US 20090099202A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0099202 A1 Shirouzu et al. (43) Pub. Date: Apr. 16, 2009

(54) EXTERNAL PREPARATION FOR ATHLETES (30) Foreign Application Priority Data FOOT TREATMENT Jun. 25, 2003 (JP) ...... 2003/181264 Dec. 5, 2003 (JP) ...... 2003/4O7136 (76) Inventors: Toshihiro Shirouzu, Tosu-shi (JP); O O Youichi Kawamura, Tosu-shi (JP); Publication Classification Hiroki Kawatsura, Tosu-shi (JP); (51) Int. Cl. Mitsuhiko Tokunaga, Tosu-shi (JP) A63L/047 (2006.01) A63L/35 (2006.01) Correspondence Address: A6IIA63L/464 3L/27 30.82006.O1 Jane Massey Licate A63/496 (2006.01) Licata & Tyrrell P.C. A6II 3/47 (2006.01) 66 East Main Street A6II 3/19 (2006.01) Marlton, NJ 08053 (US) A6IP3 L/10 (2006.01) (52) U.S. Cl...... 514/254.07: 514/738: 514/649; (21) Appl. No.: 12/338,096 514/655; 514/488: 514/396; 514/399; 514/312: 514/557 (22) Filed: Dec. 18, 2008 (57) ABSTRACT External preparations for athlete's foot treatment capable of Related U.S. Application Data enhancing patient's compliance and capable of reducing the symptom of rubefaction, comprising an anti-trichophyton (63) Continuation of application No. 10/561,499, filed on drug mixed with at least one compound selected from among Dec. 19, 2005, filed as application No. PCT/JP2004/ 1-menthol, menthol analogue compounds and bactericidal 008992 on Jun. 25, 2004. compounds. US 2009/0099202 A1 Apr. 16, 2009

EXTERNAL PREPARATION FOR ATHLETES fungal agent originally has in not a serious degree, is FOOT TREATMENT enhanced, whereby further enhancement of patient's compli ance has been desired. 0009 Patent document 1: JP. A1, 3-38522 0001. This patent application is a continuation of U.S. 0010 Patent document 2: JP. A1, 9-176014 application Ser. No. 10/561,499, filed Dec. 19, 2005, which is 0011 Patent document 3: JP. A1, 2004-35411 the National Stage of International Application No. PCT/ 0012 Patent document 4: JP. A1, 2004-1495.08 JP2004/008992, filed Jun. 25, 2004, which claims the benefit 0013 Patent document 5: JP. A1, 7-233088 of priority from Japanese Application No. 2003-407136, filed 0014 Patent document 6: JP. A1, 8-20527 Dec. 5, 2003 and Japanese Application No. 2003-181264, filed Jun. 25, 2003, teachings of each of which are herein DISCLOSURE OF THE INVENTION incorporated by reference in their entirety. Problems to be Solved by the Invention TECHNICAL FIELD 0015. Although an anti-trichophyton drug such as buten afine hydrochloride has a very excellent action 0002 The invention relates to an external preparation for even in alone, the invention provides an external preparation athlete's foot treatment, comprising an anti-trichophyton for athlete's foot treatment, having a more excellent effect in drug and at least one compound, which is selected from points such as enhancement of patient's compliance and 1-menthol, menthol analogue compounds and bactericidal reduction of the symptom of rubefaction. compounds, as an essential ingredient. Means to Solve the Invention BACKGROUND ART 0016. After extensive researches to enhance patient's 0003. As an anti-fungal agent used for an external prepa compliance on an external preparation for athlete's foot treat ration for athlete's foot treatment, various antifungal agents ment, the inventors found out that not only Trichophyton but Such as , , thiocarbamic acid, , also other fungi such as Candida albicans and a skinhabitual and morpholine types have been developed and bacteria Such as Staphylococus aureus are effectively reduced have been on the market. by an external preparation containing an anti-trichophyton 0004. However, each of anti-fungal agents has a difference drug and at least one compound selected from 1-menthol, in its width of the antifungal spectrum and the antifungal menthol analogue compounds and bactericidal compounds as activity, and there is no antifungal agent which shows a strong an essential ingredient. antibacterial activity over Tychophyton and other fungi, for 0017 Namely, the invention relates to an external prepa example, Candida albicans and the like, fungi in general, ration for athlete's foot treatment, comprising an anti-tricho whereby an external preparation and the like, in which an phyton drug mixed with at least one compound selected from antifungal activity or the like are strengthened by a combina 1-menthol, menthol analogue compounds and bactericidal tion of two or more of antifungal agents, are reported (ex. See compounds. Patent documents 1-3). 