JP6591100B1 - Pharmaceutical composition for nail and around nail - Google Patents

Abstract

[PROBLEMS] To provide a pharmaceutical composition excellent in extensibility and the like when applied to nails and around the nails. SOLUTION: (A) Antifungal agent; (B) Vinyl polymer, acrylic polymer, mucopolysaccharide, starch polymer, dextran, dextrin fatty acid ester, casein, dimethyl distearyl ammonium hectorite, (acryloyldimethyl) (Taurine ammonium / vinyl pyrrolidone) copolymer, polyethylene glycol distearate, ethylene glycol triisostearate, polyoxyethylene (20) triisostearate, methyl glucoside, bentonite, hectorite, alginic acid and / or its salt, propylene glycol alginate thickening polysaccharide And at least one selected from the group consisting of polyhydric alcohols; and (C) glycyrrhetinic acid, lidocaine, isopropylmethylphenol, or diphenhydramine hydrochloride Preparing nail containing and / or nails around pharmaceutical composition. [Selection figure] None

Description

  The present invention relates to a nail and a pharmaceutical composition for around the nail. More particularly, the present invention relates to a nail and nail circumference pharmaceutical composition containing an antifungal agent.

  Antifungal agents for inhibiting fungal growth are widely used for treating, preventing and ameliorating various diseases and symptoms resulting from fungal infection. An external preparation for antifungal purposes is used in particular for the treatment of skin infections such as ringworm, skin candida, folding screen (Patent Document 1).

  On the other hand, fungal infections may also develop in the nails and around the nails, and appropriate treatment is desired.

JP 2006-232853 A

  However, for antifungal agents related to the nails and around the nails, a suitable pharmaceutical composition has not been fully studied.

  This invention is made | formed in view of the above, and it aims at providing the pharmaceutical composition for a nail | claw and nail | claw circumference | surroundings containing an antifungal agent.

  Since the nail and the nail circumference have peculiar irregularities in the body, it is difficult to sufficiently deliver the preparation containing the antifungal agent to the affected nail and the deep area around the nail when infected with a fungus. A more detailed study is necessary for the delivery technology of a pharmaceutical composition containing an antifungal agent to the nail or around the nail.

  An object of this invention is to provide the formulation which the extensibility to a nail | claw and a nail | claw periphery is improved, and reduces drying of a nail | claw and a nail | claw periphery. The inventors are selected from the group consisting of (A) antifungal agents, (B) thickening polymers and / or polyhydric alcohols, and (C) anti-inflammatory agents, local anesthetics, bactericides, and antihistamines. It has been found that by including one or more compounds, the extensibility to the nails and around the nails is improved, and a pharmaceutical composition that can prevent drying is obtained, and the present invention has been completed. .

That is, this invention provides the pharmaceutical composition hung up below.
Item 1.
(A) an antifungal agent;
(B) vinyl polymer, acrylic polymer, starch polymer, dextran, dextrin fatty acid ester, casein, dimethyl distearyl ammonium hectorite, (acryloyldimethyl taurine ammonium / vinyl pyrrolidone) copolymer, polyethylene glycol distearate, tri At least one selected from the group consisting of ethylene glycol isostearate, polyoxyethylene (20) methylglucoside, triisostearate, bentonite, hectorite, alginic acid and / or a salt thereof, propylene glycol alginate thickening polysaccharide and polyhydric alcohol Or (C) a nail and / or a nail containing one or more compounds selected from the group consisting of anti-inflammatory agents, local anesthetics, bactericides, and antihistamines Nail-surrounding pharmaceutical composition.
Item 2.
Item 2. The pharmaceutical composition according to Item 1, wherein the nail and / or nail periphery is a nail groove and / or a groove near the yellow line part.
Item 3.
Item 3. The pharmaceutical composition according to Item 1 or 2, wherein the antifungal agent (A) is an amine antifungal agent.
Item 4.
Item 4. The pharmaceutical composition according to Item 3, wherein (A) the antifungal agent is at least one selected from the group consisting of terbinafine and a salt thereof.
Item 5.
The component (B) is at least one selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, glycerin, 1,3-butylene glycol, methyl acrylate / acrylic acid-2-ethylhexyl copolymer, and carboxyvinyl polymer. Item 5. The pharmaceutical composition according to any one of Items 1 to 4, comprising a thickening polymer or a polyhydric alcohol.
Item 6.
Item 6. The pharmaceutical composition according to any one of Items 1 to 5, further comprising ethanol.
Item 7.
Item 7. The pharmaceutical composition according to Item 6, wherein the ethanol content is 20% by mass or more based on the total amount of the composition.
Item 8.
Item 8. The pharmaceutical composition according to any one of Items 1 to 7, which is a liquid agent.

  ADVANTAGE OF THE INVENTION According to this invention, the pharmaceutical composition suitable for the use around a nail | claw and a nail | claw can be provided.

  The present invention relates to a pharmaceutical composition comprising (A) an antifungal agent and (B) a thickening polymer and / or a polyhydric alcohol, and a predetermined component (C). The medicinal composition for nail circumference of the present invention has good extensibility to the nail and the nail circumference. Furthermore, it is possible to treat, improve, and prevent skin whitening and skin turn-up due to drying around the nails and around the nails.

[(A) Antifungal agent (antifungal component)]
Antifungal agents are substances that have the function of inhibiting or suppressing fungal growth or killing fungi, and are used to treat, prevent, and improve various diseases and symptoms caused by fungal infections. .

  Examples of the antifungal agent of the present invention include amine antifungal agents such as allylamine antifungal agents, benzylamine antifungal agents, or thiocarbamine antifungal agents, imidazole antifungal agents, and triazole antifungal agents. An azole antifungal agent such as a fungal agent or a morpholine antifungal agent is exemplified. As a kind of the antifungal agent of the present invention, an amine antifungal agent and an azole antifungal agent are preferable, and an amine antifungal agent is more preferable, from the viewpoint of more remarkable effects of the present invention.

