Buprenorphine Microcapsules for Heroin Addiction

描述(由申请人提供)：该计划的总体目标是 开发一种新的更经济的缓释制剂 -丁丙诺啡，以Biotek空气悬浮剂制备的微囊为基础 进程。这种微胶囊将用于一项大型的安慰剂对照研究 SBIR计划的第二阶段。最近我们测试了30天的丁丙诺啡 约翰霍普金斯大学学院五(5)名海洛因成瘾者体内的微胶囊 行为药理学研究组，医学系。 对于所有五个受试者，仓库丁丙诺啡药物似乎提供了 在没有中毒或中毒证据的情况下戒断阿片类药物显著缓解 入库后六周的呼吸抑制观察和 评估。此外，该配方在极大程度上对 在持续时间内降低对外源性阿片类药物激发的反应性 至少几个星期。临床上，所有五名参与者都成功地实现了 阿片类药物戒毒，没有其他戒断药物，以及 没有临床上显著的戒断迹象或症状。在.期间 随后两周的门诊阶段，所有患者都报告从 阿片类药物和尿毒学样本均为阿片类药物阴性。这些 非凡和令人振奋的发现迫使我们向前推进，扩大和 加快在大量海洛因人群中检测丁丙诺啡仓库 使用适当的安慰剂对照的瘾君子。 在SBIR计划下寻求支持，以开发和优化更多 新型丁丙诺啡微囊经济配方的研究 生产高得多的微胶囊(增加5-6倍)的工艺 在可注射的尺寸范围内。在本文件中详述的初步研究中 应用后，我们已显著降低了制造成本 新旧丁丙诺啡释药曲线的等效性 配方。 在SBIR计划的第二阶段，微胶囊的开发将 完成后，将根据cGMP准备大量的瓶子。当前的工业 将被更新并提交给FDA，并带有临床方案以测试 更多海洛因成瘾者服用适当安慰剂的配方 控制。 建议的商业应用： 一种持久作用的阿片激动剂/拮抗剂配方，如丁丙诺啡微囊化，将是一个重大进展。每月治疗一次是一种经济优势，使工作人员可以将更多的时间花在患者身上，而不是花在剂量管理上。这种制剂将提供像纳曲酮一样的阿片拮抗作用，但由于类似于美沙酮或LAAM的兴奋作用，成瘾者退出治疗的动机将会减少。整个治疗计划将不需要围绕严格的剂量计划。相反，治疗可以设计为对患者最有利，并消除习惯性吸毒行为的例子。因此，这种药物成为治疗的辅助手段，而不是主要方面。

DESCRIPTION (provided by applicant): The overall objective of the program is to develop a new more economical sustained action injectable formulation of -buprenorphine, based on microcapsules prepared by BIOTEK's air suspension process. The microcapsules will be used in a large placebo controlled study in Phase II of the SBIR program. Recently we tested 30-day buprenorphine microcapsules in five (5) heroin addicts at the Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit. For all five subjects the depot buprenorphine medication appeared to provide remarkable relief from opioid withdrawal without evidence of intoxication or respiratory depression over the six weeks of post-depot observation and assessment. Furthermore, the formulation was very effective in dramatically reducing responsiveness to exogenous opioid challenge for a duration of at least several weeks. Clinically, all five participants successfully achieved opioid detoxification, without other medications for withdrawal relief, and without clinically significant withdrawal signs or symptoms. During the subsequent 2-week outpatient phase all patients reported abstinence from opioids and urine toxicology samples were negative for opioids. These remarkable and very exciting findings compel us to drive forward and expand and accelerate the testing of depot buprenorphine in a large population of heroin addicts with appropriate placebo controls. Support is sought under the SBIR program to develop and optimize a more economic formulation of depot buprenorphine microcapsules, by using a new process which produces a much higher yield (5-6 fold increase) of microcapsules in the injectable size range. In preliminary studies detailed in this application, we have demonstrated significant reduction in manufacturing costs and the equivalency of the buprenorphine release profile from the old and new formulation. During Phase II of the SBIR program, microcapsule development will be completed, a large number of vials will be prepared under cGMP. The current IND will be updated and submitted to the FDA with a clinical protocol to test the formulation in a larger population of heroin addicts with appropriate placebo controls. PROPOSED COMMERCIAL APPLICATION: A sustained action opioid agonist/antagonist formulation, such as microencapsulated buprenorphine would be a significant advance. Once a month treatment is an economic advantage and allows staff members to devote more time to patients and less to dose administration. This formulation will provide opioid antagonism like that of naltrexone, but there would be less motivation for the post addict to drop out of therapy due to the agonistic action similar to that of methadone or LAAM. The overall treatment plan would not need to revolve about a rigid dosing schedule. Rather treatment could be designed to best benefit the patient, and an example of habitual drug taking behavior is eliminated. The drug thus becomes an adjunct not the major aspect of therapy.