CN103479705A - 解烟毒的组合物 - Google Patents
解烟毒的组合物 Download PDFInfo
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- CN103479705A CN103479705A CN201310409846.6A CN201310409846A CN103479705A CN 103479705 A CN103479705 A CN 103479705A CN 201310409846 A CN201310409846 A CN 201310409846A CN 103479705 A CN103479705 A CN 103479705A
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- tobacco poisoning
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及一种解烟毒的组合物。具体地说，本发明涉及利用具有分解尼古丁的活性及消除焦油毒性的蕃茄全草提取物、白花蛇舌草提取物、花楸树提取物、紫草提取物和/或赤杨提取物作为有效成分的解烟毒的组合物。本发明可以缓和、解毒由焦油和尼古丁引起的烟毒。
Description
相关申请
本申请是申请号为201080050754.8、申请日为2010年4月20日、发明名称为“解烟毒的组合物”的中国发明专利申请的分案申请。
技术领域
本发明涉及解烟毒的组合物。更确切地说，涉及利用番茄全草提取物等解烟毒的组合物。
背景技术
目前吸烟成为全世界8大死亡原因中的6个危险疾病因素，并预测至2030年因吸烟而死亡的总人数每年会超越8百万名(Mpower,2008,WHOreport on the global tobacco epidemic,WHO)。
韩国的吸烟率，尤其成年男性的吸烟率与全世界相比还是相当高的，2005年韩国成年男性中吸烟者达52.3%。这个数值在WHO会员国中有资料的132个国家中排第13位(Mpower,2008,WHO report on the global tobaccoepidemic,WHO)，在经济合作发展组织(OECD)国家中居首位(OECD healthdata,2006)。
吸烟引起许多严重的疾病，包括肺癌，慢性阻塞性肺疾病(COPD)，冠状动脉疾病，脑中风（脑血管疾病），心脏麻痹，主动脉瘤，循环***疾病（周围血管疾病等），咽喉癌，口腔癌等（尹锡俊等，2001，因吸烟过早死亡造成的国家疾病负担，预防医学会期刊，第34卷，第3号）。
香烟烟气中含有对人体有害的致癌物质等毒性物质4,000多种，其中有害主要成分可说是由多种毒性物质混合而成的焦油和尼古丁。
香烟中的焦油含有2,000多种有毒化学物质，其中二氧芑（dioxin），苯并芘(Benzopyrene)，二甲基亚硝胺(Dimethylnitrosamine)等20多种是致癌物质（申东川，香烟烟气中的有害化学物质，韩国禁烟运动协议会发刊，1999）。
由于尼古丁是导致肺癌物质亚硝胺-4(甲基亚硝胺)-1-(3-比啶)-1-丁酮[nitrosamine-4(methylnitrosamino)-1-(3-pyridyl)-1-butanone]的前体，吸入尼古丁会引起瞳孔缩小、视力混浊、呕吐、呼吸困难、唾液和呼吸器官的分泌物增加、心跳减少等急性症状和动脉硬化、高血压等各种循环***疾病的慢性症状(Brunneman,K.D.et al.,J.Natl.Cancer Inst.89:868-73(1996);Carmella,S.G.et al.,Cancer Epidemiol Biomarkers Prev.6:113-20(1997);Wynder,E.L.et al.,Environ Health Prospect.103Suppl8:143-148(1995))。
