Hale: A Mobile-Connected Medical Vaporizer that Alleviates Nicotine Dependence

项目总结 吸烟是一个重大的公共健康问题，影响着美国3400万成年人，因为吸烟增加了 癌症和心血管疾病的风险，其中1600万人患有与吸烟有关的慢性疾病。 公共当局和其他团体推动了全国性的戒烟运动。在……里面 此外，药剂级尼古丁替代疗法(NRT)产品已经开发出来，以帮助 停止(口香糖、含片、贴片等)。可悲的是，目前的标准NRT剂量对许多吸烟者并不有效 因为尼古丁提供的剂量比香烟低得多。许多吸烟者改用电子烟 (ECS)与药筒(电子尼古丁输送系统或末端)。End与吸烟的行为非常相似 并提供可以手动缩减的快速尼古丁剂量。最近的研究表明， 有效性数据支持在戒烟计划中继续使用EC，但需要更多数据。 因此，由于成瘾是复杂的，目前的NRT缺乏类似的效果，因此仍需提高NRT的有效性 尼古丁剂量和感觉运动模仿与吸烟相比。这突出了一个重要的、 将吸烟的行为方面与自动尼古丁相结合的未满足的临床需求 给药。哈瓦健康公司利用这些行为方面的无味配方和自动化， 通过一款应用程序控制尼古丁的逐渐减少，以促进戒烟。因此，这一目标是 第一阶段项目是开发Have Health的Hale Vaporizer系统，这是一种使用 自动结束包括Hale蒸气设备、无味尼古丁配方和一款手机应用程序 随着时间的推移，自动降低尼古丁的摄入量。为实现具体目标1，将对 Hale蒸发器的性能和气雾剂安全概况以及该设备的成品版本。这将包括 雾化定制尼古丁和非尼古丁配方的设备安全性测试。在具体目标2中，有限的 体内剂量范围发现研究，将以前的发现转化为更具临床相关性的模型。研究将会是 在通过烟雾机吸入气雾剂的大鼠身上启动，进行重复剂量的鼻腔吸入毒理学研究。 在暴露于蒸汽后的特定时间点，我们建议收集和检测：a)血液中的尼古丁 浓度b)对肺组织的毒性或组织特异性影响。据我们所知，目前还没有商业化的NRT 使用无味尼古丁配方和自动化电子传递系统 由患者手动调整。建议的研究对进一步发展Hale是必要的。 将雾化器系统转化为同类最佳的NRT，通过帮助吸烟者在 及时戒烟。

PROJECT SUMMARY Cigarette smoking is a significant public health concern impacting 34 million adults in the USA by increasing their risk for cancer and cardiovascular disease, including 16 million living with chronic smoking-related diseases. National campaigns for smoking cessation have been promoted by public authorities, and other groups. In addition, pharmaceutical-grade nicotine replacement therapy (NRT) products have been developed to assist with cessation (gums, lozenges, patches, etc.). Sadly, current standard NRT dosing is not effective for many smokers since nicotine is provided at much lower doses than cigarettes. Many smokers switched to using e-cigarettes (ECs) with cartridges (electronic nicotine delivery systems or ENDS). ENDS closely mimic the act of smoking and provide rapid nicotine dosing that can be scaled back manually. Recent studies have shown limited effectiveness data in support of the continued use of EC in smoking cessation plans, but more data are needed. Hence, effectiveness must still be improved for NRTs since addiction is complex, and current NRTs lack similar nicotine dosing and sensorimotor mimicking compared to smoking cigarettes. This highlights a significant, unmet clinical need for an NRT combining the behavioral aspects of smoking with automated nicotine dosing. Hava Health Inc. leverages these behavioral aspects with flavorless formulations and automated, gradual nicotine reduction controlled by an app to improve smoking cessation. Therefore, the goal of this Phase I project is the development of Have Health’s Hale Vaporizer System, a proprietary NRT using an automated ENDS including the Hale vapor device, flavorless nicotine formulations, and a phone app that automatically lowers nicotine intake gradually over time. For Specific Aim 1, testing will be conducted of the Hale vaporizer’s performance and aerosol safety profile with a finished version of the device. This will include device safety testing in aerosolizing custom nicotine and non-nicotine formulations. In Specific Aim 2, a limited in vivo dose-range finding study to translate former findings to a more clinically relevant model. Studies will be initiated in rats introduced to aerosol via smoke machines, in a repeat dose nose-only inhalation toxicology study. At specified time points post exposure to vapor, we propose collecting and testing: a) blood for nicotine concentration b) lung tissue for toxic or tissue specific effects. To our knowledge, no commercially available NRT is available using flavorless nicotine formulations and an automated electronic delivery system that is not manually adjusted by the patient. The proposed studies are necessary for further development of the Hale Vaporizer System into a best-in-class NRT to help improve compliance by aiding smokers along the path to smoking cessation in a timely manner.