  As the amine-based antifungal agent of the present invention, any pharmaceutically or physiologically acceptable amine-based antifungal agent which is a well-known compound as an antifungal agent having an amine in common can be used. Examples of amine antifungal agents include allylamine antifungal agents such as terbinafine or naphthifine, benzylamine antifungal agents such as butenafine, and thiocarbamine antibiotics such as tolnaphthalate and rilanaphthate. Among these, from the viewpoint of achieving the effects of the present invention more remarkably, an allylamine antifungal agent is preferably used. Among them, terbinafine or a terbinafine salt such as terbinafine hydrochloride is particularly preferable.

  The azole antifungal agent of the present invention is a compound well known as an antifungal agent having a common azole skeleton (a hetero 5-membered ring compound containing one or more nitrogen atoms), and is pharmaceutically or physiologically acceptable. Any possible azole antifungal agent can be used. As the azole antifungal agent, for example, an imidazole antifungal agent having an imidazole ring (hetero 5-membered ring containing 2 nitrogen atoms) or a triazole ring (hetero 5-membered hetero ring containing 3 nitrogen atoms) is used. And triazole antifungal agents. More specifically, imidazole antifungal agents such as miconazole, ranoconazole, luriconazole, isconazole, ketoconazole, clotrimazole, neticoconazole, sulconazole, bifonazole, oxyconazole, econazole and salts thereof; fluconazole, itraconazole, phosfluconazole, Examples include voriconazole, eficonazole, butconazole, fenticonazole, sertaconazole, and triazole antifungal agents such as salts thereof, which can be suitably used in the present invention. As the azole antifungal agent of the present invention, an imidazole antifungal agent is preferable from the viewpoint of more prominently achieving the effects of the present invention, and among them, miconazole, luliconazole, and isoconazole are preferable.

  The morpholine antifungal agent of the present invention is a compound well-known as an antifungal agent having morpholine in common, and any pharmaceutically or physiologically acceptable morpholine antifungal agent is used. Can do. A typical example of the morpholine antifungal agent is amorolfine or a salt thereof. These (A) components may all be used alone or in any combination of two or more.

  (A) The total content of the antifungal agent is preferably 0.01% by mass or more, more preferably 0.1% or more based on the total amount of the pharmaceutical composition from the viewpoint of more prominently achieving the effects of the present invention. It is at least mass%, more preferably at least 0.3 mass%, particularly preferably at least 0.5 mass%. (A) The total content of the antifungal agent is preferably 10% by mass or less, more preferably 8% by mass or less, based on the total amount of the pharmaceutical composition, from the viewpoint of more prominently achieving the effects of the present invention. More preferably, it is 5 mass% or less, Most preferably, it is 2 mass% or less. The total content of the antifungal agent (A) is preferably 0.01% by mass to 10% by mass and more preferably 0% with respect to the total amount of the pharmaceutical composition, from the viewpoint of more prominently achieving the effects of the present invention. 0.1% by mass to 8% by mass, more preferably 0.3% by mass to 5% by mass, and particularly preferably 0.5% by mass to 2% by mass. Among these, 1% by mass is most preferable.

[(B) Thickening polymer and / or polyhydric alcohol]
As the (B) thickening polymer and / or polyhydric alcohol of the present invention, the following substances can be used, and there is no particular limitation as long as these are used. That is, vinyl polymer, acrylic polymer, starch polymer, dextran, dextrin fatty acid ester, casein, dimethyl distearyl ammonium hectorite, (acryloyldimethyl tauronium ammonium / vinyl pyrrolidone) copolymer, polyethylene glycol distearate, triisostearin At least one selected from the group consisting of acid ethylene glycol, triisostearate polyoxyethylene (20) methyl glucoside, bentonite, hectorite, alginic acid and / or a salt thereof, propylene glycol alginate, thickening polysaccharide and polyhydric alcohol It can be.

  Examples of the vinyl polymer include polyvinyl pyrrolidone (PVP) polyvinyl alcohol, polyvinyl methyl ether, carboxyvinyl polymer, and the like. Examples of polyvinyl pyrrolidone include polyvinyl pyrrolidone K30 and polyvinyl pyrrolidone K90. Among these, 1 type (s) or 2 or more types can also be used.

  Acrylic polymers include acrylic acid / alkyl methacrylate copolymer, hydroxyethyl acrylate / acryloyl dimethyl taurate copolymer (particularly hydroxyethyl acrylate / acryloyl dimethyl taurine sodium copolymer), sodium acrylate / Acryloyldimethyltaurine copolymer, sodium acrylate / acrylic acid sodium methacrylate / sodium methacrylate / alkyl methacrylate copolymer, steareth-10 allyl ether / acrylate copolymer, polyacrylic acid or salt thereof (carboxyvinyl polymer) , Acryloyldimethyltauronium ammonium copolymer, acrylic acid / methacrylic acid polyoxyethylene glycol ether copolymer, polyacrylamide, and acrylamide / acrylic acid Examples include ammonium copolymers, methyl acrylate / acrylic acid-2-ethylhexyl copolymers, and the like.

  Examples of the starch polymer include hydroxypropyl starch phosphate (for example, StructureXL manufactured by National Starch, LLC), modified corn starch, corn starch, and the like.

  The polyhydric alcohol is not particularly limited as long as it is used as a component of an external preparation in the pharmaceutical, quasi-drug or cosmetic field. Specific examples of the polyhydric alcohol include glycerin, diglycerin, dipropylene glycol, propylene glycol, 1,3-butylene glycol, 3-methyl-1,3-butanediol, polyethylene glycol, and polyvinyl alcohol. . Preferred from the standpoint of the effects of the present invention are polyethylene glycol, polyvinyl alcohol, glycerin, and 1,3-butylene glycol.

  In the present specification, the polysaccharide thickener includes, among those used as a component of an external preparation in the pharmaceutical, quasi-drug or cosmetic field, specifically carrageenan, xanthan gum, gum arabic, pectin, and mucopolysaccharide. . Examples of mucopolysaccharides include chondroitin sulfate (sodium salt, etc.), hyaluronic acid or salts thereof (sodium salt, etc.), hyaluronic acid derivatives or salts thereof, heparin, heparin-like glycosaminoglycans, etc. Can do.

