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术的儿科患者提供一种显著改进的肺内给药方法。目前可用的雾化装置是有限的，因为只有某些药物，并且只有一小部分(不到几个百分点)的这种药物实际上被输送到远端肺区。我们提出了一种新的肺内气雾剂发生器(IPAG)，它将是一个直径1或2 mm的管子插入到气管内管中。这种IPAG将能够产生微气雾剂，这些微气雾剂将以接近100%的效率到达偏远的呼吸道和肺泡。此外，我们的设备的独特之处在于，它使用极低的气流产生可呼吸的气雾剂，将任何潜在的气压创伤降至最低。此外，这种喷雾器可以与呼吸机循环的吸气阶段同步，而不会在流动回路中引入显著阻力。我们建议的气雾剂发生器将使包括肺炎、急性肺损伤和急性呼吸窘迫综合征在内的各种原因的广泛的呼吸机儿童患者受益。IPAG将使抗生素(用于治疗肺炎和败血症)以及葡萄糖、类固醇、止痛剂和镇静剂的输送成为可能。IPAG允许在患者复苏期间以一种简单的方式提供基本药物，并绕过了立即需要静脉注射的情况。这在新生儿复苏和从农村中心运送这类婴儿的过程中特别有用，因为在农村中心，静脉注射可能是困难和困难的。该装置的核心技术已由PowerScope公司开发，并被用于临床前工作，包括在玻璃化充气猪眼中产生气雾剂，以抑制瘢痕组织 视网膜脱离引起的生长。我们建议将这项技术转化和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。气溶胶的产生和颗粒大小分布将通过体外模型来表征。新生儿羔羊模型将被用来量化肺部分布，以及使用IPAG输送的雾化抗生素的系统生物吸收。这一第一阶段SBIR项目的完成将为第二阶段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。