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21. 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。

22. 发明申请

US20080299542A1 IDENTIFICATION OF OXIDATIVELY MODIFIED PEPTIDE SEQUENCES IN THE PROTEOME (LOSCALZO) 审中-公开
标题翻译：氧化修饰的肽段序列的鉴定（LOSCALZO）
公开(公告)号：US20080299542A1
公开(公告)日：2008-12-04
申请号：US12120501
申请日：2008-05-14
申请人： Joseph Loscalzo
发明人： Joseph Loscalzo
IPC分类号： C12Q1/00 , G01N33/00
CPC分类号： G01N33/68
摘要： The invention relates, in part, to identifying protein target(s) that undergo oxidative modification and the specific peptide sequences bearing oxidation-induced modifications.
摘要翻译：本发明部分地涉及鉴定经历氧化修饰的蛋白质靶标和具有氧化诱导修饰的特异性肽序列。

23. 发明申请

US20060211601A1 Nitrosated and nitrosylated heme proteins 审中-公开
公开(公告)号：US20060211601A1
公开(公告)日：2006-09-21
申请号：US11349178
申请日：2006-02-08
申请人： Jonathan Stamler , Joseph Loscalzo
发明人： Jonathan Stamler , Joseph Loscalzo
IPC分类号： A61K38/42 , C07K14/805
CPC分类号： A61K38/42 , C07K1/1077 , C07K14/3153 , C07K14/4702 , C07K14/76 , C07K14/765 , C07K14/775 , C07K14/805 , C07K16/00 , C12N9/6459 , C12N9/6472 , C12Y304/21069 , Y10S514/832 , Y10S530/829 , A61K2300/00
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-heme proteins, S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoproteins; and S-nitroso-immunoglobulins. The invention also relates to therapeutic use if 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.

24. 发明授权

US07033999B2 Nitrosated and nitrosylated heme proteins 失效
公开(公告)号：US07033999B2
公开(公告)日：2006-04-25
申请号：US10413220
申请日：2003-04-15
申请人： Jonathan Stamler , Joseph Loscalzo
发明人： Jonathan Stamler , Joseph Loscalzo
IPC分类号： A61K38/16 , A61K38/48 , A61K31/445 , A61K31/16 , C07K14/805
CPC分类号： A61K38/42 , C07K1/1077 , C07K14/3153 , C07K14/4702 , C07K14/76 , C07K14/765 , C07K14/775 , C07K14/805 , C07K16/00 , C12N9/6459 , C12N9/6472 , C12Y304/21069 , Y10S514/832 , Y10S530/829 , A61K2300/00
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-heme proteins, S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoproteins; and S-nitroso-immunoglobulins. The invention also relates to therapeutic use if 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.

25. 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.

26. 发明授权

US06562344B1 Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality 失效
公开(公告)号：US06562344B1
公开(公告)日：2003-05-13
申请号：US08437884
申请日：1995-05-09
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： A61K3940
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.

27. 发明授权

US06352709B1 Localized use of nitric oxide-adducts to prevent internal tissue damage 失效
标题翻译：局部使用一氧化氮加合物以防止内部组织损伤
公开(公告)号：US06352709B1
公开(公告)日：2002-03-05
申请号：US09661190
申请日：2000-09-13
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： A61F200
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.
摘要翻译：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防止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; 可以本身涂覆在医疗装置的表面上; 可以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。还公开了一种用于通过在医疗过程中引入该装置以及在该过程之前或期间，在患者中预防与使用该医疗装置有关的不利影响的方法，该方法是将所述装置的接触部位的一氧化氮加合物局部施用于任何内部组织。