能缓和、解毒由焦油和尼古丁引起的烟毒的代表性物质可包括绿茶提取物(Chung,F.L.Proc.Soc.Exp.Viol.Med.220:244-248(1999);Fujiki,H.et al.,Mutat.Res.18:307-310(1998))，鱼腥草、蒲公英和甘草等的混合提取物（韩国登记专利第04094223号），五味子提取物、桔梗提取物等的混合物（韩国公开专利第2004-0102690号）等等。
本发明也涉及利用蕃茄全草提取物等来缓和、解毒由焦油和尼古丁引起的烟毒的技术。
发明内容
本发明的目的是提供一种解烟毒的组合物。本发明的其他目的将在下文揭示。
本发明的发明人在下列实施例及实验中所确认的是制造蕃茄全草、白花蛇舌草、花楸树、紫草及赤杨的各乙醇水溶液提取物后，检测所述提取物分解尼古丁的活性及消除焦油毒性的活性，并得知所述提取物都具有所述的活性。在此，分解尼古丁的活性是根据Barlow等的方法[Barlow R.D,Stone R.B.,Clin.Chim.Acta.,165,pp45,1987]的试管(In vitro)实验和测定血液中尼古丁浓度变化的动物实验来确认的，消除焦油毒性的活性是经Brunnemann等的方法[Brunnemann,K.D.and Hoffiman D.,Toxcol,21,235(91)]来碓认的。接着本发明的发明人制造包含所述5种提取物的饮料，让实验参与者饮用这种饮料，并实施感官评价，结果大部分实验参与者在口臭、痰、咳嗽及恶心方面得到改善。
基于这些实验结果完成本发明，故本发明可理解为解烟毒的组合物。
本发明的解烟毒的组合物的特点是其有效成分为蕃茄全草提取物、白花蛇舌草提取物、花楸树提取物、紫草提取物及赤杨提取物中的至少一种提取物。
本说明书中的“烟毒”是指尼古丁和/或焦油引起的毒性，所以烟毒可以理解为与尼古丁毒性和/或焦油毒性相同的意义。
另外，本说明书中的“有效成分”是指单一目的的活性或是与自身没有活性的载体一起显示活性的成分。
另外，本说明书中，“番茄全草提取物”表示不论提取方法，包含以甲醇、乙醇、丙酮、乙酸乙酯、饱和正丁醇、氯仿、二氯甲烷、水或其混合溶剂从番茄叶、茎、花、根或其混合物等提取对象提取而获得的提取物和其提取物中由所述列举的溶剂分离获得的提取物。因此不论提取方法，只要是番茄叶、茎、花、根或其混合物等提取对象经浸泡于提取溶剂的步骤而提取即可，可选择冷浸、回流、加热、超声波等任一方式适用于提取方法。然而，优选的所述“番茄全草提取物”表示包含以水、乙醇或其混合溶剂提取番茄叶、茎、花、根或其混合物等提取对象而获得的提取物，并去除提取溶剂成液相提取物或固相提取物。
另外，本说明书中，“白花蛇舌草(Oldenlandia diffusa)提取物”除了白花蛇舌草叶、茎、花、根或其混合物等提取对象之外其定义可与所述“番茄全草提取物”一样。
另外，本说明书中，“紫草(Lithospermum erythrorhizon)提取物”也同样的除了紫草叶、茎、花、根或其混合物等提取对象之外其定义可与所述“番茄全草提取物”一样，且所述“花楸树提取物”也同样的除了花楸树叶、茎、花、根或其混合物等提取对象之外其定义可与所述“番茄全草提取物”一样，且所述“赤杨提取物”也同样的除了赤杨叶、茎、花、根或其混合物等提取对象之外其定义可与所述“番茄全草提取物”一样。
