JP2016166238A - Antimycotic medicinal composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antimycotic medicinal composition in which an antimycotic action of lanoconazole is intensified and which has a superior curative effect on a mycotic disease.SOLUTION: Provided is an antimycotic medicinal composition that is prepared by combining (a) lanoconazole with (b) at least one ingredient selected from a group consisting of local anesthetic, antihistamine, and anti-inflammatory agent.SELECTED DRAWING: None

Description

  The present invention relates to an antifungal pharmaceutical composition containing ranoconazole. More specifically, the present invention relates to an antifungal pharmaceutical composition in which the antifungal effect of ranoconazole is enhanced and can exhibit an excellent therapeutic effect against mycosis. Furthermore, the present invention relates to a method for enhancing the antifungal action of an antifungal pharmaceutical composition containing ranoconazole.

  In addition to superficial mycoses such as ringworm, superficial candidiasis and folding screen, mycosis includes actinomycosis, cryptococcosis, coccidioidomycosis, penicillosis, deep tinea, deep candidiasis, etc. Deep mycosis is known. Various antifungal agents have been developed and put into practical use as therapeutic agents for these mycoses. Among the antifungal agents that have been developed in the past, lanoconazole has an action of inhibiting the synthesis of fungal ergosterol, and exhibits a broad antifungal spectrum and strong antifungal activity, so it is widely used as an active ingredient in antifungal pharmaceutical compositions. It is used.

  Various proposals have been made for the formulation of an antifungal pharmaceutical composition containing ranoconazole. For example, for the purpose of enhancing the antifungal effect of ranoconazole, a formulation in which pyrrolnitrin (see Patent Document 1), lactoferrin (see Patent Document 2), or the like is combined with lanconazole has been proposed.

  However, in superficial mycoses such as ringworm, the fungus may have penetrated deep into the stratum corneum, and the antifungal pharmaceutical composition containing conventional ranoconazole does not have a sufficient antifungal effect, There is a disadvantage that long-term administration is forced. In addition, the use of a conventional antifungal pharmaceutical composition containing ranoconazole is satisfactory because even if the symptoms of mycosis are cured, the antifungal action is insufficient, and relapse or reinfection may occur. At present, the effect of treating mycosis has not been successful.

  Under such circumstances, development of an antifungal pharmaceutical composition capable of exhibiting an excellent antifungal action and exhibiting an excellent therapeutic effect in a short period of time is eagerly desired.

International Publication No. 00/062776 Pamphlet Japanese Unexamined Patent Publication No. 9-2970

  An object of the present invention is to solve the problems of the background art. Specifically, an object of the present invention is to provide an antifungal pharmaceutical composition in which the antifungal action of ranoconazole is enhanced and exhibits an excellent therapeutic effect against mycosis. Furthermore, an object of the present invention is to provide a method for enhancing the antifungal action of an antifungal pharmaceutical composition containing ranoconazole.

  As a result of diligent studies to solve the above problems, the present inventors have found (a) lanoconazole and (b) at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent. It has been found that the pharmaceutical composition formulated in combination has an enhanced antifungal action of ranoconazole and has an excellent therapeutic effect on mycosis. The present invention has been completed by making further improvements based on such findings.

That is, the present invention is an antifungal pharmaceutical composition listed below:
Item 1. An antifungal pharmaceutical composition comprising (a) lanoconazole, and (b) at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent.
Item 2. Item 2. The antifungal drug according to Item 1, wherein the component (b) is at least one selected from the group consisting of diphenhydramine, lidocaine, procaine, allantoin, glycyrrhetinic acid, chlorpheniramine, derivatives thereof, and salts thereof. Composition.
Item 3. Item 3. The antifungal pharmaceutical composition according to Item 1 or 2, wherein the total amount of the component (a) is 0.001 to 10% by weight and the component (b) is 0.005 to 20% by weight in total.
Item 4. Item 4. The antifungal pharmaceutical composition according to any one of Items 1 to 3, wherein the component (b) is contained at a ratio of 0.005 to 100 parts by weight relative to 1 part by weight of the component (a).
Item 5. Item 5. The antifungal pharmaceutical composition according to any one of Items 1 to 4, which is a cream, liquid, or ointment.
Item 6. Item 6. The antifungal pharmaceutical composition according to any one of Items 1 to 5, which is a therapeutic agent for superficial mycosis.
Item 7. Item 7. The antifungal pharmaceutical composition according to any one of Items 1 to 6, which is a therapeutic agent for ringworm.
Item 8. A method for enhancing the antifungal activity of an antifungal pharmaceutical composition containing ranoconazole, comprising: (a) an antifungal pharmaceutical composition containing lanoconazole, comprising (b) a local anesthetic, an antihistamine, and an anti-inflammatory agent An enhancement method comprising blending at least one component selected from the group.

