Method and Composition for Treatment of Cutaneous Lesions

Abstract

A method of treatment or prophylaxis of a cutaneous lesion in an animal the method comprising topically applying to an area of skin of the animal a composition comprising: one or more metal chelators; one or more transforming growth factor modulators; and one or more dermal penetration enhancers.

Description

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 Graph showing the predicted cumulative amount of 1,10-phenanthroline diffused across skin;

FIG. 2 Graph showing the predicted cumulative amount of estradiol diffused across skin.

The terms “topical” and “transdermal” are used herein in the broadest sense to refer to administration of a drug to the skin surface or mucosal membrane of an animal, including humans, so that the drug passes through the skin tissue. Unless otherwise stated or implied, the terms topical drug delivery and transdermal drug delivery are used interchangeably.

The term “dermal penetration enhancer” is used herein in its broadest sense to refer to an agent which improves the rate of percutaneous transport of active agents into and/or across the skin or use and delivery of active agents to organisms such as animals, whether it be for local application or systemic delivery.

Preferably the animal is a human but the invention also extends to the treatment of non-human animals.

EXAMPLE 1

Combined transdermal spray composition

Component           Amount (% w/v)
1,10-phenanthroline 5.0
Estradiol           0.5
Octyl salicylate    5.0
Ethanol 95%         to volume

FIGS. 1 and 2 depict the diffusion profile that may be obtained by transdermal administration of 1,10-phenanthroline and estradiol in accordance with the invention. Addition of the octyl salicylate to the transdermal spray formulation causes a significant marked increase in the amount of 1,10-phenanthroline and estradiol diffusing across the skin over 24 hours.

EXAMPLE 2

Combined transdermal spray composition

Component         Amount (% w/v)
Deferiprone       2.0
Estradiol         0.5
Octyl salicylate  5.0
Alcohol USP (95%) to volume

EXAMPLE 3

Combined transdermal spray composition

Component         Amount (% w/v)
Diacerein         2.0
Estradiol         0.5
Padimate-O        5.0
Alcohol USP (95%) to volume

Claims

1. A method of treatment or prophylaxis of a cutaneous lesion in an animal the method comprising topically applying to an area of skin of the animal a composition comprising: one or more metal chelators;one or more transforming growth factor modulators; andone or more dermal penetration enhancers.

2. A method according to claim 1 wherein animal is suffering CVI and the composition is applied to the gaiter area of the leg of the animal.

3. A method according to claim 1 wherein the composition contains one or more volatile liquids.

4. A method according to claim 3 wherein the one or more volatile liquids are selected from the group consisting of ethanol, isopropanol and mixtures thereof.

5. A method according to claim 1 wherein the composition is in a dosage form selected from the group consisting of gels, lotion patches and aerosol sprays.

6. A method according to claim 1 wherein the composition is applied by spraying the composition onto the skin of the animal.

7. A method according to claim 1 wherein the composition comprises at least one additional component selected from the group consisting of active agents, co-solvents, surfactants, emulsifiers, antioxidants, preservatives, stabilisers, diluents and mixtures of two or more of said components.

8. A method according to claim 1 wherein the composition comprises sufficient co-solvent and/or surfactant to maintain the chelating agent in solution or suspension at the desired concentration.

9. A method according to claim 1 wherein the composition contains from about 0.1% to about 10% of a metal chelator, from about 0.1% to about 10% of a TGF modulator, from about 0.1% to about 10% of a dermal penetration enhancer.

10. A method according to claim 9 wherein the composition comprises from about 45% to about 99.8% of a volatile solvent.

11. A method according to claim 10 wherein the volatile solvent is selected from the group consisting of ethanol, isopropanol and mixture thereof in and amount in the range of about 80 to about 98%.

12. A method according to claim 1 wherein the composition comprises from about 1 to 5% of a metal chelator, from about 1 to 5% of a TGF modulator, from about 2 to 8% of the dermal penetration enhancer, from about 45 to 90% ethanol, isopropanol or mixture thereof and 5 to 45% water.

13. A method according to claim 11 wherein the composition further comprises 0.5 to 5% of a thickening agent.

14. A method according to claim 1 wherein the chelating agent comprises at least one compound selected from the group consisting of 8-hydroxy quinoline, 8-hydroxy quinoline-5-sulphonic acid, diethyl dithiocarbamate, phenanthroline and it's derivatives, dipicolinate, diphenylthiocarbazone, dithizone, cimetidine, dipicolinic acid, deferiprone, diacerein, clioquinol, pharmaceutically acceptable salts thereof and derivatives of the aforementioned.

15. A method according to claim 1 wherein the chelating agent is 1,10-phenanthroline.

16. A method according to claim 1 wherein the composition comprises at least one oestrogen selected from the group consisting of oestradiol, oestriol, oestrone, ethinyloestradiol, mestranol, stilboestrol, dienoestrol, epioestriol, estropipate, zeranol or pharmaceutically acceptable salts or derivatives of any one of the aforementioned.

17. A method according to claim 15 wherein the oestrogen is oestradiol.

18. A method according to claim 1 wherein the one or more dermal penetration enhancers are selected from the group consisting of fatty acids, fatty acid esters, fatty alcohols, glycols and glycol esters, 1,3-dioxolanes and 1,3-dioxanes, macrocyclic ketones containing at least 12 carbon atoms, oxazolidinones and oxazolidinone derivatives, alkyl-2-(N,N-disubstituted amino)-alkanoate esters, (N,N-disubstituted amino)-alkanol alkanoates, sunscreen esters and mixtures thereof.