本说明书中没有特别定义的其它术语具有国语辞典上的意义或本领域普通技术人员通常理解的含义。
此外，本发明的解烟毒的组合物只要其番茄全草提取物等有效成分显出对烟毒的解毒活性，依据用途、剂形、配方目的等可包含任意量（有效量），但以组合物整体的总重量为基准时，通常的有效量在0.001%～99.900%重量范围内。在此“有效量”是指可导致烟毒的预防、改善、治疗或使这些毒性延迟显露的有效成分的量。像这样的有效量是通常本领域的普通技术人员做实验可决定的。
所述天然物或化合物可包括绿茶粉末或提取物、黑豆粉末或提取物、蒲公英粉末或提取物、忍冬粉末或提取物、三白草粉末或提取物、决明子草粉末或提取物、甘草粉末或提取物、山楂子粉末或提取物、槁本粉末或提取物、五加皮粉末或提取物、何首乌粉末或提取物、前胡粉末或提取物、丁香粉末或提取物、陈橘皮粉末或提取物、萝卜子粉末或提取物、车前草粉末或提取物、芦荟粉末或提取物、五味子粉末或提取物、黄耆粉末或提取物、洋葱粉末或提取物、甜菊粉末或提取物等等。所述提取物是指除了提取对象以外与如前所述番茄全草提取物相关的说明一样。所述提取物亦可混合提取对象而获得。
根据一个实施方式，本发明的组合物可以为饮料、口香糖、软糖等食品组合物。
本发明的食品组合物除了其有效成分外还可含有甜味剂、调味剂、生理活性物质、矿物质成分等。
适量甜味剂可使食品产生甜味，有天然的和合成的。优选的是天然甜味剂。所述天然甜味剂可包括玉米糖浆固形物、蜂蜜、蔗糖、果糖、乳糖、麦芽糖等的糖甜味剂。
使用调味剂可增加食品的香味，调味剂有天然的和合成的。优选的是天然调味剂。使用天然调味剂时除了调味以外可以具有加强营养的功能。天然调味剂可从苹果、柠檬、橘子、葡萄、草莓、桃子等获得或从绿茶叶、玉竹、竹叶、桂皮、菊花叶、茉莉花等获得。又可使用从人参（红参）、竹笋、芦荟叶汁、杏仁获得的天然调味剂。天然调味剂可以是液相浓缩液或是固相提取物。根据需要可以使用合成调味剂，合成调味剂可利用酯、酒精、乙醛、烯等。
作为生理活性物质可使用儿茶素、表儿茶素、没食子儿茶素、表没食子儿茶素等儿茶素类或视黄醇、抗坏血酸、维生素E、维生素D2、硫胺素、核黄素等维生素类。
作为矿物质成分可使用钙、镁、铬、钴、铜、氟化物、锗、碘、铁、锂、锰、钼、磷、钾、硒、矽、钠、硫、钒、锌等。
另外本发明的食品组合物除了所述甜味剂等以外根据需要还可以含有防腐剂、乳化剂、酸味剂、粘稠剂等。
所述防腐剂、乳化剂等只要能达到添加的用途，最好添加极微量使用。极微量是指以食品组合物整体总重量为基准，其含量在0.0005%至0.5%重量范围之内。
能使用的防腐剂可包括己二烯酸钙、己二烯酸钠、己二烯酸钾、苯甲酸钙、苯甲酸钠、苯甲酸钾、EDTA（乙烯二胺四乙酸）等。
能使用的乳化剂包括***胶、羧甲基纤维素、黄原胶、果胶等。
能使用的酸味剂包括柠檬酸、苹果酸、反丁烯二酸、己二酸、磷酸、葡萄糖酸、酒石酸、维生素C、乙酸等。所述酸味剂除了增加口味以外，还抑制微生物的繁殖。为了食品组合物具有适当的酸度，食品组合物中可添加所述酸味剂。
能使用的粘稠剂可以为悬浮剂、絮凝剂（flocculant）、成胶剂、膨胀剂等。
根据另一个实施方式，本发明的组合物可以用作药物组合物。
本发明的药物组合物除了其有效成分外还含有药学上允许的载体，赋形剂等，可制造成口服剂型（片剂、悬脬液、颗粒、乳剂、胶囊、糖浆等）、非口服剂型（灭菌注射用水性或油性悬浮液）、局部用剂型（溶液、霜剂、膏剂、胶、洗剂、贴片）等。
所述“药学上允许的”是指不抑制有效成分的活性下，对适用（处方）对象不具有适应范围以上的毒性(足够低的毒素)。
