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(申请人提供)：哮喘是美国最常见和最昂贵的疾病之一，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，而且在社会经济上处于不利地位的人群中，这一比例尤其高。计量吸入器(MDI)是最常见的治疗形式，经过近50年的患者接受、医生信任和FDA批准。在不久的过去，计量吸入器使用氯氟化碳(CFC)推进剂，但由于其高臭氧消耗潜力(ODP)，环保局和FDA正在逐步淘汰这些推进剂。较新的计量吸入器设备现在用氢氟烷烃(HFA)推进剂加压，从而克服了消耗臭氧潜能值问题。配方和设备不兼容的新问题使制药业开始使用新的推进剂HFA-134a既耗时又昂贵。使用HFA-134a的新计量吸入器的价格是旧的氟氯化碳吸入器的3-5倍，这对一些最需要它们的患者来说是一个大问题，而且HFA-134a的全球变暖潜力是二氧化碳的1300倍。Aerphase已经开发出一种廉价的二氧化碳(CO2)推进剂计量吸入器，它与氢氟烷烃计量吸入器竞争，具有高药物输送效率和剂量重复性。我们已经证明，哮喘药物可以在我们的紧凑型和可靠的吸入器中有效地配制。在我们刚刚完成的第二阶段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的行业指南草案(计量吸入器和干粉吸入器药物产品：化学、制造和控制文档，CDER，10/98)选择了两个优化设计用于SBIR持续测试和中试生产。我们建议的二氧化碳推进剂计量吸入器装置将产生竞争，因此计量吸入器的整个未来不会完全依赖一两种氢氟烷烃推进剂，这可能会在可用性、可负担性、长期毒性和/或环境影响方面产生问题。Aerphase Inc.的总体使命是通过气雾剂药物改善医疗保健。拟议项目的主要目的是缓解症状和预防哮喘死亡，特别是在像非裔美国人这样受影响最严重的群体中，使用一种与目前可用的计量吸入器一样有效、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，每年给经济造成的总成本超过180亿美元；值得注意的是，由于空气质量和获得医疗保健等各种因素，哮喘对非裔美国人的影响尤其严重。治疗哮喘最受欢迎的工具之一是计量吸入器(MDI)，这是一个装满药物和推进剂的小型气雾剂罐，用于吸入药物；这种受欢迎的设备已经使用了50年，但由于氯氟烃推进剂的逐步淘汰，今天正在经历重大变化(因为它们通过破坏同温层中的保护臭氧层来损害环境)；最受欢迎的替代MDI推进剂是氢氟烷烃(HFA)，它不会损害臭氧层；不幸的是，但并不令人惊讶的是，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贫困患者来说尤其艰难。幸运的是，Aerphase已经发明了使用二氧化碳作为推进气体的新型、廉价的MDI吸入器；来自我们新型吸入器的竞争-在实验室测试中，这种吸入器的工作效果与HFA MDI设备一样好-将有助于降低哮喘治疗成本；拟议的SBIR延续项目将使我们的新CO2 MDI设备能够满足FDA关于MDI使用和稳定性的指导方针，以便我们可以为人体临床测试制造它们。