公开(公告)号：US07838023B2

公开(公告)日：2010-11-23

申请号：US12093561

申请日：2006-11-16

申请人： David S. Garvey ,  Ramani R. Ranatunge

发明人： David S. Garvey ,  Ramani R. Ranatunge

IPC分类号： A61K9/00 ,  A61K31/4245 ,  A61K31/502 ,  A61K33/00 ,  A61P9/00 ,  C07D271/08

CPC分类号： C07D271/08

摘要： The invention provides novel furoxan compounds, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for (a) treating cardiovascular diseases; (b) inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device; (c) treating pathological conditions resulting from abnormal cell proliferation; (d) treating transplantation rejections, (e) treating autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; (f) reducing scar tissue or for inhibiting wound contraction; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; and (j) treating diseases caused by endothelial dysfunctions.

摘要翻译： 本发明提供新的呋喃糖化合物或其药学上可接受的盐，以及包含至少一种化合物和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新组合物。 本发明的化合物和组合物也可以结合到基质上。 本发明还提供了（a）治疗心血管疾病的方法; （b）抑制由血液暴露于医疗器械引起的血小板聚集和血小板粘附; （c）治疗由异常细胞增殖引起的病理状况; （d）治疗移植排斥，（e）治疗自身免疫性，炎症性，增殖性，过度增殖性或血管性疾病; （f）减少瘢痕组织或抑制伤口收缩; （g）治疗由氧化应激引起的疾病; （h）治疗内皮功能障碍; 和（j）治疗由内皮功能障碍引起的疾病。

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。

公开(公告)号：US07754772B2

公开(公告)日：2010-07-13

申请号：US11134358

申请日：2005-05-23

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： A61K31/135 ,  C07C203/04

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。

公开(公告)号：US07595313B2

公开(公告)日：2009-09-29

申请号：US12136531

申请日：2008-06-10

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： C07D285/24 ,  C07D417/04 ,  C07D513/10 ,  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。

公开(公告)号：US20080268014A1

公开(公告)日：2008-10-30

申请号：US12093561

申请日：2006-11-16

申请人： David S. Garvey ,  Ramani R. Ranatunge

发明人： David S. Garvey ,  Ramani R. Ranatunge

IPC分类号： A61K9/00 ,  C07D271/08 ,  A61K31/4245 ,  A61P9/00 ,  A61K31/502 ,  A61K33/00

CPC分类号： C07D271/08

摘要： The invention provides novel furoxan compounds, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for (a) treating cardiovascular diseases; (b) inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device; (c) treating pathological conditions resulting from abnormal cell proliferation; (d) treating transplantation rejections, (e) treating autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; (f) reducing scar tissue or for inhibiting wound contraction; (g) treating diseases resulting from oxidative stress; (h) treating endothelial dysfunctions; and (j) treating diseases caused by endothelial dysfunctions.

摘要翻译： 本发明提供了新的呋喃糖化合物或其药学上可接受的盐，以及包含至少一种化合物和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新组合物。 本发明的化合物和组合物也可以结合到基质上。 本发明还提供了（a）治疗心血管疾病的方法; （b）抑制由血液暴露于医疗器械引起的血小板聚集和血小板粘附; （c）治疗由异常细胞增殖引起的病理状况; （d）治疗移植排斥，（e）治疗自身免疫性，炎症性，增殖性，过度增殖性或血管性疾病; （f）减少瘢痕组织或抑制伤口收缩; （g）治疗由氧化应激引起的疾病; （h）治疗内皮功能障碍; 和（j）治疗由内皮功能障碍引起的疾病。

公开(公告)号：US07442802B2

公开(公告)日：2008-10-28

申请号：US11418187

申请日：2006-05-05

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： A61K31/415 ,  C07D231/12

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。

公开(公告)号：US07238814B2

公开(公告)日：2007-07-03

申请号：US10781705

申请日：2004-02-20

申请人： Przemyslaw A. Marek ,  Andzrej M. Trocha ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson

发明人： Przemyslaw A. Marek ,  Andzrej M. Trocha ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson

IPC分类号： C07D209/56 ,  C07D263/00 ,  A61K31/395 ,  A61K31/421

CPC分类号： A61B5/4368 ,  A61B5/015 ,  A61K49/0004 ,  Y10S514/929

摘要： The invention describes compositions and kits comprising 4-aza-4-(2-methyl-2-sulfanylpropyl) tricyclo(5.2.1.0 )dec-8-ene-3,5-dione; 4-aza-4-(2-methyl-2-(nitrosothio)propyl) tricyclo(5.2.1.0 )dec-8-ene-3,5-dione; 4-{1-methyl-1-((2,4,6-trimethoxyphenyl)methylthio)ethyl}-1,3-oxazolidin-2-one; 2-aAmino-3-methyl-3-((2,4,6-trimethoxyphenyl)methylthio)butan-1-ol; 4-(1-methyl-1-(nitrosothio)ethyl)-1,3-oxazolidin-2-one; or pharmaceutically acceptable salts thereof. The compositions of the invention can further comprise at least one penetration enhancer, 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 vasoactive agent.

摘要翻译： 本发明描述了包含4-氮杂-4-（2-甲基-2-硫烷基丙基）三环（5.2.1.0 2,6）癸-8-烯-3,5-二酮的组合物和试剂盒; 4-氮杂-4-（2-甲基-2-（亚硝基硫基）丙基）三环（5.2.1.0 2,6）癸-8-烯-3,5-二酮; 4- {1-甲基-1 - （（2,4,6-三甲氧基苯基）甲硫基）乙基} -1,3-恶唑烷-2-酮; 2-（2-氨基-3-甲基-3 - （（2,4,6-三甲氧基苯基）甲硫基）丁-1-醇; 4-（1-甲基-1-（亚硝基硫代）乙基）-1,3-恶唑烷-2-酮; 或其药学上可接受的盐。 本发明的组合物可进一步包含至少一种渗透增强剂，至少一种捐赠，转移或释放一氧化氮的化合物，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 合成酶和/或至少一种血管活性剂。

公开(公告)号：US08222277B2

公开(公告)日：2012-07-17

申请号：US12980077

申请日：2010-12-28

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： A61K31/445 ,  A61K31/54 ,  A61K31/44 ,  A61K31/425 ,  A61K31/42 ,  A61K31/415 ,  A61K31/335 ,  A61K31/215 ,  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 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 comprising administration of novel compositions comprising at least one nitrosated NSAID, and, optionally, 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.

摘要翻译： 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; 以及用于治疗和/或预防眼科疾病和/或病症，包括施用包含至少一种亚硝化NSAID的新组合物，和任选地至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的内源性放松 因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶和/或至少一种治疗剂的底物。

公开(公告)号：US07883714B2

公开(公告)日：2011-02-08

申请号：US12636306

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： A61K9/00 ,  A61K31/21 ,  C07C203/04

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。

公开(公告)号：US20100093708A1

公开(公告)日：2010-04-15

申请号：US12636306

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： A61K31/5415 ,  C07D471/04 ,  C07D279/22 ,  A61K31/437 ,  A61P29/00 ,  A61P1/00 ,  A61P17/02 ,  A61P27/02

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。