  These (B) components may all be used alone or in any combination of two or more.

  These (B) components are not limited, but among these, polyhydric alcohols, acrylic polymers, starch polymers, and vinyl polymers are preferred from the viewpoint of more prominently achieving the effects of the present invention. More preferred are monohydric alcohols and vinyl polymers, more preferred are vinyl polymers, and particularly preferred is polyvinylpyrrolidone.

  The total content of the component (B) is preferably 0.1% by mass or more, more preferably 0.5% by mass with respect to the total amount of the pharmaceutical composition from the viewpoint of more prominently achieving the effects of the present invention. As mentioned above, More preferably, it is 0.8 mass% or more, Most preferably, it is 1.5 mass% or more. The total content of the component (B) is preferably 5% by mass or less, more preferably, based on the total amount of the pharmaceutical composition, from the viewpoint of more prominently achieving the effects of the present invention or the feeling of use of the preparation. It is 4.5 mass% or less, More preferably, it is 3.5 mass% or less, Most preferably, it is 3 mass% or less.

  In the pharmaceutical composition of the present invention, from the viewpoint of more prominently achieving the effects of the present invention, the ratio of the component (B) to the component (A) is, for example, relative to 1 part by mass of the total content of the component (A). Preferably it is 0.5 mass part or more, More preferably, it is 0.6 mass part or more, More preferably, it is 0.7 mass part or more, Most preferably, it is 1.5 mass part or more. The total content of the component (B) is preferably 10 parts by mass with respect to 1 part by mass of the total content of the component (A) from the viewpoint of more prominently exerting the effects of the present invention and the feeling of use of the preparation. Or less, more preferably 5 parts by mass or less, further preferably 2.7 parts by mass or less, and particularly preferably 2 parts by mass or less. In the pharmaceutical composition of the present invention, the ratio of the component (B) to the component (A) can be, for example, 0.5 to 10 parts by mass with respect to 1 part by mass of the total content of the component (A). 0.6 to 5 parts by mass is preferred, 0.7 to 2.7 parts by mass is more preferred, and 1.5 to 2 parts by mass is even more preferred.

  Furthermore, for example, when the component (B) is polyvinyl pyrrolidone, the content of polyvinyl pyrrolidone is preferably 0.01 to 5% by mass with respect to the total amount of the pharmaceutical composition from the viewpoint of remarkably exhibiting the effects of the present invention. More preferably, it is 0.1-3 mass%, More preferably, it is 0.5-1 mass%. Furthermore, for example, when the component (B) is polyvinyl pyrrolidone K30 or polyvinyl pyrrolidone K90, the content of polyvinyl pyrrolidone K30 or polyvinyl pyrrolidone K90 is based on the total amount of the pharmaceutical composition from the viewpoint of remarkably exhibiting the effects of the present invention. , Preferably it is 0.01-5 mass%, More preferably, it is 0.1-3 mass%, More preferably, it is 0.5-1 mass%.

[Component (C)]
The following are mentioned as (C) component of this invention.
That is, it is 1 type, or 2 or more types of compounds selected from the group which consists of an anti-inflammatory agent, a local anesthetic, a disinfectant, and an antihistamine. Particularly preferred components (C) from the standpoint of achieving the effects of the present invention are glycyrrhetic acid, lidocaine, isopropylmethylphenol, and diphenhydramine hydrochloride, and glycyrrhetic acid and isopropylmethylphenol are more preferred.

  These components (C) are not particularly limited as long as they are grades and grades used as components of external preparations in the field of pharmaceuticals, quasi drugs, and cosmetics.

  The total content of (C) is preferably 0.1% by mass or more, more preferably 0.8% by mass or more, based on the total amount of the pharmaceutical composition, from the viewpoint of more prominently achieving the effects of the present invention. More preferably, it is 1% by mass or more, and particularly preferably 1.2% by mass or more. The total content of (C) is preferably 4.1% by mass or less, more preferably, based on the total amount of the pharmaceutical composition, from the viewpoint of more prominently achieving the effects of the present invention or the feeling of use of the preparation. Is 2.8% by mass or less, more preferably 2.5% by mass or less, and particularly preferably 2% by mass or less. The total content of (C) with respect to the total amount of the pharmaceutical composition is preferably 0.1 to 4.1% by mass, more preferably 0.8 to 2.8% by mass, and still more preferably 1-2. 0.5% by mass, particularly preferably 1.2-2% by mass.

  In the pharmaceutical composition of the present invention, the ratio of the component (C) to the component (A) is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, relative to 1 part by mass of the total content of the component (A), The total content of component (C) is preferably 0.1 to 4.1 parts by mass, more preferably 0.8 to 2.8 parts by mass, still more preferably 1 to 2.5 parts by mass, and particularly preferably 1.2 to 2 parts by mass.

  As the anti-inflammatory agent of component (C), steroidal anti-inflammatory drugs such as prednisolone valerate acetate, dexamethasone acetate, hydrocortisone acetate, or pharmacologically acceptable salts thereof, allantoin, glycyrrhetic acid, glycyrrhizic acid, aldioxa , Ufenamate, bufexamac, ibuprofen piconol, indomethacin, diclofenac, piroxicam, epsilon-aminocaproic acid, berberine, lysozyme, sodium azulenesulfonate, dimethylisopropylazulene, bromelain, serrapeptase, semi-alkaline proteinase, or pharmacologically acceptable thereof Non-steroidal anti-inflammatory drugs such as salts are exemplified. Of these drugs, non-steroidal anti-inflammatory drugs are preferable, and glycyrrhizic acid, glycyrrhetinic acid, and allantoin are more preferable from the viewpoint of achieving the effects of the present invention more remarkably. One or two or more of these drugs can be used in appropriate combination.

  (C) Component local anesthetic includes lidocaine, procaine, tetracaine, dibucaine, bupivacaine, mepivacaine, ropivacaine, levobupivacaine, oxypolyethoxydodecane, and pharmaceutically acceptable salts thereof, or ethyl aminobenzoate Is exemplified. Among these drugs, particularly preferred are lidocaine and dibucaine hydrochloride from the viewpoint of more prominently achieving the effects of the present invention. One or two or more of these drugs can be used in appropriate combination.

