CN104163849A - Separation and purification method of N(2)-L-alanyl-L-glutamine - Google Patents
Separation and purification method of N(2)-L-alanyl-L-glutamine Download PDFInfo
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- CN104163849A CN104163849A CN201410402627.XA CN201410402627A CN104163849A CN 104163849 A CN104163849 A CN 104163849A CN 201410402627 A CN201410402627 A CN 201410402627A CN 104163849 A CN104163849 A CN 104163849A
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- glutamine dipeptide
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Abstract
The invention discloses a separation and purification method of N(2)-L-alanyl-L-glutamine, which is characterized by comprising the following steps: 1. dezymotization by ceramic membrane filtration: filtering a N(2)-L-alanyl-L-glutamine enzyme reaction solution through a ceramic membrane filter plant while washing with water, and removing the residual zymoprotein in the reaction solution, thereby obtaining a ceramic membrane dialysate; 2. continuous chromatography desalting: sending the ceramic membrane dialysate into a continuous chromatography separation plant to perform continuous chromatography separation so as to separate the N(2)-L-alanyl-L-glutamine from inorganic salts, thereby obtaining a N(2)-L-alanyl-L-glutamine solution; and 3. evaporation and crystallization: carrying out vacuum distillation on the N(2)-L-alanyl-L-glutamine solution obtained by continuous chromatography, and crystallizing to obtain the N(2)-L-alanyl-L-glutamine product. The method lowers the production cost, simplifies the production technique, shortens the production cycle, enhances the total yield, and has the advantages of high product purity and the like.
Description
Technical field
The present invention relates to the production field of glutamine dipeptide, particularly a kind of separating and purifying method of glutamine dipeptide.
Background technology
Glutamine dipeptide, formal name used at school N-(2)-Ala-Gln, is a kind of modified compound of L-glutaminate, relative molecular mass is 217.22, soluble in water.L-glutaminate is the very abundant seed amino acid of body intensive amount, is the participation body of human multiple tissue metabolism, and human body lacks L-glutaminate can cause various diseases.Because L-glutaminate solubleness is low and unstable, so the outer application of the intestines of L-glutaminate is restricted.Glutamine dipeptide can be decomposed into L-glutaminate and ALANINE in vivo, and this characteristic makes to supplement L-glutaminate via parenteral nutrition transfusion becomes possibility.Glutamine dipeptide decomposes the amino acid discharge and is stored in separately the corresponding site of health and need to carries out metabolism with body as nutritive substance.Due to the singularity of glutamine dipeptide pharmaceutical use, just as physiological saline, glucose, rescue patient's requisite will be become.
The method of current industrial manufacture glutamine dipeptide mainly contains chemical synthesis and enzymic synthesis.Because chemical synthesis synthetic route is long, process control point requires high, and yield is low, so enzymic synthesis becomes the main method of suitability for industrialized production gradually.After the glutamine dipeptide reaction solution obtaining by enzymic synthesis, through follow-up extraction and purification process, obtain product again, its main method flow process as shown in Figure 1, this technique can produce solid waste when carrying out charcoal absorption, in addition after twice crystallization, the yield of product is low, and product purity is low, causes processing cost larger.
Summary of the invention
The object of the invention is to for yield and the purity of current glutamine dipeptide separating-purifying low, and the shortcomings such as cost is large, based on the advanced separation method of continuous chromatography tripping device, a kind of separating and purifying method of glutamine dipeptide of improvement is provided, to reach, reduce production costs, the object of simplified production method, shortening production cycle, raising total recovery.
For achieving the above object, the technical scheme that the present invention proposes is: a kind of separating and purifying method of glutamine dipeptide, it is characterized in that, and comprise the steps:
Step 1 ceramic membrane filter is dezymotized: glutamine dipeptide enzyme reaction solution is filtered by ceramic membrane filter equipment, add during the course water washing, remove zymoprotein residual in reaction solution, obtain ceramic membrane dialyzate;
Step 2 continuous chromatography desalination: ceramic membrane dialyzate is entered to continuous chromatography separating device and carry out continuous chromatography separation, glutamine dipeptide and inorganic salt are carried out separated, obtain glutamine dipeptide solution;
Step 3 evaporative crystallization: the glutamine dipeptide solution that continuous chromatography separation is obtained carries out underpressure distillation, then carries out crystallization, obtains glutamine dipeptide product.
