WO2014201735A1 - 一种金雀花碱替代尼古丁口腔雾化液及其制备方法 - Google Patents

一种金雀花碱替代尼古丁口腔雾化液及其制备方法 Download PDF

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Publication number
WO2014201735A1
WO2014201735A1 PCT/CN2013/078913 CN2013078913W WO2014201735A1 WO 2014201735 A1 WO2014201735 A1 WO 2014201735A1 CN 2013078913 W CN2013078913 W CN 2013078913W WO 2014201735 A1 WO2014201735 A1 WO 2014201735A1
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cytisine
nicotine
oral
document
filtrate
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PCT/CN2013/078913
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English (en)
French (fr)
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郑志炫
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昌宁德康生物科技有限公司
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Priority to US14/135,648 priority Critical patent/US9538781B2/en
Publication of WO2014201735A1 publication Critical patent/WO2014201735A1/zh

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    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A24B15/167—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes in liquid or vaporisable form, e.g. liquid compositions for electronic cigarettes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse

Definitions

  • Cypress base instead of nicotine oral atomizing liquid and preparation method thereof
  • the invention relates to a cytisine substitute nicotine oral atomization liquid and a preparation method thereof, and belongs to the technical field of chemical preparation.
  • Nicotine (Ni cot ine), commonly known as nicotine, is an alkaloid found in Solanaceae (Solanum) and an important component of tobacco. Nicotine can be addictive or dependent (one of the most difficult drug addictions), and it is often difficult to restrain yourself. Reusing nicotine also increases heart speed and raises blood pressure and reduces appetite. Large doses of nicotine can cause vomiting and nausea, and in severe cases, people die. Tobacco usually contains nicotine, which prevents many smokers from quit smoking. However, the current method of quitting smoking generally adopts the nicotine replacement method. If it is not well controlled, it still cannot reduce the dependence on nicotine.
  • the cytisine has been sold throughout the country under the name of the drug name of Tabex since 1964. As a smoking cessation drug for many years, the company used cytisine to add nicotine instead of nicotine in oral nebulizer (electron smog) to quit or Does not rely on the effect of nicotine.
  • nicotine is also extracted from tobacco and has lost its original meaning of quitting smoking. Therefore, there is a case of re-smoking.
  • Tobacco leaf extract was used, but it is still a product that mimics the taste of cigarettes and blends tobacco leaf extract with other flavors and fragrances. As more and more smokers begin to accept the use of electronic cigarettes instead of cigarettes, some of the shortcomings of electronic cigarettes used in these electronic cigarettes are becoming more and more obvious. Smokers generally reflect that although electronic cigarettes and cigarettes feel like cigarettes in shape, feel, smoke, etc., in terms of aroma, taste, etc., the difference in feeling with cigarettes is relatively large, especially products formulated with various flavors and fragrances.
  • the object of the present invention is to provide a cytisine instead of a nicotine oral atomizing solution and a preparation method thereof, which can enhance the aroma of the electronic cigarette liquid, improve the taste of the electronic cigarette liquid, and reduce the dependence on nicotine.
  • a cytisine replaces the nicotine oral atomization liquid
  • each 1 L of the oral atomization liquid is composed of the following mass percentage components: tobacco leaves 0. 1 ⁇ 1 0%, Cocoa extract 0. 3 ⁇ 15%, cytisine 0. 1 ⁇ 0. 9%, Tween 80 0. 1 ⁇ 0. 5%, primer 75 ⁇ 90%.
  • the primer is one or a mixture of propylene glycol, polyethylene glycol, glycerin.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), weighing the above-mentioned mass-volume ratio of tobacco leaves into a extraction tank with a sandwich layer according to a target volume; (2), according to the target volume, the above-mentioned mass ratio of Tween 80 and the mass to volume ratio of 60 ⁇ 80% of the primer, the Tween 80 is poured into the primer and stirred for 20 - 40 minutes, this is mixed The liquid is added to the extraction tank to soak the tobacco leaves for 30 to 90 minutes, and then heated to 40 to 60 ° C by steaming into the interlayer, and after 3 to 6 hours of heat preservation, the extract is discharged and filtered to obtain a filtrate;
  • the primer and Tween 80 are of medicinal or edible grade.
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 20 to 60 mesh, into an extraction tank with a sandwich, adding 3 to 10 times of distilled water of cocoa powder, soaking the cocoa powder for 30 to 90 minutes, and heating to 80.
  • the extract was concentrated to a specific gravity of 1. 1 ⁇ 1. 4 of the extract.
  • Ding oral nebulizer which can get closer to the aroma of cigarettes, can better cater to consumers' taste of cigarettes, and can also make the natural aroma components in the replacement of nicotine oral nebulizer into geranine for a longer time and enhance the fragrance.
  • the aroma of the electronic cigarette liquid enhances the taste of the electronic cigarette liquid and reduces the dependence on nicotine.
  • Each 1L of oral nebulizer consists of the following mass percentage components: 10% tobacco, cocoa extract 3.6%, cytisine 0.4%, Tween 80 0.2%, and primer 85.8%.
  • the primer is a mixture of propylene glycol and glycerin in a ratio of 1:3.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), a target volume of 500L, and weighing the above-mentioned mass-volume ratio of the tobacco leaves into the extraction glare of the interlayer;
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 60 mesh, into an extraction tank with an interlayer, adding 10 times of distilled water of cocoa powder, soaking the cocoa powder for 90 minutes, heating to 90 ° C, and heat-absorbing 6 After the hour, the extract was discharged and filtered, and the filtrate was concentrated under reduced pressure to an extract having a specific gravity of 1.1.
  • a cytisine replaces the nicotine oral nebulizing solution, and each 1 L of oral nebulizing liquid is composed of the following mass percentage components: tobacco leaf 10%, cocoa extract 4%, cytisine 0.3%, Tween 80 0.3%
  • the primer is 85.4%.
  • the primer is a mixture of propylene glycol and polyethylene glycol in a ratio of 1:2.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), a target volume of 500L, and weighing the above-mentioned mass-volume ratio of the tobacco leaf into the belt layer according to the target volume Extraction
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 20 mesh, into an extraction tank with an interlayer, adding 3 times of distilled water of cocoa powder, soaking the cocoa powder for 30 minutes, heating to 80 ° C, and heat-absorbing 2 0 ⁇
  • the extract, and the filtrate was concentrated to a specific gravity of 1.4.
  • each 1 L of oral nebulizing liquid consisting of the following mass percentage components: tobacco leaf 0. 1%, cocoa extract 10%, cytisine 0. 9%, spit
  • the temperature is 80. 5%, and the primer is 88.5%.
  • the primer is a mixture of polyethylene glycol and glycerin in a ratio of 1:5.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), a target volume of 300L, and weighing the above-mentioned mass-volume ratio of the tobacco leaves into the extraction glare of the interlayer;
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 40 mesh, into an extraction tank with an interlayer, adding 5 times of distilled water of cocoa powder, soaking the cocoa powder for 50 minutes, heating to 85 ° C, and heat-absorbing 3 After the hour, the extract was discharged and filtered, and the filtrate was concentrated under reduced pressure to an extract having a specific gravity of 1.2.
  • a cytisine replaces nicotine oral nebulizer, and each 1 L of oral nebulizer consists of the following mass percentage components: 5% tobacco, 15% cocoa extract, 0.1% cytisine, Tween 80 0.1% The primer is 79.8%.
  • the primer is polyethylene glycol.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), a target volume of 400L, and weighing the above-mentioned mass-volume ratio of the tobacco leaf into the extraction glare of the belt layer according to the target volume;
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 50 mesh, into an extraction tank with an interlayer, adding 8 times of distilled water of cocoa powder, soaking the cocoa powder for 60 minutes, heating to 90 ° C, and heat-absorbing extraction 5 After the hour, the extract was discharged and filtered, and the filtrate was concentrated under reduced pressure to an extract having a specific gravity of 1.4.
  • a cytisine replaces nicotine oral nebulizer, and each 1 L of oral nebulizer consists of the following mass percentage components: tobacco leaf 8.6%, cocoa extract 0.3%, cytisine 0.7%, Tween 80 0.4% , the primer is 90%.
  • the primer is glycerin.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), a target volume of 500L, and weighing the above-mentioned mass-volume ratio of the tobacco leaves into the extraction glare of the interlayer;
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 40 mesh, into an extraction tank with an interlayer, adding 7 times of distilled water of cocoa powder, soaking cocoa powder for 80 minutes, heating to 90 ° C, and heat-absorbing extraction 5 After the hour, the extract was discharged and filtered, and the filtrate was concentrated under reduced pressure to an extract having a specific gravity of 1.3.
  • Example 6
  • each 1 L of oral nebulizer consists of the following mass percentage components: tobacco 10%, cocoa extract 14%, cytisine 0.7%, Tween 80 0.3% Primer
  • the primer is a mixture of propylene glycol, polyethylene glycol, and glycerin in a ratio of 1: 1:3.
  • a preparation method of cytisine instead of nicotine oral atomization liquid comprising the following steps: (1), a target volume of 400L, and weighing the above-mentioned mass-volume ratio of the tobacco leaf into the extraction glare of the belt layer according to the target volume;
  • the cocoa bean extract is obtained by pulverizing cocoa beans to 60 mesh, into an extraction tank with an interlayer, adding 10 times of distilled water of cocoa powder, soaking the cocoa powder for 90 minutes, heating to 90 ° C, and heat-absorbing 6 After the hour, the extract was discharged and filtered, and the filtrate was concentrated under reduced pressure to an extract having a specific gravity of 1.1.

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Abstract

本发明公开了一种金雀花碱替代尼古丁口腔雾化液及其制备方法，每1L口腔雾化液由以下质量百分比的组分组成：烟叶0.1~10%、可可提取物0.3~15%、金雀花碱0.1~0.9%、吐温800.1~0.5%、底剂75~90%,经过称取烟叶投入提取罐中、放出提取液并过滤得滤液、加入可可豆提取物、加入金雀花碱、添加底剂混合均匀的步骤后即得产品。本发明的有益效果是：使植物中的天然香气成分进入金雀花碱替代尼古丁口腔雾化液，能更接近香烟的香气，更能迎合消费者的品烟感觉，还能使进入金雀花碱替代尼古丁口腔雾化液中的天然香气成分留香时间更长，增强了电子烟液的香气，提高了电子烟液的口味，减少了对尼古丁的依赖。

Description

一种金雀花碱替代尼古丁口腔雾化液及其制备方法
技术领域
本发明涉及一种金雀花碱替代尼古丁口腔雾化液及其制备方法， 属于化工 制备技术领域。
背景技术
烟碱（Ni cot ine ), 俗名尼古丁， 是一种存在于茄科植物（茄属） 中的生物 碱， 也是烟草的重要成分。 尼古丁会使人上瘾或产生依赖性（最难戒除的毒瘾 之一）， 人们通常难以克制自己， 重复使用尼古丁也增加心脏速度和升高血压并 降低食欲。 大剂量的尼古丁会引起呕吐以及恶心， 严重时人会死亡。 烟草中通 常会含有尼古丁， 这使许多吸烟者无法戒掉烟瘾。 然而目前戒烟的手段大体采 用尼古丁替代法， 控制不好依然无法减少对尼古丁的依赖。
