Uridine diphosphate production device

Abstract

The utility model discloses a production device of uridine diphosphate, and relates to the technical field of uridine diphosphate production, a conversion tank is communicated with a ceramic membrane device, the ceramic membrane device is communicated with an extraction tank, the extraction tank is communicated with an adjusting tank, an inlet of the adjusting tank is communicated with a sodium hydroxide tank, and an outlet of the adjusting tank is communicated with an anion exchange resin column. An inlet of the anion exchange resin column is communicated with a sodium phosphate buffer solution tank and a sodium chloride solution tank, an outlet of the anion exchange resin column is communicated with a nanofiltration membrane device, the nanofiltration membrane device is communicated with an alcohol precipitation tank, an outlet of the alcohol precipitation tank is communicated with a filter, and an outlet of the filter is communicated with a uridine diphosphate tank. The method has the advantages that the production cycle is short, the purity of the obtained uridine diphosphate product is high, the production process is simplified, the production cost is reduced, and the uridine diphosphate has higher potential and competitiveness in the aspects of large-scale production and application.

Description

Technical Field

[0001] The utility model relates to the technical field of uridine diphosphate production, and particularly relates to a production device for uridine diphosphate. Background Art

[0002] Uridine diphosphate is one of the raw materials for synthesizing aplidine. Aplidine is a mismatched double-stranded RNA drug with dual functions of antiviral and immunomodulatory effects, and is highly efficient and low toxic. At present, abroad, this drug is undergoing clinical trials for some diseases, including chronic fatigue syndrome, AIDS, hepatitis B, etc.

[0003] Chinese Patent CN115896212A discloses a preparation method of uridine diphosphate. Under the condition of the presence of uridine kinase, ATP or its disodium salt, uridine is phosphorylated by uridine kinase to obtain uridine monophosphate; under the condition of the presence of uridine monophosphate kinase, ATP or its disodium salt, uridine monophosphate is phosphorylated by uridine monophosphate kinase to obtain uridine diphosphate. The by-product acetic acid is produced, resulting in low purity of the obtained uridine diphosphate, and the long conversion time leads to the extension of the whole production cycle. 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 uridine diphosphate with a short production cycle and high product purity.

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

[0006] A production device for uridine diphosphate, including a fermentation broth tank, the outlet of the fermentation broth tank is connected to a conversion tank through a pipeline, the inlet of the conversion tank is respectively connected to a uridine monophosphate tank, an adenosine triphosphate tank, a magnesium salt tank and a polyphosphate tank through pipelines, and the outlet of the conversion tank is connected to a ceramic membrane device through a pipeline;

[0007] The clear liquid outlet of the ceramic membrane device is connected to an extraction tank through a pipeline, the inlet of the extraction tank is connected to an extractant tank through a pipeline, the outlet of the extraction tank is connected to an adjustment tank through a pipeline, the inlet of the adjustment tank is connected to a sodium hydroxide tank through a pipeline, the outlet of the adjustment tank is connected to an anion exchange resin column through a pipeline, the inlet of the anion exchange resin column is respectively connected to a sodium phosphate buffer solution tank and a sodium chloride solution tank through pipelines, the outlet of the anion exchange resin column is connected to a nanofiltration membrane device through a pipeline, the outlet of the nanofiltration membrane device is connected to an alcohol precipitation tank through a pipeline, the inlet of the alcohol precipitation tank is connected to an ethanol tank through a pipeline, the outlet of the alcohol precipitation tank is connected to a filter through a pipeline, and the outlet of the filter is connected to a uridine diphosphate tank.

[0008] As an improved technical solution, the outlet of the fermentation broth tank is connected to a cell disruption tank through a pipeline, and the outlet of the cell disruption tank is connected to the conversion tank through a pipeline.

[0009] 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 extraction tank through a pipeline.

[0010] As an improved technical solution, the inlet of the alcohol reduction tank is connected to a hydrochloric acid tank through a pipeline.

[0011] As an improved technical solution, the outlet of the filter is connected to a washing tank, the outlet of the washing tank is connected to the uridine diphosphate tank through a pipeline, and the inlet of the washing tank is connected to a purified water tank.

[0012] As an improved technical solution, the aperture of the ceramic membrane device is 50 - 250 nm.

