US20070099932A1

US20070099932A1 - External preparation for athlete's foot treatment

Info

Publication number: US20070099932A1
Application number: US10/561,499
Authority: US
Inventors: Toshihiro Shirouzu; Youichi Kawamura; Hiroki Kawatsura; Mitsuhiko Tokunaga
Original assignee: Hisamitsu Pharmaceutical Co Inc
Current assignee: Hisamitsu Pharmaceutical Co Inc
Priority date: 2003-06-25
Filing date: 2004-06-25
Publication date: 2007-05-03
Also published as: JP2008239626A; EP1637132A1; EP1637132B1; US20110269794A1; US20090099202A1; JP4828563B2; JP2009007365A; JPWO2005000287A1; WO2005000287A1; EP1637132A4; DE602004029465D1; US8664224B2

Abstract

External preparations for athlete's foot treatment capable of enhancing patient's compliance and capable of reducing the symptom of rube faction, comprising an anti-trichophton drug mixed with at least one compound selected from among 1-menthol, menthol analogue compounds and bactericidal compounds.

Description

DETAILED DESCRIPTION OF THE INVENTION

1. Technical Field
The invention relates to an external preparation for athlete's foot treatment, comprising an anti-trichophton drug and at least one compound, which is selected from l-menthol, menthol analogue compounds and bactericidal compounds, as an essential ingredient.
2. Background Art
As an anti-fungal agent used for an external preparation for athlete's foot treatment, various antifungal agents such as imidazole, triazole, thiocarbamic acid, benzylamine, allylamine and morpholine types have been developed and have been on the market.
However, each of anti-fungal agents has a difference in its width of the antifungal spectrum and the antifungal activity, and there is no antifungal agent which shows a strong antibacterial activity over Trychophyton and other fungi, for example, Candida albicans and the like, fungi in general, whereby an external preparation and the like, in which an antifungal activity or the like are strengthened by a combination of two or more of antifungal agents, are reported (ex. see Patent documents 1-3).
In addition, although a composition with a strengthened antifungal activity is also reported, in which an allylamine type antifungal agent and menthol are blended, this increases the activity against so called Trychophyton and does not strengthen the antifungal activity against other fungi such as Candida albicans (ex. see Patent document 4).
Further, although there are a preparation in which a peripheral vasodilator is added to an antifungal agent (ex. see Patent document 5) andapreparation in which an antifungal agent is added with a substance such as methyl salicylate, glycol salicylate, crotamitone, peppermint oil or l-menthol to improve a horny layer accumulation of the antifungal agent (ex. see Patent document 6), they do not show any excellent antifungal property against Trychophyton and other fungi including Candida albicans and the like.
In addition, any external preparation disclosed in the above documents did not suppress the growth of skin habitual bacteria such as Staphylococus aureus and did not have effects in a case that the skin habitual bacteria such as Candida albicans and Staphylococus aureus, which accelerated the discomfort of athlete's foot (itch, bad smell, etc.), grew abnormally, therefore, it could not be said that it satisfactorily enhanced patient's compliance after applying such external preparation described above.
Furthermore, in case of using the above substance improving a horny layer accumulation, a frequency of occurrence of a light symptom such as rube faction, which an antifungal agent originally has in not a serious degree, is enhanced, whereby further enhancement of patient's compliance has been desired.
Patent document 1: JP, A1, 3-38522
Patent document 2: JP, A1, 9-176014
Patent document 3: JP, A1, 2004-35411
Patent document 4: JP, A1, 2004-149508
Patent document 5: JP, A1, 7-233088
Patent document 6: JP, A1, 8-20527

