WO2020038238A1 - 一种尼古丁共晶、其制备方法及用途 - Google Patents

一种尼古丁共晶、其制备方法及用途 Download PDF

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WO2020038238A1
WO2020038238A1 PCT/CN2019/099824 CN2019099824W WO2020038238A1 WO 2020038238 A1 WO2020038238 A1 WO 2020038238A1 CN 2019099824 W CN2019099824 W CN 2019099824W WO 2020038238 A1 WO2020038238 A1 WO 2020038238A1
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nicotine
crystal
eutectic
temperature
solvent
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PCT/CN2019/099824
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English (en)
French (fr)
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韩敬美
赵晓晴
李航星
汤建国
郑绪东
雷萍
尚善斋
李志强
王程娅
孙志勇
杜琳
陈永宽
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云南中烟工业有限责任公司
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
    • C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
    • C07C65/05—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring o-Hydroxy carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • the invention belongs to the technical field of electronic cigarettes, and particularly relates to a novel nicotine eutectic, a preparation method thereof, and uses thereof in electronic cigarettes.
  • Nicotine commonly known as nicotine, is an alkaloid found in solanaceae and an important component in tobacco.
  • the industrially purified nicotine is an unpleasant, bitter and clear oily liquid with strong volatility. It is easily oxidized into a light yellow liquid in the air and under light.
  • E-cigarette also known as electronic cigarette or electronic nicotine transmission device, is a non-combustion cigarette substitute product. Because its smoke is generated by the smoke oil through atomization, it will not produce harmful substances generated by ordinary cigarettes burned at high temperature.
  • the existing e-cigarette liquid is mainly composed of flavor nicotine and solvents such as propylene glycol and glycerin.
  • the aerosol similar to cigarette smoke is generated by e-cigarette smoking.
  • Nicotine exists in the electronic cigarette liquid in a free form. The disadvantage is that free nicotine is volatile and deteriorated. It is used in transportation, storage, and use. The other links are easy to leak, and the free nicotine is more irritating to the mucous membrane when inhaled by the sucker, and there is a discomfort in the throat.
  • the current atomization temperature of e-cigarette liquid is still high.
  • the present invention has been made to solve the above problems.
  • the present invention prepares a nicotine co-crystal, solidifies liquid nicotine, and adds it to the e-cigarette liquid to solve the problem that nicotine is volatile and unstable, and at the same time improves the discomfort caused by the nicotine in the free state.
  • the nicotine eutectic of the present invention, its preparation method and its application in electronic cigarettes have not been reported.
  • the first aspect of the present invention discloses a nicotine co-crystal, which is a co-crystal of nicotine and an organic acid.
  • the nicotine eutectic is monoclinic
  • the space group is P21
  • ⁇ 109.005 (3) °
  • ⁇ 90 °
  • the diffraction angles 2 ⁇ are 12.164 ⁇ 0.2 °, 14.888 ⁇ 0.2 °, 15.090 ⁇ 0.2 °, 17.915 ⁇ 0.2 °, 18.117 ⁇ 0.2 °, 19.731 ⁇ 0.2 °, 20.034 ⁇ 0.2 °, 21.143 ⁇
  • the nicotine co-crystal is self-assembled from nicotine and 2,6-dihydroxybenzoic acid in a molar ratio of 1: 1 to 1: 5, and has a melting point of 159-163 ° C.
  • the second aspect of the present invention discloses a method for preparing the nicotine eutectic, including the following steps:
  • step (2) After the product obtained in step (1) is completely dissolved in the solvent, it is left for a certain period of time to volatilize the solvent and precipitate crystals;
  • step (3) The crystal obtained in step (2) is washed, separated, and dried to obtain the nicotine eutectic.
  • the temperature of the reaction in step (1) is 10-40 ° C, and the reaction time is 24-72 hours.
  • the solvent in step (2) is ethanol; the temperature of the solvent volatilization and crystal precipitation is 10-40 ° C, and the time is 5-20 days.
