公开(公告)号：US07544805B2

公开(公告)日：2009-06-09

申请号：US11048746

申请日：2005-02-03

申请人： Mohammed Alnabari ,  Yana Sery ,  Itai Adin ,  Oded Arad ,  Joseph Kaspi

发明人： Mohammed Alnabari ,  Yana Sery ,  Itai Adin ,  Oded Arad ,  Joseph Kaspi

IPC分类号： C07D215/12 ,  A61K31/47

CPC分类号： A61K9/1688 ,  A61K9/1617

摘要： An amorphous form of montelukast sodium and a montelukast sodium lactose co-precipitate, processes for producing same, pharmaceutical compositions containing same and methods of treatment utilizing same are disclosed.

摘要翻译： 孟鲁司特钠和孟鲁司特钠乳糖共沉淀物的无定形形式，其制备方法，含有其的药物组合物和使用其的治疗方法已公开。

公开(公告)号：US20050187245A1

公开(公告)日：2005-08-25

申请号：US11048746

申请日：2005-02-03

申请人： Mohammed Alnabari ,  Yana Sery ,  Itai Adin ,  Oded Arad ,  Joseph Kaspi

发明人： Mohammed Alnabari ,  Yana Sery ,  Itai Adin ,  Oded Arad ,  Joseph Kaspi

IPC分类号： A61K9/16 ,  A61K31/47 ,  C07D215/16

CPC分类号： A61K9/1688 ,  A61K9/1617

摘要： An amorphous form of montelukast sodium and a montelukast sodium lactose co-precipitate, processes for producing same, pharmaceutical compositions containing same and methods of treatment utilizing same are disclosed.

摘要翻译： 孟鲁司特钠和孟鲁司特钠乳糖共沉淀物的无定形形式，其制备方法，含有其的药物组合物和使用其的治疗方法已公开。

公开(公告)号：US20050142190A1

公开(公告)日：2005-06-30

申请号：US10501045

申请日：2004-01-13

申请人： Itai Adin ,  Mohammed Alnabari ,  Yana Sery ,  Oded Arad ,  Joseph Kaspi

发明人： Itai Adin ,  Mohammed Alnabari ,  Yana Sery ,  Oded Arad ,  Joseph Kaspi

IPC分类号： A61K9/14 ,  A61K9/16 ,  A61K9/19 ,  A61K31/4178 ,  A61K31/445 ,  A61K9/20 ,  A61K31/4184

CPC分类号： A61K9/1641 ,  A61K9/145 ,  A61K9/146 ,  A61K9/1623 ,  A61K9/1635 ,  A61K9/1694 ,  A61K9/19 ,  A61K31/4178 ,  A61K31/445

摘要： The invention provides a stable and easy to formulate amorphous solid, suitable for the preparation of solid pharmaceutical compositions comprising a mixture of an amorphous active pharmaceutical ingredient and at least one pharmaceutically acceptable inactive ingredient.

摘要翻译： 本发明提供了一种稳定且易于配制的无定形固体，适用于制备包含无定形活性药物成分和至少一种药学上可接受的无活性成分的混合物的固体药物组合物。

公开(公告)号：US20060183898A1

公开(公告)日：2006-08-17

申请号：US11354899

申请日：2006-02-16

申请人： Olga Etlin ,  Mohammed Alnabari ,  Yana Sery ,  Edna Danon ,  Oded Arad ,  Joseph Kaspi

发明人： Olga Etlin ,  Mohammed Alnabari ,  Yana Sery ,  Edna Danon ,  Oded Arad ,  Joseph Kaspi

IPC分类号： C07D487/04

CPC分类号： C07D487/04 ,  B01J39/07 ,  B01J41/07 ,  B01J49/00 ,  B01J49/06 ,  B01J49/07

摘要： The present invention provides a process for preparing highly pure Temozolomide base which includes recovery from the purification mother liquors by using an anionic exchange resin. By treating Temozolomide hydrochloride with a mixture of an organic acid, a water miscible organic solvent, and water, Temozolomide free base is obtained in an acidic medium. Due to the high sensitivity of Temozolomide to basic pH values the recovery-including process is especially advantageous because it enables obtaining high yields of highly pure Temozolomide base in acidic conditions. The process for producing Temozolomide base includes hydrolysis of the starting material 8-cyano-3-methyl-[3H]-imidazo[5,1-d]-tetrazin-4-one in acidic medium to obtain highly pure Temozolomide hydrochloride in high yield.

