CN105440031A - 从三颗针中提纯盐酸小檗碱的方法 - Google Patents
从三颗针中提纯盐酸小檗碱的方法 Download PDFInfo
- Publication number
- CN105440031A CN105440031A CN201510929679.7A CN201510929679A CN105440031A CN 105440031 A CN105440031 A CN 105440031A CN 201510929679 A CN201510929679 A CN 201510929679A CN 105440031 A CN105440031 A CN 105440031A
- Authority
- CN
- China
- Prior art keywords
- filtrate
- carrying
- berberine hydrochloride
- weight
- root
- 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.)
- Granted
Links
- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical compound [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000000746 purification Methods 0.000 title abstract description 4
- 240000000724 Berberis vulgaris Species 0.000 title abstract 2
- 235000016068 Berberis vulgaris Nutrition 0.000 title abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 35
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000000706 filtrate Substances 0.000 claims abstract description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000002002 slurry Substances 0.000 claims abstract description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000843 powder Substances 0.000 claims abstract description 9
- 235000008733 Citrus aurantifolia Nutrition 0.000 claims abstract description 7
- 235000011941 Tilia x europaea Nutrition 0.000 claims abstract description 7
- 238000001914 filtration Methods 0.000 claims abstract description 7
- 239000004571 lime Substances 0.000 claims abstract description 7
- 229920000742 Cotton Polymers 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 241001407382 Berberis julianae Species 0.000 claims description 10
- 238000006386 neutralization reaction Methods 0.000 claims description 6
- 235000012054 meals Nutrition 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 239000000243 solution Substances 0.000 abstract 4
- 238000010438 heat treatment Methods 0.000 abstract 2
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 238000009833 condensation Methods 0.000 abstract 1
- 230000005494 condensation Effects 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000005457 ice water Substances 0.000 abstract 1
- 239000008267 milk Substances 0.000 abstract 1
- 210000004080 milk Anatomy 0.000 abstract 1
- 235000013336 milk Nutrition 0.000 abstract 1
- 239000002244 precipitate Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- 238000012216 screening Methods 0.000 abstract 1
- 229940093265 berberine Drugs 0.000 description 13
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 13
- 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 12
- 238000000605 extraction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 235000002991 Coptis groenlandica Nutrition 0.000 description 2
- 244000247747 Coptis groenlandica Species 0.000 description 2
