CN106987608B - Dynamic crystallization method of calcium gluconate - Google Patents
Dynamic crystallization method of calcium gluconate Download PDFInfo
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- CN106987608B CN106987608B CN201710407823.XA CN201710407823A CN106987608B CN 106987608 B CN106987608 B CN 106987608B CN 201710407823 A CN201710407823 A CN 201710407823A CN 106987608 B CN106987608 B CN 106987608B
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/58—Aldonic, ketoaldonic or saccharic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
Abstract
The invention discloses a dynamic crystallization method of calcium gluconate, which comprises the following steps: s1, adding 10000kg of pure water, 3500kg of glucose and 1000kg of light calcium carbonate into a reaction tank in sequence with 5000-3A suspension; s2, adding 4-6kg of catalase and 8-10kg of glucose oxidase, introducing air, and reacting for 8-10h at 36-40 ℃; s3, heating the reaction solution to 80-90 ℃, preserving the heat for 30-40min, and filtering while the reaction solution is hot; s4, adding activated carbon into the filtrate obtained in the step S3 for decolorization, and performing solid-liquid separation again to obtain a new filtrate; s5, cooling the filtrate obtained in the step S4 to 36-45 ℃ for the first time, adding seed crystals, cooling to 16-24 ℃ for the second time, and keeping the temperature for 16-20 hours to obtain a product; and S6, centrifugally drying the product to obtain a finished calcium gluconate product. The method has the advantages of short crystallization period, high yield, high product content and good quality uniformity; and the labor intensity is low, and the method is suitable for industrial production.
Description
Technical Field
The invention relates to the field of preparation of calcium gluconate, and particularly relates to a dynamic crystallization method of calcium gluconate.
Background
Calcium gluconate (Calcium gluconate) is Calcium salt of gluconic acid and has a molecular formula of Ca (C)6H11O7)2·H2O is white crystalline or granular powder, has melting point of 201 deg.C, is odorless and tasteless, and is soluble in cold water and hot water. It is an important organic calcium, is clinically used as calcium supplement, is also a raw material for producing other gluconate and gluconolactone, and is an important chemical export product in China.
The structural formula is shown as formula 1.
At present, the method for producing calcium gluconate by domestic companies adopts a standing crystallization method during crystallization. Patent CN106399404A discloses a production method of calcium gluconate, which comprises mixing glucose, glucose oxidase and catalase, adding calcium carbonate, reacting under certain conditions, filtering after the reaction is finished, concentrating, standing for crystallization, and drying to obtain the final product. Patent CN101016239A discloses a process for extracting calcium gluconate from a mother liquor obtained after calcium gluconate crystallization, which comprises removing impurities from the mother liquor with activated carbon, concentrating, standing and crystallizing to obtain the product. Patent CN106008196A discloses a purification method of calcium gluconate, which comprises crystallizing a calcium gluconate solution after ultrafiltration and nanofiltration to obtain a product.
In the face of increasing market demand and product quality requirements, the conventional standing crystallization technology of calcium gluconate solution is difficult to achieve, and has the following main defects: (1) in the traditional standing crystallization method, the obtained product is settled at the bottom of the tank, so that the product is agglomerated, and the subsequent centrifugal separation operation is inconvenient; (2) after crystallization is finished, the traditional standing crystallization method is to discharge mother liquor firstly and then discharge crystallized products manually, so that the labor intensity is increased, and the industrial production is not facilitated; (3) the traditional standing crystallization method has low yield and higher product residue in mother liquor; (4) the product obtained by the traditional standing crystallization method has serious water-in-crystal phenomenon, easily causes the water content of the product to be higher, causes the product content to be lower and has poor product quality uniformity.
Aiming at the defects of complex process, complex operation, low product yield, poor product quality uniformity, high labor intensity and the like which are not beneficial to industrial production in the existing calcium gluconate production crystallization technology, a dynamic crystallization method of calcium gluconate is provided.
Disclosure of Invention
Based on the technical problems in the background art, the invention provides a dynamic crystallization method of calcium gluconate.
