CN103641887B - Adopt the method for D301 macroporous resin separation and purification glutamine dipeptide - Google Patents
Adopt the method for D301 macroporous resin separation and purification glutamine dipeptide Download PDFInfo
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- CN103641887B CN103641887B CN201310689791.9A CN201310689791A CN103641887B CN 103641887 B CN103641887 B CN 103641887B CN 201310689791 A CN201310689791 A CN 201310689791A CN 103641887 B CN103641887 B CN 103641887B
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Abstract
The invention belongs to medicinal chemistry art, be specifically related to a kind of method adopting D301 macroporous resin separation and purification glutamine dipeptide.Glutamine dipeptide crude product is mixed with the aqueous solution of massfraction 5% ~ 10%; Continue through D301 macroporous resin column and carry out fractionation by adsorption, when glutamine dipeptide being detected in effluent liquid, collect effluent liquid; Then use water wash D301 macroporous resin column, collect effluent liquid; Merge effluent liquid, and concentrated; Ethanol is dripped, crystallize out in concentrated solution; Filter, the solid vacuum-drying obtained, obtains pure glutamine dipeptide crude product.This adopts physical method, environmental protection; Impurity is all adsorbed in resin, reduces the usage quantity of ethanol crystallization, also improves the purity of product simultaneously, and the purity of the glutamine dipeptide product obtained after separating-purifying, more than 99.6%, uses high performance liquid chromatography to detect and finds without obvious impurity; Low to the rate of loss of glutamine dipeptide product, improve yield, reduce production cost.
Description
Technical field
The invention belongs to medicinal chemistry art, be specifically related to a kind of method adopting D301 macroporous resin separation and purification glutamine dipeptide.
Background technology
N (2)-Ala-Gln (abbreviation glutamine dipeptide) belongs to amino acid whose derivative, is amino acid dipeptide product important both at home and abroad at present, is mainly used in body-care industry; The desirable substitute products of the abundantest amino acid glutamine of body burden.
Chinese invention patent CN1392156 discloses a kind of glutamine dipeptide synthetic method; the amino acid of N end protection and triphenyl phosphorus, hexachloroethane react in organic solvent and form active ester; active ester and glutamine carry out in the mixing solutions of organic solvent and inorganic base aqueous solution; use mineral acid catalysis, then slough N and hold blocking group.Chinese invention patent 1786019 discloses a kind of manufacture method of glutamine dipeptide, and the Pfansteihl of esterification, under catalysts conditions, is hydrolyzed after reacting, then obtains glutamine dipeptide product after carrying out series reaction with sulfur oxychloride.In glutamine dipeptide production technique, the purification of product is important step, and common purification process can not get the higher glutamine dipeptide product of purity, the development of restriction glutamine dipeptide technique.
Summary of the invention
The object of this invention is to provide a kind of method adopting D301 macroporous resin separation and purification glutamine dipeptide, purification procedures adopts physical method, and environmental protection, decreases environmental pollution; Decrease the consumption of alcohol in purification process; Improve the yield of glutamine dipeptide technique, reduce production cost.
The method of employing D301 macroporous resin separation and purification glutamine dipeptide of the present invention, comprises the following steps:
(1) glutamine dipeptide crude product is mixed with the aqueous solution of massfraction 5% ~ 10%; Continue through D301 macroporous resin column and carry out fractionation by adsorption, when glutamine dipeptide being detected in effluent liquid, collect effluent liquid;
(2) then use water wash D301 macroporous resin column, collect effluent liquid;
(3) effluent liquid in described step (1) and step (2) is merged, and concentrated;
(4) ethanol is dripped, crystallize out in the concentrated solution obtained in step (3);
(5) filter, the solid vacuum-drying obtained, obtains pure glutamine dipeptide crude product.
Wherein:
Glutamine dipeptide crude product is do not limit the glutamine dipeptide crude product that any synthetic method obtains.The major impurity of more difficult separation in glutamine dipeptide crude product is L-Ala-L-Glu, and D301 macroporous resin is weakly base resin, can adsorb this impurity preferably.
D301 macroporous resin is H type D301 macroporous adsorbent resin.The solvent of D301 macroporous resin column is 40-80mL.
