Method for producing vitamin B12 by using ferricyanide complex
Through the filtration system that modifies sodium alginate and intermediate 1, the problem of flocculants and filter aids in the production of vitamin B12 is solved, and efficient filtration and recycling are achieved, reducing production costs.
Patent Information
- Application Number
- CN202510554305.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-29
- Publication Date
- 2025-07-11
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
In the prior art, the flocculant and filter aids used for filtration and purification of the solution after the conversion in the production process of vitamin B12 cannot be recycled, resulting in waste of resources.
The filtration system of modified sodium alginate combined with intermediate 1 was used for filtration and purification. Intermediate 1 was formed by reacting zirconium tetrachloride and 4-amino-3-mercaptopyridine in N,N-dimethylformamide solution. The modified sodium alginate formed a highly efficient adsorbent by combining with intermediate 1 to adsorb impurities during the fermentation of vitamin B12.
It realizes efficient filtration performance and recyclable use, reduces production costs, improves filtration efficiency, and maintains good adsorption performance after multiple uses.
Smart Images
Figure CN120289548A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of vitamin B12 production, and particularly relates to a method for producing vitamin B12 using ferrocyanide complexes. Background Art
[0002] Vitamin B12, also known as cyanocobalamin, is one of the essential vitamins for the human body. Vitamin B12 is an important water-soluble vitamin that participates in various metabolic processes in the human body, including the production of red blood cells, the synthesis of DNA, and nerve conduction. The synthesis of vitamin B12 usually requires multiple steps and reactions, including: (1) the synthesis of cobalamin: First, the precursor compound of cobalamin is synthesized through microbial fermentation or chemical synthesis methods; (2) the conversion of cobalamin: The precursor compound of cobalamin is converted into vitamin B12. This process usually needs to be carried out under specific conditions, such as controlling the reaction temperature, pH value, and reaction time, etc.; (3) the purification of vitamin B12: The converted vitamin B12 is separated and purified to obtain a high-purity vitamin B12 product.
[0003] CN116284191A discloses a method for preparing vitamin B12. During the production of vitamin B12, a flocculant and a filter aid are added to the solution after the conversion is completed to filter and purify the solution after the conversion. The flocculant and filter aid in the present invention cannot be recycled, resulting in a great waste of resources. Summary of the Invention
[0004] Based on the deficiencies of the prior art, the present invention discloses a method for producing vitamin B12 using ferrocyanide complexes, and provides a recyclable filtration system capable of filtering and purifying the solution after the conversion is completed, specifically including the following content.
[0005] The present invention provides a method for producing vitamin B12 using ferrocyanide complexes, including pretreating the fermentation broth to obtain a pretreated solution, converting the pretreated solution to obtain a converted solution, and post-treating the converted solution to obtain a finished product solution. The post-treatment is to filter and purify the converted solution through a filtration system to obtain a finished product solution.
[0006] Preferably, the filtration system is prepared by mixing modified sodium alginate and intermediate 1 in an alkaline solution and reacting after stirring.
[0007] Preferably, the modified sodium alginate is prepared by introducing sodium alginate, glycerol ether, and water into a reaction kettle, stirring and mixing evenly, and then reacting.
[0008] Preferably, the intermediate 1 is prepared by putting zirconium tetrachloride and 4-amino-3-mercaptopyridine into a reaction furnace, adding N,N-dimethylformamide as a solution, ultrasonically mixing and reacting evenly, adding an acid solution, and then reacting in a constant-temperature oven.
[0009] Preferably, the preparation method of the filtration system is as follows: Step 1: Put zirconium tetrachloride and 4-amino-3-mercaptopyridine into a reaction furnace, add N,N-dimethylformamide, ultrasonically mix evenly, add an acid solution, and then continue to ultrasonically react. Then transfer the solution in the reaction furnace to a constant-temperature oven through an acid-resistant pipeline, heat and react, and wait to cool to room temperature under natural cooling conditions. Then carry out centrifugal separation in a centrifuge, wash with N,N-dimethylformamide, then wash with deionized water. Finally, put the washed solid powder into a box-type oven for drying to obtain intermediate 1.
[0010] Step 2: Add sodium alginate and glycerol ether into a reaction kettle, add water as a solvent for dissolution, stir and mix evenly, raise the temperature to make the solution in the reaction kettle react, and after the reaction is completed, obtain modified sodium alginate.
