公开(公告)号：US06565880B2

公开(公告)日：2003-05-20

申请号：US09902822

申请日：2001-07-11

Applicant: Michael Cappola ,  George W. Gereg ,  Susan Way

Inventor： Michael Cappola ,  George W. Gereg ,  Susan Way

IPC: A61K914

CPC classification number: B82Y5/00 ,  A61K9/2018 ,  A61K9/2077 ,  A61K31/5377 ,  A61K47/6951

Abstract: A formulation comprising, and process for preparing, improved oral dosage forms of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea, a chemical entity with anti-inflammatory properties. Granulation of 1-(5-tert-but l-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea within specified ranges provides improved dissolution of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea and oral bioavailability, as well as content uniformity. Incorporation into the formulation of an aqueous soluble inclusion compound capable of forming a complex with 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea, such as beta-cyclodextrin provides enhanced stability of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea, in particular in highly ionic environments. Chipping and disintegration of tablets containing more than about 10% betacyclodextrin can be prevented by applying a polymeric coat to the surface of the tablet at a temperature below 40° C.

Abstract translation: 包含改善口服剂型1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲，具有抗炎特性的化学物质。 1-（5-叔丁基-2-对 - 甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲在1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲和口服生物利用度，以及含量均匀性。 加入能够与1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基） 乙氧基） - 萘-1-基] - 脲如β-环糊精提供了增强的1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3 - [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲，特别是在高离子环境中。 通过在低于40℃的温度下将片剂的表面施加聚合物涂层，可以防止包含超过约10％的β-环糊精的片剂的碎裂和崩解。

公开(公告)号：US20070099832A1

公开(公告)日：2007-05-03

申请号：US11539376

申请日：2006-10-06

Applicant: Stefan SIMIANER ,  Pascal Bilbault ,  Michael Cappola ,  Susan Way

Inventor： Stefan SIMIANER ,  Pascal Bilbault ,  Michael Cappola ,  Susan Way

IPC: A61K38/17 ,  A61K31/5377 ,  A61K31/573 ,  A61K31/522 ,  A61K31/66 ,  A61K31/65 ,  A61K31/60 ,  A61K31/59 ,  A61K31/4745 ,  A61K31/192

CPC classification number: A61K39/395 ,  A61K2300/00

Abstract: The present invention relates to pharmaceutical combinations therapies based on p38 kinase inhibitors and another active ingredient, pharmaceutical compositions comprising such combinations, processes for preparing them and their use in the treatment of cytokine mediated diseases.

Abstract translation: 本发明涉及基于p38激酶抑制剂和另一活性成分的药物组合疗法，包含这些组合的药物组合物，其制备方法及其在治疗细胞因子介导的疾病中的用途。

公开(公告)号：US20050148555A1

公开(公告)日：2005-07-07

申请号：US10921448

申请日：2004-08-19

Applicant: Abhya Gupta ,  Philippe Iacono ,  Linda Kelash-Cannavo ,  Jeffrey Madwed ,  Jung-Yong Park ,  Susan Way ,  Mehran Yazdanian

Inventor： Abhya Gupta ,  Philippe Iacono ,  Linda Kelash-Cannavo ,  Jeffrey Madwed ,  Jung-Yong Park ,  Susan Way ,  Mehran Yazdanian

IPC: A61K31/192 ,  A61K31/415 ,  A61K31/505 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/557 ,  A61K31/573 ,  A61K31/58 ,  A61K31/60 ,  A61K45/06

CPC classification number: A61K45/06 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5375 ,  A61K31/5377

Abstract: Disclosed are methods of treating COPD and Pulmonary Hypertension using p38 Map Kinase inhibitors in combination with one or more other active ingredients.

Abstract translation: 公开了使用p38 Map Kinase抑制剂与一种或多种其它活性成分组合治疗COPD和肺高血压的方法。

公开(公告)号：US06808721B2

公开(公告)日：2004-10-26

申请号：US10282383

申请日：2002-10-29

Applicant: Michael Cappola ,  George W. Gereg ,  Susan Way

Inventor： Michael Cappola ,  George W. Gereg ,  Susan Way

IPC: A61K928

CPC classification number: B82Y5/00 ,  A61K31/5377 ,  A61K47/6951

Abstract: A formulation comprising, and process for preparing, improved oral dosage forms of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea, a chemical entity with anti-inflammatory properties. Granulation of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea within specified ranges provides improved dissolution of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea and oral bioavailability, as well as content uniformity. Incorporation into the formulation of an aqueous soluble inclusion compound capable of forming a complex with 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea, such as beta-cyclodextrin provides enhanced stability of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea, in particular in highly ionic environments. Chipping and disintegration of tablets containing more than about 10% betacyclodextrin can be prevented by applying a polymeric coat to the surface of the tablet at a temperature below 40° C.

Abstract translation: 包含改善口服剂型1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲，具有抗炎特性的化学物质。 1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲在特定范围内提供1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基 - 乙氧基） - 萘 -1-基] - 脲和口服生物利用度，以及含量均匀性。 加入能够与1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3- [4-（2-吗啉-4-基） 乙氧基） - 萘-1-基] - 脲如β-环糊精提供了增强的1-（5-叔丁基-2-对甲苯基-2H-吡唑-3-基）-3 - [4-（2-吗啉-4-基 - 乙氧基） - 萘-1-基] - 脲，特别是在高离子环境中。 通过在低于40℃的温度下将片剂的表面施加聚合物涂层，可以防止包含超过约10％的β-环糊精的片剂的碎裂和崩解。