CN103788064A - Simulated moving bed chromatographic separation method for omeprazole enantiomer - Google Patents
Simulated moving bed chromatographic separation method for omeprazole enantiomer Download PDFInfo
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- CN103788064A CN103788064A CN201210426739.XA CN201210426739A CN103788064A CN 103788064 A CN103788064 A CN 103788064A CN 201210426739 A CN201210426739 A CN 201210426739A CN 103788064 A CN103788064 A CN 103788064A
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- omeprazole
- simulated moving
- moving bed
- enantiomer
- moving
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention relates to separation methods for enantiomer of chiral drugs, especially to a simulated moving bed chromatographic separation method for omeprazole enantiomer. According to the method, an omeprazole synthetic product is used as a raw material, simulated moving bed chromatography is applied for separation of the omeprazole enantiomer, and the stationary phase of simulated moving bed chromatography is a chiral filling material while a mobile phase is an ethanol solution. With the method, yield of the omeprazole enantiomer is high, and purity of the omeprazole enantiomer is more than 98%. Since simulated moving bed chromatography is a continuous process, the automation level and production efficiency can be improved, a production environment is greatly improved, and clean production is realized indeed.
Description
Technical field
The present invention relates to chiral drug resolution field, be specifically related to a kind of method of application simulation mobile bed chromatic fractionation omeprazole.
Background technology
Omeprazole (Omepraxole is called for short OME) molecule connects pyridine ring by benzoglyoxaline by sulfoxide group and forms, and includes chiral sulfur atom, has enantiomerism.Two isomer have different biological activitys, and wherein the administration curative effect of esomprazole is better than raceme form administration.
Simulated moving bed chromatography isolation technique is a kind of modernization isolation technique growing up the sixties in 20th century, there is separating power strong, equipment volume is little, cost of investment is low, just dry realization is automatically controlled and is particularly conducive to and separates thermo-sensitivity and be difficult to the advantages such as the system that separates, in preparative chromatography technology, be best suited for and carry out continuity large-scale industrial production, we think that preparation has good application prospect and potentiality to simulated moving bed chromatography isolation technique to chiral drug.
Summary of the invention
High in order to solve omeprazole chirality Chiral Separation cost, the technological deficiency yielding poorly, the object of the present invention is to provide a kind of novel method that adopts Omeprazole resolution by simulated moving bed chromatography.The method is produced continuously, has improved purity and the efficiency of product.
For realizing above object, the present invention by the following technical solutions:
1. the method adopts omeprazole synthetic product as raw material, and application simulation mobile bed chromatic splits omeprazole enantiomer, and the stationary phase of simulated moving bed chromatography is chirality padding, and moving phase adopts ethanol/diethylamine (100/0.1, V/V) solution;
2. as preferred, the above-mentioned omeprazole that enters simulated moving bed chromatography separation adopts dissolve with ethanol, and the concentration after dissolving is 10 ~ 40mg/ml;
3. as preferably, above-mentioned stationary phase is cellulose iii phenylcarbamate coating-type chiral column, wherein applies carrier and be the aminopropyl silica gel that Japanese Fuji company produces.The mass ratio of cellulose iii phenylcarbamate and aminopropyl silica gel is 1:4;
4. as preferably, above-mentioned be simulation moving-bedly made up of 4 ~ 8 root chromatogram columns, chromatographic column is divided into 4 regions, and every district is by 1 ~ 2 identical Coupled columns.Sample introduction flow velocity U
pbe 0.7 ~ 1.36ml/min; Eluent flow rate U
ebe 4.39 ~ 4.87 ml/min; Raffinate flow velocity U
rbe 1.60 ~ 2.27 ml/min; Extraction liquid flow velocity U
xbe 3.29 ~ 3.99 ml/min; Switching time T
sbe 0 ~ 10min;
5. as preferred, simulation moving-bed service temperature is 20 ~ 25 ℃.
Of the present invention owing to adopting technique scheme, omeprazole enantiomer product yield is high, and purity reaches more than 98%.Because simulated moving bed chromatography is successive processes, can improve the gentle production efficiency of Automated water, and production environment is greatly improved, really realize cleaner production.
