Production device and process for increasing magnesium citrate crystal content

Abstract

The invention provides a production device and process for increasing the content of magnesium citrate crystals. The problems that in the prior art, the impurity co-crystallization rate is high, and crystal forms are difficult to control are solved. The device comprises a gradient temperature control multi-stage crystallization device and a crystal form directional regulation and self-adaptive separation system. The gradient temperature control multi-stage crystallization device is composed of a main crystallizer, a gradient temperature control system, an ultrasonic-assisted system and a liquid phase partition circulating system, and the crystallization environment is accurately controlled through the temperature gradients of five independent temperature zones. The crystal form directional regulation and self-adaptive separation system is composed of a seed crystal dynamic inoculation device, an electric field auxiliary directional crystallization system, a real-time crystal morphology analysis system and a self-adaptive separation system, and the crystal morphology and particle size distribution can be accurately controlled. According to the process disclosed by the invention, the main content of magnesium citrate is increased to 98.8 + / -0.3%, heavy metal impurities and organic impurities are respectively reduced by 70% and 75%, the crystal form consistency is increased to 96 + / -2%, the production period is shortened by 33%, and the process has remarkable economic benefits and social benefits.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of inorganic compound preparation, and particularly relates to a production device and process for improving the content of magnesium citrate crystals. BACKGROUND

[0002] Magnesium citrate is an important magnesium supplement and pharmaceutical excipient, and is widely used in the fields of medicine, food and cosmetics. In the field of medicine, magnesium citrate is used for the treatment of magnesium deficiency, gastric acid neutralizer and mild laxative; in the food industry, it is widely used as a nutritional fortifier, acidity regulator and anti-caking agent; in the cosmetics industry, it is used as a stabilizer and pH regulator. High-purity magnesium citrate crystals have the characteristics of high bioavailability, good solubility and strong stability, and therefore the requirements for the purity and crystal form of magnesium citrate are increasing. With the growing demand for high-quality magnesium supplements worldwide, it is of great economic and social value to develop production technology that can improve the content and quality of magnesium citrate crystals.

[0003] At present, the main method for producing magnesium citrate in industry is to react citric acid with alkaline magnesium salt (such as magnesium oxide, magnesium hydroxide or magnesium carbonate) in aqueous solution, and then to obtain the final product through crystallization, separation and drying steps. The traditional production process mainly uses single-tank reaction crystallization device, and the crystallization process is controlled by controlling parameters such as reaction temperature, pH value and stirring speed. In the solution preparation stage, constant temperature heating and mechanical stirring are used to promote the reaction; in the crystallization stage, natural cooling or external refrigeration is usually used to reduce the solution temperature to induce the precipitation of crystals; in the separation stage, the crystals are separated from the mother liquor mainly by filtration or centrifugation, and then washed and dried to obtain the finished product. This traditional process has been applied for many years, and has the advantages of simple process and low equipment investment, but has obvious limitations in product quality and production efficiency.

[0004] The primary problem faced by existing magnesium citrate production technology is the high impurity co-crystallization rate in the crystallization process. Due to the limited temperature control accuracy in the traditional crystallization process, the temperature in the entire crystallizer is relatively uniform, and there is a lack of effective temperature gradient, which leads to the simultaneous crystallization of magnesium citrate generated by the reaction and other impurities (such as unreacted raw materials, by-products and metal ion impurities) in the solution during the cooling process. Especially when the cooling rate is not properly controlled, rapid cooling will cause the impurities in the solution to be quickly wrapped inside the magnesium citrate crystals or adsorbed on the crystal surface, forming mixed crystals containing impurities. In addition, the existing technology lacks an effective impurity separation mechanism, and it is difficult to completely remove the already co-crystallized impurities by relying solely on the subsequent washing process, resulting in low purity of the final product, usually with a main content of only 95%-97%, which is difficult to meet the needs of high-end applications.

[0005] The second major problem of the existing production technology of magnesium citrate is the difficulty in controlling the crystal form, resulting in unstable product quality. Magnesium citrate can form various crystal forms, including anhydrous crystal, dihydrate, trihydrate and tetrahydrate, etc., and different crystal forms have different physical and chemical properties and biological activity. In the traditional process, due to the lack of precise control means of the crystal growth environment, the crystallization process is mainly affected by accidental factors, resulting in significant differences in crystal form, particle size distribution and morphology between batches. Specifically, the crystal particle size is uneven, generally fluctuating between 10-200 μm; the crystal shape is irregular, and there are various morphologies such as needle-shaped, flaky and clustered; the crystal form is diversified, and there may be multiple hydrated crystals in the same batch of products. Such instability and diversity of crystal form directly affect the solubility, bioavailability and stability of the product, bringing many uncertainties to the downstream application, especially in the field of pharmaceutical preparations. SUMMARY

[0006] In view of the above problems, the present application provides a production device and process for improving the crystal content of magnesium citrate.

