ROOT EFFECT HEMOGLOBIN BASED OXYGEN TRANSPORT MATERIAL

基于血红蛋白的根效应氧运输材料

• 批准号: 2852258
• 负责人: JAMES J FISCHER
• 金额: $ 9.83万
• 依托单位: ICTHYOX, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2852258
• 关键词: biotechnology; blood filtration; hemoglobin; method development; oxygen transport; protein purification; trout /salmon

The goal of this project is to develop a Root effect hemoglobin-based oxygen transport material to enhance tissue oxygen delivery. Root effect hemoglobins are found in the blood of some fish. The Root effect is an exaggerated Bohr effect wherein oxygen affinity is greatly decreased at acid pH. Because of the local variation in pH it is possible to load hemoglobin in the lungs at ambient oxygen pressure, and to deliver it under vastly increased, even hyperbaric pressure, in acidic hypoxic tissues. A Root effect hemoglobin-based oxygen transport material has the potential to enhance oxygen delivery to any acidic tissue; a decreased value of pH is commonly found in hypoxic normal and malignant tissues. In Phase I techniques will be developed to permit isolation and purification of a Root effect hemoglobin from the blood of Salmo gairdneri in the quantities necessary for use in large animals and in human trials. In Phase II these techniques will be used to produce approximately 50kg of stroma free hemoglobin, which meets FDA standards for preclinical and eventual clinical testing. PROPOSED COMMERCIAL APPLICATION: This research is directed toward the development of a Root effect hemoglobin-based oxygen transport material which could be used to improve tumor oxygenation for radiation and chemotherapy. It would also have potential application in the treatment of a variety of diseases resulting from normal tissue hypoxia including myocardial infarction, cardiovascular accident, failure of tissue engraftment and wound healing, small vessel diseases, etc.

该项目的目标是开发一种基于Root效应的血红蛋白 氧输送材料，以增强组织氧输送。 根 在某些鱼的血液中发现了血红蛋白。 根效应 是一种夸张的玻尔效应，其中氧亲和力大大 在酸性pH值下降低。由于pH值的局部变化， 在环境氧压下可能将血红蛋白加载到肺中，并且 在巨大的压力下，甚至是高压下， 酸性缺氧组织基于血红蛋白的根效应氧转运 材料具有增强氧气输送到任何酸性环境的潜力。 组织; pH值降低通常见于缺氧正常和 恶性组织 在第一阶段，将开发各种技术， 从萨尔莫血液中纯化Root效应血红蛋白 gairdneri在必要的数量用于大型动物和 人体试验 在第二阶段，这些技术将用于生产约50公斤 无基质血红蛋白，符合FDA临床前和 最终的临床试验。 拟定商业应用： 这项研究是针对发展的根效应 血红蛋白基氧输送材料，其可用于 改善肿瘤氧合以用于放疗和化疗。 它还将 具有治疗多种疾病的潜在应用 由包括心肌梗塞的正常组织缺氧引起， 心血管意外、组织植入失败和创伤 愈合、小血管疾病等。