Claims for Patent: 7,255,984

Summary for Patent: 7,255,984

Title:	Combination therapy for osteoporosis
Abstract:	Pharmaceutical combination compositions including certain estrogen agonists/antagonists and prostaglandins or prostaglandin agonists/antagonists. The compositions are useful for the treatment of bone disorders including osteoporosis.
Inventor(s):	Ke; Hua Zhu (Ledyard, CT), Thompson; David D. (Gales Ferry, CT)
Assignee:	Pfizer Inc. (New York, NY)
Application Number:	09/736,051
Patent Claims:	1. A pharmaceutical composition comprising: a. a therapeutically effective amount of a first compound, said first compound being an estrogen agonist/antagonist; and b. a therapeutically effective amount of a second compound, said second compound being a prostaglandin or a prostaglandin agonist/antagonist. and a pharmaceutical carrier; wherein the estrogen agonist/antagonist is droloxifene, raloxifene, tamoxifen, 4-hydroxy-tamoxifen, Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)phenyl]-5,6,7,8-tet- rahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-n- aphthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrah- ydronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline. 2. A pharmaceutical composition according to claim 1 wherein the second compound is PGD.sub.1, PGD.sub.2, PGE.sub.2, PGE.sub.1, PGF.sub.2, PGF.sub.2.alpha. or 3S-(3-Hydroxy-4-phenyl-butyl)-2R-[6-(1H-tetrazol-5-yl)-hexyl]-cyclopentan- one. 3. A pharmaceutical composition according to claim 2 wherein the second compound is PGE.sub.2. 4. A pharmaceutical composition according to claim 2 wherein the second compound is 3S-(3-Hydroxy-4-phenyl-butyl)-2R-[6-(2H-tetrazol-5-yl)-hexyl]-cyclopentan- one. 5. A pharmaceutical composition according to claim 2 wherein the estrogen agonist/antagonist is Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-n- aphthalene2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrah- ydronaphthalene; 1-(4'-Pyrrolidinoethoxyphonyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin1-yl-ethoxy)-phenyl]-5,6,7,8tetr- ahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline. 6. A pharmaceutical composition according to claim 5 wherein the second compound is PGE.sub.2. 7. A pharmaceutical composition according to claim 5 wherein the second compound is 3S(3-Hydroxy-4-phenyl-butyl)-2R-[6-(2H-tetrazol-5-yl)-hexyl-4-]-cyclopent- anone. 8. A pharmaceutical composition comprising: a. a therapeutically effective amount of a first compound, said first compound being Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)phenyl]-5,6,7,8-tet- rahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-n- aphthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrah- ydronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline b. a therapeutically effective amount of a second compound, said second compound being sodium fluoride, a parathyroid hormone, or growth hormone. 9. A pharmaceutical composition as recited in claim 8 additionally comprising a pharmaceutical carrier. 10. A pharmaceutical composition as recited in claim 9 wherein the second compound is sodium fluoride. 11. A pharmaceutical a composition as recited in claim 9 wherein the second compound is a parathyroid hormone. 12. A pharmaceutical composition as recited in claim 9 wherein the second compound is growth hormone. 13. A method for treating mammals which present with low bone mass comprising administering to a mammal having a condition which presents with low bone mass the pharmaceutical composition of claim 8. 14. A kit containing a treatment for a condition which presents with low bone mass comprising: a. a therapeutically effective amount of Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)phenyl]-5,6,7,8-tet- rahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-n- aphthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrah- ydronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline; and a pharmaceutically acceptable carrier in a first unit dosage form; b. a therapeutically effective amount of sodium fluoride, a parathyroid hormone, or growth hormone and a pharmaceutically acceptable carrier in a second unit dosage form; and 15. A method for treating a mammal having a condition which presents with low bone mass comprising administering to a mammal having a condition which presents with low bone mass a. a therapeutically effective amount of a first compound, said first compound being an estrogen agonist/antagonist; and b. a therapeutically effective amount of a second compound, said second compound being a prostaglandin or a prostaglandin agonist/antagonist. wherein the estrogen agonist/antagonist is droloxifene, raloxifene, tamoxifen, 4-hydroxy-tamoxifen, idoxifene, centrachroman, Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-a- phthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetray- dronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- tahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphonyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline. 16. A method as recited in claim 15 wherein the estrogen agonist/antagonist is droloxifene, raloxifene, idoxifene, centrachroman, Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-n- aphthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrah- ydronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline. 17. A method as recited in claim 15 wherein the second compound is PGD.sub.1, PGD.sub.2, PGE.sub.2, PGE.sub.1, PGF.sub.2, PGF.sub.2.alpha. or 3S-(3-Hydroxy-4-phenyl-butyl)-2R-[6-(1H-tetrazol-5-yl)-hexyl]-cyclopen- tanone. 