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1. 发明申请

WO0234705A3 C-NITROSO COMPOUNDS AND USE THEREOF 审中-公开
标题翻译： C-NITROSO化合物及其用途
公开(公告)号：WO0234705A3
公开(公告)日：2002-07-11
申请号：PCT/US0127734
申请日：2001-09-27
申请人： UNIV DUKE , STAMLER JONATHAN S , TOONE ERIC J
发明人： STAMLER JONATHAN S , TOONE ERIC J
IPC分类号： A61K31/00 , A61K31/194 , A61K31/195 , A61K31/222 , A61K31/553 , A61K31/635 , A61K38/00 , A61L27/00 , A61L31/00 , A61P7/02 , A61P9/10 , A61P29/00 , A61P31/04 , A61P31/12 , C07C207/00 , C07C291/08 , C07D231/12 , C07D267/04 , C07C201/00 , C07D207/46
CPC分类号： C07C207/00 , A61K31/00 , A61K31/195 , A61K2300/00
摘要： A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.
摘要翻译：一种分子量范围为225〜1000（口服给药的225〜600）的C-亚硝基化合物，其中亚硝基连接到叔碳上，其通过具有pKa的碳酸的亚硝化而得到小于约25，可用作NO供体。当化合物从pKa小于约10的碳酸获得时，当以微摩尔浓度使用时，其提供血管松弛效果，并且该活性由以纳摩尔浓度获得的谷胱甘肽加强。当化合物由pKa为约15至20的碳酸获得时，在没有谷胱甘肽的纳摩尔浓度下获得血管松弛效果。在另一个实施方案中，生物相容性聚合物包含C-亚硝基部分。

2. 发明申请

WO03092763A8 CARBON NANOTUBULES FOR STORAGE OF NITRIC OXIDE 审中-公开
标题翻译：用于储存氧化氮的碳纳米管
公开(公告)号：WO03092763A8
公开(公告)日：2004-07-01
申请号：PCT/US0313289
申请日：2003-05-01
申请人： UNIV DUKE , TOONE ERIC J , STAMLER JONATHAN S
发明人： TOONE ERIC J , STAMLER JONATHAN S
IPC分类号： A61K33/00 , A61K45/06 , A61L29/10 , A61L29/16 , A61L31/08 , A61L31/16 , A61L29/12 , A61L29/14 , A61L31/12 , A61L31/14 , A61L33/00 , A61L33/02
CPC分类号： A61K33/00 , A61K45/06 , A61L29/103 , A61L29/16 , A61L31/084 , A61L31/16 , A61L2300/114 , A61L2300/416 , A61L2300/432 , A61L2300/45 , A61L2300/624
摘要： Delivering nitric oxide to a treatment site, such as in the area of an implanted stent, over a period of hours or days is desirable; however, the storage and release of nitric oxide in medically-relevant situations and amounts is a challenge, in part due to the gaseous nature of nitric oxide and its instability in the presence of oxygen, The present invention provides a method of preparing compositions of matter, particularly those comprising nanotubules, containing nitric oxide or gases with nitric oxide-like biological activity, where the gas is non-covalently bound to the composition. These compositions allow for the storage of nitric oxide or a related gas, followed by controlled release of the gas. Compositions disclosed in the present invention include polymers, articles, pills, capsules, and medical devices.
摘要翻译：将一氧化氮递送至治疗部位，例如在植入支架的区域中，需要数小时或数天的时间; 然而，一氧化氮在医学上相关的情况和量的储存和释放是一个挑战，部分是由于一氧化氮的气体性质及其在氧气存在下的不稳定性。本发明提供一种制备物质组合物的方法，特别是那些包含一氧化氮或具有一氧化氮样生物活性的气体的纳米管，其中气体非共价结合组合物。这些组合物允许存储一氧化氮或相关气体，随后控制释放气体。本发明公开的组合物包括聚合物，制品，丸剂，胶囊和医疗装置。