[0007] A production device for improving the crystal content of magnesium citrate, comprising:

[0008] A main crystallizer with a double-wall jacket design, the inner wall is made of ceramic material, the outer wall is made of stainless steel material, and the inner and outer walls form a interlayer for passing temperature control medium;

[0009] A gradient temperature control system divides the main crystallizer into multiple independent temperature zones in the vertical direction, each temperature zone is separated by an adjustable partition, and the partition is provided with a solution flow hole;

[0010] An ultrasonic auxiliary system comprising multiple groups of frequency-adjustable ultrasonic generators and ultrasonic transducers installed at different height positions of the crystallizer;

[0011] A liquid phase partition circulation system, comprising an arc-shaped partition plate for dividing the internal space of the crystallizer into a central zone and an annular zone, and a variable frequency circulating pump for controlling the circulation rate of different zones.

[0012] Further, the gradient temperature control system further comprises:

[0013] Temperature sensors installed in each temperature zone;

[0014] Independent heating / cooling units configured in each temperature zone;

[0015] A central control unit for realizing dynamic adjustment of temperature gradient.

[0016] Further, the system comprises:

[0017] A crystal seed dynamic seeding device for preparing and injecting standard crystal seeds;

[0018] The electric field assisted directional crystallization system comprises a plurality of pairs of electrode plates uniformly distributed circumferentially along the crystallizer.

[0019] The real-time crystal morphology analysis system is used for monitoring the morphology and particle size distribution in the crystal growth process.

[0020] The adaptive separation system automatically optimizes the separation, cleaning and drying parameters according to the crystal characteristic data.

[0021] Further, the seed dynamic seeding device comprises:

[0022] The microfluidic seed preparation unit has a T-shaped microchannel structure.

[0023] The seed temporary storage is equipped with a precision temperature control system.

[0024] The quantitative seeding pump system is used to control the seed injection.

[0025] The seeding position control device can accurately position in three directions inside the main crystallizer.

[0026] Further, the electric field assisted directional crystallization system comprises:

[0027] The titanium alloy electrode plate;

[0028] The high-precision electric field generator has an adjustable voltage and frequency range.

[0029] The electric field distribution monitoring unit is used to monitor the electric field intensity distribution inside the crystallizer.

[0030] The electric field parameter automatic adjustment system dynamically adjusts the electric field parameters based on the crystal growth feedback data.

[0031] The above device improves the production method of magnesium citrate crystal content, comprising the following steps:

[0032] Prepare an aqueous solution of citric acid and magnesium oxide with a molar ratio of 1:1, add a selective chelating agent, and filter to obtain a pretreated liquid;

[0033] Set the initial temperature of each temperature zone of the main crystallizer to form a temperature gradient from top to bottom.

[0034] Pump the pretreated liquid into the top temperature zone of the main crystallizer, and start the liquid phase partitioning circulation system at the same time.

[0035] When the solution supersaturation reaches the preset value, start the ultrasonic assisted system to promote nucleation.

[0036] According to the real-time monitoring of the nucleation state, automatically adjust the temperature gradient of each temperature zone through the central control unit.

[0037] The temperature gradient of the temperature interval and the liquid phase partition circulation system are used to promote the impurities to precipitate in a specific temperature zone.

[0038] The crystal suspension is collected from the bottom of the main crystallizer, and the product is obtained by centrifugal separation, washing and drying.

[0039] Further, the above method further comprises a crystal form orientation regulation step:

[0040] Uniform standard seeds are prepared in a microfluidic seed preparation unit;

[0041] When the supersaturation of the solution in the main crystallizer reaches 1.05-1.10, the seed solution is injected into the predetermined position through the quantitative seeding pump system (73);

[0042] The electric field assisted directional crystallization system is started, the electric field intensity and frequency are set, and the arrangement of magnesium citrate molecules in a specific direction is promoted;

[0043] Crystal form regulating agents are added during the crystallization process to control the growth rate of specific crystal faces;

[0044] A real-time crystal morphology analysis system is used to monitor the crystal growth process, and the process parameters are dynamically adjusted according to the monitoring results;

[0045] Crystal aging treatment is carried out to promote crystal defect self-healing and lattice rearrangement;

[0046] According to the crystal morphology analysis results, the separation, cleaning and drying parameters are optimized through the adaptive separation system.

