Nicotine lozenges for the treatment of smokeless tobacco use.

Nicotine lozenges have been shown to increase tobacco abstinence rates in cigarette smokers, but they have not been evaluated in smokeless tobacco (ST) users. We conducted an open-label, one-arm, phase II clinical trial to evaluate the efficacy of the 4-mg nicotine lozenge for the treatment of withdrawal and craving associated with tobacco abstinence among ST users. Eligible subjects received 4-mg nicotine lozenges for 6 weeks followed by a 6-week taper. Subjects completed daily tobacco withdrawal diaries, and data on lozenge use, adverse events, and lozenge acceptability were collected. Urine anabasine was collected at 3 and 6 months for biochemical confirmation of self-reported tobacco abstinence. Participants were 30 ST users with a mean age of 35.4 years (SD=6.5) using an average of 4.2 cans or pouches (SD=3.2) of ST per week for a mean of 15.1 years (SD=6.5). Among subjects continuously tobacco abstinent for the first 2 weeks, no significant increases in composite withdrawal symptoms were observed, compared with baseline symptoms, whereas craving decreased significantly. Biochemically confirmed 7-day point-prevalence tobacco abstinence was 53% (95% CI=34%-72%) at 12 weeks (end of treatment) and 47% (95% CI=28%-66%) at 6 months. Few adverse events attributable to the nicotine lozenge occurred, and the lozenge was perceived as helpful in assisting subjects quit ST. The use of the 4-mg nicotine lozenge appears promising for the clinical treatment of withdrawal symptoms and craving associated with tobacco abstinence in ST users. Future phase III clinical trials investigating the efficacy of nicotine lozenges are warranted.     

无烟气烟草制品技术发展现状及趋势研究

为把握国外无烟气烟草制品研发的技术特点和发展趋势,借助Thomson Innovation 专利分析工具对1985 ～ 2014 年间无烟气烟草制品技术专利进行分析,系统揭示近30 年来无烟气烟草制品的研发现状与态势、研发热点以及技术分布。分析结果表明:专利申请变化趋势受政策影响较大;中国和美国是无烟气烟草制品技术专利申请的主要国家;3 类无烟气烟草制品技术研发热点各有不同;以跨国烟草公司为代表的企业通过收购与并购成为无烟气烟草制品技术研发的主导力量。      

国内口用型无烟气烟草制品专利分析

为使我国烟草行业相关科技人员准确把握口用型无烟气烟草制品的研发现状,预测今后的发展趋势,对国家知识产权局1985—2018年公开公告的有关口用型无烟气烟草制品的专利进行了检索和统计分析。结果表明:(1)1985—2018年口用型无烟气烟草制品中国专利共计270件,其中发明233件、实用新型28件、外观设计9件。其中袋装口含型专利占50%以上,是目前口用型无烟气烟草制品专利的主流技术。(2)2008年以来,口用型无烟气烟草制品中国专利申请经历了活跃期和高峰期,国内烟草行业专利申请总量于2013年超过国外烟草公司,专利申请量以云南中烟工业有限责任公司和中国烟草总公司郑州烟草研究院领先。国外烟草公司申请的口用型无烟气烟草制品中国专利中,雷诺士烟草公司的申请量最多,其次是菲利浦·莫里斯烟草公司和美国无烟烟草公司,且均为发明专利。(3)袋装口含烟关键技术是产品配方、制备技术、包装技术等,含化烟关键技术是制备工艺、产品形态、产品配方等;袋装口含烟专利在包装方式、缓释技术、熟化技术等领域涉及较少,含化烟专利在缓释技术、成型技术等领域涉及较少。     

无烟气烟草制品中TSNAs的分析研究

用100 mmol/L乙酸铵溶液萃取样品后,用0.22μm水相针式过滤器过滤,采用液相色谱-电喷雾串联质谱(LC-ESI MS/MS)测定烟草特有N-亚硝胺,建立了无烟气烟草制品中4种烟草特有N-亚硝胺(TSNAs)的同时测定方法。利用建立的方法测定了72个不同品牌种类的无烟气烟草制品中TSNAs的含量。结果表明,N-亚硝基降烟碱(NNN)、4-(亚硝基甲氨基)-1-(3-吡啶基)-1-丁酮(NNK)、N-亚硝基新烟草碱(NAT)和N-亚硝基假木贼碱(NAB)的检出限分别是0.03、0.08、0.03和0.02 ng/mL,回收率在93.17%-105.25%之间,精密度在2.03%-4.80%之间。方法的检测限低,特异性好,适合于无烟气烟草制品中TSNAs的检测。实验发现不同品牌的无烟气烟草制品TSNAs的含量差别较大,TSNAs的总含量范围从0.54μg/g到31.91μg/g,相差59倍,平均含量为5.06μg/g。     

基于专利数据分析的无烟气烟草制品研发趋势研究

为了解国内外无烟气烟草制品专利申请的情况,把握无烟气烟草制品的研发趋势,为我国烟草行业无烟气烟草制品的研究开发与市场发展提供决策参考和技术依据,对国内外无烟气烟草产品技术专利进行了检索分析,并对国际大型烟草公司在无烟烟草方面的进展做了的调查。结果表明:（1）无烟气烟草制品技术专利申请量在2008、2009年这两年时间内取得了较大的进展;（2）2000年以后,无烟气烟草制品的研发热点转移到嚼烟、鼻烟领域;（3）国际大型烟草公司相继进入无烟烟草领域,无烟气烟草制品已成为各大烟草公司的研发热点。      

LC-MS/MS法测定口含烟中的4种亚硝基氨基酸

建立了液相色谱-四级杆串接质谱(LC-MS/MS)测定口含烟中N-亚硝基肌氨酸(NSAR)、3-(N-甲基亚硝基氨基)丙酸(MNPA)、4-(N-甲基亚硝基氨基)丁酸(MNBA)、亚硝基氮杂环丁烷-2-羧酸(NAzCA)的分析方法.样品经水萃取,硅藻土液液萃取柱净化后浓缩,进LC-MS-MS分析.结果表明:①NSAR、...     