3. 发明申请

WO2004054433A3 FORMING IRON NITROSYL HEMOGLOBIN 审中-公开
标题翻译：形成铁硝酸盐HEMOGLOBIN
公开(公告)号：WO2004054433A3
公开(公告)日：2005-09-09
申请号：PCT/US0337081
申请日：2003-12-10
申请人： UNIV DUKE , MONTANA STATE UNIVERSITY BOZEMAN , STAMLER JONATHAN S , SINGEL DAVID J
发明人： STAMLER JONATHAN S , SINGEL DAVID J
IPC分类号： A01N1/02 , A61B20060101 , A61B1/00 , A61K35/14 , A61K38/16 , A61M1/02 , A61M1/36 , C07K14/805
CPC分类号： C07K14/805
摘要： Contrary to current opinion that nitrite in general oxidizes hemoglobin with elimination of active nitric oxide, deoxygenated hemoglobin reacts with low concentration inorganic nitrite to produce very stable iron nitrosyl hemoglobin which on delivery into the body is converted to a hemoglobin capable of nitric oxide delivery and provides vasodilator and antiplatelet activity. This provides basis for ameliorated risk blood product transfusions.
摘要翻译：与目前的观点相反，亚硝酸盐一般通过消除活性一氧化氮氧化血红蛋白，脱氧血红蛋白与低浓度无机亚硝酸盐反应，产生非常稳定的亚硝酰基血红蛋白，其在输送到体内被转化为能够一氧化氮递送的血红蛋白，并提供血管扩张剂和抗血小板活性。这为改善风险的血液制品输血提供依据。

4. 发明申请

WO0002580A3 THERAPIES USING HEMOPROTEINS 审中-公开
标题翻译：使用HEMOPROTEINS的治疗方法
公开(公告)号：WO0002580A3
公开(公告)日：2000-04-20
申请号：PCT/US9915487
申请日：1999-07-09
申请人： UNIV DUKE , STAMLER JONATHAN S , HAUSLADEN ALFRED
发明人： STAMLER JONATHAN S , HAUSLADEN ALFRED
IPC分类号： A61K38/41 , A61K38/42 , A61K38/50 , A61K31/155 , A61K31/17 , A61K31/195 , A61K31/415
CPC分类号： A61K38/50 , A61K38/41 , A61K38/42 , A61K31/70 , A61K2300/00
摘要： Herein it is shown that hemoproteins (e.g.Ascaris hemoglobin, myoglobin, flavohemoglobins) have NO-consuming and deoxygenase activities. The invention provides a method of reducing the concentration of oxygen and/or nitric oxide in a mammal. The method of the invention comprises administering a therapeutically effective amount of a hemoprotein having NO-activated deoxygenase activity or an enzymatically active fragment thereof to a mammal. The method can be used to treat a mammal having pathologically proliferating cells, such as a tumor. The invention further provides a method of treating a mammal infected with Ascaris sp., comprising administering to said mammal a therapeutically effective amount of an inhibitor of NO-synthase. The NO-consuming activity of a hemeprotein (e.g. flavohemoglobin) can be used in a treatment where constriction of blood vessels is desirabel, or where it is otherwise desirable to reduce NO concentration, as inflammation.
摘要翻译：在本文中，显示血蛋白（例如阿司匹林血红蛋白，肌红蛋白，黄素血红蛋白）具有消耗氧化和脱氧酶活性。本发明提供了降低哺乳动物氧和/或一氧化氮浓度的方法。本发明的方法包括向哺乳动物施用治疗有效量的具有NO活化的脱氧酶活性的血液蛋白或其酶活性片段。该方法可用于治疗具有病理增殖细胞（例如肿瘤）的哺乳动物。本发明还提供了一种治疗感染蛔虫感染的哺乳动物的方法，包括向所述哺乳动物施用治疗有效量的NO合成酶抑制剂。血液蛋白（例如黄体血红蛋白）的消耗NO消耗活性可以用于血管缩窄取消的治疗，或其它方面希望降低NO浓度的炎症。

