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1. 发明申请

US20060194861A1 Cyclooxygenase-2 selective inhibitors, compositions and methods of use 失效
标题翻译：环氧合酶-2选择性抑制剂，组合物和使用方法
公开(公告)号：US20060194861A1
公开(公告)日：2006-08-31
申请号：US11418187
申请日：2006-05-05
申请人： Ipul Bandarage , Richard Earl , Maiko Ezawa , Xinqin Fang , David Garvey , Subhash Khanapure , Ramani Ranatunge , Stewart Richardson , Joseph Schroeder , Cheri Stevenson , Shiow-Jyi Wey
发明人： Ipul Bandarage , Richard Earl , Maiko Ezawa , Xinqin Fang , David Garvey , Subhash Khanapure , Ramani Ranatunge , Stewart Richardson , Joseph Schroeder , Cheri Stevenson , Shiow-Jyi Wey
IPC分类号： C07D231/06 , A61K31/415
CPC分类号： C07D231/12 , C07D261/08 , C07D401/04
摘要： The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.
摘要翻译：本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成的一氧化氮，提高内源性内源性释放因子水平，或者是一氧化氮合酶的底物和/或至少一种治疗剂。本发明还提供了包含至少一种COX-2选择性抑制剂，任选地亚硝基化和/或亚硝基化的新的试剂盒，以及任选的至少一种一氧化氮供体，和/或任选的至少一种治疗剂。本发明的新型环加氧酶2选择性抑制剂可以任选地亚硝化和/或亚硝化。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠性质; 促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管外形。

2. 发明申请

US20050222243A1 Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
标题翻译：硝化非甾体抗炎化合物，组合物和使用方法
公开(公告)号：US20050222243A1
公开(公告)日：2005-10-06
申请号：US11134358
申请日：2005-05-23
申请人： Richard Earl , Maiko Ezawa , Xinqin Fang , David Garvey , Ricky Gaston , Subhash Khanapure , L. Gordon Letts , Chia-En Lin , Ramani Ranatunga , Stewart Richardson , Joseph Schroeder , Cheri Stevenson , Shiow-Jyi Wey
发明人： Richard Earl , Maiko Ezawa , Xinqin Fang , David Garvey , Ricky Gaston , Subhash Khanapure , L. Gordon Letts , Chia-En Lin , Ramani Ranatunga , Stewart Richardson , Joseph Schroeder , Cheri Stevenson , Shiow-Jyi Wey
IPC分类号： C07D295/08 , A61K31/21 , A61K31/405 , A61K31/445 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/10 , A61P1/14 , A61P3/04 , A61P17/02 , A61P25/28 , A61P27/02 , A61P29/00 , A61P35/00 , A61P35/02 , A61P43/00 , C07C203/04 , C07C205/40 , C07C205/56 , C07C219/10 , C07C229/42 , C07C235/08 , C07C235/12 , C07C235/34 , C07C235/42 , C07C237/08 , C07C243/28 , C07C271/16 , C07C271/64 , C07C291/02 , C07C311/17 , C07C317/18 , C07C317/32 , C07C317/46 , C07C323/12 , C07C327/28 , C07D209/18 , C07D209/28 , C07D211/22 , C07D211/56 , C07D493/04 , C07F9/40 , C07D209/20
CPC分类号： C07D493/04 , C07C291/02 , C07C311/17 , C07C317/18 , C07C323/12 , C07C327/28 , C07D209/18 , C07D211/22 , C07D211/56
摘要： The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
摘要翻译：本发明描述了新型亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激一氧化氮的内源性合成升高内源性内源性松弛因子水平，或是一氧化氮合酶的底物和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物合酶和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

3. 发明申请

US20060189603A1 Nitric oxide enhancing diuretic compounds, compositions and methods of use 失效
标题翻译：一氧化氮增强利尿剂，组合物和使用方法
公开(公告)号：US20060189603A1
公开(公告)日：2006-08-24
申请号：US11360599
申请日：2006-02-24
申请人： David Garvey , L. Letts , Richard Earl , Maiko Ezawa , Xinqin Fang , Ricky Gaston , Subhash Khanapure , Chia-En Lin , Ramani Ranatunge , Cheri Stevenson , Shiow-Jyi Wey
发明人： David Garvey , L. Letts , Richard Earl , Maiko Ezawa , Xinqin Fang , Ricky Gaston , Subhash Khanapure , Chia-En Lin , Ramani Ranatunge , Cheri Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/549 , C07D417/02
CPC分类号： C07D285/30 , C07D285/28 , C07D285/32 , C07D417/04 , C07D417/06 , C07D513/10
摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.
摘要翻译：本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合征; （q）治疗性功能障碍; 和（r）高脂血症。一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

