GLUCOSE SENSITIVE MEMBRANES IN THE DELIVERY OF INSULIN

用葡萄糖调节的胰岛素递送改善糖尿病治疗 是这个项目的长期目标。 葡萄糖敏感聚合物 膜（含有胺基和葡萄糖氧化酶）， 变得对胰岛素更具渗透性。 内部pH 由膜中葡萄糖酸形成引起的减少使膜质子化， 胺基，引起静电荷排斥，随之而来的膨胀， 和增强的胰岛素渗透。 的制备与表征 具有改进的灵敏度和延长的寿命的新型葡萄糖敏感膜 操作范围以及输送装置的设计和制造 这些膜可以控制胰岛素的输送 在生理条件下，是所提出的直接目标 research. 将进行一项连续的、分段的研究计划， 使我们能够集中精力解决一个又一个关键问题 时间，按其重要性排序。 为了提高灵敏度，准备 和分析“相变”聚合物，经历大的变化， 将在第1年进行窄pH值范围内的溶胀。 第二年，我们 将开发出能提供更高氧气浓度的配置， 膜以扩大对葡萄糖的敏感范围。 两种设计 将应用实现这一点的概念， 将根据预期性能对概念进行分析：1） “鼓”的概念：一个硅橡胶气囊，，可从相邻的 组织与葡萄糖敏感膜紧密接触。 2)二维O2输送概念：一个硅橡胶管， 作为胰岛素输送屏障的葡萄糖敏感膜将允许 径向O2通过管壁输送。 第三年，设备 将最敏感的相变聚合物掺入到 将形成允许充分的氧渗透的构造， 通过测量体外胰岛素释放速率进行实验评价， 一系列生理葡萄糖浓度。 硅橡胶 试管/葡萄糖敏感膜设计旨在用于两种 可能的模式：1）作为短期植入物，经常更换; 以及2）作为连接到气体加压储存器的导管的尖端 还有尸体 这两种设备配置都是专门针对 建议作为克服潜在限制的方法（由于酶 稳定性和生物相容性 的设计.

Improved treatment of diabetics with glucose regulated delivery of insulin is the long term goal of this project. Glucose sensitive polymeric membranes (containing amine groups and glucose oxidase) that swell and become more permeable to insulin have been prepared. An internal pH decrease caused by gluconic acid formation in the membrane protonates the amine groups, causing electrostatic charge repulsion, consequent swelling, and enhanced insulin permeation. The preparation and characterization of new glucose sensitive membranes with improved sensitivity and extended range of operation, and the design and fabrication of delivery devices incorporating these membranes that can control the delivery of insulin under physiological conditions, are the immediate goals of the proposed research. A sequential, segmented research program will be conducted, allowing concentration of our efforts on the critical problems one at a time, in their order of importance. To enhance sensitivity, preparation and analysis of "phase transition" polymers that undergo large changes in swelling over narrow pH intervals will be done in year 1. In year 2, we will develop configurations that provide higher oxygen concentration to the membrane to extend the range of sensitivity to glucose. Two design concepts to achieve this will be applied and specific embodiments of each concept will be analyzed with respect to expected performance: 1) The "drum" concept: a silicon rubber air sac,, replenishable from adjacent tissue, is created in intimate contact with the glucose sensitive membrane. 2) The two-dimensional 02 delivery concept: a silicone rubber tube with a glucose sensitive membrane as a barrier to insulin delivery will permit radial 02 transport through the walls of the tube. In year three, devices incorporating the most sensitive phase transition polymer in a configuration allowing sufficient oxygen permeation will be made and experimentally evaluated by measuring in vitro insulin release rates at a series of physiological glucose concentrations. The silicone rubber tube/glucose sensitive membrane designs are intended for use in two possible modes: 1) as short term implants that are replaced frequently; and, 2) as the tip of a catheter connected to a gas pressurized reservoir and the body. Both of these device configurations are specifically proposed as methods to overcome potential limitations (due to enzyme stability and biocompatibility) of previous monolithic, long term implant designs.