公开(公告)号：EP2010169A2

公开(公告)日：2009-01-07

申请号：EP07754872.5

申请日：2007-04-04

申请人： Nitromed, Inc. ,  University of Pittsburgh of the Commonwealth System of Higher Education

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.

公开(公告)号：EP1943361A2

公开(公告)日：2008-07-16

申请号：EP06825494.5

申请日：2006-10-04

申请人： Nitromed, Inc. ,  University of Pittsburgh of the Commonwealth System of Higher Education

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.

公开(公告)号：EP1945030A2

公开(公告)日：2008-07-23

申请号：EP06816322.9

申请日：2006-10-04

申请人： Nitromed, Inc. ,  University of Pittsburgh of the Commonwealth System of Higher Education

发明人： WORCEL, Manuel ,  SABOLINSKI, Michael L. ,  TAM, Sang, William ,  McNAMARA, Dennis M.

IPC分类号： A01N43/58

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.

公开(公告)号：EP1778267A2

公开(公告)日：2007-05-02

申请号：EP05791690.0

申请日：2005-07-18

申请人： Nitromed, Inc.

发明人： WORCEL, Manuel ,  SABOLINSKI, Michael, L.

IPC分类号： A61K38/00 ,  A61K31/495 ,  A61K31/40 ,  A61K31/35 ,  A61K31/34 ,  A61K31/135

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.

公开(公告)号：EP1244455B1

公开(公告)日：2009-07-22

申请号：EP00976651.0

申请日：2000-10-27

申请人： Nitromed, Inc. ,  Trustees of Boston University

发明人： LOSCALZO, Joseph ,  VITA, Joseph, A. ,  LOBERG, Michael, D. ,  WORCEL, Manuel

IPC分类号： A61K31/535 ,  A61K31/50 ,  A61K31/495 ,  A61K31/415 ,  A61K31/355 ,  A61K31/34 ,  A61K31/19 ,  A61K31/135 ,  A01N45/00

CPC分类号： A61K31/495 ,  A61K9/0056 ,  A61K9/7023 ,  A61K31/135 ,  A61K31/19 ,  A61K31/34 ,  A61K31/355 ,  A61K31/415 ,  A61K31/50 ,  A61K31/535 ,  A61K31/7048 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention provides methods of treating and/or preventing vascular diseases where nitric oxide insufficiency is a contributing factor by administering a therapeutically effective amount of at least one antioxidant, or a pharmaceutically acceptable salt thereof, and at least one of isosorbide dinitrate and isosorbide mononitrate, and, optionally, at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated beta-adrenegic blocker, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angioetnsin II receptor antagonist, nitrosated renin inhibitor, and/or at least one compound used to treat cardiovascular diseases. The antioxidant is preferably a hydralazine compound or a pharmaceutically acceptable salt thereof. The present invention also provides methods of treating and/or preventing vascular diseases where nitric oxide insufficiency is a contributing factor by administering a therapeutically effective amount of at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated beta-adrenergic blocker, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin II receptor antagonist, nitrosated renin inhibitor, and, optionally, at least one antioxidant and/or at least one compound used to treat cardiovascular diseases. The present invention also provides methods of treating and/or preventing Raynaud's syndrome by administering a therapeutically effective amount of at least one antioxidant and at least one of isosorbide dinitrate and isosorbide mononitrate and/or at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated alcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin II receptor antagonist nitrosated renin inhibitor. The present invention also provides novel transdermal patches comprising at least one antioxydant and at least one of isosorbide dinitrate and isosorbide mononitrate and/or at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated beta-adrenergic blocker, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin II receptor antagonist, nitrosated renin inhibitor.

公开(公告)号：EP1670459A2

公开(公告)日：2006-06-21

申请号：EP04781569.1

申请日：2004-08-20

申请人： Nitromed, Inc.

发明人： GARVEY, David, S. ,  LETTS, Gordon, L. ,  WORCEL, Manuel ,  GASTON, Ricky, D.

IPC分类号： A61K31/405 ,  A61K31/44 ,  A61K31/535 ,  C07D209/04 ,  C07D221/02 ,  C07D415/00

CPC分类号： C07D493/04 ,  C07D407/04 ,  C07K5/06026

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.

公开(公告)号：EP1668008A2

公开(公告)日：2006-06-14

申请号：EP04781571.7

申请日：2004-08-20

申请人： Nitromed, Inc.

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： C07D417/12 ,  C07D417/14 ,  C07D307/00 ,  C07D295/00 ,  C07D211/00 ,  A61K31/5415 ,  A61K31/4523

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.

公开(公告)号：EP1337283A1

公开(公告)日：2003-08-27

申请号：EP01932915.0

申请日：2001-05-02

申请人： Nitromed, Inc. ,  TRUSTEES OF BOSTON UNIVERSITY

发明人： LOSCALZO, Joseph ,  VITA, Joseph, A. ,  LOBERG, Michael, D. ,  WORCEL, Manuel

IPC分类号： A61L15/16

CPC分类号： A61K45/06 ,  A61K9/0056 ,  A61K9/7023 ,  A61K31/12 ,  A61K31/198 ,  A61K31/355 ,  A61K31/375 ,  A61K31/502 ,  A61K31/7048 ,  A61K38/44 ,  A61K38/446 ,  A61K2300/00

摘要： The present invention provides methods of treating or preventing vascular diseases caused by nitric oxide (NO) insufficiency. The methods encompass administering a composition comprising an antioxidant, a compound to treat cardiovascular diseases, a nitrosated compound, a compound that donates, transfers or relases NO, or is a NO synthase substrate, or endogenously stimulates NO synthesis, or stimulates levels of endothelium derived relaxing factor. In the said composition, a hydralazine compound may be an antioxidant, isosorbide mono-or dinitrate may be the compound to donate, transfer, release, or stimulate endogenous NO synthesis. The isorsorbide may also elevate endogenous levels of endotherlium-derived relaxing factor, or be a NO synthase substrate and angiotensin enzyme inhibitor may be nitrosated compound. Disclosed in the invention is also a method to treat, or prevent Renaud's syndrome by administering a therapeutically effective amount of an antioxidant, a NO donor, a nitrosated compound and novel sustained-release formulations (e.g. a transdermal patch, See Figure 2).

公开(公告)号：EP1746882A2

公开(公告)日：2007-01-31

申请号：EP05767498.8

申请日：2005-03-31

申请人： Nitromed, Inc.

发明人： WORCEL, Manuel

IPC分类号： A01N33/26

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.

公开(公告)号：EP1667643A2

公开(公告)日：2006-06-14

申请号：EP04781570.9

申请日：2004-08-20

申请人： Nitromed, Inc.

发明人： GARVEY, David, S. ,  LETTS, Gordon, L. ,  WORCEL, Manuel

IPC分类号： A61K8/18

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.