CN114009734A - Method for producing IMP + GMP through anti-solvent cooling crystallization based on solvent spraying oscillation - Google Patents
Method for producing IMP + GMP through anti-solvent cooling crystallization based on solvent spraying oscillation Download PDFInfo
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- RJUVGHSMLKTWKM-AOQYFIQXSA-L disodium 2-[(2S,3S,4R,5R)-3,4-dihydroxy-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]-2-hydroxyacetate Chemical compound [C@@H]1([C@H](O)[C@H](O)[C@@H](C(O)C(=O)[O-])O1)N1C=NC=2C(O)=NC=NC12.[Na+].[Na+].[C@@H]1([C@H](O)[C@H](O)[C@@H](C(O)C(=O)[O-])O1)N1C=NC=2C(O)=NC=NC12 RJUVGHSMLKTWKM-AOQYFIQXSA-L 0.000 description 1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/20—Synthetic spices, flavouring agents or condiments
- A23L27/23—Synthetic spices, flavouring agents or condiments containing nucleotides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/84—Flavour masking or reducing agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/86—Addition of bitterness inhibitors
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/88—Taste or flavour enhancing agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/0081—Use of vibrations, e.g. ultrasound
Abstract
The invention discloses a method for producing IMP + GMP by anti-solvent cooling crystallization based on solvent spraying oscillation, which comprises the steps of adding IMP and GMP as raw materials into water in a crystallization kettle, heating and stirring until the IMP and GMP are completely dissolved, and adjusting PH; adding an anti-solvent dropwise, adding seed crystals for growing crystals, and cooling; forming fan-shaped water mist by solvent water through a spray head, spraying the fan-shaped water mist onto the liquid surface of the raw material of the crystallization kettle, controlling the using amount of the solvent water subjected to primary solvent spraying oscillation to be 25-50% of the total amount of the solvent, controlling the primary spraying time to be 1-2 min, recovering stirring until the temperature is raised and stirred, and cooling to form primary solvent spraying oscillation; repeating solvent spraying and shaking for 2-4 times; cooling, filtering, washing and drying to obtain a crystallized product. The product of the invention has the advantages of narrow particle size distribution, large particle size, good crystal form, high yield, easy control of operation conditions, improvement according to factory process and strong operability.
Description
Technical Field
The invention discloses a preparation method of disodium 5 '-ribonucleotide, belongs to the field of food seasonings, and particularly relates to a method for preparing disodium 5' -ribonucleotide with narrow particle size distribution and large particle size by introducing solvent spray oscillation.
Background
Disodium 5 ' -Ribonucleotide (IMP + GMP, I + G) mainly comprises Disodium 5 ' -Inosinate (5 ' -Inosinate monoposphophosphate, or, Disodium 5 ' -inosinat, or, IMP for short) and Disodium 5 ' -guanyLate (5 ' -Guanosine monoposphophosphate, or, Disodium 5 ' -guanyLate, GMP for short), has a taste development effect, produces a synergistic effect when mixed with monosodium glutamate (sodium glutamate), and can improve the freshness by several times to several times; meanwhile, the disodium 5' -ribonucleotide can improve the quality of food, has a synergistic effect on sweet taste and salty taste, and has an inhibiting or eliminating effect on acid taste, bitter taste, fishy smell, burnt taste and the like. The taste of the food added with the I + G is obviously improved, and the sweet, sour, bitter, spicy, fresh, fragrant and salty tastes are stronger and more harmonious, and are more similar to the flavor of natural food.
The high-quality flavor enhancer is usually in a crystal form with complete grains, uniform granularity, high bulk density and good fluidity. Most of crystals of monosodium glutamate, salt, sugar and the like sold in the market are rod-shaped or block-shaped, and the main particle size is large. The disodium ribonucleotide serving as a main component of the super-fresh monosodium glutamate, the chicken essence and other seasonings meets the requirements of large granularity, high bulk density, good fluidity, high purity and the like, so that the compound flavoring agent obtained by mixing the disodium ribonucleotide with the monosodium glutamate and the like still has the characteristics of uniform granularity, good fluidity and the like, and the high-quality flavoring agent is prepared.
The technological process for producing flavour development nucleotide mainly includes microbial fermentation method, enzymolysis method, enzyme catalysis method and chemical synthesis method. The crude products can be obtained by separating the working solution and the stock solution prepared by the methods through the operations of concentration, crystallization, filtration, washing, drying and the like. The crystallization process of IMP is easy to carry out, and crystals can be directly precipitated in the crystallization of solution; GMP is generally amorphous precipitated in solution, GMP crystals are required to be subjected to a crystal form transformation process, the process control is relatively complex, and the obtained crystal products are poor in shape, low in bulk density and easy to agglomerate. Because of the difference of crystal properties and powder characteristics of IMP and GMP, if a solid powder product obtained by mechanically mixing two fermentation liquors according to a proportion is simple, the operation of the mixing process is difficult and serious, and the mixing effect is not satisfactory.