0018. In addition, the invention relates to the external 0005. In addition, although a composition with a strength preparation for athlete's foot treatment, wherein the anti ened antifungal activity is also reported, in which an ally trichophyton drug and at least one compound selected from lamine type antifungal agent and menthol are blended, this 1-menthol, menthol analogue compounds and bactericidal increases the activity against so called Tychophyton and does compounds are blended in 0.1-10% by mass and 0.5-5% by not strengthen the antifungal activity against other fungi such mass respectively. as Candida albicans (ex. See Patent document 4). 0019. Further, the invention relates to the external prepa 0006 Further, although there are a preparation in which a ration for athlete's foot treatment, wherein the menthol ana peripheral vasodilator is added to an antifungal agent (ex. See logue compound is 3-1-menthoxypropane-1,2-diol. Patent document 5) and a preparation in which an antifungal 0020. The invention relates to an external preparation for agent is added with a Substance Such as methyl salicylate, athlete's foot treatment, wherein the bactericidal compound glycol salicylate, crotamitone, peppermint oil or 1-menthol to is isopropylmethylphenol. improve a horny layer accumulation of the antifungal agent 0021. In addition, the invention relates to an external (ex. see Patent document 6), they do not show any excellent preparation for athlete's foot treatment, wherein the anti antifungal property against Tychophyton and other fungi trichophyton drug is selected from benzylamine type, ally including Candida albicans and the like. lamine type, thiocarbamic acid type and imidazole type anti 0007. In addition, any external preparation disclosed in the fungal agents. above documents did not suppress the growth of skinhabitual 0022. Further, the invention relates to an external prepa bacteria Such as Staphylococus aureus and did not have ration for athlete's foot treatment, wherein the anti-trichophy effects in a case that the skin habitual bacteria Such as Can ton drug is one kind selected from hydrochloride, dida albicans and Staphylococus aureus, which accelerated hydrochloride, , , ketocona the discomfort of athlete's foot (itch, bad smell, etc.), grew Zole, neticonazole hydrochloride and lanoconazole. abnormally, therefore, it could not be said that it satisfactorily 0023. Furthermore, the invention relates to an external enhanced patient's compliance after applying such external preparation for athlete's foot treatment, wherein the anti preparation described above. trichophyton drug and 1-menthol are blended. 0008 Furthermore, in case of using the above substance 0024. The invention relates to the external preparation for improving a horny layer accumulation, a frequency of occur athlete's foot treatment, wherein butenafine hydrochloride, rence of a light symptom Such as rubefaction, which an anti 1-menthol and isopropylmethylphenol are blended. US 2009/0099202 A1 Apr. 16, 2009

0025. In addition, the invention relates to the external specifically, include butenafine hydrochloride, terbinafine preparation for athlete's foot treatment, also comprising at hydrochloride, tolnaftate, , bifonazole, ketocona least one kind of a local anesthetic, an antihistamine and an Zole, , nitrate, neticonazole hydro anti-inflammatory drug. chloride, lanoconazole, , , Sulcona 0026. Further, the invention relates to the external prepa Zole, , and , though ration for athlete's foot treatment, wherein the local anes butenafine hydrochloride, terbinafine hydrochloride, tolnaf thetic is dibucaine hydrochloride, or lidocaine or its salt. tate, bifonazole, , neticonazole hydrochloride 0027. Furthermore, the invention relates to the external and lanoconazole are preferable, and butenafine hydrochlo preparation for athlete's foot treatment, wherein the antihis ride is particularly preferable. tamine is chlorpheniramine maleate, or diphenhydramine or 0036 Although butenafine hydrochloride is high