Further, the aperture of the ceramic membrane that ceramic membrane filter equipment described in step 1 adopts is 20-100nm, and its working conditions is: between 30～50 ℃ of temperature, and pressure 0.15～0.5Mpa.
Further, in the resin column of the continuous chromatography separating device described in step 2, fill sodium type Zeo-karb.
Further, in the evaporative crystallization technique described in step 3, by underpressure distillation, the content of glutamine dipeptide is reached more than 50%, then after cooling, add ethanol, can separate out glutamine dipeptide crystal.
Adopt technique scheme, the separating and purifying method of glutamine dipeptide of the present invention, has reduced production cost, has simplified producer skill, has shortened the production cycle, has improved total recovery, and had product purity advantages of higher.
Accompanying drawing explanation
Fig. 1 is prior art glutamine dipeptide separating-purifying schematic flow sheet;
Fig. 2 is the separating and purifying method process flow sheet of glutamine dipeptide of the present invention.
Embodiment
Below in conjunction with the drawings and specific embodiments, the present invention will be further described.
Embodiment 1
In the glutamine dipeptide enzyme reaction solution making, glutamine dipeptide massfraction 43.5%, sodium-chlor massfraction 9.7%; After 50nm ceramic membrane filter, by blade diameter length ratio 1:15, fill sodium type strong-acid ion exchange resin, 25 ℃ of column temperatures, inlet amount 0.1bv, constant temperature chromatographic separation, with distilled water, carry out wash-out, control 25 ℃ of elution flow rate 0.5bv.h of column temperature, collect respectively elutriant and residual solution, glutamine dipeptide purity 96.8% in elutriant, concentration 35.2%, by underpressure distillation, then carries out crystallization, obtain glutamine dipeptide product, yield is greater than 98.9%; Sodium-chlor purity 99.1%, concentration 5.2% in residual solution.
Embodiment 2
In the glutamine dipeptide enzyme reaction solution making, glutamine dipeptide massfraction 47.4%, sodium-chlor massfraction 10.5%; After 20nm ceramic membrane filter, by blade diameter length ratio 1:20, fill sodium type strong-acid ion exchange resin, 25 ℃ of column temperatures, inlet amount 0.5bv, constant temperature chromatographic separation, with distilled water, carry out wash-out, control 25 ℃ of elution flow rate 0.4bv.h of column temperature, collect respectively elutriant and residual solution, glutamine dipeptide purity 97.8% in elutriant, concentration 37.5%, by underpressure distillation, then carries out crystallization, obtain glutamine dipeptide product, yield is greater than 98.5%; Sodium-chlor purity 97.8%, concentration 7.2% in residual solution.
Embodiment 3
In the glutamine dipeptide enzyme reaction solution making, glutamine dipeptide massfraction 44.4%, sodium-chlor massfraction 8.5%; After 100 μ m ceramic membrane filters, by blade diameter length ratio 1:50, fill sodium type strong-acid ion exchange resin, 25 ℃ of column temperatures, inlet amount 1bv, constant temperature chromatographic separation, carries out wash-out with distilled water, control 25 ℃ of elution flow rate 0.5bv.h of column temperature, collect respectively elutriant and residual solution, by underpressure distillation, then carry out crystallization, obtain glutamine dipeptide product, yield is greater than 97.5%; Sodium-chlor purity 98.9%, concentration 6.3% in residual solution.
In the above-described embodiments, only the present invention has been carried out to exemplary description, but those skilled in the art can carry out various modifications to the present invention without departing from the spirit and scope of the present invention after reading present patent application.
Claims (4)
1. a separating and purifying method for glutamine dipeptide, is characterized in that, comprises the steps:
Step 1 ceramic membrane filter is dezymotized: glutamine dipeptide enzyme reaction solution is filtered by ceramic membrane filter equipment, add during the course water washing, remove zymoprotein residual in reaction solution, obtain ceramic membrane dialyzate;
Step 2 continuous chromatography desalination: ceramic membrane dialyzate is entered to continuous chromatography separating device and carry out continuous chromatography separation, glutamine dipeptide and inorganic salt are carried out separated, obtain glutamine dipeptide solution;
Step 3 evaporative crystallization: the glutamine dipeptide solution that continuous chromatography separation is obtained carries out underpressure distillation, then carries out crystallization, obtains glutamine dipeptide product.
