Asthma Treatment with a Novel Drug Aerosol Generator

描述（由申请人提供）：哮喘是一种慢性疾病，其特征是气道和肺部炎症，引起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，并且这种疾病的患病率持续上升。最常见的方法来提供哮喘药物给病人是定量吸入器（MDI）。由于氯氟化碳的臭氧消耗作用，使用氯氟化碳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）产生的气雾剂粒径过大，不足以递送至治疗上重要的小细支气管，以及（3）配制困难。其他吸入递送平台，例如干粉吸入器和雾化器，在治疗哮喘方面也具有显著的缺点;它们包括剂型不稳定性、不一致的发射剂量和次优的气雾剂粒度。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诱导气道过敏。因此，对于当前递送系统的环境友好的替代物存在实质性需求，所述环境友好的替代物能够产生具有适合于药物递送至小细支气管的尺寸并且在制剂中没有赋形剂的气溶胶颗粒。Alexza MDC开发了一种新技术来产生高纯度的药物气雾剂。用于哮喘药物递送的设想的吸入装置将是呼吸驱动的，并且是具有适当颗粒尺寸的气雾剂，用于递送到不含赋形剂的小气道。该资助的第一阶段的目标是证明建立这样一种设备的可行性，该设备提供沙丁胺醇，一种常见的支气管扩张剂，具有高纯度和适当的颗粒大小，用于使用该技术治疗哮喘。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给药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.