4. 发明申请

US20070037821A1 Nitrosated glutamic acid compounds, compositions and methods of use 审中-公开
标题翻译：亚硝酸谷氨酸化合物，组合物和使用方法
公开(公告)号：US20070037821A1
公开(公告)日：2007-02-15
申请号：US10573030
申请日：2004-09-27
申请人： David Garvey , Richard Earl , Malko Ezawa , Xinqin Fang , Ricky Gaston , Subhash Khanapure , Chia-En Lin , Ramani Ranatunga , Cheri Stevenson , Shiow-Jyi Wey
发明人： David Garvey , Richard Earl , Malko Ezawa , Xinqin Fang , Ricky Gaston , Subhash Khanapure , Chia-En Lin , Ramani Ranatunga , Cheri Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/495 , C07D241/04 , A61K31/21 , C07C203/02
CPC分类号： C07C271/22 , C07C229/24 , C07C237/12 , C07D295/185
摘要： The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.
摘要翻译：本发明描述了新的亚硝酸化谷氨酸化合物及其药学上可接受的盐，以及包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。本发明还提供了包含至少一种亚硝酸化谷氨酸化合物和任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗由γ-谷氨酰转肽酶水平升高引起的疾病和（m）将化合物和一氧化氮靶向递送至含有γ-谷氨酰转肽酶的器官，细胞或组织。

5. 发明申请

US20050059655A1 Nitrosated and nitrosylated diuretic compounds, compositions and methods of use 失效
标题翻译：硝化和亚硝化利尿剂，组合物和使用方法
公开(公告)号：US20050059655A1
公开(公告)日：2005-03-17
申请号：US10921936
申请日：2004-08-20
申请人： David Garvey , L. Letts , Manuel Worcel , Richard Earl , Maiko Ezawa , Xinqin Fang , Subhash Khanapure , Chia-En Lin , Ramani Ranatunga , Cheri Stevenson
发明人： David Garvey , L. Letts , Manuel Worcel , Richard Earl , Maiko Ezawa , Xinqin Fang , Subhash Khanapure , Chia-En Lin , Ramani Ranatunga , Cheri Stevenson
IPC分类号： A61K20060101 , A61K31/4523 , A61K31/517 , A61K31/5415 , A61K31/549 , C07D211/00 , C07D285/22 , C07D295/00 , C07D307/00 , C07D417/12 , C07D417/14
CPC分类号： C07D403/10 , C07C205/40 , C07D233/68 , C07D235/18 , C07D257/04 , C07D307/52 , C07D401/12 , C07D401/14 , C07D405/06 , C07D405/12 , C07D405/14 , C07D409/04 , C07D409/06 , C07D409/14 , C07D413/10 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04
摘要： The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; and (l) treating nephropathy.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的利尿剂或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝基化的利尿剂化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂。本发明还提供了包含至少一种本发明的利尿剂化合物，其任选被亚硝化和/或亚硝基化的新组合物和试剂盒，以及任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂。本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; 和（l）治疗肾病。

6. 发明申请

US20070032533A1 Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use 审中-公开
标题翻译：一氧化氮增强型血管紧张素II拮抗剂化合物，组合物和使用方法
公开(公告)号：US20070032533A1
公开(公告)日：2007-02-08
申请号：US11499770
申请日：2006-08-07
申请人： David Garvey , Xiong Cai , Xinqin Fang , Ramani Ranatunge , Shiow-Jyi Wey , Hai-Xiao Zhai
发明人： David Garvey , Xiong Cai , Xinqin Fang , Ramani Ranatunge , Shiow-Jyi Wey , Hai-Xiao Zhai
IPC分类号： A61K31/433 , A61K31/4245 , A61K31/42
CPC分类号： C07D257/04 , C07D401/12 , C07D403/10 , C07D403/12 , C07D471/04
摘要： The invention describes compositions and kits comprising at least one nitric oxide enhancing angiotensin II antagonist compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing angiotensin II antagonist compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension (o) treating central nervous system disorders; (p) treating metabolic syndrome; and (q) treating hyperlipidemia. The nitric oxide enhancing angiotensin II antagonist compounds comprise at least one nitric oxide enhancing group linked to the angiotensin II antagonist compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.
摘要翻译：本发明描述了包含至少一种一氧化氮增强型血管紧张素II拮抗剂化合物或其药学上可接受的盐的组合物和试剂盒，以及包含至少一种一氧化氮增强型血管紧张素II拮抗剂化合物和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂。本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗外周血管疾病; （m）治疗门静脉高压（o）治疗中枢神经系统疾病; （p）治疗代谢综合征; 和（q）治疗高脂血症。一氧化氮增强型血管紧张素II拮抗剂化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与血管紧张素II拮抗剂化合物连接的至少一个一氧化氮增强基团。

