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1. 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。

2. 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。

3. 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.

4. 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.

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

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.

7. 发明授权

US5385937A Nitrosation of homocysteine as a method for treating homocysteinemia 失效
标题翻译：同型半胱氨酸的亚硝化作为治疗同型半胱氨酸血症的方法
公开(公告)号：US5385937A
公开(公告)日：1995-01-31
申请号：US839188
申请日：1992-02-21
申请人： Jonathan Stamler , Joseph Loscalzo
发明人： Jonathan Stamler , Joseph Loscalzo
IPC分类号： B08B3/08 , A61K31/04 , A61K31/095 , A61K31/16 , A61K31/195 , A61K31/198 , A61K31/21 , A61K31/295 , A61K31/40 , A61K31/41 , A61K31/42 , A61K38/00 , A61K38/16 , A61P7/02 , A61P9/00 , A61P9/10 , A61P9/12 , A61P25/00 , A61P43/00 , C11D7/24 , C11D7/30 , C23G5/02 , C23G5/024 , C23G5/028 , C23G5/032 , C23G5/04 , H05K3/26 , A01N37/00 , A61K31/19
CPC分类号： A61K38/16 , A61K31/04 , A61K31/095 , A61K31/16 , A61K31/195 , A61K31/21 , A61K31/295 , A61K31/40 , A61K31/41 , A61K31/42 , C23G5/024 , H05K3/26 , H05K2203/0766 , H05K2203/0783 , H05K2203/1518
摘要： Administration of a nitrosating compound, such as nitroglycerin, nitric oxide, S-nitrosothiol, S-nitroso-protein, nitroprusside, sydnonimines, furoxans, nitrosonium salts, and related compounds is used for the treatment or prevention of disease states resulting from hyperhomocysteinemia. The disease states include vascular, ocular, skeletal, neurological, and cytotoxicity disorders. In addition, nitrosating compounds may also be administered for the treatment or prevention of disease states resulting from other sulfur-containing amino acids, such as cysteine.
摘要翻译：使用亚硝化化合物如硝酸甘油，一氧化氮，S-亚硝基硫醇，S-亚硝基蛋白，硝普钠，sydnonimines，呋喃糖，亚硝基盐和相关化合物用于治疗或预防由高同型半胱氨酸血症引起的疾病状态。疾病状态包括血管，眼，骨骼，神经和细胞毒性障碍。此外，亚硝化化合物也可以用于治疗或预防由其它含硫氨基酸（例如半胱氨酸）引起的疾病状态。

8. 发明授权

US5356890A S-nitroso derivatives of ace inhibitors and the use thereof 失效
标题翻译： ace抑制剂的S-亚硝基衍生物及其用途
公开(公告)号：US5356890A
公开(公告)日：1994-10-18
申请号：US013404
申请日：1993-02-04
申请人： Joseph Loscalzo , John Cooke
发明人： Joseph Loscalzo , John Cooke
IPC分类号： C07D207/16 , A61K31/395 , A61K31/445 , A61K31/495 , C07D205/10 , C07D241/46
CPC分类号： C07D207/16
摘要： The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.
摘要翻译：本发明涉及ACE抑制剂的新S-亚硝基衍生物和包含本发明的S-亚硝基硫醇衍生物与药学上可接受的载体的药物组合物。本发明还涉及用于治疗各种病理生理状况的方法，包括急性心肌梗塞，无明显心力衰竭的左心室功能障碍，高血压，肺动脉高压，充血性心力衰竭，心绞痛，血管血栓形成，雷诺氏综合征，硬皮病，怀孕毒血症，急性肾脏失败，糖尿病性肾病和肾动脉狭窄，以及抑制ACE和影响血管舒张的方法，包括将本发明的ACE抑制剂的S-亚硝基硫代衍生物施用于动物。

9. 发明授权

US5187183A S-nitroso derivatives of ACE inhibitors and the use thereof 失效
标题翻译： ACE抑制剂的S-亚硝基衍生物及其用途
公开(公告)号：US5187183A
公开(公告)日：1993-02-16
申请号：US715588
申请日：1991-06-14
申请人： Joseph Loscalzo , John Cooke
发明人： Joseph Loscalzo , John Cooke
IPC分类号： C07D207/16
CPC分类号： C07D207/16
摘要： The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.
摘要翻译：本发明涉及ACE抑制剂的新S-亚硝基衍生物和包含本发明的S-亚硝基硫醇衍生物与药学上可接受的载体的药物组合物。本发明还涉及用于治疗各种病理生理状况的方法，包括急性心肌梗塞，无明显心力衰竭的左心室功能障碍，高血压，肺动脉高压，充血性心力衰竭，心绞痛，血管血栓形成，雷诺氏综合征，硬皮病，怀孕毒血症，急性肾脏失败，糖尿病性肾病和肾动脉狭窄，以及抑制ACE和影响血管舒张的方法，包括将本发明的ACE抑制剂的S-亚硝基硫代衍生物施用于动物。

10. 发明申请

US20070248676A1 Use of nitric oxide adducts 审中-公开
标题翻译：使用一氧化氮加合物
公开(公告)号：US20070248676A1
公开(公告)日：2007-10-25
申请号：US11819513
申请日：2007-06-27
申请人： Jonathan Stamler , Joseph Loscalzo , John Folts
发明人： Jonathan Stamler , Joseph Loscalzo , John Folts
IPC分类号： A61K33/00 , A61K31/04 , A61K31/195 , A61K38/16 , A61K39/00 , A61P7/00 , A61P9/00 , A61K9/10 , A61K38/43 , A61K33/26 , A61K31/4245
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： The invention provides 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; coated per se on a surface of the medical device; 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 locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.
摘要翻译：本发明提供一种通过向患者引入至少一部分包含预防或治疗量的一氧化氮加合物的装置来预防与患者使用医疗装置有关的不利影响的方法。一氧化氮加合物可以存在于医疗装置表面上的基质涂层中; 本身涂覆在医疗装置的表面上; 直接或间接地结合到医疗装置的表面上的反应性位点; 或者医疗装置的至少一部分可以由诸如聚合物的材料形成，其包括一氧化氮加合物。还公开了一种通过将所述装置与任何内部组织的接触部位局部施用一氧化氮加合物来预防与患者中使用医疗装置有关的不良作用的方法。

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