CN111266096B - 一种聚合物固相色谱填料及其制备方法与应用 - Google Patents

一种聚合物固相色谱填料及其制备方法与应用 Download PDF

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CN111266096B
CN111266096B CN201910836930.3A CN201910836930A CN111266096B CN 111266096 B CN111266096 B CN 111266096B CN 201910836930 A CN201910836930 A CN 201910836930A CN 111266096 B CN111266096 B CN 111266096B
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朱法科
戴威.唐戈.雷内
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Dai WeiTanggeLeinei
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Abstract

本发明公开了一种聚合物固相色谱填料及其制备方法与应用。所述制备方法包括如下步骤：(1)将苯乙烯、二乙烯苯、引发剂和制孔剂加入至液体介质中进行聚合，得到球形材料；(2)向所述球形材料中加入膨胀剂进行反应，得到具有纳米级微孔的球形材料；(3)采用甲醇浸泡所述具有纳米级微孔的球形材料，过滤即得所述固相色谱填料。本发明提供的以苯乙烯‑甲基丙烯酸酯共聚物为基质的聚合物固相色谱填料，通过对粒径、孔径结构、表面改性进行精准控制，得到分辨率高、载量大、刚性强、耐酸碱、抗污染、使用寿命长的色谱分离填料，可以有效使用于天然植物中各种化学成分的分离和纯化，特别是大麻中四氢大麻酚的分离纯化。

Description

一种聚合物固相色谱填料及其制备方法与应用
技术领域
本发明涉及一种聚合物固相色谱填料及其制备方法与应用。
背景技术
液相色谱分离是目前最有效的混合化合物的分离方法，广泛应用于制药、食品、精细化工等领域。在色谱分离体系中存在二相：固定相和流动相。色谱分离的原理就是利用待分离的各种物质在两相中的分配系数、吸附能力等亲和能力不同，随着流动相与固定相的接触和移动，混合物在两相之间经过反复多次的分配平衡，使得各种组分被固定相保留的时间不同，从而按一定次序随着流动相从固定相中流出，实现各种组分的分离。
在色谱分离过程中，分离的核心因素是固定相，固定相的各种物理化学性质直接影响各种物质的分离效果。不同的固定相有不同的物理化学性质。目前常用的固定相有无机和高分子两大类，主要有硅胶、C18、聚合物、氧化铝等类型，每一种色谱填料都具有局限性，因此提供新型、高效的色谱填料十分必要。
发明内容
本发明的目的是提供一种种聚合物固相色谱填料，是以苯乙烯-甲基丙烯酸酯共聚物为基质的聚合物固相色谱填料，通过对粒径、孔径结构、表面改性进行精准控制，得到分辨率高、载量大、刚性强、耐酸碱、抗污染、使用寿命长的色谱分离填料，可以有效使用于天然植物中各种化学成分的分离和纯化，特别是大麻中四氢大麻酚的分离纯化。
本发明所提供的固相色谱填料的制备方法，包括如下步骤：
(1)将苯乙烯、二乙烯苯、引发剂和制孔剂加入至液体介质中进行聚合，得到球形材料；
(2)向所述球形材料中加入膨胀剂进行反应，得到具有纳米级微孔的球形材料；
(3)采用甲醇浸泡所述具有纳米级微孔的球形材料，过滤即得所述固相色谱填料。
上述的制备方法中，步骤(1)中，所述聚合过程中，控制搅拌速度为100～150转/分；所述球形材料的粒度为100～200目。
上述的制备方法中，步骤(1)中，所述反应的温度为50～90℃，时间为2～3小时。
上述的制备方法中，步骤(1)中，所述液体介质为聚乙二醇和液体石蜡的混合液，两者的体积比可为1：1；
所述引发剂可为偶氮二异丁腈、过氧化苯甲酰等；
所述制孔剂可为所述聚乙二醇。
上述的制备方法中，步骤(1)中，所述苯乙烯与所述二乙烯苯的摩尔比为1：1；
所述引发剂的用量为所述苯乙烯摩尔用量的1～2％；
上述的制备方法中，步骤(2)中，所述膨胀剂可为甲醇、乙醇和氯仿的任一种。
所述膨胀剂的用量为所述苯乙烯摩尔用量的30～40％。
上述的制备方法中，步骤(2)中，所述反应的温度为30～40℃，时间为3～4小时。
本发明方法所制备得到的固相色谱填料的粒度为150～200目，孔径为0.1～0.2nm。
本发明提供的固相色谱填料可用于液相色谱分离大麻中的四氢大麻酚，所得到的THC产品的纯度可达98％以上，且可进行工业化生产。
采用本发明固相色谱填料进行色谱生产高纯度四氢大麻酚时，可按照下述步骤进行：
1)采用溶剂萃取大麻，得到萃取液，然后进行液相色谱分离；收集第4～7倍柱体积的流出液，即为含有四氢大麻酚的溶液；
2)所述流出液依次经溶剂脱除，即得到高纯度的四氢大麻酚。
具体地，采用大麻的花叶茎作为原料，其水分含量小于8％，经粉碎为粒度小于0.1mm后进行所述萃取。
具体地，步骤1)中，所述溶剂可为甲醇、乙醇、乙二醇、丙酮、乙酸乙酯、戊烷、正己烷、庚烷和石油醚中任一种，优选乙醇、戊烷或庚烷；
所述溶剂的用量为：6～8L/kg所述大麻。
具体地，步骤1)中，所述液相色谱分离的条件如下：
色谱柱可为高径比8:1的不锈钢柱，体积可为400L；
流动相为水、甲醇、乙醇、丙酮、乙酸乙酯和乙腈中至少2种的混合液或庚烷与乙酸乙酯的混合液；
等度洗脱；
流动速度为柱体积的2～3倍。
附图说明
图1为色谱生产高纯度四氢大麻酚方法的流程图。
具体实施方式
下述实施例中所使用的实验方法如无特殊说明，均为常规方法。
下述实施例中所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1、固相色谱填料的制备
1、在1000ml四口烧瓶中加入400ml聚乙二醇和100ml液体石蜡，50℃下搅拌30分钟，依次加入二乙烯苯40克、苯乙烯25克、偶氮二异丁腈0.8克，搅拌升温到80℃，保温3小时；再加入0.2克过氧化苯甲酰，继续搅拌升温至90℃，保温3小时，过程中进行搅拌，搅拌速度为150转/分，把料倒出。
2、把到出的料过滤得到球形物料(粒度为150～200目)，用热水洗涤球形物料3次至水清，甲醇洗至物料中无水；
3、把球形物料装入直径40mm、高400mm的玻璃柱内，用氯仿(苯乙烯摩尔用量的30％)浸泡3小时，温度保持在30℃，放出氯仿，并用石油醚洗至无腊。
4、放出残留的石油醚，并用甲醇泡洗至清。
5、放出甲醇，倒出球形物料得到制备的固相色谱填料，粒度为150～200目，孔径为0.1～0.15nm。
实施例2、固相色谱填料的制备
1、在1000ml四口烧瓶中加入400ml聚乙二醇、50ml液体石蜡，50℃下搅拌30分钟，依次加入二乙烯苯40克、苯乙烯25克和偶氮二异丁腈1克，搅拌升温到90℃，保温3小时，过程中进行搅拌，搅拌速度为150转/分，把料倒出。
2、把到出的料过滤得到球形物料(粒度为150～200目)，用热水洗涤球形物料3次至水清，甲醇洗至物料中无水；
3、把球形物料装入直径40mm、高400mm的玻璃柱内，用氯仿(苯乙烯摩尔用量的40％)浸泡3小时，温度保持在30℃，放出氯仿，并用石油醚洗至无腊。——同上！
4、放出残留的石油醚，并用甲醇泡洗至清。
5、放出甲醇，倒出球形物料得到制备的固相色谱填料，度为150～200目，孔径为0.1～0.15nm。
实施例3、固相色谱填料用于分离大麻中四氢大麻酚
流程图如图1所示。
1、采用粉碎机把原料粉碎到0.1mm以下，以大麻花叶茎作为原料，含水量小于8％。
2、把粉碎的原料200公斤一次装入溶剂萃取设备内，用8倍重量体积(L/kg)的90％乙醇水进行萃取，收集从萃取设备内流出的含有四氢大麻酚和其它大麻化合物的乙醇萃取液。
3、把乙醇萃取液用水调配成含水30％的溶液，过滤除去不溶物，清液用泵打入色谱系统内，采用80％的乙醇水的溶液(体积含量)作为流动相进行洗脱，分段收集从分离系统内流出的流动相，前3倍柱体积的流出液是杂质，第4～7倍是含四氢大麻酚的溶液。
4、把第三步得到的含有四氢大麻酚乙醇水溶液用膜机回收乙醇，回收的乙醇重复使用；通过膜机去掉90％以上的乙醇后得到的浓缩液进入到单效浓缩器内，脱除剩余的溶剂得到四氢大麻酚油产品。
本实施例所得四氢大麻酚油产品中四氢大麻酚的纯度为95％。
四氢大麻酚的纯度是按照下述方法测定的：
安捷伦高压液相色谱仪，型号1220；
色谱柱：EXTEND-C-18 4.6*250mm 5um；
流动相：乙腈：磷酸水溶液＝70:30；
检测波长：220nm；
流速：1.1ml/min；
柱温：35℃。

