Delivery system for inhaled nitric oxide

描述（由申请人提供）：本项目旨在开发一种技术，通过一种新方法来调节肺血管反应性，该方法可以在不存在可检测水平的有毒杂质二氧化氮（NO2）的情况下提供吸入一氧化氮（NO）。目前，氮气中浓度较高的NO在吸入前与氧气混合，在混合过程中产生有毒的NO2。GeNO方法从NO2开始，在特殊的抗坏血酸反应器中将其还原为NO，尽管这看起来似乎不合逻辑和自相矛盾。结果是给病人的一氧化氮量减少了100倍。一个基于使用储存在气瓶中的二氧化氮的系统已经建立并进行了测试。如果获得FDA的批准，GeNO准备在今年晚些时候在临床试验中使用这种设备。我们建议在第一阶段SBIR中，与GeNO， LLC和Caritas St. Elizabeth's Medical Center, Boston， MA建立研究伙伴关系，研究GeNO液体源输送系统在猪急性呼吸衰竭模型中吸入NO的生理性能和生物相容性，并与气体药盒系统进行比较。为此，我们提出以下具体目标：优化并测试用于NO吸入治疗的原型液源系统。具体目标2。在猪急性呼吸衰竭模型中评估通过新型GeNO液体系统吸入NO的生理效应，并确定可能毒性的程度和机制。考虑到吸入一氧化氮对肺血管反应性和氧合的影响，以及与现有技术相比，所提出的一氧化氮输送系统的潜在技术和经济优势，我们认为这项研究为这一全球性的公共卫生问题提供了重大的社会效益。

DESCRIPTION (provided by applicant): This project is intended to develop a technology that regulates pulmonary vascular reactivity through a new method that delivers inhaled nitric oxide (NO) without the presence of a detectable level of the toxic impurity nitrogen dioxide (NO2). Currently, concentrated NO in Nitrogen is mixed with oxygen just prior to inhalation, resulting in the formation of toxic NO2 from the very act of mixing. Although it may seem illogical and a paradox, the GeNO approach starts with NO2 and reduces it to NO in special ascorbic acid reactors which are located immediately prior to the patient. The result is a 100 fold reduction in the amount of NO delivered to the patient. A system based on the use of NO2 stored in gas bottles has been built and tested. Subject to approval from the FDA, GeNO is preparing to use this equipment in clinical trials later this year. We propose in this Phase I SBIR to establish a research partnership involving GeNO, LLC and Caritas St. Elizabeth's Medical Center, Boston, MA to study the physiological performance and biocompatibility of the GeNO liquid source delivery system for the delivery of inhaled NO compared with the gas cartridge system in a porcine model of acute respiratory failure. Accordingly, we propose the following specific aims: Specific Aim 1. Optimize and then test a prototype liquid source system for NO inhalation therapy. Specific Aim 2. Assess the physiological effect of inhaled NO delivery via the new GeNO liquid system in a swine model of acute respiratory failure, and ascertain the extent and mechanism associated with possible toxicities. Given the demonstrated effect of inhaled NO on pulmonary vasoreactivity and oxygenation, and the potential technical and economic advantages of the proposed NO delivery system compared with existing technologies, we perceive this research providing a significant societal benefit to this world-wide public health problem. PUBLIC HEALTH RELEVANCE: In order to address respiratory disease and pulmonary hypertension, GeNO has developed a means to generate inhaled nitric oxide (NO) for medical therapy through a method that is safer, simpler, and less expensive than what is now available. Currently, concentrated NO in Nitrogen is mixed with oxygen just prior to inhalation, resulting in the formation of toxic NO2 from the very act of mixing. Although it may seem illogical and a paradox, the GeNO approach starts with NO2 and reduces it to NO in a special ascorbic acid reactor which is located at the gas bottle. A redundant reactor, for safety reasons, is located immediately prior to the patient. The result is >100 fold reduction in the amount of NO2 delivered to the patient. We propose to optimize a liquid N2O4 source of the NO2, and compare its performance to the NO2 delivered from a gas tank. We also plan to study the physiological performance and biocompatibility of the two GeNO platforms for the delivery of inhaled NO in a porcine model of respiratory failure. This Phase I proposal is to optimize the liquid delivery system and begin preliminary animal studies.