Topical steroidal formulations
View Patent ↗The present invention relates to formulations of poorly water soluble pharmaceutical agents of Formula I and II. The present invention also relates to compositions containing compounds of Formula I or II, and glucocorticoids, and methods for reducing side effects from glucocorticoid treatment by co-administration of compounds of Formula I and II. The compositions herein are useful for the treatment of diabetes and obesity related diseases including metabolic syndrome.
1. A pharmaceutical composition comprising a suspension comprising a nanosized compound selected from the group consisting of 3β-methyl-5-androsten-17-one, 3β-methyl-16α-fluoro-5-androsten-17-one and 16α-fluoro-5-androsten-17-one; a lower alkyl alcohol; a surfactant; and optionally, a long chain alcohol.
2. A composition according to claim 1 , wherein said long chain alcohol corresponds to the formula CH 3 (CH 2 ) n —OH, wherein n is an integer in the range of 9-24.
3. A composition according to claim 2 , wherein said long chain alcohol is selected from the group consisting of decyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol and mixtures thereof.
4. A composition according to claim 1 , further comprising water.
5. A transdermal delivery system comprising a composition of claim 1 .
6. A topical formulation comprising a composition of claim 1 .
7. A method for the treatment of obesity, type II diabetes, arthritis or metabolic syndrome in a patient in need thereof, which comprises administering to said patient a therapeutically effective amount of a composition of claim 1 .
8. The method according to claim 7 , wherein said treatment is for type II diabetes.
9. The method according to claim 7 , wherein the treatment is for obesity.
10. A gel comprising a nanosized compound selected from the group consisting of 3β-methyl-5-androsten-17-one, 3β-methyl-16α-fluoro-5-androsten-17-one and 16α-fluoro-5-androsten-17-one; a lower alkyl alcohol; water; a surfactant; a thickening agent; and optionally a base.
11. The gel according to claim 10 , wherein said lower alkyl alcohol is selected from the group consisting of ethanol, methanol, butanol, pentanol, isopropanol and n-propanol.
12. The gel according to claim 10 , wherein said base is selected from the group consisting of triethanolamine, diethanolamine and triethylamine.
13. A method of preparing a gel comprising a nanosized compound selected from the group consisting of 3β-methyl-5-androsten-17-one, 3β-methyl-16α-fluoro-5-androsten-17-one and 16α-fluoro-5-androsten-17-one, comprising the steps of: mixing a lower alkyl alcohol, a surfactant, a base, water and said nanosized compound; adding and mixing a cross-linked acrylic acid polymer; and incubating said ingredients until gel formation.
14. A method of treating cancer comprising administering to a subject in need thereof a composition of claim 1 .
15. The method of claim 14 , wherein said cancer is prostate cancer.
16. The gel according to claim 10 wherein the surfactant is a polysorbate.
17. The gel according to claim 16 which comprises:
from about 30 to about 90% (v/v) lower alcohol; and
from about 0.01 to about 5% (v/v) surfactant.
18. A method of treating diabetes comprising administering to a mammal in need thereof a composition according to claim 1 .
19. The method according to claim 7 , wherein said treatment is for arthritis.
20. A transdermal delivery system comprising a composition of claim 10 .
21. A topical formulation comprising a composition of claim 10 .
22. A method for the treatment of obesity, arthritis, type II diabetes or metabolic syndrome in a patient in need thereof, which comprises administering to said patient a therapeutically effective amount of a composition comprising a gel according to claim 10 .
23. The method according to claim 22 , wherein said treatment is for type II diabetes.
24. The method according to claim 22 wherein the treatment is for obesity.
25. The method according to claim 22 , wherein the treatment is for rheumatoid arthritis or osteoarthritis.
26. The method according to claim 22 , wherein said lower alkyl alcohol is selected from the group consisting of ethanol, methanol, butanol, pentanol, isopropanol and n-propanol.
27. The method according to claim 22 wherein the surfactant is a polysorbate.
28. The method according to claim 27 , wherein said polysorbate is selected from the group consisting of polyoxyethylene-20-sorbitan monooleate (Tween 80), polyoxyethylene-20-sorbitan monostearate (Tween 60), polyoxyethylene-20-sorbitan monopalmitate (Tween 40), polyoxyethylene-20-sorbitan monolaurate (Tween 20), and mixtures thereof.
29. The method according to claim 13 , wherein said cross-linked acrylic acid polymer is a Carbomer.
30. The composition of claim 1 , wherein said nanosized compound is 16α-fluoro-5-androsten-17-one.
31. The method of claim 7 or 22 , wherein said nanosized compound is 16α-fluoro-5-androsten-17-one.
32. The gel according to claim 1 wherein said nanosized compound is 16α-fluoro-5-androsten-17-one.
33. The method of preparing a gel according to claim 13 wherein the nanosized compound is 16α-fluoro-5-androsten-17-one.
34. The pharmaceutical composition according to claim 1 wherein said surfactant is a polysorbate or a polyethyleneglycol substituted fatty acid.
35. The pharmaceutical composition according to claim 34 wherein said polysorbate is polyoxyethylene-20-sorbitan monooleate (Tween 80), and wherein said pharmaceutical composition comprises a lower alkyl alcohol in the range of from about 30 to about 90% (v/v), polyoxyethylene-20-sorbitan monooleate (Tween 80) in the range of from about 0.01% to about 3.5% and water in the range of from about 0% to about 60%.
36. The method according to claim 14 , wherein said cancer is a cancer of the mammary gland, skin, colon, liver or lymphatic system.
37. A composition according to claim 34 , wherein said polysorbate is selected from the group consisting of polyoxyethylene-20-sorbitan monooleate (Tween 80), polyoxyethylene-20-sorbitan monostearate (Tween 60), polyoxyethylene-20-sorbitan monopalmitate (Tween 40), polyoxyethylene-20-sorbitan monolaurate (Tween 20), polyethyleneglycol stearate, polyethyleneglycol oleate and mixtures thereof.
38. The method according to claim 19 , wherein the treatment is for rheumatoid arthritis or osteoarthritis.
39. The gel according to claim 16 , wherein said polysorbate is selected from the group consisting of polyoxyethylene-20-sorbitan monooleate (Tween 80), polyoxyethylene-20-sorbitan monostearate (Tween 60), polyoxyethylene-20-sorbitan monopalmitate (Tween 40), polyoxyethylene-20-sorbitan monolaurate (Tween 20), and mixtures thereof.