COMBINED VACUUM ULTRAFILTRATION--SEPARATION OF ENDOTOXIN

内毒素是革兰氏阴性菌的一种脂多糖产物，具有 体内的严重毒性(例如，由于以下原因导致的心血管衰竭 内毒素休克)以及各种体外生物系统 (例如，组织培养)。当前可以删除的技术 生物内毒素是一种以颗粒为基础的亲和层析 使用琼脂糖聚粘菌素的程序。就像粒子的典型情况一样 基于分离这一过程既慢又不方便，因为 亲和层析柱的特性随时间变化(例如，填充物)。 在这份提案中，我们概述了旨在优化表面的研究 用于将多粘菌素附着到非颗粒载体上的化学。 这些支撑件是刚性的，具有极好的流速，因此将具有 与大容量应用程序兼容的物理特性，例如 药物的解毒。一旦依恋的化学反应是 确定了多粘菌素的最佳构型 支持与真空超滤相结合，提供单一 一步即可灭菌和解毒的装置。如果 这项研究的成功将为开发一种 一种原型装置，经过改进，应该会在 生物技术和制药行业，仅举几例。其他内容 这种设备的积极特征是它将是廉价的， 使用方便(甚至可以重复使用)，易于接口 与其他流动过程相结合。

Endotoxin, a lipopolysaccharide product of gram negative bacteria, has profound toxicities in vivo (e.g., cardiovascular collapse due to endotoxin shock) as well as in a variety of in vitro biological systems (e.g., tissue culture). The current technology available to remove endotoxin form biological is a particle based affinity chromatography procedure utilizing Sepharose-Polymyxin. As is typical for particle based separations this process is slow ad inconvenient due to the changing characteristics of affinity columns with age (e.g., packing). In this proposal we outline studies designed to optimize surface chemistries for attachment of Polymyxin to non-particle based supports. These supports are rigid, have excellent flow rates and, thus, will have physical properties compatible with high volume applications, such as detoxification of pharmaceuticals. Once the attachment chemistry is defined we will determine the optimum configuration of the Polymyxin support in combination with vacuum ultrafiltration to provide a single unit which will both sterilize and detoxify in a single step. If successful this research should lay the groundwork for development of a prototype device which, when refined, should find widespread uses in the Biotechnology and Pharmaceutical industries, to name a few. Additional positive features of such a device is that it will be inexpensive, convenient to use (perhaps even re-useable) and amenable to interfacing with other flow-thru processes.