公开(公告)号：WO2014152207A1

公开(公告)日：2014-09-25

申请号：PCT/US2014/027072

申请日：2014-03-14

Applicant: MYLAN LABORATORIES, INC.

Inventor： XIAO, Chaoju ,  LI, Boyong

IPC: A61K9/14

CPC classification number: A61K9/2013 ,  A61K9/1617 ,  A61K9/1652 ,  A61K9/2018 ,  A61K9/2054 ,  A61K31/145

Abstract: The presently disclosed subject matter is directed to a granule, wherein the granule has an active agent and a wax dispersed therein, and the granule exhibits excellent friability when compressed to form a pharmaceutical composition. The subject matter disclosed herein is also directed to methods of preparing the granules and the pharmaceutical compositions comprising the granules. The compositions and methods disclosed provide granules and pharmaceutical compositions for immediate release of the active agent and do not substantially prolong the release of the active agent from the granule.

Abstract translation: 目前公开的主题涉及颗粒，其中颗粒具有分散在其中的活性剂和蜡，并且当压缩形成药物组合物时，颗粒显示出优异的脆性。 本文公开的主题还涉及制备颗粒的方法和包含颗粒的药物组合物。 所公开的组合物和方法提供用于立即释放活性剂的颗粒剂和药物组合物，并且基本上不延长活性剂从颗粒中的释放。

公开(公告)号：WO2006083780A2

公开(公告)日：2006-08-10

申请号：PCT/US2006/003253

申请日：2006-01-30

Applicant: MYLAN LABORATORIES, INC. ,  O'DONNELL, John, P. ,  OWENS, Walter ,  DUNCAN, Joseph ,  SHAW, Andrew

Inventor： O'DONNELL, John, P. ,  OWENS, Walter ,  DUNCAN, Joseph ,  SHAW, Andrew

CPC classification number: A61K45/06 ,  A61K31/7012 ,  A61K31/7048 ,  A61K2300/00

Abstract: This invention provides glucuronidated nebivolol metabolites and pharmaceutical compositions of glucuronidated nebivolol metabolites for treatment of cardiovascular diseases. In addition, this invention also provides compositions comprising nebivolol and/or at least one glucuronidated metabolite of nebivolol and/or at least one other active compound in a pharmaceutically acceptable carrier. This invention also provides methods of treating and/or preventing vascular diseases, by administering at least one glucuronidated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one glucuronidated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

Abstract translation: 本发明提供了用于治疗心血管疾病的葡糖醛酸化奈必洛尔代谢物和葡糖苷酸化奈必洛尔代谢物的药物组合物。 此外，本发明还提供在药学上可接受的载体中包含奈比洛尔和/或至少一种葡萄糖醛酸化的奈必洛尔代谢物和/或至少一种其它活性化合物的组合物。 本发明还提供了治疗和/或预防血管疾病的方法，其通过施用能够将治疗有效量的一氧化氮释放到受血管疾病影响的靶位的奈比洛尔的至少一种葡糖醛酸化代谢物。 此外，本发明涉及治疗和/或预防给予至少一种奈非洛尔的葡糖醛酸化代谢物的偏头痛。 本发明还可以与代谢综合征病症联合使用或作为单一治疗代用综合征病症使用。

公开(公告)号：WO2006083779A2

公开(公告)日：2006-08-10

申请号：PCT/US2006/003252

申请日：2006-01-30

Applicant: MYLAN LABORATORIES, INC. ,  O'DONNELL, John, P. ,  OWENS, Walter ,  DUNCAN, Joseph ,  SHAW, Andrew ,  WU, Jinn

Inventor： O'DONNELL, John, P. ,  OWENS, Walter ,  DUNCAN, Joseph ,  SHAW, Andrew ,  WU, Jinn

CPC classification number: C07D311/58 ,  A61K31/353

Abstract: Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy- 6,6'difluoro-, 4-hydroxy-5-phenol-6,6'difluoro-, and 4-hydroxy-8-pheno-6,6'difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof, In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

Abstract translation: 急性给药后羟化的奈比洛尔代谢物以浓度依赖的方式增加人内皮细胞制剂的NO释放。 此外，羟基化的奈比洛尔代谢物，包括但不限于4-羟基-6,6'-二氟 - ，4-羟基-5-苯酚-6,6'-二氟和4-羟基-8-苯基-6,6 “二氟”具有增加慢性给药后人体内皮细胞NO释放能力的能力。 本发明提供羟基化的奈必洛尔代谢物和包含奈比洛尔和/或至少一种羟基化的奈比洛尔代谢物和/或用于治疗心血管疾病的至少一种另外的化合物或其药学上可接受的盐的组合物。此外，本发明提供治疗和 /或通过施用能够将治疗有效量的一氧化氮释放到受血管疾病影响的靶位点的奈比洛尔的至少一种羟化化代谢物来预防血管疾病。 此外，本发明涉及治疗和/或预防给予至少一种羟基化的奈必洛尔代谢物的偏头痛。 本发明还可以与代谢综合征病症联合使用或作为单一治疗代用综合征病症使用。

公开(公告)号：WO2009158120A2

公开(公告)日：2009-12-30

申请号：PCT/US2009/045739

申请日：2009-05-29

Applicant: MYLAN LABORATORIES INC. ,  TANG, Jiashang

Inventor： TANG, Jiashang

IPC: A61M35/00 ,  A61K9/70

CPC classification number: A61K9/7061 ,  A61K9/7069 ,  A61K9/7092 ,  Y10T156/10

Abstract: A solid dispersion transdermal drug delivery system comprising a therapeutic agent in a stable amorphous form and a combination polymeric stabilizing and dispersing agent having a hydrogen bond-forming functional group, and a method of manufacturing these systems is provided. The weight ratio of the combination polymeric stabilizing and dispersing agent to the therapeutic agent is also disclosed.