- 241000218691 Cupressaceae Species 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 235000011116 calcium hydroxide Nutrition 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 208000004429 Bacillary Dysentery Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 1
- 241001529246 Platymiscium Species 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000003836 berberines Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 201000005113 shigellosis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明公开了从三颗针中提纯盐酸小檗碱的方法，它包括以下步骤：（1）、取100-120重量份的根粗粉，过20目筛后加入300-400重量份的浓度0.5%硫酸水溶液使之浸没药面，浸泡6-10h，用脱脂棉过滤；（2）、滤液中加入石灰乳中和多余硫酸，调整pH到7，静置10-20min；（3）、滤除沉淀，滤液中加入200-300重量份乙醇搅拌加热至80-90℃回流20-30min；（4）、向滤液中加入乙醇减压浓缩至滤液呈棕红色浆液；（5）、向棕红色浆液中加入浓度2-4%醋酸加热；（6）、加入盐酸和丙酮至溶液浑浊为止，用冰水冷却至盐酸小檗碱析出，干燥烘干得到精品盐酸小檗碱。
Description
技术领域
本发明涉及天然药物提纯领域，尤其涉及从三颗针中提纯盐酸小檗碱的方法。
背景技术
小檗碱又称黄连素，广泛分布在植物界，大约有4个科10个属植物都已发现有小檗碱存在。小檗碱是黄色针状晶体，表现为季铵型、醇型3种互变异构体，其中以季铵碱型最稳定。小檗碱能缓慢溶解于冷水（1∶20）或冷乙醇（1∶100），在热水或热乙醇中溶解度比较大，难溶于丙醇、氯仿或苯，盐类的溶解度都比较小，硫酸盐在水中的溶解度约为1∶30，盐酸盐微溶于冷水。小檗碱可从三颗针、黄连、黄柏等植物中提取。由于黄连生长缓慢，价格较高，黄柏来源也较少，现我国主要应用三颗针作为提取原料。小檗碱是临床上一种常用的广谱抗菌药，主要用于菌痢、胃肠炎、痈肿等细菌性感染。现代研究证明小檗碱有抗肿瘤、抗心率失常、降压、降血糖等作用，在临床上有越来越广泛的应用，需求量日益增加，而现有的小檗碱提取方法一般有5种，一是酸水法、二是石灰乳法、三是乙醇法、四是超声波法、五是微波法，但无论是那种方法，提取的小檗碱提取率都不尽如人意，平均收率较低。
发明内容
本发明要解决的技术问题是现有的小檗碱提纯方法存在诸多弊端不利于产业化生产，为此提供一种从三颗针中提纯盐酸小檗碱的方法。
本发明的技术方案是：从三颗针中提纯盐酸小檗碱的方法，它包括以下步骤：（1）、取100-120重量份的根粗粉，过20目筛后加入300-400重量份的浓度0.5%硫酸水溶液使之浸没药面，浸泡6-10h，用脱脂棉过滤；（2）、滤液中加入石灰乳中和多余硫酸，调整pH到7，静置10-20min；（3）、滤除沉淀，滤液中加入200-300重量份乙醇搅拌加热至80-90℃回流20-30min；（4）、向滤液中加入200-300重量份乙醇减压浓缩至滤液呈棕红色浆液；（5）、向棕红色浆液中加入浓度2-4%醋酸加热至150-160℃；（6）、加入浓度为60-70%的盐酸和丙酮至溶液浑浊为止，用冰水冷却至盐酸小檗碱析出，干燥烘干得到精品盐酸小檗碱。
本发明的有益效果是将酸水法、石灰乳法以及乙醇法相结合，可以一步直接制得精制小檗碱，且制得的小檗碱纯度高，平均收率达到8-9%，降低原材料的消耗，提高生产效率。
具体实施方式
下面结合实施例对本发明做进一步说明。
实施例1：从三颗针中提纯盐酸小檗碱的方法，它包括以下步骤：（1）、取100重量份的根粗粉，过20目筛后加入300重量份的浓度0.5%硫酸水溶液使之浸没药面，浸泡6h，用脱脂棉过滤；（2）、滤液中加入石灰乳中和多余硫酸，调整pH到7，静置10min；（3）、滤除沉淀，滤液中加入200重量份乙醇搅拌加热至80℃回流20min；（4）、向滤液中加入200重量份乙醇减压浓缩至滤液呈棕红色浆液；（5）、向棕红色浆液中加入浓度2%醋酸加热至150℃；（6）、加入浓度为60%的盐酸和丙酮至溶液浑浊为止，用冰水冷却至盐酸小檗碱析出，干燥烘干得到精品盐酸小檗碱。
实施例2：从三颗针中提纯盐酸小檗碱的方法，它包括以下步骤：（1）、取110重量份的根粗粉，过20目筛后加入350重量份的浓度0.5%硫酸水溶液使之浸没药面，浸泡8h，用脱脂棉过滤；（2）、滤液中加入石灰乳中和多余硫酸，调整pH到7，静置15min；（3）、滤除沉淀，滤液中加入250重量份乙醇搅拌加热至85℃回流25min；（4）、向滤液中加入250重量份乙醇减压浓缩至滤液呈棕红色浆液；（5）、向棕红色浆液中加入浓度2-4%醋酸加热至155℃；（6）、加入浓度为65%的盐酸和丙酮至溶液浑浊为止，用冰水冷却至盐酸小檗碱析出，干燥烘干得到精品盐酸小檗碱。
实施例3：从三颗针中提纯盐酸小檗碱的方法，它包括以下步骤：（1）、取120重量份的根粗粉，过20目筛后加入400重量份的浓度0.5%硫酸水溶液使之浸没药面，浸泡10h，用脱脂棉过滤；（2）、滤液中加入石灰乳中和多余硫酸，调整pH到7，静置20min；（3）、滤除沉淀，滤液中加入300重量份乙醇搅拌加热至90℃回流30min；（4）、向滤液中加入300重量份乙醇减压浓缩至滤液呈棕红色浆液；（5）、向棕红色浆液中加入浓度4%醋酸加热至160℃；（6）、加入浓度为70%的盐酸和丙酮至溶液浑浊为止，用冰水冷却至盐酸小檗碱析出，干燥烘干得到精品盐酸小檗碱。
本发明利用硫酸使之溶解，再利用石灰乳中和溶液成中性的盐类，依次加入特定比例的乙醇和醋酸析出盐酸小檗碱，最后同时加入高浓度的盐酸和丙酮直接制得精品盐酸小檗碱，且本发明制得的盐酸小檗碱平均收率达到8-9%，相比传统提取工艺缩短了流程，节省了原材料的消耗。
Claims (1)