Embodiment
The specific embodiment of the present invention is done to a detailed description below.The method of Omeprazole resolution by simulated moving bed chromatography, the method comprises the following steps:
1. by Omeprazole powder dissolve with ethanol solution, be configured to the solution of 20mg/ml, as sample introduction liquid;
2. the filling of chromatographic column and the composition of moving phase:
Stationary phase is cellulose iii phenylcarbamate coating-type chiral column, wherein applies carrier and be the aminopropyl silica gel that Japanese Fuji company produces.The mass ratio of cellulose iii phenylcarbamate and aminopropyl silica gel is 1:4.Ethanol moving phase is ethanol/diethylamine (100/0.1, V/V);
3. simulated moving bed chromatography system:
Simulated moving bed chromatography system comprises sampling pump, wash-out liquid pump, extraction pump, raffinate pump and recycle pump, electromagnetic switching valve and chromatographic column.Sample solution and elutriant inject chromatographic system from sample inlet and elutriant entrance respectively.At regular intervals, sample liquid and elutriant entrance, extraction liquid and raffinate outlet switch to next root chromatogram column outlet along moving phase direction simultaneously.Through simulation moving-bed separation, can obtain the R-omeprazole of higher degree from extraction liquid outlet, can obtain highly purified esomprazole from raffinate outlet;
4. simulated moving bed chromatography parameter:
Simulation moving-bed in the present invention forms 4 regions by 8 root chromatogram columns, switches and changes opening for feed, discharge port position through magnetic valve.Sample introduction flow velocity U
pfor 1.0ml/min; Eluent flow rate U
ebe 4.5 ml/min; Raffinate flow velocity U
rfor 2.0ml/min; Extraction liquid flow velocity U
xbe 3.5 ml/min; Switching time T
sfor 1.76min.Service temperature is 25 ℃;
5. concentrated:
The ethanolic soln vaporize draw omeprazole enantiomer of the omeprazole enantiomer of collecting.Evaporate and obtain omeprazole enantiomer by re-crystallizing in ethyl acetate again.
Claims (7)
1. the method for an Omeprazole resolution by simulated moving bed chromatography, it is characterized in that: the method adopts omeprazole synthetic product as raw material, application simulation mobile bed chromatic splits omeprazole enantiomer, and its stationary phase is chirality padding, and moving phase adopts ethanolic soln.
2. method according to claim 1, it is characterized in that: stationary phase is cellulose iii phenylcarbamate coating-type chiral column, wherein apply carrier and be the aminopropyl silica gel that Japanese Fuji company produces, the mass ratio of cellulose iii phenylcarbamate and aminopropyl silica gel is 1:4.
3. method according to claim 1, is characterized in that: the ethanol moving phase of employing is ethanol/diethylamine (100/0.1, V/V).
4. method according to claim 1, is characterized in that: enter the omeprazole employing dissolve with ethanol that simulated moving bed chromatography separates, the concentration after dissolving is 10 ~ 40mg/ml.
5. method according to claim 1, is characterized in that: be simulation moving-bedly made up of 4 ~ 8 root chromatogram columns, chromatographic column is divided into 4 regions, and every district is by 1 ~ 2 identical Coupled columns.
6. method according to claim 5, is characterized in that: sample introduction flow velocity U
pbe 0.7 ~ 1.36ml/min; Eluent flow rate U
ebe 4.39 ~ 4.87 ml/min; Raffinate flow velocity U
rbe 1.60 ~ 2.27 ml/min; Extraction liquid flow velocity U
xbe 3.29 ~ 3.99 ml/min; Switching time T
sbe 0 ~ 10min.
7. method according to claim 5, is characterized in that: simulation moving-bed service temperature is 20 ~ 25 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210426739.XA CN103788064A (en) | 2012-10-31 | 2012-10-31 | Simulated moving bed chromatographic separation method for omeprazole enantiomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210426739.XA CN103788064A (en) | 2012-10-31 | 2012-10-31 | Simulated moving bed chromatographic separation method for omeprazole enantiomer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103788064A true CN103788064A (en) | 2014-05-14 |
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| CN201210426739.XA Pending CN103788064A (en) | 2012-10-31 | 2012-10-31 | Simulated moving bed chromatographic separation method for omeprazole enantiomer |
Country Status (1)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749322A (en) * | 2015-11-23 | 2017-05-31 | 中美华世通生物医药科技（武汉）有限公司 | The method for separating Ofloxacin enantiomter |
| CN106928190A (en) * | 2015-12-29 | 2017-07-07 | 中美华世通生物医药科技（武汉）有限公司 | The method that Lansoprazole is prepared using SMBC separation |
-
2012
- 2012-10-31 CN CN201210426739.XA patent/CN103788064A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749322A (en) * | 2015-11-23 | 2017-05-31 | 中美华世通生物医药科技（武汉）有限公司 | The method for separating Ofloxacin enantiomter |
| CN106928190A (en) * | 2015-12-29 | 2017-07-07 | 中美华世通生物医药科技（武汉）有限公司 | The method that Lansoprazole is prepared using SMBC separation |
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Application publication date: 20140514 |