AU2004323577A1

AU2004323577A1 - Carrier-free composition for the treatment of onychomycosis

Info

Publication number: AU2004323577A1
Application number: AU2004323577A
Authority: AU
Inventors: Nair G. Muraleedharan
Original assignee: Michigan State University MSU
Current assignee: Michigan State University MSU
Priority date: 2004-09-24
Filing date: 2004-09-24
Publication date: 2006-04-06
Anticipated expiration: 2024-09-24
Also published as: CA2581606A1; WO2006036144A1; EP1796703A1; JP2008514596A; EP1796703A4; WO2006036144A8

Description

WO 2006/036144 PCT/US2004/031630 CARRIER-FREE COMPOSITION FOR THE TREATMENT OF ONYCHOMYCOSIS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] Not Applicable STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] Not Applicable STATEMENT REGARDING GOVERNMENT RIGHTS [0003] Not Applicable BACKGROUND OF THE INVENTION (1) Field of the Invention [0004] The present invention relates to a carrier-free composition which is an onychomycosis (fungal nail disease) therapeutic agent. In particular, the present invention relates to a composition consisting essentially of thymol, camphor, menthol and Eucalyptus citridiora oil. (2) Description of the Related Art [0005] U.S. Patent No. 6,344,190 to Nair et al describes the use of camphor, menthol, eucalyptus and thymol with a carrier which is a solvent for the ingredients; particularly, an ester of an alcohol such as isoamyl alcohol. This was done to solubilize the ingredients. It was thought that the carrier was necessary for this purpose. OBJECTS [0006] It is therefore an object of the present invention to provide a carrier-free composition wherein the ingredients are solubilized to provide a clear solution. It -1- WO2006/036144 PCT/US2004/031630 is further an object of the present invention to provide a method for the preparation of the composition. It is also an object of the present invention to provide a method for the use of the composition. These and other objects will become increasingly apparent by reference to the following description. SUMMARY OF THE INVENTION [0007] The present invention relates to a composition which consists essentially of (1) thymol, (2) camphor, (3) menthol and (4) Eucalyptus citridiora oil as ingredients in amounts which provide a colorless liquid in absence of a carrier. Preferably, the composition contains equal parts by weight of the ingredients. Further, the composition of the colorless liquid has been provided by a method which comprises stirring ingredients (1) to (3) into ingredient (4) to provide the colorless liquid. Still further, the composition of the ingredients (1) to (3) are introduced into ingredient (4) and then the mixture is heated to produce the colorless liquid. Preferably, the composition of the mixture has been heated up to about 80oC. [0008] Further, the present invention relates to a method for the preparation of a pharmaceutical composition which comprises: mixing (1) thymol, (2) camphor, and (3) menthol into (4) Eucalyptus citridiora oil; and treating the mixture to provide a colorless oil. Preferably, the present invention relates to the method wherein the treating is by heating the mixture. Still further, the present invention relates to the method wherein the treating is by mixing the ingredients over a period of time to provide the colorless mixture. [0009] Further still, the present invention relates to a method of treating toenail fungal infections which -2- WO2006/036144 PCT/US2004/031630 comprises: applying a composition which consists essentially of (1) thymol, (2) camphor, (3) menthol, and (4) Eucalyptus citridiora oil as ingredients in amounts which provide a colorless liquid in absence of a carrier. Preferably, the method of the composition contains equal parts of the ingredients. [0010] The substance and advantages of the present invention will become increasingly apparent by reference to the following description. DESCRIPTION OF THE PREFERRED EMBODIMENTS [0011] Equal weights of thymol, camphor, menthol and Eucalyptus citridiora oil were used to formulate the TNF therapeutic agent resulting to a clear liquid that penetrates the cuticles and nails. The Eucalyptus citridiora oil was weighed first and stirred with equal weights of solid thymol, menthol and camphor. The mixture was then warmed to 80oC till it forms a colorless liquid or stir at room temperature till the solids dissolve to form a colorless.liquid. The resulting product is easy to apply on infected nails using a nail polish applicator or by a cotton swab. [0012] Tests were performed with the composition on toenail fungi as follows: [0013] Components in the formulation were equal weights of the following compounds 1-4: -3- WO 2006/036144 PCT/US2004/031630

