Production device of beta-aminobutyric acid

Abstract

The utility model discloses a beta-aminobutyric acid production device, and relates to the technical field of beta-aminobutyric acid extraction, an inlet of a conversion kettle is respectively communicated with an aspartase tank, a sodium hydroxide tank, a crotonic acid tank and a calcium salt tank through pipelines, and an outlet of the conversion kettle is communicated with a ceramic membrane device through a pipeline. A clear liquid outlet of the ceramic membrane device is communicated with a chromatographic column through a pipeline, an inlet of the chromatographic column is respectively communicated with an ammonia water tank and a first ethanol tank through pipelines, and an outlet of the chromatographic column is communicated with a concentration tank through a pipeline; an outlet of the concentration tank is communicated with a first crystallizing tank through a pipeline, an inlet of the first crystallizing tank is respectively communicated with a first purified water tank and a second ethanol tank through pipelines, and an outlet of the first crystallizing tank is communicated with a beta-aminobutyric acid crude product tank through a pipeline. The whole process is simple to operate, the separation and purification effects on beta-aminobutyric acid in the material passing through the chromatographic column are good, and the purity and yield of the obtained product are high.

Description

Technical Field

[0001] The utility model relates to the technical field of β - aminobutyric acid extraction, and particularly relates to a production device for β - aminobutyric acid. Background Art

[0002] As a precursor of β - aminobutanol, a pharmaceutical intermediate, β - aminobutyric acid can be used to synthesize anti - tumor drugs such as 4 - methylcyclophosphamide, penem antibiotics, and the key intermediate of the chiral six - membered ring of the AIDS integrase inhibitor dolutegravir. Dolutegravir is a new anti - HIV drug under GlaxoSmithKline. In 2013, the FAD approved its listing and recognized the breakthrough of this drug, which has important medical and pharmaceutical value. β - aminobutyric acid also participates in the synthesis of oligopeptides composed of 5 amino acids, which are prepared by solid - phase synthesis methods and have good inhibitory effects on Penicillium digitatum, a citrus rot - causing fungus, and have the potential for citrus preservation and biological control. In addition, β - aminobutyric acid can also be used for immune cell resuscitation treatment, cirrhosis biomarker, etc.

[0003] Chinese Patent CN108374027B discloses a preparation method of R - 3 - aminobutyric acid. This method controls the ammonium ions in the reaction system to control the reverse reaction and reduce the generation of by - products; uses microfiltration and nanofiltration to intercept impurities such as bacterial sludge, enzyme proteins, sulfate ions, and pigments. However, the product yield is not high and the process steps are cumbersome. Summary of the Invention

[0004] The technical problem to be solved by the utility model is: aiming at the deficiencies existing in the prior art, to provide a production device for β - aminobutyric acid with simple process steps and high product yield.

[0005] To solve the above - mentioned technical problem, the technical solution of the utility model is:

[0006] A production device for β - aminobutyric acid includes a conversion kettle. The inlets of the conversion kettle are respectively connected to an aspartase tank, a sodium hydroxide tank, a crotonic acid tank, and a calcium salt tank through pipelines. The outlet of the conversion kettle is connected to a ceramic membrane device through a pipeline. The clear liquid outlet of the ceramic membrane device is connected to a chromatography column through a pipeline. The inlets of the chromatography column are respectively connected to an ammonia water tank and a first ethanol tank through pipelines. The outlet of the chromatography column is connected to a concentration tank through a pipeline;

[0007] The outlet of the concentration tank is connected to a first crystallization tank through a pipeline. The inlets of the first crystallization tank are respectively connected to a first purified water tank and a second ethanol tank through pipelines. The outlet of the first crystallization tank is connected to a β - aminobutyric acid crude product tank through a pipeline.

[0008] As an improved technical solution, the concentrated liquid outlet of the ceramic membrane device is connected to the inlet of the conversion kettle through a pipeline;

[0009] The pore size range of the ceramic membrane device is 50 - 200 nm.

