CN104311515A - 穿心莲内酯和脱水穿心莲内酯的分离提取工艺 - Google Patents
穿心莲内酯和脱水穿心莲内酯的分离提取工艺 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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Abstract
本发明公开了一种穿心莲内酯和脱水穿心莲及其分离提取工艺，是先取穿心莲药材地上部分干燥品，粉碎后投入提取罐中，用75%乙醇提取3次，将前2次穿心莲药材提取液减压回收乙醇，浓缩，进行高速离心分离，收集离心沉淀，称重，弃去离心液；加入离心沉淀重量7倍、浓度为80%的乙醇，搅拌；过滤，澄清，将过陶瓷膜的滤液通过装有离子交换树脂的树脂柱，再用75%乙醇洗脱，将经离子交换树脂的脱色液通过装填有精制辅料的层析柱，向氧化铝精制液中加入脱色剂，混合均匀，过滤，得脱色液；将脱色液减压回收乙醇；控制脱色液的浓缩体积与乙醇度数实现分步结晶与重结晶，提纯产品，抽滤分离得结晶；将2种结晶真空干燥得成品。本发明生产成本低，产品收率高，生产周期短，能规模化生产。
Description
技术领域
本发明涉及生物科技，具体是一种穿心莲内酯和脱水穿心莲内酯的分离提取工艺。
背景技术
穿心莲，又名一见喜、榄核莲，是广西、广东、海南等省所产的一年生草本植物。穿心莲地上部分主要含有二萜内酯化合物穿心莲乙素（穿心莲内酯）、穿心莲甲素（去氧穿心莲内酯）以及穿心莲丙素（新穿心莲内酯）等。
穿心莲内酯和脱水穿心莲内酯具有抗病原微生物、解热、抗炎、影响机体免疫功能、抗生育、利胆保肝、抗肿瘤等活性，此外，穿心莲内酯可增加肾上腺皮质功能，穿心莲甲、乙、丙、丁素在较大剂量时可使幼年小鼠胸腺萎缩。临床应用：用于菌痢、钩端螺旋体病、脑膜炎、肺炎、增强肾上腺皮质功能、上呼吸道感染。
对穿心莲有效成分的提取，现有的专利技术有：
（1）采用超临界萃取和纯化技术，但该技术设备投入大，生产成本高，生产加工量小，而穿心莲内酯和脱水穿心莲内酯的售价相对较低，不足2000元/kg。目前国内未有一家企业采用超临界萃取技术生产穿心莲提取物。
（2）采用硅胶、氧化铝等吸附层析技术，以及二氯甲烷、三氯甲烷（氯仿）、石油醚、乙酸乙酯等有机溶剂洗脱精制。但该技术使用大量吸附层析剂及有机溶剂，生产成本高，且有机溶剂有毒有害，、易挥发而引起生产成本过高。目前国内未有一家企业采用此技术生产穿心莲提取物。
（3）采用大孔吸附树脂精制，但穿心莲内酯和脱水穿心莲内酯是醇溶性成分，不易被大孔吸附树脂吸附，此技术的生产可行性，需要进一步确定。
发明内容
本发明的目的是要提供一种生产成本低，产品收率高，生产周期短，能规模化生产的穿心莲内酯含量≥98%、脱水穿心莲内酯含量≥98%、颜色白色、重金属、农药残留、微生物符合国标的提取分离工艺。
实现本发明目的的技术方案是：
一种穿心莲内酯和脱水穿心莲内酯的分离提取工艺，包括如下步骤：
（1）醇提：取穿心莲药材地上部分干燥品，粉碎后投入提取罐中，用75%乙醇、在温度50℃~60℃提取3次。加入75%乙醇量分别为药材重量的5、4、5倍；采用循环套用提取方法，提取时间分别为2h、1.5h、1h，每次过滤后的滤渣进入下一次提取；