1.从三颗针中提纯盐酸小檗碱的方法，其特征是它包括以下步骤：（1）、取100-120重量份的根粗粉，过20目筛后加入300-400重量份的浓度0.5%硫酸水溶液使之浸没药面，浸泡6-10h，用脱脂棉过滤；（2）、滤液中加入石灰乳中和多余硫酸，调整pH到7，静置10-20min；（3）、滤除沉淀，滤液中加入200-300重量份乙醇搅拌加热至80-90℃回流20-30min；（4）、向滤液中加入200-300重量份乙醇减压浓缩至滤液呈棕红色浆液；（5）、向棕红色浆液中加入浓度2-4%醋酸加热至150-160℃；（6）、加入浓度为60-70%的盐酸和丙酮至溶液浑浊为止，用冰水冷却至盐酸小檗碱析出，干燥烘干得到精品盐酸小檗碱。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510929679.7A CN105440031B (zh) | 2015-12-15 | 2015-12-15 | 从三颗针中提纯盐酸小檗碱的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510929679.7A CN105440031B (zh) | 2015-12-15 | 2015-12-15 | 从三颗针中提纯盐酸小檗碱的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105440031A true CN105440031A (zh) | 2016-03-30 |
| CN105440031B CN105440031B (zh) | 2017-09-29 |
Family
ID=55550724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510929679.7A Active CN105440031B (zh) | 2015-12-15 | 2015-12-15 | 从三颗针中提纯盐酸小檗碱的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105440031B (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878198A (zh) * | 2016-05-29 | 2016-08-24 | 山东仁和堂药业有限公司 | 含有盐酸小檗碱片的药物组合物及其制备工艺 |
| CN107892688A (zh) * | 2017-11-15 | 2018-04-10 | 湘潭大学 | 一种从黄柏中制备盐酸小檗碱的方法 |
| CN111297930A (zh) * | 2019-12-18 | 2020-06-19 | 宁波杰顺生物科技有限公司 | 一种三颗针提取物及其制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101723950A (zh) * | 2009-11-26 | 2010-06-09 | 西南大学 | 黄连碱的提取方法 |
| RU2423992C1 (ru) * | 2010-02-24 | 2011-07-20 | Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | Способ получения пакистанамина и берберина хлорида из berberis sibirica |
| CN103059017A (zh) * | 2012-12-31 | 2013-04-24 | 李玉山 | 一种三颗针植物资源的综合提取工艺设计 |
-
2015
- 2015-12-15 CN CN201510929679.7A patent/CN105440031B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101723950A (zh) * | 2009-11-26 | 2010-06-09 | 西南大学 | 黄连碱的提取方法 |
| RU2423992C1 (ru) * | 2010-02-24 | 2011-07-20 | Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | Способ получения пакистанамина и берберина хлорида из berberis sibirica |
| CN103059017A (zh) * | 2012-12-31 | 2013-04-24 | 李玉山 | 一种三颗针植物资源的综合提取工艺设计 |
Non-Patent Citations (1)
| Title |
|---|
| 杨宏健等: "正交实验优选三颗针中小檗碱的提取工艺", 《中国药师》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105878198A (zh) * | 2016-05-29 | 2016-08-24 | 山东仁和堂药业有限公司 | 含有盐酸小檗碱片的药物组合物及其制备工艺 |
| CN107892688A (zh) * | 2017-11-15 | 2018-04-10 | 湘潭大学 | 一种从黄柏中制备盐酸小檗碱的方法 |
| CN111297930A (zh) * | 2019-12-18 | 2020-06-19 | 宁波杰顺生物科技有限公司 | 一种三颗针提取物及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105440031B (zh) | 2017-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101423538B (zh) | 一种从槐米中提取芦丁的生产工艺 | |
| CN107793457B (zh) | 一种槐米芦丁的绿色制备方法 | |
| CN103342669B (zh) | 一种提取天然牛磺酸的简易方法 | |
| CN105440031A (zh) | 从三颗针中提纯盐酸小檗碱的方法 | |
| CN103923139A (zh) | 一种从槐米中提取芦丁的方法 | |
| CN103509028B (zh) | 一种叶绿素铜酸及铜钠盐的制备方法 | |
| CN112358512A (zh) | 一种制备柑橘橙皮苷的方法 | |
| CN106518829A (zh) | 一种从显齿蛇葡萄叶中分离纯化二氢杨梅素的方法 | |
