CN105497230A - 吴茱萸有效成分提取物、制备方法及其应用 - Google Patents

吴茱萸有效成分提取物、制备方法及其应用 Download PDF

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CN105497230A
CN105497230A CN201510988748.1A CN201510988748A CN105497230A CN 105497230 A CN105497230 A CN 105497230A CN 201510988748 A CN201510988748 A CN 201510988748A CN 105497230 A CN105497230 A CN 105497230A
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胡紫霞
毕开顺
李清
许华容
袁子越
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Abstract

本发明提供了一种吴茱萸生物碱和柠檬酸苦素提取物，该提取物包括如吴茱萸碱、异鼠李素和柠檬苦素，分子量在100-500D。本发明还提供了制备上述吴茱萸有效物质提取物的方法，该方法具有成本低、易于工业化生产且简便高效的特点。

Description

吴茱萸有效成分提取物、制备方法及其应用
技术领域
本发明属中药制药领域，具体涉及一种吴茱萸生物碱制备方法及其活性物质在治疗偏头痛药物中的应用。采用现代生产技术和药物经济学来实现其低成本、易于工业化的制备工艺，以保证最低成本、最大效益地满足临床治疗上对药效物质的需求。
背景技术
吴茱萸为常用中药,始载于《神农本草经》、《中国药典》2005年版一部收载的吴茱萸为芸香科植物吴茱萸、石虎及疏毛吴茱萸的干燥近成熟果实。具有散寒止痛、降逆止呕、助阳止泻功能。吴茱萸所含化学成分类型较多,包括生物碱、苦味素、萜类、黄酮、香豆精、甾体、挥发油、木脂素、多糖等。
吴茱萸内酯、吴茱萸碱和吴茱萸次碱为《中国药典》2010年版收录的吴茱萸质量控制指标，相关测定表明去氢吴茱萸碱和绿原酸的含量大于吴茱萸碱和吴茱萸次碱，也为吴茱萸中的主要成分，且现代药理学实验表明去氢吴茱萸碱具有神经保护、抗老年痴呆、抗健忘和体温调节等生理活性，绿原酸具有显著的抗氧化、抗炎和抑菌等活性，因此在对吴茱萸进行质量控制时有必要对去氢吴茱萸碱和绿原酸的含量进行监测。
目前吴茱萸的提取方法还比较落后，且提取物中的组成成分和相关药效不尽相同。传统汤洗法，相关实验表明汤洗7遍后，吴茱萸中极性成分绿原酸的含量显著下降，而生物碱类成分去氢吴茱萸碱、吴茱萸碱和吴茱萸次碱的总量和吴茱萸内酯的含量增大。大孔树脂精制技术、梯度乙醇洗脱液合并或甲醇超声提取等方法，不但具有能耗低、单级分离效果高、工艺简单，而且用于中药分离、纯化时所得制品收率高、纯度好。
发明内容
本发明提供了一种吴茱萸生物碱和柠檬酸苦素提取物，该提取物中有效成分如吴茱萸碱、异鼠李素和柠檬苦素分子量在100-500D。
本发明还提供了制备上述吴茱萸有效物质提取物的方法，其步骤如下：
1.称取吴茱萸；
2.用相当于药材10倍量的水浸泡，回流提取趁热用纱布过滤，重复回流提取一次，合并提取后的滤液；
3.减压浓缩制成干膏或冻干成粉；
4.加沸水捏溶。取上清液过HPD-100大孔树脂柱,分别用浓度为10％,30％,50％,95％乙醇(各4倍柱体积)洗脱,60％以下回收乙醇,将30％,50％乙醇洗脱部分合并；
5.置孔径500D的透析袋内，外套孔径100D的透析袋，扎口。将其浸泡在双蒸馏水烧杯，在4℃静置48小时。分别收集500D袋内(>500D部分)，100D和500D之间(100-500D部分)，以及烧杯内(<100D部分)的液体。
本发明还利用高效液相色谱对不同时间透析处理过的部分化学成分进行分析，采用KromasilC18(250mm×4.6mm，5μm)色谱柱，吴茱萸碱流动相为乙腈∶水(49∶51)，225nm检测；柠檬苦素流动相为乙腈∶水(36∶64)，207nm检测，流速均为1.0mL/min。将各测试成分有效峰面积(峰高∶峰宽≥10)代入各自的线性方程，计算各成分含量。所得数据Excel软件处理。每样本含量平行做3份，取平均值。在100D-500D之间，检测出吴茱萸碱、异鼠李素和柠檬苦素的含量分别为14.4％、3.12％和4.91％。
本发明以热板法中小鼠添足时间作为疼痛阈值，以此为药理指标，确定了吴茱萸中具有镇痛作用的生物碱和柠檬苦素分子量范围为100D-500D.
本发明确定了具有治疗厥阴头痛的吴茱萸生物碱和柠檬酸苦素的分子量范围，针对目前生物碱和柠檬酸苦素常规提取分离方法的缺点，建立一种低成本、易于工业化生产、简便高效的酸枣仁汤生物碱和柠檬酸苦素的制备方法。
具体实施方式
实施例1:吴茱萸提取物的制备
取吴茱萸9kg,粉碎后过20目筛,加6倍量95％的乙醇浸泡过夜。回流提取3次,每次1h,提取液趁热经过6层纱布过滤,合并3次滤液,用1层滤纸抽滤,减压浓缩(60％以下)回收乙醇得干膏1800g。加10L沸水捏溶,分为上清液和捏溶后剩余部分。取上清液过HPD-100大孔树脂柱,分别用10％,30％,50％,95％乙醇(各4倍柱体积)洗脱,60％以下回收乙醇,得到各部分干膏分别为86,148,145,13g。经TLC检测,将30％,50％乙醇洗脱部分合并。置孔径500D的透析袋内，外套孔径100D的透析袋，扎口。将其浸泡在双蒸馏水烧杯，在4℃静置48h。
实施例2：吴茱萸提取物的制备
取90克吴茱萸在30倍量、70℃水中，缓慢搅拌15min，以4层纱布滤出，弃去滤液，重复操作7次，将最终所得吴茱萸于60℃烘干，加十倍量水，浸泡30min，煎煮1h,煎煮液用4层纱布过滤，重复煎煮1次，合并滤液，低压浓缩至约1.5升，浓缩液冻干成粉，粉重约14.0克，得粉率为15.6％。取0.02g冻干粉，精密加1ml甲醇，超声30min，15000rpm离心3min，取上清液。置孔径500D的透析袋内，外套孔径100D的透析袋，扎口。将其浸泡在双蒸馏水烧杯，在4℃静置48h。
实施例3：吴茱萸提取物药理学实验
小鼠随机分8组,每组12只(雌雄各半),每只皮下注射利血平10mg/kg共14天。于第14天将小鼠乙醚麻醉,同时每只小鼠口服阳性对照品西比灵、镇脑宁以及吴茱萸中提取的<100D和100D-500D的成分,连续给药3天,于第3天最后一次给药后1小时通过热板法测痛阈值。
结果总结
由实例三可以得出，100D-500D的吴茱萸提取物对于小鼠的痛阈值有显著的提高，因此推测其有较好的生物活性，对于偏头痛可能有较好的疗效。