（2）减压回收乙醇：将前2次穿心莲药材提取液减压回收乙醇，浓缩；
（3）离心：将浓缩液进行高速离心分离，收集离心沉淀，称重，弃去离心液；
（4）醇溶沉淀与澄清：加入离心沉淀重量7倍、浓度为80%的乙醇，搅拌使离心沉淀完全溶解；将离心沉淀的乙醇溶液用200目不锈钢滤网过滤，滤液经澄清设备分离澄清，得澄清透明的滤液；
（5）离子交换树脂脱色：按每吨穿心莲药材用0.3吨离子交换树脂的比例，即1:0.3，将过陶瓷膜的滤液通过装有离子交换树脂的树脂柱，再用75%乙醇洗脱，自进滤液起开始收集，收集至进完料液后再收集2倍树脂体积止，得脱色液；
（6）氧化铝精制：将经离子交换树脂的脱色液通过装填有精制辅料的层析柱，进样量为每1000L脱色液用50kg精制辅料。进完料液后，用洗脱液洗脱，自进料起收集，至进完料后收集1.5倍洗脱液
（7）脱色：向氧化铝精制液中加入脱色剂，充分搅拌与混合均匀，放置20min，再搅拌5min，静置15min后用板框过滤，得澄清透明色浅的脱色液；
（8）减压回收乙醇：将脱色液减压回收乙醇；
（9）分步结晶、重结晶：控制脱色液的浓缩体积与乙醇度数实现分步结晶与重结晶，提纯产品，抽滤分离得结晶；
（10）真空干燥：将2种结晶真空干燥得成品。
步骤（1）所述的循环套用提取方法，即第1批物料的第3次提取液套用，作为第2批物料的第1次提取液。
步骤（2）所述浓缩的浓缩程度为穿心莲药材重量：浓缩液体积比= 1:0.5~1。
步骤（3）所述的离心方式为管式离心、碟片式离心或三足沉降离心。
步骤（4）所述的澄清设备为陶瓷膜成套设备；
步骤（5）所述的离子交换树脂为D301或D316或D762阴离子交换树脂。
步骤（6）所述的精制辅料为酸性氧化铝；（2）洗脱液为75%乙醇洗脱液。
步骤（7）所述的脱色剂为粉状活性炭；脱色剂的加入量：粉状活性炭为解吸液体积0.3%~0.5%。
产品经检验，成品为白色粉末，穿心莲内酯≥98%、脱水穿心莲内酯≥98%。
穿心莲内酯，又名穿心莲乙素，系天然植物穿心莲的主要有效成分，被誉为天然抗生素药物。本品为白色方棱形或片状结晶 （乙醇或甲醇），无臭，味苦；在沸乙醇中溶解，在甲醇或乙醇中略溶，极微溶于氯仿，在水或乙醚中几乎不溶；熔点230～231℃，（α）17D -126.6±2°（冰醋酸），[α]D –112.7 (c,0.53,MeOH)，与碱性2% 3,5－二硝基苯甲酸试剂，显紫红色，异羟肟酸铁反应呈阳性；密度(21℃）1.2317g/cm3。
脱水穿心莲内酯，又名穿心莲丁素，系穿心莲内酯脱水而得。本品为无色针状结晶(30%或50%乙醇)；熔点：204℃；易溶于乙醇、丙酮，可溶于氯仿，微溶于苯，几乎不溶于水。
其穿心莲内酯和脱水穿心莲内酯的结构式分别为：
穿心莲内酯Andrographolide 脱水穿心莲内酯Dehydroandrographolide
本发明的优点是：
（1）工业化批量生产出了穿心莲内酯、脱水穿心莲内酯含量≥98%、颜色为白色、重金属、农药残留、微生物符合国标的高品质穿心莲提取物，降低了生产成本，占领高端天然抗生素提取物市场，实现产品出口；