2. the separating and purifying method of a kind of glutamine dipeptide according to claim 1, it is characterized in that, the aperture of the ceramic membrane that ceramic membrane filter equipment described in step 1 adopts is 20-100nm, and its working conditions is: between 30～50 ℃ of temperature, and pressure 0.15～0.5Mpa.
3. the separating and purifying method of a kind of glutamine dipeptide according to claim 1, is characterized in that, fills sodium type Zeo-karb in the resin column of the continuous chromatography separating device described in step 2.
4. the separating and purifying method of a kind of glutamine dipeptide according to claim 1, is characterized in that, in the evaporative crystallization technique described in step 3, by underpressure distillation, the content of glutamine dipeptide is reached more than 50%, then after cooling, add ethanol, can separate out glutamine dipeptide crystal.
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| CN201410402627.XA CN104163849A (en) | 2014-08-16 | 2014-08-16 | Separation and purification method of N(2)-L-alanyl-L-glutamine |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104561202A (en) * | 2015-02-06 | 2015-04-29 | 江苏诚信药业有限公司 | Preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine |
| CN106243189A (en) * | 2016-09-23 | 2016-12-21 | 精晶药业股份有限公司 | A kind of method using composite membrane to extract alanyl glutamine |
| CN106432411A (en) * | 2016-09-23 | 2017-02-22 | 精晶药业股份有限公司 | Method for extracting alanyl-glutamine from enzymatic conversion liquid |
| CN106432412A (en) * | 2016-09-23 | 2017-02-22 | 精晶药业股份有限公司 | Method using resin to extract alanyl-glutamine |
| CN106883286A (en) * | 2017-04-24 | 2017-06-23 | 精晶药业股份有限公司 | A kind of method for extraction and purification of tyrosine derivative |
| CN107163103A (en) * | 2017-06-30 | 2017-09-15 | 山东辰龙药业有限公司 | Methanol Recovery Application way during N (2) L alanyl L glutamine productions |
| CN110372773A (en) * | 2019-07-18 | 2019-10-25 | 大连医诺生物股份有限公司 | The production method of high-purity glutamine dipeptide |
| CN110407914A (en) * | 2018-06-11 | 2019-11-05 | 合肥川迪医药技术有限公司 | A kind of process for separation and purification of glutamine dipeptide |
| CN110885357A (en) * | 2019-12-20 | 2020-03-17 | 大连医诺生物股份有限公司 | Method for separating and purifying glutamine dipeptide by nanofiltration membrane |
-
2014
- 2014-08-16 CN CN201410402627.XA patent/CN104163849A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104561202A (en) * | 2015-02-06 | 2015-04-29 | 江苏诚信药业有限公司 | Preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine |
| CN106243189A (en) * | 2016-09-23 | 2016-12-21 | 精晶药业股份有限公司 | A kind of method using composite membrane to extract alanyl glutamine |
| CN106432411A (en) * | 2016-09-23 | 2017-02-22 | 精晶药业股份有限公司 | Method for extracting alanyl-glutamine from enzymatic conversion liquid |
| CN106432412A (en) * | 2016-09-23 | 2017-02-22 | 精晶药业股份有限公司 | Method using resin to extract alanyl-glutamine |
| CN106883286A (en) * | 2017-04-24 | 2017-06-23 | 精晶药业股份有限公司 | A kind of method for extraction and purification of tyrosine derivative |
| CN107163103A (en) * | 2017-06-30 | 2017-09-15 | 山东辰龙药业有限公司 | Methanol Recovery Application way during N (2) L alanyl L glutamine productions |
| CN110407914A (en) * | 2018-06-11 | 2019-11-05 | 合肥川迪医药技术有限公司 | A kind of process for separation and purification of glutamine dipeptide |
| CN110372773A (en) * | 2019-07-18 | 2019-10-25 | 大连医诺生物股份有限公司 | The production method of high-purity glutamine dipeptide |
| CN110372773B (en) * | 2019-07-18 | 2022-06-10 | 大连医诺生物股份有限公司 | Production method of high-purity glutamine dipeptide |
| CN110885357A (en) * | 2019-12-20 | 2020-03-17 | 大连医诺生物股份有限公司 | Method for separating and purifying glutamine dipeptide by nanofiltration membrane |
| CN110885357B (en) * | 2019-12-20 | 2022-09-06 | 大连医诺生物股份有限公司 | Method for separating and purifying glutamine dipeptide by nanofiltration membrane |
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