A method for preparing calcium gluconate

Abstract

The present application relates to the technical field of enzyme catalysis, and particularly relates to a preparation method of calcium gluconate. The method comprises the following steps: taking glucose solution, liquid calcium carbonate and liquid calcium peroxide as raw materials, and performing enzyme reaction in the presence of catalase and glucose oxidase; after the enzyme reaction is completed, the enzyme is inactivated, neutralization, decolorization and crystallization are performed, and calcium gluconate wet product and crystallization mother liquor are obtained; the crystallization mother liquor is concentrated by a membrane and concentrated under reduced pressure, and then is used again; the calcium gluconate wet product is crushed, dried, sieved and mixed to obtain calcium gluconate finished product. The method can use high-concentration glucose as a substrate, improve the enzyme reaction efficiency, shorten the enzyme reaction time, and maintain a high calcium gluconate preparation yield and high product purity.

Description

Technical Field

[0001] This invention relates to the field of enzyme catalysis technology, and specifically to a method for preparing calcium gluconate. Background Technology

[0002] Calcium gluconate, as an important organic calcium supplement, is characterized by high solubility, excellent bioavailability, high physiological compatibility, and low gastrointestinal irritation. It is widely used in the treatment of hypocalcemia, as a calcium fortification additive in food, and in the feed industry. With the increasing demand for health products, the market demand for high-purity, low-impurity pharmaceutical-grade calcium gluconate continues to grow.

[0003] The mainstream methods for preparing calcium gluconate include fermentation and enzymatic methods. Compared to fermentation, enzymatic processes do not require microbial culture, culture media, or fermentation additives, nor do they require secondary seed culture as in fermentation. The production process is also significantly shorter than fermentation, making it more environmentally friendly and energy-efficient, reducing investment in equipment and plant facilities. Current enzymatic methods for preparing calcium gluconate involve using a dual-enzyme system of glucose oxidase and catalase to catalyze the oxidation of glucose to gluconic acid, which is then reacted with calcium carbonate to produce calcium gluconate. While this process is environmentally friendly, existing enzymatic methods for preparing calcium gluconate still have the following drawbacks: low enzyme reaction efficiency leads to long reaction times; incomplete enzymatic hydrolysis results in the accumulation of residual sugar and intermediate products, hindering crystallization; to avoid substrate inhibition of the enzyme reaction and low sugar concentration, evaporation and concentration are required to meet crystallization requirements, increasing the number of steps and energy consumption; furthermore, the crystallization process is uncontrollable, leading to instability and affecting product yield and purity.

[0004] Given the problems of low efficiency, long reaction time, and low product purity in existing calcium gluconate enzymes, there is an urgent need to propose a method for preparing calcium gluconate. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing calcium gluconate. This method can use a high concentration of glucose as a substrate, improve the efficiency of enzyme reaction, shorten the enzyme reaction time, and maintain a high yield and high purity of calcium gluconate.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a method for preparing calcium gluconate, comprising the following steps: S1. Using liquid calcium carbonate and liquid calcium peroxide as calcium sources, according to the ratio of glucose to calcium source Ca... 2+The molar ratio of calcium carbonate to calcium peroxide in the calcium source is 2:1.05-1.2, the molar ratio of calcium carbonate to calcium peroxide in the calcium source is 9-9.5:0.5-1, and the sugar concentration of the enzyme reaction solution is 20-22%. Calculate the amount of each raw material and prepare glucose solution, liquid calcium carbonate and liquid calcium peroxide respectively. S2. Using glucose solution, liquid calcium carbonate, liquid calcium peroxide and compound enzyme as raw materials, the enzyme reaction is carried out under the conditions of pressure 0.18-0.22MPa, temperature 30-48℃ and pH 5.0-7.0. The reaction is completed when the residual sugar drops to below 0.5%. S3. After the enzyme reaction is complete, heat the reaction solution to 95-105℃, add calcium oxide to adjust the pH to 6.0-7.0, add perlite, stir well, and filter to obtain the post-treatment solution. S4. Stir and heat the post-treatment solution to boiling, adjust the specific gravity to 1.070-1.080, add gluconolactone to adjust the pH to 5.8-6.2, add activated carbon, stir and decolorize at 90-100℃, and then filter to obtain the decolorized solution. S5. After crystallizing the decolorizing solution, centrifuge to obtain wet calcium gluconate and crystallization mother liquor; S6. Calcium gluconate wet product is obtained by crushing, drying, sieving and mixing.