The elution crystallization is to dissolve a solute in water or another solvent by utilizing a difference in an interaction force between molecules of the substance to be separated and the solvent, and then to add another solvent or to lower a temperature to lower a solubility of the solute in the original solvent, thereby precipitating and crystallizing the solute. The elution crystallization technology has important application in the fields of medicine, food, inorganic salt, high molecular material and the like. In order to solve the problems of difficult operation and uneven mixing of IMP and GMP caused by different crystal forms, powder shapes and powder characteristics, the existing method is to realize the mixing of molecular degree by preparing flavor nucleotide disodium crystals (I + G) by a mixed elution crystallization technology.
The Chinese patent 201210214154.1 discloses a process for I + G crystallization and refining. The method comprises the steps of taking pretreated I + G mother liquor as a raw material, dissolving at 45-65 ℃, precipitating crystals by ethanol dissolution, cooling to 20-40 ℃, then heating to 65 ℃, and then continuously cooling to 10 ℃, so that the average grain size of the product is improved. The method is realized by continuously adding ethanol to dissolve crystals, crystallization nucleation is not strictly controlled, the solubility of I + G in a pure water system is rapidly reduced along with the increase of the content of alcohol, explosive nucleation is easily caused, and the product crystals are relatively fine. After the temperature is reduced to a large amount of precipitated crystals, the temperature of the feed liquid is increased to 65 ℃ to eliminate fine crystals, and the method has the defects that the temperature rise range is too large (35 ℃), the reaction hysteresis effect is poor and a large amount of energy is consumed. The crystal is flaky, the bulk density of the product is low, the shape is poor, and the agglomeration is easy.
Chinese patent CN105031963A discloses a method for manufacturing undersaturation by vacuum evaporation of solvent for temperature-reducing crystallization of anti-solvent. During the preparation process, the sample is dissolved first, and sufficient anti-solvent is added to completely separate out the crystal. And (3) repeatedly carrying out vacuum evaporation operation, reducing pressure, wherein the evaporation amount of the anti-solvent is more than that of the solvent due to larger volatility difference, increasing the solubility to dissolve crystal particles, then cooling or cooling and crystallizing to the end point, filtering, washing and drying to obtain crystal particle products. The method is characterized in that an anti-solvent is added continuously for crystallization at first, and seed crystals are not added to control the supersaturation degree of the initial crystallization stage, so that the nucleation is easy to generate fine particles; although the anti-solvent is evaporated in vacuum in the later stage to increase the solubility and dissolve crystal particles, the particles are not distinguished, large particles and small particles are dissolved at the same time to consume undersaturation, the anti-solvent amount of each evaporation is less, the range of increasing the solubility is limited, the time consumption is longer, the operation is more complicated, the energy consumption is higher, the effect is limited, the anti-solvent waste is easily caused, and the cost is increased.
Comprehensive analysis shows that in the prior art, in order to obtain I + G crystals with large particle sizes and narrow distribution, the supersaturation degree needs to be controlled in the crystallization process, so that the supersaturation degree is maintained in a metastable zone, and the crystals tend to grow rather than nucleate. And the primary explosion nucleation after the accumulation of supersaturation and the secondary nucleation caused by the complexity of crystallization environment also generate fine particles, and important factors which seriously influence the particle size distribution of the product need to be effectively controlled.
Disclosure of Invention
The invention aims to overcome the adverse effects that the existing fine particle dissolving technology is generally low in feasibility, unobtrusive in effect and high in energy consumption, and the batch production time is greatly prolonged. The process for cooling and crystallizing the anti-solvent by using solvent spraying oscillation is provided, so that the efficient dissolution of solid small particles in the solution is realized, and the effective control of the product granularity is realized.
The principle of the invention is as follows:
according to the method, the efficiency of pretreatment such as dissolution and decoloration is generally improved at a higher temperature in a factory, a crystallization liquid with a slightly high concentration can be prepared at the moment, a part of volume of the solution is reserved for solvent oscillation, a seed crystal adding mode is adopted for controlling primary explosion nucleation, and solvent spray oscillation is used for dissolving fine crystals of secondary nucleation. Two modes of high temperature and pressurized spray feeding are introduced to improve the feasibility of solvent oscillation, the solvent has higher dissolving power by increasing the temperature of the solvent, the solvent is added almost without time lag by the pressurized spray feeding, and the upper solution can form instantaneous local under saturation. The reduced stirring speed results from natural sedimentation and stratification of the particles according to Stokes' law, and the fine particles are dissolved faster than the large particles. Therefore, fine particles can be dissolved in a targeted manner, and when the solute is separated out again, because a certain amount of solvent is added, the supersaturation degree is low, the solute can grow on the surface of enough crystals instead of nucleating.
