CN106939006B - 一种从赛北紫堇中提取分离白毛茛碱的方法 - Google Patents
一种从赛北紫堇中提取分离白毛茛碱的方法 Download PDFInfo
- Publication number
- CN106939006B CN106939006B CN201710172755.3A CN201710172755A CN106939006B CN 106939006 B CN106939006 B CN 106939006B CN 201710172755 A CN201710172755 A CN 201710172755A CN 106939006 B CN106939006 B CN 106939006B
- Authority
- CN
- China
- Prior art keywords
- solution
- corydalis
- hydrastine
- extraction
- flow rate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241000218176 Corydalis Species 0.000 title claims abstract description 27
- CRAVBINFWZGLSC-UHFFFAOYSA-N Hydrastine Natural products COC1=C(OC)C2C(C=C1)C(OC2=O)C3N(C)CCc4cc5OCOc5cc34 CRAVBINFWZGLSC-UHFFFAOYSA-N 0.000 title claims abstract description 26
- JZUTXVTYJDCMDU-MOPGFXCFSA-N Hydrastine Chemical compound CN1CCC2=CC=3OCOC=3C=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 JZUTXVTYJDCMDU-MOPGFXCFSA-N 0.000 title claims abstract description 26
- JZUTXVTYJDCMDU-UHFFFAOYSA-N d-alpha-hydrastine Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 JZUTXVTYJDCMDU-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 229930005369 hydrastine Natural products 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000000926 separation method Methods 0.000 title abstract description 6
- 238000000605 extraction Methods 0.000 claims abstract description 23
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000012528 membrane Substances 0.000 claims abstract description 10
- 239000003729 cation exchange resin Substances 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 241001495448 Impatiens <genus> Species 0.000 claims description 21
- 229930190166 impatien Natural products 0.000 claims description 21
- 229930013930 alkaloid Natural products 0.000 claims description 18
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000001471 micro-filtration Methods 0.000 claims description 11
- 238000000108 ultra-filtration Methods 0.000 claims description 9
- 238000010828 elution Methods 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 241000783421 Corydalis saxicola Species 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 238000011068 loading method Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- ONBIUAZBGHXJDM-UHFFFAOYSA-J bismuth;potassium;tetraiodide Chemical compound [K+].[I-].[I-].[I-].[I-].[Bi+3] ONBIUAZBGHXJDM-UHFFFAOYSA-J 0.000 claims description 4
