Lung Drug Delivery with Carbon Dioxide Aerosol Inhalers

使用二氧化碳气溶胶吸入器进行肺部药物输送

• 批准号: 7385072
• 负责人: Brian N Hansen
• 金额: $ 76.25万
• 依托单位: AEROPHASE, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-09 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385072
• 关键词: Address; Aerosols; African American; Air; American; Asthma; Back; Breathing; Carbon Dioxide; Caring; Cessation of life; Charge; Chemistry; Chlorofluorocarbons; Clinical; Clinical Trials; Communication; Data Collection; Development; Device or Instrument Development; Devices; Disadvantaged; Documentation; Dose; Drug Delivery Systems; Drug Formulations; Drug Industry; Employee; Environment; Environmental Impact; Funding; Future; Gases; Generations; Global Warming; Goals; Grant; Guidelines; Healthcare; Human; Human Resources; Industry; Inhalators; Laboratories; Laws; Letters; Lung; Mails; Marketing; Medical; Medical Research; Medicine; Metered Dose Inhaler Device; Methods; Mission; Modeling; Ozone; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physicians; Plants; Population; Powder dose form; Preclinical Testing; Price; Principal Investigator; Process; Production; Purpose; Range; Rate; Regulation; Reproducibility; Safety; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Standards of Weights and Measures; Stress Tests; Symptoms; System; Test Result; Testing; Therapeutic; Time; Today; Toxic effect; Treatment Cost; United States Environmental Protection Agency; United States Food and Drug Administration; Work; Writing; base; cost; day; design; desire; expectation; experience; follower of religion Jewish; improved; interest; manufacturing process; pre-clinical; prescription document; prescription procedure; pressure; prevent; programs; propellant; prototype; research and development; research clinical testing; size; socioeconomics; tool; usability

DESCRIPTION (provided by applicant): Asthma is one of the most common and costly illnesses in the US, with over 20 million Americans suffering from asthma with an annual societal cost of over $18 billion. Sadly, about 5000 Americans die every year from asthma, even though most asthma death is preventable with proper treatment, and the rates are especially high among the socioeconomically disadvantaged. The metered dose inhaler (MDI) is the most common form of treatment, with nearly 50 years of patient acceptance, physician confidence, and FDA approval. In the near past, MDIs used chlorofluorocarbon (CFC) propellants, but these are in the process of being phased out by the EPA and FDA due to their high ozone depletion potential (ODP). Newer MDI devices are now pressurized with hydrofluoroalkane (HFA) propellants, which overcome the ODP problem. New problems with formulations and device incompatibility made it time-consuming and expensive for the pharmaceutical industry to begin to use the new propellant HFA-134a. The new MDIs that use HFA-134a are 3-5 times more expensive than the old CFC inhalers, which is a big problem for some of the patients that need them the most, and the global warming potential is 1300 times higher for HFA-134a than for carbon dioxide. Aerophase has developed an inexpensive carbon dioxide (CO2) propellant MDI that is competitive with the HFA MDIs, with high drug delivery efficiency and dose reproducibility. We have demonstrated that asthma drugs can be effectively formulated in our compact and reliable inhalers. In our just-completed phase II SBIR project we developed inhalers using several different designs, and selected two optimized designs for SBIR Continuation testing and pilot-scale production according to the FDA Draft Guidance for Industry (Metered Dose Inhaler and Dry Powder Inhaler Drug Products: Chemistry, Manufacturing, and Controls Documentation, CDER, 10/98). Our proposed CO2 propellant MDI devices will create competition so that the entire future of the MDI is not totally dependent upon one or two HFA propellants that could develop problems with availability, affordability, long term toxicity, and/or environmental impacts. The overall mission of Aerophase Inc. is to improve healthcare through aerosol medicine. The primary purpose of the proposed project is to relieve symptoms and prevent death from asthma, especially among the hardest hit groups like African Americans, with a CO2 propellant inhaler that is as effective as and less expensive than currently available MDIs. In the US, 10% of the population has asthma, 5000 people die from it each year, and the total cost to the economy is over $18 billion per year; notably the impact of asthma is especially hard on African Americans due to a variety of factors including air quality and access to medical care. One of the most popular tools in the treatment of asthma is the metered dose inhaler (MDI), a small aerosol canister filled with drug and propellant which administers a puff of medicine for inhalation; this popular device has been used for 50 years, but is going through major changes today due to the phase-out of the use of chlorofluorocarbon propellants (because they harm the environment by damaging the protective ozone layer in the stratosphere); the most popular replacement MDI propellant has been hydrofluoroalkane (HFA), which does not harm the ozone layer; unfortunately, but not surprisingly, the prices for the new HFA inhalers are much higher than for the old inhalers, which is especially hard on socioeconomically disadvantaged patients that need asthma therapy the most. Fortunately, Aerophase has invented new, inexpensive, MDI inhalers that use carbon dioxide as the propellant gas; competition from our new inhalers-which work just as well as the HFA MDI devices in laboratory tests-will help keep asthma treatment costs down; the proposed SBIR Continuation project will allow us to make our new CO2 MDI device meet the FDA guidelines for MDI usage and stability so that we can manufacture them for human clinical testing.