[0013] As a preferred technical solution, the aperture of the nanofiltration membrane device is 150 - 300 Da.

[0014] As a preferred technical solution, the aperture of the ultrafiltration membrane device is 5000 - 10000 Da.

[0015] Due to the adoption of the above technical solutions, the beneficial effects of the present utility model are as follows:

[0016] A production device for uridine diphosphate of the utility model includes a fermentation broth tank. The outlet of the fermentation broth tank is connected to a conversion tank through a pipeline. The inlet of the conversion tank is respectively connected to a uridine monophosphate tank, an adenosine triphosphate tank, a magnesium salt tank and a polyphosphate tank through pipelines. The outlet of the conversion tank is connected to a ceramic membrane device through a pipeline. The clear liquid outlet of the ceramic membrane device is connected to an extraction tank through a pipeline. The inlet of the extraction tank is connected to an extractant tank through a pipeline. The outlet of the extraction tank is connected to a regulation tank through a pipeline. The inlet of the regulation tank is connected to a sodium hydroxide tank through a pipeline. The outlet of the regulation tank is connected to an anion exchange resin column through a pipeline. The inlet of the anion exchange resin column is respectively connected to a sodium phosphate buffer solution tank and a sodium chloride solution tank through pipelines. The outlet of the anion exchange resin column is connected to a nanofiltration membrane device through a pipeline. The outlet of the nanofiltration membrane device is connected to an alcohol precipitation tank through a pipeline. The inlet of the alcohol precipitation tank is connected to an ethanol tank through a pipeline. The outlet of the alcohol precipitation tank is connected to a filter through a pipeline. The outlet of the filter is connected to a uridine diphosphate tank. By adding uridine and uridine monophosphate to the selective culture medium, high-quality bacteria capable of improving the conversion rate of uridine diphosphate are screened out. Then, the screened high-quality bacteria are subjected to high-density fermentation. The obtained fermentation broth is added to the conversion tank and converted together with uridine monophosphate, adenosine triphosphate, magnesium salt and polyphosphate. The obtained conversion liquid is filtered by the ceramic membrane device. The clear liquid of the ceramic membrane is subjected to layered purification under the action of extractants such as ethyl acetate, diethyl ether, petroleum ether and n-butanol. The lower layer of the liquid material is taken and added to the regulation tank, and then sodium hydroxide is added to adjust the pH to 7-8. Then it enters the anion exchange resin column. By adding sodium phosphate buffer solution, negatively charged substances such as extracellular proteins are desorbed from the resin. Then sodium chloride solution is added for elution until no UDP spots are detected in the eluate by rapid paper electrophoresis. The eluate enters the nanofiltration membrane device for concentration, and then alcohol precipitation is carried out in the alcohol precipitation tank. The filter cake obtained after filtration is uridine diphosphate. The production cycle is short, the obtained uridine diphosphate product has high purity, the production process is simplified, the production cost is reduced, and uridine diphosphate has more potential and competitiveness in large-scale production and application.

[0017] The outlet of the fermentation broth tank of the utility model is connected to a cell disruption tank through a pipeline. The outlet of the cell disruption tank is connected to the conversion tank through a pipeline. By disrupting the bacteria in the fermentation broth, the target product can be effectively released from the cells, and at the same time, impurities can be removed, so as to obtain a pure target product, which is convenient for subsequent conversion and reduces the enzyme dosage.

[0018] 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 extraction tank through a pipeline. The ultrafiltration membrane device can intercept small molecule impurities and improve the purity of uridine diphosphate.

[0019] The inlet of the alcohol reduction tank is connected to a hydrochloric acid tank through a pipeline, and the precipitation effect of uridine diphosphate is better.

[0020] The outlet of the filter is connected to a washing tank. The outlet of the washing tank is connected to the uridine diphosphate tank through a pipeline. The inlet of the washing tank is connected to a purified water tank. By rinsing, impurities in the product are further removed, improving the quality of the product.

[0021] The pore size of the ceramic membrane device is 50 - 250 nm, the pore size of the nanofiltration membrane device is 150 - 300 Da, and the pore size of the ultrafiltration membrane device is 5000 - 10000 Da, resulting in high-purity uridine diphosphate. Description of the Drawings

[0022] The present utility model will be further described below in conjunction with the drawings and embodiments.

