Novel olanzapine forms and related methods of treatment 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2004089313 A2 2004-10-21 [WO200489313]WO2004089313 A3 2005-11-24 [WO200489313] / 2004-10-212005-11-24
申请号/申请日
2004WO-US09947 / 2004-03-31
发明人
HICKEY MAGALI BOURGHOL;REMENAR JULIUS;
申请人
TRANSFORM PHARMACEUTICALS;
主分类号
IPC分类号
A01N-043/62A61KA61K-009/64A61K-031/55A61P-025/00C07D-233/74C07D-243/06C07D-243/10
摘要
(WO200489313) The invention provides novel soluble olanzapine forms.  These forms include salts, co-crystals, and solvates of olanzapine.  The invention also provides novel pharmaceutical compositions comprising these novel soluble forms and related methods of treatment.  Compositions and methods of the invention of the invention are useful in the treatment of psychosis and functional bowel disorders.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
2003US-10660202 2003-09-11 2003US-10747742 2003-12-29 2003US-60459501 2003-04-01 2003US-60486713 2003-07-11 2003US-60487064 2003-07-11 2003WO-US27772 2003-09-04 2003WO-US41642 2003-12-29 2004US-60548343 2004-02-27 2004WO-US06288 2004-02-26
主权利要求
(WO200489313) What is claimed is: 1. An olanzapine salt made by reacting olanzapine with an organic or inorganic acid in a crystallization solvent, wherein the form has an aqueous solubility of approximately 5 micrograms/mL to approximately 100 mg/mL. 2. The olanzapine salt of claim 1, comprising an olanzapine fumarate salt that is crystallized in a crystallization solvent comprising methanol. 3. The olanzapine salt of claim 1, comprising an olanzapine maleate salt that is crystallized in a crystallization solvent comprising THF. 4. The olanzapine salt of claim 1, comprising an olanzapine malonate salt that is crystallized in a crystallization solvent comprising THF. 5. An olanzapine salt comprising olanzapine fumarate. 6. The olanzapine salt of claim 5, wherein: (a) the salt is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (i) said X-ray diffraction pattern comprises peaks at 9.49, 13.99, and 15.83 degrees; (ii) said X-ray diffraction pattern comprises peaks at 12.71, 17.13, and 19.67 degrees; (iii)said X-ray diffraction pattern comprises peaks at 21.43, 22.29, and 22.99 degrees; (iv)said X-ray diffraction pattern comprises a peak at 9.49 degrees; (v) said X-ray diffraction pattern comprises peaks at 9.49 and 13.99 degrees; or (vi)said X-ray diffraction pattern comprises peaks at 15.83 and 22.29 degrees; or (b) the salt is characterized by a DSC endothermic transition at about 238 degrees C. 7. The olanzapine salt of claim 5, wherein the form is crystallized in a crystallization solvent comprising methanol. 8. An olanzapine salt comprising olanzapine maleate. 9. The olanzapine salt of claim 8, wherein: (a) the salt is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (i) said X-ray diffraction pattern comprises peaks at 5.57, 12.95, and 16.79 degrees; (ii) said X-ray diffraction pattern comprises peaks at 11.97, 19.25, and 21.11 degrees; (iii)said X-ray diffraction pattern comprises peaks at 5.57, 19.25, and 22.23 degrees; (iv)said X-ray diffraction pattern comprises a peak at 5.57 degrees; (v)said X-ray diffraction pattern comprises peaks at 5.57 and 12.95 degrees; or (vi)said X-ray diffraction pattern comprises peaks at 16.79 and 19.25 degrees; or (b) the salt is characterized by a DSC endothermic transition at about 196 degrees C. 10. The olanzapine salt of claim 9, wherein the form is crystallized in a crystallization solvent comprising THF. 11. An olanzapine salt comprising olanzapine malonate. 12. The olanzapine salt of claim 11, wherein the salt is characterized by a powder X- ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (a) said X-ray diffraction pattern comprises peaks at 7.37, 9.45, and 12.41 degrees; (b) said X-ray diffraction pattern comprises peaks at 14.83, 20.51, and 21.35 degrees; (c) said X-ray diffraction pattern comprises peaks at 7.37, 17.71, and 23.19 degrees; (d) said X-ray diffraction pattern comprises a peak at 7.37 degrees; (e) said X-ray diffraction pattern comprises peaks at 9.45 and 12.95 degrees; or (f) said X-ray diffraction pattern comprises peaks at 9.85 and 17.71 degrees. 