DISCLOSURE OF THE INVENTION

[Problems to be Solved by the Invention]
Although an anti-trichophton drug such as butenafine hydrochloride has a very excellent antifungal action even in alone, the invention provides an external preparation for athlete's foot treatment, having a more excellent effect in points such as enhancement of patient's compliance and reduction of the symptom of rube faction.
[Means to Solve the Invention]
After extensive researches to enhance patient's compliance on an external preparation for athlete's foot treatment, the inventors found out that not only Trichophyton but also other fungi such as Candida albicans and a skin habitual bacteria such as Staphylococus aureus are effectively reduced by an external preparation containing an anti-trichophton drug and at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds as an essential ingredient.
Namely, the invention relates to an external preparation for athlete's foot treatment, comprising an anti-trichophyton drug mixed with at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds.
In addition, the invention relates to the external preparation for athlete's foot treatment, wherein the anti-trichophton drug and at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds are blended in 0.1-10% by mass and 0.5-5% by mass respectively.
Further, the invention relates to the external preparation for athlete's foot treatment, wherein the menthol analogue compound is 3-l -menthoxypropane-1,2-diol.
The invention relates to an external preparation for athlete's foot treatment, wherein the bactericidal compound is isopropylmethylphenol.
In addition, the invention relates to an external preparation for athlete's foot treatment, where in the anti-trichophyton drug is selected from benzylamine type, allylamine type, thiocarbamic acid type and imidazole type antifungal agents.
Further, the invention relates to an external preparation for athlete's foot treatment, wherein the anti-trichophyton drug is one kind selected from butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, bifonazole, ketoconazole, neticonazole hydrochloride and lanoconazole.
Furthermore, the invention relates to an external preparation for athlete's foot treatment, wherein the anti-trichophton drug and l-menthol are blended.
The invention relates to the external preparation for athlete's foot treatment, wherein butenafine hydrochloride, l-menthol and isopropylmethylphenol are blended.
In addition, the invention relates to the external preparation for athlete's foot treatment, also comprising at least one kind of a local anesthetic, an antihistamine and an anti-inflammatory drug.
Further, the invention relates to the external preparation for athlete's foot treatment, wherein the local anesthetic is dibucaine hydrochloride, or lidocaine or its salt.
Furthermore, the invention relates to the external preparation for athlete's foot treatment, wherein the antihistamine is chlorpheniramine maleate, or diphenhydramine or its salt.
Further, the invention relates to the external preparation for athlete's foot treatment, wherein the anti-inflammatory drug is glycyrrhetinic acid or its salt, or allantoin.
Further, the invention relates to the external preparation for athlete's foot treatment, wherein butenafine hydrochloride, l-menthol, dibucaine hydrochloride, chlorpheniramine maleate and glycyrrhetinic acid are blended.
Consequently, in an anti-trichophton drugs of which antibacterial action against fungi except Trichophyton is not necessarily satisfactory, the external preparation for athlete's foot treatment of the invention suppresses the growth of skin habitual fungi such as Staphylococus aureus and Candida albicans, which become a cause of a bad smell of foot due to athlete's foot, aggravation athlete's foot and the like, without combination of an antifungal agent, and not only improves a therapeutic effect for athlete's foot compared with a case simply to reduce Trichophyton but has effect to enhance patient's compliance.
In addition, by blending at least one kind of compound, preferably two kinds of compounds in combination, which were selected from l-menthol, a menthol analogue compound and a bactericidal compound, it was found that an anti-trichophyton drug could synergistically suppress the growth of Staphylococus aureus and Candida albicans in a lower blend amount.
