of the pharmaceutical composition, from the viewpoint of achieving the effects of the present invention more significantly. For this, the amount is usually 0.01% by mass, preferably 0.1% by mass or more, and more preferably k is 0.5% by mass or more, more preferably 0.8% by mass or more, and particularly preferably 1 (B) The total content of component (B) is determined from the perspective of the feel and ease of use of the formulation. The amount of the pharmaceutical composition is usually 10% by mass or less, preferably 5% by mass or less. More preferably 4.5% by mass or less, even more preferably 3.5% by mass or less, particularly preferred The amount is 2.5% by mass or less. The total amount of component (B) relative to the total amount of the pharmaceutical composition is From the viewpoint of achieving a more pronounced brightening effect, the amount is usually 0.01 to 10% by mass, preferably 0 It is 0.1 to 5% by mass, more preferably 0.5 to 4.5% by mass, and even more preferably The amount is 0.8 to 3.5% by mass, and particularly preferably 1.5 to 2.5% by mass.

[0023] In the pharmaceutical composition of the present invention, from the viewpoint of achieving the effects according to the present invention more significantly, (A) The ratio of component (B) to component (A) is, for example, the ratio of component (B) to the total content of component (A) per 1 part by mass. The total content of component B) is usually 0.1 to 20 parts by mass, and 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 to use 2.7 parts by mass. Also, 1.4 to 2.5 parts by mass, 1.5 to 2 parts by mass The parts can also be presented as a favorable ratio.

[0024] Furthermore, for example, if component (B) is hydroxypropyl methylcellulose, From the perspective of achieving a more pronounced effect, the inclusion of hydroxypropyl methylcellulose The amount is preferably 0.1 to 1.5% by mass, and more preferably, based on the total amount of the pharmaceutical composition. The amount is 0.2 to 1.3% by mass, more preferably 0.3 to 1.2% by mass, and particularly preferably It is 0.4 to 1 mass%. Also, 0.5 to 5 mass%, 0.75 mass% to 2.5 mass%, A preferred blending amount of 1-2% by mass can also be suggested. For example, if component (B) is hydrophobized hydroxypropyl methylcellulose, the present invention From the perspective of achieving a more pronounced effect, hydrophobized hydroxypropyl methylcellulose The content is preferably 0.1 to 0.9% by mass, and more preferably, based on the total amount of the pharmaceutical composition. More preferably 0.2 to 0.8 mass%, more preferably 0.3 to 0.7 mass%, and especially preferred More specifically, it is 0.4-0.6 mass%. Also, 0.5-5 mass%, 1-2.5 mass%, 1. A preferred blending amount of 2-2% by mass can also be suggested.

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

[0026] These (C) components are used in topical preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. The term is not particularly limited to any grade or level used as a unit of measurement.

[0027] The total amount of (C) is determined from the viewpoint of achieving the effects of the present invention more significantly, relative to the total amount of the pharmaceutical composition. And it is usually 0.01% by mass or more, preferably 0.1% by mass or more, more preferably The amount is 0.8% or more by mass, more preferably 1% or more by mass, and particularly preferably 1.2% by mass. That is all. The total content of (C) is determined from the viewpoint of achieving the effects of the present invention more significantly, in the pharmaceutical composition It is usually 5% by mass or less of the total amount of the substance, preferably 4.1% by mass or less, and more Preferably 2.8% by mass or less, more preferably 2.5% by mass or less, and especially preferably 2% by mass. The amount is less than %. The total content of (C) relative to the total amount of the pharmaceutical composition is usually 0.01 to 5 by mass. %, preferably 0.1 to 4.1% by mass, more preferably 0.8 to 2.8% by mass, More preferably, it is 1 to 2.5% by mass, and particularly preferably 1.2 to 2% by mass.

[0028] In the pharmaceutical composition of the present invention, from the viewpoint of achieving the effects according to the present invention more significantly, (A) The ratio of component (C) to the component is, for example, ( 1 part by mass of the total content of component (A) The total content of component C is usually 0.01 to 5 parts by mass, preferably 0.1 to 4.1 parts by mass. More preferably 0.8 to 2.8 parts by mass, even more preferably 1 to 2.5 parts by mass, particularly preferred The amount is 1.2 to 2 parts by mass.

[0029] (C) Anti-inflammatory agents include prednisolone acetate valerate, dexamethasone acetate, and vinegar. Steroidal anti-inflammatory drugs such as hydrocortisone acid or pharmacologically acceptable salts thereof. Medicine, allantoin, glycyrrhetinic acid, glycyrrhizic acid, stearyl glycyrrhetinate Aldioxa, Ufenamate, Bufexamac, Ibuprofen piconol, India Metacin, diclofenac, piroxicam, epsilon-aminocaproic acid, berberine Lysozyme, sodium azulene sulfonate, dimethylisopropylazulene, brome Rhein, serrapeptase, semi-alkaline proteinase, or their pharmacologically acceptable Examples of nonsteroidal anti-inflammatory drugs include salts. Among these drugs, the efficacy of the present invention From the viewpoint of achieving more pronounced results, non-steroidal anti-inflammatory drugs are preferred, and glycyrrhizic acid , glycyrrhetinic acid, salts of glycyrrhetinic acid, salts of glycyrrhizic acid (for example, glycyrrhizic acid Dipotassium lysinate, monoammonium glycyrrhizinate, and allantoin are preferred. One or more of these drugs can be used in appropriate combinations.