公开(公告)号：US07612202B2

公开(公告)日：2009-11-03

申请号：US11354899

申请日：2006-02-16

申请人： Olga Etlin ,  Mohammed Alnabari ,  Yana Sery ,  Edna Danon ,  Oded Arad ,  Joseph Kaspi

发明人： Olga Etlin ,  Mohammed Alnabari ,  Yana Sery ,  Edna Danon ,  Oded Arad ,  Joseph Kaspi

IPC分类号： C07D487/04 ,  A61K31/395 ,  A61P35/00

CPC分类号： C07D487/04 ,  B01J39/07 ,  B01J41/07 ,  B01J49/00 ,  B01J49/06 ,  B01J49/07

摘要： The present invention provides a process for preparing highly pure Temozolomide base which includes recovery from the purification mother liquors by using an anionic exchange resin. By treating Temozolomide hydrochloride with a mixture of an organic acid, a water miscible organic solvent, and water, Temozolomide free base is obtained in an acidic medium. Due to the high sensitivity of Temozolomide to basic pH values the recovery-including process is especially advantageous because it enables obtaining high yields of highly pure Temozolomide base in acidic conditions.The process for producing Temozolomide base includes hydrolysis of the starting material 8-cyano-3-methyl-[3H]-imidazo[5,1-d]-tetrazin-4-one in acidic medium to obtain highly pure Temozolomide hydrochloride in high yield.

摘要翻译： 本发明提供了制备高纯度替莫唑胺碱的方法，其包括通过使用阴离子交换树脂从纯化母液中回收。 通过用有机酸，水混溶性有机溶剂和水的混合物处理盐酸替莫唑胺，在酸性介质中获得替莫唑胺游离碱。 由于替莫唑胺对碱性pH值的高敏感性，回收包含的方法是特别有利的，因为它能够在酸性条件下获得高产量的高纯度替莫唑胺碱。 制备替莫唑胺碱的方法包括在酸性介质中水解原料8-氰基-3-甲基 - [3 H] - 咪唑并[5,1-d] - 四嗪-4-酮，以高产率得到高纯度的替莫唑胺盐酸盐 。

公开(公告)号：US20060122227A1

公开(公告)日：2006-06-08

申请号：US11235105

申请日：2005-09-27

申请人： Lior Zelikovitch ,  Oded Arad ,  Mohammed Alnabari ,  Yana Sery ,  Orna Kurlat ,  Moshe Bentolila ,  Aric Abadayev ,  Hanit Marom ,  Hila Isenberg ,  Joseph Kaspi

发明人： Lior Zelikovitch ,  Oded Arad ,  Mohammed Alnabari ,  Yana Sery ,  Orna Kurlat ,  Moshe Bentolila ,  Aric Abadayev ,  Hanit Marom ,  Hila Isenberg ,  Joseph Kaspi

IPC分类号： C07D211/06 ,  A61K31/445

CPC分类号： C07D211/34

摘要： The present invention relates to an improved process of alkylating secondary amines, more particularly of alkylating compounds having amino piperidinic group, which are useful as donepezil intermediates, wherein an alcohol serves as reaction facilitator thus enabling to obtain donepezil and salts thereof in high quality and yield. The present invention also relates to the prevention of unwanted alkylation of donepezil precursors, having amino piperidinic group, by using suitable reaction conditions.

摘要翻译： 本发明涉及一种改进的仲胺烷基化方法，更特别是烷基化化合物，具有氨基哌啶基，其可用作多奈哌齐中间体，其中醇用作反应促进剂，从而能够以高质量和产率获得多奈哌齐和其盐 。 本发明还涉及通过使用合适的反应条件来防止具有氨基哌啶基的多奈哌齐前体的不需要的烷基化。

公开(公告)号：US06844440B2

公开(公告)日：2005-01-18

申请号：US10459662

申请日：2003-06-11

申请人： Ori Lerman ,  Joseph Kaspi ,  Oded Arad ,  Mohammed Alnabari ,  Yana Sery

发明人： Ori Lerman ,  Joseph Kaspi ,  Oded Arad ,  Mohammed Alnabari ,  Yana Sery

IPC分类号： A61P25/28 ,  C07D211/32 ,  C07D211/34 ,  C07D211/06

CPC分类号： C07D211/34 ,  C07D211/32 ,  Y02P20/55

摘要： The invention provides a process for the preparation of a compound of the formula 6 comprising the hydrolysis and decarboxylation of a compound of the formula 5 according to the reaction: wherein R and R2 independently a C1-C4 alkyl group or an aralkyl group.

