NOVEL PEG HEMOGLOBIN MODIFICATION FOR BLOOD REPLACEMENT

用于血液替代的新型 PEG 血红蛋白修饰

• 批准号: 2868107
• 负责人: KIM VANDEGRIFF
• 金额: $ 9.96万
• 依托单位: SANGART, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-05 至 1999-11-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2868107
• 关键词: blood /plasma substitute; blood transfusion; chemical synthesis; drug design /synthesis /production; hemoglobin; maleimides; osmotic pressure; oxygen transport; polyethylene glycols; thermodynamics; viscosity

The goal of Phase I is to design a new class of hemoglobin molecules that work safely and effectively as oxygen carriers. The long-term goal is to optimize these solutions for blood replacement therapies based on efficacy of oxygen transport and expansion of blood volume. The chemistry must be cost-effective for commercialization. In Phase I, we describe a new chemistry for specific, controlled attachment of synthetic polyethylene glycol polymers (PEG) to the surface of the hemoglobin molecule. Critical physicochemical properties of hemoglobin solutions have been defined that work effectively at blood replacement. This is due primarily to the absence of a vasoconstrictive response to these solutions, a side-effect that is the rule rather than the exception in commercial hemoglobin-based oxygen carriers that are in clinical trials today. The key physicochemical properties are: I) high viscosity, 2) high colloid osmotic pressure, and 3) high oxygen affinity. The strategy to achieve this objective is already well- established . Phase I research will correlate number of PEG surface attachments versus length of PEG chains to optimize these properties. Phase II is designed to test these formulations in vitro for diffusive oxygen transport and in vivo for maintenance of tissue oxygenation. PROPOSED COMMERCIAL APPLICATIONS: The method to modify hemoglobin with polyethylene glycol has significant potential to be developed into a commercial product for use as a blood replacement. Such a product can be used in emergencies, war time, or any time blood is not available. Moreover, this product has the potential to be inexpensive and universally compatible with recipients.

The goal of Phase I is to design a new class of hemoglobin molecules that work safely and effectively as oxygen carriers.长期目标是根据氧气输送和血容量扩张的功效来优化这些血液替代疗法解决方案。该化学物质必须具有成本效益才能实现商业化。在第一阶段，我们描述了一种新的化学方法，用于将合成聚乙二醇聚合物（PEG）特异性、受控地附着到血红蛋白分子的表面。血红蛋白溶液的关键物理化学特性已被定义，可以有效地进行血液替代。这主要是由于这些溶液缺乏血管收缩反应，这种副作用是目前临床试验中商业血红蛋白氧载体的常见现象，而不是例外。关键的物理化学特性是：1）高粘度，2）高胶体渗透压，3）高氧亲和力。实现这一目标的战略已经制定完毕。第一阶段研究将关联 PEG 表面附着物的数量与 PEG 链的长度，以优化这些特性。第二阶段的目的是测试这些制剂在体外的扩散氧运输和体内组织氧合的维持。拟议的商业应用：用聚乙二醇修饰血红蛋白的方法具有开发成用作血液替代品的商业产品的巨大潜力。这种产品可以在紧急情况、战时或任何无法获得血液的时候使用。此外，该产品具有价格低廉且与接受者普遍兼容的潜力。