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    Oxime and/or hydrozone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use
    3.
    发明授权
    Oxime and/or hydrozone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use 失效
    含有亚硝基化和/或亚硝基化的环氧合酶-2选择性抑制剂的肟和/或水合物，组合物和使用方法

    公开(公告)号：US07211598B2

    公开(公告)日：2007-05-01

    申请号：US10608333

    申请日：2003-06-30

    申请人： David S. Garvey ,  Ramani R. Ranatunge ,  Stewart K. Richardson

    发明人： David S. Garvey ,  Ramani R. Ranatunge ,  Stewart K. Richardson

    IPC分类号： A61K31/415 ,  C07D231/04

    CPC分类号： C07D231/12

    摘要： The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor having at least one oxime group or hydrazone 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 therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor having at least one oxime group or hydrazone group, 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 having at least one oxime group or hydrazone group 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： 本发明描述了具有至少一个肟基或腙基团的新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种具有至少一个肟基或腙基团的至少一种环加氧酶2（COX-2）选择性抑制剂的新组合物， 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，提高内源性内皮衍生的松弛因子水平，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具有至少一个肟基或腙基团，任选亚硝基化和/或亚硝基化的COX-2选择性抑制剂和任选地至少一种一氧化氮供体，和/或任选地在 至少一种治疗剂。 具有至少一个肟基或腙基团的本发明的新型环加氧酶2选择性抑制剂可任选被亚硝化和/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。

    Nitrosated and nitrosylated compounds, and compositions and their use for treating respiratory disorders
    5.
    再颁专利
    Nitrosated and nitrosylated compounds, and compositions and their use for treating respiratory disorders 有权
    亚硝化和亚硝化化合物，以及组合物及其用于治疗呼吸系统疾病的用途

    公开(公告)号：USRE37116E1

    公开(公告)日：2001-03-27

    申请号：US09219476

    申请日：1998-12-23

    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： A61K3158

    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&Circlesolid;) 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＆circlef））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。

    Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use
    6.
    发明授权
    Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
    硝化非甾体抗炎化合物，组合物和使用方法

    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。

    Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders
    9.
    发明授权
    Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders 失效
    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：US07345037B2

    公开(公告)日：2008-03-18

    申请号：US11604677

    申请日：2006-11-28

    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： A61K31/40 ,  C07D451/00

    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 β-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, β-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基团或基团上的基团的类固醇，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 其在体内刺激NO或EDRF的内源性产生; （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个部分取代，或刺激内源性产生NO 或EDRF，以及作为带电物质，即亚硝酸盐（硝酸）或硝酰基（NO +）的一氧化氮，或NOX + 作为中性物种，一氧化氮（NO））或者在体内刺激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。

    Infrared thermography and methods of use
    10.
    发明授权
    Infrared thermography and methods of use 失效
    红外热像仪及其使用方法

    公开(公告)号：US06762202B2

    公开(公告)日：2004-07-13

    申请号：US09850081

    申请日：2001-05-08

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

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

    IPC分类号： A01N4740

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

    摘要： The present invention describes rapid noninvasive methods for measuring vasodilation or changes in blood flow in a patient following administration of 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 method comprises the administration of 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 to the patient followed by monitoring the temperature change of an area of interest using infrared thermography. The present invention provides methods for diagnosing diseases or disorders related to vasodilation and changes in blood flow, such as, sexual dysfunction, Raynaud's syndrome, inflammation, hypertension, gastrointestinal disorders and central nervous system disorders. The sexual dysfunction is preferably female sexual dysfunction and female sexual arousal. The vasoactive agents include potassium channel activators, calcium channel blockers, &agr;-adrenergic receptor antagonists, &bgr;-blockers, phosphodiesterase inhibitors, adenosine, ergot alkaloids, vasoactive intestinal peptides, prostaglandins, dopamine agonists, opioid antagonists, endothelin antagonists and thromboxane inhibitors. The present invention can also be used to screen and identify drug candidates for treating diseases, disorders and conditions resulting from vasodilation or changes in blood flow. The present invention also describes compositions comprising at least one S-nitrosothiol compound for diagnosing, monitoring and/or treating female sexual dysfunctions.

    摘要翻译： 本发明描述了在给予至少一种捐赠，转移或释放一氧化氮的化合物，升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之后测量患者血管舒张或血流变化的快速非侵入性方法 或者是用于一氧化氮合酶和/或至少一种血管活性剂的底物。 该方法包括施用至少一种捐赠，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和/或至少一种血管活性物质的底物 然后使用红外热像仪监测感兴趣区域的温度变化。 本发明提供了用于诊断与血管舒张和血流变化有关的疾病或病症的方法，例如性功能障碍，雷诺综合征，炎症，高血压，胃肠道疾病和中枢神经系统疾病。 性功能障碍最好是女性性功能障碍和女性性唤起。 血管活性剂包括钾通道激活剂，钙通道阻滞剂，α-肾上腺素能受体拮抗剂，β-阻断剂，磷酸二酯酶抑制剂，腺苷，麦角生物碱，血管活性肠肽，前列腺素，多巴胺激动剂，阿片样物质拮抗剂，内皮素拮抗剂和血栓烷抑制剂。 本发明还可用于筛选和鉴定用于治疗由血管舒张或血流变化引起的疾病，病症和病症的候选药物。 本发明还描述了包含至少一种S-亚硝基硫醇化合物用于诊断，监测和/或治疗女性性功能障碍的组合物。