Pharmaceutical composition for the treatment of fungal infections
There is provided pharmaceutical compositions suitable for topical application to the nail for the treatment of nail diseases such as onychomycosis, comprising a urea-based component, a diol component, such as propylene glycol, an organic acid component, such as lactic acid, and a triol component, such a glycerol. There is further provided methods of improving the storage stability of a pharmaceutical composition suitable for topical application to the skin and/or nails comprising such urea-based components, diol components, organic acid components, and, optionally, an aqueous base, which method comprises adding a triol component, such a glycerol, to that composition prior to said storage.
1. A pharmaceutical composition in the form of a liquid or solution, which comprises:
(a) about 3% to about 30% by weight based upon the total weight of the composition of urea and/or urea peroxide;
(b) about 40% to about 80% by weight based upon the total weight of the composition of one or more of the group selected from ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol and mixtures thereof;
(c) about 2% to about 15% by weight based upon the total weight of the composition of one or more of the group a hydroxybutyric acid, a hydroxypropionic acid, glycolic acid, citric acid, malic acid and tartaric acid;
(d) about 5% to about 12% by weight based upon the total weight of the composition of glycerol; and
(e) an amount of aqueous base sufficient to provide a final pH of the composition in the range of about 2 to about 6.
2. The pharmaceutical composition of claim 1 , which comprises:
(a) about 3% to about 30% by weight based upon the total weight of the composition of urea;
(b) about 40% to about 80% by weight based upon the total weight of the composition of propylene glycol;
(c) about 2% to about 15% by weight based upon the total weight of the composition of lactic acid;
(d) about 5% to about 12% by weight based upon the total weight of the composition of glycerol; and
(e) an amount of aqueous sodium hydroxide sufficient to provide a final pH of the composition in the range of about 3 to about 5.
3. The pharmaceutical composition of claim 1 , which further comprises about 0.01% to about 5% by weight based upon the total weight of the composition of ethylenediaminetetraacetic acid.
4. The pharmaceutical composition of claim 2 , which further comprises about 0.01% to about 5% by weight based upon the total weight of the composition of ethylenediaminetetraacetic acid.
5. A pharmaceutical composition in the form of a liquid or solution, which comprises:
(a) about 5% to about 25% by weight based upon the total weight of the composition of urea and/or urea peroxide;
(b) about 45% to about 75% by weight based upon the total weight of the composition of one or more of the group selected from ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol and mixtures thereof;
(c) about 3% to about 15% by weight based upon the total weight of the composition of one or more of the group a hydroxybutyric acid, a hydroxypropionic acid, glycolic acid, citric acid, malic acid and tartaric acid;
(d) about 5% to about 12% by weight based upon the total weight of the composition of glycerol; and
(e) an amount of aqueous base sufficient to provide a final pH of the composition in the range of about 2 to about 6.
6. The pharmaceutical composition of claim 5 , which comprises:
(a) about 5% to about 25% by weight based upon the total weight of the composition of urea;
(b) about 45% to about 75% by weight based upon the total weight of the composition of propylene glycol;
(c) about 3% to about 15% by weight based upon the total weight of the composition of lactic acid;
(d) about 5% to about 12% by weight based upon the total weight of the composition of glycerol; and
(e) an amount of aqueous sodium hydroxide sufficient to provide a final pH of the composition in the range of about 3 to about 5.
7. The pharmaceutical composition of claim 5 , which further comprises 0.03% to about 0.5% by weight based upon the total weight of the composition of ethylenediaminetetraacetic acid.
8. The pharmaceutical composition of claim 6 , which further comprises 0.03% to about 0.5% by weight based upon the total weight of the composition of ethylenediaminetetraacetic acid.
9. A pharmaceutical composition in the form of a liquid or solution, which comprises:
(a) about 8% to about 25% by weight based upon the total weight of the composition of urea and/or urea peroxide;
(b) about 50% to about 75% by weight based upon the total weight of the composition of one or more of the group selected from ethylene glycol, propylene glycol, butanediol, pentanediol, hexanediol and mixtures thereof;
(c) about 4% to about 12% by weight based upon the total weight of the composition of one or more of the group a hydroxybutyric acid, a hydroxypropionic acid, glycolic acid, citric acid, malic acid and tartaric acid;
(d) about 5% to about 10% by weight based upon the total weight of the composition of glycerol; and
(e) an amount of aqueous base sufficient to provide a final pH of the composition in the range of about 2 to about 6.
10. The pharmaceutical composition of claim 9 , which comprises:
(a) about 8% to about 25% by weight based upon the total weight of the composition of urea;
(b) about 50% to about 75% by weight based upon the total weight of the composition of propylene glycol;
(c) about 4% to about 12% by weight based upon the total weight of the composition of lactic acid;
(d) about 5% to about 10% by weight based upon the total weight of the composition of glycerol; and
(e) an amount of aqueous sodium hydroxide sufficient to provide a final pH of the composition in the range of about 3 to about 5.
11. The pharmaceutical composition of claim 9 which further comprises 0.03% to about 0.5% by weight based upon the total weight of the composition of ethylenediaminetetraacetic acid.
12. The pharmaceutical composition of claim 10 which further comprises 0.03% to about 0.5% by weight based upon the total weight of the composition of ethylenediaminetetraacetic acid.
13. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 1 to a person suffering from, or susceptible to, that disease.
14. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 2 to a person suffering from, or susceptible to, that disease.
15. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 3 to a person suffering from, or susceptible to, that disease.
16. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 4 to a person suffering from, or susceptible to, that disease.
17. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 5 to a person suffering from, or susceptible to, that disease.
18. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 6 to a person suffering from, or susceptible to, that disease.
19. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 7 to a person suffering from, or susceptible to, that disease.
20. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 8 to a person suffering from, or susceptible to, that disease.
21. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 9 to a person suffering from, or susceptible to, that disease.
22. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 10 to a person suffering from, or susceptible to, that disease.
23. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 11 to a person suffering from, or susceptible to, that disease.
24. A method of treatment of a fungal infection of the nail, which method comprises administration of a pharmaceutical composition of claim 12 to a person suffering from, or susceptible to, that disease.
25. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 1 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
26. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 2 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
27. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 3 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
28. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 4 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
29. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 5 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
30. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 6 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
31. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 7 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
32. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 8 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
33. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 9 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
34. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 10 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
35. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 11 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.
36. A method of treatment of onychomycosis, which method comprises administration of a pharmaceutical composition of claim 12 to a person suffering from, or susceptible to, that disease, wherein the treatment comprises applying the composition in the form of a liquid or solution to an affected nail.