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1. 发明授权

US07708989B2 Methods of treating vascular diseases characterized by nitric oxide insufficiency 失效
标题翻译：治疗以一氧化氮不足为特征的血管疾病的方法
公开(公告)号：US07708989B2
公开(公告)日：2010-05-04
申请号：US10692724
申请日：2003-10-27
申请人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
IPC分类号： A61K38/43 , A01N43/04
CPC分类号： A61K31/135 , A61K9/0056 , A61K9/7023 , A61K31/19 , A61K31/34 , A61K31/355 , A61K31/415 , A61K31/495 , A61K31/50 , A61K31/535 , A61K45/06 , A61K2300/00
摘要： The invention provides methods of treating and/or preventing vascular diseases characterized by nitric oxide insufficiency by administering a therapeutically effective amount of at least one nitrosated angiotensin-converting enzyme inhibitor, nitrosated beta-adrenergic blocker, nitrosated cholesterol reducer, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin II receptor antagonist, nitrosated renin inhibitor, and optionally at least one compound used to treat cardiovascular diseases and/or at least one antioxidant, or a pharmaceutically acceptable salt thereof, and/or at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase. The antioxidant may preferably be a hydralazine compound or a pharmaceutically acceptable salt thereof. The compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase may preferably be isosorbide dinitrate and/or isosorbide mononitrate. The vascular diseases characterized by nitric oxide insufficiency include a cardiovascular disease and a disease resulting from oxidative stress.
摘要翻译：本发明提供治疗和/或预防以一氧化氮不足为特征的血管疾病的方法，其通过施用治疗有效量的至少一种亚硝化血管紧张素转换酶抑制剂，亚硝化β-肾上腺素能阻断剂，亚硝化胆固醇降低剂，亚硝化钙通道阻断剂，亚硝化内皮素拮抗剂，亚硝化血管紧张素II受体拮抗剂，亚硝化肾素抑制剂和任选的至少一种用于治疗心血管疾病的化合物，和/或至少一种抗氧化剂或其药学上可接受的盐，和/或至少一种可以转移的化合物或释放一氧化氮，提高内源性内源性舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮合成酶的底物。抗氧化剂可优选为肼屈嗪化合物或其药学上可接受的盐。捐赠，转移或释放一氧化氮的化合物提高内源性内皮衍生的松弛因子水平，刺激一氧化氮的内源性合成，或者是一氧化氮合酶的底物可优选为硝酸异山梨酯和/或一硝酸异山梨酯。以一氧化氮不足为特征的血管疾病包括心血管疾病和由氧化应激引起的疾病。

2. 发明申请

US20100068267A1 COMPOSITIONS FOR TREATING VASCULAR DISEASES CHARACTERIZED BY NITRIC OXIDE INSUFFICIENCY 审中-公开
标题翻译：用于治疗由氮氧化物缺乏症表征的血管疾病的组合物
公开(公告)号：US20100068267A1
公开(公告)日：2010-03-18
申请号：US12564550
申请日：2009-09-22
申请人： Joseph LOSCALZO , Joseph A. VITA , Michael D. LOBERG , Manuel WORCEL
发明人： Joseph LOSCALZO , Joseph A. VITA , Michael D. LOBERG , Manuel WORCEL
IPC分类号： A61K9/54 , A61K9/26 , A61K9/14 , A61K31/502
CPC分类号： A61K31/135 , A61K9/0056 , A61K9/7023 , A61K31/19 , A61K31/34 , A61K31/355 , A61K31/415 , A61K31/495 , A61K31/50 , A61K31/535 , A61K45/06 , A61K2300/00
摘要： The invention provides methods of treating a cardiovascular disease comprising administering a sustained release formulation of hydralazine hydrochloride and at least one of isosorbide dinitrate and/or isosorbide mononitrate in therapeutically effective dosage of each of the aforementioned compounds.
摘要翻译：本发明提供治疗心血管疾病的方法，其包括给予盐酸肼屈嗪的缓释制剂和硝酸异山梨酯和/或一硝酸异山梨酯中的至少一种治疗有效剂量的每种上述化合物。

