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Artificial Oxygen Carriers as Oxygen Therapeutics

人工氧气载体作为氧气治疗剂

基本信息

批准号：
16209037
负责人：
KAWAGUCHI Akira
金额：
$ 32.2万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

We studied protective effects of three artificial oxygen carries of our own original development as follows;1. Liposome-encapsulated hemoglobin (LEH),2. Nitric-Oxide-Sulfonyl-Polyethyleneglycol-Hemoglobin (SNO-PEG-Hb)3. Per fluorocarbon Compounds (PFC).These artificial oxygen carriers have been tested in animal models of organ ischemia or hypoxic conditions; A. Cerebral infarction, B. Myocardial ischemia, C. Cardiac arrhythmias, D. Cancer Radiation Therapy, E. Wound Healing, F. Human Immune System, G. Skeletal Muscle Ischemia, H. Total Brain Ischemia, I. Human Platelet.On these models, influence or difference on effects of,α) Dose-Response relationship: 10 mL/kg, 2 mL/kg, 0.4 mL/kg, 0.08 mL/kg, 0.016 ml/kgβ) Oxygen Affinity: P50O2=45 mmHg (low) and P5002=10 mmHg (high)γ) Individual Oxygen Carriers: LEH, SNO-PEG-Hb, PFCδ) Prospective Utility in Blood Bank, has been explored and reported.In summary, these artificial oxygen carriers, specifically LEH, have been proved to be protective of organ ischemia (cerebral, myocardial, skeletal muscle, arrhythmia), to facilitate wound healing, and to potentiate cancer radiation therapy at minimal effective doses of 0.08 mL/kg to 2 mL/kg depending on application and oxygen affinity, which is found to be more potent with a higher affinity (P_<50>O_2=10 mmHg). Moreover, LEH proves to be non-immunogenic to human lymphocytes, and no-interferent with human platelets, suggesting a safe, innovative, and effective clinical application once approved for human use.

我们研究了自己研制的三种人工氧载体的保护作用。脂质体包裹血红蛋白（莱赫），2.一氧化氮-磺酰基-聚乙二醇-血红蛋白（SNO-PEG-Hb）3.这些人工氧载体已经在器官缺血或缺氧条件的动物模型中进行了测试;脑梗塞，B。心肌缺血，C.心律失常D.癌症放射治疗，E。伤口愈合，F。人类免疫系统，G.骨骼肌缺血，H.全脑缺血，I.人体血小板。在这些模型上，对以下效应的影响或差异：α）剂量-反应关系：10 mL/kg、2 mL/kg、0.4 mL/kg、0.08 mL/kg、0.016 ml/kgβ）氧亲和力：P50 O2 =45 mmHg（低）和P5002=10 mmHg（高）γ）单个氧载体：莱赫，SNO-PEG-Hb，PFCδ）在血库中的应用前景已被探索和报道，总之，这些人工氧载体，特别是莱赫，已被证明对器官缺血具有保护作用（脑、心肌、骨骼肌、心律失常），以促进伤口愈合，并根据应用和氧亲和力在0.08 mL/kg至2 mL/kg的最小有效剂量下加强癌症放射治疗，发现具有较高亲和力（P_<50>O_2=10 mmHg）的最小有效剂量更有效。此外，莱赫被证明对人淋巴细胞无免疫原性，对人血小板无免疫原性，这表明一旦被批准用于人类使用，它将是一种安全、创新和有效的临床应用。