In step (2), the flow velocity of water is 1-3mL/min, preferred 2mL/min.If flow velocity is too fast, adsorption effect is bad, and impurity is large, and flow velocity is too little, then affect production capacity.
The feed ratio of glutamine dipeptide crude product and water is 5:80-160, and wherein glutamine dipeptide crude product is in g, and water is in mL.
In the concentrated solution obtained in step (3), ethanol is dripped, crystallize out in step (4); Drip the product that ethanol can obtain better crystal formation.It is more that ethanol obtains product more, but purity is lower, and the ratio of concentrated solution and ethanol is preferably 2-2.5:5, and concentrated solution is in g, and ethanol is in mL.
Dripping ethanol to producing muddiness in the concentrated solution that step (4) preferably obtains in step (3), after leaving standstill 0.8-1.2h, continuing to drip ethanol, crystallize out.Add the product crystal formation that ethanol makes to obtain in two steps better, can not produce the problem that crystallization is too fast, the product that crystal formation is good is easy to filtering separation, and purity is high.
By the purity of glutamine dipeptide product that obtains after above-mentioned steps separating-purifying more than 99.6%, use high performance liquid chromatography to detect and find without obvious impurity.
In sum, the present invention has the following advantages:
(1) purification procedures adopts physical method, and environmental protection, decreases environmental pollution;
(2) impurity is all adsorbed in resin, the concentration of crude product before crystallization can be improved, thus reduce the usage quantity of ethanol crystallization, decrease the consumption of alcohol in purification process, reach the maximum protection to operator, also improve the purity of product, the purity of the glutamine dipeptide product obtained after separating-purifying, more than 99.6%, uses high performance liquid chromatography to detect and finds without obvious impurity simultaneously;
(3) rate of loss of this separating-purifying step to glutamine dipeptide product is low, improves the yield of glutamine dipeptide technique, reduces production cost.
Embodiment
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1:
Adopt D301 macroporous resin separation and purification glutamine dipeptide from the thick product of glutamine dipeptide, glutamine dipeptide crude product 5g is mixed with the aqueous solution of massfraction 5%; Solution is continued through 40cm
3d301 macroporous resin column carry out fractionation by adsorption, when glutamine dipeptide being detected in effluent liquid collect effluent liquid; By 80mL water wash D301 macroporous resin column; The flow velocity of water is 1mL/min, merges effluent liquid and concentrates; The solution received is concentrated into 20g, drips ethanol 10mL, after crystallization 1h, continue to drip ethanol 40mL, suction filtration, vacuum-drying obtains product 4.4g, purity 99.6%.
Embodiment 2:
Adopt D301 macroporous resin separation and purification glutamine dipeptide from the thick product of glutamine dipeptide, glutamine dipeptide crude product 5g is mixed with the aqueous solution of massfraction 7%; Solution is continued through 60cm
3d301 macroporous resin column carry out fractionation by adsorption, when glutamine dipeptide being detected in effluent liquid collect effluent liquid; By 120mL water wash D301 macroporous resin column; The flow velocity of water is 2mL/min, merges effluent liquid and concentrates; The solution received is concentrated into 25g, drips ethanol 10mL, after crystallization 0.8h, continue to drip ethanol 40mL, suction filtration, vacuum-drying obtains product 4.5g, purity 99.8%.
Embodiment 3:
Adopt D301 macroporous resin separation and purification glutamine dipeptide from the thick product of glutamine dipeptide, glutamine dipeptide crude product 5g is mixed with the aqueous solution of massfraction 10%; Solution is continued through 80cm
3d301 macroporous resin column carry out fractionation by adsorption, when glutamine dipeptide being detected in effluent liquid collect effluent liquid; By 160mL water wash D301 macroporous resin column; The flow velocity of water is 3mL/min, merges effluent liquid and concentrates; The solution received is concentrated into 25g, drips ethanol 10mL, after crystallization 1.2h, continue to drip ethanol 40mL, suction filtration, vacuum-drying obtains product 4.2g, purity 99.7%.
