CONTROLLED IONTOPHORETIC DELIVERY OF NARCOTICS

麻醉剂的受控离子电渗输送

• 批准号: 3504110
• 负责人: Tomasz J Petelenz
• 金额: $ 5万
• 依托单位: JMW ACQUISITION COMPANY, INC.
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1988-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3504110
• 关键词: analgesia; biomedical automation; clinical biomedical equipment; computer system design /evaluation; drug delivery systems; high performance liquid chromatography; human subject; human therapy evaluation; iontophoresis therapy; morphine; narcotics; pain threshold; placebos; radiotracer; silver chloride electrode

The aim of this proposal is to investigate and develop long-term iontophoretic procedures for delivery of narcotic agents. Iontophoresis has been known for a long time, but it application is limited to short term procedures (15-30 min.). The major impediment to long term use is the formation of electrolytic products at the electrode, lowering the efficiency of drug transport and causing complications (burns). These problems have been addressed by our group: long-term delivery has been studied both theoretically and experimentally with morphine as a model drug. As a result, treatment times have been extended up to 2 hrs with significant morphine levels in blood and no complications. The proposed study involves: 1) Laboratory in-vitro determinations of iontophoretic electrode efficiency and delivery rates over long (12-24 hrs) application times using an automated, computer controlled sampling system. 2) Animal experiments using nude rats with isolated skin flaps in order to determine long-term delivery rates with 14C morphine HCl. 3) A controlled, double blind clinical study involving patients afflicted by severe post-operative pain. In this part of the study 12 - 15 patients will be administered morphine by iontophoresis at a predetermined rate and the same number of patients will receive an iontophoretically delivered placebo. The results will be assessed statistically by comparison of frequency of IV/PCA requirements in both groups. The result of these studies will be a new iontophoretic drug delivery system for narcotic analgesics, primarily morphine. In Phase II, new electrode formulations and an iontophoretic control device will be designed, fabricated and used in large scale long-term clinical trials.

本提案的目的是调查和制定长期 用于输送麻醉剂的离子电渗疗法。 离子电渗疗法 早已为人所知，但应用仅限于短期 程序（15-30 分钟）。 长期使用的主要障碍是 在电极处形成电解产物，降低 药物运输效率和引起并发症（烧伤）。 这些 我们集团已解决问题：长期交付已 以吗啡为模型进行了理论和实验研究 药品。 结果，治疗时间延长至 2 小时 血液中吗啡含量显着，且无并发症。 拟议的研究涉及：1）实验室体外测定 长时间（12-24 小时）离子电渗电极效率和输送率 使用自动化、计算机控制的采样系统的施用时间。 2）使用带有分离皮瓣的裸鼠进行动物实验，以 确定 14C 吗啡盐酸盐的长期给药率。 3）受控， 涉及患有严重疾病的患者的双盲临床研究 术后疼痛。 在这部分研究中，将有 12 - 15 名患者 以预定的速率通过离子电渗疗法施用吗啡 许多患者将接受离子电渗疗法递送的安慰剂。 结果将通过比较频率进行统计评估 两组的 IV/PCA 要求。 这些研究的结果将是 用于麻醉镇痛药的新型离子电渗给药系统，主要 吗啡。 在第二阶段，新的电极配方和离子电渗控制装置 将被设计、制造并用于大规模长期临床 试验。