The purpose of the invention is realized by the following technical scheme:
a method for producing IMP + GMP by anti-solvent cooling crystallization based on solvent spraying oscillation comprises the following steps: adding IMP and GMP as raw materials into water in a crystallization kettle, heating and stirring until the IMP and GMP are completely dissolved, and adjusting the pH value; adding an anti-solvent dropwise, adding seed crystals for growing crystals, cooling to 45-55 ℃, and reducing the stirring speed to enable precipitated crystal particles to settle and stratify; forming fan-shaped water mist by solvent water through a spray head, spraying the fan-shaped water mist onto the liquid surface of the raw material of the crystallization kettle, controlling the using amount of the solvent water subjected to primary solvent spraying oscillation to be 25-50% of the total amount of the solvent, controlling the primary spraying time to be 1-2 min, recovering stirring until the temperature is raised and stirred, and cooling to form primary solvent spraying oscillation; repeating solvent spraying oscillation for 2-4 times, wherein the temperature of solvent spraying oscillation for each time is reduced by 10-20 ℃, and the temperature of solvent spraying oscillation for the last time is above 25 ℃; cooling, filtering, washing and drying to obtain a crystallized product.
In order to further achieve the purpose of the invention, preferably, the solvent water forms fan-shaped water mist through a spray head and is sprayed on the liquid surface of the raw material of the crystallization kettle, and the air pressure and the solvent water pressure from an air compressor and a jacket vacuum cup are respectively controlled through an air pressurization atomizer, so that the spraying speed of the solvent water is 0.5-1 mL/s; the volume ratio of the air to the solvent water is 800-1500: 1.
Preferably, the amount of the solvent water for solvent spraying oscillation is 30-50% of the amount of the solvent water for dissolution in the initial crystallization kettle; after the raw materials IMP and GMP are added into water in a crystallization kettle, the concentration of the IMP and GMP is 20-35% g/mL.
Preferably, the time of one-time spraying is controlled to be 1-2 min.
Preferably, the mass ratio of IMP to GMP in the raw materials IMP and GMP is 0.95-1.05: 1.
Preferably, the temperature is increased and stirred to be 60-70 ℃ until the mixture is completely dissolved; the PH value is adjusted to 7.5-8.5.
Preferably, the volume ratio of the addition amount of the anti-solvent to water in the crystallization kettle is 1: 2-2.3; the anti-solvent is ethanol water solution with volume concentration of more than 90.
Preferably, the seed crystal is a crystal of IMP and GMP, and the mass ratio of IMP to GMP is 1: 2-2: 1; the adding amount of the seed crystal is 3 to 10 percent of the mass of the IMP and GMP; the time for growing the crystals is 15-30 min.
Preferably, the rotation speed of stirring in the processes of heating, dissolving and crystallizing is 150-200 rpm; the rotating speed for reducing the stirring speed is 50-100 rpm.
Preferably, the temperature reduction and filtration is to reduce the temperature to 10-15 ℃, and the temperature is reduced to 10-15 ℃ in the temperature reduction process according to the speed of 4-6 ℃/h, 7-9 ℃/h, 10-12 ℃/h, 12-14 ℃/h and 14-16 ℃/h for 5-6 hours.
Compared with the prior art, the invention has the following advantages:
(1) based on the solubility data of I + G in an ethanol-water system, the anti-solvent is added until the solution is saturated, and the seed crystal is added to effectively inhibit primary burst nucleation caused by supersaturation accumulation. The cooling speed is reasonably designed, the solubility of the solution at the early stage is reduced rapidly along with the reduction of the temperature, the total surface of crystals capable of providing crystal growth in the solution is small, and the low supersaturation is controlled by adopting the slow cooling speed; later solution solubility decreases with temperature change, the total surface area of the crystal increases, and the rate of cooling is accelerated to meet the consumption of supersaturation.
(2) The crystallization process is reduced to a proper stirring speed after being carried out to a certain degree, the particle size can be layered by utilizing natural sedimentation according to the Stokes law, and large particles are settled to the bottom and small particles are suspended on the upper layer. At the moment, the solvent is quickly and uniformly added into the upper layer, fine particles generated by secondary nucleation can be effectively dissolved, and are precipitated under a lower supersaturation degree after dissolution, and the growth on the surface of crystals is favored instead of nucleation to generate new small particles. The final product has large granularity and good crystal form.
(3) The solvent for oscillation is insulated in a jacketed cup connected with the crystallization kettle in series in a water bath, so that the temperature fluctuation of the solvent during oscillation can be ensured to be small, and the solvent at the temperature higher than room temperature has relatively better dissolving strength; the feeding mode of pressurized spraying not only consumes short time, but also can generate instant local undersaturation dissolved fine particles on the upper layer solution due to mixing time lag at low stirring speed. Both measures allow better results with a limited amount of solvent to be used. Compared with other fine particle dissolving technologies, the method is simpler and easier to implement on the premise of ensuring the effect, and has no influence on batch production time.