3. 发明授权

US07537785B2 Composition for treating vascular diseases characterized by nitric oxide insufficiency 有权
标题翻译：用于治疗以一氧化氮不足为特征的血管疾病的组合物
公开(公告)号：US07537785B2
公开(公告)日：2009-05-26
申请号：US10687706
申请日：2003-10-20
申请人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
IPC分类号： A61K9/14 , A61K9/52 , B82B3/00
CPC分类号： A61K45/06 , A61K9/0056 , A61K9/7023 , A61K31/135 , A61K31/19 , A61K31/34 , A61K31/355 , A61K31/415 , A61K31/495 , A61K31/50 , A61K31/535 , Y10S977/773 , A61K2300/00
摘要： The present invention provides a composition comprising an antioxidant, and at least one of isosorbide dinitrate and isosorbide mononitrate in therapeutically effective dosage of each of the aforementioned compounds to treat cardiovascular diseases caused by nitric oxide (NO) insufficiency. The antioxidant is a hydralazine compound.
摘要翻译：本发明提供一种组合物，其包含抗氧化剂和硝酸异山梨酯和一硝酸异山梨酯中的至少一种治疗有效剂量的上述化合物，用于治疗由一氧化氮（NO）不足引起的心血管疾病。抗氧化剂是肼屈嗪化合物。

4. 发明授权

US06635273B1 Methods of treating vascular diseases characterized by nitric oxide insufficiency 有权
公开(公告)号：US06635273B1
公开(公告)日：2003-10-21
申请号：US09697317
申请日：2000-10-27
申请人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
IPC分类号： A61L1516
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 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-adrenergic blocker, nitrosated calcium channel blocker, nitrosated endothelin antagonist, nitrosated angiotensin 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 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 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 calcium 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 antioxidant 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.

5. 发明授权

US07556824B2 Transdermal patch composition for treating vascular diseases characterized by nitric oxide insufficiency 有权
标题翻译：用于治疗以一氧化氮不足为特征的血管疾病的透皮贴片组合物
公开(公告)号：US07556824B2
公开(公告)日：2009-07-07
申请号：US10679257
申请日：2003-10-07
申请人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
IPC分类号： A61F13/00 , A61K9/70 , A61L15/12 , A61L15/44
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 novel transdermal patch comprising a therapeutic amount of a hydralazine compound and at least one of isosorbide dinitrate and isosorbide mononitrate in therapeutically effective dosage of each of the aforementioned compounds.
摘要翻译：本发明提供新颖的透皮贴剂，其包含治疗量的肼azine嗪化合物和硝酸异山梨酯和硝酸异山梨酯中的至少一种，其治疗有效剂量为上述每种化合物。

6. 发明授权

US07235237B2 Methods of treating vascular diseases characterized by nitric oxide insufficiency 失效
标题翻译：治疗以一氧化氮不足为特征的血管疾病的方法
公开(公告)号：US07235237B2
公开(公告)日：2007-06-26
申请号：US10415136
申请日：2001-05-02
申请人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph A. Vita , Michael D. Loberg , Manuel Worcel
IPC分类号： A61K38/43 , A61K31/215 , A01N37/12 , A01N33/18
CPC分类号： A61K45/06 , A61K31/12 , A61K31/198 , A61K31/355 , A61K31/375 , A61K31/502 , 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).
摘要翻译：本发明提供治疗或预防由一氧化氮（NO）不足引起的血管疾病的方法。所述方法包括施用包含抗氧化剂，治疗心血管疾病的化合物，亚硝化化合物，提供，转移或者中和NO的化合物或NO合成酶底物或内源性刺激NO合成或刺激内皮衍生物的水平的组合物放松因子。在所述组合物中，肼屈嗪化合物可以是抗氧化剂，异山梨醇单或二硝酸酯可以是捐赠，转移，释放或刺激内源性NO合成的化合物。异山梨醇也可以提高内源性内源性释放因子水平，或者是NO合成酶底物，血管紧张素酶抑制剂可以是亚硝化化合物。在本发明中公开的方法也是通过施用治疗有效量的抗氧化剂，NO供体，亚硝化化合物和新的缓释制剂（例如透皮贴剂）来治疗或预防Renaud综合征的方法。

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