5. 发明申请

WO2005000229A3 COMPOSITIONS AND METHODS FOR MODULATING S-NITROSOGLUTATHIONE REDUCTASE 审中-公开
标题翻译：用于调节S-硝基脱氨酶的组合物和方法
公开(公告)号：WO2005000229A3
公开(公告)日：2007-04-05
申请号：PCT/US2004017758
申请日：2004-06-04
申请人： UNIV DUKE , STAMLER JONATHAN S , LIMIN LIN
发明人： STAMLER JONATHAN S , LIMIN LIN
IPC分类号： C12N5/00 , A01N37/18 , A61K20060101 , A61K31/198 , A61K38/18 , A61K48/00 , C12N3/00
CPC分类号： G01N33/573 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/035 , A61K31/155 , A61K31/41 , A61K38/44 , C12N9/0008 , C12N15/8509 , C12Q1/26 , C12Y102/01046 , G01N2333/90212 , G01N2800/00 , A61K2300/00
摘要： Disclosed herein are methods and compositions for modulating the levels and/or activity of S-nitrosoglutathione reductase (GSNOR) in vivo or in
摘要翻译：本文公开了用于在体内或在体内调节S-亚硝基谷胱甘肽还原酶（GSNOR）的水平和/或活性的方法和组合物

6. 发明申请

WO2006113540A2 USE OF AN AGENT THAT RESTORES TISSUE PERFUSION AND OXYGENATION 审中-公开
标题翻译：使用恢复组织灌注和氧化的药剂
公开(公告)号：WO2006113540A2
公开(公告)日：2006-10-26
申请号：PCT/US2006014257
申请日：2006-04-13
申请人： UNIV DUKE , DEWHIRST MARK W , STAMLER JONATHAN S , MCMAHON TIMOTHY J , SONVEAUX PIERRE
发明人： DEWHIRST MARK W , STAMLER JONATHAN S , MCMAHON TIMOTHY J , SONVEAUX PIERRE
IPC分类号： A61K38/42 , A61K31/21
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.
摘要翻译：目前公开的主题提供了在受试者的组织的缺氧区域中增加灌注的方法。还提供了用于治疗受试者与缺氧相关的疾病和/或病症的方法，用于增加肿瘤对放射和/或化疗治疗的敏感性的方法，用于延迟受试者的肿瘤生长的方法，以及用于抑制受试者的肿瘤血管生长的方法。在一些实施方案中，本发明公开的方法包括向有需要的受试者施用选自亚硝基化血红蛋白和诱导受试者内源性血红蛋白亚硝基化的试剂的第一组合物和包含高氧气体的第二组合物。在一些实施方案中，本发明公开的方法还包括用放射治疗，化疗，光动力疗法，免疫治疗或其组合治疗肿瘤。还提供了可在本公开的方法中使用的可吸入气体。

7. 发明申请

WO2004004664A3 METHODS FOR TREATING OR PREVENTING ISCHEMIC INJURY 审中-公开
标题翻译：治疗或预防缺血性损伤的方法
公开(公告)号：WO2004004664A3
公开(公告)日：2004-07-29
申请号：PCT/US0321828
申请日：2003-07-08
申请人： UNIV DUKE , STAMLER JONATHAN S
发明人： STAMLER JONATHAN S
IPC分类号： A61K38/18 , A61K38/26 , A61K38/00 , A61K38/16 , A61K38/24
CPC分类号： A61K38/1816 , A61K38/26 , A61K2300/00
摘要： A therapeutic or prophylactic treatment method of myocardial ischemia, such as due to myocardial infarction, by administering erythropoietin, alone or in combination with other drugs, to a patient suffering from or at risk of cardiac injury, such as myocardial ischemia. The erythropoietin is administered in a concentration such that the subject's hematocrit level or production of red blood cells is not significantly affected.
摘要翻译：通过将促红细胞生成素单独或与其他药物联合给予患有心肌损伤或有心肌损伤危险的患者如心肌缺血等心肌缺血的治疗或预防性治疗方法，例如心肌梗塞。促红细胞生成素以这样的浓度施用，使得受试者的血细胞比容水平或红细胞产量不受显着影响。

8. 发明申请

WO2010117423A2 A METHOD FOR TREATING A PATIENT HAVING OR AT RISK FOR DEVELOPING A DISORDER ASSOCIATED WITH DECREASED EXPRESSION OF ß2 ADRENERGIC RECEPTORS OR NEED FOR INCREASED ß2 ADRENERGIC RECEPTOR ACTIVITY 审中-公开
标题翻译：用于治疗患有或有风险的患者的方法用于发展与β2ADRENERGIC受体的减少表达相关的疾病或需要增加的β2ADRENERGIC受体活性
公开(公告)号：WO2010117423A2
公开(公告)日：2010-10-14
申请号：PCT/US2010000956
申请日：2010-03-31
申请人： UNIV DUKE , STAMLER JONATHAN S , XIE LIANG
发明人： STAMLER JONATHAN S , XIE LIANG
IPC分类号： A61K48/00
CPC分类号： A61K31/00 , A61K31/198 , A61K45/06
摘要： This present invention relates to methods, compositions, and kits useful for treating a patient having or at risk for developing a disorder associated with decreased expression of ß2 adrenergic receptors or need for increased ß2 adrenergic receptor activity.
摘要翻译：本发明涉及可用于治疗患有或具有发展与β2肾上腺素能受体表达降低相关的病症或有风险的患者或需要增加β2肾上腺素能受体活性的患者的方法，组合物和试剂盒。