Drawings
Fig. 1 is a schematic diagram of a device for producing IMP + GMP by oscillating anti-solvent cooling crystallization based on solvent spraying.
Figure 2 is a graph of malvern particle size data for crystal particles of the products obtained in the examples and comparative examples.
FIG. 3 is an optical microscope photograph of crystal particles of the product obtained in example 1.
FIG. 4 is an optical microscope photograph of crystal particles of the product obtained in example 2.
FIG. 5 is an optical microscope photograph of crystal particles of the product obtained in example 3.
FIG. 6 is an optical microscope photograph of crystal particles of the product obtained in example 4.
FIG. 7 is an optical microscope photograph of crystal particles of the product obtained in comparative example 1.
Detailed Description
The present invention will be further described with reference to the following examples for better understanding, but it should be noted that the scope of the present invention as claimed is not limited to the scope expressed by the following examples.
As shown in fig. 1, the device for producing IMP + GMP by temperature reduction and crystallization based on solvent spraying oscillation anti-solvent is obtained by improvement on the basis of the existing crystallizer, and the main improvement point is that a spray head 5 is arranged in a crystallization kettle, and the spray head 5 is connected with one end of an air pressurization atomizer 4; the other end of the air pressurization atomizer 4 is provided with an air inlet 6 and a water inlet 7 respectively, the air inlet 6 is connected with an air compressor 8 through an air pipe, the water inlet 7 is connected with a jacket vacuum cup 11 through a hose, and the hose is provided with a metering pump 9. An electric thermocouple thermometer 12 and a material ejecting type stirring paddle 3 are arranged in the crystallization kettle 1, the material ejecting type stirring paddle 3 is connected with the stirrer 2, and the stirring speed is controlled by the stirrer 2. The crystallization kettle 1 is connected in series with a jacket vacuum cup 11 and a high-low temperature constant temperature groove 10 through a heat preservation hose.
The device for producing IMP + GMP based on solvent spraying oscillation antisolvent cooling crystallization in figure 1 is mainly characterized in that an air pressurization atomizer 4 is additionally arranged on an original basic crystallizer and used for adding a solvent in a crystallization process to realize a fine particle dissolving technology, liquid conveyed by a metering pump is accelerated by air pressurization conveyed by an air compressor 8 in a cavity of the atomizer 4 and is ejected out from a nozzle 5 together, and the ejected liquid is fan-shaped and has certain penetrating power. Since the stirring speed is reduced when the solvent is added, large particles settle, and the solvent which is uniformly sprayed and mixed into the upper layer can well dissolve suspended fine particles. The feeding of the conventional metering pump can only be carried out by single-point feeding, the feeding is uneven, the penetrating power does not exist, and the mixing depends on the stirring speed. And when the stirring speed is higher, the particles are difficult to naturally stratify, and the undersaturation degree can be consumed by the dissolution of large particles, so that no pertinence is provided for the dissolution of fine particles, and the effect is relatively poor.
Weighing IMP and GMP raw materials with required mass by using an analytical balance, and measuring a solvent with required volume by using a measuring cylinder. Opening a feeding port on the crystallization kettle 1, placing a feeding funnel, firstly pouring the solid raw materials IMP and GMP from the feeding funnel, then pouring the solvent, taking down the feeding funnel, closing the feeding port, and starting a dissolving process; after the dissolution is finished, the anti-solvent is directly input through a metering pump through a feeding port, the addition of the anti-solvent is finished, the feeding port is closed, and the subsequent steps are started.
Example 1
A method for producing IMP + GMP based on solvent spraying oscillation antisolvent cooling crystallization comprises the following steps:
the first step is as follows: 30g of each of IMP and GMP is weighed by an analytical balance, 200mL of water is weighed by a measuring cylinder, the IMP and the GMP are added into a 500mL crystallization kettle 1, the solute is fully dissolved by controlling the temperature of a high-low temperature constant temperature bath 10 in a water bath to be raised to 65 ℃ and stirring speed of 180rpm, and the pH is adjusted to 7.9. 80mL of water was then held in a jacketed thermos cup 11 in series with a crystallizer water bath. Adding 100mL of anti-solvent 90% ethanol at an addition rate of 4mL/min, adding 2.8g of IMP + GMP seed crystal (the mass ratio of IMP to GMP seed crystal is 1: 1), mixing IMP and GMP, recrystallizing for 20min, starting the program to cool to 5 ℃/h, 8 ℃/h, 12 ℃/h, 14 ℃/h and 16 ℃/h, and cooling to the end point within 5 hours.
