CN101230080B - simulated moving bed chromatography separation of 20(S) and 20(R)-ginsenoside Rg3 enantiomer - Google Patents
simulated moving bed chromatography separation of 20(S) and 20(R)-ginsenoside Rg3 enantiomer Download PDFInfo
- Publication number
- CN101230080B CN101230080B CN2007100552492A CN200710055249A CN101230080B CN 101230080 B CN101230080 B CN 101230080B CN 2007100552492 A CN2007100552492 A CN 2007100552492A CN 200710055249 A CN200710055249 A CN 200710055249A CN 101230080 B CN101230080 B CN 101230080B
- Authority
- CN
- China
- Prior art keywords
- ginsenoside
- moving bed
- simulated moving
- rg3s
- bed chromatography
- 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.)
- Expired - Fee Related
Links
Landscapes
- Treatment Of Liquids With Adsorbents In General (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a chromatographic fractionation method used for the simulated moving bed of ginseng saponin Rg3 antimer. In the invention, a simulated moving bed chromatographic system is adopted, fixed phase containing octadecylsilanized silica gel (C18) is adopted, mixture of methyl alcohol and water is adopted for the mobile phase, and high-purity 20(R)-ginseng saponin Rg3 and 20(S)-ginseng saponin Rg3 are separated from the mixture of 20(R)-ginseng saponin and 20(S) ginseng saponin Rg3. Because the chromatographic fractionation of the simulated moving bed is a continuous process, the automaticity of the production of the invention is high, the production efficiency is high, the solvent can be reutilized, and noxious solvent is not contacted during the entire fractionation process.
Description
Technical field
The present invention relates to the disassemble technique of being subjected to property medicine, especially, relate to and split 20 (S)-and the simulated moving bed chromatographic separation process of 20 (R)-ginsenoside Rg3 enantiomorphs.
Background technology
20 its chemical names of (S)-ginsenoside Rg3 are respectively: 3-0-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-Da Ma-24-alkene-3 β, 12 β, 20 (S)-triols.20 (R)-ginsenoside Rg3 chemical names are respectively: 3-0-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-Da Ma-24-alkene-3 β, 12 β, 20 (R)-triols.The two is an enantiomorph, and biological activity test shows all have stronger antitumour activity, and wherein 20 (R)-ginsenoside Rg3s have been developed listing, and nomenclature of drug is " joining a capsule ", and inferior safe medical limited-liability company produces by Jilin.
20 (R)-ginsenoside Rg3 anticancer mechanisms mainly are to suppress the effect of sticking that tumor neogenetic blood vessels generated and suppressed tumour cell, are subjected to the favor of extensive patients deeply.And 20 (S)-ginsenoside Rg3s are also carrying out the II phase clinical study stage, and find that it has antiviral activity.Therefore it is very significant splitting the two.
Anshan University of Science and Technology's patent carboprost methylate simulated moving bed chromatographic separation process.Application number: 00110348.2 the invention discloses a kind of simulated moving bed chromatographic separation process of carboprost methylate, problem such as solved solvent that batch processing method exists, the filler consumption is big, purity is restricted.And improved operating environment, improved production automation level.Feature of the present invention is: adopt simulated moving bed chromatography system, filler is a reverse phase silica gel, is moving phase with the mixed solution of methyl alcohol, water.Raw material enters simulated moving bed chromatography system through the impurity elimination pre-treatment.Product that simulated moving bed chromatography system is come out through concentrating, to obtain purity be qualified product more than 90% in processing such as recrystallization.
Anshan University of Science and Technology's patent method of simulated moving bed chromatography separation and Extraction teicoplanin.Application number: 02132707.3, the present invention adopts simulated moving bed chromatography (being called for short SMBC) system, replaces the smart extracting method of existing activated carbon method.The activated carbon method that the present invention and present essence are carried teicoplanin is relatively tired and is brought up to more than 900 by original 829, and purity brings up to 97% by 95%, and yield brings up to 70% by 35%.Simulated Moving-Bed Parex Process is a successive processes in addition, and active carbon method is intermittently, so the introducing of simulated moving bed technology improved the automatization level of producing, production efficiency, and production environment is improved greatly.
Do not see the report that relevant simulated moving bed chromatography separation divides 20 (S) and 20 (R)-ginsenoside Rg3 enantiomorphs at present, belong to first and finding.