- 239000000919 ceramic Substances 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 4
- 229910021641 deionized water Inorganic materials 0.000 claims description 4
- 239000012510 hollow fiber Substances 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- 229920000172 poly(styrenesulfonic acid) Polymers 0.000 claims description 4
- 229940005642 polystyrene sulfonic acid Drugs 0.000 claims description 4
- 238000007873 sieving Methods 0.000 claims description 4
- 238000002791 soaking Methods 0.000 claims description 4
- 238000000194 supercritical-fluid extraction Methods 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 3
- 229920002521 macromolecule Polymers 0.000 claims description 3
- 239000000084 colloidal system Substances 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- 239000003456 ion exchange resin Substances 0.000 claims description 2
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000013618 particulate matter Substances 0.000 claims description 2
- 239000000049 pigment Substances 0.000 claims description 2
- 229920002492 poly(sulfone) Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 241000218180 Papaveraceae Species 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 16
- 230000001276 controlling effect Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 5
- 241000876833 Emberizinae Species 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 108010001202 Cytochrome P-450 CYP2E1 Proteins 0.000 description 1
- 102100024889 Cytochrome P450 2E1 Human genes 0.000 description 1
- 101000987297 Homo sapiens Serine/threonine-protein kinase PAK 4 Proteins 0.000 description 1
- LWPLPJQNBQQUKR-UHFFFAOYSA-N Hydrastidine Natural products COc1ccc2C(OC(=O)c2c1O)C3N(C)CCc4cc5OCOc5cc34 LWPLPJQNBQQUKR-UHFFFAOYSA-N 0.000 description 1
- LWPLPJQNBQQUKR-IEBWSBKVSA-N Hydrastidine Chemical compound [H][C@@]1([C@@H]2OC(=O)C3=C(O)C(OC)=CC=C23)N(C)CCC2=C1C=C1OCOC1=C2 LWPLPJQNBQQUKR-IEBWSBKVSA-N 0.000 description 1
- 241000735432 Hydrastis canadensis Species 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- GTRPODKMSBFDOI-UHFFFAOYSA-N Protopine Natural products CN1Cc2c3OCOc3ccc2C4C1Cc5cc6OCOc6cc5C4=O GTRPODKMSBFDOI-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- ZAALQOFZFANFTF-UHFFFAOYSA-N Pseudoprotipine Natural products C1=C2C(=O)CC3=CC=4OCOC=4C=C3CN(C)CCC2=CC2=C1OCO2 ZAALQOFZFANFTF-UHFFFAOYSA-N 0.000 description 1