Claims (3)

1.一种吴茱萸有效成分提取物，包括吴茱萸碱、异鼠李素和柠檬苦素，分子量在100-500D。
2.如权利要求1所述提取物的制备方法，其步骤如下：
（1）称取吴茱萸；
（2）用相当于药材10倍量的水浸泡，回流提取趁热用纱布过滤，重复回流提取一次，合并提取后的滤液；
（3）减压浓缩制成干膏或冻干成粉；
（4）加沸水捏溶：取上清液过HPD-100大孔树脂柱,分别用4倍柱体积、浓度为10%,30%,50%,95%乙醇洗脱,60%以下回收乙醇,将30%,50%乙醇洗脱部分合并；
（5）置孔径500D的透析袋内，外套孔径100D的透析袋，扎口，将其浸泡在双蒸馏水烧杯，在4℃静置48小时，收集分子量在100D和500D之间的液体。
3.如权利要求1所述的提取物在制备治疗偏头痛药物中的应用。
CN201510988748.1A 2015-12-24 2015-12-24 吴茱萸有效成分提取物、制备方法及其应用 Pending CN105497230A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110049766A (zh) * 2016-12-06 2019-07-23 Sg株式会社 以吴茱萸提取物或吴茱萸碱为有效成分的用于预防或治疗由咖啡因中毒导致的疾病的组合物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
李慧颖等: "不同孔径透析袋对吴茱萸汤提取物入血成分透过的影响-体外药理实验中中药提取物样品前处理的可行性", 《世界科学技术（中药现代化）》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110049766A (zh) * 2016-12-06 2019-07-23 Sg株式会社 以吴茱萸提取物或吴茱萸碱为有效成分的用于预防或治疗由咖啡因中毒导致的疾病的组合物

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