Pharmaceutical composition

• US 7,608,608 B2
• Filed: 01/23/2009
• Issued: 10/27/2009
• Est. Priority Date: 04/19/2002
• Status: Expired due to Fees

• Current Assignee: FCB I LLC (Xstelos Holdings)
• Original Assignee: CPEX Pharmaceuticals Incorporated
• Inventors: Gyurik, Robert J.
• Primary Examiner(s): Krass; Frederick
• Assistant Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US12/359,162
• Publication Number:
  US 20090118251A1
• Time in Patent Office: 277 Days
• Field of Search: None
• 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 2000 to about 6000 cps and a pH of about 4 to about 8, and comprises:

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

(B) about 0.5 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 1 to about 6 wt. % of a thickening agent;

(D) a mixture of solvents which include;

(i) about 60 to about 75 wt. % of ethanol or isopropanol; and

(ii) propylene glycol and glycerin as co-solvents.

2. The method of claim 1 further comprising about 0.001 to about 5 wt. % of polyethylene glycol as a crystallization inhibitor.

3. 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.

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

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

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

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

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