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持续作用注射制剂， - 丁丙诺啡，基于BIOTEK空气悬浮液制备的微胶囊 过程微胶囊将用于一项大型安慰剂对照研究， SBIR计划的第二阶段。最近我们测试了30天丁丙诺啡 在约翰霍普金斯大学学院的5名海洛因成瘾者中使用微胶囊 行为药理学研究中心 对于所有5名受试者，长效丁丙诺啡药物似乎提供了 阿片类药物戒断症状显著缓解，无中毒证据，或 储药后观察6周内的呼吸抑制， 考核此外，该制剂非常有效， 降低对外源性阿片样物质激发的反应性，持续时间为 至少几个星期。临床上，所有五名参与者都成功地实现了 阿片类药物解毒，不使用其他药物缓解戒断症状，以及 无临床显著戒断体征或症状。期间 随后的2周门诊期，所有患者均报告戒断 阿片类药物和尿液毒理学样本对阿片类药物呈阴性。这些 令人激动的重大发现迫使我们继续前进， 加速在大量海洛因人群中检测长效丁丙诺啡 适当的安慰剂对照。 在SBIR计划下寻求支持，以开发和优化一个更 通过使用一种新的 生产微胶囊的产率高得多（增加5-6倍）的方法 在可注射的尺寸范围内。在本报告详细介绍的初步研究中， 应用，我们已经证明了制造成本的显着降低 以及新旧制剂中丁丙诺啡释放曲线的等效性 公式化。 在SBIR计划的第二阶段，微胶囊的开发将 完成后，将在cGMP下制备大量小瓶。当前IND 将更新并提交给FDA，同时提交一份临床方案， 在较大的海洛因成瘾者人群中使用适当的安慰剂 对照 拟定商业应用： 持续作用阿片激动剂/拮抗剂制剂，如微囊化丁丙诺啡将是一个重大进展。每月一次治疗具有经济优势，可使工作人员将更多的时间用于患者，减少给药时间。该制剂将提供类似于纳洛酮的阿片样物质拮抗作用，但由于类似于美沙酮或LAAM的激动作用，成瘾后患者退出治疗的动机较小。总体治疗计划不需要围绕严格的给药方案。相反，治疗可以被设计成最有利于患者，并且消除习惯性吸毒行为的例子。因此，药物成为一种辅助手段，而不是治疗的主要方面。

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.