CARRIER-FREE COMPOSITION FOR THE TREATMENT OF ONYCHOMYCOSIS

COMPOSITION SANS EXCIPIENT POUR LE TRAITEMENT DE L'ONYCHOMYCOSE

English Abstract

A composition for the treatment of onychomycosis (fungal nail disease) is
described. The composition consists essentially of thymol, camphor, menthol
and Eucalyptus citridiora as a colorless liquid oil without any carrier or
solvent for these ingredients.

French Abstract

L'invention concerne une composition pour le traitement de l'onychomycose (infection fongique de l'ongle). Cette composition comprend principalement du thymol, du camphre, du menthol et de l'Eucalyptus citridiora en tant qu'huile liquide incolore. La composition de l'invention ne comprend ni excipient ni solvant pour les ingrédients qui la constitue.

Claims

I CLAIM:


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°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
(b) treating the mixture to provide a
colorless oil.



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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.



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Description

CA 02581606 2007-03-23
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
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CA 02581606 2007-03-23
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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 80 C.
[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
ingredi,ents 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
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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 80 C 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:

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H3C CH3

4
H3C O
1. Camphor

CH3

OH
H3CCH3

2. Menthol

OH CH3

CH3
H3C
3. Thymol

4. E. citridiora oil
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[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. Fae,riefungin: 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 ~L 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
~1/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
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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 loo) is shown in Table 1 for each
organism.

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Table 1. MICIoo ( g/mL) for the mixture containing equal weights of camphor,
menthol,
thymol and Eucalyptus citriodora oil against organisms causing onychomycosis.
Organism MIC
>20
Acremonium chrysogenunz

A. strictum >_20
AspergilZus flavus >30
_30
A. terreus

Candida albicans' _50
C. kruseii >_50
C. parapsilosis >_50
Epidernzoplzyton floccosum ?30
Fusarium oxysporum ?30
F. proliferatum >_30
Microsporum canis ?40
_30
Scopulariopsis brevicaulis
>_30
Scytalidium dinzidiatum

S. hyalinum >_30
Trichophyton mentagroplZytes ~:30
T. rubruni >_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.

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