BIOELASTIC MATERIALS FOR DRUG ADDICTION INTERVENTION

发展麻醉药品拮抗剂控释的第一阶段工作 车辆演示：一、阳离子麻醉剂拮抗剂， 纳曲酮可被加载到超过300毫克/厘米~3的水平 含有阴离子羧酸中心的蛋白质基聚合物植入物，II。 实现了持续的线性释药剖面，在此期间 释放的浓度需要超过10天才能达到 减去两倍。这些结果为实验提供了依据。 对于基于蛋白质的聚合物可以通过控制释放原理 设计了更有利的、更持久的释放曲线。这是一个 双重方法：一种可注射的植入物，在释放的同时分散 周期长达数周，套管针植入的植入物能够释放 一个月或更长时间的合格剂量。 此二期SBIR应用的具体目标是：1.设计 三种不同的蛋白质聚合物结构和优化的药物 加载(每毫升0.25、0.5和1毫摩尔)和持续释放 Profile，2.进行基因的构建和表达设计 基于蛋白质的聚合物，并获得具有一系列n值的基因 可分散注射剂的n值较低的基本基因 植入物和较大的n值制备的交联物， 生物可降解基质棒植入物，3.蛋白质类聚合物基因的提纯 产品达到FDA标准的内毒素水平，4.确定 体外释药研究的最佳聚合物构筑，5.至 将含药植入物包装在无菌包装中，包装等级为10,000 用于样品处理和包装的净化室和2.5毫拉的伽马- 在密封包装中进行一次辐照灭菌，6.进行 纳曲酮血药浓度的体内释放研究 由狗的皮下植入引起的，并检查植入部位 用于分散和降解；7.测定生物相容性 (毒理学)所选的几种控制释放装置。 建议的商业应用：世界性的药物成瘾问题 不需要详细说明。仅在美国，估计就有300万人 3000万吸毒者将从援助中受益。保险箱和 有效的麻醉性拮抗剂纳曲酮可以提供这种帮助， 但缺乏继续使用的耐心动力。植入物 正在开发的麻醉药品拮抗剂递送系统是一种手段， 引发犯罪、摧毁生命的药物依赖可以在没有戒毒的情况下消除 依赖于吸毒者的顺从。商业价值和更广泛的 可注射植入物和可生物降解但可移除的社会价值 棒状植入物是很坚固的。

The Phase I effort to develop narcotic antagonist controlled release vehicles demonstrated: i. that the cationic narcotic antagonist, Naltrexone, can be loaded to levels of more than 300 mg/cm3 into a protein-based polymer implant containing anionic carboxylate sites, ii. that sustained linear release profiles were achieved in which a period of greater than ten days was required for the released concentration to decrease by a factor of two. These results provide an experimental basis for a controlled release rationale whereby protein-based polymers can be designed with even more favorable, sustained release profiles. It is a dual approach: an injectable implant which disperses as it releases for periods up to weeks, and a trocar-emplaced implant capable of releasing competent doses for a month or more. The specific aims of this Phase II SBIR application are: 1. to design three different protein-based polymer constructs with optimized drug loading (0.25, 0.5, and 1 mmole per cc) and with sustained release profiles, 2. to carry out gene construction and expression of the designed protein-based polymers and to obtain genes with a series of values for n of the basic gene with lower values of n for the dispersible injectable implants and the larger values of n to prepare the cross-linked, biodegradable matrix rod implants, 3. to purify protein-based polymer gene products to endotoxin levels meeting the FDA standards, 4. to determine the optimal polymer constructs by means of in vitro release studies, 5. to package the drug-laden implants in sterile packets using a class 10,000 clean room for sample handling and packaging and 2.5 Mrads of gamma- irradiation for sterilization once in the sealed package, 6. to carry out in vivo release studies by following Naltrexone levels in the plasma resulting from subcutaneous implants in the dog and examine implant sites for dispersal and degradation, and 7. to determine the biocompatibility (toxicology) of the several chosen controlled release devices. PROPOSED COMMERCIAL APPLICATION: The worldwide drug addiction problem needs no elaboration. In the U.S. alone, it is estimated that between 3 and 30 million drug users would benefit from assistance. The safe and effective narcotic antagonist, Naltrexone, could provide that assistance, but suffers from patient motivation to continue use. The implantable narcotic antagonist delivery systems being developed are means whereby the crime-causing, life-destroying drug dependency could be removed without relying on the addict's compliance. The commercial value and the broader societal value of injectable implants and of biodegradable but removable rod implants are substantial.