Methods and compositions for administration of TRPV1 agonists
View Patent ↗Compositions are provided that contain a TRPV1 agonist, such as capsaicin, and a solvent system. Topical application of the composition results in rapid delivery of agonist to the dermis and epidermis. Method of using the compositions for reducing nociceptive nerve fiber function in subjects, and for treatment of capsaicin-responsive conditions are also provided.
1. A method comprising topically applying a liquid formulation to a surface of a mammal the liquid formulation comprising between about 10% (w/v) to about 30% (w/v) of a TRPV1 agonist, at least a first penetration enhancer and a second penetration enhancer, wherein the first penetration enhancer is propylene glycol or diethylene glycol monoethyl ether and the second penetration enhancer is selected from the group consisting of ethyl oleate, oleic acid, oleyl alcohol, benzyl alcohol and menthone, and optional additional components comprising not more than 5% (w/v) of the liquid formulation, and wherein a single application of the liquid formulation results in pain relief for at least two weeks.
2. The method of claim 1 wherein the TRPV1 agonist is capsaicin.
3. The method of claim 1 wherein the mammal is a human.
4. The method of claim 3 wherein the human suffers from a capsaicin-responsive condition.
5. The method of claim 1 wherein 2 to 7 days after topically applying the liquid formulation to the surface of a mammal, the density of functional nociceptive nerve fibers in the epidermis and dermis of the mammal is decreased by at least about 20%.
6. A liquid formulation comprising:
between about 10% (w/v) to about 30% (w/v) of a TRPV1 agonist,
at least a first penetration enhancer and a second penetration enhancer, wherein the first penetration enhancer is propylene glycol or diethylene glycol monoethyl ether and the second penetration enhancer is selected from the group consisting of ethyl oleate, oleic acid, oleyl alcohol, benzyl alcohol and menthone; and
optional additional components comprising not more than 5% (w/v) of the liquid formulation.
7. A liquid formulation comprising:
between about 10% (w/v) to about 30% (w/v) of capsaicin;
at least a first penetration enhancer and a second penetration enhancer, wherein the first penetration enhancer is propylene glycol or diethylene glycol monoethyl ether and the second penetration enhancer is selected from the group consisting of ethyl oleate, oleic acid, oleyl alcohol, benzyl alcohol, and menthone; and
optional additional components comprising not more than 5% (w/v) of the liquid formulation.
8. The liquid formulation of claim 6 wherein said first and second penetration enhancers, taken together, comprise at least 50% (v/v) of the liquid formulation.
9. The liquid formulation of claim 8 wherein said first and second penetration enhancers, taken together, comprise at least 75% (v/v) of the liquid formulation.
10. The liquid formulation of claim 9 wherein said first and second penetration enhancers, taken together, comprise at least 90% (v/v) of the liquid formulation.
11. The liquid formulation of claim 6 wherein the TRPV1 agonist is capsaicin.
12. The liquid formulation of claim 6 further comprising a local anesthetic.
13. The liquid formulation of claim 6 wherein the liquid formulation is contained in a microemulsion.
14. A system for treating a capsaicin-responsive condition, the system comprising the liquid formulation of claim 6 and a non-occlusive and/or non-adherent applicator device for applying the liquid formulation.
15. The system of claim 14 wherein the applicator device is pre-filled with the liquid formulation.
16. The system of claim 14 wherein the liquid formulation is contained in a container separate from the device.
17. The system of claim 14 further comprising measuring marks on the applicator device for assisting a user in determining the amount of the liquid formulation in the applicator device.
18. The system of claim 14 wherein the applicator device is a metered dose aerosol, a stored-energy metered dose pump or a manual metered dose pump.
19. The system of claim 14 wherein the applicator device is a sponge, brush, or swab.
20. A kit comprising the system of claim 14 and a cleaning composition for removal of residual agonist.
21. The kit of claim 20 wherein the cleaning composition comprises at least about 60% polyethylene glycol.
22. A therapeutic bath apparatus comprising a basin capable of receiving an affected area of tissue therein, wherein the basin has a bottom surface and a wall structure extending upwardly therefrom, and wherein the basin contains a fluid comprising the TRPV1 agonist microemulsion of claim 13 .
23. The method of claim 1 wherein the liquid formulation comprises between about 10% (w/v) to about 20% (w/v) of the TRPV1 agonist.
24. The method of claim 1 wherein the liquid formulation comprises about 10% (w/v) of the TRPV1 agonist.
25. The method of claim 1 wherein a single application of the liquid formulation results in pain relief for at least one month.
26. The method of claim 25 wherein the single application of the liquid formulation results in pain relief for at least three months.
27. The method of claim 25 wherein the single application of the liquid formulation results in pain relief for at least six months.
28. The method of claim 1 wherein a single application of the liquid formulation results in neuropathic pain relief.
29. The liquid formulation of claim 6 wherein the liquid formulation comprises between about 10% (w/v) to about 20% (w/v) of the TRPV1 agonist.
30. The liquid formulation of claim 6 comprising about 10% (w/v) of the TRPV1 agonist.
31. The liquid formulation of claim 6 wherein a single application of the liquid formulation results in pain relief for at least one month.
32. The liquid formulation of claim 31 wherein the single application of the liquid formulation results in pain relief for at least three months.
33. The liquid formulation of claim 32 wherein the single application of the liquid formulation results in pain relief for up to about six months.
34. The liquid formulation of claim 6 wherein a single application of the liquid formulation results in neuropathic pain relief.