[0007] The above method uses calcium carbonate and calcium peroxide as a composite calcium source. Calcium peroxide can be hydrolyzed in the system into calcium hydroxide and hydrogen peroxide. The generated calcium hydroxide can immediately neutralize the acidity of the enzyme reaction, avoid excessive acidity of the enzyme reaction solution, maintain pH stability, which is beneficial to maintain high enzyme activity, and reduce carbon dioxide in the reaction system to promote the rightward shift of the main synthesis reaction of calcium gluconate. The hydrogen peroxide generated by the hydrolysis of hydrogen peroxide can provide additional dissolved oxygen to increase the oxygen partial pressure in the reaction system. The enzyme reaction of this application can maintain high enzyme reaction efficiency at high sugar concentration, shorten the enzyme reaction time, achieve complete enzymatic hydrolysis, and eliminate the need for concentration after the enzyme reaction, thus reducing reaction energy consumption.

[0008] Furthermore, by first preparing each raw material into a liquid state according to the feeding ratio and sugar solution concentration, the reaction raw materials can be quickly and evenly mixed in the enzyme reaction vessel. According to the specific implementation scheme of this application, the raw material preparation method in S1 is as follows: glucose is dissolved in water at 10-45℃ to prepare a glucose solution with a concentration of 28-32%; calcium carbonate is dispersed in water at 10-45℃ to prepare liquid calcium carbonate with a concentration of 20-25%; and calcium peroxide is dispersed in water at 5-10℃ to prepare liquid calcium peroxide with a concentration of 8-12%.

[0009] Further, in step S2, glucose solution and liquid calcium carbonate are first added to the enzyme reaction vessel and mixed thoroughly. Liquid calcium peroxide is then placed in a storage tank with a cooling jacket to maintain its temperature at 5-10°C. A composite enzyme is then added to the enzyme reaction vessel to initiate the enzyme reaction. During the reaction, liquid calcium peroxide is added dropwise at a uniform rate below the liquid surface using a dropper. This method helps stabilize the calcium peroxide before it is added to the enzyme reaction vessel. Furthermore, since the enzyme reaction is generally exothermic, uniformly adding low-temperature liquid calcium peroxide below the surface helps maintain a stable reaction temperature and prevents enzyme inactivation.

[0010] Furthermore, in S2, the complex enzymes are glucose oxidase and catalase. The activity of glucose oxidase is 14,000-20,000 U / ml, the activity of catalase is 800,000-1,600,000 U / g, the amount of catalase added is 1.0-1.4 wt‰ of glucose, and the amount of glucose oxidase added is 1.8-2 wt‰ of glucose.

[0011] High-temperature treatment after the enzyme reaction is completed can inactivate the enzyme protein and terminate the enzyme reaction process. It also facilitates the aggregation and sedimentation of suspended matter such as proteins and colloids in the reaction solution. Adding calcium oxide after high-temperature treatment can neutralize residual acid. Using perlite as a filter aid can intercept impurities. After perlite filtration, the post-treatment solution is stirred and heated to boiling. After adding an appropriate amount of purified water to adjust the specific gravity, a small amount of gluconolactone is added at high temperature to hydrolyze into gluconic acid, which reacts with residual calcium particles in the system, which helps to improve the clarity of the reaction solution and the product yield.

[0012] Furthermore, in S3, the amount of perlite used is 1.8-2 wt‰ of the weight of glucose.

[0013] Further, in S4, the decolorization method involves adding 1-2 wt% of activated carbon (by weight of glucose) to the filtrate, stirring and decolorizing at 90-100°C for 1 hour, and then filtering.

[0014] Furthermore, in S5, the crystallization method is as follows: the decolorizing solution is sent into a sealed crystallizer with a cooling jacket, and cooling water is used to exchange heat between the jacket and the decolorizing solution to cool the decolorizing solution. In the early stage, the temperature is lowered to about 45-50℃ at a rate of 1-2℃ / min, and in the later stage, the temperature is lowered to 18-22℃ at a rate of 3-4℃ / min. Then, the solution is left to stand at this temperature for 18-24 hours. At the end of crystallization, the specific gravity of the mother liquor is 1.025-1.035.

[0015] Further, in S5, after crystallization is completed, the mother liquor in the crystallizer is drawn into the mother liquor tank, the auger in the crystallizer is started to open the feeding valve so that the material is fed into the container and sent to the centrifuge to separate the mother liquor. The mother liquor is washed with purified water and centrifuged until no water flows out. The centrifugation is completed to obtain the wet calcium gluconate and the crystallization mother liquor.

