公开(公告)号：US20090306027A1

公开(公告)日：2009-12-10

申请号：US12296630

申请日：2007-04-04

申请人： Manuel Worcel ,  Michael Sabolinski ,  Sang W. Tam ,  Dennis M. McNamara

发明人： Manuel Worcel ,  Michael Sabolinski ,  Sang W. Tam ,  Dennis M. McNamara

IPC分类号： A61K31/56 ,  A61K31/34 ,  A61K31/502

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。

公开(公告)号：US20090253662A1

公开(公告)日：2009-10-08

申请号：US12088924

申请日：2006-10-04

申请人： Manuel Worcel ,  Michael Sabolinski ,  Sang W. Tam ,  Dennis M. McNamara

发明人： Manuel Worcel ,  Michael Sabolinski ,  Sang W. Tam ,  Dennis M. McNamara

IPC分类号： A61K31/56 ,  A61K31/34 ,  A61K31/502 ,  A61K31/40 ,  A61K31/403 ,  A61K31/352 ,  A61P9/00

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; (l) 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 CYP11B2 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; （Ic）降低B型利尿钠蛋白的水平; （l）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CYP11B2基因中具有-344（T / T）多态性或-344（C / C）多态性，其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。

公开(公告)号：US20060014828A1

公开(公告)日：2006-01-19

申请号：US11182886

申请日：2005-07-18

申请人： Manuel Worcel ,  Michael Sabolinski

发明人： Manuel Worcel ,  Michael Sabolinski

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 antiinflammatory compound (i.e., NSAIDs); (k) treating a heart failure patient who has a history of hypertension (but who is not currently diagnosed with hypertension); (l) 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, β-adrenergic antagonists, angiotensin II antagonists, aldosterone antagonists, cardiac glucosides (digitalis), and diuretic compounds.

公开(公告)号：US20060014829A1

公开(公告)日：2006-01-19

申请号：US11182887

申请日：2005-07-18

申请人： Manuel Worcel ,  Michael Sabolinski

发明人： Manuel Worcel ,  Michael Sabolinski

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; (e) reducing the number of hospital admissions for heart failure; and (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) 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, β-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）减少患者在医院内多次住院心衰的总天数; （e）减少住院心脏病的人数; 和（f）在有需要的患者中降低死亡率并减少心力衰竭的住院时间（例如，医院的总天数和/或住院次数），包括向患者施用治疗有效量的（i ）二氢肼屈嗪化合物或其药学上可接受的盐，（ii）硝酸异山梨酯和/或单硝酸异山梨酯，和（iii）任选的至少一种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。