CONTROLLED-RELEASE IMPLANTS OF DISULFIRAM METABOLITES

双硫仑代谢物的控释植入物

• 批准号: 2044972
• 负责人: KELLY L SMITH
• 金额: $ 24.6万
• 依托单位: BEND RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2044972
• 关键词: alcoholism /alcohol abuse chemotherapy; alcoholism antagonist; antiseptic sterilization; bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial evaluation; disulfiram; dosage; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; high performance liquid chromatography; implant; laboratory rat; nonhuman therapy evaluation; pharmacokinetics; plastics; polymers

The goal of this program is to develop a bioerodible, controlled-release implant for the treatment of alcoholism. Specific Phase II aims are 1) to determine essential in vivo characteristics of a potent metabolite of disulfiram, 5-methyl N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO); 2) to develop candidate bioerodible implants to deliver that metabolite; and 3) to test the efficacy of those candidate implants in rats. The dose- response characteristics, toxicity, and basic pharmacokinetics of DETC- Meso will be determined to identify the target performance of the implants. A series of bioerodible beads will be prepared, and their controlled-release and biodegradation characteristics determined. Candidate beads will then be implanted into rats for in vivo determination of efficacy via inhibition of aldehyde dehydrogenase. The use of bioerodible implants should greatly improve patient compliance in alcoholism programs. The use of DETC-MeSO, which is much more potent than disulfiram, should enable reasonably small implants to be effective, and it is also expected to be a more effective drug than disulfiram. Substantial commercial interest in this technology for treatment of alcoholism is expected if the results of this program are successful, and the technology may also be useful for other types of drugs, such as narcotic antagonists and chemotherapeutic agents.

该计划的目的是开发可生物反应的释放 用于治疗酒精中毒的植入物。 特定的第二阶段目标是1） 确定有效代谢产物的体内特征 二硫仑，5-甲基N，N-二乙基硫醇甲酸磺酸盐（detc-Meso）； 2） 开发候选生物剂量植入物以提供代谢物；和 3）测试这些候选植入物在大鼠中的功效。 剂量 - 响应特征，毒性和基本药代动力学 将确定中索以确定 植入物。 将准备一系列生物剂的珠子，他们的 确定的受控释放和生物降解特征。 然后将候选珠植入大鼠以进行体内测定 通过抑制醛脱氢酶的抑制作用。 使用 可生物化植入物应大大提高患者的依从性 酒精中毒计划。 使用destc-meso，比 二硫仑，应使合理的植入物能够有效，并且 预计它将比二硫酸酯更有效。 这项技术的重大商业兴趣用于治疗 如果该计划的结果成功，则期望酒精中毒，并且 该技术也可能对其他类型的药物有用，例如 麻醉拮抗剂和化学治疗剂。