[0047] Further, in the electric field assisted directional crystallization step, the electric field intensity is 200-500 V / m, the frequency is 50 Hz, and the electric field direction is along the axis of the crystallizer to promote the arrangement of magnesium citrate molecules along the c-axis direction.

[0048] Further, the crystal form regulating agent adding step comprises:

[0049] 0.01% (w / w) polyvinylpyrrolidone is added in temperature zone 22 as a {110} crystal face growth inhibitor;

[0050] 0.005% (w / w) sodium dodecyl sulfate is added in temperature zone 23 as a {101} crystal face growth promoter;

[0051] The pH value is adjusted to 6.2±0.1 and the ionic strength is adjusted to 0.15 mol / L in temperature zone 24 to promote the growth of flaky crystals.

[0052] Further, the initial temperatures of the five temperature zones of the main crystallizer are set as follows:

[0053] Temperature zone 21: 60±0.1℃;

[0054] Temperature zone 22: 55±0.1℃;

[0055] Temperature zone 23: 50±0.1℃;

[0056] Temperature zone 24: 45±0.1℃;

[0057] Temperature zone 25: 40±0.1℃.

[0058] Advantages of the present application:

[0059] 1. The gradient temperature control multi-stage crystallization device of the present application adopts a five-independent-temperature-zone design, forming a precisely controlled temperature gradient during crystallization, so that magnesium citrate is crystallized under ideal conditions, while impurities are separated in specific temperature zones. The ultrasonic auxiliary system promotes uniform nucleation through an adjustable acoustic field, avoiding the phenomenon of impurity wrapping caused by rapid cooling. The liquid phase partition circulation system design makes solutions of different concentrations circulate in different temperature zones, further improving the impurity separation efficiency. Experimental verification shows that the main content of magnesium citrate crystals produced by the process of the present application can reach 98.8±0.3%, which is 2.6 percentage points higher than the traditional process of 96.2±1.5%; the content of heavy metal impurities is reduced from ≤50ppm to ≤15ppm, a decrease of 70%; the content of organic impurities is reduced from ≤0.8% to ≤0.2%, a decrease of 75%. This purity level enables the product to meet the most stringent pharmacopoeia standards and high-end application requirements, greatly expanding the application field of the product.

[0060] 2. The crystal form directional regulation and adaptive separation system of the present application realizes precise control of crystal morphology, particle size and hydration state through multiple innovative mechanisms. High-purity standard seeds prepared by microfluidic technology provide an ideal crystallization basis; the electric field assisted directional crystallization system utilizes the dipole moment characteristics of magnesium citrate molecules to promote molecular alignment in a specific direction; the precise addition of crystal form regulators controls the growth rate of specific crystal faces; the real-time crystal morphology analysis system and the adaptive separation system ensure product consistency. Through these technical measures, the present application successfully increases the crystal form consistency from 75±8% of the traditional process to 96±2%, an increase of 21 percentage points; the average particle size of the crystals can be precisely controlled within the range of 100±5μm, which is significantly better than the traditional process of 85±25μm. The batch stability of the product (RSD%) is reduced from 8.5% to 2.1%, an improvement of 75%. This highly consistent crystal form and stable quality characteristics make the product have a higher dissolution rate (an increase of 51%) and more predictable biological activity, which is particularly suitable for medical applications that require strict quality consistency.

[0061] 3.The whole technical scheme of the present application not only improves the product quality, but also greatly improves the production efficiency and environmental performance. The synergistic effect of the gradient temperature control multi-stage crystallization device and the crystal form directional regulation system shortens the production cycle from 24 hours of the traditional process to 16 hours, increasing by 33%; the product yield is increased from 82% to 94%, an increase of 12 percentage points. At the same time, the energy consumption is reduced from 1200kWh / t to 920kWh / t, saving 23%; the water resource consumption is reduced from 15t / t to 9t / t, reducing 40%; the wastewater discharge is reduced from 12t / t to 6.5t / t, reducing 46%. In addition, the equipment floor area is reduced by 29%, and the operator demand is reduced by 50%. The comprehensive improvement of these indicators not only significantly reduces the production cost and improves the economic benefit, but also reduces the resource consumption and environmental pollution, which meets the concept of green chemical production and brings long-term sustainable development advantages to the enterprise. BRIEF DESCRIPTION OF DRAWINGS

[0062] In order to more clearly illustrate the technical solutions in the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description only illustrate the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0063] Figure 1 The structural schematic diagram of the gradient temperature control multi-stage crystallization device of the embodiment of the present application;

[0064] Figure 2 The schematic diagram of the crystal form directional regulation and self-adaptive separation system of the embodiment of the present application;

[0065] Figure 3 The process flow schematic diagram of the gradient temperature control multi-stage crystallization process of the embodiment of the present application;

[0066] Figure 4 The process schematic diagram of the crystal form directional regulation process of the embodiment of the present application;

[0067] Figure 5 The product quality comparison schematic diagram of the embodiment of the present application;

[0068] Figure 6 The production efficiency comparison schematic diagram of the embodiment of the present application.

