ROOT EFFECT HEMOGLOBIN BASED OXYGEN TRANSPORT MATERIAL

该项目的目标是开发一种基于根效应的血红蛋白 氧气输送材料，以增强组织的氧气输送。根部 在一些鱼的血液中发现了有效的血红蛋白。根效应 是一种夸张的玻尔效应，其中氧气亲和力大大 在酸性pH条件下降低。由于酸碱度的局部变化， 可以在环境氧气压力下将血红蛋白加载到肺中，以及 在极大增加的，甚至是高压的压力下交付它， 酸性缺氧组织。根效应--基于血红蛋白的氧转运 材料有可能增强对任何酸性物质的氧气输送 组织；pH值降低通常见于低氧正常和 恶性组织。 在第一阶段，将开发技术以允许隔离和 鲑鱼血液中一种根效应血红蛋白的纯化 Gairdneri的数量是用于大型动物和 人体试验。 在第二阶段，这些技术将被用于生产大约50公斤 无基质血红蛋白，符合FDA的临床前和 最终的临床测试。 建议的商业应用： 这项研究针对的是根效应的发展 基于血红蛋白的氧传输材料可用于 改善肿瘤的氧合，用于放疗和化疗。它还会 在多种疾病的治疗中有潜在的应用 由包括心肌梗死在内的正常组织缺氧引起， 心血管意外、组织移植失败和创伤 治疗、小血管疾病等。

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.