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1. 发明授权

US07282519B2 Nitrosated and nitrosylated diuretic compounds, compositions and methods of use 失效
标题翻译：硝化和亚硝化利尿剂，组合物和使用方法
公开(公告)号：US07282519B2
公开(公告)日：2007-10-16
申请号：US10921936
申请日：2004-08-20
申请人： David S. Garvey , L. Gordon Letts , Manuel Worcel , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson
发明人： David S. Garvey , L. Gordon Letts , Manuel Worcel , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson
IPC分类号： A61K31/34 , A61K31/44 , A61K31/497 , C07D307/52
CPC分类号： C07D403/10 , C07C205/40 , C07D233/68 , C07D235/18 , C07D257/04 , C07D307/52 , C07D401/12 , C07D401/14 , C07D405/06 , C07D405/12 , C07D405/14 , C07D409/04 , C07D409/06 , C07D409/14 , C07D413/10 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04
摘要： The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic 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 diuretic 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 (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; and (l) treating nephropathy.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的利尿剂或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝基化的利尿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。本发明还提供了包含至少一种本发明的利尿剂化合物，其任选被亚硝化和/或亚硝基化的新组合物和试剂盒，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（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; 和（l）治疗肾病。

2. 发明申请

US20050059655A1 Nitrosated and nitrosylated diuretic compounds, compositions and methods of use 失效
标题翻译：硝化和亚硝化利尿剂，组合物和使用方法
公开(公告)号：US20050059655A1
公开(公告)日：2005-03-17
申请号：US10921936
申请日：2004-08-20
申请人： David Garvey , L. Letts , Manuel Worcel , Richard Earl , Maiko Ezawa , Xinqin Fang , Subhash Khanapure , Chia-En Lin , Ramani Ranatunga , Cheri Stevenson
发明人： David Garvey , L. Letts , Manuel Worcel , Richard Earl , Maiko Ezawa , Xinqin Fang , Subhash Khanapure , Chia-En Lin , Ramani Ranatunga , Cheri Stevenson
IPC分类号： A61K20060101 , A61K31/4523 , A61K31/517 , A61K31/5415 , A61K31/549 , C07D211/00 , C07D285/22 , C07D295/00 , C07D307/00 , C07D417/12 , C07D417/14
CPC分类号： C07D403/10 , C07C205/40 , C07D233/68 , C07D235/18 , C07D257/04 , C07D307/52 , C07D401/12 , C07D401/14 , C07D405/06 , C07D405/12 , C07D405/14 , C07D409/04 , C07D409/06 , C07D409/14 , C07D413/10 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04
摘要： The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic 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 diuretic 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 (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; and (l) treating nephropathy.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的利尿剂或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝基化的利尿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。本发明还提供了包含至少一种本发明的利尿剂化合物，其任选被亚硝化和/或亚硝基化的新组合物和试剂盒，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（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; 和（l）治疗肾病。

3. 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

4. 发明授权

US07176238B1 Nitrostated and nitrosylated prostaglandins, compositions and methods of use 失效
标题翻译：硝基化和亚硝酰化前列腺素，组合物和使用方法
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。

5. 发明授权

US07772278B2 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：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

6. 发明申请

US20090088366A1 NITROSATED AND NITROSYLATED PROSTAGLANDINS, COMPOSITIONS AND METHODS OF USE 失效
标题翻译：硝基和硝基化前体，组合物和使用方法
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

