Contaminate Removal for Laboratory Pharmaceutical Synthesis

描述（由申请人提供）：Compact Membrane Systems，Inc.提议修订授权1 R43 GM 084478 - 01 A1，标题为“实验室药物合成的污染物去除”，以响应通知NOT-OD-09-058，“NIH宣布恢复法案资金可用于竞争性修订申请”。在此修订申请中，我们提议去除污染物，如未反应的反应物，废催化剂和废有机溶剂的副产物。这是原始程序范围的二维变化：1）膜的操作模式与原始程序不同2）分离范围远远超出从溶剂中去除水和氧污染物。最初的项目集中在开发小型和低成本的膜基系统，用于从有机合成溶剂中去除氧和水污染物。大多数有机药物化学合成是在有机溶剂中进行的。有机溶剂中的氧和/或水污染物会破坏许多有机反应物和有机金属试剂和催化剂。因此，氧和水的去除对于成功的有机合成至关重要。不幸的是，氧气和水都是普遍存在的，并且必须引入显著的努力来去除氧气和水并继续将它们保持在系统之外。这一修订也是对NIH RFP PA-09-100“能源效率和可再生能源系统技术研究与开发”的响应。通过使用压力驱动的纳米过滤与热驱动的分离（例如用于回收制药废溶剂的蒸馏），我们也直接响应NIH的RFP以实现节能工艺。额外的资源将被添加到该计划，包括必要的设备，以执行的努力，以及新的雇员，包括经验丰富的和新的大学毕业生。紧凑型膜系统有许多工业和大学合作伙伴，他们对这项技术表现出浓厚的兴趣。这些合作伙伴将有助于第一阶段计划和随后的第二阶段活动和商业化。 公共卫生相关性：该项目将开发一种膜产品和工艺，不仅可以从反应溶剂和反应物中去除溶解氧和水，而且还可以扩展到包括未反应的化学品，废催化剂和废有机溶剂的副产品。膜系统原则上是通用的并且成本非常低。这一发展将代表CMS膜技术的应用，对制药相关的生产成本具有相当大的意义。

DESCRIPTION (provided by applicant): Compact Membrane Systems, Inc. is proposing a revision to grant 1 R43 GM084478-01A1 entitled "Contaminate Removal for Laboratory Pharmaceutical Synthesis" in response to notice NOT-OD-09-058, "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications" In this revision application, we are proposing to remove contaminants such as un-reacted reactants, spent catalysts and by-products from spent organic solvents by the membrane separation technique of nanofiltration. This is a two dimensional change in the scope of the original program: 1) the mode of operation of the membrane is different from the original program 2) scope of separations is well beyond removing water and oxygen contaminants from solvents. The original program was focused on developing small and low cost membrane based system for removal of oxygen and water contaminants from organic synthesis solvents. Most organic pharmaceutical chemical syntheses are done in organic solvents. Oxygen and/or water contaminants in organic solvents will destroy many organic reactants and organometallic reagents and catalysts. As such, the removal of oxygen and water are critical to successful organic synthesis. Unfortunately both oxygen and water are ubiquitous and significant effort must be introduced to both remove oxygen and water and continue to keep them out of the system. This revision is also responsive to NIH RFP PA-09-100 entitled "Energy Efficiency and Renewable Energy System Technology Research & Development". By using a pressure-driven nanofiltration versus a thermal- driven separation such as distillation for recovery of pharmaceutical spent solvents, we also are directly responsive to this NIH's RFP for energy efficient processes. Additional resources will be added to the program including necessary equipment to carry out the effort as well as new hires including both experienced and new college graduates. Compact Membrane Systems has numerous industrial and university partners which have shown a strong interest in this technology. These partners will be helpful in the Phase I program and subsequent Phase II activity and commercialization. PUBLIC HEALTH RELEVANCE: This project will develop a membrane product and process to not only remove dissolved oxygen and water from reaction solvents and reactants but also be expanded to include un-reacted chemicals, spent catalysts and by-products from spent organic solvents. The membrane system is in principle universal and very low cost. This development will represent an application of CMS membrane technology that has considerable significance to production costs related to pharmaceutical manufacturing.