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41. 发明授权

US6143734A 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：US6143734A
公开(公告)日：2000-11-07
申请号：US495251
申请日：2000-01-31
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 , A61K31/4245 , 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。

42. 发明申请

US20080300292A1 Nitrosated and Nitrosylated Compounds, Compositions and Methods for the Treatment of Ophthalmic Disorders 审中-公开
标题翻译：硝基化和亚硝基化化合物，组合物和治疗眼科疾病的方法
公开(公告)号：US20080300292A1
公开(公告)日：2008-12-04
申请号：US11667272
申请日：2005-11-08
申请人： L. Gordon Letts , David S. Garvey
发明人： L. Gordon Letts , David S. Garvey
IPC分类号： A61K31/4025 , A61P27/12 , A61P27/06
CPC分类号： A61K31/04 , A61K31/21 , A61K31/216 , A61K31/24 , C07D493/04 , C07K5/06026
摘要： The invention describes novel nitrosated and/or nitrosylated compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated 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 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 treating ophthalmic disorders. The nitrosated and/or nitrosylated compounds are preferably nitrosated and/or nitrosylated (3-adrenergic antagonists and nitrosated and/or nitrosylated angiotensin-converting enzyme (ACE) inhibitors.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化化合物或其药学上可接受的盐，以及包含至少一种亚硝基化和/或亚硝基化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本发明的化合物，其任选被亚硝化和/或亚硝基化的组合物和试剂盒，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。本发明还提供了治疗眼科疾病的方法。亚硝基化和/或亚硝基化化合物优选为亚硝化和/或亚硝基化（3-肾上腺素能拮抗剂和亚硝化和/或亚硝酰化的血管紧张素转化酶（ACE）抑制剂）。

43. 发明授权

US07166618B2 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：US07166618B2
公开(公告)日：2007-01-23
申请号：US10463671
申请日：2003-06-18
申请人： Ramani R. Bandarage , David S. Garvey , L. Gordon Letts , Joseph D. Schroeder , Sang William Tam
发明人： Ramani R. Bandarage , David S. Garvey , L. Gordon Letts , Joseph D. Schroeder , Sang William Tam
IPC分类号： C07D263/04 , A61K31/42 , C07D207/325
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, such as, steroids, nonsteroidal antiinflammatory 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, H2antagonists, antineoplastic agents, antiplatelet agents, 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 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，提高内源性内皮水平的内皮衍生的松弛因子，或是一氧化氮合酶的底物，和/或任选的至少一种治疗剂，例如类固醇，非甾体抗炎化合物（NSAID），5-脂氧合酶（5-LO）抑制剂，白细胞三烯B 4（LTB 4 N）受体拮抗剂，白细胞三烯A 4（LTA 5-HT激动剂，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）抑制剂，H 2 N 2拮抗剂，抗肿瘤剂，抗血小板剂，减充血剂，利尿剂，镇静剂或非镇静抗组胺，诱导型一氧化氮合酶避孕药，阿片样物质，镇痛药，幽门螺杆菌抑制剂，质子泵抑制剂，异前列烷烷抑制剂及其混合物。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。

44. 发明授权

US06869973B2 Nitrosated and nitrosylated taxanes, compositions and methods of use 失效
标题翻译：硝化和亚硝化紫杉烷，组合物和使用方法
公开(公告)号：US06869973B2
公开(公告)日：2005-03-22
申请号：US10682923
申请日：2003-10-14
申请人： David S. Garvey , L. Gordon Letts , Chia-En Lin , Stewart K. Richardson , Tiansheng Wang
发明人： David S. Garvey , L. Gordon Letts , Chia-En Lin , Stewart K. Richardson , Tiansheng Wang
IPC分类号： A61F2/84 , A61K31/145 , A61K31/15 , A61K31/335 , A61K31/337 , A61K35/14 , A61K45/00 , A61K45/06 , A61K47/30 , A61K47/32 , A61K47/34 , A61K47/48 , A61L29/00 , A61L31/00 , A61P1/04 , A61P7/02 , A61P7/04 , A61P7/10 , A61P9/00 , A61P9/10 , A61P9/12 , A61P9/14 , A61P11/00 , A61P11/02 , A61P13/12 , A61P17/00 , A61P17/02 , A61P25/28 , A61P27/02 , A61P27/16 , A61P29/00 , A61P31/06 , A61P35/00 , A61P35/02 , A61P37/02 , A61P41/00 , A61P43/00 , C07D305/14 , C07D409/12
CPC分类号： C07D409/12 , A61K31/335 , A61K45/06 , A61K47/54 , A61K47/55 , A61K47/555 , B82Y5/00 , C07D305/14 , Y10S977/775 , Y10S977/907 , Y10S977/915 , Y10S977/926 , A61K2300/00
摘要： The present invention describes novel nitrosated and/or nitrosylated taxanes, and novel compositions comprising at least one nitrosated and/or nitrosylated taxane, 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. The present invention also provides novel compositions comprising at least one taxane 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 compounds and compositions of the present invention can also be bound to a matrix. The present invention also provides methods for treating or preventing cardiovascular diseases and disorders, autoimmune diseases, pathological conditions resulting from abnormal cell proliferation, polycystic kidney disease, inflammatory disease, preserving organs and/or tissues or to inhibit wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis, by administering nitrosated and/or nitrosylated taxane or parent taxanes in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的紫杉烷类，以及包含至少一种亚硝化和/或亚硝基化的紫杉烷和任选的至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内源水平的内皮衍生舒张因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶和/或至少一种治疗剂的底物。本发明还提供了包含至少一种紫杉烷和至少一种捐赠，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者是一氧化氮合酶的底物和/或至少一种治疗剂。本发明的化合物和组合物也可以与基质结合。本发明还提供治疗或预防心血管疾病和病症，自身免疫性疾病，由异常细胞增殖引起的病理状况，多囊肾病，炎性疾病，保存器官和/或组织或抑制伤口收缩的方法，特别是预防和/ 或治疗性再狭窄，通过将硝基化和/或亚硝基化的紫杉烷或母体紫杉烷与能够释放一氧化氮或间接地将一氧化氮递送或转移到生理条件下的靶位点的一氧化氮供体组合。

