公开(公告)号：US20050192254A1

公开(公告)日：2005-09-01

申请号：US11096924

申请日：2005-03-31

申请人： David Wink ,  Martin Feelisch ,  David Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

发明人： David Wink ,  Martin Feelisch ,  David Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

IPC分类号： A61K31/13 ,  A61K31/16 ,  A61K31/655 ,  A61K31/137

CPC分类号： A61K31/655 ,  A61K31/13 ,  A61K31/16 ,  A61K33/00 ,  A61K2300/00

摘要： Administration of an HNO/NO− donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO− donating compound isopropylamine (IPA)/NO(Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO− donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO+ donors, administration of an HNO/NO− donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO− exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.

摘要翻译： 施用HNO / NO - 辅助化合物，例如Angeli盐，增加心肌收缩力，同时降低经历心力衰竭的受试者的左心室预负荷。 此外，给予HNO / NO - 供体化合物异丙胺（IPA）/ NO（Na（CH 3）2 CHNHN（O）NO ）令人惊讶地在经历心力衰竭的受试者中表现出正向的变力作用，其优于由提供HNO /供体化合物Angeli盐引起的那些。 另外，与使用NO + +供体观察到的效果相反，与正性肌力药物组合施用HNO / NO + - 供体不会损害正性肌力作用 正性肌力药。 此外，HNO / NO 发挥其与肾上腺素能系统无关的正性肌力作用，即使在接受β-拮抗剂治疗的受试者中也增加收缩力。

公开(公告)号：US20110081427A1

公开(公告)日：2011-04-07

申请号：US12949533

申请日：2010-11-18

申请人： David A. Wink ,  Martin Feelisch ,  David A. Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

发明人： David A. Wink ,  Martin Feelisch ,  David A. Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

IPC分类号： A61K33/00 ,  A61P9/04 ,  A61K31/655

CPC分类号： A61K31/655 ,  A61K31/13 ,  A61K31/16 ,  A61K33/00 ,  A61K2300/00

摘要： Administration of an HNO/NO− donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO− donating compound isopropylamine (IPA)/NO (Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO− donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO− donors, administration of an HNO/NO− donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO− exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.

摘要翻译： 施用HNO / NO供体化合物，例如Angeli盐可增加心肌收缩力，同时降低心衰患者的左心室预负荷。 此外，HNO / NO供体化合物异丙胺（IPA）/ NO（Na（CH 3）2 CHNHN（O）NO）的给药令人惊讶地在经历心力衰竭的受试者中表现出优于HNO / NO- 捐赠化合物Angeli的盐。 另外，与使用NO-供体观察到的效果相反，将HNO / NO供体与正性肌力药物联合给药不会损害正性肌力药物的正性肌力作用。 此外，HNO / NO-不依赖于肾上腺素能系统发挥其正性肌力作用，即使在接受β-拮抗剂治疗的受试者中也能增加收缩力。

公开(公告)号：US07863262B2

公开(公告)日：2011-01-04

申请号：US11096924

申请日：2005-03-31

申请人： David A. Wink ,  Martin Feelisch ,  David A. Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

发明人： David A. Wink ,  Martin Feelisch ,  David A. Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

IPC分类号： A01N51/00 ,  A61K31/655 ,  A61K31/13 ,  A61K33/26

CPC分类号： A61K31/655 ,  A61K31/13 ,  A61K31/16 ,  A61K33/00 ,  A61K2300/00

摘要： Administration of an HNO/NO− donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO− donating compound isopropylamine (IPA)/NO(Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO− donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO− donors, administration of an HNO/NO− donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO− exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.