[0069] In the figure: 10, main crystallizer; 11, inner wall; 12, outer wall; 13, interlayer; 14, partition; 15, solution flow hole; 16, feeding pipe; 17, discharge port; 20, gradient temperature control system; 21-25, temperature zone; 26, temperature sensor; 27, heating / cooling unit; 28, central control unit; 30, ultrasonic auxiliary system; 31, ultrasonic generator; 32, ultrasonic transducer; 40, liquid phase partition circulation system; 41, arc-shaped partition; 42, central zone; 43, annular zone; 45, variable frequency circulating pump; 60, centrifugal separator; 70, crystal seed dynamic seeding device; 71, microfluidic crystal seed preparation unit; 72, crystal seed temporary storage; 73, quantitative seeding pump system; 74, seeding position control device; 80, electric field assisted directional crystallization system; 81, electrode plate; 82, high-precision electric field generator; 83, electric field distribution monitoring unit; 84, electric field parameter automatic adjustment system; 90, real-time crystal morphology analysis system; 91, laser diffraction particle size analyzer; 92, high-resolution digital microscope system; 93, image recognition and analysis software; 94, data processing unit; 100, adaptive separation system; 101, variable parameter centrifugal separator; 102, multi-stage cleaning system; 103, fluidized bed dryer; 104, parameter self-adaptive control unit. DETAILED DESCRIPTION

[0070] The present application will be described in detail below with reference to the drawings and specific embodiments. It should be noted that, in order to make the embodiments more detailed, the following embodiments are the best, preferred embodiments, and other alternative ways can also be implemented by those skilled in the art for some known technologies; and the drawings are only used to more specifically describe the embodiments, and are not intended to specifically limit the present application.

[0071] It should be noted that in the specification, "one embodiment", "embodiment", "exemplary embodiment", "some embodiments" and the like indicate that the described embodiment can include a specific feature, structure or property, but not necessarily every embodiment includes the specific feature, structure or property. In addition, when a specific feature, structure or property is described in combination with an embodiment, it should be within the knowledge of those skilled in the related art to implement such a feature, structure or property in combination with other embodiments, whether or not it is explicitly described.

[0072] Generally, the terms can be understood at least in part from the use in context. For example, depending at least in part on the context, the term "one or more" as used herein can be used to describe any feature, structure or property that can exist singularly or in combination with other features, structures or properties. In addition, the term "based on" can be understood as not necessarily intended to convey a set of exclusive factors, but can instead, depending at least in part on the context, allow the existence of other factors not necessarily explicitly described.

[0073] I. Gradient temperature control multi-stage crystallization device and process

[0074] Example 1: Composition and working principle of gradient temperature control multi-stage crystallization system

[0075] Referring to Figure 1 The gradient temperature control multi-stage crystallization device 100 of the present embodiment mainly comprises:

[0076] The main crystallizer 10 is a cylindrical vertical structure with a height of 2.5 meters, an inner diameter of 0.8 meters, and an effective volume of 1.2 cubic meters. The main crystallizer 10 adopts a double-wall jacket design, the inner wall 11 is made of alumina-based special ceramic material, the wall thickness is 15 mm, and it has a thermal conductivity of 18 W / (m·K) and an acid and alkali resistance pH range of 2-12. The outer wall 12 is made of 316L stainless steel material, and the wall thickness is 10 mm. The interlayer 13 between the inner and outer walls is used to pass the temperature control medium.

[0077] The main crystallizer 10 is divided into five independent temperature zones 21-25 in the vertical direction, and each temperature zone has a height of 0.5 meters. Each temperature zone is separated by an adjustable partition 14, and the partition 14 is provided with a solution flow hole 15, and the hole diameter can be adjusted in the range of 5-50 mm to realize controllable flow between the temperature zones.