  (C) Component fungicides include decalinium chloride, decalinium acetate, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkyldiaminoethylglycine hydrochloride, cetylpyridinium chloride, sodium benzoate, chlorobutanol, Isopropylmethylphenol, thymol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, acrinol, hinokitiol , Resorcin, berberine benzoate, or biguanide compounds. One or two or more of these drugs can be used in appropriate combination. Of these drugs, isopropylmethylphenol is preferred from the viewpoint of more prominently achieving the effects of the present invention.

  The antihistamine of component (C) is not limited, but includes chlorpheniramine, isothipenzil, ketotifen, bepotastine, dimenhydrinate, cyproheptadine, diphenylpyralin, promethazine, iproheptin, emedastine, clemastine, azelastine, levocabastine, hydroxyzine, mequitazine, Examples include loratadine, fexofenadine, cetirizine, oxatomide, terfenadine, epinastine, astemizole, ebastine, diphenylimidazole, diphenhydramine, or salts of these compounds.

  From the viewpoint of more prominently achieving the effects of the present invention, preferred examples of the antihistamine are diphenhydramine, diphenylpyralin, chlorpheniramine, diphenylimidazole, or a salt thereof, and more preferred examples are chlorpheniramine, diphenhydramine, or theirs. More preferred examples are chlorpheniramine, chlorpheniramine maleate, diphenhydramine, diphenhydramine, and hydrochloride. One or two or more of these drugs can be used in appropriate combination.

Furthermore, for example, when the component (C) is glycyrrhetinic acid, the content of glycyrrhetic acid is preferably 0.1 to 1% by mass with respect to the total amount of the pharmaceutical composition from the viewpoint of more prominently achieving the effects of the present invention. More preferably, it is 0.2-0.8 mass%, More preferably, it is 0.25-0.5 mass%.
For example, when the component (C) is lidocaine, the content of lidocaine is preferably 0.25 to 2.5% by mass with respect to the total amount of the pharmaceutical composition from the viewpoint of more prominently achieving the effects of the present invention. Yes, more preferably 0.5 to 2% by mass.
For example, when the component (C) is isopropylmethylphenol, the content of isopropylmethylphenol is preferably 0.3 to 3 mass based on the total amount of the pharmaceutical composition from the viewpoint of more prominently achieving the effects of the present invention. %, And more preferably 0.5 to 1% by mass.
For example, when the component (C) is diphenhydramine and salts thereof, the content of diphenhydramine and salts thereof is preferably relative to the total amount of the pharmaceutical composition from the viewpoint of more prominently achieving the effects of the present invention. Is 0.1 to 2% by mass, more preferably 0.5 to 1% by mass.

  In the present invention, in addition to (A) an antifungal agent, (B) a thickening polymer and / or a polyhydric alcohol, and (C) component, a pharmaceutical, a quasi drug, Any known ingredient that can be used as a cosmetic or the like can be contained in the pharmaceutical composition. As an optional component, ethanol can be particularly preferably contained.

[ethanol]
Ethanol used in the pharmaceutical composition of the present invention is not particularly limited as long as it is a grade and grade used in pharmaceuticals, quasi drugs, cosmetics and the like. For example, 95% ethanol, 99% ethanol (anhydrous ethanol), or the like can be appropriately used as the ethanol used as the raw material of the pharmaceutical composition.

  From the viewpoint of usability, the content of ethanol is preferably 20% by mass or more, more preferably 30% by mass or more, and further preferably 40% by mass or more, based on the total amount of the pharmaceutical composition. . The content of ethanol is preferably 90% by mass or less, more preferably 80% by mass or less, and still more preferably 70% by mass or less with respect to the total amount of the pharmaceutical composition from the viewpoint of ease of handling of the preparation. . The content of ethanol is preferably 20 to 90% by mass, more preferably 30 to 80% by mass, and further preferably 40 to 70% by mass with respect to the total amount of the pharmaceutical composition.

  In the pharmaceutical composition of the present invention, the ratio of ethanol to the component (A) is, for example, from the viewpoint of feeling of use, for example, the ethanol content is 15 to 180 mass with respect to 1 mass part of the total content of the component (A). It is preferably 25 to 140 parts by mass, more preferably 35 to 100 parts by mass, still more preferably 45 to 90 parts by mass, and particularly preferably 60 parts by mass.

[salt]
Examples of the “salt” as used herein include organic salts and inorganic salts. Examples of the organic salt include ammonium, diethanolamine, triethanolamine, ethylenediamine, and the like, and examples of the inorganic salt include salts with sodium, potassium, calcium, magnesium, and the like. In addition, for example, salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, Malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, salts with organic acids such as salicylic acid; or aspartic acid, glutamic acid And salts with acidic amino acids such as The “salt” may include a solvate or hydrate of a salt. In particular, the form of the salt of the component (A) is not particularly limited, but from the viewpoint of easy availability, a salt of an inorganic acid is preferable, and a hydrochloride or nitrate is more preferable.

[container]
The container filled with the pharmaceutical composition of the present invention is not particularly limited. What is necessary is just to be used as a pharmaceutical external preparation, a quasi-drug, and a container for cosmetics. As such a container material, for example, part or all of the contact surface with the pharmaceutical composition, preferably all are polyolefin resin, acrylic resin, polyester, polycarbonate, fluororesin, polyvinyl chloride, polyamide, ABS resin, Examples include containers made of at least one material selected from the group consisting of AS resin, polyacetal, modified polyphenylene ether, polyarylate, polysulfone, polyimide, cellulose acetate, aluminum, and glass.

  From the viewpoint of ease of handling of the preparation, polyethylene (PE) (including high density polyethylene (HDPE), low density polyethylene (LDPE), ultra low density polyethylene, linear low density polyethylene (LLDPE), ultra high molecular weight polyethylene, etc.) ), Polypropylene (PP) (including isotactic polypropylene, syndiotactic polypropylene, atactic polypropylene, etc.), and polyolefin resins such as ethylene-propylene copolymer, polymethylpentene, polybutene-1,1,2-polybutadiene, polyethylene Terephthalate, polybutylene terephthalate and polyethylene naphthalate are preferred, and polyethylene or polypropylene is more preferred.