[0011] Step 3: Add the modified sodium alginate and intermediate 1 into an alkaline solution, react for a period of time, and generate a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.
[0012] Preferably, in Step 1, weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:100-200:20-30. Add the zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, ultrasonically react at a power of 150-200 w for 3-5 min, then transfer the solid powder in the reaction furnace to a constant-temperature oven, adjust the temperature to 1100-1200 °C, continuously heat for 24-48 h, and then naturally cool to 25-30 °C. Then transfer the solid powder in the constant-temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, and then wash the solid powder with N,N-dimethylformamide with a mass 50-100 times that of the solid powder. Repeat the washing operation 3 times, and then wash the solid powder with deionized water with a mass 50-100 times that of the solid powder. Repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying, set the drying temperature to 40-50 °C, set the drying time to 1-2 h, and obtain intermediate 1 after drying.
[0013] Preferably, in Step 2, sodium alginate and glycerol ether are weighed at a mass ratio of 1:2, added to a reaction vessel, stirred evenly at a rate of 150 - 200 r / min for 30 - 60 min, then placed in a water bath for heating. The water bath temperature is 80 - 90 °C, and the water bath heating time is 6 - 8 h. While heating, the liquid in the reaction vessel is stirred at a rate of 300 - 450 r / min for 15 - 30 min. After the reaction is completed, modified sodium alginate is obtained.
[0014] Preferably, in Step 2, the glycerol ether is at least one of 1,2 - cyclohexanediol diglycidyl ether, furfuryl glycidyl ether, polyethylene glycol diglycidyl ether, and neopentyl glycol glycidyl ether.
[0015] Preferably, in Step 2, the reaction process is as follows:
[0016] Among them, the glycerol ether in the reaction process is 1,2 - cyclohexanediol diglycidyl ether.
[0017] Preferably, in Step 3, the modified sodium alginate and Intermediate 1 are mixed at a mass ratio of 8 - 10:1 to obtain a mixture. A 0.05 mol / L sodium hydroxide solution with a mass 50 - 100 times that of the mixture is added as a solvent to dissolve the mixture. The temperature is raised to 50 - 60 °C and heated for 1 - 2 h to react and generate a filtration system for adsorbing impurities in the conversion liquid during the fermentation process of vitamin B12.
[0018] Compared with the prior art, the present invention has the following beneficial effects: (1) In the post - treatment step of the conversion liquid of vitamin B12, the present invention uses a filtration system as an adsorbent to replace polyaluminum chloride to adsorb and filter impurities in the conversion liquid of vitamin B12, with high filtration performance and recyclable performance.
[0019] (2) The present invention generates a modified sodium alginate by mixing and reacting sodium alginate and glycerol ether. The ether bond of the modified sodium alginate has an excellent adsorption effect on metal ions and can be used for the post - treatment of the conversion liquid of vitamin B12, with high - efficiency filtration performance. Intermediate 1 generated by mixing and reacting zirconium tetrachloride powder and 4 - amino - 3 - mercaptopyridine is a porous structure with high adsorption efficiency. The filtration system of the present invention is generated by mixing and reacting Intermediate 1 and modified sodium alginate. Among them, the amino group of Intermediate 1 combines with the carboxyl group of the modified sodium alginate to form an amide bond with high stability and good binding performance, and the adsorption efficiency remains unchanged after multiple uses, with good recyclable performance.
[0020] (3) In the filtration system described in a method for producing vitamin B12 using ferrocyanide complexes of the present invention, Intermediate 1 can interact after binding with modified sodium alginate, improving the filtration efficiency. The filtration efficiency of the control group is only 94%, indicating that the filtration system described in a method for producing vitamin B12 using ferrocyanide complexes of the present invention has high filtration efficiency and good filtration performance when filtering and adsorbing the solution after the conversion of vitamin B12 is completed. The filtration system described in a method for producing vitamin B12 using ferrocyanide complexes of the present invention still has good filtration efficiency during the fifth filtration, indicating that the filtration system utilized in the adsorption and filtration treatment of the solution after the conversion of vitamin B12 is completed in a method for producing vitamin B12 using ferrocyanide complexes of the present invention has the performance of being recyclable, saving production costs, and is worthy of promotion. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 It is a flow chart of a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12 described in the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS
[0022] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts shall fall within the protection scope of the present invention.