Further, if said external preparation for athlete's foot treatment contains at least one kind among a local anesthetic, an antihistamine and an anti-inflammatory drug, it suppresses rube faction which an anti-trichophyton drug rarely produces even if in a slight degree, and further favorable enhancement of compliance can be obtained. Although this effect can be obtained by blending at least one kind among the local anesthetic, the antihistamine and the anti-inflammatory drug, it is possible to get further favorable effect by combination of two or more kinds.
[Best Embodiment for Carrying out the Invention]
As described above, in the external preparation for athlete's foot treatment, an anti-trichophton drug is blended in a specific concentration, that is, 0.1-10.0% by mass, preferably 1-5% by mass, with at least one kind of compound selected from l-menthol, a menthol analogue compound and a bactericidal compound in the range of 0.5-5% by mass, preferably 1-3% by mass in total.
By making the blend amount of the anti-trichophton drug not less than 0.1% by mass, the effect as an anti-trichophyton agent can easily be obtained, and even if blending not less than 10% by mass, the effect as the anti-trichophton agent is hardly improved.
The anti-trichophton drugs used in the invention are benzylamine type, allylamine type, thiocarbamic acid type and imidazole type and triazole type antifungal agents, specifically, include butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, miconazole, bifonazole, ketoconazole, clotrimazole, econazole nitrate, neticonazole hydrochloride, lanoconazole, isoconazole, oxiconazole, sulconazole, tioconazole, fluconazole and itraconazole, though butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, bifonazole, ketoconazole, neticonazole hydrochloride and lanoconazole are preferable, and butenafine hydrochloride is particularly preferable.
Although butenafine hydrochloride is high in activity against Trichophyton, the activity against Candida albicans and Staphylococus aureus can not be expected much, and therefore, by using it with at least one kind of compound in combination, which are selected from l-menthol, a menthol analogue compound and a bactericidal compound, preferably the activity against Trichophyton as well as Candida albicans and Staphylococus aureus can synergistically be enhanced.
Compounds used together with the anti-trichophton drug in the invention include l-menthol, in addition, menthol analogue compounds such as dl -menthol, 3-l-menthoxypropane-1,2-diol, isopulegol, neoisopulegol, neomenthol, isomenthol, neo-isomenthol, citronellol and linallol, and bactericidal compounds such as isopropylmethylphenol, dequalinium chloride, dequalinium acetate, benzethonium chloride, benzalkonium chloride, chlorhexidine chloride, chlorhexidine gluconate, hinokitiol and resorcin, though 3-l-menthoxypropane-1,2-diol, isopropylmethylphenol and the like are preferably used.
Further, combined use of l-menthol and isopropyl-methylphenol are particularly preferable.
In addition, by blending at least one kind of compound in not less than 0.5% by mass in total, which are selected from l-menthol, a menthol analogue compound and a bactericidal compound, the growth of Candida albicans and Staphylococus aureus can preferably be suppressed, and making it not more than 5% by mass is preferable because a problem of difficult drying in a liquid preparation does not occur.
Although the kinds of antihistamines used in the invention include cholorpheniramine or its salts, diphenhydramine or its salts, promethazine, mequitazine and the like, cholorpheniramine, diphenhydramine or its salts are preferable.
The concentration of the antihistamine is preferably 0.05-5.0% by mass, more preferably 0.05-2.0% by mass. By making the blend amount of the antihistamine not less than 0.5% by mass, the effect as the antihistamine can easily be obtained, and even if making it not less than 5.0% by mass it does not improve the effect as the antihistamine.
Although the kinds of local anesthetics used in the invention include lidocaine or its salts, dibucaine or its salts, tetracaine or its salts, procaine or its salts, ethyl aminobenzoate and the like, dibucaine hydrochloride, or lidocaine or is salts are preferable.
The concentration of the local anesthetic is preferably 0.01-5.0% by mass, more preferably 0.05-2.0% by mass. By making the blend amount of the local anesthetic not less than 0.01% by mass, the effect as the local anesthetic can easily be obtained, and even if making it not less than 5.0% by mass it does not improve the effect as the local anesthetic.
