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11. 发明授权

US07220749B2 Nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use 失效
标题翻译：亚硝化和/或亚硝基化的环氧合酶-2选择性抑制剂，组合物和使用方法
公开(公告)号：US07220749B2
公开(公告)日：2007-05-22
申请号：US10718060
申请日：2003-06-10
申请人： L. Gordon Letts , David S. Garvey
发明人： L. Gordon Letts , David S. Garvey
IPC分类号： A61K31/495 , A61K31/216 , A61K31/34 , C07D241/04 , C07D493/04 , C07C229/42
CPC分类号： C07D295/185 , A61K45/06 , C07C229/42 , C07C317/18 , C07C323/12 , C07D493/04
摘要： The invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated 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. The invention also provides novel compositions comprising at least one COX-2 selective inhibitor, that is optionally sitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的环氧合酶2（COX-2）选择性抑制剂和包含至少一种亚硝化和/或亚硝基化的环氧合酶2（COX-2）选择性抑制剂的新组合物，和任选的至少一种可以提供的化合物，转移或释放一氧化氮，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，或者是一氧化氮合酶的底物和/或任选的至少一种治疗剂。本发明还提供了包含至少一种COX-2选择性抑制剂（其任选被亚硝化和/或亚硝基化）和任选地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。

12. 发明授权

US07211590B2 Nitrosated proton pump inhibitors, compositions and methods of use 失效
标题翻译：亚硝化质子泵抑制剂，组合物和使用方法
公开(公告)号：US07211590B2
公开(公告)日：2007-05-01
申请号：US10631782
申请日：2003-08-01
申请人： Xinqin Fang , David S. Garvey , L. Gordon Letts
发明人： Xinqin Fang , David S. Garvey , L. Gordon Letts
IPC分类号： C07D401/04 , A61K31/44
CPC分类号： C07D401/12
摘要： The invention describes novel nitrosated proton pump inhibitor compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated proton pump inhibitor compound, 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 proton pump inhibitor compound, 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 proton pump inhibitor compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating bacterial infections and/or viral infections.
摘要翻译：本发明描述了新的亚硝化质子泵抑制剂化合物及其药学上可接受的盐，以及包含至少一种亚硝化质子泵抑制剂化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，刺激内源性硝酸合成的新型组合物氧化物，提高内源性内源性水平的内源性松弛因子，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亚硝化质子泵抑制剂化合物和至少一种捐赠，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松弛因子水平，刺激一氧化氮的内源性合成或是底物用于一氧化氮合酶和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化质子泵抑制剂化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明还提供了治疗胃肠道疾病的方法; 促进溃疡愈合; 减少溃疡复发; 改善胃保护性质，抗幽门螺旋杆菌性质或质子泵抑制剂的抗酸性; 降低或减少与使用非甾体抗炎化合物相关的胃肠道毒性; 治疗细菌感染和/或病毒感染。

13. 发明授权

US06852739B1 Methods using proton pump inhibitors and nitric oxide donors 失效
标题翻译：使用质子泵抑制剂和一氧化氮供体的方法
公开(公告)号：US06852739B1
公开(公告)日：2005-02-08
申请号：US09512829
申请日：2000-02-25
申请人： David S. Garvey , L. Gordon Letts , Sang William Tam
发明人： David S. Garvey , L. Gordon Letts , Sang William Tam
IPC分类号： A61K31/00 , A61K31/4184 , A61K31/433 , A61K31/437 , A61K31/4439 , A61K31/444 , A61K31/4706 , A61K31/506 , A61K45/06 , C07D401/12
CPC分类号： C07D401/12 , A61K31/00 , A61K31/4184 , A61K31/433 , A61K31/437 , A61K31/4439 , A61K31/444 , A61K31/4706 , A61K31/506 , A61K45/06 , A61K2300/00
摘要： The present invention describes novel nitrosated and/or nitrosylated proton pump inhibitor compounds, and novel compositions comprising at least one proton pump inhibitor compound that is optionally substituted with at least one NO and/or N02 group, 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 nonsteroidal antiinflammatory drug, selective COX-2 inhibitor, antacid, bismuth-containing reagent, acid-degradable antibacterial compound, and mixtures thereof. The present invention also provides methods for treating and/or preventing gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump-inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating Helicobacter pylori and viral infections. 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化和/或亚硝化的质子泵抑制剂化合物，以及包含至少一种任选被至少一个NO和/或NO 2基团取代的至少一种质子泵抑制剂化合物的新组合物，和任选的至少一种化合物，捐赠，转移或释放一氧化氮，刺激一氧化氮的内源性合成，提高内源性内皮衍生的松弛因子水平，或是一氧化氮合酶的底物和/或至少一种非甾体抗炎药，选择性COX-2抑制剂，抗酸剂，含铋试剂，酸降解抗菌化合物及其混合物。本发明还提供了治疗和/或预防胃肠道疾病的方法; 促进溃疡愈合; 减少溃疡复发; 改善胃保护性质，抗幽门螺杆菌特性或质子泵抑制剂的抗酸性; 降低或减少与使用非甾体抗炎化合物相关的胃肠道毒性; 治疗幽门螺杆菌和病毒感染。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。