- 102100027940 Serine/threonine-protein kinase PAK 4 Human genes 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- -1 apophenanthrene Chemical compound 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OWUNMSGLMUPGEZ-UHFFFAOYSA-N benzo[k]phenanthridine Chemical compound C1=CC=CC2=C3C4=CC=CC=C4C=CC3=CN=C21 OWUNMSGLMUPGEZ-UHFFFAOYSA-N 0.000 description 1
- IZTUINVRJSCOIR-UHFFFAOYSA-N benzylisoquinoline Chemical compound N=1C=CC2=CC=CC=C2C=1CC1=CC=CC=C1 IZTUINVRJSCOIR-UHFFFAOYSA-N 0.000 description 1
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
- 229940093265 berberine Drugs 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- CHWPMFMUQATVNK-ARYYTZDLSA-N dihydrosporogen AO-1 Natural products O[C@H]1[C@]2(C(C)=C)O[C@@H]2[C@]2(C)[C@@H](C)[C@H](O)CCC2=C1 CHWPMFMUQATVNK-ARYYTZDLSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000825 effect on plasmodium Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 235000005679 goldenseal Nutrition 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229930013397 isoquinoline alkaloid Natural products 0.000 description 1
- PDFVZBYHNGBJOU-UHFFFAOYSA-N isoquinoline phenol Chemical compound C1=NC=CC2=CC=CC=C12.C1(=CC=CC=C1)O PDFVZBYHNGBJOU-UHFFFAOYSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种从赛北紫堇中提取分离白毛茛碱的方法,属于天然产物提取分离技术领域,该方法以罂粟科紫堇属植物赛北紫堇为原料,经过粉碎碱化、超临界CO2萃取、膜分离技术结合阳离子交换树脂和重结晶的方法实现了赛北紫堇中高***毛茛碱的分离。本发明所用的方法有毒试剂用量少,产率高达0.43%,且白毛茛碱的纯度可达99.0%。
Description
技术领域
本发明涉及一种从罂粟科紫堇属植物中提取、分离白毛茛碱的方法,具体是一种从赛北紫堇中大量制取高***毛茛碱的方法。
背景技术
赛北紫堇(Corydalis impatiens)为罂粟科紫堇属植物,收载于《中华本草》藏药卷,其根、茎、叶、花均可入药,具有除热消肿、活血散瘀、收敛止痒、祛风利气等功效。赛北紫堇广泛分布在青海、西藏、甘肃、四川及内蒙古等地,为藏药常用药材。本属植物主要含苄基异喹啉类、苯酚异喹啉类、苯并菲啶类、小檗碱类、阿朴菲类、普罗托品类及螺苄异喹啉类等结构类型的生物碱。
白毛茛碱(hydrastine)又称北美黄连碱,是一种苯酚异喹啉类生物碱,由阿尔弗雷德·杜兰德发现于1851年。有研究表明,白毛茛碱可以显著抑制耐甲氧西林金黄色葡萄球菌(MRSA),有预防感染的功效;对具有多药耐药性的恶性疟原虫菌株有明显的抑制效果,且对正常细胞没有毒性;白毛茛碱可以抑制CYP2E1的活性,对对乙酰氨基酚引起的肝脏损伤起到防护作用;抑制PAK4激酶活性从而抑制下游与肿瘤增长有关的信号分子,引起肺癌细胞凋亡,起到抗肿瘤的作用。此外,白毛茛碱还有降血压、调节平滑肌和止血等功能。
目前只有从赛北紫堇中提取总生物碱的文献,而分离白毛茛碱的文献较少,且所得白毛茛碱的产率低于万分之一。如专利CN103610762(一种塞北紫堇总生物碱提取物及提取方法,申请号201310680353.6)采用碱性乙醇回流提取总生物碱,其中白毛茛碱的含量较低。由于生物碱在天然植物中的含量较低,用水提或有机溶剂提取的方法会引入其他成分,为了得到高纯度的白毛茛碱单体必须对其进行精制纯化。
发明内容
