Novel Inhalation Device for Delivering Vapor-State Drugs

描述（由申请人提供）：食欲不振是癌症患者感到最令人沮丧的主观症状之一，由此产生的恶病质是癌症死亡的常见原因。此外，恶心是癌症治疗的常见副作用。大麻素激动剂屈大麻酚的口服递送被FDA批准作为止吐剂和食欲增强剂。然而，其临床应用受到广泛的首过代谢和导致的口服生物利用度不一致的限制。在该资助申请的第一阶段，我们已经证明了形成高纯度、小粒径的屈大麻酚气雾剂的能力，用于通过吸入进行可靠的全身递送。这些气溶胶可以通过简单的呼吸驱动装置产生。在第II阶段的拨款中，我们现建议证明犬只吸入这些气溶胶后，其系统吸收的一致性。此外，我们计划进行动物毒理学实验，并生产启动吸入屈大麻酚人体研究所需的临床试验材料。II期这些目标的实现将直接导致对具有成本效益的、商业上可行的屈大麻酚吸入递送系统的人体临床测试。除了提供改善的屈大麻酚输送，这种药物产品还解决了癌症领域的一个主要未满足的需求：一种增强食欲和减轻恶心的药物，快速起效，不需要痛苦的注射，也不需要胃肠道不适患者口服药物。

DESCRIPTION (provided by applicant): Poor appetite is one of the subjective symptoms that cancer patients find most frustrating, and resulting cachexia is a common cause of death from cancer. In addition, nausea is a frequent side effect of cancer treatment. Oral delivery of the cannabinoid agonist dronabinol is approved by the FDA as both an anti-emetic agent and an appetite-enhancer. Its clinical utility, however, is limited by extensive first pass metabolism and resulting inconsistent oral bioavailability. In Phase I of this grant application, we have demonstrated the ability to form high purity, small particle size aerosols of dronabinol for reliable systemic delivery through inhalation. These aerosols can be produced by simple, breath-actuated devices. In Phase II of the grant, we now propose to prove the consistency of systemic absorption of these aerosols when inhaled by dogs. In addition, we plan to conduct the animal toxicology experiments and produce the clinical trial materials required to initiate human studies of inhaled dronabinol. Accomplishment of these goals of Phase II will lead directly to human clinical testing of a cost effective, commercially viable dronabinol inhalation delivery system. Beyond providing for improved dronabinol delivery, this drug product addresses a major unmet need in the cancer area: an appetite-enhancing and nausea-decreasing medication that works rapidly and does not require painful injection or for patients with gastrointestinal distress to consume oral medication.