[0016] The crystallization method employed in this invention utilizes a sealed crystallizer equipped with a cooling device. The cooling process begins with a slower initial cooling rate followed by a faster cooling rate, which reduces early nucleation and promotes later crystal growth, thereby stabilizing crystal form and grain size and increasing yield. Compared to open crystallizers, the sealed crystallizer improves the production environment by preventing moisture leakage. The use of a auger for material feeding eliminates the need for manual material handling, reducing labor intensity. The cooling system facilitates stable and controlled crystallization processes, further increasing crystallization yield.

[0017] Due to the high solubility of calcium gluconate, a significant amount of calcium gluconate product remains in the crystallization mother liquor. Therefore, collecting, concentrating, and recovering the mother liquor is a necessary procedure. Further, S5 includes membrane concentration and vacuum concentration of the crystallization mother liquor to obtain a concentrated solution. This concentrated solution is reused in the next batch of post-processing liquid, or the concentrated solution is sequentially crystallized, pulverized, dried, sieved, and mixed. The membrane concentration method involves heating the mother liquor to 65-70℃, performing membrane concentration at a pressure of 1.5-2 MPa and a temperature of 65-70℃, concentrating to a specific gravity of 1.050-1.060. The vacuum concentration method involves controlling the steam pressure above 0.2 MPa, concentrating at a temperature of 65-70℃, and concentrating to a specific gravity of 1.108-1.110.

[0018] In the above method, the mother liquor concentration first employs membrane concentration, followed by vacuum concentration, which reduces steam usage, achieving energy saving and consumption reduction, and improving the efficiency of the concentration process. After concentration, the crystallization mother liquor can be directly reused in the next batch of post-treatment liquid. Concentrating the mother liquor to a specific gravity of 1.108-1.110 avoids dilution of the post-treatment liquid and reduces the need for mother liquor recovery. Reusing it in the post-treatment liquid and utilizing activated carbon decolorization can remove impurities from the mother liquor. In the method provided in this application, the mother liquor can also be directly crystallized, pulverized, dried, sieved, and mixed after concentration, depending on the circumstances.

[0019] Furthermore, in S6, the methods for crushing, drying, sieving, and mixing are as follows: wet calcium gluconate is crushed in a vibrating granulator and passed through a 10-mesh sieve. Then, it is dried using a fluidized bed dryer. When the temperature inside the dryer is above 95°C, the material is cooled and discharged. The dried material is then poured into a vibrating screen and passed through a 10-mesh sieve. Finally, the material is drawn into a mixer by a vacuum feeder and mixed for 30 minutes to obtain the final product.

[0020] Compared with the prior art, the beneficial effects of the present invention are: 1. The present invention provides an enzymatic method for preparing calcium gluconate, which uses calcium carbonate and calcium peroxide as a composite calcium source, high-concentration glucose as a substrate, and glucose oxidase and catalase as a dual-enzyme system. The method of this application can maintain high enzyme reaction efficiency at high sugar concentration, shorten the enzyme reaction time, achieve complete enzymatic hydrolysis, eliminate the need for concentration after enzyme reaction, reduce reaction energy consumption, and achieve high yield and product purity.

[0021] 2. The method for preparing calcium gluconate provided by this invention employs a sealed crystallizer with a cooling device and optimizes the crystallization process, resulting in stable crystal form and particle size, high yield, improved production environment, and reduced labor intensity. The method for recycling the crystallization mother liquor provided in this application is flexible; concentrating the mother liquor and reusing it in the next batch reduces the number of mother liquor recycling procedures. Reusing it in the next batch of post-treatment liquid and then utilizing activated carbon decolorization removes impurities from the crystallization mother liquor, obtaining a high-purity calcium gluconate product while ensuring yield. Detailed Implementation

[0022] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. The described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Unless otherwise specified, all methods described herein are conventional methods, and all raw materials described herein are available from publicly available commercial sources.

[0024] Example 1 This embodiment provides a method for preparing calcium gluconate, including the following steps: 1. According to the ratio of glucose to calcium in the raw materials 2+ The molar ratio of calcium carbonate to calcium peroxide is 2:1.1, the molar ratio of calcium carbonate to calcium peroxide is 9:1, and the sugar concentration after mixing is about 21%. Glucose is dissolved in room temperature water to prepare a 30% glucose solution, calcium carbonate is dispersed in room temperature water to prepare a 23% liquid calcium carbonate solution, and calcium peroxide is dispersed in water at 5°C to prepare a 10% liquid calcium peroxide solution, which are ready for use. 2. Add glucose solution to the enzyme reaction vessel, then add liquid calcium carbonate and stir until homogeneous. Pour the liquid calcium peroxide into a storage tank with a cooling jacket to maintain the temperature of the liquid calcium peroxide at 5°C. 3. Add catalase and glucose oxidase to the enzyme reaction vessel. The activity of glucose oxidase is 14000 U / ml, and the activity of catalase is 800000 u / g. The amount of catalase added is 1.4 wt‰ of glucose, and the amount of glucose oxidase added is 1.8 wt‰ of glucose. Pressurized air is introduced to bring the vessel pressure to 0.2 MPa. The reaction is carried out at a temperature of 30-48℃ and a pH of 5.0-7.0. During the enzyme reaction, liquid calcium peroxide is added dropwise at a uniform rate through a dropper until it is below the liquid surface. The reaction is complete when the residual sugar drops below 0.5%. 4. After the enzyme reaction is complete, heat the reaction solution to 100℃, add calcium oxide while stirring to adjust the pH to 6.8, add 1.8wt‰ perlite (based on the weight of glucose) and stir evenly. Press the neutralized solution into a filter using air pressure and filter to obtain the post-processed solution. 5. Stir and heat the post-treatment solution to boiling, add purified water to adjust the specific gravity to 1.070, add gluconolactone to adjust the pH to 6.0, add 1.5wt% activated carbon (based on the weight of glucose) to the filtrate, stir and decolorize at 95℃ for 1 hour, and pump the solution into a filter to obtain the decolorized solution. 6. Pump the decolorizing solution into a sealed crystallizer with a cooling jacket. Use cooling water to exchange heat between the jacket and the decolorizing solution to cool the solution. Initially, cool the solution to 48°C at a rate of 1.5°C / min, and later cool it to 20°C at a rate of 3.5°C / min. Then let it stand at this temperature for 20 hours.

[0025] 7. After crystallization is completed, the mother liquor in the crystallizer is drawn into the mother liquor tank. The auger in the crystallizer is started to open the feeding valve so that the material is fed into the container and sent to the centrifuge for centrifugation. The material is washed with purified water for 1 minute and centrifuged until no water flows out. After centrifugation, the wet product of calcium gluconate is obtained. The filtrate is transferred to the mother liquor tank. 8. After crushing the wet calcium gluconate into a vibrating granulator and passing it through a 10-mesh sieve, dry it using a fluidized bed dryer. When the temperature inside the dryer is above 95℃, cool it down and discharge the material. Pour the dried material into a vibrating screen and pass it through a 10-mesh sieve. Then, use a vacuum feeder to draw the material into a mixer and mix for 30 minutes to obtain the final product.

[0026] 9. The mother liquor of crystallization is concentrated by membrane concentration and vacuum concentration to obtain a concentrated solution, which is then reused in the next batch of post-treatment solution. The membrane concentration method is to heat the mother liquor of crystallization to 65°C and perform membrane concentration (equipment model CJ-JM-270) at a concentration pressure of 1.5MPa and a temperature of 65°C until the specific gravity is 1.050. The vacuum concentration method is to control the steam pressure at 0.2MPa and the concentration temperature at 65°C until the specific gravity is 1.108.

[0027] Example 2 The method is the same as in Example 1, except that in step 5, a batch of concentrated crystallization mother liquor (Example 1) is added to the post-treatment liquid, stirred and heated to boiling, purified water is added to adjust the specific gravity to 1.070, gluconolactone is added to adjust the pH to 6.0, 2wt% activated carbon (based on the weight of glucose) is added to the filtrate and stirred at 95°C for 1 hour for decolorization, and the liquid is pumped into a filter for filtration to obtain the decolorized liquid.

[0028] Example 3 This embodiment provides a method for preparing calcium gluconate, including the following steps: 1. According to the ratio of glucose to calcium in the raw materials 2+ The molar ratio of calcium carbonate to calcium peroxide is 2:1.05, the molar ratio of calcium carbonate to calcium peroxide is 9.5:0.5, and the sugar concentration after mixing is about 21.5%. Glucose is dissolved in room temperature water to prepare a 30% glucose solution, calcium carbonate is dispersed in room temperature water to prepare a 25% liquid calcium carbonate solution, and calcium peroxide is dispersed in water at 5°C to prepare a 10% liquid calcium peroxide solution, which are ready for use. 2. Add glucose solution to the enzyme reaction vessel, then add liquid calcium carbonate and stir until homogeneous. Pour the liquid calcium peroxide into a storage tank with a cooling jacket to maintain the temperature of the liquid calcium peroxide at 5°C. 3. Add catalase and glucose oxidase to the enzyme reaction vessel. The activity of glucose oxidase is 14000 U / ml, and the activity of catalase is 800000 u / g. The amount of catalase added is 1.2 wt‰ of glucose, and the amount of glucose oxidase added is 1.8 wt‰ of glucose. Pressurize the vessel with compressed air to a pressure of 0.2 MPa, maintain the temperature at 30-48℃ and the pH at 5.0-7.0. During the enzyme reaction, liquid calcium peroxide is added dropwise at a uniform rate through a dropper until it is below the liquid surface. The reaction is complete when the residual sugar drops below 0.5%. 4. After the enzyme reaction is complete, heat the reaction solution to 100℃, add calcium oxide while stirring to adjust the pH to 6.5, add 1.8wt‰ perlite (based on the weight of glucose) and stir evenly. Press the neutralized solution into a filter using air pressure and filter to obtain the post-processed solution. 5. Stir and heat the post-treatment solution to boiling, add purified water to adjust the specific gravity to 1.080, add gluconolactone to adjust the pH to 6.0, add 1.5wt% activated carbon (based on the weight of glucose) to the filtrate, stir and decolorize at 95℃ for 1 hour, and pump the solution into a filter to obtain the decolorized solution. 6. Pump the decolorizing solution into a sealed crystallizer with a cooling jacket. Use cooling water to exchange heat between the jacket and the decolorizing solution to cool the solution. Initially, cool the solution to 50°C at a rate of 1°C / min, and later cool it to 22°C at a rate of 3°C / min. Then let it stand at this temperature for 18 hours.

[0029] 7. After crystallization is completed, the mother liquor in the crystallizer is drawn into the mother liquor tank. The auger in the crystallizer is started to open the feeding valve so that the material is fed into the container and sent to the centrifuge for centrifugation. The material is washed with purified water for 1 minute and centrifuged until no water flows out. After centrifugation, the wet product of calcium gluconate is obtained. The filtrate is transferred to the mother liquor tank. 8. After crushing the wet calcium gluconate product through a 10-mesh sieve in a vibrating granulator, dry it in a fluidized bed dryer. When the temperature inside the dryer is above 95℃, cool it down and discharge the material. Pour the dried material into a vibrating screen and pass it through a 10-mesh sieve. Then, use a vacuum feeder to draw the material into the mixer and mix for 30 minutes to obtain calcium gluconate product 1.

[0030] 9. The mother liquor for crystallization is concentrated by membrane concentration and vacuum concentration to obtain a concentrated solution. The membrane concentration method is to heat the mother liquor to 70°C and perform membrane concentration (equipment model CJ-JM-270) at a concentration pressure of 2MPa and a temperature of 70°C until the specific gravity is 1.060. The vacuum concentration method is to control the steam pressure at 0.3MPa and the concentration temperature at 70°C until the specific gravity is 1.110.

[0031] 10. Crystallize the concentrate according to steps 6-7 above. Concentrate the mother liquor according to step 9 and crystallize it again once, then discard it. Collect the obtained wet calcium gluconate product and prepare calcium gluconate product 2 according to step 8.

