Pharmaceutical composition and method for treating hypogonadism

• US 6,503,894 B1
• Filed: 08/30/2000
• Issued: 01/07/2003
• Est. Priority Date: 08/30/2000
• Status: Expired due to Term

• Current Assignee: Unimed Pharmaceuticals LLC (Abbott Laboratories Incorporated)
• Original Assignee: Unimed Pharmaceuticals LLC (Abbott Laboratories Incorporated), Laboratories Besins Iscovesco
• Inventors: Dudley, Robert E., Kottayil, S. George, Palatchi, Olivier
• Primary Examiner(s): Travers, Russell
• Assistant Examiner(s): JIANG, SHAOJIA A
• Application Number:
  US09/651,777
• Time in Patent Office: 860 Days
• Field of Search: 514/178, 514/396, 514/406, 514/415, 514/177
• US Class Current: 514/178
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 31/5685 having an oxo group in position 17, e.g. androsterone
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/26 Androgens

Abstract

A pharmaceutical composition useful for treating hypogonadism is disclosed. The composition comprises an androgenic or anabolic steroid, a C1-C4 alcohol, a penetration enhancer such as isopropyl myristate, and water. Also disclosed is a method for treating hypogonadism utilizing the composition.

Claims

1. A pharmaceutical composition, consisting essentially of:

a. about 0.5% to about 10% testosterone;

b. about 30% to about 98% alcohol selected from the group consisting of ethanol and isopropanol;

c. about 0.1% to about 5% isopropyl myristate;

d. about 1% to about 5% sodium hydroxide; and

e. about 0.1% to about 5% of a gelling agent,

wherein the percentages of components are weight to weight of the composition.

2. The composition as recited in claim 1, wherein the testosterone is present in a concentration selected from the group consisting of about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10% weight of the composition.

3. The composition as recited in claim 1, wherein the composition is contained in a packet selected from the group consisting of a unit dose packet or multiple dose packet.

4. The composition as recited in claim 1, therein the isopropyl myristate is present in a concentration selected from the group consisting of about 0.5%, 1%, 2%, 3%, 4%, and 5% weight to weight of the composition.

5. The composition as recited in claim 1, wherein the isopropyl myristate is present in a concentration of about 0.5% weight to weight of the composition.

6. The composition as recited in claim 1, wherein the gelling agent is selected from the group consisting of polyacrylic acid and carboxymethylcellulose present in a concentration of about 0.1% to about 5% weight to weight of the composition.

7. The composition as recited in claim 1, wherein the composition is the form of a gel.

8. The composition as recited in claim 1, wherein the gelling agent is polyacrylic acid present in a concentration of about 1% weight to weight of the composition.

9. A hydroalcoholic gel formulation, consisting essentially of:

a. about 1% to about 2% testosterone;

b. about 50% to about 75% ethanol;

c. about 0.5% to about 2% isopropyl myristate;

d. about 1% to about 3% sodium hydroxide;

e. about 0.5% to about 2% polyacrylic acid; and

f. water in an amount sufficient to make the formulation 100%;

wherein the percentages of components are weight to weight of the formulation.

10. A unit dose packet comprising inner and outer surfaces, and a pharmaceutical composition inside the packet, the composition consisting essentially of:

a. about 0.5% to about 5% testosterone;

b. about 30% to about 98% ethanol;

c. about 0.1% to about 5% isopropyl myristate;

d. about 1% to about 5% sodium hydroxide; and

e. about 0.1% to about 5% of a gelling agent;

wherein the percentages of components are weight to weight of the composition.

11. The packet as recited in claim 10, wherein the composition weighs about 1.0 gram to about 10.0 grams.

12. The packet as recited in claim 10, wherein the composition weighs about 2.5 grams to about 5.0 grams.

13. The packet as recited in claim 10, wherein the composition is in a form of a gel.

14. The packet as recited in claim 10, wherein the testosterone is present in a concentration selected from the group consisting of about 0.5%, 1%, 2%, 3%, 4%, and 5% weight to weight of the composition.

15. The packet recited claim 10, wherein the isopropyl myristate is present in a concentration of about 0.5% weight to weight of the composition.

16. The packet as recited in claim 10, wherein the gelling agent is selected from the group consisting of polyacrylic acid and carboxymetliylcellulose.

17. The packet as recited in claim 10, wherein the gelling agent is about 1% polyacrylic acid weight to weight of the composition.