  The shape of the container is not limited, but is preferably a tube, a dripping container, or a squeeze container.

[Dosage form]
The pharmaceutical composition of the present invention is provided in any form that can be widely used as a pharmaceutical, a quasi-drug, and the like. Preferably, it is provided as a preparation that can be used as an external preparation for skin. The pharmaceutical composition of the present invention is not particularly limited as long as it is a known form, but from the viewpoint of more prominently achieving the effects of the present invention, for example, creams, solutions, suspensions, emulsions, lotions, aerosols It is preferably provided in the form of an aqueous pharmaceutical composition such as a mist, and more preferably a cream, liquid (gel), suspension, emulsion, lotion, or mist. In particular, a liquid agent is preferable. Here, the aqueous pharmaceutical composition refers to a dosage form in which the proportion of water or a water-soluble solvent in the total amount of the composition is 10% by mass or more, and preferably 20% from the viewpoint of the stability of the preparation or the feeling of use. % Or more, more preferably 30% by mass or more.

  The preparation can be produced by mixing each component according to or in accordance with the 17th revised Japanese Pharmacopoeia General Rules.

[Production method]
The pharmaceutical composition of the present invention can be produced by a known method. If necessary, a sterilization step or a filtration step can be included.

[Base, carrier, or other ingredients]
The pharmaceutical composition of the present invention can be formulated by mixing with known bases or carriers that can be used as pharmaceuticals, quasi-drugs, cosmetics and the like within a range not impairing the effects of the present invention. In addition, the pharmaceutical composition of the present invention includes, for example, surfactants, oils, alcohols, higher fatty acids, antiseptics, antioxidants, antioxidants, cooling agents, preservatives, chelating agents, pH adjusters. Additives such as stabilizers, solubilizers, suspending agents, tonicity agents, buffers, fragrances, colorants, pigments and the like can be blended. These additives can be used alone or in combination of two or more.

  Examples of the base or carrier include hydrocarbons, silicone oils, esters, lower alcohols, purified water and the like. Examples of the hydrocarbon include liquid paraffin, squalane, gelled hydrocarbon (such as plastibase), ozokerite, α-olefin oligomer, light liquid paraffin, and the like. Examples of the silicone oil include methyl polysiloxane and cross-linked methyl. Polysiloxane, Highly polymerized methylpolysiloxane, Cyclic silicone, Alkyl-modified silicone, Cross-linked alkyl-modified silicone, Amino-modified silicone, Polyether-modified silicone, Polyglycerin-modified silicone, Cross-linked polyether-modified silicone, Cross-linked alkyl polyether-modified silicone , Silicone-alkyl chain co-modified polyether-modified silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branch Examples of the esters include isopropyl, acrylic silicon, phenyl-modified silicone, and silicone resin. Examples of the esters include isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and tetra-2-ethylhexanoic acid. An example is pentaerythlit, and examples of lower alcohols include isopropanol.

  A base or a support | carrier can be used individually by 1 type or in combination of 2 or more types.

  Examples of the surfactant include nonionic surfactants. Nonionic surfactants include, for example, sorbitan fatty acid esters, propylene glycol fatty acid esters, castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyalkylene alkyl ethers, amines, silicone surfactants, Examples thereof include oxyethylene lauryl alcohol ether. Examples of sorbitan fatty acid esters include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, etc. Examples of the propylene glycol fatty acid esters include propylene glycol fatty acid esters such as propylene glycol monostearate, and castor oil derivatives include polyoxyethylene hydrogenated castor oil and polyoxyethylene castor oil. Examples of polyoxyethylene sorbitan fatty acid esters include, for example, polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), monos Examples include polyoxyethylene (20) sorbitan (20) sorbitan monooleate, polyoxyethylene (20) sorbitan monooleate (polysorbate 80), polyoxyethylene (20) sorbitan isostearate and the like. For example, polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; polyoxyethylene cetyl ether and the like. Examples of amines include stearylamine and oleylamine, and silicone surfactants. Examples thereof include polyoxyethylene / methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. Etc. The.

  Other examples of the surfactant include an anionic surfactant and an amphoteric surfactant. Examples of the anionic surfactant include laurate, palmitate, cocoyl glutamate, coconut oil methylalanine salt, acylmethyl taurate, polyoxyethylene lauryl sulfate, and the amphoteric surfactant. Examples thereof include lauryl diaminoethyl glycine salt, coconut oil fatty acid betaine salt and the like.

  Examples of the oil include natural animal and plant oils, hydrocarbon oils, ester oils, silicone oils, higher alcohols, higher fatty acids, animals and plants, and synthetic essential oils.

  Examples of natural animal and plant oils and fats include avocado oil, linseed oil, almond oil, olive oil, cacao oil, beef tallow, giraffe 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, pork fat, grape oil, jojoba oil, macadamia nut oil, mink oil, cottonseed oil, owl, beeswax, Examples include honey beeswax, coconut oil, hydrogenated coconut oil, peanut oil, lanolin, egg yolk oil, and rosehip oil.

  Examples of the hydrocarbon oil include paraffinic hydrocarbons and olefinic hydrocarbons, and examples include squalane, squalene, ceresin, paraffin, pristane, microcrystalline wax, liquid paraffin, and petroleum jelly.

  As ester oils, synthetic esters, esters of higher alcohols and higher fatty acids are used, for example, diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, isostearyl isostearate, Trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, neopentyl glycol di-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, Oleyl oleate, octyldodecyl oleate, decyl oleate, neopentyl glycol dicaprate, 2-ethylhexyl succinate, isocetyl stearate, butyl stearate, diisopropyl sebacate, cetyl lactate Tetradecyl lactate, isopropyl myristate, octyldodecyl myristate, cetyl myristate, myristyl myristate, octyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, 12-hydroxystearin Examples thereof include cholesteryl acid, phytosteryl oleate, diisostearyl malate, paramethoxycinnamate, and pentarosyl tetrarosinate.