in activ its salt. ity against Trichophyton, the activity against Candida albi 0028. Further, the invention relates to the external prepa cans and Staphylococus aureus can not be expected much, ration for athlete's foot treatment, wherein the anti-inflam and therefore, by using it with at least one kind of compound matory drug is glycyrrhetinic acid or its salt, or allantoin. in combination, which are selected from 1-menthol, a menthol 0029. Further, the invention relates to the external prepa analogue compound and a bactericidal compound, preferably ration for athlete's foot treatment, wherein butenafine hydro the activity against Trichophyton as well as Candida albicans chloride, 1-menthol, dibucaine hydrochloride, chlorphe and Staphylococus aureus can synergistically be enhanced. niramine maleate and glycyrrhetinic acid are blended. 0037 Compounds used together with the anti-trichophy 0030 Consequently, in an anti-trichophyton drugs of ton drug in the invention include 1-menthol, in addition, men which antibacterial action against fungi except Trichophyton thol analogue compounds Such as d1-menthol, 3-1-menthoX is not necessarily satisfactory, the external preparation for ypropane-1,2-diol, isopulegol, neoisopulegol, neomenthol, athlete's foot treatment of the invention suppresses the growth isomenthol, neo-isomenthol, citronellol and linallol, and bac of skinhabitual fungi such as Staphylococus aureus and Can tericidal compounds such as isopropylmethylphenol, dequal dida albicans, which become a cause of a bad smell of foot inium chloride, dequalinium acetate, benzethonium chloride, due to athlete's foot, aggravation athlete's foot and the like, benzalkonium chloride, chlorhexidine chloride, chlorhexi without combination of an antifungal agent, and not only dine gluconate, hinokitiol and resorcin, though 3-1-menthox improves atherapeutic effect for athlete's foot compared with ypropane-1,2-diol, isopropylmethylphenol and the like are a case simply to reduce Trichophyton but has effect to preferably used. enhance patient's compliance. 0038. Further, combined use of 1-menthol and isopropyl 0031. In addition, by blending at least one kind of com methylphenol are particularly preferable. pound, preferably two kinds of compounds in combination, 0039. In addition, by blending at least one kind of com which were selected from 1-menthol, a menthol analogue pound in not less than 0.5% by mass in total, which are compound and a bactericidal compound, it was found that an selected from 1-menthol, amenthol analogue compoundanda anti-trichophyton drug could synergistically Suppress the bactericidal compound, the growth of Candida albicans and growth of Staphylococus aureus and Candida albicans in a Staphylococus aureus can preferably be Suppressed, and lower blend amount. making it not more than 5% by mass is preferable because a 0032. Further, if said external preparation for athlete's foot problem of difficult drying in a liquid preparation does not treatment contains at least one kind among a local anesthetic, OCCU. an antihistamine and an anti-inflammatory drug, it suppresses 0040 Although the kinds of antihistamines used in the rubefaction which an anti-trichophyton drug rarely produces invention include cholorpheniramine or its salts, diphenhy even if in a slight degree, and further favorable enhancement dramine or its salts, promethazine, meduitazine and the like, of compliance can be obtained. Although this effect can be cholorpheniramine, diphenhydramine or its salts are prefer obtained by blending at least one kind among the local anes able. thetic, the antihistamine and the anti-inflammatory drug, it is 0041. The concentration of the antihistamine is preferably possible to get further favorable effect by combination of two 0.05-5.0% by mass, more preferably 0.05-2.0% by mass. By or more kinds. making the blend amount of the antihistamine not less than 0.5% by mass, the effect as the antihistamine can easily be BEST EMBODIMENT FOR CARRYING OUT obtained, and even if making it not less than 5.0% by mass it THE INVENTION does not improve the effect as the antihistamine. 