BIOERODIBLE NARCOTIC ANTAGONIST DELIVERY DEVICE

这项研究的主要目标是开发一种 释放纳曲酮的植入式生物给药装置 由接近于零的动力学控制的侵蚀过程 秩序。纳曲酮分散在交联聚(邻位)中 酯)，在基质中含有易水解性的键。 纳曲酮的释放受扩散控制 以及这些联系割裂的速度。因为聚(正交) 酯)是酸敏感的水解率可以通过 加入酸性辅料或共聚的方法 含有侧链羧酸基的单体。速度 聚合物的水解度随着这些物质浓度的增加而增加 赋形剂或酸性单体。此外，水解率 随着聚合物亲水性的增加而增加。因此， 相当精确地控制聚合物的水解率和 随后的药物释放可以确定。圆柱形装置 可以很容易地通过简单地挤压粘性液体来生产 预聚体，然后在中等温度下固化，或微球 可以通过将粘性液体预聚体分散在 惰性介质，然后固化。聚(邻苯二甲酸酯)已被 被首席调查员广泛调查 左炔诺孕酮的释放及IND的毒理学研究 立案工作即将启动。我们建议发展送货业务 一种用于治疗毒品成瘾并获得 更好地了解治疗剂的释放 水的溶解度比水高得多- 不溶的左旋诺孕酮。

The principal objective of this research is to develop an implantable, bioerod drug delivery device that releases naltrexone by an erosion-controlled process by kinetics approaching zero order. The naltrexone is dispersed in a crosslinked poly(ortho ester) that contains hydrolytically labile linkages in the matrix. Release of naltrexone is controlled by a combination of diffusion and rate at which these linkages cleave. Because poly(ortho esters) are acid sensitive rate of hydrolysis can be controlled by means of incorporated acidic excipients or by copolymerized monomers that contain pendant carboxylic acid groups. Rate of polymer hydrolysis increases with increasing concentration of these excipients or acidic monomers. In addition, rate of hydrolysis increases as the hydrophilicity of the polymer increase. Thus, fairly precise control over rate of polymer hydrolysis and consequent drug release can be established. Cylindrical devices can be readily produced by simple extrusion of a viscous liquid prepolymer and then cured at moderate temperatures, or microspheres can be produced by dispersing the viscous liquid prepolymer in an inert medium, followed by curing. Poly(ortho esters) have been extensively investigated by the principal Investigator for the release of levonorgestrel, and toxicological studies for an IND filing are about to be initiated. We propose to develop delivery system useful for the treatment of narcotic addiction and to gain a better understanding of the release of therapeutic agents having water solubilities considerably higher than the very water- insoluble levonorgestrel.