  Examples of the silicone oil include dimethylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, stearoxysilicone, etc. Higher alkoxy-modified silicone, alkyl-modified silicone, higher fatty acid ester-modified silicone, and the like.

  Examples of the alcohol include lower alcohols and higher alcohols. Examples of the lower alcohol include isopropanol, and examples of the higher alcohol include octyldodecanol, isostearyl alcohol, oleyl alcohol, stearyl alcohol, cetanol, and behenyl alcohol.

  As the higher fatty acid, a saturated or unsaturated linear or branched fatty acid having 12 to 22 carbon atoms can be used. For example, isostearic acid, oxystearic acid, oleic acid, stearic acid, palmitic acid, behenic acid, Examples include myristic acid, lauric acid, lanolinic acid, linoleic acid, and linolenic acid.

  Preferable examples of the preservative include benzoic acid, acetic acid, phenol, iodotin tincture, paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid and the like.

  Preferable examples of the antioxidant include sulfite and ascorbic acid.

  Examples of the antioxidant include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), sodium sulfite, erythorbic acid, L-cysteine hydrochloride, vitamin Cs, vitamin Es and the like. Examples of vitamin C include ascorbigen-A, ascorbic acid stearate, ascorbyl palmitate, dipalmitate L-ascorbyl, ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, ascorbine Examples thereof include sodium acid phosphate, magnesium ascorbate phosphate, and the like. Examples of vitamin E include dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, and the like.

  Examples of the refreshing agent include, but are not limited to, menthol (l-menthol, dl-menthol, etc.), camphor (d-camphor, dl-camphor, etc.), terpenoids such as borneol, terpenoid-containing essential oil (mint oil), Or the pharmacologically acceptable salt etc. are illustrated. One or two or more of these drugs can be used in appropriate combination.

  Preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, benzyl paraoxybenzoate, paraoxybenzoate Examples include methyl benzoate and phenoxyethanol.

  Examples of the chelating agent include EDTA / disodium salt, EDTA / calcium disodium salt, and the like.

  Examples of 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 (potassium hydroxide, sodium hydroxide, etc.) ) And organic bases (such as triethanolamine, diisopropanolamine, and triisopropanolamine).

  Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), and the like.

  Examples of the solubilizer include D-mannitol, benzyl benzoate, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.

  Examples of the suspending agent include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, glyceryl monostearate; for example, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose And hydrophilic polymers such as hydroxypropylmethylcellulose.

  Examples of isotonic agents include sodium chloride, glycerin, D-mannitol and the like.

  Examples of the buffer include buffer solutions of phosphate, acetate, carbonate, citrate and the like.

  Examples of the colorant include inorganic pigments and natural pigments.

  The pharmaceutical composition of the present invention may further contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of such components include antipruritic components, moisturizing components, blood circulation promoting components, astringent components, peptides or derivatives thereof, amino acids or derivatives thereof, cell activation components, vitamin agents, and the like.

As an antipruritic component, crotamiton etc. are mentioned, for example.

  As moisturizing ingredients, sugars such as trehalose, xylitol, oligosaccharides; polymer compounds such as collagen, elastin, keratin, chitin, chitosan; amino acids such as glycine, aspartic acid, arginine; sodium lactate, sodium pyrrolidone carboxylate Natural moisturizing factors such as: lipids such as ceramide, cholesterol and phospholipids; plant extract extracts such as chamomile extract, hamamelis extract, tea extract and perilla extract.

  Examples of the blood circulation promoter include acetylcholine, caffeine, capsaicin, cantharis tincture, gamma oryzanol, ginger orchid tincture, gingeron, cephalanthin, assembly extract, tannic acid, red pepper tincture, trazoline, nicotinic acid tocopherol, nicotinic acid benzyl ester, And nicotinic acid amide.

  Examples of the astringent component include zinc sulfate, chlorohydroxyaluminum, aluminum chloride, zinc sulfocolate and tannic acid.

  Peptides or derivatives thereof include keratin-degrading peptide, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin-degrading peptide , Conchiolin degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soy proteolytic peptide, hydrolyzed soy protein, wheat protein, wheat proteolytic peptide, hydrolyzed wheat protein, casein degrading peptide Acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.).

  As amino acids or their derivatives, betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine Leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine and the like.

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

  As the vitamin agent, any of vitamin B, vitamin C, vitamin D, vitamin E, nicotinic acid, vitamin K, and other vitamins can be used. Examples of vitamin B include vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinic acids, pantothenic acids, folic acid, biotin, and the like. Examples of vitamin E include dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, and the like. Examples of vitamin B2 include riboflavin and flavin Mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5′-phosphate sodium, riboflavin tetranicotinate, etc .; nicotinic acids include, for example, nicotinic acid dl-α-tocopherol, nicotinic acid Benzyl, methyl nicotinate, β-butoxyethyl nicotinate, 1- (4-methylphenyl) ethyl nicotinate and the like; examples of vitamin C include ascorbigen-A and ascorbic acid stearate Ter, ascorbyl palmitate, L-ascorbyl dipalmitate, ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, sodium ascorbate phosphate, magnesium ascorbate phosphate, etc .; vitamin D For example, methyl hesperidin, ergocalciferol, cholecalciferol, etc .; for vitamin K, for example, phylloquinone, farnoquinone, etc .; for vitamin B1, for example, dibenzoylthiamine, dibenzoylthiamine hydrochloride, thiamine hydrochloride Salt, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine Minor monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate, etc .; Examples of vitamin B6 include pyridoxine hydrochloride and acetic acid Pyridoxine, pyridoxal hydrochloride, 5′-pyridoxal phosphate, pyridoxamine hydrochloride and the like; Examples of vitamin B12 include cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin and the like; and examples of nicotinic acids include nicotinic acid and nicotinamide; Examples of pantothenic acids include pantothenic acid, calcium pantothenate, pantothenyl alcohol (D-panthenol), D-panthecin, D-panthetin, coenzyme A, pantothenyl ester. Ether and the like; biotin, folic acid and the like; and the like and vitamin-like acting factors such pharmacologically acceptable salts thereof.