The second step is that: when the temperature is reduced to 55 ℃, the stirring speed of the stirrer 2 is adjusted to be reduced to 50rpm, particles naturally settle and stratify, the air compressor 8 is firstly started, the air inlet 6 of the air pressurization atomizer 4 is adjusted, the valve controls the air flow to be 70L/min, then the metering pump 9 is started to suck the solvent in the jacket vacuum cup 11 at the speed of 0.8mL/s and convey the solvent to the air pressurization atomizer 4, at the moment, the visible spray head 5 sprays fan-shaped water mist to the liquid level of the crystallization kettle, and the water mist is not gathered into a water column under the assistance of air and has certain penetrating power. And (3) when the sprayed water amount reaches 40mL, firstly closing the metering pump 9, then closing the air compressor 8, and resuming stirring at 180rpm to complete one-time solvent oscillation. The temperature is reduced to 35 ℃, the stirring speed is reduced to 70rpm, 40mL of water is used, the flow rate of the water is adjusted to be 1mL/s, and the air flow is adjusted to be 90L/min to carry out the second solvent oscillation operation.
The third step: cooling to 10 ℃, filtering, washing and drying to obtain larger crystal particles with narrower particle size distribution. The malvern granulometer measurement result indicates that the median diameter d (50) is 418 μm, which represents the major particle size of the entire particle.
FIG. 3 is an optical microscope photograph of crystal particles of the product obtained in example 1. The IMP + GMP crystals in FIG. 3 are coarse rod-like crystals, and the particle size distribution is relatively uniform, and the amorphous powder is small. The fine particles generated by secondary nucleation in the crystallization process are well controlled by solvent spraying oscillation, and the solvent has good dissolving effect on amorphous clusters and fine crystal nuclei.
Example 2
The first step is as follows: 30g of each of IMP and GMP is weighed by an analytical balance, 200mL of water is weighed by a measuring cylinder, the IMP and the GMP are added into a 500mL crystallization kettle 1, the solute is fully dissolved by controlling the temperature of a high-low temperature constant temperature bath 10 in a water bath to be raised to 65 ℃ and stirring speed of 180rpm, and the pH is adjusted to 7.8. 105mL of water was then held in a jacketed thermos cup 11 in series with a water bath from a crystallizer. Adding 100mL of anti-solvent 90% ethanol at the adding rate of 6mL/min, adding 3.0g of IMP + GMP seed crystal (the mass ratio of the IMP seed crystal to the GMP seed crystal is 1: 2), mixing the IMP seed crystal and the GMP seed crystal for recrystallization, growing the crystal for 20min, starting the program to cool down 4 ℃/h, 6 ℃/h, 8 ℃/h, 10 ℃/h, 12 ℃/h and 14 ℃/h, and cooling down to the end point within 6 hours.
The second step is that: when the temperature is reduced to 55 ℃, the stirring speed of the stirrer 2 is adjusted to be reduced to 50rpm, particles naturally settle and stratify, the air compressor 8 is firstly started, the air inlet 6 of the air pressurization atomizer 4 is adjusted, the valve controls the air flow to be 30L/min, then the metering pump 9 is started to suck the solvent in the jacket vacuum cup 11 at the speed of 0.5mL/s and convey the solvent to the air pressurization atomizer 4, at the moment, the nozzle 5 can be seen to spray fan-shaped water mist to the liquid level of the crystallization kettle, and the water mist is not gathered into a water column and has certain penetrating power under the assistance of air. And (3) when the sprayed water amount reaches 30mL, firstly closing the metering pump 9, then closing the air compressor 8, and resuming stirring at 180rpm to complete one-time solvent oscillation. When the temperature was lowered to 45 ℃ and 30 ℃, the stirring speed was adjusted to 60rpm and 80rpm, respectively, using 35mL and 40mL of water, and the flow rate was adjusted to 0.7mL/s and the air flow rate was adjusted to 60L/min, thereby carrying out the second and third solvent shaking operations.
The third step: cooling to 11 ℃, filtering, washing and drying to obtain larger crystal particles with narrower particle size distribution. The malvern granulometer measurement result indicates that the median particle diameter d (50) is 480 μm, which represents the major particle size of the entire particle.
FIG. 4 is an optical microscope photograph of crystal particles of the product obtained in example 2. The IMP + GMP crystals in FIG. 4 exhibited coarse rod-like crystals, more uniform particle size distribution, less needle-like fine particles, and less amorphous powder, compared to example 1. The fine particles generated by secondary nucleation in the crystallization process are better controlled when the solvent spraying oscillation is adopted and the solvent amount gradient is increased progressively, and the solvent has better dissolving effect on amorphous clusters and fine crystal nuclei.