  • the temperature of the washing and separation in step (3) is lower than 10 ° C
  • the solvent used is ethanol having a temperature lower than 10 ° C.
  • the drying in step (3) is vacuum drying.
  • the third aspect of the present invention discloses the use of the nicotine eutectic in an electronic cigarette liquid.
  • the molecular formula of 2,6-dihydroxybenzoic acid used in the present invention is C 7 H 6 O 4 and the structural formula is
  • the chemical name of nicotine is 1-methyl-2- (3-pyridyl) pyrrolidine, and its molecular formula is C 10 H 14 N 2. Its structural formula is
  • the nicotine eutectic of the present invention is obtained for the first time.
  • the nicotine eutectic of the present invention solidifies the nicotine and uses it in an electronic cigarette liquid, so that the tobacco has a strong aroma, a soft aroma, and a strong sense of satisfaction.
  • the nicotine eutectic properties of the present invention are stable and easy to store. When added to the electronic cigarette liquid, the problem of volatile and deteriorating free nicotine is solved, and the shelf life of the electronic cigarette liquid can be significantly prolonged. At the same time, it is not easy to leak in the links of transportation, storage and use.
  • the nicotine eutectic of the present invention has stronger physiological satisfaction than the free nicotine.
  • the pH value of the e-cigarette liquid decreases, which reduces the strong irritation to the throat of the smoker, thereby Makes the throat smoother, suitable for high nicotine content.
  • the nicotine in the nicotine co-crystal of the present invention can be uniformly and stably volatilized, which can maintain the consistency of mouth and mouth; at the same time, the atomizing temperature of the electronic cigarette liquid can be reduced.
  • the preparation method of the nicotine eutectic of the present invention is simple in process, and the obtained nicotine eutectic has high yield and purity, low cost, and is suitable for large-scale industrial production.
  • FIG. 1 is a molecular structure diagram of a nicotine eutectic of the present invention.
  • FIG. 2 is a cell packing diagram of the nicotine eutectic of the present invention.
  • FIG. 3 is a PXRD pattern of the nicotine eutectic of the present invention.
  • FIG. 4 is an infrared spectrum of the nicotine eutectic of the present invention.
  • Figure 5 is a histogram of the nicotine content of free nicotine (sample 1) and nicotine co-crystal (sample 2) added to the e-cigarette mouth by mouth.
  • nicotine is used as a raw material, and 2,6-dihydroxybenzoic acid is used as a ligand.
  • Nicotine-2,6-dihydroxybenzoic acid co-crystals are obtained by a solvent-free mixing method and a solvent volatilization method. Adding the nicotine co-crystal obtained by the invention to the electronic cigarette liquid can obviously improve the stability of the free nicotine, reduce the irritation and lower the atomizing temperature of the electronic cigarette liquid.
  • Example 1 An X-ray single crystal diffractometer was used to measure the light yellow bulk crystals prepared in Example 1.
  • the basic structural unit is shown in FIG. 1.
  • the N atom of the pyrrole ring and the N atom on the pyridine ring are easily protonated. Among them, the N atom on the pyrrole ring is more protonated and the nicotine is easily combined with the H ion. N on the ring is bonded to H on the carboxyl group of 2,6-dihydroxybenzoic acid to form a hydrogen bond. It was found from the structure measurement that the crystal obtained in Example 1 was a nicotine-2,6-dihydroxybenzoic acid co-crystal.
  • Example 1 An X-ray diffractometer was used to detect the light yellow lumpy crystals prepared in Example 1.
  • the obtained X-ray diffraction pattern is shown in FIG. 3. It can be seen from FIG. 3 that the X-ray diffraction pattern of the crystal at the diffraction angle 2 ⁇ is 12.164 ⁇ 0.2 °, 14.888 ⁇ 0.2 °, 15.090 ⁇ 0.2 °, 17.915 ⁇ 0.2 °, 18.117 ⁇ 0.2 °, 19.731 ⁇ 0.2 °, 20.034 ⁇ There are characteristic peaks at 0.2 °, 21.143 ⁇ 0.2 °, and 24.877 ⁇ 0.2 °. It can be illustrated from FIG. 3 that the crystal prepared in Example 1 is a nicotine-2,6-dihydroxybenzoic acid co-crystal.
