Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels

• US 9,757,388 B2
• Filed: 05/14/2012
• Issued: 09/12/2017
• Est. Priority Date: 05/13/2011
• Status: Active Grant

• Current Assignee: Acerus Pharmaceuticals Srl
• Original Assignee: Acerus Pharmaceuticals Srl
• Inventors: Kreppner, Wayne, Fogarty, Siobhan, Oberegger, Werner, Maes, Paul
• Primary Examiner(s): Hui, San-Ming
• Application Number:
  US13/471,445
• Publication Number:
  US 20130059827A1
• Time in Patent Office: 1,947 Days
• Field of Search: 514178, 514170, 514182
• 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 9/0043 Nose
• 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 15/12 for climacteric disorders

Abstract

The present invention relates to lower dosage strength pernasal testosterone gel formulations for intranasal administration and treatment methods for using the lower dosage strength pernasal testosterone gel formulations for treating a female subject with anorgasmia and/or hypoactive sexual desire disorder.

Claims

1. A method of treating a subject for anorgasmia, said method comprising:

administering intranasally to the subject an effective amount of a testosterone gel which comprises;

a. about 0.6% testosterone by weight of the testosterone gel, wherein the testosterone has a particle size of great than 10 μ

m to prevent the testosterone particles from entering the respiratory tract following said intranasal administration; and

b. a pharmaceutically acceptable vehicle, wherein said intranasal administration comprises depositing the testosterone gel within each nostril of the subject at an optimal anatomical location to deliver intranasally a therapeutically effective amount of testosterone to the subject to effectively treat the anorgasmia.

7. The method of claim 1, wherein the testosterone gel further comprises a solvent, a wetting agent, and a viscosity increasing agent.

8. The method of claim 7, wherein the solvent is castor oil.

9. The method of claim 7, wherein the wetting agent is an oleoyl polyoxylglyceride.

10. The method of claim 7, wherein the viscosity increasing agent is colloidal silicon dioxide.

11. The method of claim 1, wherein the testosterone gel further comprises castor oil, oleoyl polyoxylglycerides and colloidal silicon dioxide.

12. The method of claim 1, wherein the testosterone gel is bioequivalent to another 0.6% testosterone gel.

13. The method of claim 1, wherein the testosterone gel is pharmaceutically equivalent to another 0.6% testosterone gel.

14. The method of claim 1, wherein the testosterone gel is therapeutically equivalent to another 0.6% testosterone gel.

23. The method of any one of claim 1, 2, 3, 4, 5, 6, 12, 13, 14, 20, 21, or 22, wherein the testosterone gel increases the plasma testosterone level to at least about 0.4 ng/ml within about 10 minutes following the immediate nasal administration of the testosterone gel to the subject.

24. The method of any one of claim 1, 2, 3, 4, 5, 6, 12, 13, 14, 20, 21, or 22, wherein the administration of the testosterone gel to the subject increases the plasma testosterone level in the subject to at least about 0.7 ng/ml within about 100 minutes following the immediate nasal administration of the testosterone gel to the subject.

25. The method of any one of claim 1, 2, 3, 4, 5, 6, 12, 13, 14, 20, 21, or 22, wherein administration of the testosterone gel to the subject increases the plasma testosterone level in the subject within at least about 10 minutes following the immediate nasal administration of the testosterone gel to the subject.

26. The method of any one of claim 1, 2, 3, 4, 5, 6, 12, 13, 14, 20, 21, or 22, wherein the nasal administration of the testosterone gel to the subject increases the plasma testosterone level in the subject to a level of at least about 0.3 ng/ml, and wherein the testosterone plasma level increase is maintained in the subject for about 6 hours immediately following the nasal administration of the testosterone gel to the subject.

27. The method of any one of claim 1, 2, 3, 4, 5, 6, 12, 13, 14, 20, 21, or 22, wherein the nasal administration of the testosterone gel to the subject increases the plasma testosterone level in the subject to at least about 0.4 ng/ml, and wherein the testosterone plasma level increase is maintained in the subject for at least 6 hours immediately following the nasal administration of the testosterone gel to the subject.

28. The method of any one of claim 1, 2, 3, 4, 5, 6, 12, 13, 14, 20, 21, or 22, wherein the nasal administration of the testosterone gel to the subject increases the plasma testosterone level in the subject to at least about 0.7 ng/ml within about 60 minutes immediately following the nasal administration of the testosterone gel to the subject.

29. The method of claim 23, wherein the subject is a female.

30. The method of claim 29, wherein the female is a woman.

2. An intranasal method of treating a subject diagnosed with anorgasmia with a testosterone gel for nasal administration comprising about 0.6% testosterone by weight of the testosterone gel, said method comprising:

applying the testosterone gel into each nostril of the subject at least once a day to deliver an effective amount of testosterone to treat the anorgasmia, wherein the testosterone has a particle size of greater than 10 μ

m, so that no more than an insubstantial number of testosterone particles enter the respiratory tract following said application.

3. The method of claim 2, wherein the subject receives the testosterone gel intranasally twice daily.

4. A method of treating a subject for anorgasmia, said method comprising:

administering intranasally to the subject an effective amount of a testosterone the gel which comprises;

a. about 0.72% testosterone by weight of the testosterone gel, wherein the testosterone has a particle size of greater than 10 μ

m to prevent the testosterone particles from entering the reparatory tract following said intranasal administration; and

b. a pharmaceutically acceptable vehicle, wherein said intranasal administration comprises depositing the testosterone gel within each nostril of the subject at an optimal anatomical location to deliver intranasally a therapeutically effective amount of testosterone to the subject to effectively treat the anorgasmia.