18. A method for administering an active agent to a human subject in need thereof, the method comprising:

a. providing a phannaceutical composition consisting essentially of;

(i) about 0.5% to about 5% testosterone;

(ii) about 0.1% to about 5% of a gelling agent;

(iii) about 0.1% to about 5% isopropyl myristate;

(iv) about 1% to about 5% sodium hydroxide; and

(v) about 30% to about 98% alcohol selected form the group consisting of ethanol and isopropanol;

 

wherein the percentages are weight to weight of the composition; and

b. applying a daily dose of the composition to skin of the subject in an amount sufficient for the testosterone to reach the bloodstream of the subject so as to achieve a serum concentration within a range between about 300 ng testosterone per dl serum to about 1050 ng testosterone per dl serum within at least about 36 hours of daily dosing of the composition.

19. The method as recited in claim 18, wherein the testosterone is present in a concentration of about 1% weight to weight of the composition.

20. The method as recited in claim 18, wherein the testosterone is present in a concentration of about 2% weight to weight of the composition.

21. The method as recited in claim 18, wherein the isopropyl myristate is present in a concentration of about 0.5% weight to weight of the composition.

22. The method as recited in claim 18, wherein the alcohol is ethanol present in a concentration of about 72.5% weight to weight of the composition.

23. The method as recited in claim 18, wherein the gelling agent is selected from the group consisting of polyacrylic acid and carboxymethylcellulose present in a concentration of about 0.1% to about 5% weight to weight of the composition.

24. The method as recited in claim 18, wherein the composition is the form of a gel.

25. The method as recited in claim 18, wherein the gelling agent is polyacrylic acid present in a concentration of about 1% weight to weight of the composition.

26. The method as recited in claim 18, wherein the serum testosterone concentration is substantially maintained at about 400 ng/dl or higher for at least 24 hours after the subject has applied the daily dose of the composition for at least 2 consecutive days.

27. The method as recited in claim 18, wherein the serum testosterone concentration is substantially maintained between about 500 ng/dl and about 1050 ng/dl for at least 24 hours after the subject has applied the daily dose of the composition for at least 30 consecutive days.

28. The method as recited in claim 18, wherein the serum testosterone concentration is substantially maintained at between about 600 ng/dl to about 1050 ng/dl for at least 24 hours after the subject has applied the daily dose of the composition for at least 30 consecutive days.

29. The method as recited in claim 18, wherein the serum testosterone concentration is substantially maintained at between about 700 ng/dl to about 1050 ng/dl for at least 24 hours after the subject has applied the daily dose of the composition for at least 30 consecutive days.

30. The method as recited in claim 18, wherein the dose is applied in a single or in divided doses.

31. A method for administering an active agent to a human subject in need thereof, the method comprising:

a. providing a pharmnaceutical composition consisting essentially of;

(i) about 0.5% to about 5% testosterone;

(ii) about 0.1% to about 5% isopropyl myristate;

(iii) about 30% to about 98% of an alcohol selected from the group consisting of ethanol and isopropanol; and

(iv) about 0.1% to about 5% of a gelling agent;

 

wherein the percentages are weight to weight of the composition; and

b. applying a daily dose of the composition to skin of the subject in an amount sufficient for the testosterone to reach the bloodstream of the subject wherein serum concentration is substantially maintained between about 400 ng testosterone per dl serum to about 1050 ng testosterone per dl serum for at least 24 hours after the subject has applied the daily dose of the composition for at least 2 consecutive days.

32. The method as recited in claim 31, wherein the testosterone is present in a concentration of about 1% weight to weight of the composition.

33. The method as recited in claim 31, wherein the testosterone is present in a concentration of about 2% weight to weight of the composition.

34. The method as recited in claim 31, wherein the isopropyl myristate is present in a concentration of about 0.5% weight to weight off the composition.

35. The method as recited in claim 31, wherein the alcohol is present in a concentration of about 72.5% weight to weight of the composition.

36. The method as recited in claim 31, wherein the gelling agent is selected from the group consisting of polyacrylic acid and carboxymethylcellulose.

37. The method as recited in claim 31, wherein the composition is in the form of a gel.

38. The method as recited in claim 36, wherein the gelling agent is polyacrylic acid present in a concentration of about 1% weight to weight of the composition.

39. The method as recited in claim 31, wherein the serum testosterone concentration is maintained between about 500 ng/dl and about 1050 ng/dl for at least 24 hours after the subject has applied the daily dose of the composition for at least 30 consecutive days.

40. The method as recited in claim 31, wherein the serum testosterone concentration is maintained at between about 600 ng/dl to about 1050 ng/dl for at least 24 hours after the subject has applied the daily dose of the composition for at least 30 consecutive days.

41. The method as recited in claim 31, wherein the serum testosterone concentration is maintained at between about 700 ng/dl to about 1050 ng/dl for at least 24 hours after the subject has applied the daily dose of the composition for at least 30 consecutive days.

42. The method as recited in claim 31, wherein the dose is applied in a single or in divided doses.