Stabilized prostaglandin E composition

• US 20080090911A1
• Filed: 10/11/2006
• Published: 04/17/2008
• Est. Priority Date: 10/11/2006
• Status: Active Grant

• Current Assignee: Nexmed Holdings
• Original Assignee: Nexmed Holdings
• Inventors: Wang, Yiping, Frank, Daniel W.
• Granted Patent: US 7,560,489 B2
• Time in Patent Office: Days
• US Class Current: 514/573
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• 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: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence

Abstract

A prostaglandin E composition comprises are substantially free from C₁-C₄ alcohols and include the prostaglandin E compound together with a (C₁-C₄)-alkyl (C₈-C₂₂) carboxylic ester (e.g., ethyl laurate), an N,N-di(C₁-C₈) alkylamino substituted, (C₄-C₁₈) alkyl (C₂-C₁₈) carboxylic ester and/or a pharmaceutically acceptable addition salt thereof, and optionally, a viscosity enhancing agent such as guar gum. The prostaglandin E composition can be combined with an aqueous alcoholic diluent to form a pharmaceutical composition for topical application to a patient, for example, to treat sexual dysfunction. The prostaglandin E compositions are stable for prolonged periods of storage at room temperature.

Claims

1. A storage stable prostaglandin E group composition comprising:

(a) a prostaglandin E group compound;

(b) a (C₁-C₄)-alkyl (C₈-C₂₂) carboxylic ester;

(c) an N,N-di(C₁-C₈) alkylamino substituted, (C₄-C₁₈) alkyl (C₂-C₁₈) carboxylic ester, a pharmaceutically acceptable addition salt thereof, or a combination thereof; and

(d) optionally, a viscosity enhancing agent;

the composition being substantially free from C₁-C₄ alcohols.

2. The composition of claim 1 wherein the prostaglandin E group compound is selected from the group consisting of prostaglandin E₁, prostaglandin E₂, and prostaglandin E₃.

3. The composition of claim 1 wherein the (C₁-C₄)-alkyl (C₈-C₂₂) carboxylic ester comprises ethyl laurate.

4. The composition of claim 1 wherein the N,N-di(C₁-C₈) alkylamino substituted, (C₄-C₁₈) alkyl (C₂-C₁₈) carboxylic ester comprises dodecyl 2-(N,N-dimethylamino)-propionate or a pharmaceutically acceptable addition salt thereof.

5. The composition of claim 1 including a viscosity enhancing agent selected from the group consisting of a polysaccharide, a modified polysaccharide, a cellulose derivative, and a cross-linked polyacrylic acid.

6. The composition of claim 1 comprising guar gum as the viscosity enhancing agent.

18. A multi-part dosage form suitable for preparing a topical prostaglandin E composition comprising;

(a) a sealed actives compartment comprising a composition of claim 1; and

(b) a sealed diluent compartment comprising an aqueous diluent including a C₁-C₄ alcohol, water, and optionally a pH buffering agent.

19. The multi-part dosage form of claim 18 wherein the C₁-C₄ alcohol in the diluent is ethanol.

7. A storage stable prostaglandin E group composition comprising:

(a) about 0.025 percent to about 10 percent by weight of a prostaglandin E group compound;

(b) about 0.025 to about 40 percent by weight of a (C₁-C₄)-alkyl (C₈-C₂₂) carboxylic ester;

(c) about 0.025 to about 40 percent by weight of an N,N-di(C₁-C₈) alkylamino substituted, (C₄-C₁₈) alkyl (C₂-C₁₈) carboxylic ester, a pharmaceutically acceptable addition salt thereof, or a combination thereof; and

(d) about 0.025 to about 40 percent by weight of a viscosity enhancing agent;

the composition being substantially free from C₁-C₄ alcohols.

8. The composition of claim 7 wherein the prostaglandin E group compound is selected from the group consisting of prostaglandin E₁, prostaglandin E₂, and prostaglandin E₃.

9. The composition of claim 7 wherein the (C₁-C₄)-alkyl (C₈-C₂₂) carboxylic ester comprises ethyl laurate.

10. The composition of claim 7 wherein the N,N-di(C₁-C₈) alkylamino substituted, (C₄-C₁₈) alkyl (C₂-C₁₈) carboxylic ester comprises dodecyl 2-(N,N-dimethylamino)-propionate or a pharmaceutically acceptable addition salt thereof.

11. The composition of claim 7 wherein the viscosity enhancing agent is selected from the group consisting of a polysaccharide, a modified polysaccharide, a cellulose derivative, and a cross-linked polyacrylic acid.

12. The composition of claim 7 wherein the viscosity enhancing agent comprises guar gum.

13. The composition of claim 7 wherein the prostaglandin E group compound comprises about 0.5 to about 5 percent by weight prostaglandin E₁.

14. The composition of claim 7 wherein the (C₁-C₄)-alkyl (C₈-C₂₂) carboxylic ester comprises about 0.5 to about 35 percent by weight ethyl laurate.

15. The composition of claim 7 wherein the N,N-di(C₁-C₈) alkylamino substituted, (C₄-C₁₈) alkyl (C₂-C₁₈) carboxylic ester comprises about 0.5 to about 35 percent by weight dodecyl 2-(N,N-dimethylamino)-propionate or a pharmaceutically acceptable addition salt thereof.

16. The composition of claim 7 wherein the viscosity enhancing agent comprises about 0.5 to about 35 percent by weight guar gum.

20. A multi-part dosage form suitable for preparing a topical prostaglandin E composition comprising;

(a) a sealed actives compartment comprising a composition of claim 7; and

(b) a sealed diluent compartment comprising an aqueous diluent including a C₁-C₄ alcohol, water, and optionally a pH buffering agent.

21. The multi-part dosage form of claim 20 wherein the C₁-C₄ alcohol in the diluent is ethanol.

17. A storage stable prostaglandin E group composition comprising:

(a) about 0.025 percent to about 10 percent by weight of prostaglandin E₁;

(b) about 0.025 to about 40 percent by weight of a ethyl laurate;

(c) about 0.025 to about 40 percent by weight of dodecyl 2-(N,N-dimethylamino)-propionate or a pharmaceutically acceptable addition salt thereof; and

(d) about 0.025 to about 40 percent by weight of guar gum;

the composition being substantially free from C₁-C₄ alcohols.

22. A multi-part dosage form suitable for preparing a topical prostaglandin E composition comprising;

(a) a sealed actives compartment comprising a composition of claim 17; and

(b) a sealed diluent compartment comprising an aqueous diluent including a C₁-C₄ alcohol, water, and optionally a pH buffering agent.

23. The multi-part dosage form of claim 22 wherein the C₁-C₄ alcohol in the diluent is ethanol.