  • the infrared curve was determined by using a Fourier infrared spectrometer to measure the light yellow block crystal obtained in Example 1. As shown in FIG. 4, the characteristic peaks of the crystal were at 3040.71 ⁇ 0.2cm -1 , 2952 ⁇ 0.2cm -1 , 2384.54. ⁇ 0.2cm -1 , 1624.72 ⁇ 0.2cm -1 , 1593 ⁇ 0.2cm -1 , 1580 ⁇ 0.2cm -1 , 1450 ⁇ 0.2cm -1 , 1357.82 ⁇ 0.2cm -1 . It can be seen from FIG.
  • the C O stretching vibration of the aromatic carboxylic acid at 2), and the stretching vibration of -OH at 2384.54cm -1 is due to nicotine and 2, 6-Dihydroxybenzoic acid causes the absorption band to move to a low frequency direction by OH ⁇ N hydrogen bonding. It can be shown from FIG. 4 that the crystal obtained in Example 1 is a nicotine-2,6-dihydroxybenzoic acid co-crystal.
  • Nicotine (free nicotine) and the light yellow lumpy crystals obtained in Example 1 were added to the electronic aerosolizer and evaluated by professional appraisers. The evaluation process and results are as follows:
  • the e-cigarette liquid added to the sample was added to the atomizer of the e-cigarette for suction.
  • the suction volume was 55 ml
  • the suction time was 3 s
  • the suction frequency was 30 s.
  • a total of 200 mouths were smoked.
  • the gas was adsorbed on a filter, and extracted with an organic solvent, and the content and change of nicotine in each 40 mouths were analyzed.
  • the experimental results are shown in Figure 5. From the left to the right, each group of data is the first 40 ports (ports 1-40), the second 40 ports (ports 41-80), and the third 40 (81-120) and the fourth 80 (121-200). According to the actual situation of consumers, the number of smokers who smoke an electronic cigarette at a time will not exceed 200 mouthpieces. Due to the limitation of the total amount of e-cigarette liquid, the nicotine content of the e-cigarette liquid will be significantly reduced at the end, so the last 80 counts are counted.

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  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

提供了一种尼古丁共晶，其由摩尔比为1∶1～1∶5的尼古丁和2，6-二羟基苯甲酸自组装得到，其熔点为159-163℃。还提供了所述尼古丁共晶的制备方法及在电子烟液中的用途。所述的尼古丁共晶为首次得到，用于电子烟液中，使其烟草香气浓厚、香气柔和，满足感较强。解决了游离态烟碱不稳定易挥发的问题，减少了对抽吸者的喉咙的强烈刺激感。所述的制备方法工艺简单，得到的尼古丁共晶的产量及纯度较高，成本低廉，适合大量生产。

Description

一种尼古丁共晶、其制备方法及用途 技术领域
本发明属于电子烟技术领域，具体涉及一种新型尼古丁共晶、其制备方法及其在电子烟中的用途。
背景技术
尼古丁(Nicotine)，俗称烟碱，是一种存在于茄科植物中的生物碱，也是烟草中的重要成分。工业化提纯后的尼古丁是一种难闻味苦澄清的油质液体，挥发性强，在空气中及光照下极易氧化成淡黄色液体，含量和颜色极不稳定。
电子烟又名电子香烟或电子尼古丁传输装置，是一种非燃烧的卷烟替代产品，由于其烟气是由烟油经过雾化产生，不会产生普通卷烟经高温燃烧而生成的有害物质。现有的电子烟液主要由香精烟碱以及溶剂丙二醇和甘油等组成，通过电子烟抽吸产生类似于卷烟烟气的气溶胶。目前大部分含烟碱的电子烟都是采取直接加入烟碱来满足生理强度，烟碱以游离态形式存在于电子烟液中，其缺点在于游离态的烟碱易挥发变质，在运输、保存、使用等环节容易泄露，同时游离的烟碱在抽吸者吸入时对粘膜刺激性较大，喉咙存在不适感。另外目前的电子烟烟液的雾化温度仍然较高。
为解决上述问题提出本发明。
发明内容
本发明制备了一种尼古丁共晶，使液体尼古丁固体化，添加到电子烟液中，以解决烟碱易挥发不稳定的问题，同时改善游离态烟碱所带来的抽吸者不适感。本发明的尼古丁共晶、其制备方法及应用于电子烟中未见报道。
本发明的技术方案如下：
本发明第一方面公开了一种尼古丁共晶，其为尼古丁与有机酸的共晶。
优选地，所述尼古丁共晶为单斜晶系，空间群为P21，其轴长
Figure PCTCN2019099824-appb-000001
Figure PCTCN2019099824-appb-000002
α＝90°，β＝109.005(3)°，γ＝90°，
Figure PCTCN2019099824-appb-000003
Figure PCTCN2019099824-appb-000004
其在粉末X射线衍射下，在衍射角2θ为12.164±0.2°、14.888±0.2°、15.090±0.2°、17.915±0.2°、18.117±0.2°、19.731±0.2°、20.034±0.2°、21.143±0.2°、24.877±0.2°处有特征峰。
优选地，所述尼古丁共晶由摩尔比为1:1～1:5的尼古丁和2,6-二羟基苯甲酸自组装得到，其熔点为159-163℃。
本发明第二方面公开了所述的尼古丁共晶的制备方法，包括如下步骤：
(1)将摩尔比1:1-1:5的尼古丁和2,6-二羟基苯甲酸混合并在一定温度下和自身压力下密闭反应；
(2)将步骤(1)得到的生成物加入溶剂完全溶解后，静置一定的时间使溶剂挥发和晶体析出；
(3)将步骤(2)得到的晶体洗涤分离干燥即得到所述的尼古丁共晶。
优选地，步骤(1)所述的反应的温度为10-40℃，反应时间为24-72小时。
优选地，步骤(2)所述的溶剂为乙醇；所述的溶剂挥发和晶体析出的温度为10-40℃，时间为5-20天。
优选地，步骤(3)所述的洗涤分离的温度为低于10℃，使用的溶剂为温度低于10℃的乙醇。
优选地，步骤(3)所述的干燥为真空干燥。
本发明第三方面公开了所述的尼古丁共晶用于电子烟液中的用途。
本发明使用的2,6-二羟基苯甲酸的分子式为C 7H 6O 4，结构式为
Figure PCTCN2019099824-appb-000005
尼古丁的化学名称为1-甲基-2-(3-吡啶基)吡咯烷，分子式为C 10H 14N 2，其结构式为
