Method and compositions for the treatment or amelioration of female sexual dysfunction

• US 6,756,407 B2
• Filed: 04/22/2002
• Issued: 06/29/2004
• Est. Priority Date: 04/22/1994
• Status: Expired due to Fees

• Current Assignee: PARTEQ Innovations (Queen's University)
• Original Assignee: Queen's University At Kingston
• Inventors: Adams, Michael A., Heaton, Jeremy P. W.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US10/126,933
• Publication Number:
  US 20020193442A1
• Time in Patent Office: 799 Days
• Field of Search: 514/284, 514/573, 514/772.6
• US Class Current: 514/573
• 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 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Abstract

The present invention provide a method of treating sexual dysfunction in a female, including the vasculogenic symptoms of delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse (dyspareunia), diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm, or of combating vaginal pain by stimulating peripheral pelvic nerve release of nitric oxide (NO). The method comprises administering to a female in need of such treatment a therapeutically effective amount of a compound which acts on a mid-brain pathway to increase blood flow to the ilio-hypogastric-pudendal artery bed and stimulate the release of nitric oxide (NO) from peripheral NANC nerve cells. The preferred compound for the method of this invention is apomorphine or one of its pharmaceutically acceptable salts, esters, or pro-drugs. Alternatively, the apomorphine is co-administered with an apomorphine-potentiating amount of an androgen, preferably testosterone either prior to, or concomitantly with, the administration of the apomorphine.

Claims

1. A method of treating sexual dysfunction in an ovariectomized female mammal having an altered hormonal milieu, comprising administering to said female apomorphine or a pharmaceutically acceptable salt, ester, or pro-drug thereof, such that sexual dysfunction is treated.

2. The method of claim 1, wherein said altered hormonal milieu is associated with a diminished level of at least one endogenous hormone.

3. The method of claim 1, wherein said female mammal is human.

4. The method of claim 1, wherein said apomorphine is chronically administered.

5. The method of claim 1, wherein said apomorphine is administered on an as-needed basis.

6. The method of claim 1 wherein said apomorphine is administered prior to sexual activity.

7. The method of claim 6 wherein said apomorphine is administered from about 2 minutes to about 120 minutes prior to sexual activity.

8. The method of claim 6 wherein said apomorphine is administered from about 2 minutes to about 60 minutes prior to sexual activity.

9. The method of claim 1 wherein said apomorphine is administered via a route selected from sub-cutaneous, intramuscular, transdermal, sublingual, buccal, intra-nasal, vaginal, and rectal.

10. The method of claim 1 wherein said apomorphine is administered sublingually.

11. The method of claim 1 wherein said apomorphine is administered transdermally.

12. The method of claim 1 wherein said apomorphine is administered intra-nasally.

13. The method of claim 1 wherein said apomorphine or pharmaceutically acceptable salt, ester, or prodrug thereof is administered in an amount between about 1 milligram and about 12 milligrams.

14. The method of claim 1 wherein said apomorphine or pharmaceutically acceptable salt, ester, or prodrug thereof is administered in an amount between about 2.5 milligrams and about 10 milligrams.

15. The method of claim 1 wherein said apomorphine or pharmaceutically acceptable salt, ester, or prodrug thereof is administered in an amount between about 10 and about 100 micrograms per kilogram of body weight.

17. The method of claim 1 wherein the plasma concentration of apomorphine is maintained in the range of about 0.3 to about 6 nanograms per milliliter during sexual activity.

18. The method of claim 1 wherein the plasma concentration of apomorphine is maintained in the range of about 0.3 to about 4 nanograms per milliliter during sexual activity.

19. The method of claim 1 wherein the plasma concentration of apomorphine is maintained in the range of about 1 to about 2 nanograms per milliliter during sexual activity.

16. The method of claim wherein said apomorphine or pharmaceutically acceptable salt, ester, or prodrug thereof is administered in an amount between about 25 and about 80 micrograms per kilogram of body weight.