Example 3
The first step is as follows: 30g of IMP and GMP are weighed by an analytical balance respectively, 220mL of water is weighed by a measuring cylinder, the IMP and the GMP are added into a crystallization kettle 1, the temperature is raised to 63 ℃ in a water bath by controlling a high-low temperature constant temperature bath 10, the solute is fully dissolved by stirring at the stirring speed of 200rpm, and the pH is adjusted to 7.6. 100mL of water was then held in a jacketed thermos cup 11 in series with a crystallizer water bath. Adding 110mL of anti-solvent 90% ethanol at the adding rate of 6mL/min, adding 4.0g of IMP + GMP seed crystal (the mass ratio of the IMP seed crystal to the GMP seed crystal is 2: 1), mixing the IMP seed crystal and the GMP seed crystal for recrystallization to obtain the crystal, growing the crystal for 20min, starting the program to cool down by 5 ℃/h, 7 ℃/h, 10 ℃/h, 14 ℃/h and 15 ℃/h, and cooling down to the end point within 5 hours.
The second step is that: when the temperature is reduced to 53 ℃, the stirring speed of the stirrer 2 is adjusted to be reduced to 60rpm, particles naturally settle and stratify, the air compressor 8 is firstly started, the air inlet 6 of the air pressurization atomizer 4 is adjusted to control the air flow by 60L/min, then the metering pump 9 is started to suck the solvent in the jacket vacuum cup 11 at the speed of 0.5mL/s and convey the solvent to the air pressurization atomizer 4, at the moment, the visible spray head 5 sprays fan-shaped water mist onto the liquid surface of the crystallization kettle, and the water mist is not gathered into a water column and has certain penetrating power under the assistance of air. And (3) when the sprayed water amount reaches 25mL, firstly closing the metering pump 9, then closing the air compressor 8, and resuming the stirring at 200rpm to complete the primary solvent oscillation. When the temperature was lowered to 43 ℃, 34 ℃ and 25 ℃, the stirring speed was adjusted to 70rpm, 80rpm and 90rpm, respectively, and 25mL of water was used, and the flow rate was adjusted to 0.5mL/s and the air flow rate was adjusted to 60L/min, thereby carrying out the second, third and fourth solvent shaking operations.
The third step: cooling to 12 ℃, filtering, washing and drying to obtain larger crystal particles with narrower particle size distribution. The malvern granulometer measurement result indicates that the median diameter d (50) is 405 μm, which represents the major particle size of the entire particle.
FIG. 5 is an optical microscope photograph of crystal particles of the product obtained in example 3. In this example, four times of equal spraying solvent shaking was used, and the IMP + GMP crystals in FIG. 5 appeared as thicker rod-like crystals, but the particle size distribution was slightly non-uniform, a certain amount of fine acicular particles were present, and the amount of amorphous powder was small. The use amount of solvent water sprayed each time is relatively small, the later fine particle dissolving effect is poor, the crystal quality is greatly improved compared with that of the crystal in the comparative example 1, and the solvent spraying oscillation has extremely high control efficiency on the crystallization process.
Example 4
The first step is as follows: 30g of IMP and GMP are weighed by an analytical balance respectively, 250mL of water is weighed by a measuring cylinder, the IMP and the GMP are added into a crystallization kettle 1, the temperature is raised to 63 ℃ in a water bath by controlling a high-low temperature constant temperature bath 10, the solute is fully dissolved by stirring at the stirring speed of 200rpm, and the pH is adjusted to 8.0. 75mL of water was then held in a jacketed thermos cup 11 in series with a crystallizer water bath. Adding 120mL of anti-solvent 90% ethanol at the adding rate of 6mL/min, adding 5.0g of IMP + GMP seed crystal (the mass ratio of the IMP seed crystal to the GMP seed crystal is 1: 1), mixing the IMP seed crystal and the GMP seed crystal for recrystallization, growing the crystal for 20min, starting the program to reduce the temperature by 5 ℃/h, 8 ℃/h, 11 ℃/h, 14 ℃/h and 15 ℃/h, and reducing the temperature to the end point within 5 hours.
The second step is that: when the temperature is reduced to 50 ℃, the stirring speed of the stirrer 2 is adjusted to be reduced to 60rpm, particles naturally settle and stratify, the air compressor 8 is firstly started, the air inlet 6 of the air pressurization atomizer 4 is adjusted, the valve controls the air flow to be 40L/min, then the metering pump 9 is started to suck the solvent in the jacket vacuum cup 11 at the speed of 0.5mL/s and convey the solvent to the air pressurization atomizer 4, at the moment, the nozzle 5 can be seen to spray fan-shaped water mist to the page of the crystallization kettle, and the water mist is not gathered into a water column and has certain penetrating power under the assistance of air. And (3) when the sprayed water amount reaches 30mL, firstly closing the metering pump 9, then closing the air compressor 8, and resuming the stirring at 200rpm to complete the primary solvent oscillation. When the temperature is reduced to 35 ℃, the stirring speed is reduced to 70rpm, 45mL of water is used, the flow rate of the water is adjusted to be 0.7mL/s, the air flow is adjusted to be 60L/min, and the second solvent shaking operation is carried out.