Figure PCTCN2019099824-appb-000006
本发明的有益结果：
1、本发明的尼古丁共晶为首次得到。本发明的尼古丁共晶通过将尼古丁固体化并用于电子烟液中，使其烟草香气浓厚、香气柔和，满足感较强。
2、本发明的尼古丁共晶性质稳定容易保存，加入到电子烟液中，解决了游离态烟碱易挥发变质的问题，可明显延长电子烟烟液的保质期。同时在运输、保 存、使用等环节不容易泄露。
3、本发明尼古丁共晶比游离态的烟碱的生理满足感更强，同时因为尼古丁形成共晶后，电子烟烟液的pH值降低，减少了对抽吸者喉部的强烈刺激感，从而使喉部更顺滑，适合做高尼古丁含量的烟油。
4、本发明尼古丁共晶中的尼古丁能均匀稳定挥发，可以保持口口的一致性；同时可以降低电子烟烟液的雾化温度。
5、本发明的尼古丁共晶的制备方法工艺简单，得到的尼古丁共晶的产量及纯度较高，成本低廉，适合大规模工业化生产。
附图说明
图1为本发明的尼古丁共晶的分子结构图。
图2为本发明尼古丁共晶的晶胞堆积图。
图3为本发明尼古丁共晶的PXRD图。
图4为本发明尼古丁共晶的红外谱图。
图5为游离烟碱(样品1)和尼古丁共晶(样品2)分别添加到电子烟中逐口烟碱含量的柱状图。
具体实施方式
以下结合具体实施例对本发明作进一步的详细说明。应当注意，具体实施例仅为本发明优选的实例而已，不能限定本发明实施范围，即凡依本申请范围所作均等变化与修饰，皆应仍属本发明涵盖范围内。
本发明以尼古丁为原料，2，6-二羟基苯甲酸为配体，通过无溶剂法混合，溶剂挥发法得到尼古丁-2，6-二羟基苯甲酸共晶。本发明得到的尼古丁共晶添加到电子烟液中可以明显改善游离态烟碱的稳定性、降低刺激性和降低电子烟烟液的雾化温度。
下面通过实施例，结合附图，对本发明的技术方案作进一步具体说明：
实例1 尼古丁-2，6-二羟基苯甲酸共晶的制备
用分析天平称取50mg尼古丁，按等摩尔比称量2，6-二羟基苯甲酸，在小烧杯中混匀，加磁子搅拌悬浮液48h，得到胶状粘液。取20ml乙醇溶解粘液至完全溶解，过滤、室温下静止析晶，15天后烧杯中析出淡黄色透明晶体，洗涤抽滤干燥得到淡黄色块状晶体。
实例2 尼古丁-2，6-二羟基苯甲酸共晶的大量生产(实验室放大)
采用分析天平称取2.83g的2，6-二羟基苯甲酸，溶解于28ml乙醇中，然后加入2.98g的尼古丁升温至50℃搅拌溶解，冷却至室温，放置过夜析晶，抽滤得到大量晶体，然后洗涤、室温下真空干燥得到3.77g透明淡黄色晶体。产率为65％。
实例3 尼古丁共晶的晶体结构测定
使用X射线单晶衍射仪对实施例1中制得的淡黄色块状晶体进行测定，其基本结构单元如图1所示。该尼古丁共晶为单斜晶系，如图2所示，空间群为P21，其轴长
Figure PCTCN2019099824-appb-000007
α＝90°，β＝109.005(3)°，γ＝90°，
Figure PCTCN2019099824-appb-000008
由图1可以看出一个质子化的尼古丁分子和一个2，6-二羟基苯甲酸通过氢键结合在一起构成尼古丁-2，6-二羟基苯甲酸晶体的基本结构单元。由于尼古丁的结构有吡啶环和一个吡咯环，吡咯环的N原子和吡啶环上的N原子易质子化，其中吡咯环上的N原子更容易质子化，烟碱容易与H离子结合，所以吡咯环上的N与2，6-二羟基苯甲酸羧基上的H结合，构成氢键。通过结构测定可知，实施例1中制得的晶体为尼古丁-2，6-二羟基苯甲酸共晶。
实例4 尼古丁-2，6-二羟基苯甲酸共晶的粉末X射线衍射图谱
使用X射线衍射仪对实施例1中制得的淡黄色块状晶体进行检测。所得X射线衍射图谱如图3所示。由图3可以看出该晶体的X射线衍射图谱在衍射角2θ为12.164±0.2°、14.888±0.2°、15.090±0.2°、17.915±0.2°、18.117±0.2°、19.731±0.2°、20.034±0.2°、21.143±0.2°、24.877±0.2°处有特征峰。由图3可以说明实施例1中制得的晶体为尼古丁-2，6-二羟基苯甲酸共晶。
实例5 尼古丁-2，6-二羟基苯甲酸共晶的红外图谱测定