[0078] The gradient temperature control system 20 is composed of the following parts:

[0079] Five groups of independent temperature sensors 26, model PT100, accuracy ±0.05℃, 3 evenly distributed in each temperature zone at 120°;

[0080] Five groups of independent heating / cooling units 27, using semiconductor Peltier elements, power 2kW, can realize temperature regulation range of-10℃ to 90℃;

[0081] Central control unit 28, using PLC control system, carrying special algorithm, can realize dynamic adjustment of temperature gradient, control period is 0.5 seconds;

[0082] The ultrasonic auxiliary system 30 includes:

[0083] Three groups of frequency adjustable ultrasonic generators 31, working frequency range is 20-100kHz, power 0-500W adjustable;

[0084] Special ultrasonic transducer 32, using piezoelectric ceramic material, is installed at different heights of the crystallizer;

[0085] Ultrasonic control unit, which can adjust the ultrasonic parameters in real time according to the crystal growth situation;

[0086] The liquid phase partition circulation system 40 is composed of the following components:

[0087] The specially designed arc-shaped partition 41 divides the internal space of the crystallizer into a central zone 42 and an annular zone 43.

[0088] The central zone is provided with a riser pipe with a diameter of 100 mm and a height of 2.3 m.

[0089] Two sets of variable frequency circulating pumps 45 with a flow rate of 0-5 m 3 / h can be adjusted to control the circulation rate in different zones.

[0090] Four sets of solution sampling / analysis units are used to monitor the composition and concentration of the solution in different zones in real time.

[0091] Example 2: Gradient temperature control multi-stage crystallization process

[0092] Referring to Figure 3 the drawings

[0093] In this embodiment, the production process of magnesium citrate includes the following steps:

[0094] Step S1: Raw material pretreatment

[0095] Citric acid (purity ≥ 99.5%) and magnesium oxide (purity ≥ 98%) are prepared into an aqueous solution with a concentration of 30% (w / w) according to a molar ratio of 1:1, and 0.2% (w / w) EDTA is added as a selective chelating agent. The solution is stirred at 65°C for 60 minutes, then filtered through a 0.45μm filter to obtain a pretreated solution.

[0096] Step S2: Crystallizer start-up

[0097] The five temperature zones 21-25 of the main crystallizer 10 are set to the following initial temperatures:

[0098] Temperature zone 21: 60±0.1°C;

[0099] Temperature zone 22: 55±0.1°C;

[0100] Temperature zone 23: 50±0.1°C;

[0101] Temperature zone 24: 45±0.1°C;

[0102] Temperature zone 25: 40±0.1°C.

[0103] Step S3: Solution feeding

[0104] The pretreated solution is pumped into the top temperature zone 21 of the main crystallizer 10 through the feed pipe 16 at a flow rate of 200 L / h, and the liquid phase partition circulation system 40 is started at the same time. The circulation rates of the central zone 42 and the annular zone 43 are set to 3 m 3 / h and 2 m3 / h.

[0105] Step S4: Ultrasonic-assisted nucleation

[0106] When the solution supersaturation of temperature zone 23 reaches 1.15, start the ultrasonic-assisted system 30, and set the following parameters:

[0107] Top transducer: frequency 40 kHz, power 150 W, working / stop ratio 3:1, cycle 60 seconds

[0108] Middle transducer: frequency 30 kHz, power 200 W, working / stop ratio 2:1, cycle 45 seconds

[0109] Bottom transducer: frequency 20 kHz, power 250 W, working / stop ratio 1:1, cycle 30 seconds

[0110] Step S5: Dynamic adjustment of temperature gradient

[0111] According to the real-time monitoring of nucleation conditions, the central control unit 28 automatically adjusts the temperature gradient of each temperature zone:

[0112] When the number of crystal nuclei in temperature zone 23 is monitored to reach the preset value (10^5 / mL), the temperature difference between temperature zone 22 and temperature zone 23 is reduced from 5°C to 3°C

[0113] When the average particle size of crystals in temperature zone 24 is detected to reach 50 μm, the temperature difference between temperature zone 24 and temperature zone 25 is increased from 5°C to 7°C;

[0114] Step S6: Impurity separation

[0115] Using the temperature gradient between temperature zones and the liquid phase partitioning and circulating system 40, promote the precipitation of impurities in a specific temperature zone:

[0116] In temperature zone 22, by controlling the pH value to be 5.8±0.2, promote the formation of hydroxide precipitate of metal ion impurities such as calcium and iron;

[0117] In temperature zone 24, by reducing the ionic strength of the solution to 0.1 mol / L, promote the separation of organic impurities from the main crystal;

[0118] Step S7: Crystal collection and post-processing

[0119] Collect the crystal suspension from the discharge port 17 at the bottom of the main crystallizer 10, separate the crystals by a centrifugal separator 60 at a speed of 1500 rpm for 5 minutes, then wash twice with pure water at 15°C, and finally dry at 50°C for 12 hours to obtain high-purity magnesium citrate crystal product.

[0120] II. Crystal form orientation control and self-adaptive separation system and process

[0121] As Figure 2 shown

[0122] Example 3: Crystal form directional regulation and adaptive separation system composition and working principle

[0123] As Figure 2 shown, the crystal form directional regulation and adaptive separation system 200 of the embodiment mainly includes:

[0124] The seed dynamic inoculation device 70 is composed of the following components:

[0125] The microfluidic seed preparation unit 71 adopts a T-shaped microchannel structure, with a channel width of 200 μm and a depth of 150 μm;

[0126] The seed temporary storage 72 has a volume of 5 L and is equipped with a precision temperature control system (temperature fluctuation <±0.05℃);

[0127] The quantitative inoculation pump system 73 has a flow accuracy of ±0.5% and a minimum flow rate of 0.1 mL / min;

[0128] The inoculation position control device 74 can accurately position in the X-Y-Z three directions inside the main crystallizer, with a positioning accuracy of ±2 mm;

[0129] The electric field assisted directional crystallization system 80 includes:

[0130] Four pairs of titanium alloy electrode plates 81, with a size of 200 mm×300 mm and a thickness of 2 mm, are uniformly distributed along the circumference of the crystallizer;

[0131] The high-precision electric field generator 82 has an output voltage range of 0-1000 V and a frequency range of 0-10 kHz;

[0132] The electric field distribution monitoring unit 83 can monitor the electric field intensity distribution inside the crystallizer in real time;

[0133] The electric field parameter automatic adjustment system 84 dynamically adjusts the electric field parameters based on the crystal growth feedback data;

[0134] The real-time crystal morphology analysis system 90 is composed of the following devices:

[0135] The laser diffraction particle size analyzer 91 has a measurement range of 0.1-1000 μm and an accuracy of ±1%;

[0136] The high-resolution digital microscope system 92 has a magnification of 50-500 times and is equipped with an automatic focusing function;

[0137] The image recognition and analysis software 93 can calculate parameters such as crystal shape factor, aspect ratio, and surface roughness in real time;

[0138] Data processing unit 94, using artificial neural network algorithm, processing speed 100 frames / s;

[0139] Adaptive separation system 100 includes:

[0140] Variable parameter centrifugal separator 101, speed range 500-3000 rpm, acceleration adjustable in the range of 10-100g;

[0141] Multi-stage cleaning system 102, equipped with quantitative addition device of three different solvents (water, ethanol, acetone);

[0142] Fluidized bed dryer 103, temperature range 30-80℃, air flow speed adjustable 0.5-2.5m / s;

[0143] Parameter adaptive control unit 104, based on crystal characteristic data to automatically optimize separation, cleaning and drying parameters;

[0144] Example 4: Crystal form directional regulation process flow

[0145] As shown in Figure 4

[0146] In this embodiment, the process flow of magnesium citrate crystal form directional regulation includes the following steps:

[0147] Step T1: Standard seed preparation

[0148] In the microfluidic seed preparation unit 71, 0.05mol / L citric acid solution and 0.05mol / L magnesium chloride solution are mixed at a volume ratio of 1:1 in a T-shaped microchannel at a flow rate of 2mL / min and a temperature of 40℃, to obtain uniform standard seeds with a particle size of 5±1μm. The prepared seeds are stored in the seed temporary storage 72, and the temperature is maintained at 38±0.05℃.

[0149] Step T2: Dynamic seeding

[0150] When the supersaturation of the solution in the main crystallizer 10 reaches 1.05-1.10, the seed solution is injected at a rate of 0.5mL / min by the quantitative seeding pump system 73, and the seeding position is controlled in the central region of the temperature zone 23, and the seeding concentration is 10^4 / mL.

[0151] Step T3: Electric field assisted directional crystallization

[0152] Start the electric field assisted directional crystallization system 80, and set the following parameters:

[0153] Initial electric field strength: 200V / m, frequency: 50Hz; ​

[0154] Electric field direction: along the crystallizer axis, promoting the alignment of magnesium citrate molecules along the c-axis direction;

[0155] Electric field intensity variation mode: increase by 50 V / m every 30 minutes until reaching 500 V / m;

[0156] Step T4: Crystal habit modifier addition

[0157] During the crystallization process, the crystal habit modifier is added according to the following scheme:

[0158] In temperature zone 22, 0.01% (w / w) of polyvinylpyrrolidone (PVP K30) is added as a {110} crystal face growth inhibitor;