The third step: cooling to 10 ℃, filtering, washing and drying to obtain larger crystal particles with narrower particle size distribution. The malvern granulometer measurement result indicates that the median particle diameter d (50) is 451 μm, which indicates the major particle size of the entire particle.
FIG. 6 is an optical microscope photograph of crystal particles of the product obtained in example 4. Example 4 using two solvent spray oscillations with increasing solvent gradient showed that the IMP + GMP crystals were coarse rod-like crystals with a more uniform particle size distribution, less amorphous powder and similar crystal quality to example 2.
Comparative example 1
30g of each of IMP and GMP is weighed by an analytical balance, 300mL of water is weighed by a measuring cylinder, the IMP and the GMP are added into a 500mL crystallization kettle 1, the temperature of a high-low temperature constant temperature bath 10 is controlled to be raised to 50 ℃, the solute is fully dissolved by stirring at the stirring speed of 200rpm, and the pH is adjusted to 7.9. Adding 120mL of anti-solvent 90% ethanol at an addition rate of 5mL/min, adding 6.0g of IMP + GMP seed crystal (the mass ratio of IMP to GMP seed crystal is 1: 1), recrystallizing the seed crystal by mixing IMP and GMP, growing crystal for 20min, and starting a program to cool. Cooling to 12 ℃, filtering, washing and drying to obtain crystal particles with smaller obvious particle size. The malvern granulometer measurement result indicates that the median diameter d (50) is 192 μm, which represents the major particle size of the entire particle.
FIG. 7 is an optical microscope photograph of crystal particles of the product obtained in comparative example 1. The comparative example shows that the crystal grain product is elongated needle-shaped crystals and a little amorphous, and the grain agglomeration is serious because the amount of fine grains in the crystallization process is not controlled. The combination of the particle size analyzer test result shows that by using the spray solvent oscillation technology, fine particles generated in the crystallization process are effectively dissolved, the crystal growth in the crystallization process is promoted, and the final product has larger particle size and better appearance quality.
d (50) refers to the particle size at which the cumulative distribution of particles is 50%. Also called median or median particle size, is a typical value representing the size of the particle, which accurately divides the population into two equal parts, i.e. 50% of the particles are above this value and 50% are below this value, which is most often used to represent the major particle size of the particle population as a whole.
The quality of the crystal product, such as crystal morphology, particle size and particle size distribution, can affect the crystallization process route and downstream processes, such as filtration, washing, drying, grinding, packaging, storage, etc., and further affect the equipment design and processing, investment cost, process operation, etc. The high-quality flavor enhancer generally has the advantages of good crystal grain appearance, large granularity, good fluidity and the like. Most of the commercially available crystals of monosodium glutamate, salt, sugar, etc. are in the form of rods or blocks, and the major particle size is large (200 μm or more). The I + G serving as the main component of the super-fresh monosodium glutamate, the chicken essence and other seasonings should meet the requirements of good crystal appearance, large granularity, good fluidity and the like, so that the composite flavoring agent obtained by mixing the I + G with the monosodium glutamate and the like still has the characteristics of uniform granularity, good fluidity and the like, and the high-quality flavoring agent is prepared. The IMP + GMP crystal particle product prepared by the invention is thick and rod-shaped, the amorphous precipitation is very little, the main granularity reaches 360-480 mu m, the downstream process efficiency is effectively improved, the production cost is saved, and the requirements of high-quality flavor enhancers are met.
According to the invention, the primary nucleation is controlled by adding seed crystals, the secondary nucleation fine particles are eliminated by introducing spray solvent to vibrate, the final product particles are observed to be thick and rod-shaped by a polarizing microscope, little amorphous generation is generated, and the main particle size is increased from 192 microns to 360-480 microns by a Malvern particle sizer. Although the process adds a spraying solvent oscillation step, the time consumption is short (within 2 minutes) each time, and the batch production time is not influenced when the temperature is reduced, and the additional energy consumption is extremely low.
The Chinese patent 201210214154.1 dissolves fine particles by heating the solution which is cooled and crystallized to a certain degree (the temperature rise range is 25-45 ℃), and the crystallization kettle is based on the jacket convection heat transfer principle, so that the energy loss is large, the temperature rise range is large, the time consumption is long, the energy consumption is high, and the batch production time and the production energy consumption are increased. And the crystallization process is controlled only once, the dissolution is not targeted, the control effect is poor, the final product particles are flaky crystals, and the main particle size is only 40-60 mu m.
