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    METHODS OF TREATMENT FOR HEMOLYSIS
    4.
    发明申请
    METHODS OF TREATMENT FOR HEMOLYSIS 有权
    用于溶解的治疗方法

    公开(公告)号：US20100239692A1

    公开(公告)日：2010-09-23

    申请号：US12678539

    申请日：2008-09-19

    申请人： Daniel B. Kim-Shapiro ,  S. Bruce King ,  Daniel A. Sweeney ,  Mark T. Gladwin

    发明人： Daniel B. Kim-Shapiro ,  S. Bruce King ,  Daniel A. Sweeney ,  Mark T. Gladwin

    IPC分类号： A61K33/00 ,  A61K31/185 ,  A61P7/04

    CPC分类号： A61K31/58 ,  Y02A50/411

    摘要： Provided herein are methods of treating hemolysis by administering an active compound in an amount sufficient to treat said hemolysis. It has been found that nitroxyl donors or similar compounds preferentially react with cell-free OxyHb, as compared to OxyHb encapsulated in a red blood cell, and reacts with MetHb to form iron-nitrosyl Hb or nitrite bound MetHb. It has also been found that such compounds reduce cell-free Hb and hemolysis. Active compounds are also contemplated for use in combination therapies, for example, in combination with the administration of red blood cells and/or an agent that promotes hematopoiesis, or in combination with the administration of a nitric oxide donor.

    摘要翻译： 本文提供了通过施用足以治疗所述溶血的量的活性化合物来治疗溶血的方法。 已经发现，与包封在红细胞中的OxyHb相比，硝酰基供体或类似化合物优先与无细胞的OxyHb反应，并与MetHb反应形成亚硝酰基Hb或亚硝酸盐结合的MetHb。 还已经发现，这些化合物减少无细胞的Hb和溶血。 还考虑活性化合物用于组合疗​​法，例如与施用红细胞和/或促进造血作用的药剂组合，或与施用一氧化氮供体组合使用。

    COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARBOXYHEMOGLOBINEMIA
    6.
    发明申请
    COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARBOXYHEMOGLOBINEMIA 审中-公开
    用于治疗羧基血红蛋白的组合物和方法

    公开(公告)号：US20160039910A1

    公开(公告)日：2016-02-11

    申请号：US14776363

    申请日：2014-03-11

    申请人： Mark T. GLADWIN ,  Jesus TEJERO BRAVO

    发明人： Mark T. Gladwin ,  Jesus Tejero Bravo

    IPC分类号： C07K14/795 ,  A61K9/00 ,  A61K38/41

    摘要： Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.

    摘要翻译： 本文描述的是用于从血红蛋白（包括脑，心脏和红细胞血红蛋白）中快速消除一氧化碳的新的解毒剂。 所公开的治疗涉及使用修饰的人球蛋白，特别是在残基64处修饰的神经球蛋白和在残基81修饰的细胞球蛋白，其以极高的亲和力结合一氧化碳。 单体突变体珠蛋白注入血液，其中它们快速且不可逆地螯合一氧化碳，从而限制一氧化碳对细胞呼吸和氧气运输和利用的毒性作用。

    TREATMENT OF SPECIFIC CARDIOVASCULAR CONDITIONS WITH NITRITE
    7.
    发明申请
    TREATMENT OF SPECIFIC CARDIOVASCULAR CONDITIONS WITH NITRITE 有权
    用NITRITE治疗特异性心脏病

    公开(公告)号：US20120195983A1

    公开(公告)日：2012-08-02

    申请号：US13407118

    申请日：2012-02-28

    申请人： Mark T. Gladwin ,  Alan N. Schechter ,  Christian J. Hunter ,  Gordon G. Power ,  Daniel B. Kim-Shapiro ,  Richard O. Cannon, III

    发明人： Mark T. Gladwin ,  Alan N. Schechter ,  Christian J. Hunter ,  Gordon G. Power ,  Daniel B. Kim-Shapiro ,  Richard O. Cannon, III

    IPC分类号： A61K33/00 ,  A61P9/10 ,  A61P9/12

    CPC分类号： A61K33/00 ,  A61K45/06 ,  A61K2300/00

    摘要： It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.