（2）成功开发了一条切实可行的工业化生产工艺路线，批量生产穿心莲内酯、脱水穿心莲内酯产品。根据穿心莲地上部分的化学成分特点，将陶瓷膜澄清、离子交换树脂脱色、氧化铝精制、活性炭脱色、分步结晶与重结晶等关键生产工艺环节有效结合起来。
附图说明
图1为本发明分离提取工艺的工艺流程图；
图2为实施例的工艺流程图。
具体实施方式
实施例：
如图2所示。
Claims (10)
1.一种穿心莲内酯和脱水穿心莲的分离提取工艺，其特征是：包括如下步骤：
（1）醇提：取穿心莲药材地上部分干燥品，粉碎后投入提取罐中，用75%乙醇、在温度50℃~60℃提取3次；加入75%乙醇量分别为药材重量的5、4、5倍；采用循环套用提取方法，提取时间分别为2h、1.5h、1h，每次过滤后的滤渣进入下一次提取；
（2）减压回收乙醇：将前2次穿心莲药材提取液减压回收乙醇，浓缩；
（3）离心：将浓缩液进行高速离心分离，收集离心沉淀，称重，弃去离心液；
（4）醇溶沉淀与澄清：加入离心沉淀重量7倍、浓度为80%的乙醇，搅拌使离心沉淀完全溶解；将离心沉淀的乙醇溶液用200目不锈钢滤网过滤，滤液经澄清设备分离澄清，得澄清透明的滤液；
（5）离子交换树脂脱色：按每吨穿心莲药材用0.3吨离子交换树脂的比例，即1:0.3，将过陶瓷膜的滤液通过装有离子交换树脂的树脂柱，再用75%乙醇洗脱，自进滤液起开始收集，收集至进完料液后再收集2倍树脂体积止，得脱色液；
（6）氧化铝精制：将经离子交换树脂的脱色液通过装填有精制辅料的层析柱，进样量为每1000L脱色液用50kg精制辅料；进完料液后，用洗脱液洗脱，自进料起收集，至进完料后收集1.5倍洗脱液
（7）脱色：向氧化铝精制液中加入脱色剂，充分搅拌与混合均匀，放置20min，再搅拌5min，静置15min后用板框过滤，得澄清透明色浅的脱色液；
（8）减压回收乙醇：将脱色液减压回收乙醇；
（9）分步结晶、重结晶：控制脱色液的浓缩体积与乙醇度数实现分步结晶与重结晶，提纯产品，抽滤分离得结晶；
（10）真空干燥：将2种结晶真空干燥得成品。
2.根据权利要求1所述的分离提取工艺，其特征是：步骤（1）所述的循环套用提取方法，即第1批物料的第3次提取液套用，作为第2批物料的第1次提取液。
3.根据权利要求1所述的分离提取工艺，其特征是：步骤（2）所述浓缩的浓缩程度为穿心莲药材重量：浓缩液体积比= 1:0.5~1。
4.根据权利要求1所述的分离提取工艺，其特征是：步骤（3）所述的离心方式为管式离心、碟片式离心或三足沉降离心。
5.根据权利要求1所述的分离提取工艺，其特征是：步骤（4）所述的澄清设备为陶瓷膜成套设备。
6.根据权利要求1所述的分离提取工艺，其特征是：步骤（5）所述的离子交换树脂为D301或D316或D762阴离子交换树脂。
7.根据权利要求1所述的分离提取工艺，其特征是：步骤（6）所述的精制辅料为酸性氧化铝；（2）洗脱液为75%乙醇洗脱液。
8.根据权利要求1所述的分离提取工艺，其特征是：步骤（7）所述的脱色剂为粉状活性炭；脱色剂的加入量：粉状活性炭为解吸液体积0.3%~0.5%。
9.用权利要求1-8之一所述的分离提取工艺提取的纯度≥98%的穿心莲内酯。
10.用权利要求1-8之一所述的分离提取工艺提取的纯度≥98%的脱水穿心莲内酯。
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