药学上允许的载体可包括乳糖、葡萄糖、蔗糖、淀粉（例如玉米淀粉、马铃薯淀粉等）、纤维素、纤维素衍生物（例如纳羧甲基纤维素、羟乙基纤维素等）、麦芽、明胶、滑石粉、固体润滑剂（例如硬脂酸、硬脂酸镁等）、硫酸钙、植物性油（例如花生油、棉籽油、芝麻油、橄榄油等）、多元醇（例如丙二醇、甘油等）、藻胶酸、乳化剂（例如TWEENS）、润湿剂（例如硫酸月桂酸钠）、着色剂、调味剂、稳定剂、抗氧化剂、保存剂、水、食盐水、磷酸缓冲溶液等。根据本发明的药物组合物的剂型从所述载体中可选择使用一种以上合适的载体。
根据药物组合物的剂型，亦可选择使用合适的赋形剂，例如本发明的药物组合物制成水性悬浮剂时，合适的赋形剂可包括纳羧甲基纤维素、甲基纤维素、羟丙基甲基纤维素、藻胶酸钠、聚乙烯比咯烷酮等悬浮剂或分散剂；制成注射液时，合适的赋形剂可包括林格液、生理食盐水等。
本发明的药物组合物可口服给药或非口服给药，依需要亦可局部给药。
本发明的药物组合物的1日给药量通常在0.001～150mg/kg体重范围之内，其可1次或分成多次给药。然而，本发明的药物组合物的给药量是经考虑给药方式、患者的年龄、性别、体重、患者的症状程度等多种相关因素决定，所以所述给药量在任何情况下不得理解为限制本发明的范围。
如前所述，根据本发明可提供利用番茄全草提取物等解烟毒的组合物。本发明的组合物可以用作如口香糖、饮料等的食品组合物或药物组合物。
附图说明
图1是显示番茄全草提取物消除尼古丁活性的试管实验结果的示意图。
图2是显示白花蛇舌草提取物消除尼古丁活性的试管实验结果的示意图。
图3是显示花楸树提取物消除尼古丁活性的试管实验结果的示意图。
图4是显示紫草提取物消除尼古丁活性的试管实验结果的示意图。
图5是显示赤杨提取物消除尼古丁活性的试管实验结果的示意图。
具体实施方式
以下将参照实施例及实验例对本发明进行说明。然而以下实施例及实验例旨在对本发明进行进一步说明，并不用于限制本发明。
实施例：番茄全草、白花蛇舌草、花楸树、紫草或赤杨提取物的制备
实施例1：番茄全草提取物的制备
将1kg切细的番茄全草（叶、茎及根）浸泡于5公升50%的乙醇中，在50℃提取10小时后去除提取残渣，再经减压浓缩去除提取溶剂而获得固相提取物。
实施例2：白花蛇舌草提取物的制备
将1kg切细的白花蛇舌草叶、茎及根浸泡于5公升50%的乙醇中，在50℃提取10小时后去除提取残渣，再经减压浓缩去除提取溶剂而获得固相提取物。
实施例3：花楸树提取物的制备
将1kg切细的花楸树叶、茎及根浸泡于5公升50%的乙醇中，在50℃提取10小时后去除提取残渣，再经减压浓缩去除提取溶剂而获得固相提取物。
实施例4：紫草提取物的制备
将1kg切细的紫草叶、茎及根浸泡于5公升50%的乙醇中，在50℃提取10小时后去除提取残渣，再经减压浓缩去除提取溶剂而获得固相提取物。
实施例5：赤杨提取物的制备
将1kg切细的赤杨叶、茎及根浸泡于5公升50%的乙醇中，在50℃提取10小时后去除提取残渣，再经减压浓缩去除提取溶剂而获得固相提取物。
制备例：混合饮料的制备
通过混合下面表1所列的量的实施例1至5的提取物制备饮料。
表1饮料的成分及含量
| 含量（重量%） | |
| 实施例1的提取物 | 2.0 |
| 实施例2的提取物 | 2.0 |
| 实施例3的提取物 | 2.0 |
| 实施例4的提取物 | 2.0 |
| 实施例5的提取物 | 2.0 |
| 蜂蜜 | 10.0 |
| 葡萄柚子提取物(天然防腐剂) | 1.0 |
| 蒸溜水 | 残量（至100） |
实验例：分解尼古丁和消除焦油毒性的效果实验及感官评价实验
实验例1：分解尼古丁的效果实验
实验列1-1：试管(In vitro)实验