[0030] (C) Examples of local anesthetics containing component (C) include lidocaine, dibucaine, mepivacaine, and bupivacaine. Aphrodactyl rhinoplaque, lopivacaine, levobupivacaine, and pharmaceutically acceptable salts thereof Amide-type local anesthetics having amine and amide structures, procaine, chloroprocaine, tetra Ester-type local anesthetics having amine and ester structures, such as lacine and its salts. Examples include ethyl aminobenzoate, oxypolyethoxide decane, and / or this Among these drugs, but not limited to, amide-type local anesthetics having amine and amide structures. A suitable agent is preferred, and from the viewpoint of more significantly exhibiting the effects of the present invention, lidocaine is particularly preferred. Dibucaine hydrochloride is an example. One or more of these drugs may be used in appropriate combinations. It can also be used.

[0031] (C) Examples of disinfectants include decalinium chloride, decalinium acetate, and benzalcohol chloride. nium, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, salt Alkyldiaminoethylglycine acid, cetylpyridinium chloride, sodium benzoate, Lolobutanol, isopropylmethylphenol, thymol, sorbic acid, sorbate Lium, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate L, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, f Ethyl alcohol, benzyl alcohol, acrinol, hinokitiol, resorcinol Examples include berberine benzoate or biguanide compounds. Choose one of these drugs. Alternatively, two or more types can be used in appropriate combinations. Among these drugs, the present invention From the viewpoint of achieving a more pronounced effect, isopropylmethylphenol is preferred.

[0032] (C) The antihistamine component is not limited to chlorpheniramine, iso Chipendyl, Ketotifen, Bepotastine, Dimenhydrinate, Cyproheptadine, Di Phenylpyraline, promethazine, iproheptin, emedastine, clemastine, aze Rustin, levocabastine, hydroxyzine, mequitazine, loratadine, fexofena Zin, cetirizine, oxatomide, terfenadine, epinastine, astemizole, e Bastin, diphenylimidazole, diphenhydramine, or salts of these compounds Examples are given.

[0033] From the viewpoint of achieving the effects of the present invention more significantly, preferred examples of antihistamines are: Fenhydramine, diphenylpyraline, chlorpheniramine, diphenylimidazole , or their salts, more preferably examples being chlorpheniramine, diphenhydramine These are chlorpheniramine or salts thereof, and more preferably examples include chlorpheniramine, chlorpheniramine maleate. These are lupheniramine, diphenhydramine, diphenhydramine hydrochloride. One or more of the agents can be used in appropriate combinations.

[0034] All of these (C) components may be used individually or in any combination of two or more. It can also be used in combination.

[0035] From the viewpoint of achieving the effects of the present invention more significantly, preferred component (C) is glycyrrhetinic acid, Amide-type local anesthetics having amine and amide structures, isopropylmethylphenol, dif One or more selected from the group consisting of phenhydramine and diphenhydramine salts. The above is true. A particularly preferred component (C) from the viewpoint of more significantly exhibiting the effects of the present invention is glycyrrhizin. Retinic acid, lidocaine, isopropylmethylphenol, diphenhydramine, and diph One or more substances selected from the group consisting of salts of diphenhydramine. While not limited to a specific salt of mine, diphenhydramine hydrochloride is preferred. Furthermore, The preferred (C) component is glycyrrhetinic acid and / or isopropylmethylphenol. That is the case.

[0036] Furthermore, for example, component (C) is glycyrrhetinic acid and its salts, glycyrrhizic acid and so If it is at least one selected from the group consisting of salts of glycyrrhetinic acid and so The content of the salt, glycyrrhizic acid and its salts is important from the viewpoint of achieving the effects of the present invention. Furthermore, the amount is preferably 0.1 to 1% by mass, and more preferably 0. The amount is 2 to 0.8% by mass, more preferably 0.25 to 0.5% by mass.

[0037] For example, if component (C) is an amide-type local anesthetic having an amine and amide structure, The preferred content of each amide-type local anesthetic relative to the total amount of the pharmaceutical composition is The amount is 0.25 to 2.5% by mass, and more preferably 0.5 to 2% by mass. In particular, For example, if component (C) is lidocaine or / or dibucaine or a salt thereof, From the viewpoint of achieving the effects of the present invention more significantly, lidocaine, dibucaine, or salts thereof may be used. The content of each is preferably 0.25 to 2.5% by mass, relative to the total amount of the pharmaceutical composition. Yes, and more preferably 0.5 to 2% by mass.

[0038] For example, if component (C) is isopropylmethylphenol, the effects of the present invention will be demonstrated. From the perspective of achieving the desired effect, the isopropylmethylphenol content should be relative to the total amount of the pharmaceutical composition. Preferably, it is 0.3 to 3% by mass, and more preferably 0.5 to 1% by mass.