[0023] Example 1 This example provides a method for producing vitamin B12 using ferrocyanide complexes (1) Mix the solution after the conversion of vitamin B12 is completed with the filtration system at a mass ratio of 1:500, add it to the post-treatment container, stir at a rate of 100 r / min for 60 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished vitamin B12 solution.
[0024] (2) Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the next round of filtration operation of the solution after the conversion of vitamin B12 is completed.
[0025] Among them, the preparation steps of the filtration system are as follows: S1. Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:200:20. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 150 w for 5 min, then transfer the solid powder in the reaction furnace to a constant-temperature oven, adjust the temperature to 1200 °C, continuously heat for 48 h, then naturally cool to 30 °C. Then transfer the solid powder in the constant-temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, and then wash the solid powder with N,N-dimethylformamide with a mass 100 times that of the solid powder. Repeat the washing operation 3 times, and then wash the solid powder with deionized water with a mass 100 times that of the solid powder. Repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying. Set the drying temperature to 50 °C and the drying time to 2 h. After drying, intermediate 1 is obtained.
[0026] S2. Weigh sodium alginate and glycerol ether according to a mass ratio of 1:2. Add sodium alginate and glycerol ether into the reaction container, stir evenly at a rate of 200 r / min for 60 min, then put it into a water bath for heating. The water bath temperature is 80 °C and the water bath heating time is 6 h. While heating, stir the liquid in the reaction container at a rate of 450 r / min for 30 min. After the reaction is completed, modified sodium alginate is obtained.
[0027] S3. Mix modified sodium alginate and intermediate 1 according to a mass ratio of 10:1 to obtain a mixture. Add 0.05 mol / L sodium hydroxide solution with a mass 100 times that of the mixture as a solvent to dissolve the mixture, raise the temperature to 60 °C, and heat for 2 h. A filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12 is generated by the reaction.
[0028] Example 2 This example provides a method for producing vitamin B12 using ferrocyanide complex (1) Mix the solution after the conversion of vitamin B12 and the filtration system according to a mass ratio of 1:500, add them into a post-treatment container, stir at a rate of 50 r / min for 60 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished product liquid of vitamin B12.
[0029] (2) Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the next round of filtration operation of the solution after the conversion of vitamin B12.
[0030] Among them, the preparation steps of the filtration system are as follows: S1. Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:100:20. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 200 w for 5 min, then transfer the solid powder in the reaction furnace to a constant-temperature oven, adjust the temperature to 1100 °C, continuously heat for 24 h, then naturally cool to 25 °C. Then transfer the solid powder in the constant-temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, and then wash the solid powder with N,N-dimethylformamide with a mass 50 times that of the solid powder. Repeat the washing operation 3 times, and then wash the solid powder with deionized water with a mass 50 times that of the solid powder. Repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying. Set the drying temperature to 40 °C and the drying time to 1 h. After drying, intermediate 1 is obtained.
[0031] S2. Weigh sodium alginate and glycerol ether according to a mass ratio of 1:2. Add sodium alginate and glycerol ether into the reaction vessel, stir evenly at a rate of 150 r / min for 30 min, then put it into a water bath for heating. The water bath temperature is 90 °C and the water bath heating time is 6 h. While heating, stir the liquid in the reaction vessel at a rate of 450 r / min for 15 min. After the reaction is completed, modified sodium alginate is obtained.
[0032] S3. Mix the modified sodium alginate and intermediate 1 according to a mass ratio of 8:1 to obtain a mixture. Add a 0.05 mol / L sodium hydroxide solution with a mass 50 times that of the mixture as a solvent to dissolve the mixture, raise the temperature to 50 °C, and heat for 2 h. A filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12 is generated by the reaction.
[0033] Example 3 This example provides a method for producing vitamin B12 using iron cyanide complex (1) Mix the solution after the conversion of vitamin B12 and the filtration system according to a mass ratio of 1:500, add them into the post-treatment container, stir at a rate of 70 r / min for 45 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished product liquid of vitamin B12.
[0034] (2) Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the filtration operation of the solution after the conversion of vitamin B12 in the next round.