7. 发明申请

US20050059665A1 Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use 审中-公开
公开(公告)号：US20050059665A1
公开(公告)日：2005-03-17
申请号：US10969079
申请日：2004-10-21
申请人： Subhash Khanapure , David Garvey , Richard Earl , Maiko Ezawa , Xinqin Fang , Ricky Gaston
发明人： Subhash Khanapure , David Garvey , Richard Earl , Maiko Ezawa , Xinqin Fang , Ricky Gaston
IPC分类号： A61K31/10 , A61K31/357 , A61K31/36 , A61K31/443 , A61K31/4525 , A61K45/00 , A61K45/06 , A61P1/04 , A61P1/14 , A61P7/02 , A61P7/04 , A61P9/10 , A61P11/00 , A61P11/06 , A61P11/08 , A61P13/02 , A61P13/12 , A61P15/04 , A61P15/08 , A61P17/00 , A61P17/02 , A61P19/02 , A61P21/02 , A61P25/28 , A61P27/02 , A61P27/16 , A61P29/00 , A61P31/04 , A61P35/00 , A61P35/02 , A61P37/08 , A61P39/02 , A61P43/00 , C07C317/14 , C07C317/22 , C07C317/24 , C07D317/56 , C07D319/08 , C07D319/18 , C07D319/20 , C07D405/06 , C07D413/06 , A61K31/501 , A61K31/21 , A61K31/444
CPC分类号： C07D319/08 , A61K45/06 , C07D317/56 , C07D319/18 , C07D319/20 , C07D405/06
摘要： The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal anti-inflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2 antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton-pump-inhibitors, isoprostane inhibitors, and mixtures thereof. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity or other toxicities; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

8. 发明授权

US08304409B2 Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
标题翻译：硝化非甾体抗炎化合物，组合物和使用方法
公开(公告)号：US08304409B2
公开(公告)日：2012-11-06
申请号：US12636329
申请日：2009-12-11
申请人： Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/54 , A61K31/44 , A61K31/445 , A61K31/425 , A61K31/42 , A61K31/415 , A61K31/335 , A61K31/24 , A61K31/12
CPC分类号： C07D493/04 , C07C291/02 , C07C311/17 , C07C317/18 , C07C323/12 , C07C327/28 , C07D209/18 , C07D211/22 , C07D211/56
摘要： The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
摘要翻译：本发明描述了新型亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激一氧化氮的内源性合成升高内源性内源性松弛因子水平，或是一氧化氮合酶的底物和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物合酶和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

9. 发明授权

US07396829B2 Nitric oxide enhancing diuretic compounds, compositions and methods of use 失效
标题翻译：一氧化氮增强利尿剂，组合物和使用方法
公开(公告)号：US07396829B2
公开(公告)日：2008-07-08
申请号：US11360599
申请日：2006-02-24
申请人： David S. Garvey , L. Gordon Letts , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Ricky D. Gaston , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： David S. Garvey , L. Gordon Letts , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Ricky D. Gaston , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： C07D417/02 , A61K31/549
CPC分类号： C07D285/30 , C07D285/28 , C07D285/32 , C07D417/04 , C07D417/06 , C07D513/10
摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.
摘要翻译：本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合症; （q）治疗性功能障碍; 和（r）高脂血症。一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

10. 发明申请

US20090005350A1 CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： CYCLOOXYGENASE-2选择性抑制剂，组合物和使用方法
公开(公告)号：US20090005350A1
公开(公告)日：2009-01-01
申请号：US12210776
申请日：2008-09-15
申请人： Upul K. Bandarage , Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Subhash P. Khanapure , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： Upul K. Bandarage , Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Subhash P. Khanapure , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/60 , A61K31/415 , C07D231/10
CPC分类号： C07D231/12 , C07D261/08 , C07D401/04
摘要： The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.
摘要翻译：本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成的一氧化氮，提高内源性内源性释放因子水平，或者是一氧化氮合酶的底物和/或至少一种治疗剂。本发明还提供了包含至少一种COX-2选择性抑制剂，任选地亚硝基化和/或亚硝基化的新的试剂盒，以及任选的至少一种一氧化氮供体，和/或任选的至少一种治疗剂。本发明的新型环加氧酶2选择性抑制剂可以任选地亚硝化和/或亚硝化。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠性质; 促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管外形。

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