技术问题:本发明的目的在于提供一种从赛北紫堇中提取分离白毛茛碱的方法,该方法成本低、操作简单,得到的白毛茛碱产量大且纯度高达99%。
技术方案:本发明提供的一种从赛北紫堇中提取分离白毛茛碱的方法,包括以下步骤:
步骤1.粉碎、碱化:将赛北紫堇全草阴干,粉碎至40-60目,得到赛北紫堇粉末,加入Na2CO3溶液浸泡3-4小时,晾干后过40-60目筛;
步骤2.超临界提取:将处理好的赛北紫堇粉末装入超临界萃取釜中,超临界CO2萃取,用乙醇溶液为夹带剂动态提取,解析萃取液并回收乙醇,得到粗生物碱;
步骤3.微滤:将粗生物碱浸膏溶解在酸水中并调节溶液pH值至2-3,将此溶液用孔径在0.5-1.0微米的陶瓷膜进行微滤处理,控制微滤温度在25-35℃,微滤压力在0.5-0.7MPa,除去颗粒物和高分子物质;
步骤4.超滤:将微滤后的溶液用聚砜中空纤维超滤膜进行超滤处理,分子截留量在4000-8000D,控制超滤压力在0.1-0.3MPa,操作温度为25-35℃,溶液pH值维持在2-3,除去大分子物质如多糖、胶质、蛋白质及色素;
步骤5.离子交换树脂分离:将所得滤液过处理好的酸性阳离子交换树脂柱,调节上样流速,先用去离子水冲洗至中性,除去水溶性小分子杂质,再调节洗脱流速用1%Na2CO3溶液碱化50-80%乙醇洗脱,收集洗脱液用碘化铋钾显色剂检测,直至无生物碱流出为止,合并检测呈阳性的洗脱液;
步骤6.重结晶:将所得的上述洗脱液减压浓缩、干燥,加入二氯甲烷溶解过滤,然后用常规方法重结晶,过滤,得到结晶物即为白毛茛碱。
其中,
所述的步骤1中,加入的Na2CO3溶液pH值为10-11,赛北紫堇粉末与Na2CO3溶液的质量比为1:1.5-1:2。
所述的步骤2中,调节萃取温度为30~45℃,萃取压力为20~30MPa,夹带剂为90%的乙醇溶液,萃取时间为2-4小时状态为动态提取,流速为1.0-1.5mL/min。
所述的步骤3中,粗生物碱与酸水的质量比为1:20-1:40;酸水溶液为盐酸或硫酸溶液。
所述的步骤5中,所述的酸性阳离子交换树脂采用001×7聚苯乙烯磺酸型阳离子交换树脂;上样流速为1-2BV/h,洗脱流速为2-3BV/h。
有益效果:与现有技术相比,本发明的有益效果为:
(1)超临界流体萃取温度较低,生物碱不易分解,且超临界流体在高压低温时对生物碱的溶解性比传统的有机溶剂法要强,提高了提取率。
(2)膜分离技术,设备简单常温下操作,药材中的生物碱不易分解变质,采用不同孔径的膜依次过滤,大分子物质有效分离,操作过程能耗低,不消耗试剂且经过处理后的膜可重复使用。
(3)整个操作过程均在常温下进行,具有制取过程简单,收率高,所制得的白毛茛碱纯度高等特点。
附图说明
图1是利用本发明制备的高***毛茛碱的色谱出峰图谱。
图2是利用本发明制备的白毛茛碱的1H-NMR图谱。
图3是利用本发明制备的白毛茛碱的13C-NMR图谱。
具体实施方式
下面对本发明技术方案进行详细说明,但是本发明的保护范围不局限于所述实施案例。
实施案例1:
首先将干燥赛北紫堇全草重约5.0kg,全草粉碎至40目,加入pH为11的Na2CO3溶液10L,浸泡4h,晾干后过40目筛。将碱化后的赛北紫堇粉末加入到萃取釜中,调节萃取温度为35℃,萃取压力为20MPa,用90%乙醇为夹带剂,调节夹带剂的流速为1.0mL/min,动态萃取2小时。萃取完成后减压回收溶剂。上述生物碱浸膏50g用1L盐酸水溶液溶解,调节pH值为2.0,控制压力为0.5MPa,温度为25℃用陶瓷微滤。收集滤液保持温度不变,用截留分子量为6000D的中空纤维超滤膜超滤,控制压力为0.3MPa。所得滤液过001×7聚苯乙烯磺酸型阳离子交换树脂,控制上样流速为1BV/h,用去离子水洗脱除去中性及酸性杂志,控制洗脱流速为2BV/h。再用1%Na2CO3溶液碱化,50%乙醇洗脱,每100mL接收一次洗脱液,薄层色谱检测,收集碘化铋钾呈阳性的洗脱液。将洗脱液浓缩,用二氯甲烷溶解,过滤,重结晶即得到白毛茛碱。
实施案例2:
首先将干燥赛北紫堇全草重约5.0kg,全草粉碎至60目,加入pH为10的Na2CO3溶液12L,浸泡4h,晾干后过60目筛。将碱化后的赛北紫堇粉末加入到萃取釜中,调节萃取温度为45℃,萃取压力为25MPa,用90%乙醇为夹带剂,调节夹带剂的流速为1.5mL/min,动态萃取4小时。萃取完成后减压回收溶剂。上述生物碱浸膏45g用1.8L硫酸水溶液溶解,调节pH值为3.0,控制压力为0.6MPa,温度为30℃用陶瓷微滤。收集滤液保持温度不变,用截留分子量为8000D的中空纤维超滤膜超滤,控制压力为0.2MPa。所得滤液过001×7聚苯乙烯磺酸型阳离子交换树脂,控制上样流速为2BV/h,用去离子水洗脱除去中性及酸性杂志,控制洗脱流速为3BV/h。再用1%Na2CO3碱化,70%乙醇洗脱,每100mL接收一次洗脱液,薄层色谱检测,收集碘化铋钾呈阳性的洗脱液。将洗脱液浓缩,用二氯甲烷溶解,过滤,重结晶即得到白毛茛碱。
上述所得固体经过HPLC,波长254nm下测定其纯度为99.0%,液相图参照附图1。
将得到的化合物通过1H-NMR、13C-NMR进行结构鉴定,结合相关文献报道确定该化合物为白毛茛碱。Blasko G,Gula D J,Shamma M.The phthalideisoquinolinealkaloids.Journal of Natural Products,1982,45(2):105-122.