[0159] In temperature zone 23, 0.005% (w / w) of sodium dodecyl sulfate (SDS) is added as a {101} crystal face growth promoter;

[0160] In temperature zone 24, the pH value is adjusted to 6.2±0.1 and the ionic strength is adjusted to 0.15 mol / L to promote the growth of plate-like crystals;

[0161] Step T5: Real-time morphology monitoring and parameter adjustment

[0162] The crystal growth process is monitored using a real-time crystal morphology analysis system 90:

[0163] Crystal images are collected every 5 minutes, and the shape factor and aspect ratio are calculated;

[0164] When the aspect ratio of the crystals is detected to be <1.5, the electric field intensity is increased by 50 V / m;

[0165] When the surface roughness of the crystals is detected to be >0.2, the temperature of the temperature zone is decreased by 1°C;

[0166] According to the crystal particle size distribution data, the ultrasonic power and frequency are dynamically adjusted.

[0167] Step T6: Crystal aging treatment

[0168] When the average particle size of the crystals reaches 100 μm, the temperature is reduced to 35°C for 4 hours for crystal aging treatment, promoting the self-healing of crystal defects and lattice rearrangement.

[0169] Step T7: Adaptive separation and post-processing

[0170] Based on the real-time crystal morphology analysis results, the adaptive separation system 100 automatically sets the optimal separation parameters:

[0171] Centrifugal separation parameters: speed 1800 rpm, time 4.5 minutes;

[0172] Washing parameters: first, 10℃ pure water washing twice, each time the amount of 3 times the mass of the crystal; then 5℃ 50% ethanol solution washing once;

[0173] Drying parameters: initial temperature 40℃, air flow rate 1.2m / s, then the temperature slowly rises to 60℃, drying time 8 hours.

[0174] III. Experimental verification and effect comparison

[0175] Example 5: product quality comparison analysis

[0176] As shown in Figure 5 As shown in

[0177] The magnesium citrate product produced by the gradient temperature control multi-stage crystallization device and crystal form directional regulation system of the application is compared with the traditional process product, and the results are shown in Table 1:

[0178] Table 1. Product quality comparison analysis

[0179]

[0180]

[0181] Example 6: comparison of production efficiency and environmental indicators

[0182] As shown in Figure 6 As shown in

[0183] The process of the application is compared with the traditional process in terms of production efficiency and environmental indicators, and the results are shown in Table 2:

[0184] Table 2. Comparison of production efficiency and environmental indicators

[0185] Index item Conventional process Process of the present invention Improvement range Production cycle (h) 24 16 33％ Energy consumption (kWh / t) 1200 920 23％ Water resource consumption (t / t) 15 9 40％ Waste water discharge (t / t) 12 6.5 46％ Equipment floor area (m2) 120 85 29％ Operation personnel requirement (person-time / shift) 4 2 50％ Batch stability (RSD %) 8.5 2.1 75％

[0186] The innovative device and process of the application not only significantly improves the content and quality stability of magnesium citrate crystals, but also greatly reduces production costs and environmental burden, with significant economic and social benefits.

[0187] The application covers any substitution, modification, equivalent method and scheme made on the essence and scope of the application. In order to make the public have a thorough understanding of the application, specific details are described in the following preferred embodiments of the application, and the application can also be fully understood without the description of these details. In addition, in order to avoid unnecessary confusion to the essence of the application, well-known methods, processes, procedures, elements and circuits, etc. are not described in detail.

[0188] The above merely describes the preferred embodiments of the present application, and it should be pointed out that, for those skilled in the art, some improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. A production device for increasing the content of magnesium citrate crystals, characterized in that: include: The main crystallizer (10) has a double-wall jacket design, the inner wall (11) is made of ceramic material, the outer wall (12) is made of stainless steel, and an interlayer (13) is formed between the inner and outer walls for passing a temperature control medium; A gradient temperature control system (20) divides the main crystallizer (10) into a plurality of independent temperature zones (21-25) in a vertical direction, each temperature zone being separated by an adjustable partition (14) having a solution flow hole (15); An ultrasonic auxiliary system (30) comprising a plurality of frequency-adjustable ultrasonic generators (31) and ultrasonic transducers (32) installed at different heights of the crystallizer; The liquid phase partition circulation system (40) includes an arc-shaped partition (41) for dividing the internal space of the crystallizer into a central area (42) and an annular area (43), and a variable frequency circulation pump (45) for controlling the circulation rate of different areas.

