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1. 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。

2. 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.

3. 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。

4. 发明授权

US07157500B2 Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality 失效
标题翻译：蛋白质SH基团和氨基酸残基的亚硝化作为治疗方式
公开(公告)号：US07157500B2
公开(公告)日：2007-01-02
申请号：US10216865
申请日：2002-08-13
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： A01N33/18
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.
摘要翻译：蛋白质和氨基酸基团的亚硝化可以选择性调节蛋白质功能，并赋予蛋白质和氨基酸更多的平滑肌松弛剂和血小板抑制能力。因此，本发明涉及通过蛋白质硫醇的亚硝基化实现的新化合物。这些化合物包括：S-亚硝基-t-PA，S-亚硝基组织蛋白酶; S-亚硝基脂蛋白; 和S-亚硝基 - 免疫球蛋白。本发明还涉及S-亚硝基蛋白化合物用于调节蛋白质功能，细胞代谢和影响血管舒张，血小板抑制，非血管平滑肌松弛以及通过血红蛋白和肌红蛋白增加血氧转运的治疗用途。这些化合物也用于以最具生物活性的形式递送一氧化氮，以达到上述效果，或用于身体中存在的分子的体外亚硝基化。本发明还涉及存在于蛋白质和氨基酸上的氧，碳和氮部分的亚硝基化，以及其用于实现上述生理作用的用途。

5. 发明授权

US5648393A Treatment of male impotence with s-nitrosylated compounds 失效
标题翻译：用s-亚硝基化化合物治疗男性阳。
公开(公告)号：US5648393A
公开(公告)日：1997-07-15
申请号：US297698
申请日：1994-08-29
申请人： Jonathan Stamler , Joseph Loscalzo , Adam Slivka , Daniel Simon , Robert Brown , Jeffrey Drazen
发明人： Jonathan Stamler , Joseph Loscalzo , Adam Slivka , Daniel Simon , Robert Brown , Jeffrey Drazen
IPC分类号： A61K38/00 , C07C381/00 , C07K5/02 , A61K31/195 , A61K31/13
CPC分类号： C07C381/00 , C07K5/0215 , A61K38/00
摘要： Methods of relaxing corpus cavernosum smooth muscle, treating disease states responsive to prevention or relaxation of undesirable contractions of corpus cavernosum smooth muscle and of treating male impotence by administering an S-nitrosothiol such as a low molecular weight S-nitrosothiol, S-nitroso-ACE-inhibitor or S-nitroso-protein.
摘要翻译：放松海绵体平滑肌的方法，通过施用S-亚硝基硫醇如低分子量S-亚硝基硫醇，S-亚硝基ACE，治疗响应于预防或放松海绵体平滑肌不期望的收缩和治疗男性阳states的疾病状态抑制剂或S-亚硝基蛋白。

6. 发明授权

US5593876A Nitrosylation of protein SH groups and amino acid residues as a therapeutic modality 失效
标题翻译：蛋白质SH基团和氨基酸残基的亚硝化作为治疗方式
公开(公告)号：US5593876A
公开(公告)日：1997-01-14
申请号：US287830
申请日：1994-08-09
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： 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 , C12N9/96
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.
摘要翻译：蛋白质和氨基酸基团的亚硝化可以选择性调节蛋白质功能，并赋予蛋白质和氨基酸更多的平滑肌松弛剂和血小板抑制能力。因此，本发明涉及通过蛋白质硫醇的亚硝基化实现的新化合物。这些化合物包括：S-亚硝基-t-PA，S-亚硝基组织蛋白酶; S-亚硝基脂蛋白; 和S-亚硝基 - 免疫球蛋白。本发明还涉及S-亚硝基蛋白化合物用于调节蛋白质功能，细胞代谢和影响血管舒张，血小板抑制，非血管平滑肌松弛以及通过血红蛋白和肌红蛋白增加血氧转运的治疗用途。这些化合物也用于以最具生物活性的形式递送一氧化氮，以达到上述效果，或用于身体中存在的分子的体外亚硝基化。本发明还涉及存在于蛋白质和氨基酸上的氧，碳和氮部分的亚硝基化，以及其用于实现上述生理作用的用途。

7. 发明授权

US06174539B1 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：US06174539B1
公开(公告)日：2001-01-16
申请号：US09433550
申请日：1999-11-04
申请人： Jonathan Stamler , Joseph Loscalzo , John D. Folts
发明人： Jonathan 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.
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。