核磁谱图参照附图2-3,所得白毛茛碱数据如下:无色块状晶体,溶于氯仿,分子式为C21H21NO6,分子量为383.3。
1H-NMR(400MHz,CDCl3),δH6.51(1H,d,J=8.2Hz,H-7’),7.07(1H,d,J=8.2Hz,H-6’),6.38(1H,s,H-8),6.58(1H,s,H-5),3.98(1H,d,J=3.9Hz,H-1),5.49(1H,d,J=3.9Hz,H-1’),5.90(2H,d,J=1.7Hz,-OCH2O-),3.88(3H,s,-OCH3),4.06(3H,s,-OCH3),2.55(3H,s,-NCH3),2.26-2.89(4H,m)。
13C-NMR(100MHz,CDCl3),66.1(C-1),49.1(C-3),26.7(C-4),124.6(C-4α),108.5(C-5),146.7(C-6),145.8(C-7),107.8(C-8),130.3(C-8α),82.9(C-1’α),167.7(-CO),118.6(C-3’α),148.0(C-4’),152.5(C-5’),119.7(C-6’),117.6(C-7’),140.8(C-7’α),100.8(-OCH2O-),61.6(-OCH3),56.6(-OCH3),44.9(N-CH3)。
Claims (5)
1.一种从赛北紫堇中提取分离白毛茛碱的方法,其特征在于该方法的具体步骤如下:
步骤1.粉碎、碱化:将赛北紫堇全草阴干,粉碎至40-60目,得到赛北紫堇粉末,加入Na2CO3溶液浸泡3-4小时,晾干后过40-60目筛;
步骤2.超临界提取:将处理好的赛北紫堇粉末装入超临界萃取釜中,超临界CO2萃取,用乙醇溶液为夹带剂动态提取,解析萃取液并回收乙醇,得到粗生物碱;
步骤3.微滤:将粗生物碱浸膏溶解在酸水中并调节溶液pH值至2-3,将此溶液用孔径在0.5-1.0微米的陶瓷膜进行微滤处理,控制微滤温度在25-35℃,微滤压力在0.5-0.7MPa,除去颗粒物和高分子物质;
步骤4.超滤:将微滤后的溶液用聚砜中空纤维超滤膜进行超滤处理,分子截留量在4000-8000D,控制超滤压力在0.1-0.3MPa,操作温度为25-35℃,溶液pH值维持在2-3,除去大分子物质的多糖、胶质、蛋白质及色素;
步骤5.离子交换树脂分离:将所得滤液过处理好的酸性阳离子交换树脂柱,调节上样流速,先用去离子水冲洗至中性,除去水溶性小分子杂质,再调节洗脱流速用1%Na2CO3溶液碱化50-80%乙醇洗脱,收集洗脱液用碘化铋钾显色剂检测,直至无生物碱流出为止,合并检测呈阳性的洗脱液;
步骤6.重结晶:将所得的上述洗脱液减压浓缩、干燥,加入二氯甲烷溶解过滤,然后用常规方法重结晶,过滤,得到结晶物即为白毛茛碱。
2.根据权利要求1所述的一种从赛北紫堇中提取分离白毛茛碱的方法,其特征在于:所述的步骤1中,加入的Na2CO3溶液pH值为10-11,赛北紫堇粉末与Na2CO3溶液的质量比为1:1.5-1:2。
3.根据权利要求1所述的一种从赛北紫堇中提取分离白毛茛碱的方法,其特征在于:所述的步骤2中,调节萃取温度为30~45℃,萃取压力为20~30MPa,夹带剂为90%的乙醇溶液,萃取时间为2-4小时状态为动态提取,流速为1.0-1.5mL/min。
4.根据权利要求1所述的一种从赛北紫堇中提取分离白毛茛碱的方法,其特征在于:步骤3中,粗生物碱与酸水的质量比为1:20-1:40;酸水溶液为盐酸或硫酸溶液。
5.根据权利要求1所述的一种从赛北紫堇中提取分离白毛茛碱的方法,其特征在于:步骤5中,所述的酸性阳离子交换树脂采用001×7聚苯乙烯磺酸型阳离子交换树脂;上样流速为1-2BV/h,洗脱流速为2-3BV/h。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710172755.3A CN106939006B (zh) | 2017-03-22 | 2017-03-22 | 一种从赛北紫堇中提取分离白毛茛碱的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710172755.3A CN106939006B (zh) | 2017-03-22 | 2017-03-22 | 一种从赛北紫堇中提取分离白毛茛碱的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106939006A CN106939006A (zh) | 2017-07-11 |
CN106939006B true CN106939006B (zh) | 2019-01-29 |
Family
ID=59463599
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710172755.3A Active CN106939006B (zh) | 2017-03-22 | 2017-03-22 | 一种从赛北紫堇中提取分离白毛茛碱的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106939006B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111562332B (zh) * | 2020-06-29 | 2022-04-26 | 济宁海关综合技术服务中心 | 一种中空纤维萃取检测火锅底料中罂粟壳成分的方法 |