[PH]
The pH of the pharmaceutical composition of the present invention is appropriately set according to the type of component (A), the type and content of other ingredients, the formulation form, the method of use, etc., and within the physiologically or pharmaceutically acceptable range. Although there will be no restriction | limiting if it exists, from a viewpoint of safety, it can be set to pH 2-9, for example, Preferably, it is about 3-8, More preferably, it can be set to about 5-7.

  [Viscosity] The viscosity of the pharmaceutical composition of the present invention is preferably 1 mPa · s to 10 Pa · s, more preferably 2 mPa · s to 8 Pa, based on the total amount of the pharmaceutical composition, from the viewpoint of ease of handling of the preparation. · S, more preferably 3 Pa · s to 4 Pa · s. The viscosity in the present specification is the result obtained when measured at a rotational speed of 12 rpm and a measurement time of 1 minute using an RB80 viscometer manufactured by Toki Sangyo Co., Ltd. and an M3 rotor.

[Usage]
The pharmaceutical composition of the present invention is not limited, but is preferably used for the treatment of athlete's foot or beetle, candidiasis and the like. The pharmaceutical composition of the present invention comprises nail and nail circumference, in particular nail groove and / or groove near yellow line part, nail mother, nail root, nail half moon, nail plate, toe, yellow line, posterior nail contour It can be used for nails such as cuticle, lateral nail fold, nail bed, and nail lower skin, and around the nail, and is used for the treatment of athlete's foot or bugs. From the viewpoint of exhibiting the effects of the present invention more remarkably, it can be applied particularly preferably to athlete's foot in a place where the active ingredient is difficult to reach near the groove and / or yellow line part.

  Athlete's foot is a skin symptom caused by ringworm. Symptoms and features around the nail and nail include itching, small stubble, peeling, drying around the nail and nail, hardening, powder blowing, and raggedness. Ringworms are particularly prone to appear on the nail and around the nail, where the keratinous component keratin is present, and the keratinous component is likely to appear.

  Beetles are skin symptoms caused by ringworm bacteria. There is a small red circle on the skin, which gradually spreads. Itchy and similar to athlete's foot, but the beetles tend to form in thin areas of the skin.

  Candidiasis is caused by Candida spp. Symptoms of the skin surface of the hand, skin peeling between fingers, and discoloration of the base of the nail to white appear.

  Although not limited, the pharmaceutical composition of the present invention can be used for the treatment of symptoms caused by ringworm, folding screen, candidiasis, interdigital erosion, and interrash.

  The pharmaceutical composition of the present invention is not limited, but is preferably provided as a therapeutic agent for athlete's foot, which is a solution for the nail and around the nail, from the viewpoint of more prominently achieving the effects of the present invention.

  Moreover, although the usage method of the pharmaceutical composition of this invention changes with conditions, age, sex, etc. of the nail | claw and the skin around a nail | claw, what is necessary is just to be the following method, for example. That is, several times a day (for example, about 1 to 5 times, preferably 1 to 3 times, more preferably 1 time), an appropriate amount (for example, about 0.5 to 2 g) is applied to the nail and the nail circumference (for example, the nail groove and (Or a groove near the yellow line portion). In addition, the composition is applied to the nail and around the nail so that the daily use amount of the antifungal agent (for example, terbinafine or a salt thereof) is, for example, about 5 to 20 mg (for example, the nail groove and / or the groove near the yellow line part). Apply to the above. The application method is carried out according to the dosage form, preferably coating. The application period is preferably about 30 days or longer, for example.

[Promoting the spread of pharmaceutical compositions]
In the present invention, (A) an antifungal agent, (B) a thickening polymer and / or a polyhydric alcohol, and (C) a pharmaceutical composition containing these components by coexisting them, in particular nail and nail Spreading around can be promoted. Here, the promotion of spread is also referred to as “extensibility” in the present specification. In the present invention, “extensibility” of the pharmaceutical composition means that the pharmaceutical composition is not only in the nail and nail circumference, in particular, in the nail groove and / or in the vicinity of the yellow line, but also in the nail mother, nail root, nail meniscus. , Nail plate, toe, yellow line, posterior nail fold, cuticle, side nail fold, nail bed, nail bed, etc. In order to promote such spread, the same conditions as the concentration, pH, viscosity, formulation conditions, etc. of each component in the pharmaceutical composition of the present invention described above are employed.

[Glossy or moisturizing feeling of pharmaceutical composition]
In the present invention, (A) an antifungal agent, (B) a thickening polymer and / or a polyhydric alcohol, and (C) component are allowed to coexist in the pharmaceutical composition. And / or a moisturizing feeling can be provided. In the present invention, in order to exert such glossiness or moisturizing feeling, the same conditions as the concentration, pH, viscosity, formulation and the like of each component in the pharmaceutical composition of the present invention described above are employed.

  Next, the present invention will be specifically described with reference to examples and test examples, but the present invention is not limited to the following examples and test examples.

[Test Example 1. Surface tension measurement test]
Pharmaceutical compositions (solutions) having the compositions of Examples and Comparative Examples shown in Tables 1 to 5 were prepared according to a conventional method. Next, the surface tension of the compositions of Examples and Comparative Examples was measured. That is, an appropriate amount of each composition was taken and subjected to measurement using a capillary lift type surface tension meter (capillary size φ6 × 160 mm, capillary inner diameter size φ0.5 mm; manufactured by ASONE, model number 2380-05-10). The surface tension reduction rate of each example relative to a predetermined comparative example was calculated according to Equation 1. Two significant digits were used. The results are shown in Tables 1 to 5. The lower the surface tension, the more the composition extends, so that the drug can be delivered to the fungus more appropriately after application to the affected area. Formula 1: Surface tension reduction rate = (Surface tension of comparative example−surface tension of each example or reference example) / surface tension of comparative example × 100 (%)

In the compositions of the examples, it was confirmed that the surface tension was lowered as compared with the compositions of the comparative examples. Therefore, the extensibility of the composition was improved by allowing terbinafine hydrochloride to coexist with (B) thickening polymer or polyhydric alcohol, and (C) isopropylmethylphenol, glycyrrhetinic acid, lidocaine or diphenhydramine hydrochloride. Such a composition can deliver the composition more appropriately to the nail and the fungus existing in the deep part around the nail.