Summary of the invention
The object of the present invention is to provide a kind of technological method that utilizes simulated moving bed chromatography separation to divide 20 (S) and 20 (R)-ginsenoside Rg3 enantiomorphs.
The technical scheme that the present invention adopts for achieving the above object is as follows: a kind of simulated moving bed chromatographic separation process of ginsenoside Rg3 enantiomorph, it is characterized in that, with containing octadecylsilane chemically bonded silica is the weighting agent phase that fixes, mixture with the first alcohol and water is made moving phase, separates with the mixture of simulated moving bed chromatography system with 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s.
Further, may further comprise the steps:
(1) mixture with 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s is dissolved in moving phase, and concentration is 1mg/mL～200mg/mL.
(2) from simulated moving bed chromatography system, tell 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3 solution.
(3) concentrate respectively, recrystallization, filtration, drying obtain purity and be higher than 90% 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s.
Beneficial effect of the present invention: the present invention's simulated moving bed chromatography, 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3 enantiomorphs to be separated, purity reaches more than 90%.Technology is simple, but produces industrialization, and product is stable.Moving phase is recyclable, reduces cost, reduces pollution, has really realized cleaner production.
Embodiment
The present invention can further specify by following experimental example.
1. adopt simulated moving bed chromatography (being called for short SMBC) system, this system is many thoughtful.Sample solution and elutriant inject chromatographic system from sample inlet and elutriant inlet respectively, and 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3 enantiomorphs are respectively from raffinate and two outlets of extraction liquid outflow system, 20～60 ℃ of service temperatures.The optimal operations temperature is 25 ℃.
2. chromatographic column filler and moving phase are selected
Filler is an octadecylsilane chemically bonded silica, adopts the known method preparation, and the filler grain is through 20～60 μ m, and grain is through more little, and separating effect is good more.Best grain is through being 40～45 μ m.Moving phase is the first alcohol and water, and volume ratio is 30～70:70～30.Optimum volume ratio is 83:17.
3. separating step
20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3 mixtures are dissolved in moving phase, and concentration is 1mg/mL～200mg/mL.The increase of sample introduction concentration helps improving productive rate, but its concentration is subjected to the restriction of ginsenoside Rg3 solubleness.Chromatographic system is made up of 4～24 preparative columns, and pillar is many more, and separating effect is good more, but the non-linear one-tenth degree of system is high more, and best pillar number is 4～8.Sample solution and elutriant inject chromatographic system from sample inlet and elutriant inlet respectively, separate through SMBC, can obtain highly purified 20 (R)-ginsenoside Rg3 solution from extraction liquid outlet, from the raffinate outlet then obtain highly purified 20 (S)-ginsenoside Rg3 solution.Obtain 20 (R)-ginsenoside Rg3s and the pure product of 20 (S)-ginsenoside Rg3s through concentrated, recrystallization, filtration, drying etc. respectively.
4. pure product check
Moving phase: methyl alcohol: water (83:17)
Flow velocity: 1ml/min
Chromatographic column: 4.6 * 250mm, 5 μ m, C18 filler
Detector: SPD-10AVP (Japan) UV-detector
The detection wavelength is 203nm
Further specify the present invention below in conjunction with embodiment
1. the selection of moving phase
In the moving phase, the content of first alcohol and water is very big to separating the influence of 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s, and then influences the separating effect of simulated moving bed chromatography.At first (4.6 * 250mm) select moving phase with analyzing chromatographic column.As table 1,20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3 resolution increase along with the minimizing of methanol content, but retention time obviously increases, and the post of simultaneity factor is pressed also obviously to be increased.
The selection of table 1 moving phase
2.SMBC separate
Below list two separate instance.
Separate instance 1
A. operational condition
Operational mode: 1-4-3 (8 chromatographic columns)
Moving phase: methanol (70/30)
Sample introduction concentration: ginsenoside Rg3 mixture concentration: 20mg/ml
Sample introduction flow velocity: U
F=4ml/min
Eluent flow rate: U
E=40ml/min
Raffinate flow velocity: 20ml/min
Extraction liquid flow velocity: 24ml/min
Switching time: 350S
Column temperature: 20 ℃
B. check analysis
Analyze raffinate and extraction liquid composition with the octadecylsilane chemically bonded silica post.20 (R)-ginsenoside Rg3 purity are 92.5% in the raffinate; 20 (S)-ginsenoside Rg3 purity are 90.3% in the extraction liquid.
