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    • 54. 发明公开
    • Prevention of tissue ischemia, related methods and compositions
    • 组织缺血的预防于此的方法和组合物相关的
    • EP2695896A2
    • 2014-02-12
    • EP13180563.2
    • 2007-10-05
    • The Government of the United States of America as represented by the Secretary of the Department of Health and Human ServicesThe Washington University
    • Isenberg, Jeffrey S.Roberts, David D.Frazier, William A.
    • C07K14/78G01N33/68C07K16/00
    • C07K16/18A61K39/3955A61K45/06A61K48/00A61K2039/505B01J21/063B01J21/12B01J23/002B01J23/30B01J27/188B01J37/0205B01J2523/00C07C45/002C07C45/52C07C51/235C07C51/252C07C253/26C07K14/78C07K2317/76G01N33/6887G01N33/6893G01N2333/705C07C47/22C07C57/04B01J2523/15B01J2523/51B01J2523/69B01J2523/41
    • Provided herein are compositions and methods for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival.; This in turn reduces or prevents tissue necrosis and death. The therapeutics identified herein allow for precise regulation of blood flow to tissues and organs which need it, while substantially avoiding systemic complications. Methods and compositions described herein can be used to increase tissue survival under conditions of trauma and surgery, as well as conditions of chronic vascular disease. Also disclosed are methods for the treatment of elderly subjects using agents that affect TSP1 and CD47 and thereby affect tissue perfusion. Additionally, provided herein are compositions and methods for influencing blood coagulation, allowing for controlled increased or decreased blood clotting. Additionally, provided herein are compositions and methods for decreasing blood flow, as in the case of cancer through mimicking the effects of TSP1 and CD47 on blood vessel diameter and blood flow.
    • 提供在组合物和用于预防,改善方法,和/或减少组织局部缺血和/或由于缺血组织损伤,血管疾病,包括外周血管疾病的存在增加血管直径,血流和组织灌注,动脉粥样硬化性血管疾病 ,冠状动脉疾病,中风和其他条件影响,通过抑制CD47和/或阻断TSP1和/或CD47的活性或交互。 影响CD47-TSP1的血管中的相互作用允许对血管直径和血流的控制,并允许血压和心脏功能的修饰。 下减少血流量,例如通过损伤或动脉粥样硬化,条件阻断TSP1-CD47相互作用允许血管扩张和增加血流量,组织灌注和组织存活。 这又减少或防止组织坏死和死亡。 确定了治疗允许血液流向组织和需要器官的精确调节,同时基本上避免全身并发症。 方法和组合物描述在可以被用来增加创伤和外科手术的条件下组织的生存,以及慢性血管疾病的条件。 所以光盘游离缺失是使用代理没有影响TSP-1和CD47,从而影响组织灌注老年患者的治疗方法。 另外,提供在组合物和用于影响血液凝固的方法,允许受控的增加或减少的血液凝固。 另外,在是组合物和方法,用于通过模拟TSP1和CD47对血管直径和血流的影响减少血流量,如在癌症的情况下提供的。