Low Cost Electrochemical Gas Phase Nitric Oxide Generator for Biomedical Applications

用于生物医学应用的低成本电化学气相一氧化氮发生器

• 批准号: 10026450
• 负责人: Robert H. Bartlett
• 金额: $ 60.26万
• 依托单位: NOTA LABORATORIES, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10026450
• 关键词: Adult; Animal Model; Area; Blood; Carbon; Cardiopulmonary Bypass; Cathodes; Cells; Chronic; Clinical; Clinical Trials; Complex; Conduct Clinical Trials; Copper; Cystic Fibrosis; Development; Devices; Effectiveness; Electrodes; Electrolytes; Electrons; Elements; Engineering; Extracorporeal Circulation; Family suidae; Feedback; Fiber; Gases; Generations; Home; Hospital Design; Hospitals; Infection; Inhalation; Ink; Intensive Care; Intuition; Ions; Laboratories; Lead; Leukocytes; Ligands; Local Anti-Infective Agents; Lung; Lung Transplantation; Lung diseases; Lung infections; Mediator of activation protein; Medical; Medicine; Metals; Methods; Michigan; Monitor; Neonatology; Nitric Oxide; Nitrites; Nitrogen; Nitrogen Dioxide; Operative Surgical Procedures; Output; Oxygenators; Patients; Performance; Permeability; Phase; Platelet Activation; Preparation; Procedures; Production; Pulmonary Hypertension; Reaction; Regulation; Research Personnel; Respiratory Failure; Safety; Scientist; Silicone Elastomers; Silicones; Sinusitis; Small Business Technology Transfer Research; Source; Stream; Surface; System; Systemic Inflammatory Response Syndrome; Techniques; Technology; Testing; Therapeutic Uses; Thrombosis; Time; Tuberculosis; Universities; Vasodilator Agents; Ventilator; Work; base; clinical application; cost; cystic fibrosis infection; cystic fibrosis patients; design; inhaled nitric oxide; instrument; neonatal pulmonary hypertension; neonate; point of care; porcine model; portability; prevent; prototype; respiratory gas; sensor

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.

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。从第一 在20多年前的医学应用中，吸入性一氧化氮（INO）已经成为强化治疗的主要手段。 肺衰竭患者的护理。作为肺血管扩张剂，INO在血液学、肺 移植和肺动脉高压。作为一种吸入式抗菌剂，NO已经在美国专利申请中提出。 治疗囊性纤维化、鼻窦炎和肺结核引起的慢性气道感染。均不会及无须 在体外循环（ECC）中加入到吹扫气体中，防止血小板活化（防止 血栓形成）和白色血细胞（预防全身炎症反应综合征（SIRS））。电流 用于这些应用的产生和监测气相NO的方法是昂贵和不方便的 这是由于常规气瓶内高浓度NO的不稳定性。在这一合并阶段 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 为了进一步开发一种全新的、成本非常低的基于电化学（E-chem）的致密物， 便携式仪器，以产生用于临床应用的高纯度气相NO（NOGEN）。该方法 基于通过优化的Cu（II）-配体络合物将简单亚硝酸根离子还原为NO气体的电化学还原， 从工作电极输送电子以有效地将NO2-还原为NO（g）。在第一阶段， 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，在关键组件方面（例如，使用各种金属网或泡沫，或金属/碳墨电极， 一种优化的气体分离器，由高NO渗透性的硅树脂中空纤维、最佳的亚硝酸盐和Cu（II）- 溶液相中的复杂水平，以及用于反馈/严格控制NO的NO/NO2传感器的结合 生产等）。产生目标气相NO水平的准确性与所需的高纯度， 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整合到一个紧凑的NOGEN装置中， 可更换的电极和电解质溶液模块。此外，新的原型NOGEN系统将 在密歇根大学的CPB和INO动物模型中进行测试，以证明其临床潜力和安全性 新的低成本系统。NOTA计划首先销售NOGEN系统，用于预防血小板减少 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 患者