H

3 C CH 3

H

3 G O 1. Camphor

CH

3 OH

H

3 C CH3 2. Menthol OH

CH

3

CH

3

H

3 C 3. Thymol 4. E. citridiora oil -4- WO2006/036144 PCT/US2004/031630 [0014] Microbial cultures. All organisms, except the Fusarium and Candida spp., were purchased from American Type Culture Collection (ATCC), Manassas, Virginia, USA. The Fusarium and Candida spp. were Michigan State University (MSU) strains (Nair, M.G., Putnam, A.R., Mishra, S.K., Mulks, M.H., Taft, W.H., Keller, J.E., Miller, J.R., Zhu, P.P., Meinhart, J.D., Lynn, D.G. 1989. Faeriefungin: A new broad-spectrum antibiotic from Streptomyces griseus var. autotrophicus. J Nat Prod 52: 797-809). [0015] Antimicrobial assay. M. canis (ATCC 42888), E. floccosum (ATCC 44685) , F. oxysporum (MSU strain), F. proliferatum (MSU strain), A. chrysogenum (ATCC 22571), A. strictum (ATCC 46646), A. terreus (ATCC 52293), and A. flavus (ATCC 60040) were cultured in Petri dishes containing PDA medium (20 mL). T. rubrum (ATCC 28202), T. mentagrophytes (ATCC 42194), S. brevicaulis (ATCC 36139), and S. dimidiatum (ATCC 46921) were cultured in Petri dishes containing Emmon's modification of Sabouraud's agar medium (20 mL). S. hyalinum (ATCC 66093) was cultured in Petri dishes containing Malt extract agar medium (20 mL). The test organisms C. albicans (MSU strain), C. kruseii (MSU strain), and C. parapsilosis (MSU strain) were cultured in Petri dishes containing YMG media (20 mL). [0016] The cells from a fully- grown plate of each organism were suspended in saline solution (5 mL) and diluted to obtain 5 x 106 CFU/mL using a hemacytometer. 50 OL of this suspension was used to inoculate I mL of respective growth medium of each test organism. Test formulation was added to the inoculated tubes at concentrations ranging from 250 to 5 O1/mL. The tubes containing cell cultures and compounds were incubated at 27 'C for 72- 96 h. At the end of the incubation period, the tubes were examined for growth of the -5- WO2006/036144 PCT/US2004/031630 organism and further monitored for 7 days after which they were recorded for growth or no growth. The concentration at which no growth was observed or minimum concentration for 100 % inhibition (MIC 100oo) is shown in Table 1 for each organism. -6- WO 2006/036144 PCT/US2004/031630 Table 1. MICo 100 ( tg/mL) for the mixture containing equal weights of camphor, menthol, thymol and Eucalyptus citriodora oil against organisms causing onychomycosis. Organism MIC Acremonium chrysogenumn 20 A. strictum >20 >30 Aspergillus flavus A. terreus 30 Candida albicans' -50 C. kruseii >50 C. parapsilosis 50 >30 Epidermophyton floccosum Fusarium oxysporum 30 >30 F. proliferatum30 Microsporum canis >40 ?30 Scopulariopsis brevicaulis 30 >30 Scytalidiumn dimnzidiatum 30 S. hyalinum -30 >30 Trichophyton mentagrophytes 30 T. rubrunm >30 [0017] The composition had a very broad spectrum of activity as can be seen from the results. [0018] It is intended that the foregoing description be only illustrative of the present invention and that the present invention be limited only by the hereinafter appended claims. -7-

Claims

1. A composition which consists essentially of (1) thymol, (2) camphor, (3) menthol and (4) Eucalyptus citridiora oil as ingredients in amounts which provide a colorless liquid in absence of a carrier.

2. The composition of Claim 1 wherein the composition contains equal parts by weight of the ingredients.

3. The composition of Claims 1 or 2 wherein the colorless liquid has been provided by stirring ingredients (1) to (3) into ingredient (4) to provide the colorless liquid.

4. The composition of Claims 1 or 2 wherein the ingredients (1) to (3) are introduced into ingredient (4) and then the mixture is heated to produce the colorless liquid.

5. The composition of Claims 1 or 2 wherein the mixture has been heated up to about 80 0 C.

6. A method for the preparation of a pharmaceutical composition which comprises: (a) mixing (1) thymol, (2) camphor, and (3) menthol into (4) Eucalyptus citridiora oil; and 5 (b) treating the mixture to provide a colorless oil. -8- WO 2006/036144 PCT/US2004/031630

7. The method of Claim 6 wherein the treating is by heating the mixture.

8. The method of Claim 6 wherein the treating is by mixing the ingredients over a period of time to provide the colorless mixture.

9. A method of treating toenail fungal infections which comprises: applying a composition which consists essentially of (1) thymol, (2) camphor, (3) menthol, and (4) Eucalyptus citridiora oil as ingredients in amounts which provide a colorless liquid in absence of a carrier.

10. The method of Claim 9 wherein the composition contains equal parts of the ingredients. -9-