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1. 发明申请

US20080107637A1 Use of an agent that restores tissue perfusion and oxygenation 有权
公开(公告)号：US20080107637A1
公开(公告)日：2008-05-08
申请号：US12006842
申请日：2008-01-07
申请人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
发明人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
IPC分类号： A61K35/18 , A61K38/16 , A61K33/00 , A61P43/00 , A61K31/04
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.

2. 发明申请

US20080113901A1 Use of an agent that restores tissue perfusion and oxygenation 有权
标题翻译：使用恢复组织灌注和氧合的药物
公开(公告)号：US20080113901A1
公开(公告)日：2008-05-15
申请号：US12006849
申请日：2008-01-07
申请人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
发明人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
IPC分类号： A61K38/42 , A61P35/00
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。

3. 发明申请

US20060276374A1 Use of an agent that restores tissue perfusion and oxygenation 有权
公开(公告)号：US20060276374A1
公开(公告)日：2006-12-07
申请号：US11404494
申请日：2006-04-13
申请人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
发明人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
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.

4. 发明申请

US20060088942A1 Measuring nitric oxide in blood gases and treatments based thereon 审中-公开
标题翻译：测量血液中的一氧化氮及其处理
公开(公告)号：US20060088942A1
公开(公告)日：2006-04-27
申请号：US10516250
申请日：2003-05-27
申请人： Jonathan Stamler , Timothy McMahon
发明人： Jonathan Stamler , Timothy McMahon
IPC分类号： G01N33/50
CPC分类号： G01N33/84 , G01N33/4925
摘要： Nitric oxide is measured in blood as a marker of tissue blood flow and oxygenation. Where nitric oxide is measured to be below physiological or to be below average, in a patient having a disease associated with oxygen delivery deficiency, nitric oxide is infused alone or with nitrite. Where nitric oxide is measured to be normal, nitrite is infused. The storage time of whole blood or red blood cells is increased and the vasodilator response of outdated or NO depleted whole blood and red blood cells are increased by treatment with nitric oxide and/or nitrite. A patient in need of a transfusion is transfused with whole blood or red blood cells treated to increase vasodilator response therein.
摘要翻译：在血液中测量一氧化氮作为组织血流和氧合的标志物。当一氧化氮被测量为低于生理或低于平均值时，在具有与氧输送缺陷相关的疾病的患者中，一氧化氮单独或与亚硝酸盐注入。当一氧化氮测量正常时，输入亚硝酸盐。全血或红细胞的储存时间增加，通过用一氧化氮和/或亚硝酸盐处理可以增加过期或NO耗尽的全血和红细胞的血管扩张反应。需要输血的患者输入全血或红细胞，以增加血管扩张反应。

5. 发明申请

US20060024283A1 Red blood cells loaded with S-nitrosothiol and uses therefor 有权
标题翻译：装有S-亚硝基硫醇的红细胞并用于此
公开(公告)号：US20060024283A1
公开(公告)日：2006-02-02
申请号：US11179349
申请日：2005-07-12
申请人： Jonathan Stamler , Joseph Bonaventura , John Pawloski , Timothy McMahon
发明人： Jonathan Stamler , Joseph Bonaventura , John Pawloski , Timothy McMahon
IPC分类号： C12Q1/68 , A61K35/18
CPC分类号： A61K31/00 , A61K31/04 , A61K31/095 , A61K31/195 , A61K33/00 , A61K38/1816 , A61K47/54 , A61K47/6445 , A61K47/6901 , C07K14/00 , G01N21/631 , G01N21/76 , G01N33/721
摘要： Red blood cells can be loaded with low molecular weight nitrosylating agents, such as S-nitrosothiols, to act as a delivery system for NO+ groups to tissues. Loaded red blood cells can be used in methods of therapy for conditions which are characterized by abnormal O2 metabolism of tissues, oxygen-related toxicity, abnormal vascular tone, abnormal red blood cell adhesion, or abnormal O2 delivery by red blood cells. Such treatment of red blood cells can be extended to in vivo therapies, with the object to achieve an increase in the ratio of red blood cell S-nitrosothiol to hemoglobin.
摘要翻译：红细胞可以装载低分子量亚硝酰化剂，如S-亚硝基硫醇，作为组织的NO + +组的递送系统。加载的红细胞可以用于治疗方法，其特征在于组织的异常O 2代谢，氧相关毒性，异常血管紧张度，异常红细胞粘附或异常的O < 通过红细胞递送SUB> 2 。红细胞的这种治疗可以延伸到体内治疗，其目的是实现红细胞S-亚硝基硫醇与血红蛋白的比例的增加。