[0032] Example 4 This embodiment provides a method for preparing calcium gluconate, including the following steps: 1. According to the ratio of glucose to calcium in the raw materials 2+ The molar ratio of calcium carbonate to calcium peroxide is 2:1.1, the molar ratio of calcium carbonate to calcium peroxide is 9:1, and the sugar concentration after mixing is about 20%. Glucose is dissolved in room temperature water to prepare a 30% glucose solution, calcium carbonate is dispersed in room temperature water to prepare a 20% liquid calcium carbonate solution, and calcium peroxide is dispersed in water at 5°C to prepare a 10% liquid calcium peroxide solution, which are ready for use. 2. Add glucose solution to the enzyme reaction vessel, then add liquid calcium carbonate and stir until homogeneous. Pour the liquid calcium peroxide into a storage tank with a cooling jacket to maintain the temperature of the liquid calcium peroxide at 5°C. 3. Add catalase and glucose oxidase to the enzyme reaction vessel. The activity of glucose oxidase is 14000 U / ml, and the activity of catalase is 800000 u / g. The amount of catalase added is 1.4 wt‰ of glucose, and the amount of glucose oxidase added is 1.8 wt‰ of glucose. Pressurize the vessel with compressed air to a pressure of 0.2 MPa, maintain the temperature at 30-48℃ and the pH at 5.0-7.0. During the enzyme reaction, liquid calcium peroxide is added dropwise at a uniform rate through a dropper until it is below the liquid surface. The reaction is complete when the residual sugar drops below 0.5%. 4. After the enzyme reaction is complete, heat the reaction solution to 100℃, add calcium oxide while stirring to adjust the pH to 6.8, add 2wt‰ perlite (based on the weight of glucose) and stir evenly. Press the neutralized solution into a filter using air pressure to obtain the post-processed solution. 5. Stir and heat the post-treatment solution to boiling, add purified water to adjust the specific gravity to 1.07, add gluconolactone to adjust the pH to 6.0, add 2wt% activated carbon (based on the weight of glucose) to the filtrate, stir and decolorize at 95℃ for 1 hour, and pump the solution into a filter to obtain the decolorized solution. 6. Pump the decolorizing solution into a sealed crystallizer with a cooling jacket. Use cooling water to exchange heat between the jacket and the decolorizing solution to cool the solution. Initially, cool the solution to 45°C at a rate of 2°C / min, and later cool it to 18°C ​​at a rate of 4°C / min. Then let it stand at this temperature for 24 hours.

[0033] 7. After crystallization is completed, the mother liquor in the crystallizer is drawn into the mother liquor tank. The auger in the crystallizer is started to open the feeding valve so that the material is fed into the container and sent to the centrifuge for centrifugation. The material is washed with purified water for 1 minute and centrifuged until no water flows out. After centrifugation, the wet product of calcium gluconate is obtained. The filtrate is transferred to the mother liquor tank. 8. After crushing the wet calcium gluconate product through a 10-mesh sieve in a vibrating granulator, dry it in a fluidized bed dryer. When the temperature inside the dryer is above 95℃, cool it down and discharge the material. Pour the dried material into a vibrating screen and pass it through a 10-mesh sieve. Then, use a vacuum feeder to draw the material into the mixer and mix for 30 minutes to obtain calcium gluconate product 1.

[0034] 9. The mother liquor for crystallization is concentrated by membrane concentration and vacuum concentration to obtain a concentrated solution. The membrane concentration method is to heat the mother liquor to 65°C and concentrate it using a membrane (equipment model CJ-JM-270) at a concentration pressure of 1.5 MPa and a temperature of 65°C until the specific gravity is 1.050. The vacuum concentration method is to control the steam pressure at 0.2 MPa and the concentration temperature at 65°C until the specific gravity is 1.108.

[0035] 10. Crystallize the concentrate according to steps 6-7 above. Concentrate the mother liquor according to step 9 and crystallize it again once, then discard it. Collect the obtained wet calcium gluconate product and prepare calcium gluconate product 2 according to step 8.

[0036] Comparative Example 1 This comparative example provides a method for preparing calcium gluconate, comprising the following steps: 1. According to the ratio of glucose to calcium in the raw materials 2+ The molar ratio is 2:1.1. Glucose is dissolved in room temperature water to prepare a 30% glucose solution, and calcium carbonate is dispersed in room temperature water to prepare a 20% liquid calcium carbonate solution, which is ready for use. 2. Add glucose solution to the enzyme reaction vessel, then add liquid calcium carbonate and stir until homogeneous; 3. Add catalase and glucose oxidase to the enzyme reaction vessel. The activity of glucose oxidase is 14000 U / ml, and the activity of catalase is 800000 u / g. The amount of catalase added is 1.4 wt‰ of glucose, and the amount of glucose oxidase added is 1.8 wt‰ of glucose. Pressurize the vessel with compressed air to 0.2 MPa, and maintain the reaction at a temperature of 30-48℃ and a pH of 5.0-7.0. The reaction is complete when the residual sugar drops below 0.5%. The methods for steps 4-10 are the same as in Example 4.