临床用金雀花碱 0. 15%水溶液供肌肉或静脉注射， 抢救因手术和各种创伤 引起的反射性呼吸暂停、 休克和新生儿窒息等。 近期研究表明， 该类生物碱还 具有抗心率失常、 抗微生物感染、 抗溃疡、 升高白细胞等多方面的药理作用， 特别是该类化合物较强的抗癌活性， 可用于生产戒烟药、 急救药、 止咳药。
金雀花碱自 1964年便开始以 Tabex的药品名在整个东欧销售， 作为戒烟药 物使用多年， 本公司采用金雀花碱加入口腔雾化液（电子烟液） 中替代尼古丁， 起到戒除或不依赖尼古丁的效果。 现有的戒烟产品， 包括电子烟， 均采用尼古 丁来达到满足烟瘾的效果。 但是尼古丁同样是从烟草提取， 已经失去戒烟的本 义， 因此存在复吸香烟的情况。
金雀花碱替代尼古丁口腔雾化液（或称电子烟雾化液）是目前流行的香烟 替代产品。 关于电子烟液的调配处方、 制备过程， 以及其保健功能等方面， 已 经有许多的文献或专利报道。 中国专利 20091 0104922. 6公开的一种电子模拟香 烟雾化液， 以聚乙二醇 25-90份， 丙二醇 9-50份， 以及口感味道调节剂 0. 3-52 份调配而成， 属于典型的香精香料调配产品。 中国专利 20091 031 05 36. 2公开的 电子香烟雾化液， 以烟叶提取物 3_5%w/v , 烟草香精 3_5% w/v , 烟碱 0_3% w/v , 稳定剂 0. 2- 1% w/v , 增稠剂 3- 8% w/v , 纯水 5- 1 0% w/v , 丙二醇 50- 70% w/v , 以及其它如磷酸可待因、 朴尔敏等调配而成， 虽然使用了烟叶提取物， 但仍然 是模仿香烟口味以烟叶提取物与其它香精香料调配的产品。 由于越来越多的吸 烟者开始接受使用电子烟代替香烟， 用于这些电子烟的电子烟液的一些不足也 就越来越明显。 吸烟者普遍反映， 电子烟与香烟相比， 虽然形状、 手感、 烟雾 等感觉像香烟， 但在香气、 口味等方面， 与品香烟的感觉差距比较大， 尤其以 各种香精香料调配成的产品， 他们难以接受或习惯其香气和口味。 另外， 目前 电子烟液的香气成分难以长期保留， 最好的也只能存放半年左右， "烟味" 就很 淡或几乎没有了， 这也是使用者普遍反映的问题。 这些不足， 大大影响了电子 烟的品质， 同时也制约着电子烟的普及和流行。 发明内容
本发明的目的在于提供一种金雀花碱替代尼古丁口腔雾化液及其制备方 法， 增强电子烟液的香气， 提高电子烟液的口味， 减少对尼古丁的依赖。
本发明的目的是通过以下技术方案来实现的： 一种金雀花碱替代尼古丁口 腔雾化液， 每 1L口腔雾化液由以下质量百分比的组分组成： 烟叶 0. 1 ~ 1 0%、 可 可提取物 0. 3 ~ 15%、 金雀花碱 0. 1 ~ 0. 9%、 吐温 80 0. 1 ~ 0. 5%、 底剂 75 ~ 90%。
所述的底剂为丙二醇、 聚乙二醇、 甘油的一种或混合物。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1 ), 按目标体积称取上述质量体积比的烟叶投入带夹层的提取罐中； ( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 60 ~ 80% 的底剂， 将吐温 80倒入底剂中并搅拌混合 20 - 40分钟，将此混合液加入至提取 罐中浸泡烟叶 30 ~ 90分钟，然后向夹层中通入蒸汽加热升温至 40 ~ 60 °C , 保温 浸提 3 ~ 6小时后， 放出提取液并过滤得滤液；
( 3 )、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 30 ~ 60分 钟；
( 4 )、 向滤液中加入上述质量百分比的金雀花碱；
( 5 )、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 20 ~ 40分 钟， 混合均匀后即得产品。
所述的底剂及吐温 80均为药用或食用级别。
所述的可可豆提取物是将可可豆粉碎至 20 ~ 60目， 投入带夹层的提取罐， 加入可可豆粉重量的 3 ~ 10倍蒸馏水， 浸泡可可豆粉 30 ~ 90分钟， 加热升温至 80 ~ 90 °C ,保温提取 2 ~ 6小时，放出并过滤提取液，滤液减压浓缩至比重为 1. 1 ~ 1. 4的浸膏。 丁口腔雾化液， 能更接近香烟的香气，更能迎合消费者的品烟感觉， 还能使进入 金雀花碱替代尼古丁口腔雾化液中的天然香气成分留香时间更长， 增强了电子 烟液的香气， 提高了电子烟液的口味， 减少了对尼古丁的依赖。 具体实施方式
下面结合实施例进一步描述本发明的技术方案， 但要求保护的范围并不局 限于所述。
实施例 1
每 1L 口腔雾化液由以下质量百分比的组分组成： 烟叶 10%、 可可提取物 3.6%、 金雀花碱 0.4%、 吐温 80 0.2%、 底剂 85.8%。
所述的底剂为丙二醇和甘油按 1: 3比例的混合物。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1)、 目标体积 500L, 按目标体积称取上述质量体积比的烟叶投入带夹层 的提取耀中；
( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 70%的底 剂， 将吐温 80倒入底剂中并搅拌混合 30分钟，将此混合液加入至提取罐中浸泡 烟叶 50分钟，然后向夹层中通入蒸汽加热升温至 50°C, 保温浸提 4小时后， 放 出提取液并过滤得滤液；
( 3)、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 40分钟；
(4)、 向滤液中加入上述质量百分比的金雀花碱；
( 5 )、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 30分钟， 混合均匀后即得产品。
所述的可可豆提取物是将可可豆粉碎至 60目， 投入带夹层的提取罐， 加入 可可豆粉重量的 10倍蒸馏水， 浸泡可可豆粉 90分钟， 加热升温至 90°C, 保温 提取 6小时， 放出并过滤提取液， 滤液减压浓缩至比重为 1.1的浸膏。
实施例 2
一种金雀花碱替代尼古丁口腔雾化液， 每 1L口腔雾化液由以下质量百分比 的组分组成： 烟叶 10%、 可可提取物 4%、 金雀花碱 0.3%、 吐温 80 0.3%、 底剂 85.4%。
所述的底剂为丙二醇和聚乙二醇按 1: 2比例的混合物。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1)、 目标体积 500L, 按目标体积称取上述质量体积比的烟叶投入带夹层 的提取耀中；
( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 76%的底 剂， 将吐温 80倒入底剂中并搅拌混合 30分钟，将此混合液加入至提取罐中浸泡 烟叶 60分钟，然后向夹层中通入蒸汽加热升温至 60 °C , 保温浸提 6小时后， 放 出提取液并过滤得滤液；
( 3 )、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 40分钟；
( 4 )、 向滤液中加入上述质量百分比的金雀花碱；
( 5 )、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 30分钟， 混合均匀后即得产品。
所述的可可豆提取物是将可可豆粉碎至 20目， 投入带夹层的提取罐， 加入 可可豆粉重量的 3倍蒸馏水， 浸泡可可豆粉 30分钟， 加热升温至 80 °C , 保温提 取 2小时， 放出并过滤提取液， 滤液减压浓缩至比重为 1. 4的浸膏。
实施例 3
一种金雀花碱替代尼古丁口腔雾化液， 每 1L口腔雾化液由以下质量百分比 的组分组成： 烟叶 0. 1%、 可可提取物 10%、 金雀花碱 0. 9%、 吐温 80 0. 5%、 底 剂 88. 5%。
所述的底剂为聚乙二醇和甘油按 1: 5比例的混合物。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1 )、 目标体积 300L, 按目标体积称取上述质量体积比的烟叶投入带夹层 的提取耀中；
( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 80%的底 剂， 将吐温 80倒入底剂中并搅拌混合 20分钟，将此混合液加入至提取罐中浸泡 烟叶 30分钟，然后向夹层中通入蒸汽加热升温至 55 °C , 保温浸提 3小时后， 放 出提取液并过滤得滤液；
( 3)、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 30分钟；
(4)、 向滤液中加入上述质量百分比的金雀花碱；
( 5 )、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 20分钟， 混合均匀后即得产品。
所述的可可豆提取物是将可可豆粉碎至 40目， 投入带夹层的提取罐， 加入 可可豆粉重量的 5倍蒸馏水， 浸泡可可豆粉 50分钟， 加热升温至 85°C, 保温提 取 3小时， 放出并过滤提取液， 滤液减压浓缩至比重为 1.2的浸膏。
实施例 4
一种金雀花碱替代尼古丁口腔雾化液， 每 1L口腔雾化液由以下质量百分比 的组分组成： 烟叶 5%、 可可提取物 15%、 金雀花碱 0.1%、 吐温 80 0.1%、 底剂 79.8%。
所述的底剂为聚乙二醇。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1)、 目标体积 400L, 按目标体积称取上述质量体积比的烟叶投入带夹层 的提取耀中；
( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 60%的底 剂， 将吐温 80倒入底剂中并搅拌混合 40分钟，将此混合液加入至提取罐中浸泡 烟叶 90分钟，然后向夹层中通入蒸汽加热升温至 40°C, 保温浸提 6小时后， 放 出提取液并过滤得滤液；
( 3)、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 60分钟；
(4)、 向滤液中加入上述质量百分比的金雀花碱；
( 5 ), 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 40分钟， 混合均匀后即得产品。
所述的可可豆提取物是将可可豆粉碎至 50目， 投入带夹层的提取罐， 加入 可可豆粉重量的 8倍蒸馏水， 浸泡可可豆粉 60分钟， 加热升温至 90°C, 保温提 取 5小时， 放出并过滤提取液， 滤液减压浓缩至比重为 1.4的浸膏。
实施例 5
一种金雀花碱替代尼古丁口腔雾化液， 每 1L口腔雾化液由以下质量百分比 的组分组成： 烟叶 8.6%、 可可提取物 0.3%、 金雀花碱 0.7%、 吐温 80 0.4%、 底 剂 90%。
所述的底剂为甘油。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1)、 目标体积 500L, 按目标体积称取上述质量体积比的烟叶投入带夹层 的提取耀中；
( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 65%的底 剂， 将吐温 80倒入底剂中并搅拌混合 35分钟，将此混合液加入至提取罐中浸泡 烟叶 40分钟，然后向夹层中通入蒸汽加热升温至 45°C, 保温浸提 5小时后， 放 出提取液并过滤得滤液；
( 3)、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 45分钟；
(4)、 向滤液中加入上述质量百分比的金雀花碱；
(5)、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 30分钟， 混合均匀后即得产品。
所述的可可豆提取物是将可可豆粉碎至 40目， 投入带夹层的提取罐， 加入 可可豆粉重量的 7倍蒸馏水， 浸泡可可豆粉 80分钟， 加热升温至 90°C, 保温提 取 5小时， 放出并过滤提取液， 滤液减压浓缩至比重为 1.3的浸膏。 实施例 6
一种金雀花碱替代尼古丁口腔雾化液， 每 1L口腔雾化液由以下质量百分比 的组分组成： 烟叶 10%、 可可提取物 14%、 金雀花碱 0.7%、 吐温 80 0.3%、 底剂
75%。
所述的底剂为丙二醇、 聚乙二醇、 甘油按 1: 1： 3比例的混合物。
一种金雀花碱替代尼古丁口腔雾化液的制备方法， 它包含以下步骤： ( 1)、 目标体积 400L, 按目标体积称取上述质量体积比的烟叶投入带夹层 的提取耀中；
( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 75%的底 剂， 将吐温 80倒入底剂中并搅拌混合 35分钟，将此混合液加入至提取罐中浸泡 烟叶 60分钟，然后向夹层中通入蒸汽加热升温至 50°C, 保温浸提 4小时后， 放 出提取液并过滤得滤液；
( 3)、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 40分钟；
(4)、 向滤液中加入上述质量百分比的金雀花碱；
( 5 )、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 30分钟， 混合均匀后即得产品。
所述的可可豆提取物是将可可豆粉碎至 60目， 投入带夹层的提取罐， 加入 可可豆粉重量的 10倍蒸馏水， 浸泡可可豆粉 90分钟， 加热升温至 90°C, 保温 提取 6小时， 放出并过滤提取液， 滤液减压浓缩至比重为 1.1的浸膏。

Claims

权 利 要 求 书
1、 一种金雀花碱替代尼古丁口腔雾化液， 其特征在于： 每 1L口腔雾化液 由以下质量百分比的组分组成： 烟叶 0. 1 ~ 10%、 可可提取物 0. 3 ~ 15%、 金 雀花碱 0. 1 ~ 0. 9%、 吐温 80 0. 1 - 0. 5%、 底剂 75 ~ 90%。
2、 根据权利要求 1所述的金雀花碱替代尼古丁口腔雾化液， 其特征在于： 所述的底剂为丙二醇、 聚乙二醇、 甘油的一种或混合物。
3、 一种金雀花碱替代尼古丁口腔雾化液的制备方法， 其特征在于： 它包含 以下步骤：
( 1 )、 按目标体积称取上述质量体积比的烟叶投入带夹层的提取罐中； ( 2 )、 按目标体积分别量取上述质量比的吐温 80和质量体积比为 60 ~ 80% 的底剂， 将吐温 80倒入底剂中并搅拌混合 20 - 40分钟，将此混合液加入至提取 罐中浸泡烟叶 30 ~ 90分钟，然后向夹层中通入蒸汽加热升温至 40 ~ 60 °C , 保温 浸提 3 ~ 6小时后， 放出提取液并过滤得滤液；
( 3 )、 向滤液中加入上述质量百分比的可可豆提取物， 搅拌混合 30 ~ 60分 钟；
( 4 )、 向滤液中加入上述质量百分比的金雀花碱；
( 5 )、 添加底剂将滤液体积补足到目标体积 100%为止， 搅拌混合 20 ~ 40分 钟， 混合均匀后即得产品。
4、 根据权利要求 1-3任一权利要求所述的金雀花碱替代尼古丁口腔雾化液 的制备方法， 其特征在于： 所述的底剂及吐温 80均为药用或食用级别。
5、根据权利要求 1或 3所述的金雀花碱替代尼古丁口腔雾化液的制备方法， 其特征在于： 所述的可可豆提取物是将可可豆粉碎至 20 ~ 60目， 投入带夹层的 提取罐， 加入可可豆粉重量的 3 ~ 10倍蒸馏水， 浸泡可可豆粉 30 ~ 90分钟， 加 热升温至 80 ~ 90 °C , 保温提取 2 ~ 6小时， 放出并过滤提取液， 滤液减压浓缩至 比重为 1. 1 ~ 1. 4的浸膏。 International application No.
INTERNATIONAL SEARCH REPORT PCT/CN2013/078913
A. CLASSIFICATION OF SUBJECT MATTER
See the extra sheet
According to International Patent Classification (IPC) or to both national classification and IPC
B. FIELDS SEARCHED
Minimum documentation searched (classification system followed by classification symbols)
IPC: A24B 15/-; A24F 47/-
Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
WPI, EPODOC, CNKI, CNPAT, GOOGLE SCHOLAR: glycerin, nicotine, tobacco leave?, laburnine, cocoa, tween, propylene glycol.
polyethylene glycol, liquid
C. DOCUMENTS CONSIDERED TO BE RELEVANT
Category : Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No.
Y CN 102349699 A (ZHENG, Junxiang et al.) 15 February 2012 (15.02.2012) description,
embodiment 1, page 1, the last paragraph and the last paragraph but one
Y CN 101428021 A (JIANGSU ZEUKOV PHARMACEUTICAL S. & T. INC.) 13 May 2009
(13.05.2009) description, the abstract
A CN 101461566 A (HUA, Jian) 24 June 2009 (24.06.2009) the whole document
A CN 101926505 A (RUYAN BIOSCIENCE INTERNATIONAL CO., LTD) 29 December 2010
(29.12.2010) the whole document
ΓΊ Further documents are listed in the continuation of Box C. 1^1 See patent family annex.
* Special categories of cited documents: "T" later document published after the international filing date or priority date and not in conflict with the application but
"A" document defining the general state of the art which is not cited to understand the principle or theory underlying the considered to be of particular relevance invention
"E" earlier application or patent but published on or after the "X" document of particular relevance; the claimed invention international filing date cannot be considered novel or cannot be considered to involve an inventive step when the document is taken alone
"L" document which may throw doubts on priority claim(s) or
"Y" document of particular relevance; the claimed invention which is cited to establish the publication date of another
cannot be considered to involve an inventive step when the citation or other special reason (as specified) document is combined with one or more other such
"O" document referring to an oral disclosure, use, exhibition or documents, such combination being obvious to a person other means skilled in the art
"P" document published prior to the international filing date "&" document member of the same patent family
but later than the priority date claimed
Figure imgf000011_0001
Form PCT/ISA/210 (second sheet) (July 2009)
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