| CN107722132B (zh) | 一种从海藻中联产海藻多糖和海藻蛋白的方法 | |
| CN107513086B (zh) | 一种从黄芩茎叶中提取分离高纯度野黄芩苷的方法及野黄芩苷 | |
| CN112028865A (zh) | 一种从藤茶中提取制备高含量二氢杨梅素的方法 | |
| CN102327312A (zh) | 一种从金银花叶茎藤中提取有效成份的方法 | |
| CN103923050B (zh) | 利用芦丁制备槲皮素的方法 | |
| CN104151389A (zh) | 一种快速提取纯化甘草酸及其盐类的方法 | |
| CN104119411A (zh) | 一种高纯度橙皮苷的制备方法 | |
| CN108218948B (zh) | 一种七叶皂苷钠的制备方法 | |
| CN110770218B (zh) | 一种制备木犀草素的方法 | |
| CN101985439B (zh) | 从毛冬青地上部分分离提取98%槲皮素的工艺 | |
| CN116941696A (zh) | 同步制备显齿蛇葡萄叶黄酮粉末与莓茶饮料的加工方法 | |
| CN103965153B (zh) | 利用芦丁制备槲皮素和鼠李糖的方法 | |
| CN111056941B (zh) | 一种利用银杏叶提取物层析废液制备高纯度莽草酸的方法 | |
| KR20100107862A (ko) | 함초 유래의 소금 및 된장의 제조 방법 | |
| CN108707149A (zh) | 一种黄连素的提取方法 | |
| CN109232288B (zh) | 一种藜豆生产左旋多巴的方法 | |
| CN106518951A (zh) | 一种从金露梅中提取熊果酸的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Ji Zhenhua Inventor before: Zhang Qunzhi |
|
| CB03 | Change of inventor or designer information | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170825 Address after: 043500 Shanxi County of Yicheng Province Town Bridge Village No. 22 Nantou Village Applicant after: Ji Zhenhua Address before: Long Huai village Tongguanshan District 244000 in Anhui province Tongling city 3 building 104 room Applicant before: Zhang Qunzhi |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200323 Address after: 330114 Jiangxi city of Nanchang province new village natural village Fang Zhen Xia District Lehua No. 7 of 3. Patentee after: Lu Jing Address before: 043500 Shanxi County of Yicheng Province Town Bridge Village No. 22 Nantou Village Patentee before: Ji Zhenhua |
|
| TR01 | Transfer of patent right | ||
| CP02 | Change in the address of a patent holder |
Address after: No. 16, Tongjiang Avenue, Chengguan Town, Nandan county, Hechi City, Guangxi Zhuang Autonomous Region Patentee after: Lu Jing Address before: 330114 Jiangxi city of Nanchang province new village natural village Fang Zhen Xia District Lehua No. 7 of 3. Patentee before: Lu Jing |
|
| CP02 | Change in the address of a patent holder | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210712 Address after: No.13, Guangzhou road, Pingdu City, Qingdao City, Shandong Province 266000 Patentee after: Qingdao anmeirui Biotechnology Industrial Park Co.,Ltd. Address before: No.16 Tongjiang Avenue, Chengguan Town, Nandan county, Hechi City, Guangxi Zhuang Autonomous Region 547200 Patentee before: Lu Jing |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230625 Address after: No. 13, Guangzhou Road, Pingdu Economic Development Zone, Qingdao, Shandong 266705 Patentee after: Qingdao Anmeirui Testing and Certification Co.,Ltd. Address before: No.13, Guangzhou road, Pingdu City, Qingdao City, Shandong Province 266000 Patentee before: Qingdao anmeirui Biotechnology Industrial Park Co.,Ltd. |
|
| TR01 | Transfer of patent right |