所述实施例的提取物分解尼古丁的效果试管实验采用Barlow等提出的方法（Barlow R.D,Stone R.B.,Clin.Chim.Acta.,165,pp45,1987）实施如下。
在微型管(microtube,5ml)中放入1mM的尼古丁(Sigma Co.,USA)200μl和同量的10%(w/v)各实施例的提取物（溶解在蒸溜水中），在25℃每过一段时间（0、10、20、30、60及90分钟）测定尼古丁分解生成可替宁的量。对照组使用200μl蒸溜水（替代实施例的提取物）和1mM的尼古丁200μl的混合物。接着依次添加4M醋酸钠缓冲液(sodium acetate buffer)(pH4.7)100μl，1.5M氰酸钾(potassium cyanate)40μl，0.4M氯胺-T(chloramine-T)40μl，以及溶解在50%(v/v)乙腈(acetonitrile)的78mM巴比妥酸(barbituric acid)200μl后混合10秒，再将混合物在常温反应15分钟，用1M偏重亚硫酸钠(sodium metabisulphite)40μl终止反应，在490nm测定吸光度以测定出可替宁的变化量。所有实验各实施3次，其结果在图1至图5中以MEAN±SD表示。参见图1至图5就可了解所述实施例的提取物都以时间依赖性把尼古丁转换成可替宁。
实验例1-2：动物实验
购买体重260-280g，6周龄，Sprague-Dawley系无病菌的实验用小鼠（中央实验室，动物公司，韩国），在实验动物室，温度是21±2℃，照明时间是12L/12D明暗周期，实验开始前提供充分的水和固体饲料，五只为一组分离饲养2周以适应实验环境。
实验动物以5只为一组分成6组(对照组：1组，实验组：5组)，所述各实施例的提取物以1.0g/kg/1日的量与固体饲料混合和水一起口服给药给实验组7天，然后把尼古丁以3mg/kg的量腹腔给药给实验组。所述各实施例的提取物不给药给对照组，只把尼古丁以3mg/kg的量腹腔给药给对照组。下一步从心藏采血1ml测定血液中的尼古丁浓度。尼古丁浓度的测定，以稀氨水把血液调至pH9.0后，在液液萃取柱（EXTRELUT COLUMN;Merck公司）维持15分钟，用15ml的乙酸乙酯洗提，减压蒸馏去除洗提的乙酸乙酯，并将蒸馏物形成的粉末溶解在100μl的乙酸乙酯中作为分析样品。分析使用气相层析质谱仪(gas chromatography-mass spectrophotometer,FISONSInstruments Co.)。
下面表2中血液中尼古丁浓度以平均值±标准偏差（MEAN±SD）表示。
表2血液中尼古丁浓度
实验例2：消除焦油毒性的效果实验
所述各实施例的提取物消除焦油毒性的效果实验采用Brunnemann等的方法[Brunnemann,K.D.and Hoffiman D.,Toxcol,21,235(91)]实施如下。
5只为一个实验组，把焦油以30mg/kg/10ml的量腹腔给药给实验动物后，所述各实施例的提取物以1.0g/kg/1日的量如所述实验例1-2一样口服给药7天，期间观察实验动物的生死。对照组提供蒸溜水以替代实施例的提取物。
下面表3给出7天期间死亡的个体数的结果。
表3死亡个体数
实验例3：感官评价实验
使用所述制备例的饮料对吸烟者的吸烟症状改善的效果如下。
成年男性及成年女性中选出一天抽一盒烟的吸烟者100名，让这些人每天2次饮用所述制备例的饮料一个月。1次饮用量是140ml。
测定项目是口臭、痰、咳嗽及恶心等4个项目，每个项目用5分测定法分成大有改善（5分）、很有改善（4分）、普通改善（3分）、稍有改善（2分）、无效果（0分）等，实施结果列于表4。
表4尼古丁分解效果(单位：名)
