Lung Drug Delivery with Carbon Dioxide Aerosol Inhalers

描述(申请人摘要)：哮喘是最常见和最昂贵的疾病之一 美国的疾病和通过计量器提供的药物配方 吸入器(MDI)是哮喘患者的主要治疗方法。一个 目前这一领域的关键问题是氯氟化碳(CFC) 传统上用于计量吸入器的推进剂正被政府逐步淘汰 由于它们具有很高的臭氧消耗潜力，因此需要一种 安全、有效、经济的更换。虽然氢氟烷烃 (HFA)推进剂被认为是一个很好的候选，潜在的问题 包括毒性、与设备不兼容、与 FDA批准的吸入器表面活性剂，以及一些药物的生物利用度降低。 在第一阶段，气相清楚地证明了使用二氧化碳作为 用于肺气雾剂释放的新一代推进剂 制药公司。优点包括零臭氧消耗潜力，低 毒性，以及给肺部注射亲脂性药物的能力 目前不能通过任何其他方法交付。一场新奇的高性能演出 微爆MDI设计得到了成功的测试。建议的第二期工程 这将允许Aerphase优化候选的基于二氧化碳的配方(例如 沙丁胺醇、二丙酸倍氯米松和布地奈德)，并完成 设计、开发和验证一个或多个计量吸入器，以准备 FDA的批准和最终的商业化。 拟议的商业应用：除了生产用于有效治疗哮喘的基于二氧化碳的药物配方和计量吸入器的最初目标外，我们正在追求的系统还可以有效地用于提供抗生素以减少肺炎死亡，可能取代注射胰岛素的需要，提供无法通过任何其他方法给予的药物，提供有针对性的肺癌治疗，以及提供针对化学战剂的快速干预。

DESCRIPTION (Applicant's abstract): Asthma is one of the most common and costly illnesses in the United States, and drug formulation delivered via metered inhalers (MDIs) represent the primary treatment method for asthma sufferers. A key current issue in this arena is that the chlorofluorocarbon (CFC) propellants traditionally used in MDIs are being phased out by the government due to their high ozone-depletion potential--thus presenting a need for a replacement that is safe, effective, and economical. Although hydrofluoroalkane (HFA) propellants were thought to be a good candidate, potential problems include toxicity, incompatibility with devices, incompatibility with FDA-approved inhaler surfactants, and reduced bioavailability of some drugs. During Phase I Aerophase clearly demonstrated the feasibility of using CO2 as the next-generation propellant for pulmonary aerosol delivery of pharmaceuticals. Advantages include zero ozone-depletion potential, low toxicity, and the ability to administer to the lungs lipophilic drugs that cannot currently be delivered by any other method. A novel, high performance MicroBurst MDI design was tested successfully. The Phase II project proposed here would allow Aerophase to optimize candidate CO2-based formulations (e.g. albuterol, beclomethasone dipropionate, and budesonide) and to complete the design, development, and validation of the one or more MDIs in preparation for FDA approval and ultimate commercialization. PROPOSED COMMERCIAL APPLICATION: Beyond the initial goal of producing CO2-based drug formulations and MDIs for the effective treatment of asthma, the system we are pursuing could also be used effectively to deliver antibiotics to reduce death from pneumonia, possibly replace the need to inject insulin, deliver drugs that cannot be administered by any other method, provide targeted lung cancer therapy, and deliver rapid intervention against chemical warfare agents.