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1. 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。

2. 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.

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

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.

5. 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。

6. 发明申请

WO2005018561A3 NITROSATED AND NITROSYLATED CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
公开(公告)号：WO2005018561A3
公开(公告)日：2005-03-03
申请号：PCT/US2004/026909
申请日：2004-08-20
申请人： NITROMED, INC. , GARVEY, David, S. , LETTS, Gordon, L. , WORCEL, Manuel , GASTON, Ricky, D.
发明人： GARVEY, David, S. , LETTS, Gordon, L. , WORCEL, Manuel , GASTON, Ricky, D.
IPC分类号： A61K31/405
摘要： 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.

7. 发明申请

WO2005107384A2 METHODS FOR TREATING BLOOD DISORDERS WITH NITRIC OXIDE DONOR COMPOUNDS 审中-公开
标题翻译：用硝酸氧化钴化合物治疗血液病症的方法
公开(公告)号：WO2005107384A2
公开(公告)日：2005-11-17
申请号：PCT/US2005/010935
申请日：2005-03-31
申请人： NITROMED, INC. , WORCEL, Manuel
发明人： WORCEL, Manuel
CPC分类号： A61K31/198 , A61K31/21 , A61K31/34 , A61K31/502 , A61K45/06 , A61K2300/00
摘要： 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.
摘要翻译：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。血液病症优选为镰状细胞性贫血。由血液病引起的并发症优选为肺动脉高压。

8. 发明申请

WO2005023183A2 NITROSATED AD NITROSYLATED DIURETIC COMPOUDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸盐的硝酸盐溶液，组合物和使用方法
公开(公告)号：WO2005023183A2
公开(公告)日：2005-03-17
申请号：PCT/US2004/026911
申请日：2004-08-20
申请人： NITROMED, INC. , GARVEY, David, S. , LETTS, L., Gordon , WORCEL, Manuel , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A.
发明人： GARVEY, David, S. , LETTS, L., Gordon , WORCEL, Manuel , EARL, Richard, A. , EZAWA, Maiko , FANG, Xinqin , KHANAPURE, Subhash, P. , LIN, Chia-En , RANATUNGE, Ramani, R. , STEVENSON, Cheri, A.
IPC分类号： A61K
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 (1) 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（1）治疗肾病。

9. 发明申请

WO2005023182A2 NITROSATED AND NITROSYLATED CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝酸和硝基化血管化合物，组合物和使用方法
公开(公告)号：WO2005023182A2
公开(公告)日：2005-03-17
申请号：PCT/US2004/026910
申请日：2004-08-20
申请人： NITROMED, INC. , GARVEY, David, S. , LETTS, Gordon, L. , WORCEL, Manuel
发明人： GARVEY, David, S. , LETTS, Gordon, L. , WORCEL, Manuel
IPC分类号： A61K
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 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.
摘要翻译：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。

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