Claims for Patent: 6,458,811

Summary for Patent: 6,458,811

Title:	Benzothiophenes formulations containing same and methods
Abstract:	This invention provides compounds of formula I and pharmaceutically acceptable salts and solvates thereof, characterized that the compound is in particulate form and having a specific size range. The present invention further provides pharmaceutical compositions containing or formulated using compounds of formula I, and the use of such compounds for alleviating human pathologies, including osteoporosis, serum lipid lowering, and breast cancer.
Inventor(s):	Gordon Nelson Arbuthnot, Brian Weston Dalder, Kerry John Hartauer, Wayne Douglas Luke, Robert Eugene Stratford, Jr.
Assignee:	Eli Lilly and Co
Application Number:	US08/812,896
Patent Claims:	1. A compound of formula I and pharmaceutically acceptable salts and solvates thereof, characterized in that the compound is in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns. 2. The compound of claim 1 wherein said particles have a mean particle size of between about 5 and about 20 microns. 3. The compound of claim 2 wherein at least 90% of said particles have a size of less than about 35 microns. 4. A compound of claim 1 which is the non-solvated crystalline 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride having substantially the following X-ray diffraction pattern obtained with copper radiation: d-line spacing I/Io (Angstroms) (x100) 13.3864 71.31 9.3598 33.16 8.4625 2.08 7.3888 7.57 6.9907 5.80 6.6346 51.04 6.1717 29.57 5.9975 5.67 5.9135 9.87 5.6467 38.47 5.4773 10.54 5.2994 4.74 4.8680 4.03 4.7910 5.98 4.6614 57.50 4.5052 5.75 4.3701 9.03 4.2516 69.99 4.2059 57.64 4.1740 65.07 4.0819 12.44 3.9673 22.53 3.9318 100.00 3.8775 9.07 3.7096 33.38 3.6561 21.65 3.5576 3.36 3.5037 7.97 3.4522 18.02 3.4138 4.65 3.2738 10.23 3.1857 8.90 3.1333 6.24 3.0831 9.43 3.0025 12.13 2.9437 4.96 2.8642 7.70 2.7904 11.95 2.7246 3.05 2.6652 3.32 2.5882 7.30. 5. A pharmaceutical formulation comprising or formulated using the compound of claim 4 and one or more pharmaceutically acceptable carriers, diluents, or excipients. 6. A pharmaceutical composition comprising or formulated using a compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, in combination with one or more pharmaceutically acceptable carriers, diluents or excipients. 7. A non-solvated crystalline hydrochloride salt of a compound of formula I characterized in that the compound is in particulate form, said particles having a mean particle size of between about 5 and about 20 microns, at least about 90% of said particles having a size of less than about 35 microns. 8. A compound of claim 7 which is the non-solvated crystalline 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride, having substantially the following x-ray diffraction pattern obtained with copper radiation: d-line spacing I/Io (Angstroms) (x100) 13.3864 71.31 9.3598 33.16 8.4625 2.08 7.3888 7.57 6.9907 5.80 6.6346 51.04 6.1717 29.57 5.9975 5.67 5.9135 9.87 5.6467 38.47 5.4773 10.54 5.2994 4.74 4.8680 4.03 4.7910 5.98 4.6614 57.50 4.5052 5.75 4.3701 9.03 4.2516 69.99 4.2059 57.64 4.1740 65.07 4.0819 12.44 3.9673 22.53 3.9318 100.00 3.8775 9.07 3.7096 33.38 3.6561 21.65 3.5576 3.36 3.5037 7.97 3.4522 18.02 3.4138 4.65 3.2738 10.23 3.1857 8.90 3.1333 6.24 3.0831 9.43 3.0025 12.13 2.9437 4.96 2.8642 7.70 2.7904 11.95 2.7246 3.05 2.6652 3.32 2.5882 7.30. 9. A pharmaceutical formulation comprising or formulated using the compound of claim 8 and one or more pharmaceutically-acceptable carriers, diluents, or excipients. 10. A pharmaceutical composition comprising or formulated using a compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, with one or more pharmaceutically acceptable carriers, diluents or excipients. 11. A compound of claim 1 which is non-solvated crystalline 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride. 12. A method of inhibiting osteoporosis comprising administering an effective amount of a compound of claim 1 to a person in need thereof. 13. A method of lowering serum lipid levels comprising administering a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, to a person in need thereof. 14. A method for preventing breast cancer comprising administering to a woman in need thereof an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof. 15. A method of inhibiting osteoporosis comprising administering an effective amount of a compound of claim 7 to a person in need thereof. 16. A method of lowering serum lipid levels comprising administering a compound of claim 7, or a pharmaceutically acceptable salt or solvate thereof, to a person in need thereof. 17. A method for preventing breast cancer comprising administering to a woman in need thereof an effective amount of a compound of claim 7, or a pharmaceutically acceptable salt or solvate thereof.