The invention provides a dynamic crystallization method of calcium gluconate, which comprises the following steps:
s1, adding 10000kg of pure water of 5000-3The mixed suspension A of (a);
s2, sequentially adding 4-6kg of catalase and 8-10kg of glucose oxidase into the mixed suspension A, introducing air, and reacting at the temperature of 36-40 ℃ for 8-10h to obtain a mixture B;
s3, heating the mixture B to 80-90 ℃, preserving the heat for 30-40min, and carrying out solid-liquid separation while the mixture B is hot to obtain a filtrate C;
s4, adding activated carbon into the filtrate C for decolorization, and continuing to perform solid-liquid separation to obtain a filtrate D;
s5, adding the filtrate D into a crystallizing tank, cooling to 36-45 ℃ for the first time, adding seed crystals under the condition of medium-low speed stirring, and cooling to 16-24 ℃ for the second time; stopping stirring, keeping the temperature at 16-24 ℃, and standing for 16-20h to obtain a mixture E;
and S6, putting the mixture E into a centrifuge, separating to obtain a solid product F, putting the product F into a fluidized bed dryer, and drying to obtain a finished product of the calcium gluconate.
Preferably, in the S1, the glucose is medicinal grade or food grade, and the calcium carbonate is industrial grade or food grade; in the S2, catalase and glucose oxidase are in industrial grade or food grade.
Preferably, in S2, the air flow rate is kept at 1000-3H, keeping the pressure of the reaction tank at 0.16-0.20 MPa.
Preferably, in the S3 and S4, the solid-liquid separation mode is to use a liquid filter or a plate-and-frame filter pressing method.
Preferably, in the S1 and S5, the stirring speed of the medium-low speed stirring is 5-30 rad/min;
preferably, in the S4 and S5, the temperature of the filtrate D is 60-80 ℃.
Preferably, in S6, the temperature of the fluidized bed dryer is controlled at 135-145 DEG C
Compared with the prior art, the invention has the beneficial effects that:
1. the dynamic crystallization method provided by the invention adopts the medium-low speed stirring crystallization, so that the obtained product is not hardened, and the subsequent centrifugal operation is convenient;
2. after the crystallization is finished, the dynamic crystallization method provided by the invention does not need manual discharging, and the dynamic crystallization method can be directly introduced into a centrifuge for centrifugation, so that the working efficiency is greatly improved;
3. the yield of the dynamic crystallization method provided by the invention is higher, and the product residue in the mother liquor is lower;
4. the product obtained by the dynamic crystallization method provided by the invention has good quality uniformity and higher product content.
The production method simplifies the preparation and purification steps, and ensures the reaction efficiency and the product yield by controlling the consumption of raw materials and the reaction temperature; a two-step cooling mode is adopted during crystallization, and crystal seeds and stirring conditions are added, so that the crystallization purity is improved, and the product quality and the product yield are improved; meanwhile, the whole process does not need manual discharging, the production cost is low, and the requirement of industrial production is met.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail with reference to the following embodiments. It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments.
Example 1:
the invention provides a dynamic crystallization method of calcium gluconate, which comprises the following steps:
s1, adding 10000kg of pure water into a reaction tank, starting stirring, sequentially adding 2800kg of glucose and 800kg of calcium carbonate, stirring at a medium and low speed for 5-10min, adding pure water, and preparing into a product with a volume of 20m3The mixed suspension A of (a);
s2, sequentially adding 4.5kg of catalase and 9kg of glucose oxidase into the mixed suspension A, uniformly stirring, injecting air, and reacting at 38 ℃ for 8 hours to obtain a mixture B;
s3, heating the mixture B to 80-90 ℃, preserving the heat for 30-40min, and carrying out solid-liquid separation while the mixture B is hot to obtain a filtrate C;
s4, adding activated carbon into the filtrate C for decolorization, and continuing to perform solid-liquid separation to obtain a filtrate D;
s5, adding the filtrate D into a crystallizing tank, cooling to 45 ℃ for the first time, adding seed crystals under the condition of medium and low-speed stirring, and cooling to 20 ℃ for the second time; stopping stirring, keeping the temperature at 16-24 ℃, and standing for 20h to obtain a mixture E;
and S6, putting the mixture E into a centrifuge, separating to obtain a solid product F, putting the product F into a fluidized bed dryer, and drying to obtain a finished product of the calcium gluconate.
