A method for preparing magnesium citrate

Abstract

This invention discloses a method for preparing magnesium citrate. The method includes: first, preparing citric acid solution and magnesium salt solution of specific concentrations, and introducing them separately into specific microfluidic chip channels; then, precisely controlling the flow rate of the solutions in the channels, and the temperature and pressure of the reaction zone, to promote thorough mixing and efficient reaction of the two solutions in the region, thereby constructing a stable pure liquid reaction system. This invention, through precise control, rigorously manages the reaction process and mixing degree, effectively avoiding drawbacks such as uneven product quality, inconsistent crystal morphology and size caused by premature crystallization. The prepared magnesium citrate exhibits many superior properties: its magnesium content is close to the theoretical value of 16.2%; its purity is over 95%; the reaction time is significantly shortened; it possesses excellent reproducibility and reduces the occurrence of side reactions, providing a novel and efficient approach for the preparation of magnesium citrate.

Description

Technical Field

[0001] This invention relates to the field of organic trace element chelate processing technology, specifically to a method for preparing magnesium citrate. Background Technology

[0002] Magnesium, an essential mineral for many physiological processes, plays a vital role in maintaining human health. Numerous studies have confirmed its positive impact on the prevention and treatment of various diseases, with potential benefits including preventing heart disease and metabolic disorders, relieving migraines, promoting mental health, and slowing bone loss. However, in reality, most people cannot obtain sufficient magnesium to meet their basic needs through their daily diet alone. Against this backdrop, taking magnesium supplements becomes a highly attractive option, allowing the body to fully benefit from this important mineral.

[0003] Magnesium citrate, as a magnesium source with good absorption, has attracted much attention. Meanwhile, citric acid itself also has several important physiological functions for the human body: First, citric acid can effectively enhance appetite by stimulating the secretion of digestive juices and promoting intestinal peristalsis, thus powerfully promoting the digestion process; second, citric acid can significantly enhance the body's antioxidant capacity, helping to eliminate free radicals in the body, thereby reducing the damage caused by oxidative reactions to various tissues; third, citric acid also has the effect of strengthening the body's immune function, effectively increasing cellular immune activity, and thus improving the body's ability to resist disease.

[0004] Magnesium citrate has wide applications in many fields such as medicine, food, and chemicals. Traditional methods for preparing magnesium citrate, such as solution precipitation and crystallization, generally suffer from low production efficiency and unstable product quality. For example, the method for producing a magnesium citrate-magnesium oxide composite product disclosed in patent application number CN202010563121.2 requires pulverization and screening to obtain powder, which is cumbersome, time-consuming, and labor-intensive. Furthermore, the prepared magnesium citrate has poor taste (bitter and metallic) and low bioavailability. Similarly, patent number CN202210003385.1 also points out that current magnesium citrate crystal production processes are prone to reactant inclusion and excess, resulting in low purity and yield. Based on these issues, there is an urgent need to develop a novel method for producing magnesium citrate that can effectively overcome the existing shortcomings. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing magnesium citrate. This method can realize the reaction of citric acid solution and magnesium salt solution in a pure liquid system, thereby improving the reaction efficiency and increasing the magnesium content in the prepared magnesium citrate to about 16%.

[0006] This invention provides a method for preparing magnesium citrate, comprising the following steps:

[0007] Step (1) Solution preparation: Prepare citric acid solution and magnesium salt solution; in step (1), the concentration of the citric acid solution is limited to the range of 0.1-1.0 mol / L, and the concentration of the magnesium salt solution is limited to the range of 0.1-1.0 mol / L.

[0008] Step (2) Solution introduction: The citric acid solution and magnesium salt solution prepared in step (1) are introduced into the microfluidic channel of the microfluidic chip; the microfluidic chip is provided with a microfluidic channel, which is selected from one of the following: T-shaped cross-flow geometry channel, Y-shaped cross-flow geometry channel and continuous flow channel to achieve orderly introduction of solution;

[0009] Step (3) Reaction control: By setting the channel structure of the microfluidic chip and the flow rate of the solution in the microfluidic chip, the two solutions are fully mixed and react efficiently in the reaction area of ​​the microfluidic chip, thereby forming a pure liquid reaction system to prepare magnesium citrate solution; in step (3), the flow rates of the citric acid solution and magnesium salt in the microfluidic chip are both controlled at 10-40 mL / min; the temperature of the reaction area of ​​the microfluidic chip is limited to the range of 30-70℃; the pressure of the reaction area of ​​the microfluidic chip is controlled at 0.1 kPa-50 kPa; the reaction time of step (3) is 10-30 min;

[0010] Step (4) Product post-processing: After the reaction is carried out in the microfluidic chip according to the preset conditions, the magnesium citrate solution generated in step (3) is filtered, collected, crystallized, centrifuged and dried to obtain magnesium citrate product that meets the high quality requirements.