[0039] For example, if component (C) is diphenhydramine and its salts, the effect of the present invention From the standpoint of achieving remarkable results, the content of diphenhydramine and its salts is important for the pharmaceutical composition. Preferably 0.1 to 2% by mass, and more preferably 0.5 to 1% by mass, relative to the total amount of the substance. That is the case.

[0040] In the present invention, (A) an antifungal agent, (B) a cellulose polymer, and (C) a component In addition, it may be used as a pharmaceutical, quasi-drug, cosmetic, etc., to the extent that its function is not impaired. Any known component can be included in the pharmaceutical composition. Preferably, it can contain ethanol.

[0041] [ethanol] The ethanol used in the pharmaceutical composition of the present invention is used in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular restrictions as long as it is of the grade or class specified. Used as a raw material for pharmaceutical compositions. For example, ethanol such as 95% ethanol or 99% ethanol (anhydrous ethanol) is suitable. It can be used as appropriate.

[0042] From the perspective of user experience, the ethanol content should be 20% by mass or more of the total amount of the pharmaceutical composition. Preferably, it is 30% by mass or more, and even more preferably 40% The ethanol content is 1% by mass or more. The ethanol content is determined from the viewpoint of ease of handling of the formulation, and is the total ethanol content of the pharmaceutical composition. Preferably, it is 90% by mass or less relative to the amount, more preferably 80% by mass or less, and further Preferably, it is 70% by mass or less. The ethanol content relative to the total amount of the pharmaceutical composition is Preferably 20-90% by mass, more preferably 30-80% by mass, and even more preferably It is 40-70% by mass.

[0043] In the pharmaceutical composition of the present invention, the ratio of ethanol to component (A) is determined from the viewpoint of usability. For example, if the total content of component (A) is 15 to 1 parts by mass, the ethanol content is 15 to 1 It can be 80 parts by mass, preferably 25 to 140 parts by mass, more preferably 35 to The amount is 100 parts by mass, more preferably 45 to 90 parts by mass, and particularly preferably 60 parts by mass.

[0044] [salt] In this specification, "salt" refers to, for example, organic salts and inorganic salts. Examples of organic salts include: Ammonium, or diethanolamine, triethanolamine, ethylenediamine, etc. Examples are given, and inorganic salts include sodium, potassium, calcium, magnesium, etc. Salts are an example. Also, salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, propion Acids, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoin Acids, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotine Salts with organic acids such as tinic acid and salicylic acid; or acidic acids such as aspartic acid and glutamic acid. Salts with amino acids are also examples. Note that the term "salt" includes solvates or hydrates of salts. It may be present. In particular, the form of the salt of component (A) is not limited, but is readily available. From this viewpoint, it is preferably a salt of an inorganic acid, and more preferably a hydrochloride or nitrate. be.

[0045] [container] The containers used to fill the pharmaceutical composition of the present invention are not particularly limited. These include pharmaceutical topical preparations and quasi-drugs. Any material suitable for use as a cosmetic container is acceptable. Examples of such container materials include: , part or all, preferably all, of the contact surface with the pharmaceutical composition is made of polyolefin resin, acrylic resin. Rilic acid resin, polyester, polycarbonate, fluororesin, polyvinyl chloride, polyaluminium D, ABS resin, AS resin, polyacetal, modified polyphenylene ether, polyaryl Polysulfone, polyimide, cellulose acetate, aluminum, and glass Examples include containers made of at least one material selected from the following groups.

[0046] From the viewpoint of ease of handling of the formulation, the material of the container for filling the pharmaceutical composition of the present invention 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) (including isotactic polypropylene, syndiode) (including 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 seems so.

[0047] The shape of the container is not limited, but it should be a tube, a dropper, or a squeezing container. preferable.

[0048] [Dosage form] The pharmaceutical composition of the present invention can be provided in any form that can be widely used as a pharmaceutical product, quasi-drug, etc. The present invention is provided. Preferably, it is provided as a formulation that can be used as a topical skin agent. The pharmaceutical composition is not particularly limited as long as it is in a known form, but the present invention will exhibit the effects more significantly. From this perspective, for example, creams, liquids, suspensions, emulsions, gels, lotions, air Preferably provided in the form of an aqueous pharmaceutical composition such as a zole or mist, or a gel. It is more preferable that the formulation be a cream, liquid, suspension, emulsion, lotion, or mist. In particular, a gel formulation is preferred. Here, the aqueous pharmaceutical composition is defined as the proportion of the total composition The proportion of water or water-soluble solvent is 10% by mass or more, preferably 20% by mass or more, Preferably, this refers to a dosage form containing 30% by mass or more.

[0049] The preparation shall be prepared by mixing each component in accordance with or in accordance with the General Provisions of the 17th Revised Japanese Pharmacopoeia. It can be manufactured by doing so.

[0050] [Manufacturing method] The pharmaceutical composition of the present invention can be manufactured by known methods. Sterilization may be performed as needed. Processes and filtration processes can be included.

