Reaction device for producing natural folic acid

Abstract

The utility model discloses a reaction device for natural folic acid. The reaction device comprises a reaction kettle with a kettle cover, a hydrogen collecting tank, a deoxidizing and purifying device and a hydrogenase hatching tank, a discharge hole is formed in the bottom of the reaction kettle, the hydrogen collecting tank is arranged at the bottom of the reaction kettle and is communicated with a pipeline above the reaction kettle, the upper part of the hydrogen collecting tank is communicated with the deoxidizing and purifying device, the deoxidizing and purifying device is communicated with the hydrogenase hatching kettle, and the hydrogenase hatching tank is communicated with a pipeline of the reaction kettle; a valve body is arranged at the top of the hydrogen collecting tank, a drain pipe is arranged below the hydrogen collecting tank, and an opening of the drain pipe is formed above the hydrogen collecting tank; the deoxidization purification device is provided with an air inlet, a one-way valve, a microporous aeration plate and an activated carbon packed column, the microporous aeration plate and the one-way valve are arranged below the activated carbon packed column, and an eluent storage column is further arranged on the activated carbon packed column; an air compressor is arranged at the connecting part of the hydrogenase hatching tank and the deoxidization purification device; and the hydrogenase hatching tank is provided with a pressure gauge, a pressure release valve and a stirring device.

Description

Technical Field

[0001] The utility model belongs to the field of green chemical synthesis and relates to a reaction device for producing natural folic acid. Background Art

[0002] Folic acid is an essential nutritional factor for human life activities. It has multiple biochemical functions, such as promoting the maturation of young cells in the bone marrow. If humans lack folic acid, it can cause megaloblastic anemia and leukocytopenia. It is especially important for pregnant women. However, due to the very active nature of natural folic acid and its rapid degradation, it is difficult to extract and obtain. Therefore, under the conditions at that time, people could not extract and use folic acid products except for direct consumption. Generally speaking, the folic acid raw material currently used by people is a synthetic form of folic acid that does not exist in nature. After absorption, synthetic folic acid should be converted into L-5-methyltetrahydrofolate (5-MTHF) to be active. Therefore, the true face of folic acid should refer to natural folic acid, and synthetic folic acid is a substitute for natural folic acid.

[0003] At present, the synthesis method of L-5-methyl tetrahydrofolate calcium mainly uses folic acid as a raw material for reduction to obtain tetrahydrofolate. After that, the conversion of the SP2 carbon atom on the pteridine ring of dihydrofolate to the SP3 carbon atom in the reduction process will be accompanied by the generation of a chiral center. Chemical synthesis will inevitably use a resolving agent, and some waste materials will pollute the environment. The mainstream method of using biological enzymes is to use glucose and glucose dehydrogenase, but high-concentration glucose inevitably brings about a decrease in cost and product purity. Using hydrogen and hydrogenase as NADPH regeneration system, the byproduct hydrogen of the reaction can be used, and the efficiency of the reaction is higher than that of glucose / glucose dehydrogenase, but the conditions of using this method are harsher. The hydrogenase reaction of the present invention needs to be highly active in an anaerobic environment, and a process of incubation to improve activity is also required. Therefore, if there is no suitable reactor, the efficiency in the reaction will be reduced, which seriously affects subsequent production. Summary of the invention

[0004] The technical problem to be solved by the utility model is to provide a reaction device for producing naturalized folic acid with reasonable design and good sealing effect in view of the deficiencies of the prior art.

[0005] In order to achieve the above purpose, the utility model adopts the following technical solutions:

[0006] A reaction device for producing natural folic acid, characterized in that it comprises a reactor with a reactor cover, a hydrogen collecting tank, a deoxygenation purification device and a hydrogenase incubation tank, a discharge port is arranged at the bottom of the reactor, the reactor cover of the reactor is connected to a pipeline below the hydrogen collecting tank, the top of the hydrogen collecting tank is connected to the deoxygenation purification device, the hydrogen collecting tank is arranged below the reactor, the bottom of the hydrogen collecting tank is fixedly connected to a drain pipe, the drain pipe opening is arranged above the hydrogen collecting tank, the deoxygenation purification device is connected to the hydrogenase incubation reactor, the hydrogenase incubation tank is connected to the hydrogenase incubation tank, and the hydrogenase incubation tank is connected to the hydrogenase incubation tank. A connecting pipeline is provided between the hydrogenation tank and the reactor; a valve body is provided on the top of the hydrogen collection tank, and the deoxygenation purification device is provided with an air inlet, a one-way valve, a microporous aeration plate, and an activated carbon filling column. The microporous aeration plate and the one-way valve are arranged below the activated carbon filling column, and an eluent reserve column is also provided on the activated carbon filling column; an air compressor is provided at the connection between the hydrogenase incubation tank and the deoxygenation purification device, the hydrogenase incubation tank is provided with a pressure gauge, a pressure relief valve, and a feed port, and a liquid delivery pump is provided in the connecting pipeline between the hydrogenase incubation tank and the reactor.