[0010] As an improved technical solution, the clear liquid outlet of the ceramic membrane device is connected to an ultrafiltration membrane device through a pipeline, and the clear liquid outlet of the ultrafiltration membrane device is connected to the chromatography column through a pipeline;

[0011] The molecular weight cut-off of the ultrafiltration membrane device is 5000 - 10000 Da.

[0012] As an improved technical solution, the concentrated liquid outlet of the ultrafiltration membrane device is connected to a recovery kettle through a pipeline. The inlet of the recovery kettle is respectively connected to a chitosan tank and a diatomite tank through pipelines. The outlet of the recovery kettle is connected to a filter through a pipeline, and the filtrate outlet of the filter is connected to the crotonic acid tank through a pipeline.

[0013] As an improved technical solution, the clear liquid outlet of the ultrafiltration membrane device is connected to a first nanofiltration membrane device through a pipeline, and the concentrated liquid outlet of the first nanofiltration membrane device is connected to the chromatography column through a pipeline;

[0014] The pore size range of the first nanofiltration membrane device is 100 - 200 Da.

[0015] As an improved technical solution, the outlet of the chromatography column is connected to a second nanofiltration membrane device through a pipeline, and the outlet of the second nanofiltration membrane device is connected to the concentration tank through a pipeline;

[0016] The pore size range of the second nanofiltration membrane device is 100 - 200 Da.

[0017] As a preferred technical solution, the outlet of the chromatography column is connected to the inlet of the chromatography column through a pipeline.

[0018] As a preferred technical solution, the outlet of the crude β-aminobutyric acid tank is connected to a decolorization tank through a pipeline. The inlet of the decolorization tank is respectively connected to a second purified water tank and an activated carbon tank through pipelines. The outlet of the decolorization tank is connected to a second crystallization tank through a pipeline. The inlet of the second crystallization tank is connected to a third ethanol tank through a pipeline. The outlet of the second crystallization tank is connected to the β-aminobutyric acid finished product tank.

[0019] Due to the adoption of the above technical solutions, the beneficial effects of the present utility model are:

[0020] A production device for β-aminobutyric acid of the utility model includes a conversion kettle. The inlets of the conversion kettle are respectively connected to an aspartase tank, a sodium hydroxide tank, a crotonic acid tank and a calcium salt tank through pipelines. The outlet of the conversion kettle is connected to a ceramic membrane device through a pipeline. The clear liquid outlet of the ceramic membrane device is connected to a chromatography column through a pipeline. The inlets of the chromatography column are respectively connected to an ammonia water tank and a first ethanol tank through pipelines. The outlet of the chromatography column is connected to a concentration tank through a pipeline. The outlet of the concentration tank is connected to a first crystallization tank through a pipeline. The inlets of the first crystallization tank are respectively connected to a first purified water tank and a second ethanol tank through pipelines. The outlet of the first crystallization tank is connected to a β-aminobutyric acid crude product tank through a pipeline. Crotonic acid undergoes biocatalytic conversion under the action of aspartase whole cells and calcium salt to obtain a conversion liquid of β-aminobutyric acid. Sodium hydroxide controls the pH of the conversion process. The conversion liquid is separated by the ceramic membrane device. After the aspartase cells are filtered out from the conversion liquid, it enters the chromatography column. Under the elution of ammonia water and ethanol, the target component containing β-aminobutyric acid is collected and enters the first crystallization tank. It is dissolved in purified water and cooled and crystallized under the action of the poor solvent ethanol to obtain β-aminobutyric acid crude product. The whole process is simple to operate, and the separation and purification effect of β-aminobutyric acid in the material after passing through the chromatography column is good, and the obtained product has high purity and yield.

[0021] The concentrated liquid outlet of the ceramic membrane device of the utility model is connected to the inlet of the conversion kettle through a pipeline; the pore size range of the ceramic membrane device is 50-200 nm. The aspartase cells in the conversion liquid are intercepted and collected and reused for the conversion of crotonic acid, which improves the utilization rate of the cells and saves costs.