[0051] [Base, carrier, or other component] The pharmaceutical composition of the present invention may be used in pharmaceuticals, quasi-drugs, and cosmetics, to the extent that it does not impair the effects of the present invention. It can be formulated by mixing it with a known base or carrier that can be used as a product, etc. In addition, the pharmaceutical composition of the present invention may contain, for example, surfactants, oils, alcohols, and higher lipids. Fatty acids, preservatives, antioxidants, antioxidants, cooling agents, various polymers, preservatives, chelating agents, p H adjusters, stabilizers, solubilizers, suspending agents, isotonic agents, buffering agents, fragrances, colorants, pigments, etc. These additives can be incorporated. These additives can be used individually or in combination of two or more. They can be used together.

[0052] Examples of bases or carriers include hydrocarbons, silicone oils, esters, and lower alcohols. Examples include polyhydric alcohols, purified water, etc. Examples of hydrocarbons include liquid paraffin. Squalane, gelling hydrocarbons (such as Plastibase), ozokerite, α-olefin Examples include oligomers and light liquid paraffins, and as silicone oils, for example, methyl Methylpolysiloxane, cross-linked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic methyl Lycorn, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone Polyether-modified silicone, polyglycerin-modified silicone, cross-linked polyether Silicone-modified silicone, cross-linked alkyl polyether-modified silicone, silicone-alkyl Chain-comodified polyether-modified silicone, silicone-alkyl chain-comodified polyglycerin Silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, Examples include acrylic silicone, phenyl-modified silicone, silicone resin, and esters. Examples of similar substances include isopropyl myristate, octyldodecyl myristate, and palladium. Isopropyl mitate, cetyl palmitate, isononyl isononanoate, tetra-2-eth Examples include pentaerythritol hexanoate, and lower alcohols include, for example, Examples include sopropanol, and as for polyhydric alcohols, for example, diethylene glycol. Glycol ethers such as monomethyl ether and diethylene glycol monoethyl ether Polyethylene glycol, propylene glycol, 1,3-butylene glycol, Examples include glycerin and isoprene glycol.

[0053] The base or carrier can be used individually or in combination of two or more types.

[0054] Examples of surfactants include nonionic surfactants. Examples of sterilizing agents include sorbitan fatty acid esters and propylene glycol fatty acid esters. Tel compounds, castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxy Alkylene alkyl ethers, amines, silicone-based surfactants, polyoxyethylene Examples include lauryl alcohol ether. Sorbitan fatty acid esters include: For example, sorbitan monoisostearate, sorbitan monolaurate, sorbitan mono Palmitate, sorbitan monostearate, diglyceryl penta-2-ethylhexylate Examples include diglycerol sorbitan tetra-2-ethylhexyl sorbitan. Examples of propylene glycol fatty acid esters include propylene monostearate. Examples include propylene glycol fatty acid esters such as propylene glycol, and castor oil. Examples of derivatives include polyoxyethylene hydrogenated castor oil and polyoxyethylene castor oil. For example, polyoxyethylene sorbitan fatty acid esters include monolauric acid. Polyoxyethylene (20) sorbitan (polysorbate 20), monostearate Polyoxyethylene (20) sorbitan (polysorbate 60), polio monooleate Xyethylene(20) sorbitan (polysorbate 80), polyoxyethylene isostearate Examples include ethylene(20)sorbitan, and as a polyoxyalkylene alkyl ether. For example, polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl Examples include ethers, alkyl glucosides, polyoxyethylene cetyl ethers, etc. Examples of such compounds include stearylamine and oleylamine, and are found in the silicone ecosystem. Examples of surfactants include polyoxyethylene methylpolysiloxane copolymer and lauryl methylpolysiloxane copolymer. Lyl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxy Examples include ethyl dimethicone.

[0055] Other types of surfactants include anionic surfactants and amphoteric surfactants. Examples of anionic surfactants include laurate, palmitate, and cocoyl. Glutamate, coconut oil methylalanine salt, acyl methyl taurine salt, polyoxyethylene Examples include lauryl sulfate, and amphoteric surfactants include, for example, lauryl diaminoethanol. Examples include glycine salt and coconut oil fatty acid betaine salt.

[0056] The oils include natural animal and vegetable oils and fats, hydrocarbon oils, ester oils, silicone oils, and higher-grade aluminum. Examples include coal, 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. Oils, 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, peach oil, palm Oils, palm kernel oil, castor oil, sunflower oil, lard, grape oil, jojoba oil, macadamia nuts Oil, mink oil, cottonseed oil, Japanese wax, beeswax, bleached beeswax, coconut oil, hydrogenated coconut oil, cleaning Examples include peanut oil, lanolin, egg yolk oil, and rosehip oil.

[0058] As hydrocarbon oils, paraffinic hydrocarbons and olefinic hydrocarbons are used, for example ba, squalane, squalene, ceresin, paraffin, pristane, microcrystalline Examples include wax, liquid paraffin, and petrolatum.