[0011] In the above technical solution, this invention applies precise and meticulous control to the channel structure of the microfluidic chip and simultaneously sets the flow rate of the solution within the microfluidic chip. This promotes a fully mixed and highly efficient reaction between the two solutions in the reaction region within the microfluidic chip, thereby forming a pure liquid reaction system for the preparation of magnesium citrate. This pure liquid reaction system significantly differs from the conventional method of simultaneous reaction and crystallization in the preparation of amino acid salts. Throughout the reaction process, it effectively avoids the following two key problems caused by premature intervention in the crystallization process:

[0012] In cases of uneven reaction, the unique reaction environment and precise fluid control mechanism created by this microfluidic technology can ensure that citric acid and magnesium salt can achieve a full and uniform chemical reaction in a pure environment completely free from crystallization interference, thereby ensuring that the reaction can proceed in a balanced and consistent state at each reaction site.

[0013] Regarding the challenge of controlling crystal morphology and size, by maintaining a pure liquid reaction environment throughout the entire reaction process until the reaction progresses to a specific stage, the subsequently formed magnesium citrate crystals can be formed under more controllable conditions. This allows for precise control of crystal morphology and size to meet the specific requirements of different application scenarios for magnesium citrate crystal properties.

[0014] In step (1), the magnesium salt solution is a magnesium chloride solution or a magnesium sulfate solution.

[0015] Preferably, in step (2), the channel structure of the microfluidic chip is a Y-shaped cross-flow geometry channel.

[0016] Preferably, in step (1), the mass ratio of citric acid to magnesium salt is 1:0.5 to 1:3, and the total reactant concentration is 30% to 75% (mass ratio of dry matter to water).

[0017] Preferably, in step (1), the concentration of the citric acid solution is precisely maintained within a specific range of 0.3-0.7 mol / L, and the concentration of the magnesium salt solution is also strictly limited to the range of 0.3-0.7 mol / L.

[0018] Preferably, in step (3), the flow rate of the solution in the microfluidic chip is 20 mL / min. This precise setting of the flow rate is based on a comprehensive consideration of reaction kinetics and fluid mixing effect, aiming to ensure that the two solutions can be quickly and fully mixed after entering the reaction area, thereby promoting the preparation reaction of magnesium citrate in an efficient and stable manner.

[0019] Preferably, the temperature of the reaction zone is controlled at 45-65℃. This temperature range is set based on a comprehensive consideration of factors such as the chemical equilibrium and reaction rate of the magnesium citrate preparation reaction, aiming to ensure that the reaction can proceed efficiently under suitable temperature conditions, while avoiding problems such as abnormal reaction or product quality degradation caused by excessively high or low temperatures.

[0020] Preferably, in step (3), the pressure in the reaction region of the microfluidic chip is controlled at 15 kPa.

[0021] Furthermore, in step (4), after the reaction is completed, the magnesium citrate solution after the reaction in step (3) is filtered and collected through a filter membrane with a pore size of 0.1 to 0.45 mm, and then introduced into a microfluidic crystallizer. It is slowly stirred and crystallized at 10°C for 3 hours, and the crystal size is set to 10 μm. After the magnesium citrate crystals are centrifuged at 2000 r / min, they are dried with hot air at 85°C for 8 hours. The product is collected to obtain the magnesium citrate product.