Nicotine delivery, cardiovascular profile, and subjective effects of an oral tobacco product for smokers.

The tobacco industry markets potential reduced exposure products (PREPs) to smokers, including oral products that are intended to be used in situations where cigarettes cannot. For example, Ariva, marketed by Star Scientific, is a tablet made from compressed tobacco powder and is intended for "adult smokers in situations where they cannot or choose not to smoke." No objective data are available regarding Ariva's effects in smokers, including its nicotine delivery, cardiovascular profile, or subjective effects. In this single-session, clinical laboratory study, 10 overnight-abstinent cigarette smokers were administered one Ariva tablet, followed 90 min later by two Ariva tablets, followed 90 min later by three Ariva tablets. Participants allowed each dose to dissolve in their mouths according to package instructions. Blood was sampled, heart rate monitored, and subjective effects assessed regularly. Ariva delivered nicotine in a dose-dependent manner; mean (SD) nicotine levels increased from 2.4 ng/ml (0.9) at baseline, to 3.4 ng/ml (1.4) 45 min post-1 tablet, 7.3 ng/ml (4.0) 45 min post-2 tablets, and 9.7 ng/ml (4.4) 45 min post-3 tablets. Heart rate increased after tablet administration, independent of dose. The tablets also significantly decreased subjective ratings of craving and urge, and increased ratings of nausea. Based on this short-term laboratory evaluation, Ariva exposes users to nicotine and may suppress some symptoms of tobacco abstinence, though its nausea-inducing characteristics may limit initial acceptability.     

Minors' tobacco possession law violations and intentions to smoke: implications for tobacco control

Objectives: To test: (1) whether citation under the Minors in Possession (MIP) law, vicarious citation (knowing someone who was cited), and threat of driving licence suspension are associated with decreased intentions to smoke next year; and (2) whether the policy is differentially enforced.     

Determination of l- and d-amino acids in smokeless tobacco products and tobacco

Quantities of free l- and d-amino acids were determined by GC-SIM-MS in 25 European snuff tobaccos (from Germany, England and Sweden) and eight chewing tobaccos (from the Philippines, Africa and Denmark) and compared to those of cigar, cigarillo, and freshly harvested tobacco leaves of cultivars of Nicotiana tabacum L. Amino acids were isolated from tobacco samples by treatment with 70% aqueous methanol and purified by a cation exchanger. Next they were converted into their N(O)-pentafluoropropionylamino acid-(2)-propyl esters, and enantiomers separated and quantified by GC-SIM-MS on a Chirasil^®-l-Val capillary column. Among l-amino acids the most abundant were Pro, Asx and Glx in the low milligram range (about 2–6 mg/g) whereas the other l-amino acids were in the submilligram range. Though native tobacco leaves contained low amounts of few d-AAs (0.2–1.9%), all processed tobacco samples had d-amino acids in varying amounts and patterns.     

Source and health implications of high toxic metal concentrations in illicit tobacco products

A significant flux of heavy metals, among other toxins, reaches the lungs through smoking. Consequently, contaminated soil is usually avoided for tobacco cultivation. Here we compare the heavy metal concentrations in tobacco from a sample of 47 counterfeit products, representative of the substantial market for these products in the U.K., with their genuine equivalents and find significantly higher concentrations of heavy metals in the counterfeits. Trace element patterns suggest that over-application of fertilizers (phosphate and/or nitrate) is the most likely cause. Nitrogen isotopes showed no significant enrichment in 15N (delta15N range from +1.1 to +4.6% in counterfeits and from +2.5 to +3.3% in genuine tobaccos) as might be expected from a sewage or manure source of nitrate, and a mineral phosphate source is considered the more likely source of metals. Stable carbon isotopes in the same tobaccos have a wide range (delta13C -18.3 to -26.4%), indicating the influence of multiple controls during cultivation and possibly post-harvesting. A review of the health effects of heavy metal transfer from tobacco via smoke to the lungs indicates that habitual smokers of counterfeits may be risking additional harm from high levels of cadmium and possibly other metals.     

Use of smokeless tobacco is a risk factor for cigarette smoking.

This study assessed the risk of smoking uptake over 2 years in adolescent boys (in grades 7 and 9) who had used smokeless tobacco (ST). We used logistic regression to determine whether the odds of adolescent boys taking up regular smoking over a period of 2 years were greater among initial nonsmokers who used ST, compared with nonusers of ST, after accounting for six well-established predictors of smoking. Initiation of weekly smoking 2 years after baseline was associated with ST use at baseline, even after including dichotomous measures of parent, sibling, or close friend smoking; low academic grades; 30-day alcohol use; and a scale measure of deviant behavior. With these other predictors included in the model, the odds ratio for the association of ST use with weekly smoking after 2 years was strong and significant (OR = 2.55, 95% CI 1.45-4.47, p<.001). The use of ST in the 7th and 9th grades is a significant risk factor for subsequent smoking even when controlling for other factors.