Methods and compositions for treating polycystic ovary syndrome

• US 20040266678A1
• Filed: 07/30/2003
• Published: 12/30/2004
• Est. Priority Date: 01/22/2002
• Status: Active Grant

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Young, Andrew A., Hathaway, David R., Beeley, Nigel Robert Arnold, Prickett, Kathryn S.
• Granted Patent: US 7,105,490 B2
• Time in Patent Office: Days
• US Class Current: 514/1.1
• 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 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/24 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/28 Antiandrogens

Abstract

The present invention relates to methods of treating polycystic ovary syndrome (PCOS) comprising administering glucagon-like peptide-1 (GLP-1), exendin, and analogs and agonists thereof, to subjects suffering therefrom.

Claims

1. A method of treating a subject suffering from PCOS comprising the step of administering a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, wherein the subject exhibits at least one symptom of PCOS, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

2. The method according to claim 1, wherein the symptom is selected from the group consisting of insulin resistance, hyperinsulinemia, type-2 diabetes, obesity, hypertension, hyperlipidemia, anovulation or irregular ovulation, infertility, hyperandrogenism, hirsutism, alopecia, acne, enlarged multifollicular ovaries, abnormal uterine bleeding, and spontaneous abortion.

3. The method according to claim 1, wherein the subject is a human.

4. The method according to claim 1, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

5. The method according to claim 1, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

6. The method according to claim 1 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

7. The method according to claim 6, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

8. The method according to claim 6, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactone, flutamide, and finasteride.

9. The method according to claim 6, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

10. The method according to claim 6, wherein the glucose is administered intravenously.

11. The method according to claim 6, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.

34. The method according to claim 1, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

12. A method of reducing insulin resistance in a subject suffering from PCOS comprising the step of administering a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

13. The method according to claim 12, wherein the subject is a human.

14. The method according to claim 12, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

15. The method according to claim 12, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

16. The method according to claim 12 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

17. The method according to claim 16, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

18. The method according to claim 16, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactohe, flutamide, and finasteride.

19. The method according to claim 16, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

20. The method according to claim 16, wherein the glucose is administered intravenously.

21. The method according to claim 16, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.

22. A method of preventing the onset of type-2 diabetes in a subject suffering from PCOS comprising the step of administering a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

23. The method according to claim 22, wherein the subject is a human.

24. The method according to claim 22, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

25. The method according to claim 22, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

26. The method according to claim 22 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

27. The method according to claim 26, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

28. The method according to claim 26, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactone, flutamide, and finasteride.

29. The method according to claim 26, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

30. The method according to claim 26, wherein the glucose is administered intravenously.

31. The method according to claim 26, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.

32. A method of restoring regular menses in a subject suffering from PCOS comprising the step of administering a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

33. The method according to claim 32, wherein the subject is a human.

35. The method according to claim 32, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

36. The method according to claim 32 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

37. The method according to claim 36, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

38. The method according to claim 36, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactone, flutamide, and finasteride.

39. The method according to claim 36, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

40. The method according to claim 36, wherein the glucose is administered intravenously.

41. The method according to claim 36, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.

42. A method of restoring regular ovulation in a subject suffering from PCOS comprising the step of administering a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

43. The method according to claim 42, wherein the subject is a human.

44. The method according to claim 42, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

45. The method according to claim 42, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

46. The method according to claim 42 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

47. The method according to claim 46, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

48. The method according to claim 46, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactone, flutamide, and finasteride.

49. The method according to claim 46, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

50. The method according to claim 46, wherein the glucose is administered intravenously.

51. The method according to claim 46, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.

52. A method of restoring fertility in a subject suffering from PCOS comprising the step of administering a a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

53. The method according to claim 52, wherein the subject is a human.

54. The method according to claim 52, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

55. The method according to claim 52, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

56. The method according to claim 52 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

57. The method according to claim 56, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

58. The method according to claim 56, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactone, flutamide, and finasteride.

59. The method according to claim 56, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

60. The method according to claim 56, wherein the glucose is administered intravenously.

61. The method according to claim 56, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.

62. A method for preventing spontaneous abortion in a subject suffering from PCOS comprising the step of administering a compound selected from the group consisting of GLP-1, exendin, and agonists and analogs thereof, with the proviso that the analogs of exendin do not include the peptides of SEQ ID NOs:

7-13.

63. The method according to claim 62, wherein the subject is a human.

64. The method according to claim 62, wherein GLP-1 is selected from the group consisting of GLP-1 (7-36)NH₂, GLP-4(7-37), GLP-1(9-36) and exendin-4.

65. The method according to claim 62, wherein the GLP-1, exendin, or agonists or analogs thereof is administered by an infusion pump or by subcutaneous injection of a slow release formulation.

66. The method according to claim 62 wherein the GLP-1, exendin, or agonists or analogs thereof is administered with an agent selected from the group consisting of an ovulation inducing drug, an anti-androgenic drug, an insulin-sensitizing agent and glucose.

67. The method according to claim 66, wherein the ovulation inducing drug is selected from the group consisting of clomiphene, follistim, and Gonal-F.

68. The method according to claim 66, wherein the anti-androgenic drug is selected from the group consisting of a birth control pill, spironolactone, flutamide, and finasteride.

69. The method according to claim 66, wherein the insulin-sensitizing agent is selected from the group consisting of metformin, D-Chiro-inositol, diazoxide, and PPAR inhibitors (e.g., troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos)).

70. The method according to claim 66, wherein the glucose is administered intravenously.

71. The method according to claim 66, wherein the GLP-1, exendin, or agonists or analogs thereof and the agent are administered either sequentially or concurrently.