14. 发明授权

US06579863B1 Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders 失效
标题翻译：亚硝化和亚硝化化合物及其组合物及其用于治疗呼吸系统疾病的用途
公开(公告)号：US06579863B1
公开(公告)日：2003-06-17
申请号：US09689851
申请日：2000-10-13
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Stewart K. Richardson
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Stewart K. Richardson
IPC分类号： A61K3156
CPC分类号： C07D451/06 , C07C313/36 , C07D311/22 , C07D451/10 , C07D471/04 , C07J5/00 , C07J7/00 , C07J31/00 , C07J71/00 , C07J71/0031
摘要： Disclosed are (i) compounds of a steroid, a &bgr;-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, &bgr;-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO•) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
摘要翻译：公开的是（i）直接或间接连接到NO或NO 2基团或刺激NO或EDRF的内源性产生的基团的类固醇，β-激动剂，抗胆碱能药，肥大细胞稳定剂和磷酸二酯酶（PDE）抑制剂的化合物体内; （ii）类固醇，β-激动剂，抗胆碱能药物，肥大细胞稳定剂和PDE抑制剂的组合物，其可任选地被至少一个NO或NO 2部分或刺激体内NO或EDRF内源性产生的基团取代;以及化合物捐赠，转移或释放一氧化氮作为带电物质，即亚硝酸盐（NO +）或硝酰基（NO-），或作为中性物质，一氧化氮（NO））或刺激体内NO或EDRF的内源性产生; 和（iii）用于预防和/或治疗呼吸系统疾病。

15. 发明授权

US6057347A Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs 失效
公开(公告)号：US6057347A
公开(公告)日：2000-05-02
申请号：US931564
申请日：1997-09-16
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
IPC分类号： C07D417/04 , A61K31/00 , A61K31/19 , A61K31/403 , A61K31/404 , A61K31/405 , A61K31/54 , A61K31/541 , A61K38/00 , A61K45/00 , A61P1/00 , A61P1/04 , A61P29/00 , A61P43/00 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07D417/12 , C07J41/00 , C07K5/02 , A61K31/12 , C07C207/00 , C07C207/02 , C07C207/04
CPC分类号： C07D417/12 , A61K31/343 , A61K31/60 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07J41/0055 , C07K5/0215 , A61K38/00
摘要： Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; compositions comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed. The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.

16. 发明授权

US6051588A Nitroso esters of .beta.-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs 失效
标题翻译：非甾体抗炎药的β-氧代酰胺和芳基丙酸衍生物的亚硝基酯
公开(公告)号：US6051588A
公开(公告)日：2000-04-18
申请号：US425090
申请日：1995-04-19
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
IPC分类号： A61K38/00 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07D417/12 , C07J41/00 , C07K5/02 , C07D403/02 , A61K31/38 , A61K31/40 , A61K31/405 , A61K31/42 , C07D263/30 , C07D333/02 , C07D403/14
CPC分类号： C07D417/12 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07J41/0055 , C07K5/0215 , A61K38/00
摘要： A compound comprising a non-steroidal antiinflammatory agent to which is directly or indirectly linked an NO group, a pharmaceutical composition including the compounds and methods of treatment of pain and/or inflammation using the compounds and compositions are disclosed. Also disclosed is a composition comprising a non-steroidal antiinflammatory agent and a compound that donates, transfers or releases nitric oxide.
摘要翻译：公开了一种化合物，其包含直接或间接连接NO基团的非甾体抗炎剂，包含该化合物的药物组合物和使用该化合物和组合物治疗疼痛和/或炎症的方法。还公开了包含非甾体抗炎剂和捐赠，转移或释放一氧化氮的化合物的组合物。