  According to the antifungal pharmaceutical composition of the present invention, since the antifungal action of ranoconazole is remarkably enhanced, it is useful for the treatment of superficial mycosis and deep mycosis, particularly for the treatment of ringworm.

  Furthermore, the antifungal pharmaceutical composition of the present invention has a local anesthetic action, an antihistamine action, and / or an anti-inflammatory action based on the physiological or pharmacological action of the component (b) in addition to the excellent antifungal action. Since it can be expressed, it is useful in terms of physiology or pharmacological action other than antifungal action, and has high practical value.

  In addition, according to the method for enhancing antifungal action of the present invention, the antifungal action of ranoconazole can be enhanced by a simple method, so that it is possible to improve the practical value and versatility of ranoconazole.

In Test Example 2, it is a figure which shows the result of having evaluated the antifungal action with respect to Trichophyton mentagrophytes of an antifungal composition (Example 6 and Comparative Examples 7-10).

Hereinafter, the present invention will be described in detail.
1. Antifungal Pharmaceutical Composition The antifungal pharmaceutical composition of the present invention contains lanoconazole (hereinafter sometimes simply referred to as component (a)). Ranoconazole is a compound known as an imidazole antifungal agent. In the present invention, as lanoconazole, any of d-form, l-form and dl-form may be used.

  The blending ratio of the component (a) in the antifungal pharmaceutical composition of the present invention is appropriately set according to the use, formulation form, etc. of the composition. Usually, the blending ratio of the component (a) in the antifungal pharmaceutical composition is such that the total amount of the component (a) is 0.001 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.1 to 2% by weight, particularly preferably. Is exemplified by 0.5 to 1% by weight.

  The antifungal pharmaceutical composition of the present invention has at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent together with the component (a) (hereinafter simply referred to as component (b). In some cases).

  In the present invention, the local anesthetic used as the component (b) is not particularly limited as long as it is pharmacologically or physiologically acceptable. Specific examples of the local anesthetic include lidocaine, oxybuprocaine, dibucaine, procaine, ethyl aminobenzoate, meprilucaine, mepivacaine, bupivacaine, cocaine, diethylaminoethyl, oxypolyethoxydodecane, derivatives thereof and salts thereof Is done. Examples of the salt of the compound include various salts such as organic acid salt, inorganic acid salt, and metal salt. Specific examples of the salt of the above compound include lidocaine hydrochloride, procaine hydrochloride, dibucaine hydrochloride, meprilucaine hydrochloride, and oxybuprocaine hydrochloride. From the viewpoint of more effectively enhancing and expressing the antifungal action, the local anesthetics preferably include lidocaine, dibucaine, procaine and salts thereof, and particularly preferably include lidocaine, procaine and salts thereof. It is done. In the present invention, these local anesthetics may be used alone or in any combination of two or more.

  In the present invention, the antihistamine used as component (b) is not particularly limited as long as it is pharmacologically or physiologically acceptable. Specific examples of the anti-stamine agent include bepotastine, chlorpheniramine, diphenhydramine, diphenylpyraline, diphenylimidazole, iproheptin, emedastine, clemastine, azelastine, levocabastine, olopatadine, mequitazine, loratadine, fexofenadine, cetirizine, oxatonamide, Examples include epinastine, astemizole, ebastine, derivatives thereof, and salts thereof.

  Examples of the salt of the above compound include various salts such as an organic acid salt, an inorganic acid salt, and a metal salt. Specific examples include chlorpheniramine maleate, diphenhydramine hydrochloride, diphenhydramine salicylate, iproheptin hydrochloride, ketotifen fumarate, emedastine fumarate, clemastine fumarate, azelastine hydrochloride, levocabastine hydrochloride, olopatadine hydrochloride, diphenylpyralin hydrochloride, and the like. From the viewpoint of more effectively enhancing the antifungal action of the component (a), the antihistamine is preferably diphenylpyraline, diphenylimidazole, diphenhydramine, chlorpheniramine, and salts thereof, more preferably diphenhydramine, chlorpheniramine. , Derivatives thereof and salts thereof, particularly preferably diphenhydramine and salts thereof. In the present invention, these antihistamines may be used alone or in any combination of two or more.

