SmartStop: Programmable Transdermal Nicotine Replacement Therapy

SmartStop：可编程透皮尼古丁替代疗法

• 批准号: 8396057
• 负责人: Kuowei Chang
• 金额: $ 36.97万
• 依托单位: CHRONO THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8396057
• 关键词: Adverse effects; Cadaver; Cause of Death; Centers for Disease Control and Prevention (U.S.); Cessation of life; Cigarette Smoker; Clinical; Dependence; Devices; Diffusion; Dose; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Electronics; Ensure; Goals; Health Care Costs; Human; In Vitro; Lead; Legal patent; Malignant neoplasm of lung; Marketing; Miniaturization; Monitor; Nature; Nicotine; Patients; Pattern; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiologic pulse; Plasma; Pump; Quality Control; Regimen; Risk; Safety; Sales; Sampling; Science; Skin; Small Business Innovation Research Grant; Smoke; Smoker; Smoking; Smoking Behavior; Specific qualifier value; System; Technology; Testing; Therapeutic; Time; Tobacco use; Transdermal substance administration; Visual; Weaning; cigarette smoking; cost; craving; disorder prevention; dosage; experience; human subject; in vivo; innovation; miniaturize; nicotine replacement; preempt; programs; prototype; smoking cessation; success; uptake; wasting

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.

描述（由申请人提供）：根据疾病控制和预防中心的数据，吸烟导致绝大多数肺癌和每年超过40万人死亡，总金钱成本超过1900亿美元。虽然4500多万美国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利用尼古丁替代疗法（NRT）范例，但提供的戒烟率低于10%。因此，迫切需要提供比目前市售的戒烟产品更高功效的戒烟产品。拥有700万NRT用户和超过8亿美元的美国年销售额，NRT市场已经建立。即使吸烟者在一天中可预测的时间经历高峰渴望和吸烟，现有的NRT方案也不能系统地预先预防这些发作。因此，可编程NRT（PNRT）产品存在商业机会，该产品利用吸烟行为的这一重要特征来提高疗效，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治疗公司(CTI)该公司计划生产一种可编程的手表式设备SmartStopTM，通过贴片介质全天脉冲式透皮输送尼古丁。通过定制脉冲来预先阻止吸烟者经历的常规渴望和吸烟高峰期，SmartStopTM可能会显着提高NRT的疗效。这个快速通道SBIR项目的最终目标是生产一套六个原型的设备，并展示其功能 人体药代动力学（PK）试验。气候技术倡议将以下列方式执行这一项目： 尼古丁制剂分配单元通过测试泵和测试其性能。(ii)证明分配装置通过皮肤样本输送尼古丁的能力。(iii)生产六个SmartStopTM原型用于临床PK研究，采用上述（i）中开发的泵送技术。(iv)证明原型使用尼古丁制剂的程控脉冲调节人类受试者血浆尼古丁的能力。 SmartStopTM将是唯一一款将NRT久经考验的原则与最新的吸烟可预测性科学相结合的产品。治疗创新包括以下能力：（i）自动确保对多剂量方案的依从性，（ii）针对患者特定的依赖水平和吸烟模式进行定制，（iii）在醒来前自动给予尼古丁，以缓解早晨高峰期的渴望，而没有夜间给药的副作用，以及（iv）通过逐渐“定制”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）小型化与完整功能和视觉吸引力相结合，以及（iii）关键安全特征，包括尼古丁储存器与皮肤的绝缘以及限制过量剂量风险的输送和吸收机制，这些都是现有透皮NRT产品所不具备的。 公共卫生关系：根据疾病控制和预防中心的数据，吸烟导致绝大多数肺癌和每年超过40万人死亡，总金钱成本超过1900亿美元。虽然4500多万美国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治疗公司(CTI)该公司计划生产一种类似手表的可编程设备SmartStopTM，通过贴片全天脉冲提供量身定制的尼古丁剂量，以预先控制吸烟者的常规渴望和吸烟高峰期，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。