13. The olanzapine salt of claim 12, wherein the form is crystallized in a crystallization solvent comprising THF. 14. An olanzapine solvate formed by the crystallization of olanzapine and either urea or a urea derivative in a crystallization solvent comprising an alcohol, wherein the solvate has an aqueous solubility of at least about 100 micrograms/mL. 15. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising one or more alcohols. 16. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising methanol. 17. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising ethanol. 18. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising isopropanol. 19. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising ethyl acetate. 20. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising acetone. 21. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising 1,2- dichloroethane. 22. The olanzapine solvate of claim 14, wherein the solvate is formed by the crystallization of olanzapine and urea in a crystallization solvent comprising THF. 23. An olanzapine solvate, wherein: (a) the solvate is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (i) said solvate is a methanol solvate and said X-ray diffraction pattern comprises peaks at 8.61, 16.45, and 18.85 degrees; (ii) said solvate is a methanol solvate and said X-ray diffraction pattern comprises peaks at 16.45, 19.97, and 23.09 degrees; (iii)said solvate is a methanol solvate and said X-ray diffraction pattern comprises peaks at 20.85, 22.05, and 24.73 degrees; (iv)said solvate is a methanol solvate and said X-ray diffraction pattern comprises a peak at 8.61 degrees; (v)said solvate is a methanol solvate and said X-ray diffraction pattern comprises peaks at 8.61 and 16.45 degrees; or (vi)said solvate is a methanol solvate and said X-ray diffraction pattern comprises peaks at 18.85 and 19.97 degrees; (b) the solvate is a methanol solvate and is characterized by a DSC endothermic transition at about 141 degrees C; (c) the solvate is a methanol solvate and is characterized by a DSC endothermic transition at about 196 degrees C; (d) the solvate is a methanol solvate and is characterized by TGA with a weight loss of about 23 percent between about 130 and 150 degrees C; or (e) the solvate is a methanol solvate and exhibits a single-crystal x-ray analysis with crystal parameters that are approximately equal to the following: Crystal system, space group: Monoclinic, P2(l)/c Unit cell dimensions a = 10.1416(8) angstroms alpha = 90 deg b = 12.2793(9) angstroms beta =91.7860(10) deg c = 14.1147(11) angstroms gamma = 90 deg Volume: 1756.9(2) angstroms3 Z, Calculated density 4, 1.302 Mg/m3 R indices (all data) Rl = 0.0465, wR2 = 0.1167. 24. An olanzapine:nicotinamide co-crystal formed by the crystallization of olanzapine and nicotinamide in a crystallization solvent, wherein the co-crystal has an aqueous solubility of at least about 100 micrograms/mL. 25. The olanzapine icotinamide co-crystal of claim 24, wherein the co-crystal is formed by the crystallization of olanzapine and nicotinamide in a crystallization solvent comprising 1,2-dichloroethane. 26. The olanzapine:nicotinamide co-crystal of claim 24, wherein the co-crystal is formed by the crystallization of olanzapine and nicotinamide in a crystallization solvent comprising isopropyl acetate. 27. An olanzapine :nicotinamide co-crystal comprising olanzapine and nicotinamide. 