TESTOSTERONE GEL AND METHOD OF USE

• US 20130203720A1
• Filed: 03/14/2013
• Published: 08/08/2013
• Est. Priority Date: 10/12/2005
• Status: Active Grant

• Current Assignee: Besins Healthcare Luxemborg SARL (Besins Healthcare, Inc.)
• Original Assignee: Unimed Pharmaceuticals LLC (Abbott Laboratories Incorporated), Laboratoire Besins International SAS
• Inventors: Malladi, Ramana, Stahlman, Jodi
• Granted Patent: US 8,729,057 B2
• Time in Patent Office: Days
• US Class Current: 514/178
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 5/26 Androgens

Abstract

The present invention relates to an improved transdermal hydroalcoholic testosterone gen formulation that provides, among other things, a desirable pharmacokinetic hormone profile, and methods of use.

Claims

1. (canceled)

2. (canceled)

3. (canceled)

4. (canceled)

5. A gel pharmaceutical composition consisting essentially of:

a) 1.3% to 1.7% (w/w) testosterone;

b) 0.9% to 1.0% (w/w) isopropyl myristate;

c) 67.0% to 74.0% (w/w) of a lower alcohol selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, and tert-butanol;

d) 0.6% to 1.4% (w/w) of a gelling agent, which gelling agent is an anionic polymer that has been neutralized with an amount of neutralizer sufficient to form a gel; and

e) water.

6. The gel pharmaceutical composition of claim 5, wherein the lower alcohol is ethanol.

7. The gel pharmaceutical composition of claim 6, wherein the ethanol is absolute ethanol.

8. The gel pharmaceutical composition of claim 6, wherein the ethanol is 95% (v/v) ethanol.

9. The gel pharmaceutical composition of claim 5, wherein the anionic polymer is a polyacrylic acid.

10. The gel pharmaceutical composition of claim 5, wherein the anionic polymer is a carbomer.

11. The gel pharmaceutical composition of claim 5, wherein the neutralizer is selected from the group consisting of:

sodium hydroxide, ammonium hydroxide, potassium hydroxide, arginine, aminomethyl propanol, tetrahydroxypropyl ethylenediamine, triethanolamine, tromethamine, PEG-15 cocamine, diisopropanolamine and triisopropanolamine and combinations thereof.

12. The gel pharmaceutical composition of claim 11, wherein the neutralizer is sodium hydroxide.

13. The gel pharmaceutical composition of claim 5, wherein the testosterone in the gel pharmaceutical composition is in the range of 1.50% to 1.70% (w/w) testosterone.

14. The gel pharmaceutical composition of claim 5, which consists essentially of:

a) 1.3% to 1.7% (w/w) testosterone;

b) 0.9% to 1.0% (w/w) isopropyl myristate;

c) 67.0% to 74.0% (w/w) of absolute ethanol;

d) 0.6% to 1.4% (w/w) of a carbomer which has been neutralized with sodium hydroxide; and

e) water.

15. The gel pharmaceutical composition of claim 5, which consists essentially of:

a) 1.3% to 1.7% (w/w) testosterone;

b) 0.9% to 1.0% (w/w) isopropyl myristate;

c) 67.0% to 74.0% (w/w) of absolute ethanol;

d) 0.6% to 1.4% (w/w) of a carbomer;

e) an amount of sodium hydroxide sufficient to form a gel; and

f) water.

16. The gel pharmaceutical composition of claim 15, wherein the amount of sodium hydroxide is in the range of 1.0% to 10% (w/w) of 0.1 N sodium hydroxide.

17. The gel pharmaceutical composition of claim 5, wherein a therapeutically effective dose of the gel pharmaceutical composition for treatment of hypogonadism in a human male subject is 2.5 grams.

18. The gel pharmaceutical composition of claim 17, wherein the therapeutically effective dose comprises 40.5 milligrams of testosterone.

19. A gel pharmaceutical composition consisting of:

a) 1.3% to 1.7% (w/w) testosterone;

b) 0.9% to 1.0% (w/w) isopropyl myristate;

c) 67.0% to 74.0% (w/w) of a lower alcohol selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, and tert-butanol;

d) 0.6% to 1.4% (w/w) of a gelling agent, which gelling agent is an anionic polymer that has been neutralized with an amount of neutralizer sufficient to form a gel; and

e) water.

20. The gel pharmaceutical composition of claim 19, wherein the lower alcohol is ethanol.

21. The gel pharmaceutical composition of claim 20, wherein the ethanol is absolute ethanol.

22. The gel pharmaceutical composition of claim 20, wherein the ethanol is 95% (v/v) ethanol.

23. The gel pharmaceutical composition of claim 19, wherein the anionic polymer is a polyacrylic acid.

24. The gel pharmaceutical composition of claim 19, wherein the anionic polymer is a carbomer.

25. The gel pharmaceutical composition of claim 19, wherein the neutralizer is selected from the group consisting of:

sodium hydroxide, ammonium hydroxide, potassium hydroxide, arginine, aminomethyl propanol, tetrahydroxypropyl ethylenediamine, triethanolamine, tromethamine, PEG-15 cocamine, diisopropanolamine and triisopropanolamine and combinations thereof.

26. The gel pharmaceutical composition of claim 25, wherein the neutralizer is sodium hydroxide.

27. The gel pharmaceutical composition of claim 19, wherein the testosterone in the gel pharmaceutical composition is in the range of 1.50% to 1.70% (w/w) testosterone.

28. The gel pharmaceutical composition of claim 19, which consists of:

a) 1.3% to 1.7% (w/w) testosterone;

b) 0.9% to 1.0% (w/w) isopropyl myristate;

c) 67.0% to 74.0% (w/w) of absolute ethanol;

d) 0.6% to 1.4% (w/w) of a carbomer which has been neutralized with sodium hydroxide; and

e) water.

29. The gel pharmaceutical composition of claim 19, which consists of:

a) 1.3% to 1.7% (w/w) testosterone;

b) 0.9% to 1.0% (w/w) isopropyl myristate;

c) 67.0% to 74.0% (w/w) of absolute ethanol;

d) 0.6% to 1.4% (w/w) of a carbomer;

e) an amount of sodium hydroxide sufficient to form a gel; and

f) water.

30. The gel pharmaceutical composition of claim 29, wherein the amount of sodium hydroxide is in the range of 1.0% to 10% (w/w) of 0.1 N sodium hydroxide.

31. The gel pharmaceutical composition of claim 19, wherein a therapeutically effective dose of the gel pharmaceutical composition for treatment of hypogonadism in a human male subject is 2.5 grams.

32. The gel pharmaceutical composition of claim 31, wherein the therapeutically effective dose comprises 40.5 milligrams of testosterone.