PHARMACEUTICAL COMPOSITION

• US 20090131387A1
• Filed: 02/02/2009
• Published: 05/21/2009
• Est. Priority Date: 04/19/2002
• Status: Active Grant

• Current Assignee: FCB I LLC (Xstelos Holdings)
• Original Assignee: CPEX Pharmaceuticals Incorporated
• Inventors: Gyurik, Robert J.
• Granted Patent: US 7,608,610 B2
• Time in Patent Office: Days
• US Class Current: 514/179
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• 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 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• 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 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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 15/10 for impotence
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/06 Anabolic agents androgens A61P5/26
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/26 Androgens

Abstract

A pharmaceutical composition comprising: (A) an androgen; (B) a cyclic enhancer of the type used in the compositions and methods claimed by U.S. Pat. No. 5,023,252 to Hsieh; and (C) a thickening agent; including, for example, a composition in which the cyclic enhancer is a macrocyclic ester or a macrocyclic ketone; the use of the composition to treat a condition, for example, male hypogonadism, in a patient by applying the composition to the membrane of the patient; and a method for making the composition.

Claims

1. A method for maintaining a therapeutically effective concentration of testosterone in the blood serum of a male for treating hypogonadism which comprises transdermally delivering to the male by applying to the skin a composition which is in the form of a topical gel, which has a viscosity of about 500 to about 20,000 cps and a pH of about 3 to about 9, and comprises:

(A) about 0.1 to about 5 wt. % of testosterone;

(B) about 0.01 to about 25 wt. % of a macrocyclic enhancer selected from the group consisting of 3-methylcyclopentadecanone, 9-cycloheptadecen-1-one, cyclohexadecanone, cyclopentadecanone, oxacyclohexadecan-2-one and mixtures thereof;

(C) about 0.1 to about 10 wt. % of a thickening agent;

(D) a mixture of solvents which include about 40 wt. % to about 80 wt. % of a lower alkanol.

2. The method of claim 1 further comprising a crystallization inhibitor that is capable of inhibiting crystallization of testosterone.

3. The method of claim 2 further comprising about 0.001 to about 5 wt. % of polyethylene glycol as a crystallization inhibitor.

4. The method of claim 1 wherein said composition is maintained on said skin for a period of time sufficient for delivery of the testosterone to the body of the male and is applied to the skin in the form of a unit dose which contains about 1 to about 300 mg of testosterone and such that, following a single application of the unit dose to the skin, the amount of circulating testosterone (AUC_0-24) in the blood serum of the male achieved in the 24-hour period following the application is about 100 to about 35,000 ng.h/dL greater than the amount of circulating testosterone (AUC_0-24) in the blood serum of the male than would have been achieved in the same 24-hour period had the dose not been administered.

5. The method of claim 1 wherein the viscosity ranges from about 1,000 cps to about 9,000 cps.

6. The method of claim 5 wherein the viscosity ranges from about 2,000 cps to about 8,000 cps.

7. The method of claim 6 wherein the viscosity ranges from about 3,000 cps to about 7,000 cps.

8. The method of claim 1 wherein the pH ranges from about 4 to about 8.

9. The method of claim 1 wherein the lower alkanol ranges from about 50 wt. % to about 75 wt. %.

10. The method of claim 9 wherein the lower alkanol ranges from about 60 wt. % to about 75 wt. %.

11. The method of claim 10 wherein the lower alkanol comprises ethanol.

12. The method of claim 10 wherein the lower alkanol comprises isopropanol.

13. The method of claim 10 further comprising propylene glycol.

14. The method of claim 13 further comprising glycerin.

15. The method of claim 1 wherein the macrocyclic enhancer is 3-methylcyclopentadecanone.

16. The method of claim 1 wherein the macrocyclic enhancer is 9-cycloheptadecen-1-one.

17. The method of claim 1 wherein the macrocyclic enhancer is cyclohexadecanone.

18. The method of claim 1 wherein the macrocyclic enhancer is cyclopentadecanone.

19. The method of claim 1 wherein the macrocyclic enhancer is oxacyclohexadecan-2-one.

20. A method for maintaining a therapeutically effective concentration of testosterone in the blood serum of a male for treating hypogonadism which comprises transdermally delivering to the male by applying to the skin a composition which is in the form of a topical gel, which has a viscosity of about 500 to about 20,000 cps and a pH of about 3 to about 9, and comprises:

(A) about 0.1 to about 5 wt. % of testosterone;

(B) about 0.01 to about 25 wt. % of a macrocyclic enhancer selected from the group consisting of 3-methylcyclopentadecanone, 9-cycloheptadecen-1-one, cyclohexadecanone, cyclopentadecanone, oxacyclohexadecan-2-one and mixtures thereof;

(C) about 0.1 to about 10 wt. % of a thickening agent;

(D) a mixture of solvents which include about 40 wt. % to about 80 wt. % of a lower alkanol;

(E) a crystallization inhibitor capable of inhibiting crystallization of testosterone, wherein said composition is maintained on said skin for a period of time sufficient for delivery of the testosterone to the body of the male and is applied to the skin in the form of a unit dose which contains about 1 to about 300 mg of testosterone and such that, following a single application of the unit dose to the skin, the amount of circulating testosterone (AUC_0-24) in the blood serum of the male achieved in the 24-hour period following the application is about 100 to about 35,000 ng.h/dL greater than the amount of circulating testosterone (AUC_0-24) in the blood serum of the male than would have been achieved in the same 24-hour period had the dose not been administered.