[0037] Comparative Example 2 The method is the same as in Example 4, except that step 1 is as follows: The glucose in the raw materials and the Ca in the calcium source are... 2+ The molar ratio of calcium carbonate to calcium peroxide in the calcium source is 2:1.1. The molar ratio of calcium carbonate to calcium peroxide in the calcium source is 8:2. Glucose is dissolved in room temperature water to prepare a 30% glucose solution. Calcium carbonate is dispersed in room temperature water to prepare a 20% liquid calcium carbonate solution. Calcium peroxide is dispersed in water at 5℃ to prepare a 10% liquid calcium peroxide solution. These are ready for use. Comparative Example 3 The method is the same as in Example 4, except that in step 3, the amount of catalase added is 1 wt‰ of glucose.

[0038] Comparative Example 4 The method of Example 4 differs in that the crystallization method in step 6 is as follows: the decolorizing liquid is pumped into a sealed crystallizer with a cooling jacket, and the decolorizing liquid is cooled by heat exchange between the jacket and the decolorizing liquid using cooling water. The liquid is cooled to 18°C ​​at a rate of 4°C / min, and then left to stand at this temperature for 24 hours.

[0039] The yields and enzyme reaction times of calcium gluconate prepared in the examples and comparative examples were statistically analyzed and calculated. The content of the obtained calcium gluconate samples was determined according to the methods of the Chinese Pharmacopoeia. The residual sugar content was monitored every hour in the early stage of the reaction and every half hour in the later stage. The time when the residual sugar content was first <0.5% was counted as the enzyme reaction time. If the change in residual sugar content was less than 5% in two consecutive measurements, the time of the first residual sugar content measurement was used as the reaction endpoint for calculating the enzyme reaction time and residual sugar content. The yield of calcium gluconate was calculated as: actual weight of product × purity / theoretical yield of product × 100%. The total yield was calculated as: product 1 yield + product 2 yield. The experimental results are shown in Table 1. Table 1: Test Results of Calcium Gluconate Products

[0040] *: The crystallization mother liquor from Example 1 was reused in Example 2, therefore the total yield only included data for calcium gluconate product 1.

[0041] As can be seen from the above, the preparation methods of calcium gluconate in Examples 1-4 of this application can maintain high enzyme reaction efficiency at high sugar concentrations, shorten the enzyme reaction time, control the enzyme reaction time to 5-6 hours, achieve complete enzymatic hydrolysis, and produce products with high purity. In terms of yield, the total yield of Examples 2-4 can reach 94.8-96.6%, indicating that the preparation method of calcium gluconate in this application has a high yield.

[0042] Comparative Example 1 used only calcium carbonate as the calcium source. In step 3, the enzyme reaction time required to reduce the residual sugar to below 0.5% was longer, resulting in a decrease in the overall reaction yield.

[0043] Comparative Example 2 used calcium carbonate and calcium peroxide in a molar ratio of 8:2 as calcium sources. In step 3, the residual sugar content was high, the enzyme reaction time was long, and the overall reaction yield and product purity were reduced.

[0044] In Comparative Example 3, the amount of catalase added was 1 wt‰ of glucose. The enzyme reaction time was longer, and the total reaction yield and product content were both reduced.

[0045] In Comparative Example 4, step 6 involved cooling the temperature to 18°C ​​at a rate of 4°C / min, which resulted in a decrease in the overall reaction yield and the content of the final product.

[0046] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application and not to limit them; although this application has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of this application or equivalent substitutions can be made to some technical features, all of which should be covered within the scope of the technical solutions claimed in this application.

Claims

1. A method for preparing calcium gluconate, characterized in that, Includes the following steps: S1. Using liquid calcium carbonate and liquid calcium peroxide as calcium sources, according to the ratio of glucose to calcium source Ca... 2+ The molar ratio of calcium carbonate to calcium peroxide in the calcium source is 2:1.05-1.2, the molar ratio of calcium carbonate to calcium peroxide in the calcium source is 9-9.5:0.5-1, and the sugar concentration after mixing is 20-22%. Calculate the amount of each raw material and prepare glucose solution, liquid calcium carbonate and liquid calcium peroxide respectively. S2. Using glucose solution, liquid calcium carbonate, liquid calcium peroxide, and a compound enzyme as raw materials, an enzymatic reaction is carried out under a pressure of 0.18-0.22 MPa, a temperature of 30-48℃, and a pH of 5.0-7.