Abstract translation: 提供了包含稳定无定形形式的治疗剂和具有形成氢键的官能团的聚合稳定分散剂的固体分散透皮药物递送系统及其制造方法。 还公开了组合聚合物稳定剂和分散剂与治疗剂的重量比。

公开(公告)号：WO2010033179A1

公开(公告)日：2010-03-25

申请号：PCT/US2009/005153

申请日：2009-09-16

Applicant: MYLAN LABORATORIES, INC. ,  LI, Boyong ,  REYNOLDS, Thomas D.

Inventor： LI, Boyong ,  REYNOLDS, Thomas D.

IPC: A61K9/14

CPC classification number: A61K9/2027 ,  A61K9/2018 ,  A61K9/2059 ,  A61K31/277

Abstract: A granulate for use in a pharmaceutical composition and a pharmaceutical composition manufacture using the granulate, where the granule comprises an active pharmaceutical ingredient (API) having a poor water solubility (i.e., less than about 1 mg/mL) which is intimately associated with at least one pharmaceutically acceptable hydrophilic polymer. The granule optionally contains one or more pharmaceutically acceptable excipients, such as disintegrants, wetting agents, diluents, binders, lubricants, glidants, coloring agents and flavoring agents. The invention also relates to a process for preparing the pharmaceutical granulate and pharmaceutical compositions containing the granulate.

Abstract translation: 用于药物组合物的颗粒和使用该颗粒的药物组合物制造，其中颗粒包含具有差的水溶性（即小于约1mg / mL）的活性药物成分（API），其与 至少一种药学上可接受的亲水性聚合物。 颗粒任选地含有一种或多种药学上可接受的赋形剂，例如崩解剂，润湿剂，稀释剂，粘合剂，润滑剂，助流剂，着色剂和调味剂。 本发明还涉及制备含有颗粒的药物颗粒和药物组合物的方法。

公开(公告)号：WO2006130174A2

公开(公告)日：2006-12-07

申请号：PCT/US2005/041275

申请日：2005-11-16

Applicant: MYLAN LABORATORIES, INC. ,  DAVIS, Eric ,  O'DONNELL, John ,  BOTTINI, Peter Bruce ,  MASON, Preston ,  SHAW, Andrew Preston

Inventor： DAVIS, Eric ,  O'DONNELL, John ,  BOTTINI, Peter Bruce ,  MASON, Preston ,  SHAW, Andrew Preston

IPC: A61K31/352 ,  A61K31/403 ,  A61K31/40 ,  A61K31/41 ,  A61K31/155 ,  A61K31/427 ,  A61P9/00

CPC classification number: A61K31/403 ,  A61K31/155 ,  A61K31/35 ,  A61K31/352 ,  A61K31/353 ,  A61K31/40 ,  A61K31/41 ,  A61K31/427 ,  A61K45/06 ,  A61K2300/00

Abstract: Nebivolol has been shown to be beneficial in the treatment of cardiovascular diseases such hypertension, congestive heart failure, arterial stiffness and endothelial dysfunction. The present invention features a pharmaceutical composition comprising nebivolol and at least one other active agent, wherein the at least one other active agent is a cardiovascular agent.

Abstract translation: 奈比洛尔已被证明对心血管疾病如高血压，充血性心力衰竭，动脉僵硬和内皮功能障碍的治疗有益。 本发明的特征在于包含奈比洛尔和至少一种其它活性剂的药物组合物，其中所述至少一种其它活性剂是心血管药剂。

公开(公告)号：WO2005117858A2

公开(公告)日：2005-12-15

申请号：PCT/US2005/019111

申请日：2005-06-01

Applicant: MYLAN LABORATORIES, INC. ,  DAVIS, Eric ,  O'DONNELL, John ,  BOTTINI, Peter, Bruce

Inventor： DAVIS, Eric ,  O'DONNELL, John ,  BOTTINI, Peter, Bruce

IPC: A61K31/35

CPC classification number: A61K31/35 ,  A61K31/353

Abstract: Nebivolol has been shown to be beneficial in the treatment of cardiovascular diseases such hypertension, congestive heart failure, arterial stiffness and endothelial dysfunction. The present invention features a pharmaceutical composition comprising nebivolol and at least one other active agent, wherein the at least one other active agent is a cardiovascular agent.

Abstract translation: 奈比洛尔已被证明对心血管疾病如高血压，充血性心力衰竭，动脉僵硬和内皮功能障碍的治疗有益。 本发明的特征在于包含奈比洛尔和至少一种其它活性剂的药物组合物，其中所述至少一种其它活性剂是心血管药剂。