[0059] Ester oils include synthetic esters and esters of higher alcohols and higher fatty acids. Used, for example, diisobutyl adipate, 2-hexyldecyl adipate, adipin Di-2-heptyl undecyl acid, isostearyl isostearate, triisostearin Trimethylolpropane acid, cetyl 2-ethylhexanoate, di-2-ethylhexanoate Opentyl glycol, trimethylolpropane tri-2-ethylhexanoate, tetra- Pentaerythritol 2-ethylhexanoate, cetyl octanoate, oleyl oleate, Octyldodecyl oleate, decyl oleate, neopentyl glycol dicaprate 2-ethylhexyl succinate, isocetyl stearate, butyl stearate, sebaci Diisopropyl myristate, cetyl lactate, tetradecyl lactate, isopropyl myristate, myristate Octyldodecyl stine, cetyl myristate, myristyl myristate, palmitin Octyl acetate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, palm 2-Heptylundecyl Mitinate, Cholesteryl 12-Hydroxystearate, Ole Phytosteryl phosphate, diisostearyl malate, paramethoxycinnamate, tetramethyl phosphate Examples include pentaerythritol larosinate.

[0060] Examples of silicone oils include dimethylpolysiloxane and highly polymerized methylpolysiloxane. Methylphenylpolysiloxane, methylhydrogenpolysiloxane, octameth Lucyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclo Xasiloxane, stearoxysilicone and other higher alkoxy-modified silicones, alkyl Examples include modified silicones and higher fatty acid ester-modified silicones.

[0061] Examples of alcohols include lower alcohols and higher alcohols. Examples of alcohols include isopropanol, and higher alcohols include For example, octyldodecanol, isostearyl alcohol, oleyl alcohol, Examples include tearyl alcohol, cetanol, and behenyl alcohol.

[0062] Higher fatty acids are saturated or unsaturated straight-chain or branched-chain fats with 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, li Examples include oleic acid and linolenic acid.

[0063] Suitable examples of preservatives include, for example, benzoic acid, acetic acid, phenol, iodine tincture, and Laoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol Examples include chol and dehydroacetic acid.

[0064] Suitable examples of antioxidants include, for example, sulfites and ascorbic acid.

[0065] Antioxidants include dibutylhydroxytoluene (BHT) and butylhydroxyani Sole (BHA), sodium sulfite, erythorbic acid, L-cysteine ​​hydrochloride, vitamin Examples include vitamin C compounds and vitamin E compounds. Examples of vitamin C compounds include ascorbic acid. N-A, ascorbic acid stearate, ascorbic acid palmitate, L-ascorbyl dipalmitate, ascorbic acid, sodium ascorbate, dehydr Ascorbic acid, sodium ascorbic acid phosphate, sodium ascorbic acid phosphate Examples include thorium salts and magnesium ascorbic acid phosphate. Vitamin E compounds. Examples include dl-α-tocopherol, dl-α-tocopherol acetate, succin Examples include dl-α-tocopherol acid and dl-α-tocopherol calcium succinate. It can be done.

[0066] While not limited to cooling agents, menthol (l-menthol, dl-menthol) is also a possibility. Terpenes such as ru (e.g., d-camphor, dl-camphor, etc.), camphor (d-camphor, dl-camphor, etc.), and borneol. Essential oils containing terpenoids (e.g., peppermint oil), or pharmacologically acceptable salts thereof. Examples include the following. Use one or more of these drugs in appropriate combinations. It's also possible.

[0067] Examples of polymers include vinyl polymers, acrylic polymers, mucopolysaccharides, and starch polymers. Molecules, dextran, dextrin fatty acid ester, pectin, casein, dimethyl disulfide Tearylammonium hectorite, (Acryloyldimethyltaurate ammonium / B Nylpyrrolidone copolymer, polyethylene glycol distearate, triisostearate Ethylene glycol phosphate, polyoxyethylene (20) methyl triisostearate Lucoside, bentonite, hectorite, alginate and / or its salts, propyl alginate Examples include ethylene glycol esters, polyethylene glycol, and thickening polysaccharides.

[0068] Examples of vinyl polymers include polyvinylpyrrolidone, polyvinyl alcohol, or polyvinyl Examples include methyl ethers, and one or more of these can be used. It is also possible.

[0069] Examples of acrylic polymers include acrylic acid / alkyl methacrylate copolymers and acrylic acid Hydroxyethyl acryloyldimethyl taurate copolymer (especially hydro acrylate) (Sodium oxyethyl acryloyldimethyl taurate copolymer), sodium acrylate Mu-acryloyldimethyltaurine copolymer, sodium acrylate, methacrylate Sodium lylate, sodium methacrylate, alkyl methacrylate copolymer, steare Su-10 allyl ether / acrylate copolymer, polyacrylic acid or its salt (carboco (Vinyl polymer), ammonium acryloyldimethyltaurate copolymer, acrylic acid • Polyoxyethylene glycol ether copolymer of methacrylate, polyacrylamide, Examples include acrylamide-ammonium acrylate copolymers.

[0070] As a thickening polysaccharide, it is used as an ingredient in topical preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Among the substances used, specifically, carrageenan, xanthan gum, gum arabic, and pe Examples include chondroitin sulfate (sodium). Salts, etc.), hyaluronic acid or its salts (sodium salts, etc.), and hyaluronic acid derivatives or Examples include the salt, heparin, heparin-like substances, and glycosaminoglycans. can.

[0071] Examples of starch-based polymers include hydroxypropyl starch phosphate (for example, Natio nal Starch, LLC (Structure XL), Modified Corn Starch Examples include cornstarch and the like.