2. The device according to claim 1, characterized in that The gradient temperature control system (20) further comprises: Temperature sensors (26) installed in each temperature zone; Independent heating / cooling units (27) are provided in each temperature zone; A central control unit (28) is provided for realizing dynamic adjustment of temperature gradient.

3. The device according to claim 1, characterized in that Also included is a crystal form orientation control and adaptive separation system (200), the system comprising: A dynamic seeding device (70) for preparing and injecting standard seed crystals; An electric field assisted directional crystallization system (80) includes a plurality of pairs of electrode plates (81) uniformly distributed along the circumference of the crystallizer; A real-time crystal morphology analysis system (90) for monitoring the morphology and size distribution of crystals during growth; An adaptive separation system (100) automatically optimizes separation, cleaning and drying parameters based on crystal property data.

4. The device according to claim 3, characterized in that The dynamic seed seeding device (70) comprises: A microfluidic seed preparation unit (71) having a T-shaped microchannel structure; a temporary seed crystal storage device (72) equipped with a precise temperature control system; A quantitative seeding pump system (73) for controlling seed injection; An inoculation position control device (74) can be accurately positioned in three directions inside the main crystallizer.

5. The device according to claim 3, characterized in that The electric field assisted directional crystallization system (80) comprises: Titanium alloy electrode plate (81); A high-precision electric field generator (82) with adjustable voltage and frequency range; An electric field distribution monitoring unit (83) for monitoring the electric field intensity distribution inside the crystallizer; An electric field parameter automatic adjustment system (84) dynamically adjusts electric field parameters based on crystal growth feedback data.

6. A production method for increasing the content of magnesium citrate crystals using the device according to any one of claims 1 to 5, characterized in that: The following steps are involved: Citric acid and magnesium oxide are prepared into an aqueous solution in a molar ratio of 1:1, a selective chelating agent is added, and the solution is filtered to obtain a pre-treated solution; Setting the initial temperature of each temperature zone of the main crystallizer (10) to form a temperature gradient from top to bottom; The pre-treated liquid is pumped into the top temperature zone of the main crystallizer (10), and the liquid phase partition circulation system (40) is started at the same time; When the supersaturation of the solution reaches a preset value, an ultrasonic auxiliary system (30) is activated to promote nucleation; According to the real-time monitoring of the nucleation status, the temperature gradient of each temperature zone is automatically adjusted by the central control unit (28); Utilizing the temperature gradient between temperature zones and the liquid phase partition circulation system (40) to promote the precipitation of impurities in a specific temperature zone; The crystal suspension is collected from the bottom of the main crystallizer (10), and the product is obtained by centrifugation, washing and drying.

7. The method according to claim 6, characterized in that It also includes the crystal orientation control step: preparing standard seed crystals with uniform particle size in a microfluidic seed crystal preparation unit (71); When the supersaturation of the solution in the main crystallizer (10) reaches 1.05-1.10, the seed solution is injected into the predetermined position through the quantitative inoculation pump system (73); Starting the electric field assisted directional crystallization system (80), setting the electric field strength and frequency to promote the magnesium citrate molecules to align along a specific direction; Adding crystal form regulators during the crystallization process to control the growth rate of specific crystal faces; Using a real-time crystal morphology analysis system (90) to monitor the crystal growth process, and dynamically adjusting process parameters based on the monitoring results; Perform crystal aging treatment to promote self-healing of crystal defects and lattice rearrangement; According to the crystal morphology analysis results, the separation, cleaning and drying parameters are optimized by the adaptive separation system (100).

8. The method according to claim 7, characterized in that In the electric field assisted directional crystallization step, the electric field strength is 200-500 V / m, the frequency is 50 Hz, and the electric field direction is along the axial direction of the crystallizer to promote the alignment of magnesium citrate molecules along the c-axis direction.

9. The method according to claim 7, characterized in that The step of adding the crystal form modifier comprises: 0.01% (w / w) polyvinyl pyrrolidone was added to temperature zone 22 as a {110} crystal plane growth inhibitor; 0.005% (w / w) sodium lauryl sulfate was added to temperature zone 23 as a {101} crystal face growth promoter; In temperature zone 24, the pH value was adjusted to 6.2±0.1 and the ionic strength was adjusted to 0.15 mol / L to promote the growth of plate-like crystals.

10. The method according to claim 6, characterized in that The initial temperatures of the five temperature zones (21-25) of the main crystallizer (10) are respectively set as: Temperature zone 21: 60±0.1℃; Temperature zone 22: 55±0.1℃; Temperature zone 23: 50±0.1℃; Temperature zone 24: 45±0.1℃; Temperature zone 25:40±0.1℃.

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