45. 发明授权

US06552047B2 H2 receptor antagonist compounds in combination with nitric oxide donors, compositions and methods of use 失效
标题翻译： H2受体拮抗剂化合物与一氧化氮供体的组合物和使用方法
公开(公告)号：US06552047B2
公开(公告)日：2003-04-22
申请号：US09441891
申请日：1999-11-17
申请人： David S. Garvey , L. Gordon Letts , Tiansheng Wang
发明人： David S. Garvey , L. Gordon Letts , Tiansheng Wang
IPC分类号： A61K314164
CPC分类号： C07D233/54 , C07D233/64 , C07D277/48 , C07D295/092 , C07D295/096
摘要： The present invention describes novel nitrosated and/or nitrosylated H2 receptor antagonist compounds, and novel compositions comprising at least one H2 receptor antagonist compound that is optionally substituted with at least one NO and/or NO2 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. The present invention also describes methods for treating and/or preventing gastrointestinal disorders; improving gastroprotective properties of H2 receptor antagonists; decreasing the recurrence of ulcers; facilitating ulcer healing; preventing and/or treating inflammations and microbial infections, ophthalmic diseases and disorders, multiple sclerosis, and viral infections; and decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的H 2受体拮抗剂化合物，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H 2受体拮抗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，提高内源性内源性舒张因子水平，或是一氧化氮合酶的底物。本发明还描述了治疗和/或预防胃肠道疾病的方法; 改善H2受体拮抗剂的胃保护性能; 减少溃疡复发; 促进溃疡愈合; 预防和/或治疗炎症和微生物感染，眼科疾病和病症，多发性硬化和病毒感染; 并减少或减少与使用非甾体抗炎化合物相关的胃肠道毒性。

46. 发明授权

US06083515A Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs 失效
公开(公告)号：US06083515A
公开(公告)日：2000-07-04
申请号：US235801
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 , A61K9/08 , A61K31/41 , C07D249/16
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.

47. 发明授权

US5843441A Use of endothelial-leukocyte adhesion molecule-1 specific antibodies in the treatment of asthma 失效
标题翻译：使用内皮 - 白细胞粘附分子-1特异性抗体治疗哮喘
公开(公告)号：US5843441A
公开(公告)日：1998-12-01
申请号：US504257
申请日：1995-07-19
申请人： Robert H. Gundel , Craig D. Wegner , L. Gordon Letts , C. Wayne Smith
发明人： Robert H. Gundel , Craig D. Wegner , L. Gordon Letts , C. Wayne Smith
IPC分类号： A61K35/14 , A61K31/70 , A61K38/00 , A61K39/395 , A61P11/00 , A61P11/06 , C07K14/00 , C07K14/705 , C07K16/00 , C07K16/28 , C12N5/10 , C12N15/02 , C12N15/09 , C12P19/44 , C12P21/08
CPC分类号： A61K31/70 , C07K14/70564 , C07K16/2854 , C12P19/44 , A61K38/00
摘要： A method for treating asthma in a patient using an agent selected from the group consisting of: (a) an antibody capable of binding to ELAM-1; (b) a fragment of the antibody (a), the fragment being capable of binding to ELAM-1; (c) ELAM-1, being substantially free of natural contaminants; (d) a functional derivative of ELAM-1; (e) an antibody capable of binding to an ELAM-1 receptor; (f) a fragment of the antibody (e), the fragment being capable of binding to an ELAM-1 receptor; (g) an ELAM-1 receptor, being substantially free of natural contaminants; and . (h) a functional derivative of an ELAM-1 receptor.
摘要翻译：一种使用选自以下的试剂治疗患者哮喘的方法：（a）能结合ELAM-1的抗体; （b）抗体（a）的片段，该片段能够结合ELAM-1; （c）ELAM-1基本上不含天然污染物; （d）ELAM-1的功能衍生物; （e）能够结合ELAM-1受体的抗体; （f）抗体（e）的片段，所述片段能够结合ELAM-1受体; （g）基本上不含天然污染物的ELAM-1受体; 和。（h）ELAM-1受体的功能衍生物。

