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    Methods Using Hydralazine Compounds and Isosorbide Dinitrate or Isosorbide Mononitrate
    3.
    发明申请
    Methods Using Hydralazine Compounds and Isosorbide Dinitrate or Isosorbide Mononitrate 审中-公开
    方法使用肼屈嗪化合物和硝酸异山梨酯或一硝酸异山梨酯

    公开(公告)号：US20080293724A1

    公开(公告)日：2008-11-27

    申请号：US12096875

    申请日：2007-02-12

    申请人： Michael D. Loberg

    发明人： Michael D. Loberg

    IPC分类号： A61K31/502 ,  A61P9/04

    CPC分类号： A61K45/06 ,  A61K31/15 ,  A61K31/34 ,  A61K31/50 ,  A61K31/502 ,  A61K31/5025 ,  A61K2300/00

    摘要： The invention provides methods for (a) treating decompensated heart failure; (b) treating compensated heart failure; (c) treating renovascular diseases and (d) treating end-stage renal diseases 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 compound selected from the group consisting of an angiotensin converting enzyme inhibitor, a β-adrenergic antagonist, an angiotensin II antagonist, an aldosterone antagonist, a cardiac glycoside (digitalis) and a diuretic compound or a combination of two or more thereof. The hydralazine compound may be hydralazine hydrochloride.

    摘要翻译： 本发明提供（a）治疗失代偿性心力衰竭的方法; （b）治疗补偿性心力衰竭; （c）治疗肾血管疾病和（d）在有需要的患者中治疗终末期肾病，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/ 或单硝酸异山梨酯，和（iii）任选的至少一种选自血管紧张素转换酶抑制剂，β-肾上腺素能拮抗剂，血管紧张素II拮抗剂，醛固酮拮抗剂，强心苷（洋地黄）和利尿剂 或其两个或多个的组合。 肼屈嗪化合物可以是盐酸肼屈嗪。

    NITRIC OXIDE DONATING DIURETIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    4.
    发明申请
    NITRIC OXIDE DONATING DIURETIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE 失效
    硝酸氧化物滴定化合物，组合物和使用方法

    公开(公告)号：US20080255101A1

    公开(公告)日：2008-10-16

    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： A61K31/549 ,  A61P9/00 ,  A61P13/00 ,  C07D285/24 ,  C07D417/04 ,  C07D513/10

    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。

    Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders
    5.
    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。

    NITROSATED PROTON PUMP INHIBITORS, COMPOSITIONS AND METHODS OF USE
    7.
    发明申请
    NITROSATED PROTON PUMP INHIBITORS, COMPOSITIONS AND METHODS OF USE 审中-公开
    硝基脲泵抑制剂，组合物和使用方法

    公开(公告)号：US20070179150A1

    公开(公告)日：2007-08-02

    申请号：US11689568

    申请日：2007-03-22

    申请人： Xinqin Fang ,  David Garvey ,  L. Letts

    发明人： Xinqin Fang ,  David Garvey ,  L. Letts

    IPC分类号： A61K31/496 ,  A61K31/4745 ,  A61K31/4709 ,  C07D471/02 ,  C07D401/02 ,  C07D403/02

    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。

    Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use
    8.
    发明申请
    Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use 审中-公开
    一氧化氮增强型血管紧张素II拮抗剂化合物，组合物和使用方法

    公开(公告)号：US20070032533A1

    公开(公告)日：2007-02-08

    申请号：US11499770

    申请日：2006-08-07

    申请人： David Garvey ,  Xiong Cai ,  Xinqin Fang ,  Ramani Ranatunge ,  Shiow-Jyi Wey ,  Hai-Xiao Zhai

    发明人： David Garvey ,  Xiong Cai ,  Xinqin Fang ,  Ramani Ranatunge ,  Shiow-Jyi Wey ,  Hai-Xiao Zhai

    IPC分类号： A61K31/433 ,  A61K31/4245 ,  A61K31/42

    CPC分类号： C07D257/04 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D471/04

    摘要： The invention describes compositions and kits comprising at least one nitric oxide enhancing angiotensin II antagonist compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing angiotensin II antagonist compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension (o) treating central nervous system disorders; (p) treating metabolic syndrome; and (q) treating hyperlipidemia. The nitric oxide enhancing angiotensin II antagonist compounds comprise at least one nitric oxide enhancing group linked to the angiotensin II antagonist 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型血管紧张素II拮抗剂化合物或其药学上可接受的盐的组合物和试剂盒，以及包含至少一种一氧化氮增强型血管紧张素II拮抗剂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。 本发明还提供了（a）治疗心血管疾病的方法; （b）治疗血管性疾病; （c）治疗糖尿病; （d）治疗由氧化应激引起的疾病; （e）治疗内皮功能障碍; （f）治疗由内皮功能障碍引起的疾病; （g）治疗肝硬化; （h）治疗先兆子痫; （j）治疗骨质疏松症; （k）治疗肾病; （l）治疗外周血管疾病; （m）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; 和（q）治疗高脂血症。 一氧化氮增强型血管紧张素II拮抗剂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血管紧张素II拮抗剂化合物连接的至少一个一氧化氮增强基团。

    Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use
    9.
    发明授权
    Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use 失效
    亚硝化和亚硝基化H 2受体拮抗剂化合物，组合物和使用方法

    公开(公告)号：US07129251B2

    公开(公告)日：2006-10-31

    申请号：US11180790

    申请日：2005-07-14

    申请人： David S. Garvey ,  L. Gordon Letts ,  Chia-En Lin ,  Tiansheng Wang

    发明人： David S. Garvey ,  L. Gordon Letts ,  Chia-En Lin ,  Tiansheng Wang

    IPC分类号： C07D295/14 ,  A61K31/445 ,  A61P1/04

    CPC分类号： C07D233/54 ,  C07D233/64 ,  C07D277/48 ,  C07D295/092 ,  C07D295/096

    摘要： The 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 and/or at least one nonsteroidal antiinflammatory drug, antacid, bismuth-containing reagent or anti-viral agent. The 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 O 2受体拮抗剂化合物，以及包含至少一种H 2受体拮抗剂化合物的新组合物，其任选被至少一个NO 和/或NO 2个基团，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，提高内源性内皮水平的内源性松弛因子，或者是 一氧化氮合酶的底物和/或至少一种非甾体抗炎药，抗酸剂，含铋试剂或抗病毒剂。 本发明还描述了治疗和/或预防胃肠道疾病的方法; 改善H 2受体拮抗剂的胃保护性质; 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。

    Compositions and methods related to heart failure
    10.
    发明申请
    Compositions and methods related to heart failure 审中-公开

    公开(公告)号：US20060014828A1

    公开(公告)日：2006-01-19

    申请号：US11182886

    申请日：2005-07-18

    申请人： Manuel Worcel ,  Michael Sabolinski

    发明人： Manuel Worcel ,  Michael Sabolinski

    IPC分类号： A61K31/34 ,  A61K31/15

    CPC分类号： A61K31/15 ,  A61K31/34 ,  A61K31/502 ,  A61K45/06 ,  A61K2300/00

    摘要： The invention provides methods for (a) prolonging time to hospitalization for heart failure; (b) prolonging time to first hospitalization for heart failure; (c) reducing the total number of days a patient with heart failure spends in the hospital for heart failure for a single hospital stay (i.e., reducing the duration of a single hospital stay for a patient with heart failure); (d) reducing the total number of days a patient spends in the hospital for heart failure for multiple hospital stays (i.e., two or more hospital stays); (e) reducing the number of hospital admissions for heart failure; (f) reducing mortality and reducing hospitalizations for heart failure (e.g., the total number of days in the hospital and/or the number of hospital visits); (g) increasing the left ventricular ejection fraction in a heart failure patient; (h) treating a sexual dysfunction (e.g., erectile dysfunction and female sexual dysfunction) (j) treating a headache in a heart failure patient by administering a non-steroidal antiinflammatory compound (i.e., NSAIDs); (k) treating a heart failure patient who has a history of hypertension (but who is not currently diagnosed with hypertension); (l) improving the quality of life in a heart failure patient based on the Minnesota Living with heart failure questionnaire; (m) decreasing the levels of B-type natriuretic peptide; (n) treating hypertension in a heart failure patient; (o) lowering blood pressure in a heart failure patient; (p) treating labile hypertension; (q) treating idiopathic hypertension; (r) increasing patient compliance with medication dosing in a heart failure patient; (s) treating hypertension in a patient with a dilated heart; (t) treating ischemic disease and/or coronary artery disease; and (u) reducing cardiomegaly in a patient in need thereof comprising administering to the patient a therapeutically effective amount of (i) a hydralazine compound or pharmaceutically acceptable salt thereof, (ii) isosorbide dinitrate and/or isosorbide mononitrate, and (iii) optionally at least one compound selected from the group consisting of angiotensin converting enzyme inhibitors, β-adrenergic antagonists, angiotensin II antagonists, aldosterone antagonists, cardiac glucosides (digitalis), and diuretic compounds.