采用傅里叶红外光谱仪测定实施例1中制得的淡黄色块状晶体得到红外曲线，如图4所示，该晶体的特征峰在3040.71±0.2cm -1、2952±0.2cm -1、2384.54±0.2cm -1、1624.72±0.2cm -1、1593±0.2cm -1、1580±0.2cm -1、1450±0.2cm -1、1357.82±0.2cm -1处。由图4可以看出在2000～4000cm -1的高波数区域，峰数少且简单，主 要归属于＝CH(苯环)、-CH 3和-OH的伸缩振动。从图4可以看出，该化合物在2952cm -1处存在弱峰，与指纹区1357.82cm -1处存在一个强峰，说明该物质中存在-CH 3；在3000cm -1附近有4个弱吸收峰，这是苯环和-CH 3的C-H伸缩振动；在1624.72cm -1、1593cm -1、1580cm -1、1450cm -1处峰代表苯环的骨架振动；在1624.72cm -1(由于羰基上的O与羟基的H之间形成氢键，使吸收带向低频区方向移动)处芳香羧酸的C＝O伸缩振动，并且2384.54cm -1处-OH的伸缩振动，是由于尼古丁与2，6-二羟基苯甲酸通过O-H···N氢键作用使得吸收带向低频方向移动。由图4可以说明实施例1中制得的晶体为尼古丁-2，6-二羟基苯甲酸共晶。
实例6 尼古丁共晶添加到电子烟液中的抽吸测评
取尼古丁(游离烟碱)和实施例1中制得的淡黄色块状晶体分别加入到电子烟雾化器中，由专业评吸人员评吸，评价过程方式及结果如下：
表1 电子烟液样品及测评结果
Figure PCTCN2019099824-appb-000009
将样品添加的电子烟液中，并加入电子烟的雾化器中分别进行抽吸，抽吸容量为55ml，抽吸时长3s，抽吸频率为30s，共抽吸200口，每40口烟气吸附到一张滤片上，用有机溶剂提取，分析每40口中烟碱含量及变化情况。实验结果如图5所示，图中，每一组数据从左到右依次为第一个40口(第1-40口)，第二个40口(第41-80口)，第三个40口(第81-120口)，第四个80口(第121-200口)。根据消费者的实际情况，一般抽吸者一次吸食电子烟的口数不会超过200口。由于受到电子烟液总量的限制，最后电子烟液的烟碱含量会明显降低，故第四次统计最后80口。
作为对照，研究了游离烟碱及烟碱共晶在烟气中的释放情况，电子烟共抽吸 200口，从图5中可以看出，样品1(游离烟碱)第二个40口比第一个40口下降15.8％、第三个40口比第二个40口下降8.69％；样品2(实施例1制得的尼古丁共晶)第一个40口、第二个40口和第三个40口并没有表现出较大的烟碱释放差别，而是轻微的递减波动，表现出均匀的释放情况。
上述实验表明，将尼古丁共晶添加到电子烟液中，可以提高烟碱的稳定性，使烟碱可以缓慢稳定的释放；同时感官测评结果表明，添加尼古丁-2，6-二羟基苯甲酸共晶的电子烟液抽吸，烟草香气浓郁，香气柔和，满足感较强，对咽喉部刺激性小，抽吸感舒适。

Claims (9)

  1. 一种尼古丁共晶，其特征在于，其为尼古丁与有机酸的共晶。
  2. 根据权利要求1所述的尼古丁共晶，其特征在于，所述尼古丁共晶为单斜晶系，空间群为P21，其轴长
    Figure PCTCN2019099824-appb-100001
    Figure PCTCN2019099824-appb-100002
    α＝90°，β＝109.005(3)°，γ＝90°，
    Figure PCTCN2019099824-appb-100003
    其在粉末X射线衍射下，在衍射角2θ为12.164±0.2°、14.888±0.2°、15.090±0.2°、17.915±0.2°、18.117±0.2°、19.731±0.2°、20.034±0.2°、21.143±0.2°、24.877±0.2°处有特征峰。
  3. 根据权利要求1所述的尼古丁共晶，其特征在于，所述尼古丁共晶由摩尔比为1:1～1:5的尼古丁和2,6-二羟基苯甲酸自组装得到，其熔点为159-163℃。
  4. 根据权利要求1-3任一项所述的尼古丁共晶的制备方法，其特征在于，包括如下步骤：
    (1)将摩尔比1:1～1:5的尼古丁和2,6-二羟基苯甲酸混合并在一定温度下和自身压力下密闭反应；
    (2)将步骤(1)得到的生成物加入溶剂完全溶解后，静置一定的时间使溶剂挥发和晶体析出；
    (3)将步骤(2)得到的晶体洗涤分离干燥即得到所述的尼古丁共晶。
  5. 根据权利要求5所述的制备方法，其特征在于，步骤(1)所述的反应的温度为10-40℃，反应时间为24-72小时。
