Asthma Treatment with a Novel Drug Aerosol Generator

描述(申请人提供)：哮喘是一种慢性疾病，以呼吸道和肺部炎症为特征，导致以喘息和呼吸短促为特征的发作。在美国，大约5%的人口患有哮喘，这种疾病的患病率还在继续上升。向患者提供哮喘药物的最常见方法是计量吸入器(MDI)。由于氯氟烃的臭氧消耗作用，使用氯氟烃的传统计量吸入器将很快被淘汰；正在开发一种新的推进剂来取代氯氟烃。然而，计量吸入器一般不是治疗哮喘的最佳药物，因为(1)难以协调驱动和吸气，(2)产生的气雾剂颗粒过大，不足以输送到具有治疗意义的小细支气管处，以及(3)难以配制。其他吸入给药平台，如干粉吸入器和雾化器，在治疗哮喘方面也有明显的缺点；它们包括剂量形式不稳定、发射剂量不一致以及气雾剂颗粒尺寸不佳。目前所有的吸入给药系统都含有大量的赋形剂；肺部给药中的赋形剂可能会导致呼吸道过敏。因此，大量需要一种环境友好的替代目前的给药系统，它能够产生大小适合给小细支气管所给药的气雾剂颗粒，并且配方中不含赋形剂。Alexza MDC开发了一种产生高纯度药物气雾剂的新技术。设想的哮喘药物吸入装置将是呼吸驱动的，气雾剂将具有适当的颗粒大小，以不含辅料的方式输送到小气道。赠款第一阶段的目标是证明建造这样一种设备的可行性，这种设备可以输送沙丁胺醇，一种常见的支气管扩张剂，具有高纯度和适当的颗粒尺寸，用于使用这项技术治疗哮喘。第一阶段活动的成功完成将是朝着开发用于哮喘治疗的改进的吸入性药物输送平台迈出的重要一步。

DESCRIPTION (provided by applicant): Asthma is a chronic disease characterized by inflammation of the airways and lung, causing attacks characterized by wheezing and shortness of breath. Around 5% of the population in the United States suffers from asthma, with the prevalence of this disease continuing to rise. The most common method to deliver asthma medications to patients is metered dose inhalers (MDIs). Traditional MDIs using chlorofluorocarbons (CFCs) will soon be phased out due to CFCs' ozone-depleting effect; a new class of propellants is being developed to replace CFCs. However, MDIs in general are not optimal for asthma treatment because of (1) the difficulty in coordinating actuation and inspiration, (2) excessively large particle size of generated aerosols inadequate for delivery to therapeutically important small bronchioles, and (3) difficulty in formulation. Other inhalation delivery platforms, such as dry powder inhalers and nebulizers, also have significant disadvantages in treating asthma; they include dose form instability, inconsistent emitted dose, and suboptimal aerosol particle size. All current inhalation delivery systems contain significant amounts of excipients; excipients in pulmonary delivery may induce airway hypersensitivity. Thus, there is a substantial need for an environmentally friendly alternative to current delivery systems that is able to generate aerosol particles with sizes suitable for drug delivery to small bronchioles and without excipients in the formulation. Alexza MDC has developed a novel technology to generate drug aerosol of high purity. The envisioned inhalation device for asthma drug delivery will be breath actuated and aerosols with appropriate particle sizes for delivery to small airways free of excipients. The goal in Phase I of the grant is to demonstrate the feasibility of building such a device that delivers albuterol, a common bronchodilator, with high purity and appropriate particle size for asthma treatment using this technology. Successful completion of activities in Phase I would present a significant step towards developing an improved inhalation drug delivery platform for asthma treatment.