[0022] The clear liquid outlet of the ceramic membrane device is connected to an ultrafiltration membrane device through a pipeline. The clear liquid outlet of the ultrafiltration membrane device is connected to the chromatography column through a pipeline; the cut-off molecular weight of the ultrafiltration membrane device is 5000-10000 Da. The β-aminobutyric acid is further separated by the ultrafiltration membrane device, which improves the purity of the product.

[0023] The concentrated liquid outlet of the ultrafiltration membrane device is connected to a recovery kettle through a pipeline. The inlets of the recovery kettle are respectively connected to a chitosan tank and a diatomite tank through pipelines. The outlet of the recovery kettle is connected to a filter through a pipeline. The filtrate outlet of the filter is connected to the crotonic acid tank through a pipeline. The ultrafiltration concentrated liquid is treated with chitosan and diatomite. The crotonic acid in the obtained filtrate is relatively high and can be used for the preparation of crotonic acid, avoiding waste of raw materials and saving costs.

[0024] The clear liquid outlet of the ultrafiltration membrane device is connected to a first nanofiltration membrane device through a pipeline, and the concentrated liquid outlet of the first nanofiltration membrane device is connected to the chromatography column through a pipeline; the pore size range of the first nanofiltration membrane device is 100 - 200 Da. Concentrating the material through the first nanofiltration membrane device saves energy and facilitates subsequent chromatography separation.

[0025] The outlet of the chromatography column is connected to a second nanofiltration membrane device through a pipeline, and the outlet of the second nanofiltration membrane device is connected to the concentration tank through a pipeline; the pore size range of the second nanofiltration membrane device is 100 - 200 Da. The second nanofiltration membrane device preliminarily concentrates the target component containing β - aminobutyric acid, facilitating subsequent concentration crystallization and shortening the crystallization cycle.

[0026] The outlet of the chromatography column is connected to the inlet of the chromatography column through a pipeline, and the material other than the target component containing β - aminobutyric acid is re - input into the chromatography column for separation and extraction, improving the product yield.

[0027] The outlet of the β - aminobutyric acid crude product tank is connected to a decolorization tank through a pipeline. The inlet of the decolorization tank is respectively connected to a second purified water tank and an activated carbon tank through pipelines. The outlet of the decolorization tank is connected to a second crystallization tank through a pipeline. The inlet of the second crystallization tank is connected to a third ethanol tank through a pipeline, and the outlet of the second crystallization tank is connected to a β - aminobutyric acid finished product tank. Dissolving the β - aminobutyric acid crude product obtained from the first crystallization in purified water, then decolorizing it with activated carbon, and adding ethanol again to the decolorized material for crystallization further purifies the product, greatly improving the product purity. Description of the Drawings

[0028] The present utility model will be further described below in conjunction with the drawings and embodiments.

[0029] Figure 1 is a schematic structural diagram of an embodiment of the present utility model;

[0030] Among them: 1, conversion kettle; 2, aspartase tank; 3, sodium hydroxide tank; 4, crotonic acid tank; 5, calcium salt tank; 6, ceramic membrane device; 7, chromatography column; 8, ammonia water tank; 9, first ethanol tank; 10, concentration tank; 11, first crystallization tank; 12, first purified water tank; 13, second ethanol tank; 14, β - aminobutyric acid crude product tank; 15, ultrafiltration membrane device; 16, recovery kettle; 17, chitosan tank; 18, diatomite tank; 19, filter; 20, first nanofiltration membrane device; 21, second nanofiltration membrane device; 22, decolorization tank; 23, second purified water tank; 24, activated carbon tank; 25, second crystallization tank; 26, third ethanol tank; 27, β - aminobutyric acid finished product tank. Detailed Embodiments

[0031] The present utility model will be further described below in conjunction with the accompanying drawings and embodiments.