[0035] Among them, the preparation steps of the filtration system are as follows: S1. Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:150:25. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 200 w for 5 min, then transfer the solid powder in the reaction furnace to a constant-temperature oven, adjust the temperature to 1100 °C, continuously heat for 48 h, then naturally cool to 30 °C, then transfer the solid powder in the constant-temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, then wash the solid powder with N,N-dimethylformamide with a mass 75 times that of the solid powder, repeat the washing operation 3 times, then wash the solid powder with deionized water with a mass 75 times that of the solid powder, repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying, set the drying temperature to 40 - 50 °C, set the drying time to 1 - 2 h, and obtain Intermediate 1 after drying.
[0036] S2. Weigh sodium alginate and glycerol ether according to a mass ratio of 1:2. Add sodium alginate and glycerol ether into the reaction vessel, stir evenly at a rate of 150 - 200 r / min, with the stirring time being 30 - 60 min, then put it into a water bath for heating, the water bath temperature is 80 - 90 °C, the water bath heating time is 6 - 8 h, and stir the liquid in the reaction vessel at a rate of 300 - 450 r / min for 15 - 30 min while heating. After the reaction is completed, modified sodium alginate is obtained.
[0037] S3. Mix modified sodium alginate and Intermediate 1 according to a mass ratio of 8 - 10:1 to obtain a mixture. Add 0.05 mol / L sodium hydroxide solution with a mass 50 - 100 times that of the mixture as a solvent to dissolve the mixture, raise the temperature to 50 - 60 °C, heat for 1 - 2 h, and react to generate a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.
[0038] Example 4 This example provides a method for producing vitamin B12 using iron cyanide complex (1) Mix the solution after the completion of vitamin B12 conversion and the filtration system according to a mass ratio of 1:500, add them into a post-treatment container, stir at a rate of 100 r / min for 60 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished product solution of vitamin B12.
[0039] (2) Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the filtration operation of the solution after the completion of the next round of vitamin B12 conversion.
[0040] Among them, the preparation steps of the filtration system are as follows: S1. Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:200:25. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 200 w for 4 min, then move the solid powder in the reaction furnace to a constant temperature oven, adjust the temperature to 1100 °C, continuously heat for 36 h, then naturally cool to 30 °C. Then transfer the solid powder in the constant temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, and then wash the solid powder with N,N-dimethylformamide with a mass 100 times that of the solid powder. Repeat the washing operation 3 times, and then wash the solid powder with deionized water with a mass 100 times that of the solid powder. Repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying. Set the drying temperature to 40 °C and the drying time to 2 h. After drying, intermediate 1 is obtained.
[0041] S2. Weigh sodium alginate and glycerol ether according to a mass ratio of 1:2. Add sodium alginate and glycerol ether into the reaction vessel, stir evenly at a rate of 200 r / min, and the stirring time is 60 min. Then put it into a water bath for heating. The water bath temperature is 90 °C and the water bath heating time is 8 h. While heating, stir the liquid in the reaction vessel at a rate of 300 r / min for 15 min. After the reaction is completed, modified sodium alginate is obtained.
[0042] S3. Mix the modified sodium alginate and intermediate 1 according to a mass ratio of 10:1 to obtain a mixture. Add 0.05 mol / L sodium hydroxide solution with a mass 100 times that of the mixture as a solvent to dissolve the mixture. Raise the temperature to 50 °C and heat for 2 h to react to generate a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.
[0043] Example 5 This example provides a method for producing vitamin B12 using iron cyanide complex (1) Mix the solution after the conversion of vitamin B12 and the filtration system according to a mass ratio of 1:500, add them into the post-treatment container, stir at a rate of 100 r / min for 30 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished product liquid of vitamin B12.
[0044] (2) Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the filtration operation of the solution after the completion of the next round of vitamin B12 conversion.
[0045] Among them, the preparation steps of the filtration system are as follows: S1. Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:150:25. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 150 w for 3 min, then move the solid powder in the reaction furnace to a constant temperature oven, adjust the temperature to 1200 °C, continuously heat for 48 h, then naturally cool to 30 °C, then transfer the solid powder in the constant temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, and then wash the solid powder with N,N-dimethylformamide with a mass 50 times that of the solid powder, repeat the washing operation 3 times, and then wash the solid powder with deionized water with a mass 50 times that of the solid powder, repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying, set the drying temperature to 40 °C, set the drying time to 2 h, and obtain intermediate 1 after drying.
