SmartStop: Programmable Transdermal Nicotine Replacement Therapy

描述(申请人提供)：根据疾病控制和预防中心的数据，吸烟每年导致绝大多数肺癌和超过40万人死亡，总金钱损失超过1900亿美元。尽管美国4500多万吸烟者中的大多数都想戒烟，但实际上只有一小部分人成功了。最受欢迎的戒烟产品使用尼古丁替代疗法(NRT)范例，但戒烟率不到10%。因此，迫切需要比目前市场上销售的戒烟产品更有效的戒烟产品。NRT拥有700万用户，在美国的年销售额超过8亿美元，NRT市场根深蒂固。尽管吸烟者在一天中的可预测时间会经历渴望和吸烟的高峰，但现有的NRT方案并没有为系统地预防这些发作而量身定做。因此，利用吸烟行为的这一重要特征来提高疗效的可编程NRT(PNRT)产品存在商业机会，有可能挽救或延长数百万人的生命，并大幅降低美国的医疗成本。Chrono Treateutics，Inc.(CTI)计划生产一种可编程的手表状设备SmartStopTM，它可以通过一种贴片介质全天以脉冲形式经皮传递尼古丁。通过定制脉搏来预防吸烟者经历的常规渴望和吸烟高峰期，SmartStopTM可能会显著提高NRT的疗效。该Fast-Track SBIR项目的最终目标是生产该设备的六个原型，并演示它们的功能 在人体药代动力学(PK)试验中。CTI将按如下方式实施该项目：(I)原型 尼古丁配方分配单元通过对泵进行小型化并测试其性能。(2)展示配药单位通过皮肤样本输送尼古丁的能力。(Iii)制作6个SmartStopTM原型，用于采用上文(I)中开发的泵送技术的临床PK研究。(4)使用尼古丁配方的程序化脉冲演示原型调节人体血浆尼古丁的能力。SmartStopTM将是唯一一款将NRT久经考验的原则与关于吸烟的可预测性质的最新科学相结合的产品。治疗创新包括：(I)自动确保遵守多剂量方案，(Ii)根据患者特定的依赖程度和吸烟模式定制，(Iii)在醒来前自动给予尼古丁，以缓解早晨高峰时的渴望，而不会出现长夜服药的副作用，以及(Iv)通过逐渐“减少”剂量来降低对尼古丁的耐受性，以使吸烟者戒烟。技术创新包括(I)尼古丁给药的自动“开-关”，(Ii)结合全功能和视觉吸引力的小型化，以及(Iii)关键的安全特征，包括尼古丁储存库与皮肤的隔绝以及限制过量剂量风险的输送和摄取机制，这是现有的经皮NRT产品所不具备的。 与公共健康相关：根据疾病控制和预防中心的数据，吸烟导致了绝大多数肺癌和每年超过40万人的死亡，总金钱损失超过1900亿美元。尽管美国4500多万吸烟者中的大多数都想戒烟，但实际上只有一小部分人成功了。Chrono Treateutics，Inc.(CTI)计划生产一种可编程的类似腕表的设备SmartStopTM，该设备通过全天的脉搏贴片提供量身定制的尼古丁，以预防吸烟者经常出现的渴望和吸烟高峰，从而显著提高尼古丁替代疗法的疗效，延长或挽救数百万人的生命。

DESCRIPTION (provided by applicant): According to the Centers for Disease Control and Prevention, cigarette smoking causes the vast majority of lung cancers and over 400,000 deaths annually with a total monetary cost exceeding $190 billion. While the majority of the 45+ million US smokers want to quit, a small fraction of this number actually succeeds. The most popular smoking cessation products utilize the nicotine replacement therapy (NRT) paradigm, but deliver cessation rates of less than 10%. Therefore, there is an urgent need for smoking cessation products that deliver higher efficacy than those currently marketed. With 7 million NRT users and over $800 million in annual US sales, the NRT market is well-established. Even though smokers experience peak cravings and smoke at predictable times throughout the day, existing NRT regimens are not tailored to systematically preempt these episodes. Therefore, there is a commercial opportunity for a programmable NRT (PNRT) product that leverages this important feature of smoking behavior to increase efficacy, with potential to save or prolong millions of lives and dramatically cut US healthcare costs. Chrono Therapeutics, Inc. (CTI) plans to produce a programmable wristwatch-like device, SmartStopTM, that delivers nicotine transdermally through a patch medium in pulses throughout the day. By tailoring the pulses to preempt the regular craving and peak smoking episodes that smokers experience,SmartStopTM is likely to significantly increase the efficacy of NRT. The end goal of this Fast-Track SBIR project is to produce a set of six prototypes of this device and to demonstrate their functionality in human pharmacokinetic (PK) trials. CTI will implement this project as follows: (i) Prototype the nicotine formulation dispensing unit by miniaturizing a pump and testing its performance. (ii) Demonstrate the ability of the dispensing unit to deliver nicotine through a skin sample. (iii) Produce six SmartStopTM prototypes for a clinical PK study that employs the pumping technology developed in (i) above. (iv) Demonstrate the capability of the prototypes to regulate plasma nicotine in human subjects using programmed pulses of nicotine formulation. SmartStopTM will be the only product that combines the time-tested principles of NRT with the latest science on the predictable nature of smoking. Therapeutic innovations include the ability to (i) automatically ensure compliance with a multi-dose regimen, (ii) customize for patient-specific levels of dependence and smoking patterns, (iii) administer nicotine automatically prior to waking to relieve peak morning craving without the side effects of night-long dosing, and (iv) decrease tolerance to nicotine by gradually "tailoring-down" the dose to wean the smoker off cigarettes. Technical innovations include (i) automated "on-off" for nicotine administration, (ii) miniaturization combined with full functionality and visual appeal, and (iii) key safety features including insulation of the nicotine reservoir from the skin and delivery and uptake mechanisms that limit risk of excessive dosage, which are absent from existing transdermal NRT products. PUBLIC HEALTH RELEVANCE: According to the Centers for Disease Control and Prevention, cigarette smoking causes the vast majority of lung cancers and over 400,000 deaths annually with a total monetary cost exceeding $190 billion. While the majority of the 45+ million US smokers want to quit, a small fraction of this number actually succeeds. Chrono Therapeutics, Inc. (CTI) plans to produce a programmable wristwatch-like device, SmartStopTM, that delivers tailored doses of nicotine through a patch in pulses throughout the day to preempt the regular craving and peak smoking episodes that smoker's experience, thereby significantly increasing the efficacy of nicotine replacement therapy and prolonging or saving millions of lives.