  Furthermore, in the present invention, the anti-inflammatory agent used as component (b) is not particularly limited as long as it is pharmacologically or physiologically acceptable. Specific examples of the anti-inflammatory agent include allantoin, aldioxa, ictamol, glycyrrhizic acid, glycyrrhetinic acid, salicylic acid, dimethylisopropylazulene, indomethacin, epsilon-aminocaproic acid, berberine, pranoprofen, azulenesulfonic acid, diclofenac, bromfenac, these Derivatives thereof (methyl salicylate, monoglycolic salicylate, etc.) and salts thereof. Examples of the salt of the above compound include various salts such as an organic acid salt, an inorganic acid salt, and a metal salt. Specific examples include aluminum chlorohydroxy allantoinate, dipotassium glycyrrhizinate, diammonium glycyrrhizinate, sodium azulenesulfonate, sodium diclofenac, sodium bromfenac, berberine chloride, berberine sulfate and the like. From the viewpoint of more effectively enhancing the antifungal action of the component (a), the anti-inflammatory agent is preferably allantoin, aldioxa, ictamol, glycyrrhizic acid, glycyrrhetinic acid, salicylic acid, dimethylisopropylazulene, derivatives thereof, and These salts are mentioned, More preferably, allantoin, glycyrrhetinic acid, and these salts are mentioned. In the present invention, these anti-inflammatory agents may be used alone or in any combination of two or more.

  In the present invention, the component (b) preferably used is one or two selected from the group consisting of diphenhydramine, lidocaine, procaine, allantoin, glycyrrhetinic acid, chlorpheniramine, derivatives thereof, and salts thereof. The above components can be mentioned.

The blending ratio of the component (b) in the antifungal pharmaceutical composition of the present invention varies depending on the use and formulation of the composition, the type and blending ratio of the component (a), the type of the component (b), etc. In general, the total amount of component (b) in the antifungal pharmaceutical composition is 0.005 to 20% by weight, preferably 0.01 to 10% by weight, more preferably 0.02 to 5% by weight, particularly preferably 0.04 to 2.5% by weight. Is done. More specifically, the blending ratio of the component (b) in the antifungal pharmaceutical composition is as follows:
When the component (b) is a local anesthetic: usually 0.01 to 20% by weight, preferably 0.05 to 10% by weight, more preferably 0.1 to 5% by weight, particularly preferably 0.5 to 2.5% by weight.
When the component (b) is an antihistamine: usually 0.01 to 20% by weight, preferably 0.05 to 10% by weight, more preferably 0.1 to 5% by weight, particularly preferably 0.2 to 2% by weight.
When the component (b) is an anti-inflammatory agent: usually 0.005 to 6% by weight, preferably 0.01 to 3% by weight, more preferably 0.02 to 2.5% by weight, particularly preferably 0.04 to 2.0%.

In addition, it is desirable that the component (b) contained in the antifungal pharmaceutical composition of the present invention satisfies the above blending ratio, and further the blending ratio with the component (a) satisfies the following range: (a) The component (b) is usually 0.005 to 100 parts by weight, preferably 0.01 to 50 parts by weight, more preferably 0.02 to 10 parts by weight, and particularly preferably 0.04 to 5 parts by weight with respect to 1 part by weight of the component. By containing the components (a) and (b) at such a ratio, it is possible to further enhance the effect of enhancing the antifungal action. More specifically, the following range is suitably exemplified as a blending ratio of the component (b) to 1 part by weight of the component (a): When the component (b) is a local anesthetic: Usually 0.025 to 100 weights Parts, preferably 0.05 to 50 parts by weight, more preferably 0.1 to 10 parts by weight, particularly preferably 0.5 to 5 parts by weight. When the component (b) is an antihistamine: usually 0.025 to 100 parts by weight, preferably 0.05 to 50 parts by weight. Parts by weight, more preferably 0.1 to 10 parts by weight, particularly preferably 0.2 to 4 parts by weight,
When the component (b) is an anti-inflammatory agent: usually 0.005 to 30 parts by weight, preferably 0.01 to 25 parts by weight, more preferably 0.02 to 5 parts by weight, particularly preferably 0.04 to 4 parts by weight.