The kinds of anti-inflammatory drugs used in the invention include glycyrrhetinic acid or its salts, non-steroidal types such as methyl salicylate, glycol salicylate, indometacin, diclofenac, felbinac, piroxicam, ketoprofen, ibuprofenpiconol, bufexamac or allantoin, and steroidal types such as amcinonide, prednisolone valerate, diflucortolone valerate, dexamethasone valerate, betamethasone valerate, dexamethasone acetate, hydrocortisone acetate, dexamethasone, triamcinolone acetonide, halcinonide, betamethasone dipropionate, fluocinonide, fluocinolone acetonide, prednisolone, deprodone propionate, clobetasol propionate or betamethasone, though glycyrrhetinic acid or its salts,or allantoin are preferable.
The concentration of the anti-inflammatory drug is preferably 0.05-10.0% by mass, more preferably 0.05-2.0%by mass. By making the blend amount of the anti-inflammatory drug not less than 0.05% by mass, the effect as the anti-inflammatory drug can easily be obtained, and even if making it not less than 5.0% by mass it does not improve the effect as the anti-inflammatory drug.
The formula in which dibucaine hydrochloride, cholorpheniramine maleate and glycyrrhetinic acid are blended for an external preparation for athlete's foot treatment consisting of butenafine hydrochloride and l-menthol is particularly preferable because it can synergistically enhance the compliance.
Further, the external preparation described in the invention includes a liquid preparation, a cream, a lotion, an aerosol preparation, a patch and the like.
The external preparation of the invention may contain a usual base according to its form, and in the case of the liquid preparation or the lotion, a lower alcohol, apolyhydric alcohol, water or the like may be contained.
In the case of the cream, an oily base, a higher alcohol, a fatty acid ester, or a polyhydric alcohol or its derivative, a surfactant, a gellant, water or the like may be contained.
As the aerosol preparation, a lower alcohol, a polyhydric alcohol or the like may be contained to dissolve the drug of the invention.
As the lower alcohol used in the above formulas, methanol, ethanol, denatured ethanol, isopropanol and the like may be illustrated.
As the oily base, liquid paraffin, vaseline, paraffin-wax and the like may be illustrated, and the higher alcohol is C_10-20alcohol, preferably cetyl alcohol, stearyl alcohol, cetostearyl alcohol and oleyl alcohol are preferable. As the polyhydric alcohol and its derivative, there are glycerol, ethylene glycol. propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, and these 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 acid, stearic acid or oleic acid, with a lower alcohol (C_1-6) may be illustrated.
The surfactant may be an anionic surfactant such as polyoxyethylenealkylether phosphate or sodium alkylsulfate, a sorbitan fatty acid ester such as sorbitan sesquioleate, sorbitan trioleate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene sorbitan stearate, a nonionic surfactant such as polyoxyethylene nonylether, monooxyethylene cetylether or monooxyethylene laurylether, in addition, a cationic surfactant such as benzethonium chloride or benzalkonium chloride, or an amphoteric surfactant.
The gel-type vehicle includes carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl-cellulose, ethylcellulose, carboxymethyl cellulose and the like.
The external preparation for athlete's foot treatment of the invention may contain a percutaneous absorption promoter, and if said percutaneous absorption promoter is one or more compounds in which a percutaneous absorption promoting action of the anti-trichophton drug is recognized, any compound may be used.
Examples include C₆-C₂₀fatty acids, fatty alcohols, fatty acid esters or fatty acid ethers, aromatic organic acids, aromatic alcohols, aromatic organic acid esters or aromatic organic acid ethers, furthermore lactic acid esters, acetic acid esters, monoterpene compounds, sesquiterpene compounds, Azone or Azone derivatives, glycerol fatty acid esters, sorbitan fatty acidesters, polysorbates, polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oils and sucrose fatty acid esters. Fatty acid esters and fatty alcohols are preferable, in particular, isopropyl miristate, isopropyl palmitate, sorbitan monooleate and oleyl alcohol are preferable.
Further, the external preparation for athlete's foot treatment of the invention may contain an antioxidant, an antiseptic agent, a preservative, a moisturizing agent, ache late agent and other additive which are usually blended in a skin external preparation.
In the following, the invention is explained in more detail by the examples. The invention, however, is not limited to these examples, and various changes may be made without departing from the spirit of the invention. Further, in the examples, ‘%’ means ‘% by mass’ unless otherwise specified.