[0022] In the above technical solution, after the reaction is completed, a series of post-processing operations are carried out on the magnesium citrate solution after the reaction in step (3), including but not limited to filtration and collection through a filter membrane with a pore size of 0.1 to 0.45 mm, crystallization under specific conditions in a microfluidic crystallizer (temperature of 10°C, slow stirring and crystallization for 3 hours, crystal size set to 10 μm), as well as subsequent centrifugation (2000 r / min speed) and hot air drying (85°C, 8 hours). These are all based on a comprehensive consideration of improving the quality of magnesium citrate products and optimizing the post-processing process. The aim is to obtain high-quality magnesium citrate products through these refined and standardized post-processing procedures.

[0023] The method for preparing magnesium citrate described in this invention exhibits a highly integrated reaction system. Specifically, the entire reaction process can be completed within extremely small chip channels. Compared to traditional methods that involve simultaneous reaction and crystallization, this significantly reduces the space required for the reaction, lowering it to below 70% of the original space. Simultaneously, it drastically reduces reagent consumption, effectively decreasing it to below 80% of the original amount. This highly integrated reaction system not only achieves efficient resource utilization and reduces production costs but also alleviates environmental pressure to a certain extent, demonstrating the significant advantages of this preparation method in resource conservation and environmental friendliness.

[0024] The method for preparing magnesium citrate described in this invention involves a rapid and efficient reaction process. By precisely and meticulously controlling numerous fluid parameters within the microfluidic chip (including key elements such as channel structure, flow rate, and reaction zone temperature), the raw materials can achieve full contact and rapid reaction instantly upon entering the reaction zone. Compared to traditional methods that involve simultaneous reaction and crystallization, the reaction time can be significantly reduced to less than 60% of the original time. This rapid and efficient reaction process not only effectively improves production efficiency but also effectively avoids many adverse factors that may arise from excessively long reaction times, such as increased side reactions, thereby comprehensively improving product quality and production efficiency, and providing solid technical support for the large-scale industrial production of magnesium citrate.

[0025] The microfluidic technology-assisted preparation method for magnesium citrate exhibits excellent reproducibility. Multiple repeated preparation experiments verified that the deviations in key indicators such as purity and performance of the prepared magnesium citrate product could be precisely controlled within 2%. In stark contrast, the traditional reaction-crystallization method, with the same number of repetitions, showed deviations in the corresponding indicators far exceeding 5%. This reproducibility ensures the stability and consistency of the quality of magnesium citrate obtained each time, providing a reliable and solid technical guarantee for large-scale, standardized industrial production, and effectively ensuring the controllability and stability of product quality.

[0026] Furthermore, the present invention also provides a system for the preparation of magnesium citrate assisted by the microfluidic technology, including a microfluidic chip, a peristaltic pump, a reaction monitoring device, and a product collection device.

[0027] The microfluidic chip has a precisely designed channel structure for mixing and reacting solutions; the peristaltic pump accurately delivers citric acid solution and magnesium salt solution to the corresponding channels of the microfluidic chip; the reaction monitoring device monitors parameters such as temperature, pressure, and flow rate in real time during the reaction; and the product collection device collects the magnesium citrate product generated by the reaction and performs subsequent processing.

[0028] Compared with the prior art, the present invention has the following advantages:

[0029] (1) The method for preparing magnesium citrate described in this invention employs microfluidic technology. This microfluidic technology directly obtains the desired finished product through a series of devices including a microfluidic chip, a solution delivery device, a reaction monitoring device, and a product collection device. This eliminates processes such as vacuuming and filtration, significantly shortening the reaction time, reducing reagent consumption, lowering production costs, and providing strong environmental friendliness. Production conditions are easy to control, the system operation is simple, and the obtained magnesium citrate meets food-grade requirements and is easily industrialized. This invention utilizes microfluidic technology to achieve precise operation and control at the microscale by allowing raw materials to flow into the reaction chamber through different channels. This improves reaction efficiency and product purity, and the magnesium citrate prepared by this method exhibits high bioavailability and aqueous solution stability. Meanwhile, microfluidic systems require precise control of parameters such as reactant concentration, solubility, reaction conditions, mixing, and mass transfer efficiency during use to ensure high efficiency and selectivity of the reaction and prevent problems such as uneven concentration distribution of reactants and low reaction rates. In addition, the materials of microfluidic devices need to be compatible with magnesium citrate and its reactants to avoid corrosion or reaction, which may limit the choice of materials (this application uses microfluidic devices made of glass). When scaling up and manufacturing, the construction of microfluidic devices, pressure-driven devices (such as syringes or peristaltic pumps), connection systems between devices, and detection equipment for large-scale droplet production analysis should also be considered, especially the precise design of microfluidic channels.