The antifungal pharmaceutical composition of the present invention can contain various pharmacologically active components and physiologically active components in addition to the above components, as long as the effects of the present invention are not hindered. The type of such components is not particularly limited, and examples include bactericidal components, antipruritic components, vitamins, analgesic components, astringent protecting components, vasoconstrictor components, herbal medicine components, keratolytic agents, and the like. Examples of suitable components include the following components.
Bactericidal ingredients: Acrinol, alkylpolyaminoethylglycine, isopropylmethylphenol, cetylpyridinium, decalinium, benzalkonium, chlorhexidine, cetrimide, resorcin, benzethonium, hinokitiol, benzoic acid, chlorobutanol, acetic acid, phenol, iodotin and their salts (for example Cetylpyridinium chloride, decalinium chloride, benzalkonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, decalinium chloride, benzethonium chloride, etc.).
Terpenoids: borneol, menthol, camphor, geraniol, cineole, anethole, limonene, eugenol, thymol, etc.
Antipruritic ingredients: crotamiton etc.
Vitamins: vitamin A, vitamin B, vitamin C, vitamin E, derivatives thereof, and salts thereof (for example, tocopherol acetate, flavin adenine dinucleotide sodium, pyridoxine hydrochloride, retinol acetate, retinol palmitate, sodium ascorbate, etc.) .
Analgesic ingredients: ketoprofen, flurbiprofen, piroxicam, ibuprofen, mefenamic acid, etc.
Astringent protective components: zinc oxide, tannic acid, chlorohydroxyaluminum, etc.
Vasoconstriction component: ephedrine, tetrahydrozoline, naphazoline, phenylephrine, derivatives thereof, and salts thereof (for example, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, etc.).
Herbal medicine ingredients: Sikon, Hamamelis, Taisan, Toki, Horse Chestnut seeds and their powders and extracts.
Keratolytic agent: urea, diethyl phthalate, etc. Among the above components, terpenoids such as menthol and camphor are particularly suitable components. By further containing a terpenoid, it is possible to provide a composition having further antifungal action and excellent in terms of use. A particularly preferred component is menthol.

Moreover, in the antifungal pharmaceutical composition of the present invention, as long as the effects of the invention are not impaired, a substrate, a carrier and an additive are appropriately selected according to the use and form, and one or more kinds are selected. Can be used in combination. As those base materials, carriers or additives, for example, carriers (water, aqueous solvents, aqueous or oily bases, etc.) generally used for the preparation of solid agents, semisolid agents, liquid agents, etc., pH adjusting agents, Various additives such as a buffer, a stabilizer, a thickener, a surfactant, and a preservative can be exemplified. Although the typical component used for the antifungal pharmaceutical composition of this invention is illustrated below, it is not limited to these.
Base material or carrier component: water, ethanol, other aqueous solvent, sodium carboxymethyl starch, crystalline cellulose, magnesium stearate, cellulose, lactose, hard fat, octyldodecanol, glycerin, light liquid paraffin, gelled hydrocarbon, sucrose Fatty acid ester, tartaric acid, silicone resin, diethanolamine, glyceryl monostearate, dimethylpolysiloxane, squalane, stearyl alcohol, behenyl alcohol, methyl ethyl ketone, stearic acid, glyceryl stearate, cetanol, cetostearyl alcohol, D-sorbitol, hydrogen carbonate Sodium, medium chain fatty acid triglyceride, corn starch, paraffin, palmitic acid, cetyl palmitate, propylene glycol, propylene Glycol fatty acid esters, 1,3-butylene glycol, polyoxyethylene cetyl ether, isopropyl myristate, palmitic acid isopropyl, octyldodecyl myristate, cetyl myristate, glyceryl monostearate, petrolatum and the like.
pH adjusters: inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid; lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, Organic acids such as aspartic acid, glutamic acid, aminoethylsulfonic acid; inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide; monoethanolamine, triethanolamine, di Organic bases such as isopropanolamine, triisopropanolamine and lysine.
Buffer: borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, aspartate, aspartate, etc.
Stabilizer: Dibutylhydroxytoluene (BHT), sodium edetate, sodium sulfite, dry sodium sulfite, butylhydroxyanisole (BHA) and the like.
Thickener: xanthan gum, hydroxypropylmethylcellulose, hydroxypropylcellulose, macrogol 400, macrogol 1500, macrogol 4000, carboxyvinyl polymer, etc.
Surfactant: Polysorbate 60, sorbitan stearate, sorbitan monostearate, diethyl sebacate, polyoxyl stearate, polyoxyethylene hydrogenated castor oil 60, polysorbate 80 and the like.
Preservatives: butyl paraben, methyl paraben, propyl paraben, ethyl paraben, sodium benzoate, benzyl alcohol and the like.

