公开(公告)号：US09700578B2

公开(公告)日：2017-07-11

申请号：US14589324

申请日：2015-01-05

申请人： The United States of America as represented by the Secretary of the Department of Health and Human Services ,  The Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, Acting through Louisiana State University Health Sciences Center ,  The UAB Research Foundation ,  Loma Linda University ,  Wake Forest University

发明人： Mark T. Gladwin ,  Alan N. Schechter ,  David J. Lefer ,  Rakesh P. Patel ,  Christian J. Hunter ,  Gordon G. Power ,  Daniel B. Kim-Shapiro ,  Ryszard Marek Pluta ,  Edward H. Oldfield ,  Richard O. Cannon, III

IPC分类号： A61K33/00 ,  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.

公开(公告)号：US20150125553A1

公开(公告)日：2015-05-07

申请号：US14589324

申请日：2015-01-05

申请人： The Government of the United States of America as represented by the Secretary of the Department of ,  The Board of Supervisors of Louisiana State Univer and Agricultural and Mechanical College, Acting t ,  The UAB Research Foundation ,  Loma Linda University ,  Wake Forest University

发明人： Mark T. Gladwin ,  Alan N. Schechter ,  David J. Lefer ,  Rakesh P. Patel ,  Christian J. Hunter ,  Gordon G. Power ,  Daniel B. Kim-Shapiro ,  Ryszard Marek Pluta ,  Edward H. Oldfield ,  Richard O. Cannon, III

IPC分类号： A61K33/00

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。

公开(公告)号：US20170087181A1

公开(公告)日：2017-03-30

申请号：US15146190

申请日：2016-05-04

申请人： The Government of the U.S.A. as represented by the Secretary of the Department of Health and Human S ,  The UAB Research Foundation ,  Wake Forest University

发明人： Mark T. Gladwin ,  Daniel B. Kim-Shapiro ,  Rakesh P. Patel ,  Jeffrey Kerby

IPC分类号： A61K33/26 ,  A61K33/00 ,  A61K31/555

CPC分类号： A61K33/26 ,  A61K31/555 ,  A61K33/00 ,  Y02A50/387 ,  A61K2300/00

摘要： This disclosure relates to methods of using nitrite to detoxify stroma-free hemoglobin based blood substitutes. In particular, methods are described for using a blood substitute comprised of about equimolar amounts of nitrite and hemoglobin (e.g., nitrite-metHb) to treat, prevent, or ameliorate diseases of the blood in a subject, or as a blood replacement in a subject.

公开(公告)号：US20170281673A1

公开(公告)日：2017-10-05

申请号：US15630017

申请日：2017-06-22

申请人： The Government of the U.S.A. as represented by the Sec. of the Dept. of Health and Human Services ,  Loma Linda University ,  Wake Forest University

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 ,  A61K45/06

CPC分类号： A61K33/00 ,  A61K45/06 ,  Y02A50/411 ,  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.

公开(公告)号：US20140017342A1

公开(公告)日：2014-01-16

申请号：US14028850

申请日：2013-09-17

申请人： The Government of the United States of America as represented by the Secretary of the Department of ,  Wake Forest University ,  University of Alabama at Birmingham

发明人： Mark T. Gladwin ,  Daniel B. Kim-Shapiro ,  Rakesh P. Patel ,  Jeffrey Kerby

IPC分类号： A61K33/00 ,  A61K31/555

CPC分类号： A61K33/26 ,  A61K31/555 ,  A61K33/00 ,  Y02A50/387 ,  A61K2300/00

摘要： This disclosure relates to methods of using nitrite to detoxify stroma-free hemoglobin based blood substitutes. In particular, methods are described for using a blood substitute comprised of about equimolar amounts of nitrite and hemoglobin (e.g., nitrite-metHb) to treat, prevent, or ameliorate diseases of the blood in a subject, or as a blood replacement in a subject.

摘要翻译： 本公开涉及使用亚硝酸盐来解毒基于无基质血红蛋白的血液代用品的方法。 特别地，描述了使用由等摩尔量的亚硝酸盐和血红蛋白（例如，亚硝酸盐-metHb）组成的血液替代物来治疗，预防或改善受试者的血液疾病或作为受试者的血液置换的方法 。

公开(公告)号：US20150306183A1

公开(公告)日：2015-10-29

申请号：US14795115

申请日：2015-07-09

申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education ,  Wake Forest University

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

IPC分类号： A61K38/41 ,  A61K45/06 ,  A61K9/00

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。