[0046] S2. Weigh sodium alginate and glycerol ether according to a mass ratio of 1:2. Add sodium alginate and glycerol ether into the reaction container, stir evenly at a rate of 150 r / min, stir for 30 min, then put it into a water bath for heating, the water bath temperature is 80 °C, the water bath heating time is 7 h, and stir the liquid in the reaction container at a rate of 450 r / min for 15 min while heating. After the reaction is completed, modified sodium alginate is obtained.
[0047] S3. Mix the modified sodium alginate and intermediate 1 according to a mass ratio of 10:1 to obtain a mixture, add 0.05 mol / L sodium hydroxide solution with a mass 100 times that of the mixture as a solvent to dissolve the mixture, raise the temperature to 60 °C, heat for 1 h, and react to generate a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.
[0048] Example 6 This example provides a method for producing vitamin B12 using iron cyanide complex (1) Mix the solution after the completion of vitamin B12 conversion and the filtration system according to a mass ratio of 1:500, add them into the post-treatment container, stir at a rate of 75 r / min for 30 min, stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished vitamin B12 solution.
[0049] (2) Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the filtration operation of the solution after the completion of the next round of vitamin B12 conversion.
[0050] Among them, the preparation steps of the filtration system are as follows: S1. Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:150:20. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 150 w for 4 min, then move the solid powder in the reaction furnace to a constant temperature oven, adjust the temperature to 1100 °C, continuously heat for 24 h, then naturally cool to 30 °C, and then transfer the solid powder in the constant temperature oven to a sedimentation centrifuge. Centrifuge the solid powder with the sedimentation centrifuge, and then wash the solid powder with N,N-dimethylformamide with a mass 50 times that of the solid powder. Repeat the washing operation 3 times, and then wash the solid powder with deionized water with a mass 50 times that of the solid powder. Repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying. Set the drying temperature to 45 °C and the drying time to 1.5 h. After drying, intermediate 1 is obtained.
[0051] S2. Weigh sodium alginate and glycerol ether according to a mass ratio of 1:2. Add sodium alginate and glycerol ether into the reaction container, stir evenly at a rate of 200 r / min for 45 min, and then place it in a water bath for heating. The water bath temperature is 80 °C and the water bath heating time is 7 h. While heating, stir the liquid in the reaction container at a rate of 300 - 450 r / min for 20 min. After the reaction is completed, modified sodium alginate is obtained.
[0052] S3. Mix the modified sodium alginate and intermediate 1 according to a mass ratio of 9:1 to obtain a mixture. Add 0.05 mol / L sodium hydroxide solution with a mass 75 times that of the mixture as a solvent to dissolve the mixture, raise the temperature to 55 °C, and heat for 1.5 h. The reaction generates a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.
[0053] Comparative Example 1 This comparative example provides a method for producing vitamin B12 using iron cyanide complex The difference between this comparative example and Example 1 is that intermediate 1 is not added in the preparation steps of the filtration system in this comparative example.
[0054] (1)Mix the solution after the conversion of vitamin B12 with the filtration system at a mass ratio of 1:500, add it to the post-treatment container, stir at a rate of 100 r / min for 60 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished vitamin B12 solution.
[0055] (2)Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the filtration operation of the solution after the conversion of vitamin B12 in the next round.
[0056] Among them, the preparation steps of the filtration system are as follows: Weigh sodium alginate and glycerol ether at a mass ratio of 1:2, add sodium alginate and glycerol ether to the reaction container, stir evenly at a rate of 200 r / min, the stirring time is 60 min, then put it into a water bath for heating, the water bath temperature is 80 °C, the water bath heating time is 6 h, and stir the liquid in the reaction container at a rate of 450 r / min for 30 min while heating. After the reaction is completed, the modified sodium alginate is obtained, which is the filtration system.
[0057] Comparative Example 2 This comparative example provides a method for producing vitamin B12 using iron cyanide complex The difference between this comparative example and Example 1 is that the modified sodium alginate is not added in the preparation steps of the filtration system in this comparative example.
[0058] (1)Mix the solution after the conversion of vitamin B12 with the filtration system at a mass ratio of 1:500, add it to the post-treatment container, stir at a rate of 100 r / min for 60 min, let it stand for 15 min, and filter out the supernatant in the post-treatment container, which is the finished vitamin B12 solution.
[0059] (2)Wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, and then wash and dry it with deionized water, and it can be used for the filtration operation of the solution after the conversion of vitamin B12 in the next round.
[0060] Among them, the preparation steps of the filtration system are as follows: Weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:200:20. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 150 w for 5 min, then transfer the solid powder in the reaction furnace to a constant-temperature oven, adjust the temperature to 1200 °C, continuously heat for 48 h, then naturally cool to 30 °C. Then transfer the solid powder in the constant-temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge. After that, wash the solid powder with N,N-dimethylformamide with a mass 100 times that of the solid powder, repeat the washing operation 3 times, then wash the solid powder with deionized water with a mass 100 times that of the solid powder, repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying, set the drying temperature to 50 °C, set the drying time to 2 h. After drying, intermediate 1 is obtained, which is the filtration system.
[0061] Detection Example 1 This detection example is used to detect the recycling performance of the filtration system described in a method for producing vitamin B12 using iron cyanide complex in Examples 1-6 of the present invention. After each adsorption filtration of the solution after the completion of vitamin B12 conversion in Examples 1-6, wash the remaining flocculent filtration system in the post-treatment container with 0.1 mol / L dilute hydrochloric acid, then wash and dry with deionized water, and use it for the filtration operation of the solution after the completion of the next round of vitamin B12 conversion. Repeat the above steps 4 times. After each adsorption is completed, perform drying and weighing, with the weight efficiency of the first adsorption in each group being 100%.
[0062] Table 1 Recycling Performance Table
[0063] As can be seen from Table 1, the filtration system described in a method for producing vitamin B12 using iron cyanide complex in Examples 1-6 still has good filtration efficiency during the 5th filtration, indicating that the filtration system utilized in the adsorption filtration treatment of the solution after the completion of vitamin B12 conversion in the method for producing vitamin B12 using iron cyanide complex in the present invention has good recyclability.
[0064] Detection Example 2 The present invention is used to detect the filtration performance of the filtration system described in a method for producing vitamin B12 using iron cyanide complex in the present invention. 8 experimental groups and 1 control group were set up. Before and after the adsorption filtration of the solution after the conversion of vitamin B12 was completed, the mass change after the adsorbent was dried was measured. In experimental groups 1-8, the same mass of the filtration systems prepared in Examples 1-6 and Comparative Examples 1-2 was added as the adsorbent, and the same mass of polyaluminum chloride was added as the adsorbent in the control group. The weight efficiency of adsorption in Example 1 was taken as 100%.
[0065] Table 2 Filtration performance table
[0066] As can be seen from Table 2, the filtration performance of the examples was significantly improved compared with that of the comparative examples, indicating that in the filtration system described in the method for producing vitamin B12 using ferrocyanide complexes of the present invention, intermediate 1 can interact with modified sodium alginate after binding, improving the filtration efficiency; the filtration efficiency of the control group was only 93.8%, indicating that the filtration system described in the method for producing vitamin B12 using ferrocyanide complexes of the present invention has high filtration efficiency and good filtration performance when filtering and adsorbing the solution after the conversion of vitamin B12 is completed.
[0067] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention. All equivalent changes and improvements made in accordance with the scope of the present invention application shall still fall within the scope covered by the patent of the present invention.
Claims
1. A method for producing vitamin B12 using ferrocyanide complex, comprising pretreating a fermentation broth to obtain a pretreated solution, converting the pretreated solution to obtain a converted solution, and post-treating the converted solution to obtain a finished product solution, characterized in that, The post-treatment is to filter and purify the conversion liquid through a filtration system to obtain the finished liquid.
2. A method for producing vitamin B12 using ferrocyanide complex according to claim 1, characterized in that, The filtration system is prepared by mixing modified sodium alginate and intermediate 1 in an alkaline solution, reacting after stirring.
3. A method for producing vitamin B12 using a ferrocyanide complex according to claim 2, characterized in that, The modified sodium alginate is prepared by feeding sodium alginate, glycerol ether and water into a reaction kettle, stirring and mixing evenly and then reacting.
