CLOSED LOOP BIOERODIBLE INSULIN DELIVERY DEVICE

我们的目标是继续开发一种生物可蚀性 能够以动力学释放胰岛素含胰岛素植入物 由外部葡萄糖浓度控制。 主要 出于安全考虑我们正在研发一种双重植入物 一个植入物 以预定的速率输送胰岛素 外部葡萄糖浓度，另一个植入物输送 胰岛素对外部葡萄糖的反应，并被设计为 补充由第一植入物递送的量， 葡萄糖水平升高超过正常的100 mg%。 这两种设备都使用 pH敏感的聚原酸酯体系。 胰岛素和葡萄糖 氧化酶分散在葡萄糖敏感的基质中， 聚合物，并且聚合物的侵蚀速率随着温度的变化而变化。 葡萄糖酸浓度变化的结果 在器件的表面层中， 葡萄糖氧化酶的作用。 实现所需的pH灵敏度 在聚原酸酯体系中， 在聚合物主链中起作用。 这两种设备都是制造的 通过首先制备线性乙烯酮缩醛封端的预聚物， 在室温下是一种粘稠的液体， 预聚物胰岛素和葡萄糖氧化酶（如果使用的话）连同三醇一起沿着 交联剂，并在40 ℃下固化过夜。 无变性 在温和的条件下发生。 一旦工作 聚合物体系已经发展起来，它的特点将是： 体外研究了一种独特的计算机程序 灌注/灌注系统，然后使用 糖尿病大鼠

The objective is to continue the development of a bioerodible insulin-containing implant capable of releasing insulin at kinetics that are controlled by external glucose concentration. Principally for safety reasons we are developing a dual implant. One implant delivers insulin at a predetermined rate that is independent of external glucose concentration, and the other implant delivers insulin in response to external glucose and is designed to supplement the amount delivered by the first implant when glucose levels rise above the normal 100 mg%. Both devices use a pH-sensitive poly(ortho ester) system. The insulin and glucose oxidase are dispersed within the matrix of the glucose-sensitive polymer, and the erosion rate of the polymer changes as a consequence of changing concentrations of gluconic acid generated in the surface layers of the device by the oxidation of glucose by glucose oxidase. To achieve the desired pH sensitivity of the poly(ortho ester) system, we incorporated tertiary amine functions into the polymer backbone. Both devices are fabricated by first preparing a linear ketene acetal-terminated prepolymer that is a viscous liquid at room temperature, dispersing it into the prepolymer insulin and glucose oxidase (if used) along with triol crosslinker, and curing at 40 degree C overnight. No denaturation of the proteins occurs at those mild conditions. Once a working polymer system has ben developed, it will be characterized by in vitro studies a unique computer programmable perifusion/perfusion system followed by in vivo studies using diabetic rats.