Separate instance 2
C. operational condition
Operational mode: 1-4-3 (8 chromatographic columns)
Moving phase: methanol (30/70)
Sample introduction concentration: ginsenoside Rg3 mixture concentration: 10mg/ml
Sample introduction flow velocity: U
F=5ml/min
Eluent flow rate: U
E=50ml/min
Raffinate flow velocity: 30ml/min
Extraction liquid flow velocity: 25ml/min
Switching time: 360S
Column temperature: 60 ℃
D. check analysis
Analyze raffinate and extraction liquid composition with the octadecylsilane chemically bonded silica post.20 (R)-ginsenoside Rg3 purity are 93.5% in the raffinate; 20 (S)-ginsenoside Rg3 purity are 91.8% in the extraction liquid.
Separate instance 3
E. operational condition
Operational mode: 1-4-3 (8 chromatographic columns)
Moving phase: methanol (50/50)
Sample introduction concentration: ginsenoside Rg3 mixture concentration: 15mg/ml
Sample introduction flow velocity: U
F=6ml/min
Eluent flow rate: U
E=49ml/min
Raffinate flow velocity: 30ml/min
Extraction liquid flow velocity: 25ml/min
Switching time: 360S
Column temperature: 40 ℃
F. check analysis
Analyze raffinate and extraction liquid composition with the octadecylsilane chemically bonded silica post.20 (R)-ginsenoside Rg3 purity are 92.5% in the raffinate; 20 (S)-ginsenoside Rg3 purity are 93.8% in the extraction liquid.
Claims (3)
1. the simulated moving bed chromatographic separation process of a ginsenoside Rg3 enantiomorph, it is characterized in that, with containing octadecylsilane chemically bonded silica is the weighting agent phase that fixes, mixture with the first alcohol and water is made moving phase, the volume ratio of first alcohol and water is 30～70: 70～30 in the described moving phase, separates with the mixture of simulated moving bed chromatography system with 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s.
2. according to the simulated moving bed chromatographic separation process of the described ginsenoside Rg3 enantiomorph of claim 1, it is characterized in that, may further comprise the steps:
(1) mixture with 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s is dissolved in moving phase, and concentration is 1mg/mL～200mg/mL;
(2) from simulated moving bed chromatography system, tell 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3 solution;
(3) concentrate respectively, recrystallization, filtration, drying obtain purity and be higher than 90% 20 (R)-ginsenoside Rg3s and 20 (S)-ginsenoside Rg3s.
3. according to the simulated moving bed chromatographic separation process of the described ginsenoside Rg3 enantiomorph of claim 1, it is characterized in that the temperature of described simulated moving bed chromatography system is 20～60 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100552492A CN101230080B (en) | 2007-01-22 | 2007-01-22 | simulated moving bed chromatography separation of 20(S) and 20(R)-ginsenoside Rg3 enantiomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100552492A CN101230080B (en) | 2007-01-22 | 2007-01-22 | simulated moving bed chromatography separation of 20(S) and 20(R)-ginsenoside Rg3 enantiomer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101230080A CN101230080A (en) | 2008-07-30 |
| CN101230080B true CN101230080B (en) | 2011-08-17 |
Family
ID=39896939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100552492A Expired - Fee Related CN101230080B (en) | 2007-01-22 | 2007-01-22 | simulated moving bed chromatography separation of 20(S) and 20(R)-ginsenoside Rg3 enantiomer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101230080B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101781351B (en) * | 2009-01-21 | 2012-11-21 | 重庆华森制药有限公司 | Method for extracting ginsenoside Rb1 from American ginseng and powder-injection thereof |
| CN102516068B (en) * | 2011-12-21 | 2014-04-09 | 温州大学 | Method for splitting ketoprofen enantiomer by temperature gradient simulated moving bed chromatogram |
| CN104644654A (en) * | 2013-11-20 | 2015-05-27 | 富力 | Application of 20(R)-ginsenoside Rg3 in preparation of drug for treating mammary gland proliferation and the drug thereof |
| CN104644661A (en) * | 2013-11-21 | 2015-05-27 | 富力 | Application of 20(R)-ginsenoside Rg3 in preparation of medicament for relieving or/and treating hepatitis B and medicament |
| CN104688753B (en) * | 2014-12-15 | 2018-09-14 | 中国农业科学院特产研究所 | Purposes of the ginsenoside monomer compound in the drug for preparing treatment flaviviridae infections |