According to the Chinese patent CN105031963A, the solution which is cooled and crystallized to a certain degree is vacuumized (the pressure is reduced to 20-60 kPa), and the evaporation of the anti-solvent is more than that of the solvent by utilizing the volatility difference of the anti-solvent and the solvent, so that the proportion of the anti-solvent in the solution is reduced, the solubility is increased, and particles are dissolved. Most of the anti-solvents are organic alcohol reagents, the waste of the reagents is added by the measures, the recovery cost is increased, the pollution risk is increased, and the implementation process is difficult to control. And the evaporation solution has small amplitude and many times, the dissolution of particles with sizes which are not distinguished is lack of pertinence, the batch production time is increased, the increase of the main particle size of the product in each embodiment is limited (the increase is 20-40 mu m), and the control effect is poor.
Chinese patent CN201921832883.7 discloses a spray crystallization device and a sugar alcohol production device, which essentially comprises melting spray crystallization, scattering the raw material slurry in a molten state by using compressed air, making it dispersedly attached to the surface of the seed crystal particles in the crystallizer, and then cooling and solidifying the crystals. The technology has requirements on the properties of raw materials, requires low melting point of the raw materials and stable properties at high temperature, and is often used for producing small-particle spherical crystal products. The technology of the patent is a solution crystallization category, the penetrating power and the uniformity when the solvent is added are increased by utilizing compressed air and an atomizing spray head in the solution crystallization process, the crystal particles are distinguished according to the size by matching with the reduction of the stirring speed, the fine particles which are not expected to be generated in the solution crystallization process are eliminated efficiently, and the thick and large rod-shaped crystal particle products are produced.
The embodiments of the present invention are not limited to the above-described embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which are made without departing from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A method for producing IMP + GMP by anti-solvent cooling crystallization based on solvent spraying oscillation is characterized in that: adding IMP and GMP as raw materials into water in a crystallization kettle, heating and stirring until the IMP and GMP are completely dissolved, and adjusting the pH value; adding an anti-solvent dropwise, adding seed crystals for growing crystals, cooling to 45-55 ℃, and reducing the stirring speed to enable precipitated crystal particles to settle and stratify; forming fan-shaped water mist by solvent water through a spray head, spraying the fan-shaped water mist onto the liquid surface of the raw material of the crystallization kettle, controlling the using amount of the solvent water subjected to primary solvent spraying oscillation to be 25-50% of the total amount of the solvent, controlling the primary spraying time to be 1-2 min, recovering stirring until the temperature is raised and stirred, and cooling to form primary solvent spraying oscillation; repeating solvent spraying oscillation for 2-4 times, wherein the temperature of solvent spraying oscillation for each time is reduced by 10-20 ℃, and the temperature of solvent spraying oscillation for the last time is above 25 ℃; cooling, filtering, washing and drying to obtain a crystallized product.
2. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the solvent water forms fan-shaped water mist through a spray head and is sprayed on the liquid surface of the raw material of the crystallization kettle, and the air pressure and the solvent water pressure from an air compressor and a jacket vacuum cup are respectively controlled through an air pressurization atomizer, so that the spraying speed of the solvent water is 0.5-1 mL/s; the volume ratio of the air to the solvent water is 800-1500: 1.
3. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the amount of the solvent water for solvent spraying oscillation is 30-50% of the amount of the solvent water for dissolving in the initial crystallization kettle; after the raw materials IMP and GMP are added into water in a crystallization kettle, the concentration of the IMP and GMP is 20-35% g/mL.
4. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the primary spraying time is controlled to be 1-2 min.
5. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the mass ratio of IMP to GMP in the raw materials IMP and GMP is 0.95-1.05: 1.
6. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the temperature is increased and stirred until the temperature for complete dissolution is 60-70 ℃; the PH value is adjusted to 7.5-8.5.
7. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the volume ratio of the addition amount of the anti-solvent to the water in the crystallization kettle is 1: 2-2.3; the anti-solvent is ethanol water solution with volume concentration of more than 90.
8. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the crystal seed is crystal of IMP and GMP, and the mass ratio of IMP to GMP is 1: 2-2: 1; the adding amount of the seed crystal is 3 to 10 percent of the mass of the IMP and GMP; the time for growing the crystals is 15-30 min.
9. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the rotation speed of stirring in the processes of heating, dissolving and crystallizing is 150-200 rpm; the rotating speed for reducing the stirring speed is 50-100 rpm.
10. The method for producing IMP + GMP based on spraying solvent, shaking anti-solvent and cooling crystallization according to claim 1, which is characterized in that: the temperature reduction and filtration is to reduce the temperature to 10-15 ℃, and the temperature is reduced to 10-15 ℃ in the temperature reduction process according to the speed of 4-6 ℃/h, 7-9 ℃/h, 10-12 ℃/h, 12-14 ℃/h and 14-16 ℃/h for 5-6 hours.
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