[0007] As a further solution of the utility model, the hydrogenase incubation tank is also provided with a stirring device, a motor is fixedly installed on the top of the incubation tank, the stirring device is a stirring shaft extending from the incubation tank to the inside of the incubation tank, and the top end of the stirring shaft is fixedly connected to the output shaft of the motor.

[0008] As a further solution of the utility model, a control valve is provided on the hydrogen bottom connecting and discharging pipe, the hydrogen collecting tank is also provided with an observation device, the observation device is a viewing window of the collecting tank body, and the hydrogen collecting tank is also provided with a water inlet.

[0009] As a further solution of the utility model, the microporous aerator is specifically a microporous titanium plate or a microporous ceramic plate.

[0010] As a further solution of the utility model, the eluent storage column in the deoxygenation purification device is filled with eluent, and the eluent is a mixture of formate and hydrogen peroxide.

[0011] In the utility model, the byproduct hydrogen of the 6S-5-methyltetrahydrofolate reaction is collected through the combined arrangement of a reaction kettle, a hydrogen collection tank, a deoxygenation purification device, and a hydrogenase incubation tank, and the collected byproduct hydrogen is applied to the hydrogenase incubation reaction, further realizing the enzymatic reduction of dihydrofolate, and achieving a circular, pollution-free green chemical reaction effect.

[0012] It should be noted that the reactor, hydrogen collection tank, deoxygenation purification device, and hydrogenase incubation tank in the present invention are placed vertically. When placed vertically, the by-product hydrogen in the reactor can be autonomously transported into the hydrogen collection tank and autonomously input into the deoxygenation purification device. No material conveying device is required and energy consumption is consumed, thereby realizing continuous production.

[0013] As a preferred technical solution of the utility model, the top of the reactor is also provided with an air inlet, and the air inlet is used for inputting inert gas.

[0014] As a preferred technical solution of the utility model, a gas flow meter is also arranged on the connecting pipeline between the hydrogen collection tank and the deoxygenation purification device, and further the gas flow meter is a velocity flow meter or a volume flow meter.

[0015] It should be noted that the inert gas in the present invention can be nitrogen, argon, etc., and those skilled in the art can make adaptive adjustments according to actual conditions.

[0016] It should be noted that the present invention does not impose any special restrictions on the specific dimensions, feeding methods, etc. of the reactor, hydrogen collection tank, deoxygenation purification device, hydrogenase incubation tank and their facilities, and those skilled in the art can make adaptive adjustments according to actual conditions.

[0017] In the utility model, an inert gas argon is introduced into the reactor, and phosphoric acid is added after reducing folic acid to generate zinc phosphate and remove unreacted zinc powder to generate hydrogen. Since the density of hydrogen is much smaller than that of argon, the hydrogen will be transported to the pipeline above the reactor and enter the hydrogen collection tank. The hydrogen collection tank is filled with water, and after hydrogen enters from the bottom of the hydrogen collection tank, the water in the tank will be automatically discharged from the drain pipe. The valve above the hydrogen collection tank is opened, and water is input. The hydrogen is transported to the deoxygenation purification device, dispersed into microbubbles by a microporous aerator and then contacted with activated carbon, and then passed through an eluent, and the oxygen in the hydrogen will react quickly with the eluent, thereby achieving the purpose of deoxygenation. The oxygen-free hydrogen is incubated under high pressure in the hydrogenase incubation tank to improve the enzyme activity, transported to the reactor, and hydrogen is continuously passed to the reactor to achieve the synthesis of tetrahydrofolate.

[0018] Compared with the prior art, the beneficial effects of the utility model are:

[0019] In the utility model, by-product hydrogen in the folic acid reduction reaction is collected and processed through the combined design of a reactor, a hydrogen collection tank, a deoxygenation purification device, and a hydrogenase incubation tank, the hydrogen is purified and incubated together with the hydrogenase, the incubated enzyme liquid is further transported to the reactor, dihydrofolate is further reduced to tetrahydrofolate, the hydrogenase liquid does not contact the outside air, the hydrogenase activity is high after high-pressure incubation, and the reaction is efficient; continuous production is achieved, the reaction effect is efficient, and the requirements of green chemistry with circulation and pollution-free are met. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The present invention is a schematic structural diagram of a reaction device for producing naturalized folic acid provided in a specific embodiment of the present invention.

[0021] In the figure: 1-reactor body, 2-reactor cover, 3-stirring shaft, 4-inert gas input port, 5-hydrogen collecting tank, 6-hydrogen collecting tank observation window, 7-water inlet, 8-drain pipe, 9-check valve, 10-microporous aeration plate, 11-activated carbon filling column, 12-eluent reserve column, 13-deoxygenation purification device, 14-air compressor, 15-pressure gauge, 16-hydrogenase incubation tank, 17-hydrogenase incubation tank observation window, 18-liquid delivery pump, 19-valve body, 20-discharge port, 21-feed port, 22-pressure relief valve. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments.

[0023] In the description of the present invention, it should be understood that the terms "upper", "lower", "front", "back", "left", "right", "top", "bottom", "inside", "outside", etc., indicating directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation on the present invention.

[0024] like Figure 1As shown, in order to realize the recovery and utilization of byproduct hydrogen in the synthesis of 6S-5-methyltetrahydrofolate. The utility model proposes a reaction device for producing natural folic acid, comprising a reactor body 1 with a reactor cover 2, a hydrogen collection tank 5, a deoxygenation purification device 13, and a hydrogenase incubation tank 16. An inert gas input port 4 is arranged on the reactor cover 2, a stirring structure 3 is arranged in the reactor, and a discharge port 20 is arranged at the bottom of the reactor. The reactor is designed as a closed structure to prevent air from entering and causing adverse effects such as oxidation. A hydrogen collecting tank 5 is arranged at the bottom of the reactor body, and the bottom of the hydrogen collecting tank 5 is connected to a pipeline above the reactor 2, and the pipeline is provided with a valve body 19. A water inlet 7 is provided above the hydrogen collecting tank 5, and a drain pipe 8 is provided below the hydrogen collecting tank 5. The opening of the drain pipe 8 is arranged above the hydrogen collecting tank 5, and the top of the hydrogen collecting tank is connected to a deoxygenation purification device 13, and the deoxygenation purification device is provided with a one-way valve 9, a microporous aeration plate 10, an activated carbon filling column 11, and an eluent reserve column 12. The one-way valve 9 and the microporous aeration plate 10 are arranged below the activated carbon filling column 11, and an eluent reserve liquid is also provided above the activated carbon filling column 11; the top of the deoxygenation purification device 13 is connected to a hydrogenase incubation tank 16 pipeline, and the pipeline is provided with an air compressor 14, and the hydrogenase incubation tank 16 is also provided with a pressure gauge 15 and an observation window 17; the bottom of the hydrogenase incubation tank 16 is connected to the reactor 1 pipeline, and a liquid delivery pump is also provided on the pipeline.

[0025] Example

[0026] Open the water inlet 7 until the hydrogen collection tank is full of water, and then close the water inlet 7. Add 50kg of folic acid (96% content) into the reactor 1, then add 150kg of sodium hydroxide and 280L of water, stir until the folic acid is completely dissolved, then add 25kg of zinc powder, input argon gas at the inert gas input port 4, add phosphoric acid after stirring under the protection of inert gas. Open the valve body 19. Since the density of the reaction byproduct hydrogen is much smaller than that of argon gas, most of the hydrogen collected in the pipeline above the reactor will be transported to the hydrogen collection tank 5. The gas entering the hydrogen collection tank 5 will compress the water in the tank, so that the water is discharged from the drain port 8. Open the one-way valve 9, the water inlet 7, the hydrogen enters the deoxygenation purification device 13, the hydrogen passes through the microporous aeration plate 10, the oxygen-containing hydrogen passes through the microporous aeration plate 10 to disperse into microbubbles, and then contacts the activated carbon in the activated carbon filling column 11, and then passes through the eluent reserve column 12. The eluent contains formate and hydrogen peroxide, which can react quickly with oxygen to achieve the purpose of deoxygenation, and the activated carbon can also remove other impurities in the gas to obtain high-purity hydrogen. Under argon protection, take 5g of hydrogenase (p. furiosus hydrogenase I, purity 30%) (enzyme activity is about 270000U / g), dissolve in 5L of 100mM Tris hydrochloride buffer, and add 0.8g of sodium dithionite. Transfer to the hydrogenase incubation tank 16, compress the hydrogen and pass it into the hydrogenase buffer for 2 hours for incubation, the pressure is 1.3bar. Under the protection of argon, add 28L of dihydrofolate reductase enzyme solution (enzyme activity 65000U / L), 0.6Kg of coenzyme NADP+ to the dihydrofolate reactor 1, and add Tris hydrochloride buffer to a concentration of 100mM. Draw the incubated hydrogenase buffer solution and hydrogen from the hydrogenase incubation tank into the reactor, and stir the reactor for 3 hours. Use hydrogen and soluble hydrogenase as the NADPH regeneration system, use dihydrofolate reductase to stereoselectively reduce dihydrofolate to obtain (6S)-tetrahydrofolate; use formic acid process to convert (6S)-tetrahydrofolate into (6S)-5-methyltetrahydrofolate, and separate (6S)-5-methyltetrahydrofolate after salt formation.

[0027] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes within the technical scope disclosed by the present invention according to the technical scheme and the utility model concept of the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A reaction device for producing naturalized folic acid, characterized in that: The invention comprises a reactor with a reactor cover and a stirring device, a hydrogen collecting tank, a dehydrogenation purification device and a hydrogenase incubation tank; a discharge port is arranged at the bottom of the reactor, the reactor cover of the reactor is connected with a pipeline below the hydrogen collecting tank, the pipeline is provided with a valve body, the top of the hydrogen collecting tank is connected with the deoxygenation purification device, the hydrogen collecting tank is arranged below the reactor, the bottom of the bottom of the hydrogen collecting tank is fixedly connected with a drain pipe, the drain pipe opening is arranged above the hydrogen collecting tank, the deoxygenation purification device pipeline is connected with the hydrogenase incubation tank, the hydrogenase incubation tank The tank and the reactor are provided with a connecting pipeline; a valve body is provided on the top of the hydrogen collection tank, and the deoxygenation purification device is provided with a one-way valve, a microporous aeration plate, and an activated carbon filling column. The microporous aeration plate and the one-way valve are arranged below the activated carbon filling column, and an eluent reserve column is also arranged on the activated carbon filling column; an air compressor is provided at the connection between the hydrogenase incubation tank and the deoxygenation purification device, the hydrogenase incubation tank is provided with a pressure gauge, a pressure relief valve, and a closed feed port, and a liquid delivery pump is arranged in the connecting pipeline between the hydrogenase incubation tank and the reactor.

2. A reaction device for producing naturalized folic acid according to claim 1, characterized in that: The hydrogenase incubation tank is also provided with a stirring device. A motor is fixedly installed on the top of the incubation tank. The stirring device is a stirring shaft extending from the incubation tank to the inside of the incubation tank. The top end of the stirring shaft is fixedly connected to the output shaft of the motor.

3. A reaction device for producing naturalized folic acid according to claim 1, characterized in that: A control valve is provided on the drainage pipe connected to the bottom of the hydrogen collection tank. The hydrogen collection tank is also provided with an observation device, which is a viewing window of the collection tank body. The hydrogen collection tank is also provided with a water inlet.

4. A reaction device for producing naturalized folic acid according to claim 1, characterized in that: The microporous aerator in the deoxygenation and purification device is a microporous titanium plate or a microporous ceramic plate.

5. The reaction device for producing naturalized folic acid according to claim 1, characterized in that: The top of the reactor is provided with an air inlet, and the air inlet is used for inputting inert gas.

6. A reaction device for producing naturalized folic acid according to claim 1, characterized in that: A gas flow meter is also arranged on the connecting pipeline between the hydrogen collection tank and the deoxygenation purification device, and further the gas flow meter is a velocity flow meter or a volume flow meter.

Images