| CN112679572A (en) * | 2020-12-24 | 2021-04-20 | 高陵蓝晓科技新材料有限公司 | Novel process for preparing high-purity chenodeoxycholic acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1473841A (en) * | 2003-08-05 | 2004-02-11 | 吉林农大珍源参业高科技有限公司 | High yield environmental protection type industrial separating method for ginseng saponin Rb1 |
| CN1713944A (en) * | 2002-12-21 | 2005-12-28 | 奥代科公司 | Simulated moving bed chromatographic focusing |
-
2007
- 2007-01-22 CN CN2007100552492A patent/CN101230080B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1713944A (en) * | 2002-12-21 | 2005-12-28 | 奥代科公司 | Simulated moving bed chromatographic focusing |
| CN1473841A (en) * | 2003-08-05 | 2004-02-11 | 吉林农大珍源参业高科技有限公司 | High yield environmental protection type industrial separating method for ginseng saponin Rb1 |
Non-Patent Citations (2)
| Title |
|---|
| 李鹏等."人参皂苷Rg3异构体的简易分离制备".《中国新药杂志》.2004,第13卷(第9期),第816-818页. |
| 郭伟芳等."高效液相色谱法分离20(S)和20(R)-人参皂苷Rg2 构型异构体".《中国卫生工程学》.2005,第4卷(第6期),第361-363页. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101230080A (en) | 2008-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101230080B (en) | simulated moving bed chromatography separation of 20(S) and 20(R)-ginsenoside Rg3 enantiomer | |
| CN101619028B (en) | Method for preparing capsicine monomer | |
| CN104513286B (en) | A method of isolating and purifying Fei Da meter stars | |
| CN105859803B (en) | A kind of preparation method of galloyl glucose | |
| CN110437059B (en) | Method for extracting pachymic acid A and pachymic acid B from Poria peel | |
| CN114988979B (en) | Method for preparing high-purity lycopene by macro separation | |
| CN106226426A (en) | A kind of high performance liquid chromatography splits the method for canagliflozin five-membered ring impurity enantiomer | |
| CN108186790B (en) | Rehmannia root extract, preparation method and application in promoting CIK cell in-vitro proliferation | |
| CN105859715A (en) | Critical fluid chromatographic method for separating and purifying evodiamine and rutaecarpine from fructus evodiae | |
| CN113698309A (en) | Method for extracting and separating betaine ester from bolete | |
| CN101210039B (en) | Method for separating and preparing madecassoside chemical reference substance | |
| CN108191933B (en) | Method for preparing new astilbin by taking rhizoma smilacis glabrae as raw material | |
| CN113754526A (en) | High-purity coenzyme Q10 purification process | |
| CN102432489A (en) | Method for preparing capsicine monomer and dihydrocapsaicin std monomer | |
| CN105771311A (en) | Method for purifying mixed extract by adopting dynamic axial compression column | |
| CN113801201A (en) | Preparation method of caspofungin acetate impurity B | |
| Zhang et al. | Isolation and purification of ergosterol and ergosterolperoxide from an edible and medicinal higher ascomycete mushroom Xylaria striata by high-speed countercurrent chromatography | |
| CN110229089A (en) | A kind of solvent pairs combination medium pressure liquid chromatography divides the method for purification of high-purity canthaxanthin | |
| CN115097046B (en) | Method for separating rapamycin and impurities thereof | |
| CN109406685B (en) | High performance liquid chromatography method for separating carfilzomib and isomers thereof | |
| CN114405063B (en) | Method for enriching and purifying diosmetin from dandelion on line | |
| CN111808066B (en) | Extraction method of schisandrin B extract | |
| CN111686136B (en) | Method for purifying triterpenoids | |
| CN114177650B (en) | Continuous chromatographic separation method and application | |
| CN112457285B (en) | Preparation method of naphthopyrone enrichment substance |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: JILIN CHINA GENSENG PRODUCE CO., LTD. Free format text: FORMER OWNER: LI PINGYA Effective date: 20121221 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 130021 CHANGCHUN, JILIN PROVINCE TO: 133000 YANBIAN KOREAN AUTONOMOUS PREFECTURE, JILIN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20121221 Address after: 133000 new Wangqing County of Jilin Province Street No. 18 Patentee after: Jilin Province Chinese ginseng processing Co. Ltd. Address before: Xinmin Street, Jilin province 130021 Changchun No. 126 Patentee before: Li Pingya |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110817 Termination date: 20170122 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |