Controlled Delivery System for Naltrexone

纳曲酮控释系统

• 批准号: 6620594
• 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
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620594
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse chemotherapy; biodegradable product; bioengineering /biomedical engineering; chemical synthesis; dosage forms; drug delivery systems; drug design /synthesis /production; high performance liquid chromatography; laboratory rat; male; microcapsule; naltrexone; nanotechnology; narcotic antagonists; pharmacokinetics; polymers; scanning electron microscopy; slow release drug; subcutaneous drug administration; transmission electron microscopy

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，酗酒人数约为7.5% 百分之百的美国人口(约1400万美国人)虐待和/或 对酒精的依赖。与酒精有关的死亡约占5% 在美国所有的死亡中，除了人类的痛苦，这是很难 量化，据估计，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：心血管、神经、胃肠、免疫学、 精神科和产科并发症。治疗的主要途径 酒精中毒包括戒毒、非药物性、(心理社会) 治疗方法，以及药物治疗。心理社会的有效性 治疗方法尚未建立：它们很少或根本没有遇到 在治疗酒精中毒方面取得成功。药物开发的重点是治疗 成瘾障碍，如酗酒，已从戒断状态转为复发。 预防。 纳曲酮(已获食品药品监督管理局批准)的有效性 美国食品和药物管理局(FDA)受到合规问题的限制：酗酒者显示 尤其是服药依从率很低。此外，纳曲酮是一种 高萃取率药物，母体药物含量较低 大脑。因此，有必要开发一种受控的 其中的递送系统，不仅可以维持药物的长时间释放 时间，但可以通过一次释放药物来维持恒定的血液水平 吸收部位的恒定速率。如果递送系统是 可注射的纳曲酮可以避免肝脏的首过效应。在我们的 初步研究，我们已经开发出聚合物可注射纳米和 纳曲酮微粒控释系统可持续 纳曲酮的体外可利用度超过三个月。 我们的目标是持续提供纳曲酮6至12个月。 可生物降解和生物相容共聚物的合成及其在生物材料中的应用 纳曲酮控释系统的制备工艺优化及其性能 在大鼠身上进行评估是这项提案的重点。受控的使用 释放纳曲酮制剂将确保遵从性，因为需要 决定服药的患者将被最小化；它还可能 通过产生更多的 母体药物的可预测和恒定的血浆浓度，并使其 在大脑中可用。