Compositions and methods for treatment of premature ejaculation

• US 20040241245A1
• Filed: 03/22/2004
• Published: 12/02/2004
• Est. Priority Date: 03/21/2003
• Status: Active Grant

• Current Assignee: Nexmed Holdings
• Original Assignee: Nexmed Holdings
• Inventors: Wang, Qin, Mo, Y. Joseph, Lu, Mingqi, Yeager, James L.
• Granted Patent: US 8,841,345 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4453 only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/736 Glucomannans or galactomannans, e.g. locust bean gum, guar gum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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 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: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives

Abstract

Compositions and methods for the treatment of premature ejaculation are provided wherein a composition comprising a topical anesthetic, a shear-thinning polymeric thickener, a lipophilic component that is selected from the group consisting of an aliphatic C₁ to C₈ alcohol, an aliphatic C₈ to C₃₀ ester, a liquid polyol and a mixture thereof, water and a buffer system that provides a buffered pH value for the composition in the range of about 3 to about 7.4 is administered to the penile meatus.

Claims

1. A topical composition comprising:

a topical anesthetic;

a polymeric thickener selected from the group consisting of shear-thinning polysaccharide gums and shear-thinning polyacrylic acid polymers;

a lipophilic component that is selected from the group consisting of an aliphatic C₁ to C₈ alcohol, an aliphatic C₈ to C₃₀ ester, a liquid polyol and a mixture thereof;

water; and

a buffer system that provides a buffered pH value for said composition in the range of about 3 to about 7.4.

2. The composition of claim 1 further comprising a vasoactive prostaglandin selected from the group consisting of PGE₁, PGA₁, PGB₁, PGF_1α

, 19-hydroxy-PGA₁, 19-hydroxy-PGB₁, PGE₂, PGA₂, PGB₂, 19-hydroxy-PGA₂, 19-hydroxy-PGB₂, PGE₃, PGF₃ and mixtures thereof.

3. The composition of claim 2 wherein the vasoactive prostaglandin is selected from the group consisting of prostaglandin E₁, prostaglandin E₂, a pharmaceutically acceptable salt thereof, a lower alkyl ester thereof and a mixture thereof.

4. The composition of claim 2 wherein the vasoactive prostaglandin is present in the amount of about 0.1 mg to about 0.5 mg.

5. The composition of claim 2 wherein the vasoactive prostaglandin is present in the amount of about 0.2 mg to about 0.3 mg.

6. The composition of claim 1 wherein the topical anesthetic is an aminoamide local anesthetic selected from the group consisting of lidocaine, bupivacaine, mepivacaine, dibucaine, propivacaine, etidocaine, tocainide, a pharmaceutically acceptable salt thereof and a mixture thereof.

7. The composition of claim 1 wherein the topical anesthetic is a local anesthetic selected from the group consisting of lidocaine, bupivacaine, dyclonine, a pharmaceutically acceptable salt thereof and a mixture thereof.

8. The composition of claim 1 wherein the topical anesthetic comprises about 0.01 to about 10 percent by weight based on the weight of the composition.

9. The composition of claim 1 wherein the polymeric thickener is a shear-thinning polyacrylic acid polymer.

10. The composition of claim 1 wherein the shear-thinning polysaccharide gum is a galactomannan gum.

11. The composition of claim 10, wherein the shear-thinning polysaccharide gum is a modified galactomannan gum.

12. The composition of claim 11 wherein the modified galactomannan gum is a modified guar gum.

13. The composition of claim 1 further comprising a penetration enhancer selected from the group consisting of an alkyl-(N-substituted amino) alkanoate, an alkyl-2-(N,N-disubstituted amino) alkanoate, an (N-substituted amino) alkanol alkanoate, an (N,N-disubstituted amino) alkanol alkanoate, a pharmaceutically acceptable salt thereof and a mixture thereof.

14. The composition of claim 13 wherein the penetration enhancer is dodecyl 2-(N,N-dimethylamino)-propionate or a pharmaceutically acceptable salt.

15. The composition of claim 1 wherein the lipophilic component comprises at least one glyceryl ester selected from the group consisting of monoglycerides, diglycerides, triglycerides, and mixtures thereof.

16. The composition of claim 1 wherein the lipophilic component comprises at least one glyceryl ester selected from the group consisting of glyceryl monooleate, triolein, trimyristin, tristearin, and mixtures thereof.

17. The composition of claim 1 wherein the composition further comprises an emulsifier selected from the group consisting of sucrose esters, polyoxyethylene sorbitan esters, long chain alcohols, and glyceryl esters.