  Even when polyvinyl alcohol, polyethylene glycol, 1,3-butylene glycol, methyl acrylate / acrylic acid-2-ethylhexyl copolymer or carboxyvinyl polymer is used as the component (B), a decrease in surface tension is also confirmed. .

[Test Example 2. Surface tension measurement test]
Pharmaceutical compositions (solutions) having the compositions of Examples and Comparative Examples shown in Table 6 were prepared according to a conventional method. Next, the surface tension of the compositions of Examples and Comparative Examples was measured in the same manner as in Test Example 1. In each test example, the surface tension reduction rate of each example relative to each comparative example was calculated according to Equation 1. Two significant digits were used. The results are shown in Table 6. The lower the surface tension, the more the composition extends, so that the drug can be appropriately delivered to the fungus by application to the affected area.

  In Test Example 2-1, it was confirmed that the surface tension of the composition of the example was lower than that of the composition of the comparative example. Therefore, it can be understood that the extensibility of the composition is improved by allowing (B) polyvinylpyrrolidone K30 and (C) glycyrrhetinic acid to coexist with butenafine hydrochloride. Such a composition can deliver a composition more appropriately with respect to the nail and fungi existing in the deep part around the nail.

  In Test Example 2-2, it was confirmed that the surface tension of the composition of the example was lower than that of the composition of the comparative example. Therefore, it can be understood that the extensibility of the composition is improved by allowing (B) polyvinylpyrrolidone K30 and (C) lidocaine to coexist in miconazole nitrate. Such a composition can deliver a composition more appropriately with respect to the nail and fungi existing in the deep part around the nail.

  In Test Example 2-3, it was confirmed that the surface tension of the composition of the example was lower than that of the composition of the comparative example. Therefore, it can be understood that the extensibility of the composition is improved by allowing (B) polyvinylpyrrolidone K30 and (C) glycyrrhetinic acid to coexist with isconazole nitrate. Such a composition can deliver a composition more appropriately with respect to the nail and fungi existing in the deep part around the nail.

  For Test Examples 2-1 to 2-3, when glycerin, polyvinyl alcohol, polyethylene glycol, 1,3-butylene glycol, methyl acrylate / acrylic acid-2-ethylhexyl copolymer or carboxyvinyl polymer is used as component (B) Similarly, a decrease in surface tension is confirmed.

[Test Example 3. sensory evaluation]
For 5 subjects, the pharmaceutical compositions (solutions) of Examples and Comparative Examples shown in Table 7 were applied in appropriate amounts around the nails and around the nails, and glossiness, extensibility, and moisturizing feeling immediately after application or 30 minutes after application. Was evaluated by the VAS (Visual Analogue Scale) method. That is, for each question item, the length from the left end of the line segment with a length of 100 mm to the shaded position where the answer was made was measured and used as the answer value. In the case of glossiness, regarding the state of the nail after 30 minutes of application, “not feel at all” is answered as 0 mm (the left end of the line segment), and “feels so strong that it looks bright” is set as 100 mm (the right end of the line segment) The answer was determined and the glossiness of each composition was evaluated. In the case of the extensibility of the preparation, as for the state of the preparation around the nail immediately after application, “No extension” is set as 0 mm (the left end of the line segment), “Extended to every corner” is set as 100 mm (the right end of the line segment) The degree of extensibility of each composition was evaluated. In the case of a moisturizing sensation, “no feeling at all” about the state of the nail and the area around the nail 30 minutes after application is set as 0 mm (the left end of the line segment), and “feeling very strong” is set as 100 mm (the right end of the line segment). The answer was defined and the degree of moisturizing feeling of each composition was evaluated. The test was carried out with the composition of each composition lying down. The results are shown in Table 7.

  Terbinafine hydrochloride alone had low glossiness, extensibility, and moisturizing feeling around the nails and around the nails (Comparative Example 5), while (B) thickening polymer or polyhydric alcohol, and (C) isopropylmethylphenol and glycyrrhetic acid By coexisting, it was confirmed that all the subjects felt improvement in glossiness, extensibility, and moisturizing feeling around the nails and around the nails.

Test example using polyvinyl alcohol, polyethylene glycol, 1,3-butylene glycol, methyl acrylate / acrylic acid-2-ethylhexyl copolymer or carboxyvinyl polymer as component (B), lidocaine or diphenhydramine hydrochloride as component (C) Similarly, in the case where No. 3 is carried out, improvement in glossiness, extensibility, nail and moisturizing feeling around the nail are confirmed.

  Hereinafter, the formulation example of this invention is shown. A pharmaceutical composition was prepared by a conventional method according to the formulation shown in Table 8. All the preparations can be used in a container made of PE.

Claims (4)

(A) terbinafine, butenafine, miconazole, isoconazole, and at least one or more selected from the group consisting of salts thereof;
(B) polyvinylpyrrolidone or glycerin;
(C) glycyrrhetinic acid, lidocaine, isopropylmethylphenol, diphenhydramine, or a salt of diphenhydramine ;
40-70% by weight of ethanol; and
A pharmaceutical composition for grooves in the vicinity of nail grooves and / or yellow line portions, containing water . The pharmaceutical composition according to claim 1, which is a liquid. (A) terbinafine, butenafine, miconazole, isoconazole, and more at least one or two species selected from the group consisting of salts,
(B) polyvinylpyrrolidone or glycerin;
(C) glycyrrhetinic acid, lidocaine, isopropylmethylphenol, diphenhydramine, or a salt of diphenhydramine ;
40-70% by weight of ethanol; and
A method for improving the extensibility of a nail groove containing the component (A) and / or a groove pharmaceutical composition in the vicinity of the yellow line portion by coexisting water . The method according to claim 3, wherein the pharmaceutical composition is a liquid.