0033. As described above, in the external preparation for 0042. Although the kinds of local anesthetics used in the athlete's foot treatment, an anti-trichophyton drug is blended invention include lidocaine or its salts, dibucaine or its salts, in a specific concentration, that is, 0.1-10.0% by mass, pref tetracaine or its salts, procaine or its salts, ethyl aminoben erably 1-5% by mass, with at least one kind of compound Zoate and the like, dibucaine hydrochloride, or lidocaine or is selected from 1-menthol, a menthol analogue compound and salts are preferable. a bactericidal compound in the range of 0.5-5% by mass, 0043. The concentration of the local anesthetic is prefer preferably 1-3% by mass in total. ably 0.01-5.0% by mass, more preferably 0.05-2.0% by mass. 0034. By making the blend amount of the anti-trichophy By making the blend amount of the local anesthetic not less ton drug not less than 0.1% by mass, the effect as an anti than 0.01% by mass, the effect as the local anesthetic can trichophyton agent can easily be obtained, and even if blend easily be obtained, and even if making it not less than 5.0% by ing not less than 10% by mass, the effect as the anti mass it does not improve the effect as the local anesthetic. trichophyton agent is hardly improved. 0044) The kinds of anti-inflammatory drugs used in the 0035. The anti-trichophyton drugs used in the invention invention include glycyrrhetinic acid or its salts, non-steroi are benzylamine type, allylamine type, thiocarbamic acid dal types such as methyl salicylate, glycol salicylate, type and imidazole type and triazole type antifungal agents, indometacin, diclofenac, felbinac, piroXicam, ketoprofen, US 2009/0099202 A1 Apr. 16, 2009

ibuprofen piconol, bufeXamac or allantoin, and steroidal 0055. The external preparation for athlete's foot treatment types such as amcinonide, prednisolone Valerate, diflucor of the invention may contain a percutaneous absorption pro tolone Valerate, dexamethasone Valerate, betamethasone val moter, and if said percutaneous absorption promoter is one or erate, dexamethasone acetate, hydrocortisone acetate, dex more compounds in which a percutaneous absorption pro amethasone, triamcinolone acetonide, halcinonide, moting action of the anti-trichophyton drug is recognized, betamethasone dipropionate, fluocinonide, fluocinolone any compound may be used. acetonide, prednisolone, deprodone propionate, clobetasol propionate or betamethasone, though glycyrrhetinic acid or 0056. Examples include C-C fatty acids, fatty alcohols, its salts, or allantoin are preferable. fatty acid esters or fatty acid ethers, aromatic organic acids, 0045. The concentration of the anti-inflammatory drug is aromatic alcohols, aromatic organic acid esters or aromatic preferably 0.05-10.0% by mass, more preferably 0.05-2.0% organic acid ethers, furthermore lactic acid esters, acetic acid by mass. By making the blend amount of the anti-inflamma esters, monoterpene compounds, sesquiterpene compounds, tory drug not less than 0.05% by mass, the effect as the AZone or AZone derivatives, glycerol fatty acid esters, Sorbi anti-inflammatory drug can easily be obtained, and even if tan fatty acid esters, polysorbates, polyethylene glycol fatty making it not less than 5.0% by mass it does not improve the acid esters, polyoxyethylene hydrogenated castor oils and effect as the anti-inflammatory drug. Sucrose fatty acid esters. Fatty acid esters and fatty alcohols 0046. The formula in which dibucaine hydrochloride, are preferable, in particular, isopropyl miristate, isopropyl cholorpheniramine maleate and glycyrrhetinic acid are palmitate, Sorbitan monooleate and oleyl alcohol are prefer blended for an external preparation for athlete's foot treat able. ment consisting ofbutenafine hydrochloride and 1-mentholis 0057. Further, the external preparation for athlete's foot particularly preferable because it can synergistically enhance treatment of the invention may contain an antioxidant, an the compliance. antiseptic agent, a preservative, a moisturizing agent, a che 0047. Further, the external preparation described in the late agent and other additive which are usually blended in a invention includes a liquid preparation, a cream, a lotion, an skin external preparation. aerosol preparation, a patch and the like. 0058. In the following, the invention is explained in more 0048. The external preparation of the invention may con detail by the examples. The invention, however, is not limited tain a usual base according to its form, and in the case of the to these examples, and various changes may be made without liquid preparation or the lotion, a lower alcohol, a polyhydric departing from the spirit of the invention. Further, in the alcohol, water or the like may be contained. examples, '%' means '96 by mass unless otherwise specified. 