Low Cost Electrochemical Gas Phase Nitric Oxide Generator for Biomedical Applications

摘要： 气相一氧化氮(NO)的治疗用途在医学上有几个重要的应用。从它的第一个 医疗应用20多年前，吸入性一氧化氮(INO)已成为强化治疗的中流砥柱 关爱肺衰竭患者。作为一种肺血管扩张剂，INO在新生儿、肺 移植和肺动脉高压。作为一种吸入型防腐剂，一氧化氮已在 治疗囊性纤维化、鼻窦炎和肺结核引起的慢性呼吸道感染。更进一步说，不 添加到体外循环(ECC)中的扫气可防止血小板激活(防止 血栓)和白细胞(预防全身炎症反应综合征)。当前 用于这些应用的产生和监测气相NO的方法昂贵且不方便 由于传统气瓶中高浓度的NO不稳定。在此合并阶段中 I/II STTR应用，NOTA实验室有限责任公司将与密歇根大学的研究人员合作 (U Of M)进一步开发一种全新的、非常低成本的基于电化学(E-Chem)的紧凑型材料， 便携式临床用高纯度气相NO生成仪器(NOGEN)。方法是 基于通过优化的铜(II)配体络合物将简单的亚硝酸根离子还原为NO气体的E-Chem还原 引导电子从工作电极有效地将NO2-还原为NO(G)。在第一阶段，加州大学的研究人员 M和NOTA的科学家/工程师将共同努力优化E-Chem nogen的设计 系统在关键部件方面(例如，使用各种金属网或泡沫，或金属/碳墨水电极， 用不透气的有机硅中空纤维、最佳的亚硝酸盐和铜(II)制成的优化气体分离器- 溶液阶段的复杂程度，以及用于反馈/严格控制NO的NO/NO2传感器 制作等)。在创建具有高纯度所需的高纯度的目标气相NO水平方面的准确性 医疗应用也将在第一阶段得到验证。在第二阶段，进一步开发原型产品。 将继续将所有组件完全合并到一个紧凑型NOGEN单元中，该单元将具有 可更换电极和电解液模块。此外，新的Nogen原型系统将 在密歇根大学CPB和INO的动物模型上进行测试，以证明这种方法的临床潜力和安全性 新的低成本系统。NOTA打算首次将nogen系统推向市场，用于预防血小板 CPB期间的激活和SIRS，然后继续应用NOGEN系统治疗新生儿/成人 肺动脉高压，并进一步用作家庭INO单位治疗囊性纤维化的慢性肺部感染 病人。

ABSTRACT: Therapeutic use of gas phase nitric oxide (NO) has several important applications in medicine. Since its first medical application more than 20 years ago, inhaled nitric oxide (INO) has become a mainstay of intensive care for lung failure patients. As a pulmonary vasodilator, INO is essential in neonatology, lung transplantation, and pulmonary hypertension. As an inhaled antiseptic agent, NO has been proposed in the treatment of chronic airway infection that occurs in cystic fibrosis, sinusitis, and tuberculosis. Further, NO added to the sweep gas in extracorporeal circulation (ECC) prevents activation of platelets (preventing thrombosis) and white blood cells (preventing systemic inflammatory response syndrome (SIRS)). Current methods of creating and monitoring gas phase NO for these applications are expensive and inconvenient owing to the instability of high concentrations of NO within conventional gas cylinders. In this combined Phase I/II STTR application, NOTA Laboratories LLC will collaborate with researchers at the University of Michigan (U of M) to further develop a completely new and very low-cost electrochemical (E-chem) based compact, portable instrument to generate high purity gas phase NO for clinical applications (NOGEN). The method is based on the E-chem reduction of simple nitrite ions to NO gas via an optimized Cu(II)-ligand complex that channels electrons from a working electrode to efficiently reduce NO2- to NO(g). In Phase I, researchers at U of M and scientists/engineers at NOTA will work together to optimize the design of the E-chem NOGEN system, in terms of key components (e.g., using various metal mesh or foam, or metal/carbon ink electrodes, an optimized gas separator made with highly NO permeable silicone hollow fibers, optimal nitrite and Cu(II)- complex levels in the solution phase, and incorporation of NO/NO2 sensors for feedback/tight control of NO production, etc.). The accuracy in creating targeted gas phase NO levels with the high purity required for medical applications will also be verified in Phase I. In Phase II, further development of a prototype product will continue with full incorporation of all the components into a single compact NOGEN unit that will have replaceable electrode and electrolyte solution modules. In addition, the new prototype NOGEN system will be tested in animal models of CPB and INO at U of M to demonstrate the clinical potential and safety of this new, low-cost system. NOTA intends to first market the NOGEN system for use in preventing platelet activation and SIRS during CPB and then pursue applications of the NOGEN system for treating neonate/adult pulmonary hypertension, and further use as a home INO unit to treat chronic lung infections in cystic fibrosis patients.