28. 发明授权

US06255277B1 Localized use of nitric oxide-adducts to prevent internal tissue damage 失效
标题翻译：局部使用一氧化氮加合物以防止内部组织损伤
公开(公告)号：US06255277B1
公开(公告)日：2001-07-03
申请号：US08438418
申请日：1995-05-10
申请人： Jonathan Stamler , Joseph Loscalzo , John D. Folts
发明人： Jonathan Stamler , Joseph Loscalzo , John D. Folts
IPC分类号： A61K3816
CPC分类号： B82Y30/00 , A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K31/21 , A61K31/275 , A61K31/295 , A61K31/41 , A61K31/535 , A61K33/00 , A61K38/1709 , A61K38/38 , A61K38/49 , A61K38/556 , A61K45/06 , A61K47/52 , A61K47/62 , A61K47/6957 , A61L33/0011 , Y10S514/822 , Y10S514/824
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.
摘要翻译：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防止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; 可以本身涂覆在医疗装置的表面上; 可以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。还公开了一种用于通过在医疗过程中引入该装置以及在该过程之前或期间，在患者中预防与使用该医疗装置有关的不利影响的方法，该方法是将所述装置的接触部位的一氧化氮加合物局部施用于任何内部组织。

29. 发明授权

US5863890A Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality 失效
公开(公告)号：US5863890A
公开(公告)日：1999-01-26
申请号：US907217
申请日：1997-08-06
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： A61K35/14 , A61K38/00 , A61K38/02 , A61K38/16 , A61K38/38 , A61K38/42 , A61K38/46 , A61K38/49 , A61K39/395 , A61P9/00 , C07K1/06 , C07K1/107 , C07K14/00 , C07K14/315 , C07K14/47 , C07K14/76 , C07K14/765 , C07K14/805 , C07K16/00 , C07K16/18 , C12N9/00 , C12N9/48 , C12N9/64 , C12N9/70 , C12N9/72 , A61K38/17 , C07K1/113
CPC分类号： C12N9/6472 , C07K1/1077 , C07K14/3153 , C07K14/4702 , C07K14/76 , C07K14/765 , C07K14/805 , C07K16/00 , C12N9/6459 , C12Y304/21069 , A61K38/00
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.

30. 发明授权

US5346599A Capillary zone electrophoretic detection of biological thiols and their S-nitrosated and oxidized derivatives 失效
标题翻译：毛细管电泳检测生物硫醇及其S-亚硝基化和氧化衍生物
公开(公告)号：US5346599A
公开(公告)日：1994-09-13
申请号：US9469
申请日：1993-01-26
申请人： Jonathan Stamler , Joseph Loscalzo
发明人： Jonathan Stamler , Joseph Loscalzo
IPC分类号： G01N27/447 , G01N27/26
CPC分类号： G01N27/447
摘要： Individual thiols present in a biological sample are separated and identified using capillary electrophoresis. S-nitrosated and oxidized derivatives of thiols are also detected using capillary electrophoresis. In addition, capillary electrophoresis may be performed on samples which have been treated with an acid, so as to achieve a pH between 2.0 and 6.8, in order to further enhance detection. Separation and detection of S-nitrosated derivatives of thiols provides a means for monitoring the extent of a disease state associated with abnormal levels of nitric oxide. Such disease states include septic shock, cardiogenic shock, hypovolemic shock, atherosclerosis, hyperhomocysteinemia, venous thrombosis, arterial thrombosis, coronary occlusion, pulmonary embolism, cerebrovascular accidents, vascular fibrosis, ectopia lentis, osteoporosis, mental retardation, skeletal deformities, pulmonary hypertension, malignancy, infections and central nervous system disorders.
摘要翻译：使用毛细管电泳分离和鉴定存在于生物样品中的单个硫醇。也使用毛细管电泳检测硫醇的S-亚硝基化和氧化衍生物。此外，为了进一步增强检测，可以对已经用酸处理的样品进行毛细管电泳，以达到2.0至6.8之间的pH。硫醇的S-亚硝基化衍生物的分离和检测提供了监测与一氧化氮异常水平相关的疾病状态的程度的手段。这种疾病状态包括脓毒性休克，心源性休克，低血容量性休克，动脉粥样硬化，高同型半胱氨酸血症，静脉血栓形成，动脉血栓形成，冠状动脉闭塞，肺栓塞，脑血管意外，血管纤维化，胰岛异位症，骨质疏松症，精神发育迟滞，骨骼畸形，肺动脉高压，恶性肿瘤，感染和中枢神经系统疾病。

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