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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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要该第一阶段项目的目标是开发用于静脉注射气态氧气的 AS-O2-001 系统微泡输送用于治疗缺氧。缺氧是一种灾难性的疾病，可能由急性缺氧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。目前严重受影响的治疗方案患者的治疗包括体外膜肺氧合（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. 正在开发一种新颖的、最低限度的侵入式替代方案：AS-O2-001 系统将气态氧微泡输送到下腔静脉，以延迟或阻止机械通气或 ECMO。历史上，气态氧输送会导致栓塞形成。然而，今天的技术有所改进能够输送微泡（<100 µm）。微泡具有独特的特性，包括收缩性塌陷、气体加速扩散以及防止聚结成栓塞的带负电表面。过饱和氧是一种利用氧气微泡的疗法，并在急性发作中取得了成功。治疗（例如心肌梗塞），但不能轻易应用于慢性疾病，例如由于缺氧引起的液体超负荷。正在开发的其他替代处理方法，例如化学涂层微泡或血管内呼吸辅助导管，已发现不良代谢作用或心脏不耐受阻止它们的临床采用。 AS-O2-001 系统很有前途，因为它利用了过饱和微泡的安全性和有效性氧气，但消除了液体的过度负担，这对于严重缺氧的患者来说是有害的。此外，AS-O2-001系统应用于下腔静脉，借鉴了血管内呼吸辅助导管，以防止心脏不耐受，包括小型、插入尺寸小，并且使用生物相容性材料。在目标 1 中，将开发 AS-O2-001 系统并在体外模型中进行测试，以表征其安全性防止空气栓塞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这种通过静脉注射输送治疗性氧气的新颖创新方法的可行性微气泡。