0049. In the case of the cream, an oily base, a higher alcohol, a fatty acid ester, or a polyhydric alcohol or its EXAMPLES 1-6 derivative, a Surfactant, a gellant, water or the like may be contained. Aerosol Preparations 0050. As the aerosol preparation, a lower alcohol, a poly hydric alcohol or the like may be contained to dissolve the Preparation Method for Aerosol Preparations drug of the invention. 0051. As the lower alcohol used in the above formulas, 0059 A solid ingredient was dissolved in ethanol, and to methanol, ethanol, denatured ethanol, isopropanol and the this was added with other ingredients to prepare a raw solu like may be illustrated. tion. The raw solution and a propellant were filled in an 0052. As the oily base, liquid paraffin, vaseline, paraffin aerosol can to obtain the aerosol preparations of the examples wax and the like may be illustrated, and the higher alcohol is 1-6. Coo alcohol, preferably cetyl alcohol, Stearyl alcohol, ceto stearyl alcohol and oleyl alcohol are preferable. As the poly TABLE 1 hydric alcohol and its derivative, there are glycerol, ethylene glycol. propylene glycol, 1,3-butylene glycol, dipropylene Examples of aerosol preparations glycol, polyethylene glycol, polypropylene glycol, and these Examples esters or ethers. The fatty acid ester is a higher fatty acid ester, and esters of a higher fatty acid Such as myristic acid, palmitic Composition 1 2 3 acid, Stearic acid or oleic acid, with a lower alcohol (C) Butenafine hydrochloride 1 O.S 1 may be illustrated. Diphenhydraminehydrochloride O O.2 O.2 Chlorpheniraminemaleate O O.S O.S 0053. The surfactant may be an anionic surfactant such as Glycyrrhetinic acid O O O.2 polyoxyethylenealkylether phosphate or sodium alkylsulfate, I-Menthol 2 1 3 a Sorbitan fatty acid ester Such as Sorbitan sesquioleate, Sor Ethano 45 50 55 bitan trioleate, Sorbitan monostearate, Sorbitan monolaurate, Isopropyl myristate 4 4 8 polyoxyethylene Sorbitan Stearate, a nonionic Surfactant Such 1,3-Butylene glycol 16 2O 12 as polyoxyethylene nonylether, monooxyethylene cetylether Purified water 32 21.8 20.1 or monooxyethylene laurylether, in addition, a cationic Sur Raw liquid in total 100 1OO 1OO factant Such as benzethonium chloride or benzalkonium chlo Above raw liquids amount 50 30 35 Dimethyl ether 30 50 25 ride, or an amphoteric Surfactant. LP gas - A 2O 40 0054 The gel-type vehicle includes carboxyvinyl poly mer, hydroxyethyl cellulose, hydroxypropyl cellulose, Aerosol in total 100 1OO 1OO methyl-cellulose, ethylcellulose, carboxymethyl cellulose and the like. US 2009/0099202 A1 Apr. 16, 2009

TABLE 2 TABLE 3 Examples Examples of creams Composition 4 5 6 - Examples Butenafine hydrochloride 5 O.S 1 Composition 7 8 9 Lidocaine O 1.5 O.S Diphenhydraminehydrochloride O O.S O.S le By file hydrochloride 2 i 1 1 Dipotassium glycyrrhetinate O O O.2 Diphenhydramine 5 Allantoin O.2 1.5 O Glycyrrhetinic acid 5 O.S -Menthol 2 1 3 -Menthol 1 3 2 Ethanol 25 60 50 Liquid paraffin 10 10 8 Sopropyl myristate 4 4 8 Sopropyl myristate 10 5 2 Polyethylene glycol 200 27 8 13 Cetanol 2 3 Purified water 36.8 23 23.8 Stearyl alcohol 2 9 3 Polyoxyethylene cetyl ether 2 4 Raw liquid in total 100 1OO 1OO Polyoxyethylene 5 Above raw liquids amount 50 30 35 arboxyvinylt polymers 1.5 Dimethyl ether 30 50 25 Aqueous Lidocaine hydrochloride O.S LP gas 2O 2O 40 phase Dibucaine hydrochloride O.S Chlorpheniramine hydrochloride O.OS Aerosol in total 100 1OO 1OO Chlorpheniramine maleate O.S Diethanolamine O.2 O.2 O.2 Methylparaben O.2 O.2 O.2 Purified water balance balance balance Preparation Method for Creams Total 100 1OO