Claims (4)
1. adopt a method for D301 macroporous resin separation and purification glutamine dipeptide, it is characterized in that: comprise the following steps:
(1) glutamine dipeptide crude product is mixed with the aqueous solution of massfraction 5% ~ 10%; Continue through D301 macroporous resin column and carry out fractionation by adsorption, when glutamine dipeptide being detected in effluent liquid, collect effluent liquid;
(2) then use water wash D301 macroporous resin column, collect effluent liquid;
(3) effluent liquid in described step (1) and step (2) is merged, and concentrated;
(4) dripping ethanol to producing muddiness in the concentrated solution obtained in step (3), after leaving standstill 0.8-1.2h, continuing to drip ethanol, crystallize out;
(5) filter, the solid vacuum-drying obtained, obtains pure glutamine dipeptide crude product;
The feed ratio of glutamine dipeptide crude product and water is 5:80-160, and wherein glutamine dipeptide crude product is in g, and water is in mL;
In step (4), the ratio of concentrated solution and ethanol is 2-2.5:5, and concentrated solution is in g, and ethanol is in mL.
2. the method for employing D301 macroporous resin separation and purification glutamine dipeptide according to claim 1, is characterized in that: D301 macroporous resin is H type D301 macroporous adsorbent resin.
3. the method for employing D301 macroporous resin separation and purification glutamine dipeptide according to claim 1 and 2, is characterized in that: the solvent of D301 macroporous resin column is 40-80mL.
4. the method for employing D301 macroporous resin separation and purification glutamine dipeptide according to claim 1, is characterized in that: in step (2), the flow velocity of water is 1-3mL/min.
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| CN201310689791.9A CN103641887B (en) | 2013-12-16 | 2013-12-16 | Adopt the method for D301 macroporous resin separation and purification glutamine dipeptide |
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| CN103641887B true CN103641887B (en) | 2016-03-16 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680428A (en) * | 2005-02-01 | 2005-10-12 | 上海依福瑞实业有限公司 | Preparation of alanyl glutamine dipeptide compound |
| CN101062938A (en) * | 2006-04-25 | 2007-10-31 | 福建三爱药业有限公司 | Preparation method of N(2)-L-alanyl-L-glutamine |
| CN101659691A (en) * | 2009-09-28 | 2010-03-03 | 绍兴民生医药有限公司 | Industrial process for producing glutamine dipeptide |
| CN102823715A (en) * | 2012-09-19 | 2012-12-19 | 昆明理工大学 | Method for preparing bioactive peptide through full-bionic digestion model method |
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2013
- 2013-12-16 CN CN201310689791.9A patent/CN103641887B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680428A (en) * | 2005-02-01 | 2005-10-12 | 上海依福瑞实业有限公司 | Preparation of alanyl glutamine dipeptide compound |
| CN101062938A (en) * | 2006-04-25 | 2007-10-31 | 福建三爱药业有限公司 | Preparation method of N(2)-L-alanyl-L-glutamine |
| CN101659691A (en) * | 2009-09-28 | 2010-03-03 | 绍兴民生医药有限公司 | Industrial process for producing glutamine dipeptide |
| CN102823715A (en) * | 2012-09-19 | 2012-12-19 | 昆明理工大学 | Method for preparing bioactive peptide through full-bionic digestion model method |
Non-Patent Citations (2)
| Title |
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| D301大孔树脂分离纯化大黄总蒽醌的研究;许汉林等;《中国中药杂志》;20060731;第31卷(第14期);1163-1165 * |
| D301大孔阴离子树脂固定化β-淀粉酶的研究;廖春燕等;《安徽农业科学》;20091231;第37卷(第33期);16218-16220 * |
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Address after: 255129 Zichuan District Economic Development Zone, Zibo, Shandong Patentee after: SHANDONG JINCHENG PHARMACEUTICAL GROUP CO.,LTD. Address before: 255129 Zichuan District Economic Development Zone, Zibo, Shandong Patentee before: SHANDONG JINCHENG PHARMACEUTICAL CO.,LTD. Address after: 255129 Zichuan District Economic Development Zone, Zibo, Shandong Patentee after: SHANDONG JINCHENG PHARMACEUTICAL CO.,LTD. Address before: 255129 Zichuan District Economic Development Zone, Zibo, Shandong Patentee before: SHANDONG JINCHENG PHARMACEUTICAL & CHEMICAL Co.,Ltd. |