[0030] (2) This invention provides a method for preparing magnesium citrate. By using microfluidic technology, it is possible to achieve better uniform mixing of reactants, precise control of reaction conditions, and separation and purification of products, thereby improving the yield and purity of magnesium citrate. Therefore, the use of microfluidic technology provides a new, efficient, precise and controllable approach for the production of magnesium citrate, thereby improving the production efficiency of magnesium citrate, reducing costs and improving the stability of product quality.

[0031] (3) Microfluidic technology, with its advantages in channel structure, fluid parameter control and reaction environment stability, can realize the preparation reaction of magnesium citrate in a pure liquid reaction system, effectively overcoming many problems caused by the reaction-crystallization mode in the traditional preparation process. Moreover, the magnesium content in magnesium citrate prepared by microfluidic technology in this invention can be increased to about 16.2% of its theoretical value. Attached Figure Description

[0032] Figure 1 This is a schematic diagram of the microfluidic system used in this invention. 1 is a peristaltic pump, 2 is a temperature controller, 3 is a flow rate controller, 4 is a pressure controller, 5 is a Y-channel micromixer, 6 is a crystallizer, 7 is a filtration device, and 8 is a collection device. 1-5 together form a microfluidic chip reactor.

[0033] Figure 2This is the infrared spectrum of citric acid;

[0034] Figure 3 This is a schematic diagram of the near-infrared spectrum of a magnesium citrate sample in an example.

[0035] Figure 4 The effects of microfluidic systems and conventional preparation methods on the yield and purity of magnesium citrate in the examples and comparative examples are shown.

[0036] Figure 5 The effects of microfluidic systems and conventional preparation methods on the chelation rate of magnesium citrate in the examples and comparative examples are shown.

[0037] Figure 6 The effects of reactant concentration on the chelation rate of magnesium citrate are shown below.

[0038] Figure 7 The effects of temperature on the chelation rate of magnesium citrate are shown below.

[0039] Figure 8 The effects of pressure on the chelation rate of magnesium citrate are shown below;

[0040] Figure 9 The effect of microfluidic system flow rate on magnesium citrate chelation rate is shown below.

[0041] Figure 10 The effect of flow rate on yield in the preparation of magnesium citrate solution using a microfluidic system;

[0042] Figure 11 The effect of flow rate on the purity of magnesium citrate solution prepared with the aid of a microfluidic system;

[0043] Figure 12 The effect of temperature on the pH of magnesium citrate solution in Example 1;

[0044] Figure 13 The effect of temperature on the transmittance of magnesium citrate solution in Example 1. Detailed Implementation

[0045] To better understand the content of this invention, specific embodiments are described below. It should be understood that these embodiments are for further illustration only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the description of this invention, those skilled in the art may make non-essential modifications or adjustments to the invention, which still fall within the protection scope of this invention.

[0046] The method of this invention is implemented in a microfluidic system.

[0047] The microfluidic chip reactor of the microfluidic system described in this invention has a precisely designed channel structure (see attached diagram). Figure 1 A Y-channel micromixer (5) is shown for mixing and reacting solutions; a peristaltic pump is used to accurately deliver citric acid solution and magnesium salt solution to the corresponding channels of the microfluidic chip; a pressure controller, flow rate controller, and temperature controller are used to monitor parameters such as temperature, pressure, and flow rate in real time during the reaction process; and a product collection device is used to collect the magnesium citrate product generated by the reaction and perform subsequent processing.

[0048] As attached Figure 1 As shown, the present invention uses a microfluidic chip reactor; the microfluidic chip reactor includes a peristaltic pump 1, a Y-channel micromixer 5, a temperature controller 2, a flow rate controller 3, and a pressure controller 4; the microfluidic system of the present invention also includes a crystallizer 6, a filtration device 7, and a collection device 8; the crystallizer is connected to the filtration device 7 and the collection device 8 respectively.