EXAMPLES 1-6

Aerosol Preparations

(Preparation Method for Aerosol Preparations)

A solid ingredient was dissolved in ethanol, and to this was added with other ingredients to prepare a raw solution. The raw solution and a propellant were filled in an aerosol can to obtain the aerosol preparations of the examples 1-6.

TABLE 1


(Examples of aerosol preparations)

Examples

	Composition	1	2	3

Butenafine hydrochloride	1	0.5	1
Diphenhydraminehydrochloride	0	0.2	0.2
Chlorpheniraminemaleate	0	0.5	0.5
Glycyrrhetinic acid	0	0	0.2
l-Menthol	2	1	3
Ethanol	45	50	55
Isopropyl myristate	4	4	8
1,3-Butylene glycol	16	20	12
Purified water	32	21.8	20.1
Raw liquid in total	100	100	100
Above raw liquid's amount	50	30	35
Dimethyl ether	30	50	25
LP gas	20	20	40
Aerosol in total	100	100	100

	TABLE 2


	Examples

	Composition	4	5	6

Butenafine hydrochloride	5	0.5	1
Lidocaine	0	1.5	0.5
Diphenhydraminehydrochloride	0	0.5	0.5
Dipotassium glycyrrhetinate	0	0	0.2
Allantoin	0.2	1.5	0
l-Menthol	2	1	3
Ethanol	25	60	50
Isopropyl myristate	4	4	8
Polyethylene glycol 200	27	8	13
Purified water	36.8	23	23.8
Raw liquid in total	100	100	100
Above raw liquid's amount	50	30	35
Dimethyl ether	30	50	25
LP gas	20	20	40
Aerosol in total	100	100	100

(Preparation Method for Creams)

As to a preparation method for a cream, an aqueous phase and an oil phase were each heated at 80° C., mixed and emulsified under a sufficient stirring. Then, the emulsion was cooled under stirring to room temperature to obtain the creams of the examples 7-9.

TABLE 3


(Examples of creams)

Examples

	Composition	7	8	9

Oil	Butenafine hydrochloride	2	1	1
phase	Lidocaine		0.1
	Diphenhydramine		5
	Glycyrrhetinic acid	5		0.5
	l-Menthol	1	3	2
	Liquid paraffin	10	10	8
	Isopropyl myristate	10	5	2
	Cetanol	2		3
	Stearyl alcohol	2	9	3
	Polyoxyethylene cetyl ether	2		4
	Polyoxyethylene sorbitan		5
	stearate
	Carboxyvinyl polymer		1.5
Aqueous	Lidocaine hydrochloride		0.5
phase	Dibucaine hydrochloride			0.5
	Chlorpheniramine hydrochloride		0.05
	Chlorpheniramine maleate			0.5
	Diethanolamine	0.2	0.2	0.2
	Methylparaben	0.2	0.2	0.2
	Purified water	balance	balance	balance

Total	100		100

(Preparation Method for Liquid Preparations)

As to a preparation method for a liquid preparation, an active ingredient was dissolved in ethanol, and added to other ingredients to obtain the liquid preparation of the 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	1.0	1.0	1.0	1.0	1.0	1.0
Dibucaine hydrochloride	0.5	0.5	0.5	0.5	0.5	0.5
Chlorpheniramine maleate	0.5	0.5	0.5	0.5	0.5	0.5
Glycyrrhetinic acid	0.2	0.2	0.2	0.2	0.2	0.2
Isopropylmethylphenol	0	0	0	0	0	0
l-Menthol	1	2	3	0	0	0
MP20H	0	0	0	0.5	1.0	2.0
Propylene carbonate	10	10	10	10	10	10
Ethanol	30	30	30	30	30	30
Sodium hyaluronate	0.01	0.01	0.01	0.01	0.01	0.01
Purified water	balance	balance	balance	balance	balance	balance
Total	100	100	100	100	100	100

	Example	Example	Comparative	Comparative	Comparative
Composition	16	17	example 1	example 2	example 3

Butenafine hydrochloride	1.0	1.0	1.0	1.0	1.0
Dibucaine hydrochloride	0.5	0.5	0.5	0.5	0.5
Chlorpheniramine maleate	0.5	0.5	0.5	0.5	0.5
Glycyrrhetinic acid	0.2	0.2	0.2	0.2	0.2
Isopropylmethylphenol	0	0.5	0	0	0
l-Menthol	0	2	0	0	0
MP20H	4.0	0	0	0.1	0.2
Propylene carbonate	10	10	10	10	10
Ethanol	30	30	30	30	30
Sodium hyaluronate	0.01	0.01	0.01	0.01	0.01
Purified water	balance	balance	balance	balance	balance
Total	100	100	100	100	100