15. The method of claim 4, wherein the testosterone gel further comprises a solvent, a wetting agent, and a viscosity increasing agent.

16. The method of claim 15, wherein the solvent is castor oil.

17. The method of claim 15, wherein the wetting agent is an oleoyl polyoxylglyceride.

18. The method of claim 15, wherein the viscosity increasing agent is colloidal silicon dioxide.

19. The method of claim 4, wherein the testosterone gel further comprises castor oil, oleoyl polyoxylglycerides and colloidal silicon dioxide.

20. The method of claim 4, wherein the testosterone gel is bioequivalent to another 0.72% testosterone gel.

21. The method of claim 4, wherein the testosterone gel is pharmaceutically equivalent to another 0.72% testosterone gel.

22. The method of claim 4, wherein the testosterone gel is therapeutically equivalent to another 0.72% testosterone gel.

5. An intranasal method of treating a subject diagnosed with anorgasmia with a testosterone gel for nasal administration comprising about 0.72% testosterone by weight of the gel, comprising:

applying the testosterone gel into each nostril of the subject at least once a day to deliver an effective amount of testosterone to treat the anorgasmia, wherein the testosterone has a particle size of greater than 10 μ

m, so that no more than an insubstantial number of testosterone particles enter the respiratory tract following said application.

6. The method of claim 5, wherein the subject receives the testosterone gel intranasally twice daily.

31. A method of treating a female for anorgasmia, said method comprising:

(a) depositing an intranasal testosterone gel in an amount of between about 50 microliters and 150 microliters in each nasal cavity of each nostril of the female onto a mucosal membrane on an outer external nasal wall, opposite the nasal septum, preferably at about the middle to about the upper section of the outer external nasal wall and just under the cartilage section of the outer external nasal wall, to nasally deliver to the subject the intranasal testosterone gel to effectively treat the anorgasmia, wherein the testosterone gel comprises;

(i) about 0.6% testosterone by weight of the intranasal testosterone gel, wherein the testosterone has a particle size of greater than 10 μ

m to prevent the testosterone particles from entering the respiratory tract following said nasal deposition; and

(ii) a pharmaceutically acceptable vehicle; and

(b) squeezing or rubbing the exterior of the nose of the female following said nasal deposition to contact the nasally deposited intranasal testosterone gel with the nasal septum mucosal membrane within the nasal cavity, so that the deposited intranasal testosterone gel remains in contact with the mucosal membranes on the outer nasal wall and the nasal septum within the nasal cavity for sustained release of the testosterone from the intranasal testosterone gel over dose life.

32. The method of claim 31, wherein the intranasal testosterone gel is in an amount of about 100 microliters.

33. The method of claim 31, wherein said nasal deposition comprises depositing the intranasal testosterone gel into the nose of the female once or twice daily on demand.

34. The method of claim 31, wherein said nasal deposition comprises depositing the intranasal testosterone gel into the nose of the female at least once daily.

35. The method of claim 31, wherein said nasal deposition comprises depositing the intranasal testosterone gel into the nose of the female at least twice daily.

36. The method of claim 31, wherein the intranasal testosterone gel comprises:

(a) 0.6% testosterone,

(b) 91.4% castor oil,

(c) 4.0% oleoyl polyoxylglycerides, and

(d) 4% colloidal silicon dioxide.

37. A method of treating a female for anorgasmia, said method comprising:

(a) depositing an intranasal testosterone gel in an amount of between about 50 microliters and 150 microliters in each nasal cavity of each nostril of the female onto a mucosal membrane on an outer external nasal wall, opposite the nasal septum, preferably at about the middle to about the upper section of the outer external nasal wall and just under the cartilage section of the outer external nasal wall, to nasally deliver to the subject the intranasal testosterone gel to effectively treat the anorgasmia, wherein the testosterone gel comprises;

(i) about 0.72% testosterone by weight of the intranasal testosterone gel, wherein the testosterone has a particle size of greater than 10 μ

m to prevent the testosterone particles from entering the respiratory tract following said nasal deposition; and

(ii) a pharmaceutically acceptable vehicle; and

(b) squeezing or rubbing the exterior of the nose of the female following said nasal deposition to contact the nasally deposited intranasal testosterone gel with the nasal septum mucosal membrane within the nasal cavity, so that the deposited intranasal testosterone gel remains in contact with the mucosal membranes on the outer nasal wall and the nasal septum within the nasal cavity for sustained release of the testosterone from the intranasal testosterone gel over dose life.

38. The method of claim 37, wherein the intranasal testosterone gel is in an amount of about 100 microliters.

39. The method of claim 37, wherein said nasal deposition comprises depositing the intranasal testosterone gel into the nose of the female once or twice daily on demand.

40. The method of claim 37, wherein said nasal deposition comprises depositing the intranasal testosterone gel into the nose of the female at least once daily.

41. The method of claim 37, wherein said nasal deposition comprises depositing the intranasal testosterone gel into the nose of the female at least twice daily.

42. The method of claim 37, wherein the intranasal testosterone gel comprises:

(a) 0.72% testosterone,

(b) 91.4% castor oil,

(c) 4.0% oleoyl polyoxylglycerides, and

(d) 4% colloidal silicon dioxide.