0060. As to a preppreparation method for a cream, an aqueousC Preparation Method for Liquid Preparations phase and an oil phase were each heated at 80°C., mixed and emulsified under a sufficient stirring. Then, the emulsion was 0061. As to a preparation method for a liquid preparation, 9. s an active ingredient was dissolved in ethanol, and added to cooled under stirring to room temperature to obtain the other ingredients to obtain the liquid preparation of the creams of the examples 7-9. examples 10-17 and the comparative examples 1-3. TABLE 4 Examples of Liquid Preparations Example Example Example Example Example Example Composition 10 11 12 13 14 15

Butenafine hydrochloride 1.O 1.O 1.O 1.O 1.O 1.O Dibucaine hydrochloride O.S O.S O.S O.S O.S O.S Chlorpheniramine maleate O.S O.S O.S O.S O.S O.S Glycyrrhetinic acid O.2 O.2 O.2 O.2 O.2 O.2 Isopropylmethylphenol O O O O O O I-Menthol 1 2 3 O O O MP2OH O O O O.S 1.O 2.0 Propylene carbonate 10 10 10 10 10 10 Ethanol 30 30 30 30 30 30 Sodium hyaluronate O.O1 O.O1 O.O1 O.O1 O.O1 O.O1 Purified water balance balance balance balance balance balance

Total 1OO 100 1OO 100 1OO 100 Example Example Comparative Comparative Comparative Composition 16 17 example 1 example 2 example 3

Butenafine hydrochloride 1.O 1.O 1.O 1.O 1.O Dibucaine hydrochloride O.S O.S O.S O.S O.S Chlorpheniramine maleate O.S O.S O.S O.S O.S Glycyrrhetinic acid O.2 O.2 O.2 O.2 O.2 Isopropylmethylphenol O O.S O O O I-Menthol O 2 O O O MP2OH 4.0 O O O.1 O.2 Propylene carbonate 10 10 10 10 10 Ethanol 30 30 30 30 30 Sodium hyaluronate O.O1 O.O1 O.O1 O.O1 O.O1 Purified water balance balance balance balance balance

Total 1OO 1OO 100 100 1OO MP2OH: 3-1-Menthoxypropane-1,2-diol US 2009/0099202 A1 Apr. 16, 2009

Test Example 1 TABLE 6 Sensory Test Results 0062. The preparations of the examples 10-12 and the Observation results of inhibition ring comparative example 1 were applied to 20 patients with a skin diameter of inhibition ring in parentheses fungus disease, showing the number of persons who got the Test bacteria: Test bacteria: refreshing feeling and the efficacy feeling (in particular, alle Staphylococtisatiretts Candida albicans viation of itch). Butenafine Absence o Absence o hydrochloride: 1% inhibition ring inhibition ring L-Menthol: O-6 TABLE 5 Butenafine Absence o Absence o hydrochloride: 1% inhibition ring inhibition ring Sensory test L-Menthol: 0.1% Butenafine Absence o Absence o Comparative hydrochloride: 1% inhibition ring inhibition ring Example 10 Example 11 Example 12 example 1 L-Menthol: O.2% Butenafine Absence o Presence o Refreshing 12 persons 14 persons, 17 persons 8 persons hydrochloride: 1% inhibition ring inhibition feeling 20 persons 20 persons 20 persons 20 persons L-Menthol: 0.5% ring (10 mm) Efficacy 5 persons, 7 persons 10 persons, 2 persons Butenafine Presence o Presence o feeling 20 persons 20 persons 20 persons 20 persons hydrochloride: 1% inhibition inhibition (alleviation L-Menthol: 1% ring (9mm) ring (10 mm) of itch) Butenafine Presence o Presence o hydrochloride: 1% inhibition inhibition L-Menthol: 2% ring (10 mm) ring (12 mm) Butenafine Presence o Presence o hydrochloride: 1% inhibition inhibition Test Example 2 L-Menthol:4% ring (10 mm) ring (14 mm) Evaluation of Antibacterial Action by Halo Test 0077. The antibacterial action was confirmed by blend of not less than 0.5% against Candida albicans and not less than 0063 Test Method 1% against Staphylococus aureus. 0078. The evaluation of the antibacterial action by Halo 0064 1. The test bacteria (Staphylococus aureus, Candida test was carried out by the formulas in the examples 13-17 and albicans) were inoculated to a SCD agar culture medium the comparative examples 1-3, described in Table 4. The test cooled to an appropriate temperature after a high-pressure method is same with that in the test example 2, and the results wet sterilization, adjusting the bacterial count to about 10/ are shown as follows. mL. 0065 2. The test bacteria incubated in 1... were thinly TABLE 7 applied to the SCD agar culture medium formed beforehand into a multilayer, cooled and fixed at room temperature. Results 0066 3.50 uL of the following samples were applied to a Observation results of inhibition ring sterilized paper disc (diameter: 8 mm) for an antibiotic test, diameter of inhibition ring in parentheses which was placed on the culture medium of 2. Test bacteria: Test bacteria: 0067 