18. A method as recited in claim 17 wherein the estrogen agonist/antagonist is droloxifene. 19. A method as recited in claim 18 wherein the second compound is 3S-(3-Hydroxy-4-phenyl-butyl)-2R-[6-(1H-tetrazol-5-yl)-hexyl]-cyclopentan- one. 20. A method as recited in claim 18 wherein the condition which presents with low bone mass is osteoporosis. 21. A method as recited in claim 18 wherein the first compound and the second compounds are administered substantially simultaneously. 22. A method as recited in claim 18 wherein the second compound is administered for a period of from about three months to about three years. 23. A method as recited in claim 22 followed by administration of the first compound for a period of from about three months to about three years without the administration of the second compound during the period of from about three months to about three years. 24. A method as recited in claim 22 followed by administration of the first compound for a period greater than about three years without the administration of the second compound during the greater than about three year period. 25. A method as recited in claim 17 wherein the estrogen agonist/antagonist is Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8- tetrahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8- tetrahydro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8,- tetrahydro-naphthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyrridyl]-2-phenyl6-hydroxy-1,2,3,4- tetrahydronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2(4''-fluorophenyl)-6-hydroxy-1,2,3,4- tetrahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5[4 -(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8- tetrahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4- tetrahydroisoquinoline. 26. A method as recited in claim 25 wherein the second compound is PGE.sub.2. 27. A method as recited in claim 25 wherein the second compound is 3S-(3-Hydroxy-4-phenyl-butyl)-2R-[6-(1H-tetrazol-5yl)-hexyl]-cyclopentano- ne. 28. A method as recited in claim 25 wherein the condition which presents with low bone mass is osteoporosis. 29. A method as recited in claim 25 wherein the first compound and the second compounds are administered substantially simultaneously. 30. A method as recited in claim 25 wherein the second compound is administered for a period of from about three months to about three years. 31. A method as recited in claim 30 followed by administration of the first compound for a period of from about three months to about three years without the administration of the second compound during the period of from about three months to about three years. 32. A method as recited in claim 30 followed by administration of the first compound for a period greater than about three years without the administration of the second compound during the greater than about three year period. 33. A method for treating a mammal having a condition which presents with low bone mass comprising administering to a mammal having a condition which presents with low bone mass a. a therapeutically effective amount of a first compound, said first compound being Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)phenyl]-5,6,7,8-tet- rahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahyd- ro-naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-n- aphthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrah- ydronaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4''-fluorophenyl)-6-hydroxy-1,2,3,4-tet- rahydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-te- trahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoq- uinoline; and b. a therapeutically effective amount of a second compound, said second compound being sodium fluoride, a parathyroid hormone, or growth hormone. 34. A method as recited in claim 33 wherein the second compound is sodium fluoride. 35. A method as recited in claim 33 wherein the second compound is a parathyroid hormone. 36. A method as recited in claim 33 wherein the second compound is growth hormone. 37. A method as recited in claim 33 wherein the condition which presents with low bone mass is osteoporosis. 38. A method as recited in claim 33 wherein the first compound and the second compound are administered substantially simultaneously. 39. A method as recited in claim 33 wherein the second compound is administered for a period of from about three months to about three years. 40. A method as recited in claim 39 followed by administration of the first compound for a period of from about three months to about three years without the administration of the second compound during the period of from about three months to about three years. 41. A method as recited in claim 39 followed by administration of the first compound for a period greater than about three years without the administration of the second compound during the greater than about three year period.

Details for Patent 7,255,984

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2016-02-28