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1. 发明申请

WO2007041676A2 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF ALDOSTERONE SYNTHASE PROMOTER POLYMORPHISM 审中-公开
标题翻译：心脏遗传危险评估：ALDOSTERONE SYNTHASE PROMOTER POLYMORPHISM遗传变异的影响
公开(公告)号：WO2007041676A2
公开(公告)日：2007-04-12
申请号：PCT/US2006038956
申请日：2006-10-04
申请人： NITROMED INC , UNIV PITTSBURGH , WORCEL MANUEL , SABOLINSKI MICHAEL L , TAM SANG WILLIAM , MCNAMARA DENNIS M
发明人： WORCEL MANUEL , SABOLINSKI MICHAEL L , TAM SANG WILLIAM , MCNAMARA DENNIS M
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/106 , C12Q2600/118 , C12Q2600/156 , C12Q2600/172
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; (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.
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）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。

2. 发明申请

WO2006110601A2 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF THE GENETIC VARIATION OF NOS3 审中-公开
标题翻译：心脏遗传危险评估：NOS3遗传变异的影响
公开(公告)号：WO2006110601A2
公开(公告)日：2006-10-19
申请号：PCT/US2006013185
申请日：2006-04-07
申请人： NITROMED INC , UNIV PITTSBURGH , WORCEL MANUEL , SABOLINSKI MICHAEL , TAM SANG W , MCNAMARA DENNIS M
发明人： WORCEL MANUEL , SABOLINSKI MICHAEL , TAM SANG W , MCNAMARA DENNIS M
IPC分类号： A61K31/21 , C12Q1/68
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; (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.
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; （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。

3. 发明申请

WO2007041680A2 THE 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
公开(公告)号：WO2007041680A2
公开(公告)日：2007-04-12
申请号：PCT/US2006038964
申请日：2006-10-04
申请人： NITROMED INC , UNIV PITTSBURGH , WORCEL MANUEL , SABOLINSKI MICHAEL L , TAM SANG WILLIAM , MCNAMARA DENNIS M
发明人： WORCEL MANUEL , SABOLINSKI MICHAEL L , TAM SANG WILLIAM , MCNAMARA DENNIS M
IPC分类号： C12Q1/68
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; (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.
摘要翻译：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。

4. 发明申请

WO2007041676A3 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF ALDOSTERONE SYNTHASE PROMOTER POLYMORPHISM 审中-公开
公开(公告)号：WO2007041676A3
公开(公告)日：2007-04-12
申请号：PCT/US2006/038956
申请日：2006-10-04
申请人： NITROMED, INC. , UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , WORCEL, Manuel , SABOLINSKI, Michael, L. , TAM, Sang, William , McNAMARA, Dennis, M.
发明人： WORCEL, Manuel , SABOLINSKI, Michael, L. , TAM, Sang, William , McNAMARA, Dennis, M.
IPC分类号： C12Q1/68
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; (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.

5. 发明申请

WO2007120555A2 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF THE GENETIC VARIATION OF G-PROTEIN BETA 3 SUBUNIT POLYMORPHISM 审中-公开
标题翻译：遗传遗传危害评估：G蛋白β亚基多态性遗传变异的影响
公开(公告)号：WO2007120555A2
公开(公告)日：2007-10-25
申请号：PCT/US2007/008426
申请日：2007-04-04
申请人： NITROMED, INC, , UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
发明人： WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
IPC分类号： A61K31/21
CPC分类号： A61K31/21 , A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： The invention provides methods for treating various indications and diseases in a patient in need thereof, wherein the patient has a C825T polymorphism in the G protein beta3 subunit (GNB3), 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：本发明提供了在有需要的患者中治疗各种适应症和疾病的方法，其中所述患者在G蛋白β3亚基（GNB3）中具有C825T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药学上其可接受的盐; （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。

6. 发明申请

WO2006110601A3 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF THE GENETIC VARIATION OF NOS3 审中-公开
公开(公告)号：WO2006110601A3
公开(公告)日：2006-10-19
申请号：PCT/US2006/013185
申请日：2006-04-07
申请人： NITROMED, INC. , UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
发明人： WORCEL, Manuel , SABOLINSKI, Michael , TAM, Sang, W. , MCNAMARA, Dennis, M.
IPC分类号： A01N33/24 , A61K31/13
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; (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.