7. 发明授权

US07235237B2 Methods of treating vascular diseases characterized by nitric oxide insufficiency 失效
标题翻译：治疗以一氧化氮不足为特征的血管疾病的方法
公开(公告)号：US07235237B2
公开(公告)日：2007-06-26
申请号：US10415136
申请日：2001-05-02
申请人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
IPC分类号： A61K38/43 , A61K31/215 , A01N37/12 , A01N33/18
CPC分类号： A61K45/06 , A61K31/12 , A61K31/198 , A61K31/355 , A61K31/375 , A61K31/502 , A61K38/44 , A61K38/446 , A61K2300/00
摘要： The present invention provides methods of treating or preventing vascular diseases caused by nitric oxide (NO) insufficiency. The methods encompass administering a composition comprising an antioxidant, a compound to treat cardiovascular diseases, a nitrosated compound, a compound that donates, transfers or relases NO, or is a NO synthase substrate, or endogenously stimulates NO synthesis, or stimulates levels of endothelium derived relaxing factor. In the said composition, a hydralazine compound may be an antioxidant, isosorbide mono-or dinitrate may be the compound to donate, transfer, release, or stimulate endogenous NO synthesis. The isorsorbide may also elevate endogenous levels of endotherlium-derived relaxing factor, or be a NO synthase substrate and angiotensin enzyme inhibitor may be nitrosated compound. Disclosed in the invention is also a method to treat, or prevent Renaud's syndrome by administering a therapeutically effective amount of an antioxidant, a NO donor, a nitrosated compound and novel sustained-release formulations (e.g. a transdermal patch).
摘要翻译：本发明提供治疗或预防由一氧化氮（NO）不足引起的血管疾病的方法。所述方法包括施用包含抗氧化剂，治疗心血管疾病的化合物，亚硝化化合物，提供，转移或者中和NO的化合物或NO合成酶底物或内源性刺激NO合成或刺激内皮衍生物的水平的组合物放松因子。在所述组合物中，肼屈嗪化合物可以是抗氧化剂，异山梨醇单或二硝酸酯可以是捐赠，转移，释放或刺激内源性NO合成的化合物。异山梨醇也可以提高内源性内源性释放因子水平，或者是NO合成酶底物，血管紧张素酶抑制剂可以是亚硝化化合物。在本发明中公开的方法也是通过施用治疗有效量的抗氧化剂，NO供体，亚硝化化合物和新的缓释制剂（例如透皮贴剂）来治疗或预防Renaud综合征的方法。

8. 发明申请

US20090192128A1 GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF BETA 1 ADRENERGIC RECEPTOR GLY389ARG POLYMORPHISM 审中-公开
标题翻译：心脏衰竭的遗传风险评估：BETA 1 ADRENERGIC RECEPTOR GLY389ARG POLYMORPHISM的遗传变异的影响
公开(公告)号：US20090192128A1
公开(公告)日：2009-07-30
申请号：US12088923
申请日：2006-10-04
申请人： Manuel Worcel , Michael L. Sabolinski , Sang W. Tam , Dennis M. McNamara
发明人： Manuel Worcel , Michael L. Sabolinski , Sang W. Tam , Dennis M. McNamara
IPC分类号： A61K31/56 , A61K31/34 , A61K31/40 , A61K31/403 , A61K31/137 , A61K31/352
CPC分类号： C12Q1/6883 , A61K31/34 , A61K31/502 , A61K45/06 , C12Q2600/106 , C12Q2600/156 , A61K2300/00
摘要： The invention provides methods for (a) reducing mortality associated with heart failure; (b) improving oxygen consumption; (c) treating heart failure; (d) treating hypertension; (e) improving the quality of life in a heart failure patient; (f) inhibiting left ventricular remodeling; (g) reducing hospitalizations related to heart failure; (h) improving exercise tolerance; (j) increasing left ventricular ejection fraction; (k) decreasing levels of B-type natriuretic protein; (l) treating renovascular diseases; (m) treating end-stage renal diseases; (n) reducing cardiomegaly; (o) treating diseases resulting from oxidative stress; (p) treating endothelial dysfunctions; (q) treating diseases caused by endothelial dysfunctions; or (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has a Arg389Arg polymorphism and/or a Gly389Gly polymorphism in the beta 1 adrenergic receptor gene, comprising administering to the patient (i) at least one antioxidant compound or a pharmaceutically acceptable salt thereof; (ii) at least one nitric oxide enhancing compound; and (iii) optionally the best current therapy for the treatment of cardiovascular diseases. In one embodiment the antioxidant is a hydralazine compound or a pharmaceutically acceptable salt thereof and the nitric oxide enhancing compound is isosorbide dinitrate and/or isosorbide mononitrate.
摘要翻译：本发明提供了（a）降低与心力衰竭相关的死亡率的方法; （b）提高耗氧量; （c）治疗心力衰竭; （d）治疗高血压; （e）改善心力衰竭患者的生活质量; （f）抑制左心室重构; （g）减少与心力衰竭有关的住院; （h）提高运动耐力; （j）增加左心室射血分数; （k）B型利尿钠蛋白水平降低; （l）治疗血管性疾病; （m）治疗终末期肾病; （n）减轻心脏肥大; （o）治疗由氧化应激引起的疾病; （p）治疗内皮功能障碍; （q）治疗由内皮功能障碍引起的疾病; 或（r）治疗心血管疾病; 在患有需要的患者中，其中所述患者在β1肾上腺素能受体基因中具有Arg389Arg多态性和/或Gly389Gly多态性，其包括给予所述患者（i）至少一种抗氧化剂化合物或其药学上可接受的盐; （ii）至少一种一氧化氮增强化合物; 和（iii）任选的治疗心血管疾病的最佳治疗方法。在一个实施方案中，抗氧化剂是肼azine嗪化合物或其药学上可接受的盐，一氧化氮增强化合物是硝酸异山梨酯和/或硝酸异山梨酯。