17. 发明授权

US6043233A Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs 失效
标题翻译：防止非甾体抗炎药引起的毒性的组合物和方法
公开(公告)号：US6043233A
公开(公告)日：2000-03-28
申请号：US235804
申请日：1999-01-22
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
IPC分类号： C07D417/04 , A61K31/00 , A61K31/19 , A61K31/403 , A61K31/404 , A61K31/405 , A61K31/54 , A61K31/541 , A61K38/00 , A61K45/00 , A61P1/00 , A61P1/04 , A61P29/00 , A61P43/00 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07D417/12 , C07J41/00 , C07K5/02 , A61K31/192 , A61K31/407 , A61K31/60 , A61K31/603 , A61K31/606
CPC分类号： C07D417/12 , A61K31/343 , A61K31/60 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07J41/0055 , C07K5/0215 , A61K38/00
摘要： Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; compositions comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.
摘要翻译：已被一氧化氮基团取代的非甾体抗炎药; 组合物，其包含（i）非甾体抗炎药，其可以任选地被一氧化氮基团取代，和（ii）直接捐赠，转移或释放一氧化氮基团（优选作为带电物质，特别是亚硝基鎓）的化合物; 并且公开了使用所述组合物治疗炎症，疼痛，胃肠道损伤和/或发烧的方法。所述化合物和组合物可防止否则由非甾体抗炎药引起的胃肠道，肾脏和其它毒性。

18. 发明授权

US6043232A Nitroso esters of beta-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs 失效
标题翻译： β-氧代酰胺的亚硝基酯和非甾体抗炎药的芳基丙酸衍生物
公开(公告)号：US6043232A
公开(公告)日：2000-03-28
申请号：US235802
申请日：1999-01-22
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Sang William Tam
IPC分类号： A61K38/00 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07D417/12 , C07J41/00 , C07K5/02 , A61K31/407 , A61K31/245 , A61K31/4245 , C07D271/04 , C07D487/04
CPC分类号： C07D417/12 , C07C203/00 , C07C327/28 , C07C381/00 , C07D209/28 , C07J41/0055 , C07K5/0215 , A61K38/00
摘要： A compound comprising a non-steroidal antiinflammatory agent to which is directly or indirectly linked an NO group, a compound comprising an enolic anilide non-steroidal antiinflammatory agent to which is directly or indirectly linked an NO.sub.2 group, a pharmaceutical composition including the compounds and methods of treatment of pain and/or inflammation using the compounds and compositions are disclosed. Also disclosed is a composition comprising a non-steroidal antiinflammatory agent and a compound that donates, transfers or releases nitric oxide.
摘要翻译：包含与NO基团直接或间接连接的非甾体抗炎剂的化合物，包含与NO 2基团直接或间接连接的烯醇化物非甾体抗炎剂的化合物，包含该化合物的药物组合物和方法公开了使用化合物和组合物治疗疼痛和/或炎症的方法。还公开了包含非甾体抗炎剂和捐赠，转移或释放一氧化氮的化合物的组合物。

19. 发明授权

US07449595B2 Nitrosated and nitrosylated prostaglandins, compositions and methods of use 失效
标题翻译：亚硝化和亚硝酰化前列腺素，组合物和使用方法
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

20. 发明授权

US07432285B2 Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use 失效
标题翻译：亚硝基化和亚硝基化环加氧酶-2抑制剂，组合物和使用方法
公开(公告)号：US07432285B2
公开(公告)日：2008-10-07
申请号：US11599519
申请日：2006-11-15
申请人： Ramani R. Bandarage , Upul K. Bandarage , Xinqin Fang , David S. Garvey , L. Gordon Letts , Joseph D. Schroeder , Sang W. Tam
发明人： Ramani R. Bandarage , Upul K. Bandarage , Xinqin Fang , David S. Garvey , L. Gordon Letts , Joseph D. Schroeder , Sang W. Tam
IPC分类号： C07D207/325 , A61K31/415
CPC分类号： C07D207/333 , C07C317/46 , C07C381/00 , C07D209/12 , C07D209/18 , C07D231/12 , C07D231/14 , C07D233/64 , C07D237/14 , C07D261/08 , C07D263/20 , C07D307/58 , C07D311/12 , C07D413/12 , C07D471/04
摘要： The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) 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. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的环氧合酶2（COX-2）抑制剂和包含至少一种亚硝化和/或亚硝基化的环氧合酶2（COX-2）抑制剂的新组合物，和任选的至少一种可以提供，转移或释放一氧化氮，刺激一氧化氮的内源性合成，提高内皮衍生的松弛因子的内源水平，或者是一氧化氮合酶的底物和/或任选的至少一种治疗剂。本发明还提供了包含至少一种母体COX-2抑制剂和至少一种一氧化氮供体以及任选的至少一种治疗剂的新型组合物。本发明还提供用于治疗炎症，疼痛和发烧的试剂盒和方法; 用于治疗和/或改善COX-2抑制剂的胃肠性质; 促进伤口愈合; 用于治疗和/或预防肾毒性; 并且用于治疗和/或预防由环氧合酶-2水平升高引起的其它疾病。

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