Claims (5)

1.一种固相色谱填料的制备方法，包括如下步骤：
(1)将苯乙烯、二乙烯苯、引发剂和制孔剂加入至液体介质中进行聚合，得到球形材料；
步骤(1)中，所述聚合过程中，控制搅拌速度为100～150转/分；所述球形材料的粒度为100～200目；
步骤(1)中，所述反应的温度为50～90℃，时间为2～3小时；
步骤(1)中，所述液体介质为聚乙二醇和液体石蜡的混合液；
所述制孔剂为聚乙二醇；
所述苯乙烯与所述二乙烯苯的摩尔比为1：1；
所述引发剂的用量为所述苯乙烯摩尔用量的1～2％；
(2)向所述球形材料中加入膨胀剂进行反应，得到具有纳米级微孔的球形材料；
步骤(2)中，所述膨胀剂为甲醇、乙醇、氯仿的任一种；
所述膨胀剂的用量为所述苯乙烯摩尔用量的30～40％；
(3)采用甲醇浸泡所述具有纳米级微孔的球形材料，过滤即得所述固相色谱填料。
2.根据权利要求1所述的制备方法，其特征在于：步骤(1)中，所述引发剂为偶氮二异丁腈或过氧化苯甲酰。
3.根据权利要求1或2所述的制备方法，其特征在于：步骤(2)中，所述反应的温度为30～40℃，时间为3～4小时。
4.权利要求1-3中任一项所述方法制备的固相色谱填料。
5.权利要求4所述固相色谱填料在液相色谱分离大麻中四氢大麻酚中的应用。
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