[0049] Example 1

[0050] Two solutions, 0.5 mol / L citric acid and 0.5 mol / L magnesium sulfate, were prepared and introduced into the T-shaped cross-flow geometry channels of the microfluidic chip using a peristaltic pump at a flow rate of 20 ml / min. The temperature of the reaction zone of the microfluidic chip was controlled at 60 °C, the reaction time was 20 min, and the pressure was 15 kPa. After the reaction was completed, the magnesium citrate solution was filtered through a filter membrane with a pore size of 0.1–0.45 mm and collected. It was then transferred to a microfluidic crystallizer (dual-pulse platform) and slowly stirred for 3 hours at 10°C to facilitate more accurate detection of crystal nucleation and eliminate heterogeneous nucleation sites (such as impurities). The crystal size was set to 10 μm. A microfluidic biosensor was used to quickly and sensitively detect whether the content of Salmonella typhimurium, Staphylococcus aureus, molds, and yeasts in the food sample exceeded the limits for pathogenic bacteria. After meeting the national food safety standards, the magnesium citrate crystals were centrifuged at 2000 r / min and then dried with hot air at 85°C for 8 hours. The product was collected to obtain the magnesium citrate product.

[0051] Example 2

[0052] Two solutions, 0.5 mol / L citric acid and 0.5 mol / L magnesium sulfate, were prepared. Both solutions were introduced into the Y-shaped cross-flow geometry channels of the microfluidic chip using a peristaltic pump at a flow rate of 20 ml / min. The temperature of the reaction zone of the microfluidic chip was controlled at 60 °C, the reaction time was 20 min, and the pressure was 15 kPa. After the reaction was completed, the magnesium citrate solution was filtered through a filter membrane with a pore size of 0.1–0.45 mm and collected. It was then transferred to a microfluidic crystallizer (dual-pulse platform) and slowly stirred for 3 hours at 10°C to facilitate more accurate detection of crystal nucleation and eliminate heterogeneous nucleation sites (such as impurities). The crystal size was set to 10 μm. A microfluidic biosensor was used to quickly and sensitively detect whether the content of Salmonella typhimurium, Staphylococcus aureus, molds, and yeasts in the food sample exceeded the limits for pathogenic bacteria. After meeting the national food safety standards, the magnesium citrate crystals were centrifuged at 2000 r / min and then dried with hot air at 85°C for 8 hours. The product was collected to obtain the magnesium citrate product.

[0053] Example 3

[0054] Two solutions were prepared: a 0.5 mol / L citric acid solution and a 0.5 mol / L magnesium chloride solution. Both solutions were introduced into the Y-shaped cross-flow geometry channels of the microfluidic chip using a peristaltic pump at a flow rate of 20 ml / min. The temperature of the reaction zone of the microfluidic chip was controlled at 60 °C, the reaction time was 20 min, and the pressure was 15 kPa. After the reaction was completed, the magnesium citrate solution was filtered through a filter membrane with a pore size of 0.1–0.45 mm and collected. It was then transferred to a microfluidic crystallizer (dual-pulse platform) and slowly stirred for 3 hours at 10°C to facilitate more accurate detection of crystal nucleation and eliminate heterogeneous nucleation sites (such as impurities). The crystal size was set to 10 μm. A microfluidic biosensor was used to quickly and sensitively detect whether the content of Salmonella typhimurium, Staphylococcus aureus, molds, and yeasts in the food sample exceeded the limits for pathogenic bacteria. After meeting the national food safety standards, the magnesium citrate crystals were centrifuged at 2000 r / min and then dried with hot air at 85°C for 8 hours. The product was collected to obtain the magnesium citrate product.

[0055] Example 4

[0056] Two solutions, 0.5 mol / L citric acid and 0.5 mol / L magnesium sulfate, were prepared and introduced into the continuous flow channel of the microfluidic chip using a peristaltic pump at a flow rate of 20 ml / min. The temperature of the reaction zone of the microfluidic chip was controlled at 60 °C, the reaction time was 20 min, and the pressure was 15 kPa. After the reaction was completed, the magnesium citrate solution was filtered through a filter membrane with a pore size of 0.1–0.45 mm and collected. It was then transferred to a microfluidic crystallizer (dual-pulse platform) and slowly stirred for 3 hours at 10°C to facilitate more accurate detection of crystal nucleation and eliminate heterogeneous nucleation sites (such as impurities). The crystal size was set to 10 μm. A microfluidic biosensor was used to quickly and sensitively detect whether the content of Salmonella typhimurium, Staphylococcus aureus, molds, and yeasts in the food sample exceeded the limits for pathogenic bacteria. After meeting the national food safety standards, the magnesium citrate crystals were centrifuged at 2000 r / min and then dried with hot air at 85°C for 8 hours. The product was collected to obtain the magnesium citrate product.