19. A method according to claim 1 wherein the one or more dermal penetration enhancers are selected from the group consisting of oleic acid, oleyl alcohol, cyclopentadecanone (CPE-218™), sorbitan monooleate, glycerol monooleate, propylene glycol monolaurate, polyethylene glycol monolaurate, 2-n-nonyl 1,3-dioxolane (SEPA™), dodecyl 2-(N,N-dimethylamino)-propionate (DDAIP) or its salt derivatives, 2-ethylhexyl 2-ethylhexanoate, isopropyl myristate, dimethyl isosorbide, 4-decyloxazolidinon-2-one (SR-38™, TCPI, Inc.), 3-methyl-4-decyloxazolidinon-2-one, octyl dimethyl-para-aminobenzoate, octyl para-methoxycinnamate, octyl salicylate and mixtures thereof.

20. A method according to claim 1 wherein the one or more dermal penetration enhancers are selected from safe skin-tolerant ester sunscreens.

21. A method according to claim 1 wherein the one or more penetration enhancers are selected from the group consisting of octyl dimethyl-para-aminobenzoate, octyl para-methoxycinnamate and octyl salicylate.

22. A composition for transdermal administration for treatment or prophylaxis of cutaneous lesions in animals the composition comprising: one or more metal chelators;one or more transforming growth factor modulators; andone or more dermal penetration enhancers.

23. A composition according to claim 22 wherein the composition further comprises one or more volatile liquids.

24. A composition according to claim 22 wherein the one or more volatile liquids are selected from the group consisting of ethanol, isopropanol and mixtures thereof.

25. A composition according to claim 22 wherein the composition is in a dosage form selected from the group consisting of gels, lotion patches and aerosol sprays.

26. A composition according to claim 22 wherein the composition comprises at least one additional component selected from the group consisting of active agents, co-solvents, surfactants, emulsifiers, antioxidants, preservatives, stabilisers, diluents and mixtures of two or more of said components.

27. A composition according to claim 22 wherein the composition comprises sufficient of at least one of a co-solvent and surfactant to maintain the chelating agent in solution or suspension.

28. A composition according to claim 22 wherein the composition contains from about 0.1% to about 10% of the metal chelator, from about 0.1% to about 10% of the TGF modulator and from about 0.1% to about 10% of the dermal penetration enhancer.

29. A composition according to claim 28 wherein the composition comprises from about 45% to about 99.8% of a volatile solvent.

30. A composition according to claim 28 wherein the volatile solvent is selected from the group consisting of ethanol, isopropanol and mixture thereof in and amount in the range of about 80 to about 98%.

31. A composition according to claim 28 wherein the composition comprises from about 1 to 5% of a metal chelator, from about 1 to 5% of a TGF modulator, from about 2 to 8% of the dermal penetration enhancer, from about 45 to 90% ethanol, isopropanol or mixture thereof and 5 to 45% water.

32. A composition according to claim 28 wherein the composition further comprises 0.5 to 5% of a thickening agent.

33. A composition according to claim 28 wherein the chelating agent comprises at least one compound selected from the group consisting of 8-hydroxy quinoline, 8-hydroxy quinoline-5-sulphonic acid, diethyl dithiocarbamate, phenanthroline and it's derivatives, dipicolinate, diphenylthiocarbazone, dithizone, cimetidine, dipicolinic acid, deferiprone, diacerein, clioquinol, pharmaceutically acceptable salts thereof and derivatives of the aforementioned.

34. A composition according to claim 28 wherein the chelating agent is 1,10-phenanthroline.

35. A composition according to claim 28 wherein the composition comprises at least one oestrogen selected from the group consisting of oestradiol, oestriol, oestrone, ethinyloestradiol, mestranol, stilboestrol, dienoestrol, epioestriol, estropipate, zeranol or pharmaceutically acceptable salts or derivatives of any one of the aforementioned.

36. A composition according to claim 28 wherein the oestrogen is oestradiol.

37. A composition according to claim 28 wherein the one or more dermal penetration enhancers are selected from the group consisting of fatty acids, fatty acid esters, fatty alcohols, glycols and glycol esters, 1,3-dioxolanes and 1,3-dioxanes, macrocyclic ketones containing at least 12 carbon atoms, oxazolidinones and oxazolidinone derivatives, alkyl-2-(N,N-disubstituted amino)-alkanoate esters, (N,N-disubstituted amino)-alkanol alkanoates, sunscreen esters and mixtures thereof.

38. A composition according to claim 28 wherein the one or more dermal penetration enhancers are selected from the group consisting of oleic acid, oleyl alcohol, cyclopentadecanone (CPE-218™), sorbitan monooleate, glycerol monooleate, propylene glycol monolaurate, polyethylene glycol monolaurate, 2-n-nonyl 1,3-dioxolane (SEPA™), dodecyl 2-(N,N-dimethylamino)-propionate (DDAIP) or its salt derivatives, 2-ethylhexyl 2-ethylhexanoate, isopropyl myristate, dimethyl isosorbide, 4-decyloxazolidinon-2-one (SR-38™, TCPI, Inc.), 3-methyl-4-decyloxazolidinon-2-one, octyl dimethyl-para-aminobenzoate, octyl para-methoxycinnamate, octyl salicylate and mixtures thereof.

39. A composition according to claim 28 wherein the one or more dermal penetration enhancers are selected from safe skin-tolerant ester sunscreens.

40. A composition according to claim 28 wherein the one or more penetration enhancers are selected from the group consisting of octyl dimethyl-para-aminobenzoate, octyl para-methoxycinnamate and octyl salicylate.