4. A method for producing vitamin B12 using a ferrocyanide complex according to claim 2, characterized in that, The intermediate 1 is prepared by putting zirconium tetrachloride and 4-amino-3-mercaptopyridine into a reaction furnace, adding N,N-dimethylformamide as a solution, ultrasonically mixing and reacting evenly, adding an acid solution, and then reacting in a constant-temperature oven.
5. A method for producing vitamin B12 using a ferrocyanide complex according to claim 1, characterized in that, The preparation method of the filtration system is as follows: Step 1: Put zirconium tetrachloride and 4-amino-3-mercaptopyridine into a reaction furnace, add N,N-dimethylformamide, ultrasonically mix evenly, add an acid solution, continue ultrasonic reaction, then transfer the solution in the reaction furnace to a constant-temperature oven through an acid-resistant pipeline, heat and react, wait to cool to room temperature under natural cooling conditions, perform centrifugal separation in a centrifuge, wash with N,N-dimethylformamide, then wash with deionized water, and finally put the washed solid powder into a box-type oven for drying to obtain intermediate 1; Step 2: Add sodium alginate and glycerol ether into a reaction kettle, add water as a solvent for dissolution, stir and mix evenly, raise the temperature to make the solution in the reaction kettle react, and after the reaction is completed, obtain modified sodium alginate; Step 3: Add the modified sodium alginate and intermediate 1 into an alkaline solution, react for a period of time to generate a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.
6. A method for producing vitamin B12 using ferrocyanide complex according to claim 5, characterized in that, In Step 1, weigh zirconium tetrachloride powder, 4-amino-3-mercaptopyridine, N,N-dimethylformamide, and 10 mol / L concentrated hydrochloric acid according to a mass ratio of 1:1:100 - 200:20 - 30. Add zirconium tetrachloride powder and 4-amino-3-mercaptopyridine into the reaction furnace, perform ultrasonic treatment at a power of 150 - 200 w for 3 - 5 min, then transfer the solid powder in the reaction furnace to a constant-temperature oven, adjust the temperature to 1100 - 1200 °C, continuously heat for 24 - 48 h, then naturally cool to 25 - 30 °C, then transfer the solid powder in the constant-temperature oven to a sedimentation centrifuge, centrifuge the solid powder with the sedimentation centrifuge, then wash the solid powder with N,N-dimethylformamide with a mass 50 - 100 times that of the solid powder, repeat the washing operation 3 times, then wash the solid powder with deionized water with a mass 50 - 100 times that of the solid powder, repeat the washing operation 3 times. After the washing operation is completed, put the washed solid powder into a box-type oven for drying, set the drying temperature to 40 - 50 °C, set the drying time to 1 - 2 h, and obtain intermediate 1 after drying.
7. A method for producing vitamin B12 using ferrocyanide complex according to claim 5, characterized in that, In Step 2, sodium alginate and glycerol ether are weighed at a mass ratio of 1:2, added to a reaction vessel, stirred evenly at a rate of 150-200 r / min for 30-60 min, then placed in a water bath for heating. The water bath temperature is 80-90 °C, and the water bath heating time is 6-8 h. While heating, the liquid in the reaction vessel is stirred at a rate of 300-450 r / min for 15-30 min. After the reaction is completed, modified sodium alginate is obtained.
8. A method for producing vitamin B12 using a ferrocyanide complex according to claim 7, characterized in that, In Step 2, the glycerol ether is at least one of 1,2-cyclohexanediol diglycidyl ether, furfuryl glycidyl ether, polyethylene glycol diglycidyl ether, and neopentyl glycol glycidyl ether.
9. A method for producing vitamin B12 using a ferrocyanide complex according to claim 5, characterized in that, In Step 2, the reaction process is as follows: ； Among them, the glycerol ether in the reaction process is 1,2-cyclohexanediol diglycidyl ether.
10. A method for producing vitamin B12 using a ferrocyanide complex according to claim 5, characterized in that, In Step 3, the modified sodium alginate and Intermediate 1 are mixed at a mass ratio of 8-10:1 to obtain a mixture. A 0.05 mol / L sodium hydroxide solution with a mass 50-100 times that of the mixture is added as a solvent to dissolve the mixture. The temperature is raised to 50-60 °C and heated for 1-2 h to react to form a filtration system for adsorbing impurities in the conversion liquid during the fermentation of vitamin B12.