0. The reaction is completed when the residual sugar drops below 0.5%. In S2, the compound enzyme is glucose oxidase and catalase. The activity of glucose oxidase is 14,000-20,000 U / ml, and the activity of catalase is 800,000-1,600,000 U / g. The amount of catalase added is 1.0-1.4 wt‰ of glucose, and the amount of glucose oxidase added is 1.8-2 wt‰ of glucose. S3. After the enzyme reaction is complete, heat the reaction solution to 95-105℃, add calcium oxide to adjust the pH to 6.0-7.0, add perlite, stir well, and filter to obtain the post-treatment solution. S4. Stir and heat the post-treatment solution to boiling, adjust the specific gravity to 1.070-1.080, add gluconolactone to adjust the pH to 5.8-6.2, add activated carbon, stir and decolorize at 90-100℃, and then filter to obtain the decolorized solution. S5. After crystallizing the decolorizing solution, centrifuge to obtain wet calcium gluconate and crystallization mother liquor; S6. Calcium gluconate wet product is obtained by crushing, drying, sieving and mixing.

2. The method for preparing calcium gluconate according to claim 1, characterized in that, The raw material preparation method in S1 is as follows: glucose is dissolved in water at 10-45℃ to prepare a glucose solution with a concentration of 28-32%; calcium carbonate is dispersed in water at 10-45℃ to prepare a liquid calcium carbonate with a concentration of 20-25%; and calcium peroxide is dispersed in water at 5-10℃ to prepare a liquid calcium peroxide with a concentration of 8-12%.

3. The method for preparing calcium gluconate according to claim 2, characterized in that, In S2, glucose solution and liquid calcium carbonate are first added to the enzyme reaction vessel and mixed thoroughly. Liquid calcium peroxide is then placed into a storage tank with a cooling jacket to maintain the temperature of the liquid calcium peroxide at 5-10℃. A compound enzyme is then added to the enzyme reaction vessel to carry out the enzyme reaction. During the enzyme reaction, liquid calcium peroxide is added dropwise at a uniform rate to below the liquid surface through a dropper.

4. The method for preparing calcium gluconate according to claim 1, characterized in that, In S3, the amount of perlite used is 1.8-2 wt‰ of the weight of glucose.

5. The method for preparing calcium gluconate according to claim 1, characterized in that, In S4, the decolorization method involves adding 1-2 wt% of activated carbon (based on the weight of glucose) to the filtrate, stirring at 90-100°C for 1 hour to decolorize, and then filtering.

6. The method for preparing calcium gluconate according to claim 1, characterized in that, In S5, the crystallization method is as follows: the decolorizing liquid is sent into a sealed crystallizer with a cooling jacket, and cooling water is used to exchange heat between the jacket and the decolorizing liquid to cool the decolorizing liquid. In the early stage, the temperature is reduced to 45-50℃ at a rate of 1-2℃ / min, and in the later stage, the temperature is reduced to 18-22℃ at a rate of 3-4℃ / min. Then, the liquid is left to stand at this temperature for 18-24 hours.

7. The method for preparing calcium gluconate according to claim 6, characterized in that, In step S5, after crystallization is completed, the mother liquor in the crystallizer is drawn into the mother liquor tank. The auger in the crystallizer is started to open the feeding valve so that the material is fed into the container and sent to the centrifuge to separate the mother liquor. The mother liquor is washed with purified water and centrifuged until no water flows out. The centrifugation is completed, and the wet calcium gluconate and the crystallization mother liquor are obtained.

8. The method for preparing calcium gluconate according to claim 1 or 7, characterized in that, S5 also includes concentrating the crystallization mother liquor by membrane concentration and vacuum concentration to obtain a concentrate, which is then reused in the next batch of post-processing liquid, or the concentrate is sequentially crystallized, crushed, dried, sieved, and mixed. The method for membrane concentration of the crystallization mother liquor is as follows: the crystallization mother liquor is heated to 65-70℃ and concentrated by membrane at a concentration pressure of 1.5-2MPa and a temperature of 65-70℃ until the specific gravity is 1.050-1.

060. The method of vacuum concentration is as follows: the steam pressure is controlled at 0.2MPa-0.3MPa, the concentration temperature is 65-70℃, and the concentration is carried out to a specific gravity of 1.108-1.

110.

9. The method for preparing calcium gluconate according to claim 1, characterized in that, In S6, the methods for crushing, drying, sieving, and mixing are as follows: wet calcium gluconate is crushed in a vibrating granulator and passed through a 10-mesh sieve. It is then dried using a fluidized bed dryer. When the temperature inside the dryer is above 95°C, the material is cooled and discharged. The dried material is then poured into a vibrating screen and passed through a 10-mesh sieve. Finally, the material is drawn into a mixer by a vacuum feeder and mixed for 30 minutes to obtain the final product.

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