[0072] Preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, and sodium dehydroacetic acid. Um, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, parahydroxybenzoate Butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, parahydroxybenzoate Examples include benzyl benzoate, methyl parahydroxybenzoate, and phenoxyethanol.

[0073] Examples of chelating agents include EDTA-2 sodium salt and EDTA-calcium-2 sodium Examples include unsalted salt.

[0074] As pH adjusters, inorganic acids (hydrochloric acid, sulfuric acid, etc.) and organic acids (lactic acid, sodium lactate, etc.) are used. (e.g., hydroxyl compounds), inorganic bases (hydroxyl compounds) Potassium, sodium hydroxide, etc.), organic bases (triethanolamine, diisopropano Examples include sylamines and triisopropanolamines.

[0075] Stabilizers include sodium polyacrylate and dibutylhydroxytoluene (BHT). Examples include butylhydroxyanisole (BHA) and others.

[0076] Examples of solubilizers include polyethylene glycol, propylene glycol, and D-methylcellulose. Intitol, benzyl benzoate, trisaminomethane, cholesterol, triethanol Examples include amines, sodium carbonate, and sodium citrate.

[0077] Examples of suspending agents include stearyltriethanolamine and sodium lauryl sulfate. , surfactants such as laurylaminopropionic acid, lecithin, and glyceryl monostearate A drug is one example.

[0078] Examples of isotonic agents include sodium chloride, glycerin, and D-mannitol. It is possible.

[0079] Examples of buffering agents include buffer solutions such as phosphates, acetates, carbonates, and citrates. It can be done.

[0080] Examples of colorants include inorganic pigments and natural dyes.

[0081] The pharmaceutical composition of the present invention may further contain other active ingredients, to the extent that it does not impair the effects of the present invention. It may also contain the following. Specific examples of such ingredients include, for example, antipruritic ingredients, moisturizing ingredients, Blood circulation promoting ingredients, astringent ingredients, peptides or their derivatives, amino acids or their derivatives, cell activation Examples include chemical components and vitamins.

[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 Rulonic acid derivatives or salts thereof, trehalose, xylitol, oligosaccharides and other sugars; hepa Molecular-weight substances such as phosphorus-like substances, collagen, elastin, keratin, chitin, and chitosan Compounds; amino acids such as glycine, aspartic acid, and arginine; sodium lactate, pyro Natural moisturizing factors such as sodium lidonecarboxylate; ceramides, cholesterol, phospholipids Lipids like those found in chamomile extract, witch hazel extract, tea extract, and perilla extract. Examples include plant extracts.

[0084] Examples of blood circulation promoters include acetylcholine, caffeine, capsaicin, and canthari. Stinky, gamma-oryzanol, limonol tincture, gingerol, cepharanthine Swertia japonica extract, tannic acid, capsicum tincture, trazoline, tocopherol nicotinate Examples include nicotinic acid, benzyl nicotinate, and nicotinamide.

[0085] The astringent components include zinc sulfate, aluminum chlorohydrate, aluminum chloride, and Examples include zinc carbonate and tannic acid.

[0086] Examples of peptides or their derivatives include keratin-degrading peptides, hydrolyzed keratin, and collagen. Gen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin breakdown Butyrate, collagen-degraded peptide, hydrolyzed collagen, hydroxypropylammonium chloride Nium hydrolyzed collagen, elastin hydrolyzed peptide, conchiolin hydrolyzed peptide, hydrated Degraded conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk Sodium oxalate, hydrolyzed soy protein peptide, hydrolyzed soy protein, wheat protein, hydrolyzed wheat protein peptide Hydrolyzed wheat protein, casein hydrolyzed peptide, acylated peptide (palmitoyl olivine) Examples include gopeptides, palmitoyl pentapeptides, palmitoyl tetrapeptides, etc. It is possible.

[0087] Examples of amino acids or their derivatives include betaine (trimethylglycine), proline, and hydr Roxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine β-alanine, threonine, glutamic acid, glutamine, asparagine, asparagine Acids, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine Taurine, gamma-aminobutyric acid, gamma-amino-β-hydroxybutyric acid, carnitine, carnosyl Examples include corn, creatine, etc.

[0088] Cell-activating components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid. Vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids. α-hydroxy acids such as glycolic acid and lactic acid, tannins, flavonoids, saponins Examples include photosensitive element 301.