摘要翻译： 施用HNO / NO供体化合物，例如Angeli盐可增加心肌收缩力，同时降低心衰患者的左心室预负荷。 此外，HNO / NO供体化合物异丙胺（IPA）/ NO（Na（CH 3）2 CHNHN（O）NO）的给药令人惊讶地在经历心力衰竭的受试者中表现出优于HNO / NO- 捐赠化合物Angeli的盐。 另外，与使用NO-供体观察到的效果相反，将HNO / NO供体与正性肌力药物联合给药不会损害正性肌力药物的正性肌力作用。 此外，HNO / NO-不依赖于肾上腺素能系统发挥其正性肌力作用，即使在接受β-拮抗剂治疗的受试者中也能增加收缩力。

公开(公告)号：US06936639B2

公开(公告)日：2005-08-30

申请号：US10226412

申请日：2002-08-21

申请人： David A. Wink ,  Martin Feelisch ,  David A. Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

发明人： David A. Wink ,  Martin Feelisch ,  David A. Kass ,  Nazareno Paolocci ,  Katrina Miranda ,  Jon Fukuto ,  Tatsuo Katori

IPC分类号： A61K31/13 ,  A61K31/16 ,  A61K31/19

CPC分类号： A61K31/655 ,  A61K31/13 ,  A61K31/16 ,  A61K33/00 ,  A61K2300/00

摘要： Administration of an HNO/NO− donating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure Moreover, administration of the HNO/NO− donating compound isopropylamine (IPA)/NO (Na(CH3)2CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO− donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO− donors, administration of an HNO/NO− donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent Further, HNO/NO− exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy

摘要翻译： 施用HNO / NO - 辅助化合物如Angeli盐可增加心肌收缩力，同时降低经历心力衰竭的受试者的左心室预负荷。此外，给予HNO / 供体化合物异丙胺（IPA）/ NO（Na（CH 3 3）2 CHNHN（O）NO）令人惊讶地在经历心力衰竭的受试者中表现出正性肌力作用 由HNO / NO - 捐赠化合物Angeli的盐引起的那些。 另外，与使用NO-SUP供体观察到的效果相反，将HNO / NO + - 供体与正性肌力药物组合给药不会损害正性肌力作用 正性肌力药物另外，HNO / NO 发挥其与肾上腺素能系统无关的正性肌力作用，即使在接受β-拮抗剂治疗的受试者中也增加收缩力

公开(公告)号：US20050009789A1

公开(公告)日：2005-01-13

申请号：US10845619

申请日：2004-05-12

申请人： David Wink ,  Katrina Miranda ,  Christopher Bradbury ,  David Gius ,  Jon Fukuto ,  Martin Feelisch

发明人： David Wink ,  Katrina Miranda ,  Christopher Bradbury ,  David Gius ,  Jon Fukuto ,  Martin Feelisch

IPC分类号： A61K31/655

CPC分类号： A61K31/655

摘要： Nitroxyl is used to inhibit COX-2 activity and particularly to selectively inhibit COX-2 activity. Nitroxyl also is used to treat conditions that respond favorably to inhibition of COX-2 activity in subjects having such conditions. In some cases nitroxyl is used to treat conditions that respond favorably to inhibition of COX-2 activity in subjects having such conditions and who also have at least one other condition for which inhibition of COX-1 activity is disadvantageous. Nitroxyl can be provided directly, but typically is provided with the use of a nitroxyl donor. Nitroxyl donors include any agent or compound (or combination thereof) that donates HNO or NO−. Diazeniumdiolates are used in some cases as nitroxyl donors. In particular instances, diazeniumdiolates having a primary amine group are used as nitroxyl donors. Nitroxyl-donating compounds also are screened for selective COX-2 inhibition for identification as therapeutic agents.

摘要翻译： 硝酸用于抑制COX-2活性，特别是选择性抑制COX-2活性。 硝酸还用于治疗对具有这种病症的受试者中COX-2活性的抑制作用有利的病症。 在某些情况下，硝酰基用于治疗对具有这种病症的受试者中对COX-2活性的抑制作用有利的条件，并且还具有抑制COX-1活性的至少一种其它病症是不利的。 可以直接提供硝基，但通常使用硝酰基供体。 硝基供体包括提供HNO或NO - 的任何试剂或化合物（或其组合）。 在一些情况下使用二氮烯二硫代吗啉作为硝酰基供体。 在具体情况下，使用具有伯胺基团的二氮烯鎓二醇作为硝酰基供体。 硝酸氧基化合物也被筛选用于选择性COX-2抑制用于鉴定作为治疗剂。