| 分类 | 大有改善 | 很有改善 | 普通改善 | 稍有改善 | 无效果 |
| 口臭 | 72 | 18 | 4 | 4 | 2 |
| 痰 | 68 | 21 | 6 | 3 | 2 |
| 咳嗽 | 54 | 26 | 10 | 5 | 5 |
| 恶心 | 66 | 14 | 14 | 4 | 2 |
所述结果表示本发明的饮料对吸烟症状大有改善。
序列表自由文本(Free Text)
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Claims (8)
1.一种解烟毒的组合物，其有效成分为紫草提取物。
2.根据权利要求1所述的解烟毒的组合物，其中，所述紫草提取物是以甲醇、乙醇、丙酮、乙酸乙酯、饱和正丁醇、氯仿、二氯甲烷、水或其混合溶剂提取紫草叶、茎、花、根或其混合物而获得的提取物。
3.根据权利要求1所述的解烟毒的组合物，其中，所述紫草提取物是以乙醇、水或其混合溶剂提取紫草叶、茎、花、根或其混合物而获得的提取物。
4.根据权利要求1所述的解烟毒的组合物，其中，所述有效成分含有蕃茄全草提取物、白花蛇舌草提取物、花楸树提取物、紫草提取物及赤杨提取物。
5.根据权利要求1所述的解烟毒的组合物，所述解烟毒的组合物还含有选自绿茶粉末或提取物、黑豆粉末或提取物、蒲公英粉末或提取物、忍冬粉末或提取物、三白草粉末或提取物、决明子草粉末或提取物、甘草粉末或提取物、山楂子粉末或提取物、槁本粉末或提取物、五加皮粉末或提取物、何首乌粉末或提取物、前胡粉末或提取物、丁香粉末或提取物、陈橘皮粉末或提取物、萝卜子粉末或提取物、车前草粉末或提取物、芦荟粉末或提取物、五味子粉末或提取物、黄耆粉末或提取物、洋葱粉末或提取物和甜菊粉末或提取物中的至少一种粉末或提取物。
6.根据权利要求1至5中任意一项所述的解烟毒的组合物，其中，所述解烟毒的组合物是食品组合物。
7.根据权利要求6所述的解烟毒的组合物，其中，所述食品组合物是饮料、口香糖或软糖。
8.根据权利要求1至5中任意一项所述的解烟毒的组合物，其中，所述解烟毒的组合物是药物组合物。
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| CN104306580A (zh) * | 2014-11-03 | 2015-01-28 | 杨征 | 一种用于辅助戒烟的中药组合物 |
| KR102261122B1 (ko) * | 2020-07-14 | 2021-06-07 | 농업회사법인 주식회사 오케이120 | 혈중 니코틴 농도 감소용 조성물 |
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| JP5459643B2 (ja) | 2014-04-02 |
| CN103479762A (zh) | 2014-01-01 |
| JP2013510139A (ja) | 2013-03-21 |
| EP2500027A1 (en) | 2012-09-19 |
| WO2011059148A1 (ko) | 2011-05-19 |
| CN103478833A (zh) | 2014-01-01 |
| CN102596213A (zh) | 2012-07-18 |
| CN103479791A (zh) | 2014-01-01 |
| KR20110051876A (ko) | 2011-05-18 |
| US20120225140A1 (en) | 2012-09-06 |
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