7. 发明申请

WO2012078502A3 BIOMARKER TEST FOR ACUTE CORONARY SYNDROME 审中-公开
标题翻译：生物标志物检测急性冠状动脉综合征
公开(公告)号：WO2012078502A3
公开(公告)日：2012-11-01
申请号：PCT/US2011063267
申请日：2011-12-05
申请人： UNIV PITTSBURGH , LAFRAMBOISE WILLIAM A , MASTERSON ROBERT V , MARROQUIN OSCAR C , MCNAMARA DENNIS M , MULUKUTLA SURESH R , LOMAKIN ALEKSEY
发明人： LAFRAMBOISE WILLIAM A , MASTERSON ROBERT V , MARROQUIN OSCAR C , MCNAMARA DENNIS M , MULUKUTLA SURESH R , LOMAKIN ALEKSEY
IPC分类号： G01N33/68 , G01N33/53 , G06F17/10
CPC分类号： G06F19/3431 , G01N33/6893 , G01N2570/00 , G01N2800/324 , G01N2800/50 , G01N2800/60 , G16H50/30
摘要： The present invention relates to biomarker signatures and associated methods for identifying patients that are not likely to manifest significant coronary artery disease. It is based, at least in part, on a study performed on serum samples of 239 patients with clinical symptoms of cardiac distress, some of whom required invasive intervention (stent placement or bypass graft surgery). A set of biomarkers was identified as exhibiting different levels of expression in subjects that did, or did not, require invasive intervention. Further, an algorithm was developed which, using serum levels of these biomarkers, assigned a score to a given patient that was indicative of whether that patient required invasive intervention.
摘要翻译：本发明涉及用于鉴定不可能表现出显着冠状动脉疾病的患者的生物标志物标记和相关方法。它至少部分基于对239例有心脏窘迫临床症状的患者的血清样本进行研究，其中一些患者需要有创介入（支架置入或旁路移植手术）。一组生物标志物被确定为在或不需要侵入性干预的受试者中表现出不同的表达水平。此外，开发了一种算法，使用这些生物标志物的血清水平，给予给定患者的评分，该评分指示该患者是否需要侵入性干预。

8. 发明申请

WO2012078502A2 BIOMARKER TEST FOR ACUTE CORONARY SYNDROME 审中-公开
标题翻译：急性冠状动脉综合征生物标志物检测
公开(公告)号：WO2012078502A2
公开(公告)日：2012-06-14
申请号：PCT/US2011/063267
申请日：2011-12-05
申请人： UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , LAFRAMBOISE, William, A. , MASTERSON, Robert, V. , MARROQUIN, Oscar, C. , MCNAMARA, Dennis, M. , MULUKUTLA, Suresh, R. , LOMAKIN, Aleksey
发明人： LAFRAMBOISE, William, A. , MASTERSON, Robert, V. , MARROQUIN, Oscar, C. , MCNAMARA, Dennis, M. , MULUKUTLA, Suresh, R. , LOMAKIN, Aleksey
IPC分类号： G01N33/68 , G01N33/53 , G06F17/10
CPC分类号： G06F19/3431 , G01N33/6893 , G01N2570/00 , G01N2800/324 , G01N2800/50 , G01N2800/60 , G06F19/00 , G16H50/30
摘要： The present invention relates to biomarker signatures and associated methods for identifying patients that are not likely to manifest significant coronary artery disease. It is based, at least in part, on a study performed on serum samples of 239 patients with clinical symptoms of cardiac distress, some of whom required invasive intervention (stent placement or bypass graft surgery). A set of biomarkers was identified as exhibiting different levels of expression in subjects that did, or did not, require invasive intervention. Further, an algorithm was developed which, using serum levels of these biomarkers, assigned a score to a given patient that was indicative of whether that patient required invasive intervention.
摘要翻译：本发明涉及用于鉴定不太可能表现出明显的冠状动脉疾病的患者的生物标志物标志和相关方法。至少部分基于对239例心脏窘迫临床症状患者的血清样本进行的研究，其中一些患者需要侵入性干预（支架置入或旁路移植手术）。鉴定了一组生物标志物，表明在进行或不需要侵入性干预的受试者中具有不同程度的表达。此外，开发了一种算法，使用这些生物标志物的血清水平，给予给定患者一个评分，指示该患者是否需要侵入性干预。

9. 发明申请

WO2007120555A3 ASSESSMENT OF HEART FAILURE RISK USING GENETIC ASSESSMENT OF G-PROTEIN BETA-3 SUBUNIT POLYMORPHISM 审中-公开
标题翻译：使用G蛋白β-3亚基多态性的遗传评估评估心脏失效风险
公开(公告)号：WO2007120555A3
公开(公告)日：2008-11-27
申请号：PCT/US2007008426
申请日：2007-04-04
申请人： NITROMED INC , UNIV PITTSBURGH , WORCEL MANUEL , SABOLINSKI MICHAEL , TAM SANG W , MCNAMARA DENNIS M
发明人： WORCEL MANUEL , SABOLINSKI MICHAEL , TAM SANG W , MCNAMARA DENNIS M
IPC分类号： A01N43/58 , A01N33/02 , A01N33/18 , A01N33/24 , A01N43/08 , A01N43/60 , A01N45/00 , A61K31/04 , A61K31/135 , A61K31/34 , A61K31/495 , A61K31/50 , A61K31/56
CPC分类号： A61K31/21 , A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： The invention provides methods for treating various indications and diseases in a patient in need thereof, wherein the patient has a C825T polymorphism in the G protein beta3 subunit (GNB3), 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：本发明提供了在有需要的患者中治疗各种适应症和疾病的方法，其中所述患者在G蛋白β3亚基（GNB3）中具有C825T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药学上其可接受的盐; （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

WO2007041680A3 THE GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF BETA 1 ADRENERGIC RECEPTOR GLY389ARG POLYMORPHISM 审中-公开
公开(公告)号：WO2007041680A3
公开(公告)日：2007-04-12
申请号：PCT/US2006/038964
申请日：2006-10-04
申请人： NITROMED, INC. , UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION , WORCEL, Manuel , SABOLINSKI, Michael, L. , TAM, Sang, William , McNAMARA, Dennis, M.
发明人： WORCEL, Manuel , SABOLINSKI, Michael, L. , TAM, Sang, William , McNAMARA, Dennis, M.
IPC分类号： A01N43/58
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; (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.

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