公开(公告)号：US20090088366A1

公开(公告)日：2009-04-02

申请号：US12237117

申请日：2008-09-24

申请人： David S. Garvey ,  Ricky D. Gaston ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

发明人： David S. Garvey ,  Ricky D. Gaston ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

IPC分类号： A61K38/02 ,  A61K31/215 ,  A61K31/4164 ,  A61K31/4375 ,  A61P15/00 ,  A61K31/496 ,  A61K31/7076

CPC分类号： A61K31/5575

摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.

摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎

公开(公告)号：US07449595B2

公开(公告)日：2008-11-11

申请号：US11641050

申请日：2006-12-19

申请人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

发明人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

IPC分类号： C07C405/00 ,  A61K31/557

CPC分类号： A61K31/5575

摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.

摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E 1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎

公开(公告)号：US07176238B1

公开(公告)日：2007-02-13

申请号：US09516194

申请日：2000-03-01

申请人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

发明人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

IPC分类号： A61K31/557 ,  C07C405/00

CPC分类号： A61K31/5575

摘要： The present invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 vasoactive agent. The present invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions. The compounds and/or compositions of the present invention can also be provided in the form of a pharmaceutical kit.

摘要翻译： 本发明描述了新的亚硝基化和/或亚硝基化的前列腺素，以及包含至少一种亚硝基化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性的内皮水平 舒张因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E 1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供了治疗或预防男性和女性性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或 诱导堕胎。 本发明的化合物和/或组合物也可以以药物试剂盒的形式提供。

公开(公告)号：US07772278B2

公开(公告)日：2010-08-10

申请号：US12237117

申请日：2008-09-24

申请人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

发明人： David S. Garvey ,  Ricky D. Gaston ,  L. Gordon Letts ,  Inigo Saenz de Tejada ,  Sang William Tam ,  Manuel Worcel

IPC分类号： A61K31/557 ,  C07C405/00

CPC分类号： A61K31/5575

摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, 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 vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.

摘要翻译： 本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松 因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。 本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。 前列腺素优选为前列腺素E1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。 本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导 堕胎

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：US07163958B2

公开(公告)日：2007-01-16

申请号：US10612014

申请日：2003-07-03

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： A61K31/21 ,  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：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：US08088762B2

公开(公告)日：2012-01-03

申请号：US12636316

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 ,  A61K31/425 ,  C07D498/02 ,  C07D295/02 ,  C07D333/22

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 anti-inflammatory 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： 本发明描述了新的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，和任选的至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成 一氧化氮，提高内源性内源水平的内源性松弛因子，或者是一氧化氮合成酶的底物和/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。