HEPARIN REMOVAL DEVICE FOR CARDIOPULMONARY BYPASS

用于体外循环的肝素去除装置

• 批准号: 3502094
• 负责人: JAMES C MC REA
• 金额: $ 4.96万
• 依托单位: RESEARCH INDUSTRIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3502094
• 关键词: acidity /alkalinity; adsorption; affinity chromatography; anticoagulants; blood coagulation; blood proteins; bromine; chemical binding; chemical hydration; chemical reaction; chemical stability; chemical synthesis; crosslink; cryoprotective agents; cyanogen bromide; drug adverse effect; drug design /synthesis /production; dyes; electrophoresis; heart /lung bypass; heparin; ligands; lyophilization; plasmapheresis; polylysine; polysaccharides; toluene

The use of protamine sulfate is the only commercially available choice that clinicians have to counteract the anticoagulant effect of heparin. While the incidence of any one type of adverse response is generally small the sheer number of different adverse reactions translates into a significant percentage, as high as 27%. The number of patients experiencing adverse reactions associated with heparin reversal ranges from approximately 10,500 to 70,000 open heart patients per year just in the U.S. The need for an alternative means of heparin reversal which obviates the need for protamine sulfate is well recognized. It is the overall goal of the proposed work to develop a device that will reverse the anticoagulant effect of heparin at the end of cardiopulmonary bypass and do it in a safe, cost-effective, and predictable manner. The proposed heparin removal device combines two commercially available technologies to achieve a high capacity, low priming volume system that utilizes high affinity derivatized agarose to remove heparin. One novel feature of the device is that whole blood does not have to come into direct contact with the derivatized agarose. Phase I work will optimize the chemistry involved in derivatizing the high affinity agarose beads and will evaluate several approaches to dry the derivatized beads without compromising heparin-binding activity. In addition, an effort will be made to identify plasma proteins adsorbing to the beads using two-dimensional electrophoresis. By the end of Phase I a prototype device will be constructed to test this unique heparin reversal system in animals and humans during Phase II studies. Preliminary in vitro experiments indicate that a heparin clearance of 85-90 ml/min can be achieved with a less than optimal device. Roughly, one gram of wet derivatized beads can adsorb 1000 units of heparin in 15 minutes.

使用硫酸鱼精蛋白是唯一的商业化选择 临床医生必须抵消肝素的抗凝作用。 尽管 任何一种不良反应的发生率通常都很小 不同不良反应的绝对数量转化为显着的 比例高达27%。 出现不良反应的患者数量 与肝素逆转相关的反应范围约为 10,500 仅在美国每年就有 70,000 名心脏直视患者 肝素逆转的替代方法，无需鱼精蛋白 硫酸盐已被广泛认可。 拟议工作的总体目标是开发一种设备，该设备将 逆转心肺末期肝素的抗凝作用 绕过并以安全、经济高效且可预测的方式进行。 这 拟议的肝素去除装置结合了两种市售的 技术来实现高容量、低启动量系统 利用高亲和力衍生化琼脂糖去除肝素。 一本小说 该设备的特点是全血不必直接输入 与衍生化的琼脂糖接触。 第一阶段的工作将优化高活性物质衍生化所涉及的化学反应。 亲和琼脂糖珠，并将评估几种干燥琼脂糖珠的方法 衍生珠子而不影响肝素结合活性。 在 此外，将努力鉴定吸附于 使用二维电泳的珠子。 第一阶段结束时 将建造原型装置来测试这种独特的肝素逆转作用 第二阶段研究期间动物和人类的系统。 初步体外实验表明肝素清除率为 85-90 毫升/分钟可以通过不太理想的设备来实现。 大约一克 湿衍生珠可在 15 分钟内吸附 1000 单位的肝素。