  The antifungal pharmaceutical composition of the present invention is not particularly limited as long as it can be used in an external form. Specific examples of dosage forms of the antifungal pharmaceutical composition of the present invention include creams, solutions, ointments, gels, lotions, patches, sprays, aerosols and the like. Of these, creams, liquids, ointments and sprays are preferable. Particularly preferred are creams, liquids and ointments.

  The antifungal pharmaceutical composition of the present invention can be produced according to an ordinary method by appropriately selecting and blending appropriate base materials, carriers and additives according to the dosage form and the like.

  The antifungal pharmaceutical composition of the present invention is useful as a therapeutic agent for mycosis because the antifungal action is enhanced by using a combination of the component (a) and the component (b). Examples of the mycosis to be treated by the antifungal pharmaceutical composition of the present invention include athlete's foot, tinea, onychomycosis, body tinea, etc. Ringworm, crotch ringworm, folding screen, malassezia folliculitis, oral candidiasis, vulva Superficial mycosis such as candidiasis, vaginal candidiasis, cutaneous candidiasis [finger erosion, interstitial rash (including infantile parasitic erythema), periodontitis]; cutaneous cryptococcosis, deep ringworm, etc. Of deep mycosis. Among these mycoses, the antifungal pharmaceutical composition of the present invention can exert a particularly excellent therapeutic effect on superficial mycosis, particularly ringworm, and is therefore highly useful as a therapeutic agent for these. .

2. Method for enhancing antifungal action As described above, by combining (a) lanoconazole and (b) at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent in combination. The antifungal action of ranoconazole can be enhanced. Accordingly, the present invention provides, from another viewpoint, (a) an antifungal pharmaceutical composition containing lanoconazole, and (b) at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent. (A) A method for enhancing the antifungal action of the antifungal pharmaceutical composition containing the component is provided. In the method, the types and ratios of the component (a), the component (b), and other compounding components used, the form and use of the antifungal pharmaceutical composition, etc. are described in “1. Antifungal pharmaceutical composition”. It is the same as the case of “.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, a test example, etc., this invention is not limited by these.
Test Example 1 Antifungal effect evaluation test -1
Antifungal compositions (Example 1-5 and Comparative Example 1-6) shown in Table 1 were prepared, and the antifungal action of each composition was evaluated according to the following method. First, 60 mL of Mueller Hinton agar medium (manufactured by Eiken Chemical Co., Ltd.) was accurately added as a base layer to a petri dish with a diameter of 15 cm and hardened. Next, exactly 30 mL of Mueller Hinton agar medium inoculated with Trichophyton rubrum (ATCC 28188) to a final concentration of 1 × 10 ⁶ cfu / ml was added as a laminate, and the plate agar medium mixed with Trichophyton rubrum Was made. Subsequently, a paper disk having a diameter of 8 mm on which 0.1 g of the antifungal composition was placed was cultured at 33 ° C. for 5 days on the plate agar medium. After the cultivation, the size (diameter) of the inhibition circle formed on the plate agar medium was measured. The relative activity value of the antifungal action was calculated from the size of the inhibition circle when each composition was used according to the following formula.

  The obtained results are also shown in Table 1. In lidocaine hydrochloride, procaine hydrochloride, chlorpheniramine maleate, allantoin, and glycyrrhetinic acid, almost no antifungal action was observed by themselves (see Comparative Example 2-6). On the other hand, it was confirmed that the antifungal action of ranoconazole was remarkably enhanced when lanoconazole was combined with lidocaine hydrochloride, procaine hydrochloride, chlorpheniramine maleate, allantoin, or glycyrrhetinic acid (Example 1- 5). From this, the antifungal pharmaceutical composition of the present invention is advantageous in that it can exhibit an excellent therapeutic effect by a short-term administration, that is, can shorten the dosing period.