CN114507238A (zh) * | 2022-03-17 | 2022-05-17 | 曲靖师范学院 | 一种从蒙自青藤中分离纯化放线瑞香宁的方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8003136B2 (en) * | 2004-03-03 | 2011-08-23 | Randy Beavers | Standardization of botanical products utilizing biological activity as a marker |
US7964224B2 (en) * | 2004-03-03 | 2011-06-21 | Beavers Randy L | Process for extraction and standardization of pharmaceutical quality tinctures and extracts from herbal products |
-
2017
- 2017-03-22 CN CN201710172755.3A patent/CN106939006B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN106939006A (zh) | 2017-07-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111285916B (zh) | 一种积雪草总苷含量高的积雪草提取物的制备方法 | |
CN110845328A (zh) | 一种以迷迭香油膏副产品制备高纯度鼠尾草酸的方法 | |
CN101016328A (zh) | 一种分离纯化熊果酸、齐墩果酸的方法 | |
CN111793099B (zh) | 从枳实中分离橙皮苷、新橙皮苷、柚皮苷和辛弗林的方法 | |
CN111793102B (zh) | 从芷江野生甜茶中分离三叶苷和根皮苷的方法 | |
CN101396432B (zh) | 一种富集分离香椿叶黄酮类物质的方法 | |
CN106939006B (zh) | 一种从赛北紫堇中提取分离白毛茛碱的方法 | |
CN104529983B (zh) | 荸荠皮提取圣草酚的方法 | |
CN109369733B (zh) | 一种从苦荞叶中同时提取多种黄酮类化合物的方法 | |
WO2012061984A1 (zh) | 制备芍药内酯苷和芍药苷的方法 | |
CN104382968B (zh) | 穿心莲总内酯提取方法、穿心莲总内酯药物组合物及用途 | |
CN110917240B (zh) | 一种从青钱柳中分离多种有效成分的连续化方法 | |
CN115043889B (zh) | 一种从代代花中提取辛弗林、橙皮苷和柚皮苷的方法 | |
CN112830881B (zh) | 从橙皮苷废液中分离辛弗林的方法 | |
CN104926766A (zh) | 一种从荷叶中同步提取槲皮素和荷叶碱的方法 | |
CN112043733B (zh) | 一种水溶性银杏叶提取物的生产方法 | |
CN111018929B (zh) | 一种异柚皮苷的提取分离工艺 | |
CN107266510B (zh) | 灯盏花素中药提取物的制备方法 | |
CN107235988A (zh) | 一种青蒿素及次甲基青蒿素的提取方法 | |
CN109970838B (zh) | 一种长梗冬青苷的制备方法 | |
CN113480507A (zh) | 一种从洋甘菊中同时提取芹菜素和木犀草素的方法 | |
CN101879265A (zh) | 一种虎眼万年青总皂苷、多糖的联产工艺 | |
CN109232548B (zh) | 一种从檀香叶中提取高纯牡荆素和异牡荆素的方法 | |
CN110156764B (zh) | 一种提取芒果苷的方法 | |
CN110548053A (zh) | 一种富含总黄酮和天然维生素c的沙棘提取物的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB02 | Change of applicant information |
Address after: 210009 No. 87 Dingjiaqiao, Gulou District, Nanjing City, Jiangsu Province Applicant after: Southeast University Address before: 211189 No. 2 Southeast University Road, Jiangning District, Nanjing, Jiangsu Applicant before: Southeast University |
|
CB02 | Change of applicant information | ||
GR01 | Patent grant | ||
GR01 | Patent grant |