In the S1, the glucose is in a medicinal grade or a food grade, and the calcium carbonate is in an industrial grade or a food grade; in the S2, catalase and glucose oxidase are in industrial grade or food grade.
In the S2, the air flow rate is kept at 1200m when air is introduced3The pressure in the reaction tank was kept at 0.18 MPa.
In the above S3 and S4, the solid-liquid separation method is a plate-and-frame filter press method using a liquid filter.
In the S1 and S5, the stirring speed of the medium-low speed stirring is 5-30 rad/min;
in the S4 and S5, the temperature of the filtrate D is 60-80 ℃.
In S6, the temperature of the fluidized bed dryer is controlled at 135-145 DEG C
The detection method of the content of the finished product of the calcium gluconate comprises the following steps:
taking 0.5g of the finished product of the calcium gluconate, accurately weighing, adding 100ml of water, dissolving at a low temperature, adding 15ml of sodium hydroxide test solution and 0.1g of calcium purpurin indicator, and titrating by using ethylene diamine tetraacetic acid disodium titrating solution (0.05mol/L) until the solution is changed from purple to pure blue.
Every 1ml of disodium ethylenediamine tetraacetate titration solution (0.05mol/L) is equivalent to 22.42mg of C12H22CaO14·H2O。
In the formula: content of W-calcium gluconate%
Concentration of C-0.05mol/L disodium ethylene diamine tetraacetate titration solution, mol/L
V-consumption volume of disodium EDTA titration solution, ml
Mass of M-calcium gluconate, g
The clarity detection method of the solution is as follows:
4.0g of the finished product of the calcium gluconate is taken, 40ml of water is added, the mixture is boiled until the mixture is dissolved, and the solution is clarified.
Example 2:
the invention provides a dynamic crystallization method of calcium gluconate, which comprises the following steps:
s1, adding 15000kg of pure water into a reaction tank, starting stirring, sequentially adding 3200kg of glucose and 900kg of calcium carbonate, stirring at a medium and low speed for 5-10min, adding pure water, and preparing a mixed suspension A with the volume of 24m 3;
s2, sequentially adding 5kg of catalase and 10kg of glucose oxidase into the mixed suspension A, uniformly stirring, injecting air, and reacting at the temperature of 36 ℃ for 10 hours to obtain a mixture B;
s3, heating the mixture B to 80-90 ℃, preserving the heat for 30-40min, and carrying out solid-liquid separation while the mixture B is hot to obtain a filtrate C;
s4, adding activated carbon into the filtrate C for decolorization, and continuing to perform solid-liquid separation to obtain a filtrate D;
s5, adding the filtrate D into a crystallizing tank, cooling to 40 ℃ for the first time, adding seed crystals under the condition of medium-low speed stirring, and cooling to 18 ℃ for the second time; stopping stirring, keeping the temperature at 18 ℃, and standing for 16h to obtain a mixture E;
and S6, putting the mixture E into a centrifuge, separating to obtain a solid product F, putting the product F into a fluidized bed dryer, and drying to obtain a finished product of the calcium gluconate.
In the S1, the glucose is in a medicinal grade or a food grade, and the calcium carbonate is in an industrial grade or a food grade; in the S2, catalase and glucose oxidase are in industrial grade or food grade.
In the step S2, the air flow rate is kept at 1500m when air is introduced3The pressure in the reaction tank was kept at 0.16 MPa.
In the above S3 and S4, the solid-liquid separation method is a plate-and-frame filter press method using a liquid filter.
In the S1 and S5, the stirring speed of the medium-low speed stirring is 5-30 rad/min;
in the S4 and S5, the temperature of the filtrate D is 60-80 ℃.
