Pharmaceutical composition

• US 8,063,029 B2
• Filed: 10/31/2007
• Issued: 11/22/2011
• Est. Priority Date: 04/19/2002
• Status: Expired due to Fees

• Current Assignee: FCB I LLC (Xstelos Holdings)
• Original Assignee: FCB I LLC (Xstelos Holdings)
• Inventors: Gyurik, Robert J.
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): HUANG, GIGI GEORGIANA
• Application Number:
  US11/930,812
• Publication Number:
  US 20080108590A1
• Time in Patent Office: 1,483 Days
• Field of Search: 514/169
• US Class Current: 514/169
• 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 0.5 to about 25 wt. % of a Hsieh enhancer;

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

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

wherein the Hsieh enhancer is selected from the group consisting of 3-methylcyclopentadecanone, 9-cycloheptadecen-1-one, cyclohexadecanone, cyclopentadecanone and oxacyclohexadecan-2-one.

2. The method according to claim 1 in which testosterone is delivered transdermally to the blood of a male patient by use of the composition in the form of a unit dose such that, following a single application of the unit dose to the patient, the amount of circulating testosterone (AUC_0-24) in the blood serum of the patient 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 patient that would have been achieved in the same 24-hour period had the dose not been administered.

3. The method of claim 1, wherein the composition further comprises a crystallization inhibitor.

4. The method of claim 3, wherein the crystallization inhibitor is polyethylene glycol.

5. The method of claim 4, wherein the polyethylene glycol is present in an amount ranging from about 0.001 to about 5 wt. %.

6. The method of claim 1, wherein the composition has a viscosity ranging from about 1,000 to about 9,000 cps.

7. The method of claim 1, wherein the composition has a pH ranging from about 4 to about 8.

8. The method of claim 1, wherein the mixture of solvents comprises a co-solvent selected from the group consisting of glycerin, propylene glycol, polyethylene, polypropylene, silicone and mixtures thereof.

9. The method of claim 8, wherein the co-solvent comprises glycerin.

10. The method of claim 8, wherein the co-solvent comprises propylene glycol.