Asthma Treatment with a Novel Drug Aerosol Generator

描述（由申请人提供）：哮喘是一种以呼吸道和肺部炎症为特征的慢性疾病，发作时以喘息和呼吸短促为特征。美国约有5%的人口患有哮喘，而且这种疾病的患病率还在持续上升。向患者提供哮喘药物的最常见方法是计量吸入器（mdi）。由于氟氯化碳的臭氧消耗作用，使用氟氯化碳的传统计量吸入器将很快被淘汰；正在开发一种新型推进剂来取代氟氯化碳。然而，mdi通常不是哮喘治疗的最佳选择，因为(1)难以协调驱动和吸气，(2)产生的气溶胶颗粒过大，不足以输送到治疗上重要的小细支气管，以及(3)配方困难。其他吸入输送平台，如干粉吸入器和雾化器，在治疗哮喘方面也有明显的缺点；它们包括剂型不稳定、发射剂量不一致和气溶胶颗粒大小不理想。目前所有的吸入给药系统都含有大量的赋形剂；肺给药辅料可能引起气道过敏。因此，迫切需要一种对环境友好的替代方案，以替代当前的输送系统，这种系统能够产生大小适合于向小细支气管输送药物的气溶胶颗粒，并且配方中不含辅料。Alexza MDC开发了一种新技术来产生高纯度的药物气雾剂。设想的用于哮喘药物输送的吸入装置将是呼吸驱动的和具有适当粒径的气溶胶，用于输送到没有赋形剂的小气道。第一阶段的目标是证明建造这样一种设备的可行性，该设备可以使用该技术提供高纯度和合适粒径的沙丁胺醇（一种常见的支气管扩张剂），用于哮喘治疗。I期活动的成功完成将为开发用于哮喘治疗的改进吸入给药平台迈出重要的一步。

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.