描述（由申请人提供）：哮喘是美国最常见且代价最高的疾病之一，超过 2000 万美国人患有哮喘，每年造成的社会损失超过 180 亿美元。可悲的是，每年约有 5000 名美国人死于哮喘，尽管大多数哮喘死亡是可以通过适当的治疗来预防的，而且在社会经济弱势群体中，这一比例尤其高。计量吸入器 (MDI) 是最常见的治疗形式，近 50 年来得到了患者的认可、医生的信任和 FDA 的批准。不久前，计量吸入器使用氯氟烃 (CFC) 推进剂，但由于其臭氧消耗潜值 (ODP) 高，美国环保局 (EPA) 和 FDA 正在逐步淘汰这些推进剂。较新的 MDI 设备现在使用氢氟烷 (HFA) 推进剂加压，从而克服了 ODP 问题。配方和设备不兼容的新问题使得制药行业开始使用新型推进剂 HFA-134a 既耗时又昂贵。使用 HFA-134a 的新型 MDI 比旧的 CFC 吸入器贵 3-5 倍，这对于一些最需要它们的患者来说是一个大问题，而且全球变暖潜力比 HFA-134a 高 1300 倍比二氧化碳。 Aerophase 开发了一种廉价的二氧化碳 (CO2) 推进剂 MDI，可与 HFA MDI 竞争，具有较高的药物输送效率和剂量重现性。我们已经证明，哮喘药物可以在我们紧凑可靠的吸入器中有效配制。在我们刚刚完成的二期SBIR项目中，我们开发了采用多种不同设计的吸入器，并根据FDA工业指南草案（定量吸入器和干粉吸入器药物产品）选择了两种优化设计用于SBIR继续测试和中试生产：化学、制造和控制文档，CDER，10/98）。我们提出的 CO2 推进剂 MDI 装置将创造竞争，以便 MDI 的整个未来不完全依赖于一种或两种可能会出现可用性、可负担性、长期毒性和/或环境影响等问题的 HFA 推进剂。 Aerophase Inc. 的总体使命是通过气雾剂医学改善医疗保健。该项目的主要目的是缓解症状并预防哮喘死亡，特别是在非洲裔美国人等受影响最严重的群体中，使用二氧化碳推进剂吸入器，其效果与目前可用的计量吸入器一样有效，但价格更低。在美国，10%的人口患有哮喘，每年有5000人死于哮喘，每年给经济造成的总损失超过180亿美元；值得注意的是，由于空气质量和医疗服务等多种因素，哮喘对非裔美国人的影响尤其严重。治疗哮喘最常用的工具之一是计量吸入器 (MDI)，这是一种装有药物和推进剂的小型气雾罐，可吸入一股药物；这种流行的装置已经使用了 50 年，但由于氯氟烃推进剂的逐步淘汰（因为它们会破坏平流层中的保护性臭氧层，从而危害环境），如今正在经历重大变化；最流行的 MDI 推进剂替代品是氢氟烷 (HFA)，它不会损害臭氧层；不幸的是，但并不奇怪的是，新的 HFA 吸入器的价格比旧的吸入器高得多，这对于最需要哮喘治疗的社会经济弱势患者来说尤其困难。幸运的是，Aerophase 发明了新型、廉价的 MDI 吸入器，使用二氧化碳作为推进剂气体。来自我们新型吸入器的竞争（在实验室测试中其工作效果与 HFA MDI 装置一样）将有助于降低哮喘治疗成本；拟议的 SBIR Continuation 项目将使我们能够使新的 CO2 MDI 设备符合 FDA 关于 MDI 使用和稳定性的指南，以便我们可以制造它们用于人体临床测试。