Treatment of Pain by Drug Aerosol Inhalation

药物气雾吸入治疗疼痛

• 批准号: 6999110
• 负责人: WILLIAM W SHEN
• 金额: $ 71.76万
• 依托单位: ALEXZA MOLECULAR DELIVERY CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999110
• 关键词: aerosols; analgesia; biomedical equipment development; biomedical equipment safety; cancer pain; cost effectiveness; drug abuse prevention; drug delivery systems; fentanyl; inhalation drug administration; method development; naloxone; portable biomedical equipment; surface coating; vapor

DESCRIPTION (provided by applicant): Breakthrough pain is a feared symptom afflicting the majority of cancer patients at some point in their illness. It is characterized by rapid onset, with pain intensity reaching excruciating level within several minutes, and brief duration (median duration approximately 30 minutes). Although commonly used, due to their delayed onset and long duration of action, oral opioids do not relieve breakthrough pain adequately and often result in excess plasma drug concentration after the pain has subsided, thus introduce adverse effects. A recently approved oral transmucosal fentanyl product has been commercially successful by marginally accelerating the onset of breakthrough pain treatment relative to oral opioids. However, there remains a substantial unmet need for a faster onset treatment with minimal side effects. The goal of this proposal is to develop an inhalation device for rapid systemic delivery of fentanyl, a potent opioid analgesic, for the treatment of breakthrough pain. The inhalation device applies a novel technology pioneered by Alexza MDC to generate a pure fentanyl aerosol appropriate for systemic delivery through the deep lung. Preliminary animal studies have shown rapid, IV-like, systemic delivery of several FDA-approved drugs to dogs using our technology. In Phase I of this grant, we will demonstrate the feasibility of incorporating this aerosol generation technology into a handheld, multi-dose delivery device with features ensuring patient safety and minimizing opioid abuse and diversion. In Phase II, we will determine the safety of fentanyl inhalation in animal toxicology studies, design and manufacture devices for use in clinical trials, and complete all product testing required prior to human use of our device. By the end of the grant period, we will be ready to initiate human testing of the multi-dose device. Eventual FDA approval of our fentanyl product will allow cancer patients to relieve breakthrough pain more effectively, thus improving their overall quality of life. In addition, the secure, convenient multi-dose device platform for rapid systemic delivery will likely find other valuable applications in clinical practices.

描述（由申请人提供）：突破性的疼痛是一种症状，使大多数癌症患者在患病的某个时候遭受了痛苦。它的特征是快速发作，疼痛强度在几分钟内达到了痛苦的水平，并且持续时间短（中位持续时间约为30分钟）。尽管通常使用，但由于它们的发作延迟和长时间的作用持续时间，口服阿片类药物不能充分缓解突破性疼痛，并且在疼痛缓解后通常会导致过量的血浆药物浓度，从而引入不良影响。最近经过批准的口服传播芬太尼产品在商业上取得了成功，从而相对于口服阿片类药物的突破性疼痛治疗的发作略有加速。但是，对于更快的副作用，对更快的发作治疗仍然存在很大的需求。该提案的目的是开发一种吸入装置，用于快速全身递送芬太尼（一种有效的阿片类镇痛药）来治疗突破性疼痛。吸入设备应用了Alexza MDC开创的新技术，以生成适合通过深肺进行全身递送的纯芬太尼气溶胶。初步的动物研究表明，使用我们的技术将几种FDA批准的药物的几种FDA批准药物的全身性传递给了速度。在这笔赠款的第一阶段中，我们将证明将这种气溶胶生成技术纳入手持式多剂量输送设备的可行性具有确保患者安全并最大程度地减少阿片类药物滥用和转移的功能。在第二阶段，我们将确定芬太尼吸入在动物毒理学研究，设计和制造设备中用于临床试验中的安全性，并在人类使用我们的设备之前完成所有需要的产品测试。到赠款期结束时，我们将准备启动多剂量设备的人体测试。 FDA最终批准我们的芬太尼产品将使癌症患者能够更有效地缓解突破性疼痛，从而改善其整体生活质量。此外，用于快速全身交付的安全，方便的多剂量设备平台可能会在临床实践中找到其他有价值的应用。