    摘要翻译： 令人惊讶地发现，向受试者施用亚硝酸盐导致血压降低和对组织的血流量的增加。 该效果特别有利于例如低氧张力区域中的组织。 该发现提供了有用的治疗方法来调节受试者的血压和血流量，例如通过施用亚硝酸盐。 本文提供了向受试者施用药学上可接受的亚硝酸盐，用于治疗，预防或改善选自以下的病症的方法：（a）缺血再灌注损伤（例如肝脏或心脏或脑缺血再灌注损伤）; （b）肺动脉高压（如新生儿肺动脉高压）; 或（c）大脑动脉血管痉挛。

    Treatment of specific cardiovascular conditions with nitrite
    8.
    发明授权
    Treatment of specific cardiovascular conditions with nitrite 有权
    用亚硝酸盐治疗特定的心血管疾病

    公开(公告)号：US09387224B2

    公开(公告)日：2016-07-12

    申请号：US13407118

    申请日：2012-02-28

    申请人： Mark T. Gladwin ,  Alan N. Schechter ,  Christian J. Hunter ,  Gordon G. Power ,  Daniel B. Kim-Shapiro ,  Richard O. Cannon, III

    发明人： Mark T. Gladwin ,  Alan N. Schechter ,  Christian J. Hunter ,  Gordon G. Power ,  Daniel B. Kim-Shapiro ,  Richard O. Cannon, III

    IPC分类号： A01N59/00 ,  A61K33/00 ,  A01N37/12 ,  A01N37/44 ,  A61K45/06

    CPC分类号： A61K33/00 ,  A61K45/06 ,  A61K2300/00

    摘要： It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.

    摘要翻译： 令人惊讶地发现，向受试者施用亚硝酸盐导致血压降低和对组织的血流量的增加。 该效果特别有利于例如低氧张力区域中的组织。 该发现提供了有用的治疗方法来调节受试者的血压和血流量，例如通过施用亚硝酸盐。 本文提供了向受试者施用药学上可接受的亚硝酸盐，用于治疗，预防或改善选自以下的病症的方法：（a）缺血再灌注损伤（例如肝脏或心脏或脑缺血再灌注损伤）; （b）肺动脉高压（如新生儿肺动脉高压）; 或（c）大脑动脉血管痉挛。

    FIVE-COORDINATE NEUROGLOBIN AND USE THEREOF AS A BLOOD SUBSTITUTE
    9.
    发明申请
    FIVE-COORDINATE NEUROGLOBIN AND USE THEREOF AS A BLOOD SUBSTITUTE 有权
    作为血液替代品使用五种协调的神经营养因子及其使用

    公开(公告)号：US20100323029A1

    公开(公告)日：2010-12-23

    申请号：US12817085

    申请日：2010-06-16

    申请人： Mark T. Gladwin ,  Daniel B. Kim-Shapiro ,  Mauro Tiso

    发明人： Mark T. Gladwin ,  Daniel B. Kim-Shapiro ,  Mauro Tiso

    IPC分类号： A61K38/41 ,  A61K35/14 ,  A61K35/16 ,  A61K35/18 ,  A61P7/06 ,  A61P7/08 ,  A61P7/00 ,  A61P9/10 ,  A61P17/02 ,  A61P9/12

