Treatment of female sexual dysfunction with vasoactive intestinal polypeptide agonists

• US 7,226,910 B2
• Filed: 10/28/2005
• Issued: 06/05/2007
• Est. Priority Date: 10/28/1997
• Status: Expired due to Fees

• Current Assignee: Vivus Incorporated
• Original Assignee: Vivus Incorporated
• Inventors: Wilson, Leland F., Place, Virgil A.
• Primary Examiner(s): CHISM, BILLY D
• Application Number:
  US11/262,067
• Publication Number:
  US 20060041021A1
• Time in Patent Office: 585 Days
• Field of Search: None
• US Class Current: 424/450
• 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 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• 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 31/5585 having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 930/17 Vasoactive intestinal peptides; related peptides

Abstract

Methods for treating female sexual dysfunction are provided. A pharmaceutical composition containing a vasoactive agent selected from vasoactive intestinal potypeptide (VIP) and VIP agonists is administered to the vagina and/or vulvar region of the individual undergoing treatment. The formulations are also useful for improving vaginal muscle tone and tissue health, enhancing vaginal lubrication, and minimizing excess collagen deposition. Pharmaceutical formulations and kits are also provided.

Claims

1. A method for treating sexual dysfunction in a female individual caused by lack of increased blood flow in the female individual'"'"'s genitalia in response to sexual stimulation, comprising administering to the vagina and/or vulvar region of the individual a pharmaceutical formulation that comprises an amount of a vasoactive intestinal polypeptide (VIP) agonist sufficient to cause increased blood flow in the female individual'"'"'s genitalia, wherein the vasoactive intestinal polypeptide agonist is selected from SEQ ID NOs:

204–

206.

2. The method of claim 1, wherein the pharmaceutical formulation further includes a pharmaceutically acceptable carrier suited to vaginal and/or vulvar drug administration.

3. The method of claim 1, further including administering a steroid to the vagina and/or vulvar region of the individual.

4. The method of claim 3, wherein the steroid is selected from the group consisting of progestins, estrogens, androgens, and combinations thereof.

5. The method of claim 1, wherein the pharmaceutical formulation further includes a compound selected from the group consisting of steroid agonists, partial agonists, and antagonists.

6. The method of claim 1, wherein the pharmaceutical formulation is contained within a delivery system selected to provide a predetermined agent release profile.

7. The method of claim 6, wherein the agent release profile is pulsatile.

8. The method of claim 6, wherein the agent release profile is continuous.

9. The method of claim 6, wherein the agent release profile is cyclical.

10. The method of claim 6, wherein the agent release profile is diurnal.

11. The method of claim 1, wherein the pharmaceutical formulation is administered vaginally.

12. The method of claim 11, wherein the pharmaceutical formulation is in the form of an ointment, cream, gel, solid, solution, suspension, foam, or liposomal composition.

13. The method of claim 11, wherein the pharmaceutical formulation is contained within a vaginal ring, tampon, suppository, sponge, pillow, puff, or osmotic pump system.

14. The method of claim 1, wherein the pharmaceutical formulation is administered to the vulvar region.

15. The method of claim 1, wherein the VIP agonist comprises a polypeptide sequence comprising a human vasoactive intestinal polypeptide sequence having amino acid substitutions at one or more positions.

16. The method of claim 15, wherein the vasoactive intestinal polypeptide agonist is terminally modified.

17. The method of claim 4, wherein the steroid is an androgenic agent.

18. The method of claim 17, wherein the androgenic agent is selected from the group consisting of androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androstenediol, androstenediol-3-acetate, androstenediol-17-acetate, androstenediol-3,17-diacetate, androstenediol-17-benzoate, androstenediol-3-acetate-17-benzoate, androstenedione, dehydroepiandrosterone, sodium dehydroepiandrosterone sulfate, 4-dihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxymesterone, methyltestosterone, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexane-propionate, nandrolone benzoate, nandrolone cyclohexanecarboxylate, oxandrolone, oxymetholone, stanozolol, testolactone, testosterone, and pharmaceutically acceptable esters of testosterone and 4-dihydrotestosterone.

19. The method of claim 17, wherein the androgenic agent is selected from the group consisting of testosterone, C-17 esters of testosterone, 4-dihydrotestosterone, C-17 esters of 4-dihydrotestosterone, dehydroepiandrosterone, and methyltestosterone.

20. A method for maintaining the health of healthy tissue, or improving the health of unhealthy tissue of the female genitalia, comprising administering to a female individual, on an as-needed basis, a therapeutically effective amount of a vasoactive intestinal polypeptide agonist selected from SEQ ID NOs:

204–

206.

21. A method for decreasing vaginal atrophy, comprising administering to a female individual, on an as-needed basis, a therapeutically effective amount of a vasoactive intestinal polypeptide agonist selected from SEQ ID NOs:

204–

206.

22. A method for decreasing vaginal pain caused by dyspareunia during sexual intercourse, comprising administering to a female individual suffering from dyspareunia a therapeutically effective amount of a vasoactive intestinal polypeptide agonist selected from SEQ ID NOs:

204–

206.

23. A method for alleviating vaginal itching and dryness, comprising administering to a female individual in need of such treatment a therapeutically effective amount of a vasoactive intestinal polypeptide agonist selected from SEQ ID NOs:

204–

206 on an as-needed basis.