28. The olanzapine:nicotinamide co-crystal of claim 27, wherein: (a) said co-crystal is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (i) said X-ray diffraction pattern comprises peaks at 4.89, 8.65, and 17.17 degrees; (ii) said X-ray diffraction pattern comprises peaks at 23.97, 24.61, and 25.57 degrees; (iii)said X-ray diffraction pattern comprises peaks at 4.89, 17.17, and 25.57 degrees; (iv)said X-ray diffraction pattern comprises a peak at 4.89 degrees; (v)said X-ray diffraction pattern comprises peaks at 4.89 and 8.65 degrees; or (vi)said X-ray diffraction pattern comprises peaks at 17.17 and 23.97 degrees; or (b) said co-crystal is characterized by a DSC endothermic transition at about 126 degrees C. 29. The olanzapine icotinamide co-crystal of claim 27, wherein said co-crystal is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (a) said X-ray diffraction pattern comprises peaks at 8.65, 11.87, and 14.53 degrees; (b) said X-ray diffraction pattern comprises peaks at 17.53, 18.09, and 23.89 degrees; (c) said X-ray diffraction pattern comprises peaks at 8.65, 17.53, and 24.19 degrees; (d) said X-ray diffraction pattern comprises a peak at 8.65 degrees; (e) said X-ray diffraction pattern comprises peaks at 11.87 and 14.53 degrees; or (f) said X-ray diffraction pattern comprises peaks at 18.09 and 23.89 degrees. 30. The olanzapine:nicotinamide co-crystal of claim 27, wherein: (a) said co-crystal is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (i) said X-ray diffraction pattern comprises peaks at 6.43, 12.85, and 18.69 degrees; (ii) said X-ray diffraction pattern comprises peaks at 9.55, 14.91, and 21.85 degrees; (iii)said X-ray diffraction pattern comprises peaks at 6.43, 14.91, and 19.83 degrees; (iv)said X-ray diffraction pattern comprises a peak at 6.43 degrees; (v)said X-ray diffraction pattern comprises peaks at 12.85 and 18.69 degrees; or (vi)said X-ray diffraction pattern comprises peaks at 6.43 and 21.85 degrees; or (b) said co-crystal exhibits a single-crystal x-ray analysis with crystal parameters that are approximately equal to the following: Wavelength: 0.71073 A Crystal system, space group: Monoclinic, P21/c Unit cell dimensions: a = 14.0961(12)A alpha = 90° b = 12.5984(10)A beta=97.396(2)° c = 27.219(2)A gamma = 90° Volume: 4793.6(7) A3 Z, Calculated density; 4, 1.276 Mg/m3 Reflections collected / unique: 24952 / 8457 [R(int) = 0.0882] . Goodness-of-fit on FΛ2: 1.018 Final R indices [I>2sigma(I)] : RI = 0.0676, wR2 = 0.1461 R indices (all data): RI = 0.1187, wR2 = 0.1687. 31. An olanzapine propylene glycol solvate formed by the crystallization of olanzapine and a glycol in a crystallization solvent, wherein the solvate has an aqueous solubility of at least about 100 micrograms/mL. 32. The olanzapine propylene glycol solvate of claim 31, wherein the solvate is formed by the crystallization of olanzapine and propylene glycol in a crystallization solvent comprising isopropyl acetate. 33. An olanzapine propylene glycol solvate comprising olanzapine and propylene glycol. 4. The olanzapine propylene glycol solvate of claim 33, wherein: (a) said propylene glycol solvate is characterized by a powder X-ray diffraction pattern comprising peaks expressed in terms of 2-theta angles, wherein: (i) said X-ray diffraction pattern comprises peaks at 8.39, 11.71, and 15.55 degrees; (ii) said X-ray diffraction pattern comprises peaks at 13.95, 15.55, and 19.55 degrees; (iii)said X-ray diffraction pattern comprises peaks at 14.45, 17.91, and 21.47 degrees; (iv)said X-ray diffraction pattern comprises a peak at 8.39 degrees; (v)said X-ray diffraction pattern comprises peaks at 8.39 and 21.47 degrees; or (vi)said X-ray diffraction pattern comprises peaks at 11.71 and 15.55 degrees; (b) said propylene glycol solvate is characterized by a DSC endothermic transition at about 93 degrees C; (c) said propylene glycol solvate is characterized by TGA with a weight loss of about 18 percent between about room temperature and 110 degrees C; or (d) said propylene glycol solvate exhibits a single-crystal x-ray analysis with crystal parameters that are approximately equal to the following: Space Group P2(l)/c a = 10.4264(9) alpha = 90 deg b = 13.3916(11) beta = 95.503(2) deg c = 14.4424(12) gamma = 90 deg Volume 2007.2(3). 