    CPC分类号： A61K38/41 ,  A61K9/0019 ,  A61K35/14 ,  A61K35/16 ,  A61K35/18 ,  A61K38/42 ,  A61K45/06 ,  Y02A50/387

    摘要： Described herein is the finding that a mutant form of human neuroglobin (H64L) with a stable five-coordinate geometry reduces nitrite to nitric oxide approximately 2000-times faster than the wild type neuroglobin. Five-coordinate neuroglobin is also capable of binding and releasing oxygen. Based on these findings, the use of five-coordinate neuroglobin as a blood substitute is described herein. Particularly provided is a method of replacing blood and/or increasing oxygen delivery to tissues in a subject by administering to the subject a therapeutically effective amount of neuroglobin with a stable five-coordinate geometry. In some cases, five-coordinate neuroglobin is administered in combination with another therapeutic agent or composition, such as a second blood replacement product (for example, a hemoglobin-based oxygen carrier), a blood product (such as red blood cells, serum or plasma) or whole blood.

    摘要翻译： 这里描述的发现是具有稳定的五坐标几何形状的人类神经球蛋白（H64L）的突变形式将亚硝酸盐比野生型神经球蛋白的亚硝酸盐还原为大约2000倍的一氧化氮。 五配位神经球蛋白也能够结合和释放氧气。 基于这些发现，本文描述了使用五配位神经球蛋白作为血液代用品。 特别提供的是通过向受试者施用具有稳定的五坐标几何形状的治疗有效量的神经球蛋白来替代血液和/或增加对受试者组织的氧输送的方法。 在一些情况下，五配位神经球蛋白与另一种治疗剂或组合物，例如第二种血液替代产品（例如，基于血红蛋白的氧载体），血液制品（例如红细胞，血清或 血浆）或全血。

    Five-coordinate neuroglobin and use thereof as a blood substitute
    10.
    发明授权
    Five-coordinate neuroglobin and use thereof as a blood substitute 有权
    五配位神经球蛋白及其作为血液代用品

    公开(公告)号：US09114109B2

    公开(公告)日：2015-08-25

    申请号：US12817085

    申请日：2010-06-16

    申请人： Mark T. Gladwin ,  Daniel B. Kim-Shapiro ,  Mauro Tiso

    发明人： Mark T. Gladwin ,  Daniel B. Kim-Shapiro ,  Mauro Tiso

    IPC分类号： A61K35/16 ,  A61K35/18 ,  A61K35/42 ,  A61K35/14 ,  A61K38/42

    CPC分类号： A61K38/41 ,  A61K9/0019 ,  A61K35/14 ,  A61K35/16 ,  A61K35/18 ,  A61K38/42 ,  A61K45/06 ,  Y02A50/387

    摘要： Described herein is the finding that a mutant form of human neuroglobin (H64L) with a stable five-coordinate geometry reduces nitrite to nitric oxide approximately 2000-times faster than the wild type neuroglobin. Five-coordinate neuroglobin is also capable of binding and releasing oxygen. Based on these findings, the use of five-coordinate neuroglobin as a blood substitute is described herein. Particularly provided is a method of replacing blood and/or increasing oxygen delivery to tissues in a subject by administering to the subject a therapeutically effective amount of neuroglobin with a stable five-coordinate geometry. In some cases, five-coordinate neuroglobin is administered in combination with another therapeutic agent or composition, such as a second blood replacement product (for example, a hemoglobin-based oxygen carrier), a blood product (such as red blood cells, serum or plasma) or whole blood.

    摘要翻译： 这里描述的发现是具有稳定的五坐标几何形状的人类神经球蛋白（H64L）的突变形式将亚硝酸盐比野生型神经球蛋白的亚硝酸盐还原为大约2000倍的一氧化氮。 五配位神经球蛋白也能够结合和释放氧气。 基于这些发现，本文描述了使用五配位神经球蛋白作为血液代用品。 特别提供的是通过向受试者施用具有稳定的五坐标几何形状的治疗有效量的神经球蛋白来替代血液和/或增加对受试者组织的氧输送的方法。 在一些情况下，五配位神经球蛋白与另一种治疗剂或组合物，例如第二种血液替代产品（例如，基于血红蛋白的氧载体），血液制品（例如红细胞，血清或 血浆）或全血。