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1. 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.

2. 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。

3. 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.

4. 发明申请

WO2006020244A2 COMPOSITIONS AND METHODS RELATED TO HEART FAILURE 审中-公开
标题翻译：与心脏失效相关的组合物和方法
公开(公告)号：WO2006020244A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/025455
申请日：2005-07-18
申请人： NITROMED, INC. , WORCEL, Manuel , SABOLINSKI, Michael, L.
发明人： WORCEL, Manuel , SABOLINSKI, Michael, L.
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 antiinflammary compound (i.e., NSAIDs); (k) treating a heart failure patient who has a history of hypertension (but who is not currently diagnosed with hypertension); (1) 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, ß-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）减少病人在医院内为多次住院（即两个或两个以上住院期间）心衰的总天数; （e）减少住院心脏病的人数; （f）减少死亡率和减少心力衰竭的住院时间（例如医院总天数和/或住院次数）; （g）增加心力衰竭患者的左心室射血分数; （h）治疗性功能障碍（例如勃起功能障碍和女性性功能障碍）（j）通过施用非甾体抗炎症化合物（即NSAIDs）治疗心力衰竭患者的头痛; （k）治疗具有高血压病史（但目前尚未被诊断患有高血压症）的心力衰竭患者; （1）提高基于明尼苏达州心力衰竭问卷调查问卷的心力衰竭患者的生活质量; （m）降低B型利尿钠肽的含量; （n）治疗心力衰竭患者的高血压; （o）降低心力衰竭患者的血压; （p）治疗不稳定性高血压; （q）治疗特发性高血压; （r）增加患者对心力衰竭患者药物剂量的依从性; 在患有心脏扩张的患者中治疗高血压; （t）治疗缺血性疾病和/或冠状动脉疾病; 和（u）减少患有需要的患者的心脏肿大，其包括向患者施用治疗有效量的（i）肼屈嗪化合物或其药学上可接受的盐，（ii）硝酸异山梨酯和/或硝酸异山梨酯，和（iii）任选地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）和利尿剂的至少一种化合物。

5. 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。

6. 发明申请

WO2006020244A3 COMPOSITIONS AND METHODS RELATED TO HEART FAILURE 审中-公开
标题翻译：与心脏失效相关的组合物和方法
公开(公告)号：WO2006020244A3
公开(公告)日：2006-10-26
申请号：PCT/US2005025455
申请日：2005-07-18
申请人： NITROMED INC , WORCEL MANUEL , SABOLINSKI MICHAEL L
发明人： WORCEL MANUEL , SABOLINSKI MICHAEL L
IPC分类号： A61K38/00 , A61K31/135 , A61K31/34 , A61K31/35 , A61K31/40 , A61K31/495
CPC分类号： A61K31/15 , A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： The present invention is directed, in general, to methods for prolonging time to hospitalization for heart failure in a patient in need thereof which includes the administration to such patients of effective amounts of hydralazine hydrochloride and isosorbide dinitrate.
摘要翻译：本发明总体上涉及延长有需要的患者心脏衰竭住院时间的方法，包括给予这些患者有效量的盐酸肼屈嗪和硝酸异山梨酯。

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