35. An olanzapine salt formed by reacting olanzapine and a dicarboxylic acid in a heated crystallization solvent to form a reaction product, and thereafter cooling the reaction product to a temperature of between about 0° C to about 10° C over a period of about five to about fifteen hours to form the olanzapine salt, wherein the olanzapine salt has an aqueous solubility of between about 0.05 mg/ml to about 100 mg/ml. 36. An olanzapine salt formed by reacting olanzapine and a dicarboxylic acid in a heated crystallization solvent to form a reaction product, and thereafter cooling the reaction product to a temperature of between about 0° C to about 10° C over a period of less than one hour to form the olanzapine salt, wherein the olanzapine salt has an aqueous solubility of between about 0.05 mg/ml to about 100 mg/ml. 37. The olanzapine salt of claim 35, wherein the crystallization solvent prior to form formation further comprises a seed crystal comprising a salt foπned by the reaction of olanzapine and the dicarboxylic acid. 38. The olanzapine salt of claim 35, wherein the dicarboxylic acid is in the form of either a substantially pure (R)(+) enantiomer; a substantially pure (R)(-) enantiomer; a substantially pure (S)(+) enantiomer; or a substantially pure (S)(-) enantiomer. 39. A pharmaceutical dosage form comprising a phannaceutically acceptable carrier and a therapeutically effective amount of an olanzapine solvate of claim 14. 40. A pharmaceutical dosage form comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an olanzapine icotinamide co-crystal of claim 27. 41. A pharmaceutical dosage form comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an olanzapine salt, solvate, or co-crystal of any one of claims 1-38. 42. A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical dosage form of claim 41 to a patient suffering from psychosis. 43. A method of treatment comprising administering a therapeutically effective amount of a pharmaceutical dosage form of claim 41 to a patient suffering from a functional bowel disorder. 44. The method of claim 43, wherein the patient suffers from irritable bowel syndrome.
法律状态
(WO200489313) LEGAL DETAILS FOR WO2004089313  Actual or expected expiration date=2006-10-01    Legal state=DEAD    Status=LAPSED     Event publication date=2004-03-31  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2004009947  Application date=2004-03-31  Standardized application number=2004WO-US09947     Event publication date=2004-10-21  Event code=WO/A2  Event type=Examination events  International application published without international search report  Publication country=WO  Publication number=WO2004089313  Publication stage Code=A2  Publication date=2004-10-21  Standardized publication number=WO200489313     Event publication date=2004-10-21  Event code=WO/AL  Event indicator=Pos  Event type=Designated states  Designated countries for regional patents BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG    Event publication date=2004-10-21  Event code=WO/AK  Event indicator=Pos  Event type=Designated states  Designated states AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW    Event publication date=2005-11-24  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2004089313  Publication stage Code=A3  Publication date=2005-11-24  Standardized publication number=WO200489313     Event publication date=2006-10-01  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE US  Actual or expected expiration date=2009-03-31    Legal state=DEAD    Status=EXPIRED   Corresponding cc:  Designated or member state=US Corresponding appl: US2006223794    Event publication date=2005-09-29  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=US     Event publication date=2006-10-05  Event code=WO/WWP  Event indicator=Pos  Event type=Examination events  Wipo information: published in national office Corresponding cc:  Designated or member state=US     Event publication date=2009-03-31  Event code=US/EEDL  Event indicator=Neg  Event type=Event indicating Not In Force  Pending application likely abandoned Corresponding cc:  Designated or member state=US
专利类型码
A2A3
国别省市代码
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部