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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。
    • 3. 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
    • 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。