摘要翻译： 本发明提供了一种制备式6化合物的方法，其包括根据以下反应进行式5化合物的水解和脱羧作用：其中R和R 2独立地为C 1 -C 4烷基或芳烷基。

公开(公告)号：US20060009435A1

公开(公告)日：2006-01-12

申请号：US11159241

申请日：2005-06-23

申请人： Joseph Kaspi ,  Oded Arad ,  Michael Brand ,  Moty Shookrun ,  Simona Malka ,  Mohammed Alnabari ,  Shalom Hazan ,  Vlado Malesevic

发明人： Joseph Kaspi ,  Oded Arad ,  Michael Brand ,  Moty Shookrun ,  Simona Malka ,  Mohammed Alnabari ,  Shalom Hazan ,  Vlado Malesevic

IPC分类号： A61K31/573 ,  A61K9/14 ,  A61L9/04

CPC分类号： A61K9/0075 ,  A61K9/008 ,  A61K9/1688 ,  A61K31/573

摘要： An improved process for preparing fluticasone propionate, performed in the presence of water, is disclosed. Further disclosed is a process for preparing a fluticasone propionate that is highly suitable for administration by inhalation. Further disclosed are fluticasone propionate and a powdered fluticasone propionate prepared by these processes and pharmaceutical compositions for administration by inhalation containing same. A process of purifying a key intermediate in the synthesis of fluticasone propionate is also disclosed.

摘要翻译： 公开了一种在水存在下进行丙酸氟替卡松的改进方法。 进一步公开了一种制备高度适合于吸入给药的丙酸氟替卡松的方法。 进一步公开的是丙酸氟替卡松和通过这些方法制备的粉状氟替卡松丙酸酯和用于通过吸入给药的药物组合物。 还公开了在丙酸氟替卡松的合成中纯化关键中间体的方法。

公开(公告)号：US20060122226A1

公开(公告)日：2006-06-08

申请号：US11006827

申请日：2004-12-08

申请人： Itai Adin ,  Carmen Iustain ,  Oded Arad ,  Joseph Kaspi

发明人： Itai Adin ,  Carmen Iustain ,  Oded Arad ,  Joseph Kaspi

IPC分类号： C07D211/06 ,  A61K31/445

CPC分类号： C07D211/32

摘要： Novel crystalline forms of Donepezil base, processes for producing same, pharmaceutical compositions containing same and methods of treatment utilizing same are disclosed.

摘要翻译： 公开了多奈哌齐碱碱的新型结晶形式，其制备方法，含有其的药物组合物和使用其的治疗方法。

公开(公告)号：US20060069125A1

公开(公告)日：2006-03-30

申请号：US11235106

申请日：2005-09-27

申请人： Oded Arad ,  Lior Zelikovitch ,  Mohammed Alnabari ,  Michael Brand ,  Irina Gribun ,  Ada Salman ,  Meital Shiffer ,  Moty Shookrun ,  Orna Kurlat ,  Moshe Bentolila ,  Joseph Kaspi

发明人： Oded Arad ,  Lior Zelikovitch ,  Mohammed Alnabari ,  Michael Brand ,  Irina Gribun ,  Ada Salman ,  Meital Shiffer ,  Moty Shookrun ,  Orna Kurlat ,  Moshe Bentolila ,  Joseph Kaspi

IPC分类号： A61K31/445 ,  C07D211/06

CPC分类号： C07D211/32

摘要： The present invention provides a crystalline donepezil maleate, which is used as an intermediate in the preparation of donepezil hydrochloride. Also provided are novel processes for producing same in substantially pure form and a process for producing pharmaceutically pure amorphous donepezil hydrochloride therefrom.