9. 发明申请

US20090075956A1 Genetic Risk Assessment in Heart Failure: Impact of the Genetic Variation of NOS3 审中-公开
标题翻译：心力衰竭遗传风险评估：NOS3基因变异的影响
公开(公告)号：US20090075956A1
公开(公告)日：2009-03-19
申请号：US11887968
申请日：2006-04-07
申请人： Manuel Worcel , Michael L. Sabolinski , Sang William Tam , Dennis M. McNamara
发明人： Manuel Worcel , Michael L. Sabolinski , Sang William Tam , Dennis M. McNamara
IPC分类号： A61K31/58 , A61K31/34 , A61K31/502 , A61P9/00 , A61P17/00 , A61K31/40 , A61K31/403
CPC分类号： A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： The invention provides methods for (a) reducing mortality associated with heart failure; (b) improving oxygen consumption; (c) treating heart failure; (d) treating hypertension; (e) improving the quality of life in a heart failure patient; (f) inhibiting left ventricular remodeling; (g) reducing hospitalizations related to heart failure; (h) improving exercise tolerance; (j) increasing left ventricular ejection fraction; (k) decreasing levels of B-type natriuretic protein; (l) treating renovascular diseases; (m) treating end-stage renal diseases; (n) reducing cardiomegaly; (o) treating diseases resulting from oxidative stress; (p) treating endothelial dysfunctions; (q) treating diseases caused by endothelial dysfunctions; (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has at least one polymorphism in the endothelial nitric oxide synthase (NOS3) gene, comprising administering to the patient (i) at least one antioxidant compound or a pharmaceutically acceptable salt thereof; (ii) at least one nitric oxide enhancing compound; and (iii) optionally the best current therapy for the treatment of cardiovascular diseases. In one embodiment the antioxidant is a hydralazine compound or a pharmaceutically acceptable salt thereof and the nitric oxide enhancing compound is isosorbide dinitrate and/or isosorbide mononitrate.
摘要翻译：本发明提供了（a）降低与心力衰竭相关的死亡率的方法; （b）提高耗氧量; （c）治疗心力衰竭; （d）治疗高血压; （e）改善心力衰竭患者的生活质量; （f）抑制左心室重构; （g）减少与心力衰竭有关的住院; （h）提高运动耐力; （j）增加左心室射血分数; （k）B型利尿钠蛋白水平降低; （l）治疗血管性疾病; （m）治疗终末期肾病; （n）减轻心脏肥大; （o）治疗由氧化应激引起的疾病; （p）治疗内皮功能障碍; （q）治疗由内皮功能障碍引起的疾病; （r）治疗心血管疾病; 在患有需要的患者中，其中所述患者在所述内皮一氧化氮合酶（NOS3）基因中具有至少一种多态性，其包括给予所述患者（i）至少一种抗氧化剂化合物或其药学上可接受的盐; （ii）至少一种一氧化氮增强化合物; 和（iii）任选的治疗心血管疾病的最佳治疗方法。在一个实施方案中，抗氧化剂是肼azine嗪化合物或其药学上可接受的盐，一氧化氮增强化合物是硝酸异山梨酯和/或硝酸异山梨酯。

10. 发明申请

US20060014829A1 Methods for reducing hospitalizations related to heart failure 审中-公开
标题翻译：减少心力衰竭住院的方法
公开(公告)号：US20060014829A1
公开(公告)日：2006-01-19
申请号：US11182887
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; (e) reducing the number of hospital admissions for heart failure; and (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) 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.
摘要翻译：本发明提供了（a）延长心力衰竭住院时间的方法; （b）延长首次住院心脏衰竭的时间; （c）减少患有心力衰竭的患者在医院心脏衰竭的总天数，用于单次住院（即减少患有心力衰竭的患者的单次住院时间）; （d）减少患者在医院内多次住院心衰的总天数; （e）减少住院心脏病的人数; 和（f）在有需要的患者中降低死亡率并减少心力衰竭的住院时间（例如，医院的总天数和/或住院次数），包括向患者施用治疗有效量的（i ）二氢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，心脏葡萄糖苷（洋地黄）和利尿剂。

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