8. 发明授权

US5459076A Method for detecting nitric oxide, nitrosonium equivalents, S-nitrosothiols and S-nitroso-proteins in biological systems 失效
标题翻译：在生物系统中检测一氧化氮，亚硝鎓等价物，S-亚硝基硫醇和S-亚硝基蛋白的方法
公开(公告)号：US5459076A
公开(公告)日：1995-10-17
申请号：US872237
申请日：1992-04-22
申请人： Jonathan Stamler , Joseph Loscalzo
发明人： Jonathan Stamler , Joseph Loscalzo
IPC分类号： G01N21/76 , G01N21/63 , G01N30/74 , G01N30/84 , G01N30/88 , G01N33/52 , G01N33/68 , G01N33/00
CPC分类号： G01N30/84 , G01N21/631 , G01N33/68 , G01N2030/8441 , G01N2030/8813 , G01N2030/8831 , G01N30/74 , Y10T436/17 , Y10T436/170769 , Y10T436/176152 , Y10T436/177692
摘要： Nitric oxide, nitrosonium, S-nitrosothiols, and S-nitroso-proteins can be detected in biological samples, using a method which involves injection of samples into a photolysis cell, prior to detection of chemiluminescence generated by the reaction between nitric oxide and ozone. To detect S-nitrosothiols and S-nitroso-proteins separate aliquots of the same samples are subjected to pretreatment with mercurous ion, and a protein-precipitating agent, respectively, and the resulting nitric oxide signals are compared to those generated by untreated samples. This method is useful for monitoring the levels of nitric oxide bioactivity in both normal physiological states, and disease states, such as septic shock, atherosclerosis, thrombosis, hyperhomocysteinemia, pulmonary hypertension, malignancy, infections and central nervous systems disorders.
摘要翻译：在检测由一氧化氮和臭氧之间的反应产生的化学发光之前，可以使用涉及将样品注入光解细胞的方法在生物样品中检测到一氧化氮，亚硝鎓，S-亚硝基硫醇和S-亚硝基蛋白。为了检测S-亚硝基硫醇和S-亚硝基蛋白，分别将相同样品的等分试样分别用炔属离子和蛋白沉淀剂进行预处理，并将所得一氧化氮信号与未处理样品产生的一氧化氮信号进行比较。该方法可用于监测正常生理状态和疾病状态（如败血性休克，动脉粥样硬化，血栓形成，高同型半胱氨酸血症，肺动脉高压，恶性肿瘤，感染和中枢神经系统疾病）中一氧化氮生物活性的水平。

9. 发明授权

US5380758A S-nitrosothiols as smooth muscle relaxants and therapeutic uses thereof 失效
标题翻译： S-亚硝基硫醇作为平滑肌松弛剂及其治疗用途
公开(公告)号：US5380758A
公开(公告)日：1995-01-10
申请号：US943834
申请日：1992-09-14
申请人： Jonathan Stamler , Joseph Loscalzo , Adam Slivka , Daniel Simon , Robert Brown , Jeffrey Drazen
发明人： Jonathan Stamler , Joseph Loscalzo , Adam Slivka , Daniel Simon , Robert Brown , Jeffrey Drazen
IPC分类号： A61K38/00 , C07C381/00 , C07K5/02 , A61K31/195
CPC分类号： C07C381/00 , C07K5/0215 , A61K38/00
摘要： S-nitrosothiols exert a potent relaxant effect, mediated both by guanylate cyclase, and a cGMP-independent mechanism, upon non-vascular smooth muscle. Such types of smooth muscle include airway, gastrointestinal, bladder, uterine and corpus cavernosal. Thus, S-nitrosothiols may be used for the treatment or prevention of disorders associated with relaxation of smooth muscle, such as airway obstruction, and other respiratory disorders, bladder dysfunction, premature labor and impotence. Additionally, S-nitrosothiols may be used to alleviate smooth muscle contraction and spasm, and thus facilitate procedures involving diagnostic instrumentation, such as endoscopy, bronchoscopy, laparoscopy and cystoscopy. S-nitrosothiols also increase the binding affinity between hemoglobin and oxygen, and therefore, may be used to improve hemoglobin-oxygen binding, and oxygen transport to bodily tissues.
摘要翻译：在非血管平滑肌上，S-亚硝基硫醇发挥强效的松弛作用，由鸟苷酸环化酶和cGMP非依赖性机制介导。平滑肌的这种类型包括气道，胃肠道，膀胱，子宫和海绵体。因此，S-亚硝基硫醇可用于治疗或预防与平滑肌松弛相关的疾病，例如气道阻塞和其它呼吸障碍，膀胱功能障碍，早产和阳。。此外，S-亚硝基硫醇可用于缓解平滑肌收缩和痉挛，从而促进涉及诊断仪器的手术，如内窥镜检查，支气管镜检查，腹腔镜检查和膀胱镜检查。 S-亚硝基硫醇还增加血红蛋白和氧之间的结合亲和力，因此可用于改善血红蛋白 - 氧结合，以及氧输送到身体组织。

10. 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.

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