6. 发明申请

US20070092512A1 Preventing bacterial or viral infectivity and composition containing infection preventing additive 失效
标题翻译：预防细菌或病毒感染性和含有感染预防添加剂的组合物
公开(公告)号：US20070092512A1
公开(公告)日：2007-04-26
申请号：US11544559
申请日：2006-10-10
申请人： Yehia Daaka , Jonathan Stamler
发明人： Yehia Daaka , Jonathan Stamler
IPC分类号： A61K39/395 , A61K31/65
CPC分类号： C07K16/2863 , A61K31/65 , A61K2039/505 , C07K2317/77
摘要： A nitric oxide synthesis inhibitor or nitric oxide scavenger is administered to prevent development of infection, to prevent development of a cancer where overstimulation of a receptor contributes to the cancer development, and to prevent loss of beta agonist responsivity and as a treatment in combination with a receptor blocker. Compositions include nitric oxide synthesis inhibitor or nitric oxide scavenger containing spermicidal compositions, nasal steroid compositions, urinary tract infection prophylaxis compositions, compositions for prophylaxis of EGFR associated cancer and human blood component(s) composition for transfusion.
摘要翻译：施用一氧化氮合成抑制剂或一氧化氮清除剂以防止感染的发展，以防止受体过度刺激导致癌症发展的癌症的发展，并且防止β激动剂反应性的丧失以及作为与受体阻断剂。组合物包括一氧化氮合成抑制剂或含有杀精组合物的一氧化氮清除剂，鼻型类固醇组合物，尿路感染预防组合物，用于预防EGFR相关癌症的组合物和用于输血的人血液成分组合物。

7. 发明申请

US20070066546A1 Compositions for the reversible thioesterification of signaling proteins and methods of using same 有权
标题翻译：信号蛋白的可逆硫酯化的组合物及其使用方法
公开(公告)号：US20070066546A1
公开(公告)日：2007-03-22
申请号：US11488992
申请日：2006-07-18
申请人： Jonathan Stamler , Jordan Gutterman
发明人： Jonathan Stamler , Jordan Gutterman
IPC分类号： A61K31/704 , C07H15/24 , C12Q1/26 , C12P33/00 , C12N5/08 , C12N1/21
CPC分类号： A61K47/48246 , A61K38/00 , A61K47/64 , A61K47/65 , C07H15/24 , C07K1/1077 , C07K1/1133 , G01N33/5011 , G01N33/5023 , G01N33/5041 , Y02A50/473
摘要： Avicins and other thioesterification agents are used to modify cysteine groups of signaling proteins in order to modify their activity. Pathologies associated with signaling proteins which are regulatable through this method are treated using these thioesterification agents. These pathologies include those involving proteins which modulate physiologic redox status of organisms including arthersclerosis, cancer, bacterial infection, inflammation, and neurological disorders.
摘要翻译： Avicins和其他硫酯化试剂用于修饰信号蛋白的半胱氨酸基团以改变其活性。使用这些硫酯化试剂处理通过该方法可调节的与信号蛋白相关的病理学。这些病理学包括涉及调节生物体的生理氧化还原状态的蛋白质，包括硬脑膜炎，癌症，细菌感染，炎症和神经障碍。

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. 发明申请

US20060194820A1 Reactive oxygen generating enzyme inhibitor with nitric oxide bioactivity and uses thereof 有权
公开(公告)号：US20060194820A1
公开(公告)日：2006-08-31
申请号：US11430986
申请日：2006-05-10
申请人： Jonathan Stamler , Eric Toone , Joshua Hare
发明人： Jonathan Stamler , Eric Toone , Joshua Hare
IPC分类号： A61K31/519 , C07D487/02
CPC分类号： C07D487/04 , A61K31/519
摘要： A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle.

10. 发明申请

US20060100159A1 Preventing desensitization of receptors 审中-公开
公开(公告)号：US20060100159A1
公开(公告)日：2006-05-11
申请号：US11274047
申请日：2005-11-15
申请人： Jonathan Stamler , Robert Lefkowitz , Erin Whalen , Walter Koch , Claude Plantadosi
发明人： Jonathan Stamler , Robert Lefkowitz , Erin Whalen , Walter Koch , Claude Plantadosi
IPC分类号： A61K38/05
CPC分类号： A61K31/21 , A61K31/19 , A61K31/223 , A61K31/5377 , A61K38/063
摘要： Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

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