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; 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 该阶段1项目的目的是开发用于静脉注射氧气的AS-O2-001系统 微泡递送用于治疗缺氧。缺氧是一种灾难性疾病，可能由急性引起 呼吸窘迫综合征（ARDS），慢性阻塞性肺疾病（COPD），肺纤维化， Covid-19，充血性心力衰竭和心肌梗塞。严重影响的当前治疗选择 患者包括体外膜氧合（ECMO）和机械通气，它们都是 侵入性，昂贵且具有卵生序列。 Antiated Solutions Inc.正在开发一部小说，最少 侵入性替代方案：AS-O2-001系统将气态氧微泡输入下腔静脉 延迟或防止机械通气或ECMO。 历史上，气体氧的递送导致了栓子形成。但是，今天的技术改进了 实现微泡的输送（<100 µm）。微泡具有独特的特性，包括它们的收缩 塌陷，加速的加速扩散以及带负电的表面，可防止聚集成栓子。 过饱和氧是一种使用氧气微泡的疗法，并且在急性方面取得了成功 治疗（例如心肌违规），但不能轻易应用于慢性疾病（例如由于缺氧） 流体超负荷。开发中的其他替代处理，例如化学涂层的微泡或 血管内呼吸辅助导管，已经看到了不良代谢作用或心脏摄入剂， 防止其临床采用。 承诺AS-O2-001系统是因为它利用了微泡的安全性和效率 氧气，但消除了液体的覆盖，这在严重患有缺氧的患者中会有害。 此外，AS-O2-001系统应用于下腔静脉，并从中学到了教训 血管内呼吸辅助导管，以防止心脏渗透，包括小型尺寸，A 小插入尺寸以及使用生物相容性材料。 在AIM 1中，AS-O2-001系统将在体外模型中开发和测试，以表征其安全性 防止形成空气栓塞及其在提供治疗相关剂量方面的有效性。在AIM 2中 系统将在体内进行评估，以证明静脉输送氧气的安全性和证明 在常氧血症和高氧血症的猪模型中。成功完成该项目将证明 这种新颖而创新的方法的可行性，将治疗氧作为静脉注射 微泡。