18. The composition of claim 1 wherein the emulsifier comprises at least one glyceryl ester selected from the group consisting of glyceryl monooleate, triolein, trimyristin, tristearin, and mixtures thereof.

19. The composition of claim 1 wherein the composition further comprises up to about 5 percent myrtenol, based on the total weight of the composition.

20. The composition of claim 1 wherein the composition further comprises a preservative.

21. The method of claim 14 wherein the composition further comprises a fragrance.

22. A method of treating premature ejaculation in a patient needing such treatment comprising the steps of:

administering meatally an ejaculation latency prolonging amount of a semi-solid composition, comprising a topical anesthetic;

a polymeric thickener selected from the group consisting of shear-thinning polysaccharide gums and shear-thinning polyacrylic acid polymers;

a lipophilic component that is selected from the group consisting of an aliphatic C₁ to C₈ alcohol, an aliphatic C₈ to C₃₀ ester, a liquid polyol and a mixture thereof;

water; and

a buffer system that provides a buffered pH value for said composition in the range of about 3 to about 7.4.

23. The method of claim 22 wherein the composition further comprises a vasoactive prostaglandin selected from the group consisting of PGE₁, PGA₁, PGB₁, PGF_1α

, 19-hydroxy-PGA₁, 19-hydroxy-PGB₁, PGE₂, PGA₂, PGB₂, 19-hydroxy-PGA₂, 19-hydroxy-PGB₂, PGE₃, PGF₃ and mixtures thereof present in the amount of about 0.1 mg to about 0.5 mg.

24. The method of claim 22 wherein vasoactive prostaglandin is selected from the group consisting of prostaglandin E₁, prostaglandin E₂, a pharmaceutically acceptable salt thereof, a lower alkyl ester thereof and a mixture thereof.

25. The method of claim 22 wherein the vasoactive prostaglandin is present in the amount of about 0.2 mg to about 0.3 mg.

26. The method of claim 22 wherein the topical anesthetic is an aminoamide local anesthetic selected from the group consisting of lidocaine, bupivacaine, mepivacaine, dibucaine, propivacaine, etidocaine, tocainide, a pharmaceutically acceptable salt thereof and a mixture thereof.

27. The method of claim 22 wherein the topical anesthetic is a local anesthetic selected from the group consisting of lidocaine, bupivacaine, dyclonine, a pharmaceutically acceptable salt thereof and a mixture thereof.

28. The method of claim 22 wherein the topical anesthetic comprises about 0.01 to about 4 percent by weight based on the weight of the composition.

29. The method of claim 22 wherein the polymeric thickener is a shear-thinning polyacrylic acid polymer.

30. The method of claim 22 wherein the polymer is a shear-thinning polysaccharide gum.

31. The method of claim 22 wherein the shear-thinning polysaccharide gum is a galactomannan gum.

32. The method of claim 22, wherein the shear-thinning polysaccharide gum is a modified galactomannan gum.

33. The method of claim 32 wherein the modified galactomannan gum is a modified guar gum.

34. The method of claim 22 wherein the composition further comprises a penetration enhancer selected from the group consisting of an alkyl-(N-substituted amino) alkanoate, an alkyl-2-(N,N-disubstituted amino) alkanoate, an (N-substituted amino) alkanol alkanoate, an (N,N-disubstituted amino) alkanol alkanoate, a pharmaceutically acceptable salt thereof and a mixture thereof.

35. The method of claim 34 wherein the penetration enhancer is dodecyl 2-(N,N-dimethylamino)-propionate or a pharmaceutically acceptable salt.

36. The method of claim 22 wherein the lipophilic component comprises at least one aliphatic C₈ to C₃₀ ester.

37. The method of claim 22 wherein the lipophilic component comprises at least one glyceryl ester selected from the group consisting monoglycerides, diglycerides, triglycerides, and mixtures thereof.

38. The method of claim 22 wherein the lipophilic component comprises at least one glyceryl ester selected from the group consisting of glyceryl monooleate, triolein, trimyristin, tristearin, and mixtures thereof.

39. The method of claim 22 wherein the composition further comprises an emulsifier selected from the group consisting of sucrose esters, polyoxyethylene sorbitan esters, long chain alcohols, and glyceryl esters.

40. The method of claim 22 wherein the emulsifier comprises at least one glyceryl ester selected from the group consisting of glyceryl monooleate, triolein, trimyristin, tristearin, and mixtures thereof.

41. The method of claim 22 wherein the composition further comprises up to about 5 percent myrtenol, based on the total weight of the composition.

42. The method of claim 22 wherein the composition further comprises a preservative.

43. The method of claim 22 wherein the composition further comprises a fragrance.