[0032] As Figure 1 shown, a production device for β - aminobutyric acid includes a conversion kettle 1. The inlets of the conversion kettle 1 are respectively connected through pipelines to an aspartase tank 2, a sodium hydroxide tank 3, a crotonic acid tank 4, and a calcium salt tank 5. The outlet of the conversion kettle 1 is connected through a pipeline to a ceramic membrane device 6. The clear liquid outlet of the ceramic membrane device 6 is connected through a pipeline to a chromatography column 7. The inlets of the chromatography column 7 are respectively connected through pipelines to an ammonia water tank 8 and a first ethanol tank 9. The outlet of the chromatography column 7 is connected through a pipeline to a concentration tank 10. The outlet of the concentration tank 10 is connected through a pipeline to a first crystallization tank 11. The inlets of the first crystallization tank 11 are respectively connected through pipelines to a first purified water tank 12 and a second ethanol tank 13. The outlet of the first crystallization tank 11 is connected through a pipeline to a crude β - aminobutyric acid tank 14. Crotonic acid undergoes biocatalytic conversion under the action of whole - cell aspartase and calcium salt to obtain a conversion liquid of β - aminobutyric acid. Sodium hydroxide controls the pH of the conversion process. The conversion liquid is separated by the ceramic membrane device 6. After the aspartase cells are filtered out from the conversion liquid, it enters the chromatography column 7. Under the elution of ammonia water and ethanol, the target component containing β - aminobutyric acid is collected and enters the first crystallization tank 11. It is dissolved in purified water and cooled for crystallization under the action of a poor solvent ethanol to obtain crude β - aminobutyric acid. The whole process is simple to operate, and after passing through the chromatography column 7, the separation and purification effect of β - aminobutyric acid in the material is good, and the obtained product has high purity and yield.

[0033] The concentrated liquid outlet of the ceramic membrane device 6 is connected through a pipeline to the inlet of the conversion kettle 1. The pore size range of the ceramic membrane device 6 is 50 - 200 nm. The aspartase cells in the conversion liquid are intercepted and collected and reused for the conversion of crotonic acid, improving the utilization rate of the cells and saving costs.

[0034] The clear liquid outlet of the ceramic membrane device 6 is connected through a pipeline to an ultrafiltration membrane device 15. The clear liquid outlet of the ultrafiltration membrane device 15 is connected through a pipeline to the chromatography column 7. The cut - off molecular weight of the ultrafiltration membrane device 15 is 5000 - 10000 Da. Further separation of β - aminobutyric acid is carried out through the ultrafiltration membrane device 15, improving the purity of the product.

[0035] The concentrated liquid outlet of the ultrafiltration membrane device 15 is connected through a pipeline to a recovery kettle 16. The inlets of the recovery kettle 16 are respectively connected through pipelines to a chitosan tank 17 and a diatomite tank 18. The outlet of the recovery kettle 16 is connected through a pipeline to a filter 19. The filtrate outlet of the filter 19 is connected through a pipeline to the crotonic acid tank 4. The ultrafiltration concentrated liquid is treated with chitosan and diatomite. The crotonic acid content in the obtained filtrate is relatively high, which can be used for the preparation of crotonic acid, avoiding waste of raw materials and saving costs.

[0036] The clear liquid outlet of the ultrafiltration membrane device 15 is connected to a first nanofiltration membrane device 20 through a pipeline, and the concentrated liquid outlet of the first nanofiltration membrane device 20 is connected to the chromatography column 7 through a pipeline; the pore size range of the first nanofiltration membrane device 20 is 100 - 200 Da. Concentrating the material through the first nanofiltration membrane device 20 saves energy and facilitates subsequent chromatography separation.

[0037] The outlet of the chromatography column 7 is connected to a second nanofiltration membrane device 21 through a pipeline, and the outlet of the second nanofiltration membrane device 21 is connected to the concentration tank 10 through a pipeline; the pore size range of the second nanofiltration membrane device 21 is 100 - 200 Da. The second nanofiltration membrane device 21 preliminarily concentrates the obtained target component containing β - aminobutyric acid, facilitating subsequent concentration crystallization and shortening the crystallization cycle.

[0038] The outlet of the chromatography column 7 is connected to the inlet of the chromatography column 7 through a pipeline, and the material except the target component containing β - aminobutyric acid

[0039] is re - input into the chromatography column 7 for separation and extraction, improving the product yield.

