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: 10328221
• 负责人: Robert H. Bartlett
• 金额: $ 86.51万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328221
• 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; 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; Respiratory Tract Infections; 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.

抽象的： 气相一氧化氮（NO）的治疗用途在医学中具有多种重要应用。自第一个 20多年前的医疗应用，吸入一氧化氮（INO）已成为密集型的中流 照顾肺衰竭患者。作为肺血管扩张剂，INO在新生儿学中至关重要，肺 移植和肺动脉高压。作为吸入的防腐剂，在 囊性纤维化，鼻窦炎和结核病中发生的慢性气道感染的治疗。此外，不 在体外循环（ECC）中添加到清扫气体中可防止血小板激活（防止 血栓形成）和白细胞（预防全身性炎症反应综合征（SIRS））。当前的 这些应用程序创建和监视气相NO的方法昂贵且不便 由于常规气缸内NO的高浓度不稳定。在这个组合阶段 I/II STTR应用程序，Nota Laboratories LLC将与密歇根大学的研究人员合作 （M的U）进一步开发一个全新的，非常低成本的电化学（E-Chem）契约， 用于生成临床应用（Nogen）的高纯度气相NO的便携式仪器。该方法是 基于通过优化的Cu（II）配合物将简单亚硝酸盐离子降低至无气体，以 通道从工作电极从工作电极有效降低NO2-至否（G）。在第一阶段，您的研究人员 N Nota的M和科学家/工程师将共同努力优化E-Chem Nogen的设计 系统，就关键组件而言（例如，使用各种金属网格或泡沫或金属/碳墨水电极， 由高度无渗透硅纤维，最佳亚硝酸盐和Cu（II） - 制成的优化气体分离器 溶液阶段中的复杂水平，并掺入NO/NO2传感器以进行反馈/紧密控制NO 生产等）。创建目标气相的准确性无水平，并且所需的高纯度 医疗应用也将在第一阶段中进行验证。在第二阶段，原型产品的进一步开发 将继续将所有组件完全合并到一个紧凑的nogen单元中 可更换电极和电解质溶液模块。此外，新的原型NOGON系统将 在M的CPB和IO的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打算首先推销NOGON系统用于防止血小板 CPB期间的激活和SIRS，然后追求NOGON系统治疗新生儿/成人的应用 肺动脉高压，并进一步用作囊性纤维化中慢性肺部感染的家用单位 患者。