Intravenous delivery of oxygen microbubbles for the treatment of hypoxia and ARDS

项目总结 该第一阶段项目的目标是开发用于静脉、气态氧气的AS-O2-001系统 微泡给药治疗缺氧。缺氧是一种灾难性的疾病，可由急性 呼吸窘迫综合征(ARDS)、慢性阻塞性肺疾病(COPD)、肺纤维化、 新冠肺炎、充血性心力衰竭和心肌梗死。目前对严重受影响的患者的治疗方案 患者包括体外膜氧合(ECMO)和机械通气，这两种方法都是 侵入性的，昂贵的，并有医源性后遗症。激越解决方案公司正在开发一种新的、最低限度的 侵入性选择：AS-O2-001系统将气态氧气微泡输送到下腔静脉，以 延迟或阻止机械通气或ECMO。 气态氧气输送在历史上曾导致血栓的形成；然而，今天的技术有所改进 可输送微泡(&lt；100微米)。微泡具有独特的特性，包括它们的收缩 塌陷，气体加速扩散，以及带负电荷的表面防止凝聚成栓子。 过饱和氧气是一种利用氧气微泡的治疗方法，并已在急性 治疗(如心肌梗塞)，但不能轻易应用于慢性疾病，如由于以下原因造成的缺氧 液体超载。正在开发的其他替代疗法，如化学涂层微泡或 血管内呼吸辅助导管，出现不良代谢影响或心脏不耐受 阻止他们的临床采用。 AS-O2-001系统很有前景，因为它利用了微泡在过饱和状态下的安全性和有效性。 氧气，但消除了液体的负担，这对患有缺氧的重病患者是有害的。 此外，AS-O2-001系统被应用于下腔静脉，并吸取了经验教训 血管内呼吸辅助导管，以防止心脏不耐受，包括一种小型因素， 插入物尺寸小，并使用生物兼容材料。 在目标1中，AS-O2-001系统将被开发并在体外模型中进行测试，以表征其在 预防空气栓子的形成及其在提供治疗相关剂量方面的有效性。在目标2中， 系统将在体内进行评估，以证明静脉输氧的安全性和概念证明 在常氧血症和高氧血症的猪模型中。这个项目的成功完成将证明 这种新颖创新的静脉注射给氧方法的可行性 微泡。

PROJECT SUMMARY The goal of this Phase 1 project is to develop the AS-O2-001 System for intravenous, gaseous oxygen microbubble delivery for treatment of hypoxia. Hypoxia is a catastrophic illness that can result from acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, COVID-19, congestive heart failure and myocardial infarction. Current treatment options for severely affected patients include extracorporeal membrane oxygenation (ECMO) and mechanical ventilation, which are both invasive, expensive, and have iatrogenic sequalae. Agitated Solutions Inc. is developing a novel, minimally invasive alternative: the AS-O2-001 system delivers gaseous oxygen microbubbles into the inferior vena cava to delay or prevent mechanical ventilation or ECMO. Gaseous oxygen delivery has historically resulted in emboli formation; however, improved technology today enables the delivery of microbubbles (<100 µm). Microbubbles have unique properties, including their shrinking collapse, accelerated diffusion of gases, and negatively charged surface that prevents coalescence into emboli. Supersaturated oxygen is one such therapy that utilizes microbubbles of oxygen and has seen success in acute treatments (e.g. myocardial infarctions), but cannot readily be applied for chronic illness such as hypoxia due to fluid overload. Other alternative treatments in development, such as chemically coated microbubbles or intravascular respiratory assist catheters, have seen adverse metabolic effects or cardiac intolerance that prevent their clinical adoption. The AS-O2-001 system is promising because it utilizes the safety and efficacy of microbubbles in supersaturated oxygen but removes the overburden of fluids which would be deleterious in severely ill patients with hypoxia. Furthermore, the AS-O2-001 system is applied in the inferior vena cava and takes lessons learned from intravascular respiratory assist catheters in order to prevent cardiac intolerance, including a small form factor, a small insertion size, and the use of biocompatible materials. In Aim 1, the AS-O2-001 System will be developed and tested in an in vitro model to characterize its safety in preventing formation of air emboli and its effectiveness in delivering a therapeutic relevant dose. In Aim 2, the System will be evaluated in vivo to demonstrate the safety and proof of concept of intravenous delivery of oxygen in a porcine model of normoxemia and hyperoxemia. Successful completion of this project will demonstrate the feasibility of this novel and innovative method of delivering therapeutic oxygen as intravenously injected microbubbles.