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1. 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。

2. 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。

3. 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。

4. 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。

5. 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.

6. 发明申请

US20090226407A9 METHODS OF TREATING VASCULAR DISEASES CHARACTERIZED BY NITRIC OXIDE INSUFFICIENCY 失效
标题翻译：治疗由氧化氮缺乏症引起的血管疾病的方法
公开(公告)号：US20090226407A9
公开(公告)日：2009-09-10
申请号：US10692724
申请日：2003-10-27
申请人： Joseph Loscalzo , Joseph Vita , Michael Loberg , Manuel Worcel
发明人： Joseph Loscalzo , Joseph Vita , Michael 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。

7. 发明申请

US20080139525A1 ANTIOXIDANT THERAPIES 审中-公开
标题翻译：抗氧化剂治疗
公开(公告)号：US20080139525A1
公开(公告)日：2008-06-12
申请号：US11848393
申请日：2007-08-31
申请人： Joseph Loscalzo
发明人： Joseph Loscalzo
IPC分类号： A61K31/555 , A61P29/00
CPC分类号： A61K31/555
摘要： The invention relates, in part, to methods of treatment of inflammatory, autoimmune, vascular and cardiovascular conditions with a combination of a superoxide dismutase (SOD) mimetic and a selenium (Se) compound. The invention also relates to compositions comprising a SOD mimetic(s) and a Se compound.
摘要翻译：本发明部分地涉及用超氧化物歧化酶（SOD）模拟物和硒（Se）化合物的组合治疗炎症，自身免疫，血管和心血管病症的方法。本发明还涉及包含SOD模拟物和Se化合物的组合物。

8. 发明申请

US20060198831A1 Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality 审中-公开
公开(公告)号：US20060198831A1
公开(公告)日：2006-09-07
申请号：US11418367
申请日：2006-05-05
申请人： Jonathan Stamler , Joseph Loscalzo , Daniel Simon , David Singel
发明人： Jonathan Stamler , Joseph Loscalzo , Daniel Simon , David Singel
IPC分类号： A61K38/43 , A61K38/38 , A61K38/17 , C12N9/00 , C07K14/775 , C07K14/765
CPC分类号： C12N9/6472 , A61K38/00 , C07K1/1077 , C07K14/3153 , C07K14/4702 , C07K14/76 , C07K14/765 , C07K14/805 , C07K16/00 , C12N9/6459 , C12Y304/21069
摘要： Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

9. 发明授权

US6087479A Localized use of nitric oxide-adducts to prevent internal tissue damage 失效
公开(公告)号：US6087479A
公开(公告)日：2000-07-11
申请号：US460465
申请日：1995-06-02
申请人： Jonathan S. Stamler , Joseph Loscalzo , John D. Folts
发明人： Jonathan S. Stamler , Joseph Loscalzo , John D. Folts
IPC分类号： A61L33/10 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K31/21 , A61K31/275 , A61K31/295 , A61K31/35 , A61K31/405 , A61K31/41 , A61K31/415 , A61K31/495 , A61K31/535 , A61K31/54 , A61K31/60 , A61K31/715 , A61K33/00 , A61K38/00 , A61K38/17 , A61K38/38 , A61K38/49 , A61K38/55 , A61K39/395 , A61K45/00 , A61K45/06 , A61K47/48 , A61L33/00 , A61P7/02
CPC分类号： B82Y30/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K31/21 , A61K31/275 , A61K31/295 , A61K31/41 , A61K31/4245 , A61K31/535 , A61K33/00 , A61K33/26 , A61K38/1709 , A61K38/38 , A61K38/49 , A61K38/556 , A61K38/58 , A61K45/06 , A61K47/48015 , A61K47/48238 , A61K47/48992 , A61L27/54 , A61L29/16 , A61L31/16 , A61L33/0011 , A61L33/0082 , A61L2300/114 , A61L2300/606
摘要： A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

10. 发明授权

US06471978B1 Localized use of nitric oxide-adducts to prevent internal tissue damage 失效
公开(公告)号：US06471978B1
公开(公告)日：2002-10-29
申请号：US09621610
申请日：2000-07-21
申请人： Jonathan S. Stamler , Joseph Loscalzo , John D. Folts
发明人： Jonathan S. Stamler , Joseph Loscalzo , John D. Folts
IPC分类号： A61F1300
CPC分类号： B82Y30/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K31/21 , A61K31/275 , A61K31/295 , A61K31/41 , A61K31/4245 , A61K31/535 , A61K33/00 , A61K33/26 , A61K38/1709 , A61K38/38 , A61K38/49 , A61K38/556 , A61K38/58 , A61K45/06 , A61K47/52 , A61K47/62 , A61K47/6957 , A61L27/54 , A61L29/16 , A61L31/16 , A61L33/0011 , A61L33/0082 , A61L2300/114 , A61L2300/606 , A61K2300/00
摘要： A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

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