Controlled Delivery System for Naltrexone

纳曲酮控释系统

基本信息

批准号：
6700302
负责人：
EMMANUEL O AKALA
金额：
$ 15.1万
依托单位：
HOWARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-02-01 至 2006-08-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：问题的重要性报告显示酗酒，表明大约 7.5 % 的美国人口（约 1400 万美国人）遭受虐待和/或依赖酒精。与酒精相关的死亡约占百分之五占美国所有死亡人数的比例，除了人类遭受的痛苦之外，这是很难统计的量化，估计酒精依赖给社会造成的损失约为116 每年十亿美元。酒精会引起医疗并发症依赖性：心血管、神经、胃肠、免疫、精神和产科并发症。主要治疗方法酗酒的治疗包括解毒、非药物、（心理社会）治疗方法和药物治疗。社会心理的有效性治疗方法尚未确定：他们很少或没有遇到过成功治疗酗酒。药物开发的重点成瘾性疾病，例如酗酒，已经从戒断状态转变为复发状态预防。纳曲酮的有效性（已获得食品药品监督管理局批准）管理（FDA）受到合规性问题的限制：酗酒者表明用药依从率特别低。此外，纳曲酮是一种药物提取率高，母体药物含量低脑。因此，需要开发一种受控的递送系统不仅可以长时间维持药物的释放时间，但可以通过以一定的速度释放药物来维持恒定的血液浓度吸收部位的速率恒定。如果输送系统是注射后，纳曲酮可以逃避肝脏的首过效应。在我们的初步研究，我们开发了聚合物可注射纳米和微粒纳曲酮控释系统能够持续纳曲酮的体外有效性超过三个月。我们的目标是持续提供纳曲酮六至十二个月。生物可降解和生物相容性共聚物的合成及其在生物材料中的应用优化纳曲酮控释系统的制造及其大鼠评估是本提案的重点。使用受控释放纳曲酮制剂将确保合规性，因为需要患者决定服药的可能性将被最小化；它也可能通过产生更多的效果来增加治疗反应的可能性母体药物的可预测且恒定的血浆浓度并使其大脑中可用。