[0023] Figure 1 is a schematic structural diagram of an embodiment of the present utility model;

[0024] Wherein: 1. Fermentation broth tank; 2. Conversion tank; 3. Uridine monophosphate tank; 4. Adenosine triphosphate tank; 5. Magnesium salt tank; 6. Polyphosphate tank; 7. Ceramic membrane device; 8. Extraction tank; 9. Extractant tank; 10. Adjustment tank; 11. Sodium hydroxide tank; 12. Anion exchange resin column; 13. Sodium phosphate buffer solution tank; 14. Sodium chloride solution tank; 15. Nanofiltration membrane device; 16. Alcohol reduction tank; 17. Ethanol tank; 18. Filter; 19. Uridine diphosphate tank; 20. Cell disruption tank; 21. Ultrafiltration membrane device; 22. Hydrochloric acid tank; 23. Washing tank; 24. Purified water tank. Detailed Embodiments

[0025] The present utility model will be further elaborated below in conjunction with the drawings and embodiments.

[0026] As Figure 1As shown in the figure, a production device for uridine diphosphate includes a fermentation broth tank 1. The outlet of the fermentation broth tank 1 is connected to a conversion tank 2 through a pipeline. The inlet of the conversion tank 2 is respectively connected to a uridine monophosphate tank 3, an adenosine triphosphate tank 4, a magnesium salt tank 5, and a polyphosphate tank 6 through pipelines. The outlet of the conversion tank 2 is connected to a ceramic membrane device 7 through a pipeline. The clear liquid outlet of the ceramic membrane device 7 is connected to an extraction tank 8 through a pipeline. The inlet of the extraction tank 8 is connected to an extractant tank 9 through a pipeline. The outlet of the extraction tank 8 is connected to a regulation tank 10 through a pipeline. The inlet of the regulation tank 10 is connected to a sodium hydroxide tank 11 through a pipeline. The outlet of the extraction tank 8 is connected to an anion exchange resin column 12 through a pipeline. The inlet of the anion exchange resin column 12 is respectively connected to a sodium phosphate buffer solution tank 13 and a sodium chloride solution tank 14 through pipelines. The outlet of the anion exchange resin column 12 is connected to a nanofiltration membrane device 15 through a pipeline. The outlet of the nanofiltration membrane device 15 is connected to an alcohol precipitation tank 16 through a pipeline. The inlet of the alcohol precipitation tank 16 is connected to an ethanol tank 17 through a pipeline. The outlet of the alcohol precipitation tank 16 is connected to a filter 18 through a pipeline. The outlet of the filter 18 is connected to a uridine diphosphate tank 19. By adding uridine and uridine monophosphate to the selective culture medium, high-quality bacterial cells that can improve the conversion rate of uridine diphosphate are screened out. Then, the screened high-quality bacterial cells are subjected to high-density fermentation. The obtained fermentation broth is added to the conversion tank 2 and converted together with uridine monophosphate, adenosine triphosphate, magnesium salt, and polyphosphate. The obtained conversion liquid is filtered by the ceramic membrane device 7. The clear liquid of the ceramic membrane is subjected to layered purification under the action of extractants such as ethyl acetate, diethyl ether, petroleum ether, and n-butanol. The lower-layer liquid material is taken and added to the regulation tank 10, and then sodium hydroxide is added to adjust the pH to 7-8. Then, it enters the anion exchange resin column 12. By adding a sodium phosphate buffer solution, negatively charged substances such as extracellular proteins are desorbed from the resin, and then a sodium chloride solution is added for elution until no UDP spots are detected in the effluent by rapid paper electrophoresis. The eluate enters the nanofiltration membrane device 15 for concentration, and then alcohol precipitation is carried out in the alcohol precipitation tank 16. The filter cake obtained after filtration is uridine diphosphate. The production cycle is short, the obtained uridine diphosphate product has high purity, the production process is simplified, the production cost is reduced, and uridine diphosphate has greater potential and competitiveness in large-scale production and application.

