Claims
- 1. A method for treating a hormone associated condition in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating a hormone associated condition in the subject.
- 2. The method of claim 1, wherein the hormone associated condition is endometriosis.
- 3. The method of claim 1, wherein the hormone associated condition is ovarian cancer.
- 4. The method of claim 1, wherein the hormone associated condition is breast cancer.
- 5. The method of claim 1, wherein the hormone associated condition is polycystic ovary syndrome.
- 6. The method of claim 1, wherein the hormone associated condition is uterine leiomata.
- 7. The method of claim 1, wherein the hormone associated condition is dysfunctional uterine bleeding.
- 8. The method of claim 1, wherein the hormone associated condition is premenstrual syndrome.
- 9. The method of claim 1, wherein the hormone associated condition is vaginal bleeding.
- 10. The method of claim 1, wherein the hormone associated condition is uterine fibroids.
- 11. The method of claim 1, wherein the subject is a mammal.
- 12. The method of claim 1, wherein the subject is a human.
- 13. The method of claim 1, wherein the LHRH antagonist has an ED50 for histamine release in a standard in vitro histamine release assay of at least 3 μg/ml.
- 14. The method of claim 1, wherein the LHRH antagonist has an ED50 for histamine release in a standard in vitro histamine release assay of at least 5 μg/ml.
- 15. The method of claim 1, wherein the LHRH antagonist has an ED50 for histamine release in a standard in vitro histamine release assay of at least 10 μg/ml.
- 16. The method of claim 1, wherein the LHRH antagonist is a decapeptide or a nonapeptide compound having a D-asparagine, an L-asparagine, a D-glutamine, or an L-glutamine at a position corresponding to position 6 of naturally occurring LHRH, or a pharmaceutically acceptable salt thereof.
- 17. The method of claim 16, wherein the LHRH antagonist is a decapeptide.
- 18. The method of claim 16, wherein the LHRH antagonist is a nonapeptide.
- 19. The method of claim 1, wherein the LHRH antagonist is a peptide compound comprising a structure:
A-B-C-D-E-F-G-H-I-J wherein A is pyro-Glu, Ac-D-Nal, Ac-D-Qal, Ac-Sar, or Ac-D-Pal, or an analogue thereof; B is His or 4-Cl-D-Phe, or an analogue thereof; C is Trp, D-Pal, D-Nal, L-Nal-D-Pal(N—O), or D-Trp, or an analogue thereof; D is Ser, or an analogue thereof; E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile, or an analogue thereof; F is D-Asn or D-Gln; G is Leu or Trp, or an analogue thereof; H is Lys(iPr), Gln, Met, or Arg, or an analogue thereof; I is Pro, or an analogue thereof; and J is Gly-NH2 or D-Ala-NH2, or an analogue thereof; or a pharmaceutically acceptable salt thereof.
- 20. The method of claim 1, wherein the LHRH antagonist is a peptide compound comprising a structure:
A-B-C-D-E-F-G-H-I-J wherein A is pyro-Glu, Ac-D-Nal, Ac-D-Qal, Ac-Sar, or Ac-D-Pal, or an analogue thereof; B is His or 4-Cl-D-Phe, or an analogue thereof; C is Trp, D-Pal, D-Nal, L-Nal-D-Pal(N—O), or Trp, or an analogue thereof; D is Ser, or an analogue thereof; E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile, or an analogue thereof; F is D-Asn; G is Leu or Trp, or an analogue thereof; H is Lys(iPr), Gln, Met, or Arg, or an analogue thereof; I is Pro, or an analogue thereof; and J is Gly-NH2 or D-Ala-NH2, or an analogue thereof; or a pharmaceutically acceptable salt thereof.
- 21. The method of claim 1, wherein the LHRH antagonist is a peptide compound comprising a structure:
Ac-D-Nal-4-Cl-D-Phe-D-Pal-Ser-N-Me-Tyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH2; or a pharmaceutically acceptable salt thereof.
- 22. The method of claim 1, wherein the LHRH antagonist is a peptide compound comprising a structure:
Ac-D-Nal-4-Cl-D-Phe-D-Pal-Ser-Tyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH2; or a pharmaceutically acceptable salt thereof.
- 23. The method of claim 1, wherein the selective estrogen receptor modulator is raloxifene.
- 24. The method of claim 1, wherein the selective estrogen receptor modulator is tamoxifen.
- 25. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered to the subject using a sustained-release formulation.
- 26. The method of claim 25, wherein the sustained-release formulation of LHRH antagonist comprises a solid ionic complex of an LHRH antagonist and a carrier macromolecule, wherein the carrier and LHRH antagonist used to form the complex are combined at a weight ratio of carrier:antagonist of 0.5:1 to 0.1:1.
- 27. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered at a dosage of about 5-500 μg/kg/day.
- 28. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered at a dosage of about 10-400 μg/kg/day.
- 29. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered at a dosage of about 10-100 μg/kg/day.
- 30. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered to the subject simultaneously.
- 31. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered to the subject at different times.
- 32. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered to the subject in the same formulation.
- 33. The method of claim 1, wherein the LHRH antagonist and the selective estrogen receptor modulator are administered to the subject in separate formulations.
- 34. A method for treating endometriosis in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating endometriosis in the subject.
- 35. A method for treating ovarian cancer in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating ovarian cancer in the subject.
- 36. A method for treating breast cancer in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating breast cancer in the subject.
- 37. A method for treating polycystic ovary syndrome in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating polycystic ovary syndrome in the subject.
- 38. A method for treating uterine leiomata in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating uterine leiomata in the subject.
- 39. A method for treating dysfunctional uterine bleeding in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating dysfunctional uterine bleeding in the subject.
- 40. A method for treating premenstrual syndrome in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating premenstrual syndrome in the subject.
- 41. A method for treating vaginal bleeding in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating vaginal bleeding in the subject.
- 42. The method of claim 41, wherein the vaginal bleeding is due to thrombocytopenia.
- 43. The method of claim 42, wherein the thrombocytopenia is caused by chemotherapy treatment.
- 44. The method of claim 41, wherein the subject is suffering from a proliferative disorder.
- 45. The method of claim 44, wherein the proliferative disorder is acute myeloid leukemia.
- 46. A method for treating uterine fibroids in a subject, comprising administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator, thereby treating uterine fibroids in the subject.
RELATED APPLICATIONS
[0001] This application is a continuation of International Application No. PCT/US02/00751, filed Jan. 9, 2002, which claims priority to U.S. Provisional Patent Application Serial No. 60/262,494 filed Jan. 17, 2001, the entire contents of each of which are incorporated herein by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60262494 |
Jan 2001 |
US |
Continuations (1)
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Number |
Date |
Country |
Parent |
PCT/US02/00751 |
Jan 2002 |
US |
Child |
10619684 |
Jul 2003 |
US |