[0040] The outlet of the β - aminobutyric acid crude product tank 14 is connected to a decolorization tank 22 through a pipeline. The inlet of the decolorization tank 22 is respectively connected to a second purified water tank 23 and an activated carbon tank 24 through pipelines. The outlet of the decolorization tank 22 is connected to a second crystallization tank 25 through a pipeline. The inlet of the second crystallization tank 25 is connected to a third ethanol tank 26 through a pipeline. The outlet of the second crystallization tank 25 is connected to a β - aminobutyric acid finished product tank 27. The β - aminobutyric acid crude product obtained from the first crystallization is dissolved by adding purified water, then decolorized with activated carbon, and the decolorized material is crystallized again by adding ethanol, further purifying the product and greatly improving the product purity.

[0041] It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

Claims

1. A production device for β-aminobutyric acid, characterized in that: It comprises a conversion kettle, wherein the inlet of the conversion kettle is connected to an aspartase tank, a sodium hydroxide tank, a crotonic acid tank and a calcium salt tank through pipelines, the outlet of the conversion kettle is connected to a ceramic membrane device through a pipeline, the clear liquid outlet of the ceramic membrane device is connected to a chromatography column through a pipeline, the inlet of the chromatography column is connected to an ammonia water tank and a first ethanol tank through pipelines, and the outlet of the chromatography column is connected to a concentration tank through a pipeline; The outlet of the concentration tank is connected to the first crystallization tank through a pipeline, the inlet of the first crystallization tank is connected to the first purified water tank and the second ethanol tank through pipelines, respectively, and the outlet of the first crystallization tank is connected to the crude β-aminobutyric acid tank through a pipeline.

2. The β-aminobutyric acid production device according to claim 1, characterized in that: The concentrated solution outlet of the ceramic membrane device is connected to the inlet of the conversion kettle through a pipeline; The pore size of the ceramic membrane device ranges from 50 to 200 nm.

3. The production device of β-aminobutyric acid according to claim 1, characterized in that: The clear liquid outlet of the ceramic membrane device is connected to the ultrafiltration membrane device through a pipeline, and the clear liquid outlet of the ultrafiltration membrane device is connected to the chromatography column through a pipeline; The molecular weight cut-off of the ultrafiltration membrane device is 5000-10000Da.

4. A β-aminobutyric acid production device as claimed in claim 3, characterized in that: The concentrated liquid outlet of the ultrafiltration membrane device is connected to a recovery kettle through a pipeline, the inlet of the recovery kettle is connected to a chitosan tank and a diatomaceous earth tank through pipelines, the outlet of the recovery kettle is connected to a filter through a pipeline, and the filtrate outlet of the filter is connected to the crotonic acid tank through a pipeline.

5. The production device of β-aminobutyric acid according to claim 3, characterized in that: The clear liquid outlet of the ultrafiltration membrane device is connected to the first nanofiltration membrane device through a pipeline, and the concentrated liquid outlet of the first nanofiltration membrane device is connected to the chromatography column through a pipeline; The pore size range of the first nanofiltration membrane device is 100-200Da.

6. The β-aminobutyric acid production device according to claim 1, characterized in that: The outlet of the chromatography column is connected to a second nanofiltration membrane device through a pipeline, and the outlet of the second nanofiltration membrane device is connected to the concentration tank through a pipeline; The pore size range of the second nanofiltration membrane device is 100-200Da.

7. The β-aminobutyric acid production device according to claim 1, characterized in that: The outlet of the chromatography column is connected to the inlet of the chromatography column through a pipeline.

8. The β-aminobutyric acid production device according to claim 1, characterized in that: The outlet of the crude β-aminobutyric acid tank is connected to a decolorizing tank via a pipeline, the inlet of the decolorizing tank is connected to a second purified water tank and an activated carbon tank via pipelines, respectively, the outlet of the decolorizing tank is connected to a second crystallization tank via a pipeline, the inlet of the second crystallization tank is connected to a third ethanol tank via a pipeline, and the outlet of the second crystallization tank is connected to a β-aminobutyric acid finished product tank.

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