[0089] Vitamin supplements include B vitamins, C vitamins, D vitamins, E vitamins, and others. Cotinic acid derivatives, vitamin K derivatives, and other vitamins can all be used. Vitamin B1, vitamin B2, vitamin B6, and vitamin B12 are examples of vitamin B1, vitamin B2, vitamin B6, and vitamin B12. Examples include nicotinic acid derivatives, pantothenic acid derivatives, folic acid, biotin, etc. Vitamin E derivatives include Examples include dl-α-tocopherol, dl-α-tocopherol acetate, and dl succinate. -α-tocopherol, dl-α-tocopherol calcium succinate, etc.; Vitamin B2 Examples of such compounds include riboflavin, flavin mononucleotide, and flavin adenine nucleotide. Cleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-Sodium phosphate, riboflavin tetranicotinate, etc. Examples of nicotinic acids include dl-α-tocopherol nicotinate, benzyl nicotinate, Methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methylphenic acid) nicotinate (L) Ethyl, etc.; Vitamin C derivatives include, for example, ascorbic acid ethyl; Thearate ester, ascorbic acid palmitate, L-ascorbic acid dipalmitate Rubyl, ascorbic acid, sodium ascorbate, dehydroascorbic acid, ascor Sodium rubic acid phosphate, sodium ascorbic acid phosphate salt, ascorbic acid Examples of vitamin D derivatives include magnesium phosphate esters, etc.; for example, methyl hesperidin. ergocalciferol, cholecalciferol, etc.; vitamin K derivatives include, for example, Phylloquinone, phylloquinone, etc.; as for vitamin B1, for example, dibenzoyl rhizome Mine, dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine Oscyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thia Thiamine triphosphate, thiamine monophosphate phosphate, thiamine Monophosphate ester, thiamine diphosphate ester, thiamine diphosphate hydrochloride, thi Amine triphosphate, thiamine triphosphate monophosphate, etc.; Vitamin B6 Examples of such compounds include pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, and 5' - Pyridoxal phosphate, pyridoxamine hydrochloride, etc.; as for vitamin B12 compounds, for example, Cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, etc.; nicotine Examples of acids include nicotinic acid, nicotinamide, etc.; examples of pantothenic acids include For example, pantothenic acid, calcium pantothenate, pantothenyl alcohol (D-panthenol (Coenzyme A), D-panthesine, D-pantethine, coenzyme A, pantothenyl ethyl ether, etc. Examples include biotin, folic acid, and vitamin-like factors such as their pharmacologically acceptable salts. It can be done.

[0090] [pH] The pH of the pharmaceutical composition of the present invention depends on (A) the type of component, the type and content of other components, and the manufacturing process. The dosage may be set appropriately depending on the dosage form, method of use, etc., and within a range that is physiologically or pharmaceutically acceptable. While not limited to this, from a safety standpoint, for example, the pH can be set to 2-9, and is preferable. This can be approximately 3 to 8, more preferably approximately 5 to 7.

[0091] [Viscosity] The viscosity of the pharmaceutical composition of the present invention is determined from the viewpoint of ease of handling of the formulation, in terms of the total amount of the pharmaceutical composition. The pressure is preferably 1 to 10 Pa·s, more preferably 2 to 8 Pa·s, and further Preferably, it is 4 to 6 Pa·s. Note that viscosity as used herein refers to viscosity manufactured by Toki Sangyo Co., Ltd. The measurement was taken using an RB80 viscometer and an M3 rotor at a rotation speed of 12 rpm and a measurement time of 1 minute. These are the results obtained at that time.

[0092] [Application] The pharmaceutical compositions of the present invention are, but are not limited to, preferably for athlete's foot or ringworm, or candidiasis. It is used to treat conditions such as [mention specific conditions]. The pharmaceutical composition of the present invention is used for the nail and the area around the nail, particularly the nail groove and / Alternatively, 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 It can be used on the nail and surrounding areas, including the nail bed, subungual skin, and is effective in treating athlete's foot or ringworm. Used in medical treatment. From the viewpoint of more significantly demonstrating the effects of the present invention, grooves and / Alternatively, it can be applied to athlete's foot in areas near the yellow line where the active ingredient is difficult to reach.

[0093] Athlete's foot is a skin condition caused by the fungus Trichophyton. The symptoms and characteristics of the nails and surrounding areas include: Symptoms include itching, small bumps, peeling skin, dryness, hardening, flaking, and roughness of the nails and surrounding skin. There is a fungus called ringworm. Ringworm fungi are especially prevalent in the thick layers of keratin that are present in the nails and the surrounding skin. It is prone to developing, and symptoms may appear particularly on and around the nails.

[0094] Ringworm is a skin condition caused by the fungus Trichophyton. Small red rings appear on the skin and gradually disappear. The symptoms spread from place to place. It is accompanied by itching and is similar to athlete's foot, but ringworm occurs in areas with thin skin. Easy to wear.

[0095] Candidiasis is caused by the Candida fungus and is characterized by rough, dry skin on the hands and peeling skin between the fingers. Symptoms include discoloration of the base of the nails to white.

[0096] The pharmaceutical compositions of the present invention are not limited to, but are used for symptoms caused by dermatophytes, tinea versicolor, candidiasis, and finger infections. It can be used to treat intererosions, intertrigo, and other conditions.

[0097] The pharmaceutical compositions of the present invention are not limited to those that more significantly demonstrate the effects of the present invention. Preferably, it is provided as a gel or liquid preparation for treating athlete's foot for the nails and surrounding areas. .

