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    • 1. 发明申请
    • THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF BETA 1 ADRENERGIC RECEPTOR GLY389ARG POLYMORPHISM
    • 心力衰竭的遗传风险评估:β1肾上腺素能受体GLY389ARG多态性遗传变异的影响
    • WO2007041680A2
    • 2007-04-12
    • PCT/US2006038964
    • 2006-10-04
    • NITROMED INCUNIV PITTSBURGHWORCEL MANUELSABOLINSKI MICHAEL LTAM SANG WILLIAMMCNAMARA DENNIS M
    • WORCEL MANUELSABOLINSKI MICHAEL LTAM SANG WILLIAMMCNAMARA DENNIS M
    • C12Q1/68
    • C12Q1/6883A61K31/34A61K31/502A61K45/06C12Q2600/106C12Q2600/156A61K2300/00
    • 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; (1) 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, compiising 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.
    • 本发明提供了用于(a)降低与心力衰竭相关的死亡率的方法; (b)改善耗氧量; (c)治疗心力衰竭; (d)治疗高血压; (e)提高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治疗; (h)提高运动耐力; (j)增加左心室射血分数; (k)B型利钠肽蛋白水平降低; (1)治疗肾血管性疾病; (m)治疗终末期肾脏疾病; (n)减少心脏肿大; (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; 其中所述患者在所述β1肾上腺素能受体基因中具有Arg389Arg多态性和/或Gly389Gly多态性,包括向所述患者施用(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)任选地用于治疗心血管疾病的最佳当前疗法。 在一个实施方案中,所述抗氧化剂是肼屈嗪化合物或其药学上可接受的盐,并且所述一氧化氮增强化合物是二硝酸异山梨酯和/或单硝酸异山梨酯。
    • 2. 发明申请
    • THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF ALDOSTERONE SYNTHASE PROMOTER POLYMORPHISM
    • 心脏遗传危险评估:ALDOSTERONE SYNTHASE PROMOTER POLYMORPHISM遗传变异的影响
    • WO2007041676A2
    • 2007-04-12
    • PCT/US2006038956
    • 2006-10-04
    • NITROMED INCUNIV PITTSBURGHWORCEL MANUELSABOLINSKI MICHAEL LTAM SANG WILLIAMMCNAMARA DENNIS M
    • WORCEL MANUELSABOLINSKI MICHAEL LTAM SANG WILLIAMMCNAMARA DENNIS M
    • C12Q1/68
    • C12Q1/6883C12Q2600/106C12Q2600/118C12Q2600/156C12Q2600/172
    • 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; (Ic) decreasing levels of B-type natriuretic protein; (1) 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 -344 (T/T) polymorphism or a -344 (C/C) polymorphism in an aldosterone synthase CYPl1B2 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.
    • 本发明提供了(a)降低与心力衰竭相关的死亡率的方法; (b)改善耗氧量; (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)减少与心力衰竭相关的住院; (h)提高运动耐力; (j)增加左室射血分数; (Ic)降低B型利尿钠蛋白水平; (1)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; 在有需要的患者中,其中所述患者在醛固酮合酶CYP1B2基因中具有-344(T / T)多态性或-344(C / C)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,抗氧化剂是肼屈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/或单硝酸异山梨酯。
    • 4. 发明申请
    • METHODS FOR TREATING BLOOD DISORDERS WITH NITRIC OXIDE DONOR COMPOUNDS
    • 用硝酸氧化钴化合物治疗血液病症的方法
    • WO2005107384A3
    • 2006-12-07
    • PCT/US2005010935
    • 2005-03-31
    • NITROMED INCWORCEL MANUEL
    • WORCEL MANUEL
    • A01N33/26
    • A61K31/198A61K31/21A61K31/34A61K31/502A61K45/06A61K2300/00
    • The invention describes methods for treating blood disorders or for treating the symptoms and/or complications associated with blood disorders by administering a therapeutically effective amount of at least one nitric oxide donor compound and optionally at least one antioxidant, or a pharmaceutically acceptable salt thereof, and/or at least one therapeutic agent. The antioxidant is preferably a hydralazine compound or a pharmaceutically acceptable salt thereof. The nitric oxide donor compound is preferably N-hydroxy-L-arginine and/or isosorbide dinitrate and/or isosorbide mononitrate. The blood disorder is preferably sickle cell anemia. The complication resulting from a blood disorder is preferably pulmonary hypertension.
    • 本发明描述了通过施用治疗有效量的至少一种一氧化氮供体化合物和任选的至少一种抗氧化剂或其药学上可接受的盐来治疗血液病症或用于治疗与血液病症有关的症状和/或并发症的方法,以及 /或至少一种治疗剂。 抗氧化剂优选为肼azine嗪化合物或其药学上可接受的盐。 一氧化氮供体化合物优选为N-羟基-L-精氨酸和/或硝酸异山梨酯和/或一硝酸异山梨酯。 血液病最好是镰状细胞性贫血。 由血液病引起的并发症优选为肺动脉高压。
    • 7. 发明申请
    • THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF THE GENETIC VARIATION OF NOS3
    • 心脏遗传危险评估:NOS3遗传变异的影响
    • WO2006110601A2
    • 2006-10-19
    • PCT/US2006013185
    • 2006-04-07
    • NITROMED INCUNIV PITTSBURGHWORCEL MANUELSABOLINSKI MICHAELTAM SANG WMCNAMARA DENNIS M
    • WORCEL MANUELSABOLINSKI MICHAELTAM SANG WMCNAMARA DENNIS M
    • A61K31/21C12Q1/68
    • A61K31/34A61K31/502A61K45/06A61K2300/00
    • 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; (1) 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.
