Controlled Delivery System for Naltrexone

描述（由申请人提供）： 报告显示，大约7.5 美国人口（约1400万美国人）的百分之滥用和/或 依赖酒精。 与酒精有关的死亡约占百分之五 在美国所有的死亡，除了人类的痛苦，这是很难 量化，据估计，酒精依赖的成本约116社会 十亿美元。 酒精会引起并发症 依赖性：心血管、神经、胃肠道、免疫、 精神和产科并发症 治疗的主要方法 酒精中毒包括解毒，非药物，（心理社会） 治疗方法和药物治疗。 社会心理学的有效性 治疗方法尚未建立：他们遇到很少或没有 成功治疗酗酒。 药物开发的重点是 成瘾性疾病，如酗酒，已经从戒断转向复发 预防 纳洛酮的有效性（已被食品和药物管理局批准） 管理局（FDA）受到遵守问题的限制：酗酒者显示 尤其是服药依从率低。 此外，纳洛酮是一种 高度提取的药物，与少量的母体药物可在 个脑袋 因此，需要开发一种受控的 该递送系统不仅可以长时间维持药物的释放， 时间，但可以保持恒定的血液水平，通过释放药物在 在吸收部位的恒定速率。 如果输送系统 注射用纳洛酮可以逃避肝脏中的首过效应。 在我们 初步研究，我们已经开发出聚合物可注射纳米和 能够持续的微粒纳洛酮控释系统 纳洛酮的体外可用性超过三个月。 我们的目标是持续提供纳洛酮6至12个月。 生物可降解和生物相容性共聚物的合成及其在生物医学中的应用 优化纳洛酮控释系统的制备及其 在大鼠中的评价是该提议的重点。 使用控制下 释放纳洛酮制剂将确保依从性，因为需要 患者决定服用药物的可能性将被最小化;它还可以 通过产生更多的 母体药物的可预测和恒定的血浆浓度， 在大脑中可用。

DESCRIPTION (provided by applicant): The importance of the problem of alcoholism is shown by the report which indicates that approximately 7.5 percent of the U.S. population (about 14 million Americans) abuse and/or are dependent on alcohol. Alcohol-related deaths account for about five percent of all deaths in the U.S. Aside from human suffering, which is difficult to quantify, it is estimated that alcohol dependence costs the society about 116 billion dollars per year. There are medical complications from alcohol dependence: cardiovascular, neurological, gastrointestinal, immunologic, psychiatric, and obsteric complications. The main approaches to the treatment of alcoholism include detoxification, non-pharmacological, (psychosocial) treatment methods, and pharmacotherapy. The effectiveness of psychosocial treatment approaches has not been established: they have met with little or no success in treating alcoholism. The focus of medication development for addictive disorders, such as alcoholism, has moved from withdrawal to relapse prevention. The effectiveness of naltrexone (already approved by the Food and Drug Administration (FDA) is limited by problem with compliance: alcoholics show particularly low rates of medication compliance. Moreover, naltrexone is a highly extracted drug, with a low amount of the parent drug available in the brain. Consequently, there is need for the development of a controlled delivery system which can, not only sustain the release of the drug for a long time, but can maintain a constant blood level by releasing the drug at a constant rate at the site of absorption. If the delivery system is injectable, naltrexone can escape the first pass effect in the liver. In our preliminary studies, we have developed polymeric injectable nano- and microparticulate naltrexone controlled delivery systems capable of sustaining in vitro availability of naltrexone for a period greater than three months. Our goal is sustained delivery of naltrexone for six to twelve months. Synthesis of biodegradable and biocompatible copolymers and their use in optimizing the fabrication of naltrexone controlled delivery systems and their evaluation in rats are the focus of this proposal. The use of controlled release naltrexone preparations will ensure compliance because the need for the patient to decide to take his medication would be minimized; it may also increase the likelihood of a therapeutic response by yielding a more predictable and constant plasma concentration of the parent drug and making it available in the brain.