[0098] Furthermore, the method of using the pharmaceutical composition of the present invention depends on the condition of the nails and surrounding skin, age, gender, etc. It varies depending on the method, but for example, the following method can be used. That is, several times a day (for example, about 1- Five times, preferably 1 to 3 times, more preferably 1 time, an appropriate amount (for example, about 0.5 to 2 g) It should be applied to the nail and the area around the nail (for example, the nail groove and / or the groove near the yellow line). The daily dose of the antibacterial agent (e.g., terbinafine or its salts) is, for example, about 5-20 mg. If the composition is applied to the nail and the area around the nail (for example, the nail groove and / or the groove near the yellow line), Good. The application method should be carried out according to the dosage form, preferably by application. The application period is, for example, approximately It is preferable to have a period of 30 days or more.

[0099] [Promoting the widespread use of pharmaceutical compositions] In this invention, (A) an antifungal agent, (B) a cellulose polymer, and (C) a component are coexisted. By doing so, the pharmaceutical composition containing these ingredients is particularly encouraged to spread to the nails and surrounding areas. It can be advanced. Here, in particular, the promotion of spreading is also referred to as "extensibility" in this specification. In this invention, the "spreadability" of the pharmaceutical composition means that the pharmaceutical composition is spreadable on the nail and the area around the nail, 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 treatment spreading to the entire nail and surrounding area, including the cuticle, lateral nail fold, nail bed, and subnail skin. To promote dissemination, the concentration, pH, and viscosity of each component in the pharmaceutical composition of the present invention described above are important. The same conditions as those for the formulation will be adopted.

[0100] [Glossiness or moisturizing effect of pharmaceutical compositions] In this invention, the pharmaceutical composition comprises (A) an antifungal agent, (B) a cellulose polymer, and (C) By combining these ingredients, it is possible to provide shine and / or moisture to the nails and surrounding skin. This is possible. In the present invention, in order to exhibit such gloss or moisturizing effect, the above-mentioned The same conditions as those for the concentration, pH, viscosity, formulation, etc., of each component in the pharmaceutical composition of the invention are adopted. do. [Examples]

[0101] Next, the present invention will be specifically described by examples and test examples, but the present invention is described by the following examples and test examples This is not limited to case studies.

[0102] [Test Example 1. Surface Tension Measurement Test] Pharmaceutical compositions with 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. An appropriate amount of each composition was taken, and hair Tube-type surface tension meter (capillary size φ6 × 160 mm, capillary inner diameter size φ 0.5 mm; measured using AS ONE (model number 2380-05-10). The predetermined ratio The surface tension reduction rate for each example compared to the comparison example was calculated according to Equation 1. The results are shown in the table. The lower the surface tension, the more the composition spreads, allowing the drug to be more effectively delivered 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 × 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 lower surface tension compared to the composition of the comparative example. Therefore, terbinafine hydrochloride is mixed with a cellulose polymer and isopropylmethylphenyl Co-administration of glycyrrhetinic acid, lidocaine, or diphenhydramine hydrochloride This improved the spreadability of the composition. Such compositions are effective against fungi present in the nails and deep within the nail bed. This allows for more appropriate delivery of the composition.

[0109] [Test Example 2. Sensory Evaluation] For five subjects, the pharmaceutical compositions of the examples and comparative examples shown in Table 6 were applied to the nails and surrounding areas. Apply a small amount and evaluate the glossiness, spreadability of the formulation, and moisturizing effect at the time of application or 30 minutes after application using VA (Visual Assessment). The evaluation was performed using the S (Visual Analogue Scale) method. That is, each For each question item, measure the length from the left end of a 100mm line segment to the shaded area indicated in the answer. The answer value was used. For glossiness, the condition of the nails and surrounding area 30 minutes after application was "not at all noticeable". The answer is "none" as 0mm (left end of the line segment), and "feel it so strongly that it appears to shine brightly" as 1 The answer was defined as 0mm (the right end of the line segment), and the degree of glossiness of each composition was evaluated. Regarding ease of application, the ease of handling the preparation on the nails and around the nails during application is "not at all smooth." The answer is to set ' to 0mm (left end of the line segment), and 'extended well to every corner' to 10mm (right end of the line segment). The answer was determined as the end, and the degree of spreadability of each composition was evaluated. In the case of moisturizing sensation, application Regarding the condition of the nails and surrounding area after 30 minutes, "no sensation at all" is set to 0mm (left end of the line segment). the answer was defined such that "felt very strongly" corresponds to an answer at 10 mm (the right end of the line segment), and for each composition the degree of moisturizing feeling was evaluated. The test was conducted without disclosing the composition of each composition to the subjects.

[0110]

Table 6

[0111] It was confirmed that coexistence of a cellulosic polymer, isopropylmethylphenol and glycyrrhetinic acid with terbinafine hydrochloride improves the gloss, spreadability, and moisturizing feeling of nails and periungual areas .

[0112] Formulation examples of the preparation of the present invention are shown below. Pharmaceutical compositions were prepared according to a conventional method with the formulations described in Table 7 . These preparations are gel preparations that are effectively used for nails and the area around nails. All preparations can also be used by being housed in a PE container.

[0113]

Table 7

Claims

[Claim 1] (A) Antifungal agents; (B) Cellulose polymers; and (C) A pharmaceutical composition for nails and / or nails containing one or more compounds selected from the group consisting of anti-inflammatory agents, local anesthetics, disinfectants, and antihistamines.

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