In S6, the temperature of the fluidized bed dryer is controlled at 135-145 DEG C
The product quality of calcium gluconate of the above example is shown in table 1:
TABLE 1 product quality of the examples
| Content of finished product/%) | Clarity of the product | |
| Example 1 | 99.99 | <0.5 |
| Example 2 | 100.5 | <0.5 |
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (6)
1. A dynamic crystallization method of calcium gluconate is characterized by comprising the following steps:
s1, adding 10000kg of pure water of 5000-3The mixed suspension A of (a);
s2, sequentially adding 4-6kg of catalase and 8-10kg of glucose oxidase into the mixed suspension A, introducing air, and reacting at the temperature of 36-40 ℃ for 8-10h to obtain a mixture B;
s3, heating the mixture B to 80-90 ℃, preserving the heat for 30-40min, and performing solid-liquid separation by using a plate-and-frame filter pressing method of a liquid filter while the mixture B is hot to obtain a filtrate C;
s4, adding activated carbon into the filtrate C for decolorization, and continuously performing solid-liquid separation by using a plate-and-frame filter pressing method of a liquid filter to obtain a filtrate D;
s5, adding the filtrate D into a crystallizing tank, cooling to 36-45 ℃ for the first time, adding seed crystals under the condition of medium-low speed stirring, and cooling to 16-24 ℃ for the second time; stopping stirring, keeping the temperature at 16-24 ℃, and standing for 16-20h to obtain a mixture E;
and S6, putting the mixture E into a centrifuge, separating to obtain a solid product F, putting the product F into a fluidized bed dryer, and drying to obtain a finished product of the calcium gluconate.
2. The dynamic crystallization method of calcium gluconate according to claim 1, wherein in said S1, glucose is pharmaceutical grade or food grade, and calcium carbonate is industrial grade or food grade; in the S2, catalase and glucose oxidase are in industrial grade or food grade.
3. The dynamic crystallization method of calcium gluconate as claimed in claim 1, wherein in S2, the air flow rate is kept at 1000-1500m when air is introduced3H, keeping the pressure of the reaction tank at 0.16-0.20 MPa.
4. The dynamic crystallization method of calcium gluconate according to claim 1, wherein the stirring speed of the medium-low speed stirring in S1 and S5 is 5-30 rad/min.
5. The dynamic crystallization method of calcium gluconate as claimed in claim 1, wherein the temperature of filtrate D in S4 and S5 is 60-80 ℃.
6. The dynamic crystallization method of calcium gluconate as claimed in claim 1, wherein the temperature of the fluidized bed dryer in S6 is controlled at 135-145 ℃.
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| CN109329308A (en) * | 2018-11-20 | 2019-02-15 | 四川月天抗菌制剂有限公司 | A kind of Multi-purpose antibiotic agent preparation method |
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| CN101333543A (en) * | 2007-04-03 | 2008-12-31 | 浙江天益食品添加剂有限公司 | Method for manufacturing calcium gluconate by enzyme method |
| CN106365983A (en) * | 2016-08-31 | 2017-02-01 | 西王药业有限公司 | Method for preparing calcium gluconate using sodium gluconate mother liquor as raw material |
| CN106591275A (en) * | 2016-11-30 | 2017-04-26 | 温县兴发生物科技有限公司 | Method for preparing calcium gluconate through co-immobilization of glucose oxidase and catalase |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101333543A (en) * | 2007-04-03 | 2008-12-31 | 浙江天益食品添加剂有限公司 | Method for manufacturing calcium gluconate by enzyme method |
| CN106365983A (en) * | 2016-08-31 | 2017-02-01 | 西王药业有限公司 | Method for preparing calcium gluconate using sodium gluconate mother liquor as raw material |
| CN106591275A (en) * | 2016-11-30 | 2017-04-26 | 温县兴发生物科技有限公司 | Method for preparing calcium gluconate through co-immobilization of glucose oxidase and catalase |
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