MP2OH: 3-l-Menthoxypropane-1,2-diol

TEST EXAMPLE 1

Sensory test

The preparations of the examples 10-12 and the comparative example 1 were applied to 20 patients with a skin fungus disease, showing the number of persons who got the refreshing feeling and the efficacy feeling (in particular, alleviation of itch)

TABLE 5


Sensory test

			Comparative
Example 10	Example 11	Example 12	example 1

Refreshing	12	persons/	14	persons/	17	persons/	8	persons/
feeling	20	persons	20	persons	20	persons	20	persons
Efficacy	5	persons/	7	persons/	10	persons/	2	persons/
feeling	20	persons	20	persons	20	persons	20	persons
(alleviation
of itch)

TEST EXAMPLE 2

Evaluation of Antibacterial Action by Halo Test

Test method
1. The test bacteria (Staphylococus aureus, Candida albicans) were inoculated to a SCD agar culture medium cooled to an appropriate temperature after a high-pressure wet sterilization, adjusting the bacterial count to about 10⁶/mL.
2. The test bacteria incubated in 1. were thinly applied to the SCD agar culture medium formed beforehand into a multilayer, cooled and fixed at room temperature.
3. 50 μL of the following samples were applied to a sterilized paper disc (diameter: 8 mm) for an antibiotic test, which was placed on the culture medium of 2.
4. 3. was incubated at 35° C. for 24-48hours, and the presence or the absence of a growth inhibition ring which occurred around the paper disc was observed.
Test Samples
A liquid, in which butenafine hydrochloride as an anti-trichophton drug and only l-menthol as an auxiliary agent were blended, was prepared on an experimental basis (the below formula), and the antibacterial actions against Staphylococus aureus, Candida albicans were evaluated. The results are shown in Table 6.
The blend amount of l-menthol was set in 7 classes in the range of 0-4%.
Test formula of liquid preparation for athlete's foot treatment
Butenafine hydrochloride: 1%
l-Menthol: 0-4%
Macrogol 400: 20%
Ethanol: 30%

Purified Water: Residual Quantity

TABLE 6


Results

	Observation results of inhibition ring
	(diameter of inhibition ring in
	parentheses)

	Test bacteria:	Test bacteria:
	Staphylococus aureus	Candida albicans

Butenafine hydrochloride: 1%	Absence of	Absence of
L-Menthol: 0%	inhibition ring	inhibition ring
Butenafine hydrochloride: 1%	Absence of	Absence of
L-Menthol: 0.1%	inhibition ring	inhibition ring
Butenafine hydrochloride: 1%	Absence of	Absence of
L-Menthol: 0.2%	inhibition ring	inhibition ring
Butenafine hydrochloride: 1%	Absence of	Presence of
L-Menthol: 0.5%	inhibition ring	inhibition ring
		(10 mm)
Butenafine hydrochloride: 1%	Presence of	Presence of
L-Menthol: 1%	inhibition ring	inhibition ring
	(9 mm)	(10 mm)
Butenafine hydrochloride: 1%	Presence of	Presence of
L-Menthol: 2%	inhibition ring	inhibition ring
	(10 mm)	(12 mm)
Butenafine hydrochloride: 1%	Presence of	Presence of
L-Menthol: 4%	inhibition ring	inhibition ring
	(10 mm)	(14 mm)

The antibacterial action was confirmed by blend of not less than 0.5% against Candida albicans and not less than 1% against Staphylococus aureus.

The evaluation of the antibacterial action by Halo test was carried out by the formulas in the examples 13-17 and the comparative examples 1-3, described in Table 4. The test method is same with that in the test example 2, and the results are shown as follows.

