Method of increasing testosterone and related steriod concentrations in women

• US 20070154533A1
• Filed: 04/11/2006
• Published: 07/05/2007
• Est. Priority Date: 04/13/2005
• Status: Abandoned Application

• Current Assignee: Unimed Pharmaceuticals LLC (Abbott Laboratories)
• Original Assignee: Unimed Pharmaceuticals LLC (Abbott Laboratories)
• Inventors: Dudley, Robert
• Application Number:
  US11/402,986
• Publication Number:
  US 20070154533A1
• Time in Patent Office: Days
• US Class Current: 424/448
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• 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 5/24 of the sex hormones
• CPC Class Codes: A61P 5/26 Androgens
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

The present invention relates to methods, kits, combinations, and compositions for treating, preventing or reducing the risk of developing a testosterone-deficient disorder, or the symptoms associated with, or related to a testosterone-deficient disorder in a subject in need thereof. The present invention also relates to a method of administering a steroid in the testosterone synthetic pathway to a subject in need thereof.

Claims

1. A method of treating, preventing or reducing the risk of developing a testosterone-deficient disorder in a female subject in need thereof, comprising:

(i) identifying a female subject having, or at risk of developing, a testosterone-deficient disorder;

(ii) administering an amount of a hydroalcoholic gel pharmaceutical composition to an area of skin of the subject, which delivers a therapeutically-effective amount of testosterone to the blood serum of the subject such that the testosterone-deficient disorder is improved or the risk of developing a testosterone-deficient disorder is reduced, wherein the composition comprises;

a. about 0.1% to about 10% (w/w) testosterone, or a salt, ester, amide, enantiomer, isomer, tautomer, prodrug, or derivative thereof;

b. about 30% to about 98% (w/w) alcohol selected from the group consisting of ethanol or isopropanol;

c. about 0.1% to about 5% (w/w) penetration enhancer;

d. about 0.1% to about 5% (w/w) of a gelling agent; and

e. the balance purified water;

wherein the composition is capable of releasing the testosterone to the skin at a rate and duration that raises testosterone blood serum concentration to at least about 3 pg testosterone/ml blood serum within about 24 hours after administration.

2. The method of claim 1, wherein the composition comprises about 1% testosterone.

3. The method of claim 1, wherein the composition comprises about 67% alcohol.

4. The method of claim 1, wherein the penetration enhancer is isopropyl myristate.

5. The method of claim 1, wherein the composition comprises about 0.5% isopropyl myristate.

6. The method of claim 1, wherein the gelling agent is selected from the group consisting of polyacrylic acid and carboxymethylcellulose.

7. The method of claim 1, wherein the gelling agent is polyacrylic acid present in an amount of about 1% weight to weight of the composition.

8. The method of claim 1, wherein the composition comprises:

a. about 1.0% testosterone;

b. about 0.9% CARBOPOL®

;

c. about 0.5% isopropyl myristate;

d. about 67% ethanol; and

e. the balance purified water;

wherein the percentages are on a weight to weight basis of the composition.

9. The method of claim 1, wherein for each about 0.1 gram per day application of the composition to the skin, an increase of at least about 5 ng/dl in serum testosterone concentration results in the subject.

10. The method of claim 1, wherein the composition is provided to the subject for daily administration in about a 0.1 g to about a 10 g dose.

11. The method of claim 1, wherein the amount of the composition is a 0.44 g dose delivering about 0.44 mg to about 44 mg of testosterone to the skin.

12. The method of claim 1, wherein the amount of the composition is a 1.32 g dose delivering about 1.32 mg to about 132 mg of testosterone to the skin.

13. The method of claim 1, wherein the amount of the composition is a 1.32 g dose delivering 6.6 mg to about 13.2 mg of testosterone to the skin.

14. The method of claim 11, wherein the amount of the composition is either a 0.44 g dose delivering about 4.4 mg of testosterone to the skin or a 0.88 g dose delivering about 8.8 mg of testosterone to the skin.

15. The method of claim 14, wherein the subject is premenopausal with a below-normal free (unbound) testosterone concentration less than 0.5 ng/dl.

16. The method of claim 14, wherein the subject is postmenopausal with a below-normal free (unbound) testosterone concentration less than 0.5 ng/dl.

17. The method of claim 1, wherein the composition is provided to the subject in one or more packets.

18. The method of claim 17, wherein the packet comprises a polyethylene liner between the composition and inner surface of the packet.

19. The method of claim 1, wherein the composition is administered once, twice, or three times a day.

20. The method of claim 1, wherein the composition further comprises about 0.01% to about 69% of a therapeutic agent comprising an agent that inhibits the synthesis of the sex hormone binding globulin, a progesterone, a progestin, or an estrogenic hormone.

21. The method of claim 20, wherein said therapeutic agent comprises about 1% to about 10% of the composition.

22. The method of claim 20, wherein said therapeutic agent is progesterone.

23. The method of claim 22, wherein serum blood level of progesterone is raised to at least about 1 ng progesterone/ml blood serum within about 24 hours after administration.

24. The method of claim 20, wherein said therapeutic agent is estrogen.

25. The method of claim 24, wherein the serum-blood level of estrogen is raised to at least 60 pg estrogen/ml blood serum within about 24 hours after administration.

26. The method of claim 20, wherein said therapeutic agent is methyltestosterone.

27. The method of claim 20, wherein said therapeutic agent is estradiol.

28. A method for improving sexual performance in a female subject in need thereof, comprising administering to the subject:

(a) an amount of a hydroalcoholic gel pharmaceutical composition to an area of skin of the subject, which delivers a therapeutically-effective amount of testosterone to the blood serum of the subject, wherein the composition comprises;

i. about 0.1% to about 10% (w/w) testosterone, or a salt, ester, amide, enantiomer, isomer, tautomer, prodrug, or derivative thereof;

ii. about 30% to about 98% (w/w) alcohol selected from the group consisting of ethanol or isopropanol;

iii. about 0.1% to about 5% (w/w) penetration enhancer;

iv. about 0.1% to about 5% (w/w) of a gelling agent; and

v. the balance water; and

(b) an amount of an agent for improving sexual performance.

29. The method of claim 28, wherein the agent is selected from the group consisting of:

an agent that causes vasodilatation, a nitrate, an alpha-blocker, a naturally occurring prostaglandin, an endothelial-derived relaxation factor, a phosphodiesterase inhibitor, or combinations thereof.