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: 7612109
• 负责人: Brian N Hansen
• 金额: $ 77.5万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7612109
• 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; Regulation; Reproducibility; Safety; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Stress Tests; Symptoms; System; Test Result; Testing; Therapeutic; Time; Toxic effect; Treatment Cost; United States Food and Drug Administration; Work; Writing; base; cost; design; expectation; experience; follower of religion Jewish; improved; interest; manufacturing process; meetings; pre-clinical; pressure; prevent; programs; propellant; prototype; research and development; research clinical testing; 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.

哮喘是美国最常见和最昂贵的疾病之一，有超过2000万美国人患有哮喘，每年的社会成本超过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的死亡率特别高。定量吸入器（MDI）是最常见的治疗形式，有近50年的患者接受，医生的信心和FDA的批准。在不久的过去，计量吸入器使用氯氟烃（CFC）推进剂，但由于其高臭氧消耗潜能（ODP），这些正在被EPA和FDA逐步淘汰。较新的计量吸入器装置现在用氢氟烷烃推进剂加压，克服了ODP问题。配方和装置不相容性的新问题使得制药业开始使用新的推进剂HFA-134 a既费时又昂贵。使用HFA-134a的新计量吸入器比旧的氟氯化碳吸入器贵3 - 5倍，这对一些最需要它们的患者来说是一个大问题，而HFA-134a的全球变暖潜力比二氧化碳高1300倍。Aerophase开发了一种廉价的二氧化碳（CO2）推进剂MDI，与HFA MDI竞争，具有高药物输送效率和剂量重现性。我们已经证明，哮喘药物可以有效地在我们的紧凑和可靠的吸入器配制。在我们刚刚完成的II期SBIR项目中，我们使用几种不同的设计开发了吸入器，并根据FDA行业指南草案（定量吸入器和干粉吸入器药品：化学、生产和控制文件，CDER，10/98）选择了两种优化设计用于SBIR继续测试和中试规模生产。我们提出的二氧化碳推进剂计量吸入器装置将产生竞争，使计量吸入器的整个未来不完全依赖于一种或两种氢氟烷烃推进剂，因为这种推进剂可能在可获得性、可负担性、长期毒性和/或环境影响方面产生问题。Aerophase Inc.的总体使命是是通过气雾剂药物来改善医疗保健。拟议项目的主要目的是缓解哮喘症状和预防死亡，特别是在非洲裔美国人等受影响最严重的群体中，使用与现有计量吸入器一样有效且价格更低的二氧化碳推进剂吸入器。在美国，10%的人口患有哮喘，每年有5000人死于哮喘，每年的经济总成本超过180亿美元;值得注意的是，由于包括空气质量和获得医疗保健在内的各种因素，哮喘对非洲裔美国人的影响尤其严重。治疗哮喘的最流行的工具之一是计量吸入器（MDI），一种填充有药物和推进剂的小气雾剂罐，其管理用于吸入的一股药物;这种流行的设备已经使用了50年，但由于逐步淘汰含氯氟烃推进剂的使用，（因为它们通过破坏平流层中的保护性臭氧层而损害环境）;最流行的替代MDI推进剂是氢氟烷烃（HFA），它不损害臭氧层;不幸的是，但并不奇怪，新的氢氟烷烃吸入器的价格比旧的吸入器高得多，这对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公司已经发明了新的、廉价的、使用二氧化碳作为推进气体的MDI吸入器;来自我们新的吸入器的竞争--在实验室测试中与HFA MDI设备一样有效--将有助于降低哮喘治疗费用;拟议的SBIR延续项目将使我们的新CO2 MDI设备符合FDA关于MDI使用和稳定性的指南，以便我们能够为人类制造它们。临床试验