Intra-pulmonary aerosol delivery for intubated pediatric patients

气管插管儿童患者的肺内气雾剂输送

• 批准号: 8454639
• 负责人: AMIR A NAQWI
• 金额: $ 23.94万
• 依托单位: MSP CORPORATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2015-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8454639
• 关键词: Acute Lung Injury; Acute Pneumonia; Address; Adult Respiratory Distress Syndrome; Aerosols; Air; Alveolus; Analgesics; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Biodistribution; Bolus Infusion; Breathing; Bypass; Caliber; Catheters; Characteristics; Childhood; Cicatrix; Clinical Trials; Complement; Critical Illness; Deposition; Development; Device or Instrument Development; Devices; Distal; Drug Delivery Systems; Dysbarism; Ensure; Environmental air flow; Essential Drugs; Etiology; Eye; Family suidae; Future; Gamma Cameras; Gases; Generations; Glucose; Growth; Healthcare; Infant; Inhalation Device; Intravenous; Label; Legal patent; Liquid substance; Lung; Metabolic Clearance Rate; Methods; Modeling; Neonatal; Particle Size; Patients; Penetration; Pharmaceutical Preparations; Phase; Pneumonia; Premature Infant; Property; Public Health; Radio; Radionuclide Imaging; Relative (related person); Resistance; Respiratory System; Respiratory tract structure; Resuscitation; Retinal Detachment; Rural; Sepsis; Small Business Innovation Research Grant; Steroids; Technology; Tracheostomy Tube; Tracheostomy procedure; Translating; Transportation; Tube; Ventilator; Work; absorption; aerosolized; design; drug clearance; endotracheal; flexibility; improved; in vitro Model; in vitro testing; in vivo; neonatal resuscitation; novel; operation; particle; pre-clinical; public health relevance; research study; respiratory distress syndrome; safety study; sedative; septic; success; surfactant

DESCRIPTION (provided by applicant): This project will provide a significantly improved method for intra-pulmonary drug delivery in pediatric patients who are intubated or have a tracheostomy. Currently available aerosolizing devices are limited in that only certain agents and only a small fraction (less than a few percent) of such drugs are actually delivered to the distal lung zones. We propose a novel Intra-Pulmonary Aerosol Generator (IPAG), which would be a 1 or 2 mm diameter tube inserted within the endotracheal tube. This IPAG will be capable of generating micro- aerosols that would reach the remote airways and alveoli with an efficiency approaching 100%. Further, our device is unique in that it uses extremely low airflow to generate respirable aerosols to minimize any potential barotrauma. Moreover, this aerosolizer can be synchronized to the inspiratory phase of the ventilator cycle without the introduction of significant resistance within the flow circuit. A broad range of ventilated pediatric patients fro a variety of etiologies including pneumonia, acute lung injury and acute respiratory distress syndrome would benefit from our proposed aerosol generator. IPAG would enable delivery of agents such as, antibiotics (for treatment of pneumonia and sepsis), as well as glucose, steroids, analgesics, and sedatives. IPAG allows for a simple means of essential drug delivery during resuscitation of patients and bypasses the immediate need for intravenous access. This is of particular utility in neonatal resuscitation and during transport of such infants from rural centers where intravenous access can be challenging and difficult. The core technology for the proposed device has been developed by Powerscope and is being used in preclinical work involving aerosol generation in vitrectomized gas-filled porcine eyes for inhibition of scar tissue growth caused by retinal detachment. We propose to translate and develop this technology into a feasible product that can be synchronized to ventilation and complement airflow dynamics. Aerosol generation and particle size distribution will be characterized with in-vitro models. Neonatal lamb model will be used to quantify pulmonary distribution, and systemic bio-absorption of aerosolized antibiotics delivered with IPAG. Completion of this Phase I SBIR project would prepare the grounds for efficacy studies with animal models of pneumonia and acute lung injury in the Phase II project with further safety studies in order to prepare the devic for future clinical trials.

描述（由申请人提供）：该项目将为插管或气管切开的儿科患者提供一种显着改进的肺内药物输送方法。目前可用的雾化装置的局限性在于，只有某些药剂并且只有一小部分（少于百分之几）的此类药物实际上被输送到远端肺部区域。我们提出了一种新型肺内气溶胶发生器 (IPAG)，它是插入气管插管内的 1 或 2 毫米直径的管。该 IPAG 将能够产生微气溶胶，并以接近 100% 的效率到达远端气道和肺泡。此外，我们的设备的独特之处在于它使用极低的气流来产生可呼吸气溶胶，以最大限度地减少任何潜在的气压伤。此外，该气雾器可以与呼吸机周期的吸气阶段同步，而不会在流动回路中引入显着的阻力。 患有各种病因（包括肺炎、急性肺损伤和急性呼吸窘迫综合征）的各种通气儿科患者将受益于我们提出的气溶胶发生器。 IPAG 将能够输送抗生素（用于治疗肺炎和败血症）以及葡萄糖、类固醇、镇痛剂和镇静剂等药物。 IPAG 允许在患者复苏期间采用简单的基本药物输送方式，并且无需立即进行静脉注射。这在新生儿复苏和从农村中心运送此类婴儿的过程中特别有用，因为静脉通路可能具有挑战性和困难。 该装置的核心技术已由 Powerscope 开发，并用于临床前工作，涉及玻璃体切除充气猪眼中产生气溶胶以抑制疤痕组织 视网膜脱离引起的生长。我们建议将这项技术转化并开发成一种可行的产品，可以与通风同步并补充气流动力学。气溶胶的产生和粒径分布将通过体外模型进行表征。新生儿羔羊模型将用于量化 IPAG 雾化抗生素的肺部分布和全身生物吸收。 第一期 SBIR 项目的完成将为第二期项目中肺炎和急性肺损伤动物模型的疗效研究奠定基础，并进行进一步的安全性研究，以便为未来的临床试验做好准备。