  6. 根据权利要求5所述的制备方法，其特征在于，步骤(2)所述的溶剂为乙醇；所述的溶剂挥发和晶体析出的温度为10-40℃，时间为5-20天。
  7. 根据权利要求5所述的制备方法，其特征在于，步骤(3)所述的洗涤分离的温度为低于10℃，使用的溶剂为温度低于10℃的乙醇。
  8. 根据权利要求5所述的制备方法，其特征在于，步骤(3)所述的干燥为真空干燥。
  9. 根据权利要求1-3所述的尼古丁共晶用于电子烟液中的用途。
PCT/CN2019/099824 2018-08-24 2019-08-08 一种尼古丁共晶、其制备方法及用途 WO2020038238A1 (zh)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106536501A (zh) * 2014-05-27 2017-03-22 R.J.雷诺兹烟草公司 烟碱盐、共晶体和盐共晶体络合物
WO2017089931A1 (en) * 2015-11-25 2017-06-01 R. J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes
US20180051002A1 (en) * 2014-05-27 2018-02-22 R.J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes
CN108285441A (zh) * 2018-01-03 2018-07-17 云南中烟工业有限责任公司 一种尼古丁-扁桃酸盐复合物晶体、其制备方法及包含其的烟草制品
CN108323792A (zh) * 2018-01-03 2018-07-27 云南中烟工业有限责任公司 一种尼古丁-龙胆酸盐复合物晶体、其制备方法及包含其的烟草制品
CN108329296A (zh) * 2018-01-03 2018-07-27 云南中烟工业有限责任公司 一种尼古丁-酒石酸盐复合物晶体、其制备方法及包含其的烟草制品

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9896429B2 (en) * 2014-05-27 2018-02-20 R.J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106536501A (zh) * 2014-05-27 2017-03-22 R.J.雷诺兹烟草公司 烟碱盐、共晶体和盐共晶体络合物
US20180051002A1 (en) * 2014-05-27 2018-02-22 R.J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes
WO2017089931A1 (en) * 2015-11-25 2017-06-01 R. J. Reynolds Tobacco Company Nicotine salts, co-crystals, and salt co-crystal complexes
CN108285441A (zh) * 2018-01-03 2018-07-17 云南中烟工业有限责任公司 一种尼古丁-扁桃酸盐复合物晶体、其制备方法及包含其的烟草制品
CN108323792A (zh) * 2018-01-03 2018-07-27 云南中烟工业有限责任公司 一种尼古丁-龙胆酸盐复合物晶体、其制备方法及包含其的烟草制品
CN108329296A (zh) * 2018-01-03 2018-07-27 云南中烟工业有限责任公司 一种尼古丁-酒石酸盐复合物晶体、其制备方法及包含其的烟草制品

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PERFETTI THOMAS A.: "Structural Study of Nicotine Salts", BEITRAGE ZUR TABAKFORSCHUNG INTERNATIONAL, vol. 12, no. 2, 30 June 1983 (1983-06-30), XP009185158, ISSN: 0173-783X, DOI: 20191025142716X *

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