    • 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; (1)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,抗氧化剂是肼屈嗪化合物或其药学上可接受的盐,并且一氧化氮增强化合物是硝酸异山梨酯和/或一硝酸异山梨酯。
    • 9. 发明申请
    • NITROSATED AND NITROSYLATED CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 硝酸和硝基化血管化合物,组合物和使用方法
    • WO2005023182A3
    • 2006-10-19
    • PCT/US2004026910
    • 2004-08-20
    • NITROMED INCGARVEY DAVID SLETTS GORDON LWORCEL MANUEL
    • GARVEY DAVID SLETTS GORDON LWORCEL MANUEL
    • A61K31/4523A61K20060101A61K31/517A61K31/5415A61K31/549C07D211/00C07D285/22C07D295/00C07D307/00C07D417/12C07D417/14
    • C07D403/10C07C205/40C07D233/68C07D235/18C07D257/04C07D307/52C07D401/12C07D401/14C07D405/06C07D405/12C07D405/14C07D409/04C07D409/06C07D409/14C07D413/10C07D471/04C07D487/04C07D495/04C07D498/04
    • The invention describes novel nitrosated and/or nitrosylated cardiovascular compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated cardiovascular 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 cardiovascular 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 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; and (k) treating nephropathy. The nitrosated and/or nitrosylated cardiovascular compounds are preferably nitrosated and/or nitrosylated aldosterone antagonists, nitrosated and/or nitrosylated angiotensin II antagonists, nitrosated and/or nitrosylated calcium channel blockers, nitrosated and/or nitrosylated endothelin antagonists, nitrosated and/or nitrosylated hydralazine compounds, nitrosated and/or nitrosylated neutral endopeptidase inhibitors and nitrosated and/or nitrosylated renin inhibitors.
    • 本发明描述了新的亚硝化和/或亚硝基化的心血管化合物或其药学上可接受的盐,以及包含至少一种亚硝化和/或亚硝基化的心血管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组合物 。 本发明还提供了包含至少一种本发明的心血管化合物,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)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; 和(k)治疗肾病。 亚硝化和/或亚硝基化的心血管化合物优选为亚硝化和/或亚硝基化的醛固酮拮抗剂,亚硝化和/或亚硝酰化的血管紧张素II拮抗剂,亚硝化和/或亚硝酰化的钙通道阻断剂,亚硝化和/或亚硝基化的内皮素拮抗剂,亚硝化和/ 化合物,亚硝化和/或亚硝基化的中性内肽酶抑制剂和亚硝化和/或亚硝基化的肾素抑制剂。
    • 10. 发明申请
    • NITROSATED AND NITROSYLATED CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND METHODS OF USE
    • 硝酸和硝基化血管化合物,组合物和使用方法
    • WO2005018561A2
    • 2005-03-03
    • PCT/US2004026909
    • 2004-08-20
    • NITROMED INCGARVEY DAVID SLETTS GORDON LWORCEL MANUELGASTON RICKY D
    • GARVEY DAVID SLETTS GORDON LWORCEL MANUELGASTON RICKY D
    • A61K20060101A61K31/405A61K31/44A61K31/535C07D209/04C07D221/02C07D415/00A61K
    • C07D493/04C07D407/04C07K5/06026
    • The invention describes novel nitrosated and/or nitrosylated cardiovascular compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated cardiovascular 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 cardiovascular 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 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; and (k) treating nephropathy. The nitrosated and/or nitrosylated cardiovascular compounds are preferably nitrosated and/or nitrosylated P-adrenergic antagonists, nitrosated and/or nitrosylated angiotensin­converting enzyme (ACE) inhibitors, nitrosated and/or nitrosylated anti-hyperlipidemic compounds, and nitrosated and/or nitrosylated antithrombotic and vasodilator compounds.
    • 本发明描述了新的亚硝化和/或亚硝基化的心血管化合物或其药学上可接受的盐,以及包含至少一种亚硝化和/或亚硝基化的心血管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组合物 。 本发明还提供了包含至少一种本发明的心血管化合物,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)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; 和(k)治疗肾病。 亚硝化和/或亚硝基化的心血管化合物优选为亚硝化和/或亚硝化的P-肾上腺素能拮抗剂,亚硝化和/或亚硝化的血管紧张素转换酶(ACE)抑制剂,亚硝化和/或亚硝化的抗高脂血症化合物,以及亚硝化和/或亚硝化的抗血栓形成和/ 血管扩张剂化合物。