48. 发明申请

US20090306081A1 Solid Dosage Formulations of Hydralazine Compounds and Nitric Oxide Donor Compounds 审中-公开
标题翻译：肼哒嗪化合物和一氧化氮供体化合物的固体剂型
公开(公告)号：US20090306081A1
公开(公告)日：2009-12-10
申请号：US12300593
申请日：2007-05-16
申请人： L. Gordon Letts
发明人： L. Gordon Letts
IPC分类号： A61K31/50 , A61P9/08
CPC分类号： A61K9/2054 , A61K9/2059 , A61K31/34 , A61K31/502 , A61K45/06 , Y02A50/411 , A61K2300/00
摘要： The invention provides solid dosage formulations, methods of making and using the formulations comprising at least one hydralazine compound or a pharmaceutically acceptable salt thereof, and at least one excipient or carrier, wherein the formulations have less than about 0.001% to about 0.1% of a hydrazone compound based on the total weight of the formulation. The invention also provides solid dosage formulations, methods of making and using the formulations comprising at least one hydralazine compound or a pharmaceutically acceptable salt thereof, and at least one nitric oxide donor compound or a pharmaceutically acceptable salt thereof and at least one excipient or carrier, wherein the formulations have less than about 0.001% to about 0.1% of a hydrazone compound based on the total weight of the formulation.
摘要翻译：本发明提供了固体剂型，制备和使用包含至少一种肼azine嗪化合物或其药学上可接受的盐以及至少一种赋形剂或载体的制剂的方法，其中所述制剂具有小于约0.001％至约0.1％的腙化合物，基于制剂的总重量。本发明还提供固体剂型，制备和使用包含至少一种肼屈嗪化合物或其药学上可接受的盐的制剂的方法，以及至少一种一氧化氮供体化合物或其药学上可接受的盐和至少一种赋形剂或载体，其中所述制剂基于制剂的总重量具有小于约0.001％至约0.1％的腙化合物。

49. 发明申请

US20090054381A1 METHODS FOR TREATING RESPIRATORY DISORDERS 审中-公开
标题翻译：治疗呼吸道疾病的方法
公开(公告)号：US20090054381A1
公开(公告)日：2009-02-26
申请号：US12088922
申请日：2006-10-04
申请人： L. Gordon Letts
发明人： L. Gordon Letts
IPC分类号： A61K31/50 , A61K31/56 , A61P9/00 , A61P11/00
CPC分类号： A61K45/06 , A61K31/34 , A61K31/345 , A61K31/502 , A61K2300/00
摘要： The invention provides methods for treating respiratory disorders in a patient in need thereof comprising administering an effective amount of (i) at least one hydralazine compound or a pharmaceutically acceptable salt thereof, (ii) isosorbide dinitrate and/or isosorbide mononitrate, and (iii) optionally at least one therapeutic agent. The hydralazine compound may be hydralazine hydrochloride. The respiratory disorders may be chronic obstructive pulmonary disease, pulmonary hypertension, emphysema, asthma, cystic fibrosis and bronchitis.
摘要翻译：本发明提供了治疗有需要的患者呼吸系统疾病的方法，包括给予有效量的（i）至少一种肼屈嗪化合物或其药学上可接受的盐，（ii）硝酸异山梨酯和/或硝酸异山梨酯，和（iii）任选地至少一种治疗剂。肼屈嗪化合物可以是盐酸肼屈嗪。呼吸系统疾病可能是慢性阻塞性肺疾病，肺动脉高压，肺气肿，哮喘，囊性纤维化和支气管炎。

50. 发明授权

US5310551A Method for inhibiting pulmonary oxygen toxicity 失效
标题翻译：抑制肺氧毒性的方法
公开(公告)号：US5310551A
公开(公告)日：1994-05-10
申请号：US15744
申请日：1993-02-10
申请人： Craig D. Wegner , L. Gordon Letts
发明人： Craig D. Wegner , L. Gordon Letts
IPC分类号： A61K38/00 , A61K38/17 , A61K39/395 , A61P7/00 , A61P11/00 , A61P43/00 , C07K16/28 , A61K39/00 , C07K15/28
CPC分类号： C07K16/2821 , A61K38/1774 , A61K38/1777
摘要： A method for inhibiting pulmonary oxygen toxicity in a patient requiring elevated levels of inhaled oxygen, by prophylactic administration of certain adhesion molecules and antibodies thereto.
摘要翻译：一种通过预防性施用某些粘附分子及其抗体来抑制需要高水平吸入氧的患者的肺氧中毒的方法。

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