9. 发明申请

WO2005034860A3 THIOL REACTIVE AGENTS AS A THERAPEUTIC MODALITY 审中-公开
标题翻译： THIOL反应剂作为治疗模式
公开(公告)号：WO2005034860A3
公开(公告)日：2006-10-19
申请号：PCT/US2004032180
申请日：2004-10-01
申请人： UNIV DUKE , STAMLER JONATHAN S
发明人： STAMLER JONATHAN S
IPC分类号： A61K31/00 , A61K20060101 , A61K31/195 , A61K38/05
CPC分类号： A61K33/00 , A61K31/12 , A61K31/145 , A61K31/195 , A61K31/444 , A61K31/52 , A61K38/063
摘要： A patient with a disease associated with a receptor having a cysteine residue is treated with a thiol reactive agent. The diseases include neurodegenerative diseases. Diseases characterized by skeletal muscle atrophy are also treated.
摘要翻译：患有与具有半胱氨酸残基的受体相关的疾病的患者用硫醇反应剂处理。这些疾病包括神经变性疾病。也可以治疗以骨骼肌萎缩为特征的疾病。

10. 发明申请

WO0109616A3 METHOD FOR DETERMINING PHYSIOLOGICAL EFFECTS OF HEMOGLOBIN 审中-公开
标题翻译：确定血红蛋白生理影响的方法
公开(公告)号：WO0109616A3
公开(公告)日：2001-11-15
申请号：PCT/US0021101
申请日：2000-08-02
申请人： UNIV DUKE , UNIV MONTANA RES DEV INST , STAMLER JONATHAN S , GOW ANDREW J , SINGEL DAVID J
发明人： STAMLER JONATHAN S , GOW ANDREW J , SINGEL DAVID J
IPC分类号： A61K31/00 , A61K31/04 , A61K31/12 , A61K31/122 , A61K31/18 , A61K31/255 , A61K31/26 , A61K31/381 , A61K31/382 , A61K31/433 , A61K31/465 , A61K31/519 , A61K33/22 , A61K33/26 , A61K33/42 , A61K35/18 , A61K38/42 , G01N33/72 , A61P7/00
CPC分类号： G01N33/721 , A61K31/00 , A61K31/04 , A61K31/12 , A61K31/122 , A61K31/18 , A61K31/255 , A61K31/26 , A61K31/381 , A61K31/382 , A61K31/433 , A61K31/465 , A61K31/519 , A61K33/22 , A61K33/26 , A61K33/42 , A61K35/18 , A61K38/42 , G01N2333/805 , A61K2300/00
摘要： NO preferentially binds to the minor population of the hemoglobin's vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. The distribution of minor forms of hemoglobin can be tested and the results can be used to predict whether a composition of hemoglobin will scavenge, load, eliminate, or donate NO. Hemoglobin thus serves to regulate the chemistry of NO. SNO-hemoglobin transfers NO equivalents to the red blood cell anion transport protein AE1, which serves to export NO from red blood cells. Regulation of AE1 function is the basis for methods of therapy to affect levels of NO or its biological equivalent.
摘要翻译： NO以合作方式优先结合血红蛋白空白血红素的次要群体，亚硝基化血红蛋白硫醇，或与溶液中释放的超氧化物反应。可以测试次要形式血红蛋白的分布，结果可用于预测血红蛋白的组成将清除，加载，消除或捐赠NO。血红蛋白因此用于调节NO的化学性质。 SNO-血红蛋白将红细胞阴离子转运蛋白AE1的NO等价物转移，其用于从红细胞中输出NO。 AE1功能的调节是治疗方法影响NO或其生物等效水平的基础。

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