4.3. was incubated at 35°C. for 24-48 hours, and the Staphylococtisatiretts Candida albicans presence or the absence of a growth inhibition ring which Comparative Absence o Absence o occurred around the paper disc was observed. example 1 inhibition ring inhibition ring Comparative Absence o Absence o 0068 Test Samples example 2 inhibition ring inhibition ring 0069. A liquid, in which butenafine hydrochloride as an Comparative Absence o Absence o example 3 inhibition ring inhibition ring anti-trichophyton drug and only 1-menthol as an auxiliary Example 13 Presence o Presence o agent were blended, was prepared on an experimental basis inhibition inhibition (the below formula), and the antibacterial actions against ring (11 mm) ring (11 mm) Example 14 Presence o Presence o Staphylococus aureus, Candida albicans were evaluated. The inhibition inhibition results are shown in Table 6. ring (13 mm) ring (13 mm) Example 15 Presence o Presence o 0070 The blend amount of 1-menthol was set in 7 classes inhibition inhibition in the range of 0-4%. ring (14 mm) ring (15 mm) 0071 Test formula of liquid preparation for athlete's foot Example 16 Presence o Presence o inhibition inhibition treatment ring (18 mm) ring (16 mm) 0072. Butenafine hydrochloride: 1% Example 17 Presence o Presence o inhibition inhibition 0073 1-Menthol: 0-4% ring (14.5 mm) ring (16 mm) 0074) Macrogol 400: 20% 0075 Ethanol: 30% 007.9 The antibacterial action against Staphylococus 0076 Purified water: Residual quantity aureus and Candida albicans was confirmed in the concen US 2009/0099202 A1 Apr. 16, 2009 tration of not less than 0.5% of 3-1-menthoxypropane-1,2- benzylamine type, allylamine type, thiocarbamic acid type diol. In addition, in the formula in which isopropylmeth and imidazole type antifungal agents. ylphenol and 1-menthol were blended in combination, it was 4. The external preparation for athlete's foot treatment of also confirmed to be able to carry out effectively the suppres claim 1, wherein the anti-trichophyton drug is one kind sion of Staphylococus aureus and Candida albicans. selected from butenafine hydrochloride, terbinafine hydro chloride, tolnaftate, bifonazole, ketoconazole, neticonazole INDUSTRIAL APPLICABILITY hydrochloride and lanoconazole. 5. The external preparation for athlete's foot treatment of 0080. By using an external preparation for athlete's foot claim 4 wherein butenafine hydrochloride and 3-1-menthox treatment containing an anti-trichophyton drug and a com ypropane-1,2-diol are blended. pound Suppressing the growth of Staphylococus aureus and 6. The external preparation for athlete's foot treatment of Candida albicans as an essential ingredient, it becomes pos claim 1 further comprising at least one kind of a local anes sible to reduce effectively not only Trichophyton but also thetic, an antihistamine and an anti-inflammatory drug. other fungi such as Candida albicans and a skin habitual 7. The external preparation for athlete's foot treatment of bacteria Such as Staphylococus aureus, and therefore, the claim 6, wherein the local anesthetic is dibucaine hydrochlo application to a wide-ranging use such a therapy for a fungus ride, or lidocaine or its salt. infectious disease or the like can be made. 8. The external preparation for athlete's foot treatment of claim 6, wherein the antihistamine is chlorpheniramine male What is claimed is: ate, or diphenhydramine or its salt. 1. An external preparation for athlete's foot treatment, 9. The external preparation for athlete's foot treatment of comprising an anti-trichophyton drug mixed with 3-1-men claim 6, wherein the anti-inflammatory drug is glycyrrhetinic thoxypropane-1,2-diol. acid or its salt, or allantoin. 2. The external preparation for athlete's foot treatment of 10. The external preparation for athlete's foot treatment of claim 1, wherein the anti-trichophyton drug and 3-1-men claim 6 wherein butenafine hydrochloride, 3-1-menthox thoxypropane-1,2-diol are blended in 0.1-10% by mass and ypropane-1,2-diol, dibucaine hydrochloride, chlorphe 0.5-5% by mass respectively. niramine maleate and glycyrrhetinic acid are blended. 3. The external preparation for athlete's foot treatment of claim 1, wherein the anti-trichophyton drug is selected from c c c c c