[0027] The outlet of the fermentation broth tank 1 is connected to a cell disruption tank 20 through a pipeline. The outlet of the cell disruption tank 20 is connected to the conversion tank 2 through a pipeline. By disrupting the bacterial cells in the fermentation broth, the target product can be effectively released from the inside of the cells, and at the same time, impurities can also be removed, so as to obtain a pure target product, which is convenient for subsequent conversion and reduces the enzyme dosage.

[0028] The clear liquid outlet of the ceramic membrane device 7 is connected to an ultrafiltration membrane device 21 through a pipeline, and the clear liquid outlet of the ultrafiltration membrane device 21 is connected to the extraction tank 8 through a pipeline. The ultrafiltration membrane device 21 can intercept small molecule impurities, improving the purity of uridine diphosphate.

[0029] The inlet of the alcohol reduction tank 16 is connected to a hydrochloric acid tank 22 through a pipeline, and the precipitation effect of uridine diphosphate is better.

[0030] The outlet of the filter 18 is connected to a washing tank 23, the outlet of the washing tank 23 is connected to the uridine diphosphate tank 19 through a pipeline, and the inlet of the washing tank 23 is connected to a purified water tank 24. By rinsing, impurities in the product are further removed, improving the quality of the product.

[0031] The pore size of the ceramic membrane device 7 is 50 - 250 nm, the pore size of the nanofiltration membrane device 15 is 150 - 300 Da, and the pore size of the ultrafiltration membrane device 21 is 5000 - 10000 Da, resulting in high purity of uridine diphosphate.

[0032] It should be understood that these embodiments are only used to illustrate the present utility model and not to limit the scope of the present utility model. In addition, it should be understood that after reading the content taught by the present utility model, those skilled in the art can make various changes or modifications to the present utility model, and these equivalent forms also fall within the scope defined by the appended claims of this application.

Claims

1. An apparatus for producing uridine diphosphate, characterized in that: It includes a fermentation broth tank, the outlet of the fermentation broth tank is connected to a conversion tank through a pipeline, the inlet of the conversion tank is respectively connected to a uridine monophosphate tank, an adenosine triphosphate tank, a magnesium salt tank and a polyphosphate tank through pipelines, and the outlet of the conversion tank is connected to a ceramic membrane device through a pipeline; The clear liquid outlet of the ceramic membrane device is connected to an extraction tank through a pipeline, the inlet of the extraction tank is connected to an extractant tank through a pipeline, the outlet of the extraction tank is connected to an adjustment tank through a pipeline, the inlet of the adjustment tank is connected to a sodium hydroxide tank through a pipeline, the outlet of the adjustment tank is connected to an anion exchange resin column through a pipeline, the inlet of the anion exchange resin column is respectively connected to a sodium phosphate buffer solution tank and a sodium chloride solution tank through pipelines, the outlet of the anion exchange resin column is connected to a nanofiltration membrane device through a pipeline, the outlet of the nanofiltration membrane device is connected to an alcohol precipitation tank through a pipeline, the inlet of the alcohol precipitation tank is connected to an ethanol tank through a pipeline, the outlet of the alcohol precipitation tank is connected to a filter through a pipeline, and the outlet of the filter is connected to a uridine diphosphate tank.

2. The production device of uridine diphosphate according to claim 1, characterized in that: The outlet of the fermentation broth tank is connected to a cell disruption tank through a pipeline, and the outlet of the cell disruption tank is connected to the conversion tank through a pipeline.

3. The production device of uridine diphosphate according to claim 1, characterized in that: 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 extraction tank through a pipeline.

4. The production device of uridine diphosphate according to claim 1, wherein: The inlet of the alcohol precipitation tank is connected to a hydrochloric acid tank through a pipeline.

5. The production device of uridine diphosphate according to claim 1, characterized in that: The outlet of the filter is connected to a washing tank, the outlet of the washing tank is connected to the uridine diphosphate tank through a pipeline, and the inlet of the washing tank is connected to a purified water tank.

6. The production device of uridine diphosphate according to claim 1, characterized in that: The pore size of the ceramic membrane device is 50 - 250 nm.

7. The production device of uridine diphosphate according to claim 1, characterized in that: The pore size of the nanofiltration membrane device is 150 - 300 Da.

8. The production device of uridine diphosphate according to claim 3, characterized in that: The pore size of the ultrafiltration membrane device is 5000 - 10000 Da.

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