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

静脉输送氧气微泡治疗缺氧和急性呼吸窘迫综合征

• 批准号: 10384013
• 负责人: Benjamin Arcand
• 金额: $ 30.55万
• 依托单位: AGITATED SOLUTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384013
• 关键词: Acute; Acute Lung Injury; Acute Respiratory Distress Syndrome; Acute myocardial infarction; Adoption; Adverse effects; Affect; Air; Alveolar; Animals; Beak; Behavior; Biocompatible Materials; Blood; Blood Circulation; Bypass; COVID-19; Cannulas; Carbon Dioxide; Cardiac; Cardiopulmonary; Cardiovascular system; Catastrophic Illness; Catheters; Cell Membrane Permeability; Charge; Chemicals; China; Chronic Disease; Chronic Obstructive Pulmonary Disease; Clinical; Congestive Heart Failure; Continuous Infusion; Continuous Positive Airway Pressure; Critical Illness; Dangerousness; Development; Devices; Diagnostic; Diffuse; Diffusion; Dose; Dysbarism; Effectiveness; Embolism; Extracorporeal Membrane Oxygenation; FDA approved; Family suidae; Femoral vein; Fluid overload; Future; Gases; Goals; Heart; Heart failure; Hour; Hypercapnia; Hypoxemia; Hypoxemic Respiratory Failure; Hypoxia; Iatrogenesis; Inferior vena cava structure; Infusion Pumps; Infusion procedures; Injections; Intravenous; Ischemic Stroke; Knowledge; Liquid substance; Lung; Measures; Mechanical ventilation; Mechanics; Metabolic; Metals; Methods; Microbubbles; Modeling; Myocardial; Myocardial Infarction; Nitrogen Dioxide; Nose; Oxygen; Patients; Peripheral; Phase; Physiological; Practice Management; Pre-Clinical Model; Procedures; Property; Pulmonary Fibrosis; Ramp; Renal function; Safety; Sample Size; Scientist; Septic Shock; Sheep; Surface; System; Systems Development; Techniques; Technology; Testing; Therapeutic; Tissues; Translating; Treatment Efficacy; Variant; absorption; alternative treatment; clinical practice; cost; critical limb Ischemia; effective therapy; hemocompatibility; hemodynamics; high risk; hyperbaric chamber; improved; improved outcome; in vitro Model; in vivo; innovation; lung injury; minimally invasive; normoxia; novel; oxygen toxicity; porcine model; preclinical study; pressure; prevent; prototype; respiratory assist; risk minimization; success; ultrasound

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.

项目摘要 本第1阶段项目的目标是开发用于静脉内气态氧的AS-O2-001系统 用于治疗缺氧的微泡递送。缺氧是一种灾难性的疾病，可导致急性 呼吸窘迫综合征（ARDS），慢性阻塞性肺病（COPD），肺纤维化， COVID-19、充血性心力衰竭和心肌梗死。严重受影响患者的现有治疗方案 患者包括体外膜氧合（ECMO）和机械通气，这两者都是 侵入性、昂贵且具有医源性后遗症。Agitated Solutions Inc正在开发一部小说， 有创替代方案：AS-O2-001系统将气态氧微泡输送到下腔静脉， 延迟或阻止机械通气或ECMO。 气态氧输送在历史上曾导致栓塞形成;然而，如今技术的改进 能够输送微泡（<100 µm）。微泡具有独特的性质，包括其收缩性， 塌陷、气体的加速扩散和防止聚结成栓子的带负电荷的表面。 过饱和氧是利用氧气微泡的一种这样的疗法，并且已经在急性呼吸道疾病中取得了成功。 治疗（如心肌梗塞），但不能轻易地应用于慢性疾病，如缺氧，由于 体液过多正在开发的其他替代治疗方法，如化学涂层微泡或 血管内呼吸辅助导管已经出现了不利的代谢作用或心脏不耐受， 阻止其临床应用。 AS-O2-001系统是有前途的，因为它利用了微泡在过饱和环境中的安全性和有效性。 氧气，但去除了在患有缺氧的重症患者中有害的液体的过量。 此外，AS-O2-001系统应用于下腔静脉，并吸取了 血管内呼吸辅助导管，以防止心脏不耐受，包括小形状因子， 小的插入尺寸和生物相容性材料的使用。 在目标1中，将在体外模型中开发和测试AS-O2-001系统，以表征其在以下情况下的安全性： 防止空气栓塞的形成及其在输送治疗相关剂量方面的有效性。在目标2中， 将在体内对系统进行评价，以证明静脉输注氧气的安全性和概念验证 在正常氧血症和高氧血症的猪模型中。该项目的成功完成将证明 通过静脉注射输送治疗用氧气的新方法的可行性 微泡