Test Example 2 Evaluation Test 2 for Antifungal Effect
Antifungal compositions (Example 6 and Comparative Examples 7-10) shown in Table 2 were prepared, and the antifungal activity was evaluated for each composition according to the following method. First, 20 mL of Mueller Hinton agar (manufactured by Eiken Chemical Co., Ltd.) was accurately added as a base layer to a 9 cm diameter petri dish and hardened.
Next, add exactly 10 mL of Mueller Hinton agar medium inoculated with Trichophyton mentagrophytes (ATCC 9533) to a final concentration of 1 × 10 ⁷ cfu / ml, and plate agar medium mixed with Trichophyton mentagrophytes Was made. Subsequently, a paper disk having a diameter of 8 mm on which 0.1 g of the antifungal composition was placed was cultured at 33 ° C. for 5 days on the plate agar medium. After the culture, the size (diameter, mm) of the inhibition circle formed on the plate agar medium was measured.

  The results are shown in FIG. As is clear from FIG. 1, when ranoconazole was contained alone at 0.5% by weight and 1% by weight, comparable antifungal activity was shown (Comparative Example 8-9). That is, it was found that the antifungal action reached the upper limit at 0.5% by weight with lanoconazole alone, and that the antifungal action had a limit even when the concentration was further increased with ranoconazole alone. Further, diphenhydramine alone did not show any antifungal action (Comparative Example 10). On the other hand, when lanoconazole and diphenhydramine were combined, an excellent antifungal action that could not be realized with lanoconazole alone was observed (Example 6).

Formulation Example A creamy, liquid or ointment-like antifungal pharmaceutical composition (Examples 7-50) having the following composition is prepared.

Claims (12)

(a) Ranoconazole, and
(b) An antifungal pharmaceutical composition comprising at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent.   The antifungal pharmaceutical composition according to claim 1, wherein the component (b) is at least one selected from the group consisting of diphenhydramine, allantoin, chlorpheniramine, derivatives thereof, and salts thereof.   The antifungal pharmaceutical composition according to claim 1 or 2, which is a composition for treating ringworm.   The antifungal pharmaceutical composition according to any one of claims 1 to 3, wherein the total amount of the component (a) is 0.001 to 10% by weight based on the total amount of the composition.   The antifungal pharmaceutical composition according to any one of claims 1 to 4, wherein the total amount of the component (b) is 0.005 to 20% by weight based on the total amount of the composition.   The antifungal pharmaceutical composition according to any one of claims 1 to 5, wherein the component (b) is contained at a ratio of 0.005 to 100 parts by weight with respect to 1 part by weight of the component (a).   The antifungal pharmaceutical composition according to any one of claims 1 to 6, which is a cream, liquid, or ointment. The antifungal pharmaceutical composition according to any one of claims 1 to 7, wherein the fungus is Trichophyton rubrum . The antifungal pharmaceutical composition comprises
(I) Allantoin 0.2% by mass, Ranoconazole 1.0% by mass, Glycerin 20.0% by mass, Diphenhydramine 1.0% by mass, Polyoxyethylene monostearate 0.5% by mass, Isopropyl myristate 2.0% by mass, Stearyl alcohol 1.0% by mass, Carboxyvinyl polymer 0.8 A composition containing 1% by mass, diisopropanolamine and purified water, or (ii) 1.0% by mass of panthenol, 1.0% by mass of lanoconazole, 50.0% by mass of glycerol, 0.5% by mass of chlorpheniramine maleate, 0.0036% by mass of Toki extract The antifungal pharmaceutical composition according to any one of claims 1 to 8, except that the composition contains 20.0% by mass of Macrogol 400, 1.5% by mass of carboxyvinyl polymer, diisopropanolamine and purified water. .   A method for enhancing the antifungal activity of an antifungal pharmaceutical composition containing ranoconazole, comprising: (a) an antifungal pharmaceutical composition containing lanoconazole, comprising (b) a local anesthetic, an antihistamine, and an anti-inflammatory agent An enhancement method comprising blending at least one component selected from the group. A method for imparting an antifungal effect to an antifungal pharmaceutical composition containing ranoconazole, comprising:
(a) an antifungal pharmaceutical composition containing ranoconazole,
(b) A method comprising blending at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent. A potentiator of antifungal action of a composition containing ranconazole, comprising at least one component selected from the group consisting of a local anesthetic, an antihistamine, and an anti-inflammatory agent.

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