TABLE 7


Results

	Test bacteria:
	Staphylococus	Test bacteria:
	aureus	Candida albicans

Comparatvie example 1	Absence of	Absence of
	inhibition ring	inhibition ring
Comparatvie example 2	Absence of	Absence of
	inhibition ring	inhibition ring
Comparatvie example 3	Absence of	Absence of
	inhibition ring	inhibition ring
Example 13	Presence of	Presence of
	inhibition	inhibition
	ring (11 mm)	ring (11 mm)
Example 14	Presence of	Presence of
	inhibition	inhibition
	ring (13 mm)	ring (13 mm)
Example 15	Presence of	Presence of
	inhibition	inhibition
	ring (14 mm)	ring (15 mm)
Example 16	Presence of	Presence of
	inhibition	inhibition
	ring (18 mm)	ring (16 mm)
Example 17	Presence of	Presence of
	inhibition	inhibition
	ring (14.5 mm)	ring (16 mm)

The antibacterial action against Staphylococus aureus and Candida albicans was confirmed in the concentration of not less than 0.5% of 3-1-menthoxypropane-1,2-diol. In addition, in the formula in which isopropylmethylphenol and l-menthol were blended in combination, it was also confirmed to be able to carry out effectively the suppression of Staphylococus aureus and Candida albicans.

INDUSTRIAL APPLICABILITY

By using an external preparation for athlete's foot treatment containing an anti-trichophton drug and a compound suppressing the growth of Staphylococus aureus and Candida albicans as an essential ingredient, it becomes possible to reduce effectively not only Trichophyton but also other fungi such as Candida albicans and a skin habitual bacteria such as Staphylococus aureus, and therefore, the application to a wide-ranging use such a therapy for a fungus infectious disease or the like can be made.

Claims

1. An external preparation for athlete's foot treatment, comprising an anti-trichophyton drug mixed with at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds.

2. The external preparation for athlete's foot treatment according to claim 1, wherein the anti-trichophton drug and at least one compound selected from l-menthol, menthol analogue compounds and bactericidal compounds are blended in 0.1-10% by mass and 0.5-5% by mass respectively.

3. The external preparation for athlete's foot treatment according to claim 1, wherein the menthol analogue compound is 3-1-menthoxypropane-1,2-diol.

4. The external preparation for athlete's foot treatment according to claim 1, wherein the bactericidal compound is isopropylmethylphenol.

5. The external preparation for athlete's foot treatment according to claim 1, wherein the anti-trichophton drug is selected from benzylamine type, allylamine type, thiocarbamic acid type and imidazole type antifungal agents.

6. The external preparation for athlete's foot treatment according to claim 1, wherein the anti-trichophton drug is one kind selected from butenafine hydrochloride, terbinafine hydrochloride, tolnaftate, bifonazole, ketoconazole, neticonazole hydrochloride and lanoconazole.

7. The external preparation for athlete's foot treatment according to claim 1, wherein the anti-trichophton drug and l-menthol are blended.

8. The external preparation for athlete's foot treatment according to claim 1 comprising the anti-trichophton drug, l-menthol and the bactericidal compound, wherein the anti-trichophton drug is butenafine hydrochloride, the bactericidal compound is isopropylmethylphenol, and the butenafine hydrochloride l-menthol and isopropylmethylphenol are blended.

9. The external preparation for athlete's foot treatment according to claim 1, further comprising at least one kind of a local anesthetic, an antihistamine and an anti-inflammatory drug.

10. The external preparation for athlete's foot treatment according to claim 9, wherein the local anesthetic is dibucaine hydrochloride, or lidocaine or its salt.

11. The external preparation for athlete's foot treatment according to claim 9, wherein the antihistamine is chlorpheniramine maleate, or diphenhydramine or its salt.

12. The external preparation for athlete's foot treatment according to claim 9, wherein the anti-inflammatory drug is glycyrrhetinic acid or its salt, or allantoin.

13. The external preparation for athlete's foot treatment according to claim 9 comprising the anti-trichophton drug, l-menthol, local anesthetic, antihistamine and the anti-inflammatory drug, wherein the anti-trichophton drug is butenafine hydrochloride, the local anesthetic is dibucaine hydrochloride, the antihistamine is chlorpheniramine maleate, and the anti-inflammatory drug is glycyrrhetinic acid, and the butenafine hydrochloride, l-menthol, dibucaine hydrochloride, chlorpheniramine maleate and glycyrrhetinic acid are blended.