[0057] Example 5

[0058] Two solutions, 0.5 mol / L citric acid and 0.5 mol / L magnesium sulfate, were prepared and introduced into the flow focusing channel of the microfluidic chip using a peristaltic pump at a flow rate of 20 ml / min. The temperature of the reaction zone of the microfluidic chip was controlled at 60 °C, the reaction time was 20 min, and the pressure was 15 kPa. After the reaction was completed, the magnesium citrate solution was filtered through a filter membrane with a pore size of 0.1–0.45 mm and collected. It was then transferred to a microfluidic crystallizer (dual-pulse platform) and slowly stirred for 3 hours at 10°C to facilitate more accurate detection of crystal nucleation and eliminate heterogeneous nucleation sites (such as impurities). The crystal size was set to 10 μm. A microfluidic biosensor was used to quickly and sensitively detect whether the content of Salmonella typhimurium, Staphylococcus aureus, molds, and yeasts in the food sample exceeded the limits for pathogenic bacteria. After meeting the national food safety standards, the magnesium citrate crystals were centrifuged at 2000 r / min and then dried with hot air at 85°C for 8 hours. The product was collected to obtain the magnesium citrate product.

[0059] Comparative Example 1: Preparation of Magnesium Citrate by Traditional Method

[0060] Magnesium oxide was added to a 0.5 mol / L citric acid solution (the molar ratio of magnesium oxide to citric acid was 3:2.05). The reaction solution was cooled to 10 °C for crystallization. After crystallization, the solid and liquid phases were separated, the solid phase was collected, and dried at 180 °C for 5 h to obtain anhydrous magnesium citrate.

[0061] Test case

[0062] Experimental Example 1

[0063] This experimental example illustrates the infrared spectrum of magnesium citrate in Example 1.

[0064] The magnesium citrate prepared in Example 1 was analyzed using a Bruker ALPHA Fourier transform infrared spectrometer (Germany). Figure 2 , Figure 3 The infrared spectrum of citric acid. As can be seen from the figure, after the chelation reaction between citric acid and magnesium ions, the corresponding characteristic peak positions shifted significantly. Infrared spectrum of citric acid (… Figure 2 A broad OH stretching vibration peak appears in the 3200-3500 cm⁻¹ range, indicating the presence of an alcohol hydroxyl group, and a strong absorption peak appears in the 1700-1750 cm⁻¹ range, which is due to the C=O stretching vibration of the carboxyl group. Magnesium citrate (… Figure 3 The absorption peaks in the 3200-3600 cm⁻¹ range decreased or disappeared, possibly due to the lower concentration of hydroxyl (OH) groups in the anhydrous state; the C=O stretching vibration of the carboxyl group underwent a red shift. This indicates that the carboxyl group participated in the coordination reaction, confirming the formation of magnesium citrate.

[0065] Experimental Example 2

[0066] This experimental example illustrates the yield and purity of magnesium citrate in the examples and comparative examples.

[0067] The crystal structure of magnesium citrate was determined using a D8 Advance X-ray diffractometer. The experimental results were compared with the standard magnesium citrate crystal structure using MDI Jade6 software to assess the product's purity. The results are as follows: Figure 4 As shown.

[0068] First, the theoretically achievable mass of magnesium citrate needs to be calculated using the equilibrium reaction equation and molar ratio. After synthesizing magnesium citrate, the actual mass of the obtained magnesium citrate product is measured using a balance.

[0069] The percentage yield can be obtained by dividing the actual mass of magnesium citrate produced by the theoretical mass of the product and multiplying by 100%.

[0070] Yield (%) = (Actual product mass / Theoretical product mass) × 100%

[0071] When calculating yield, if the product is not 100% pure, a correction is needed based on purity. The correction formula is: Actual Yield (%) = (Actual Product Mass / Theoretical Product Mass) × Purity × 100% (Example 3)

[0072] This experimental example illustrates the determination of Mg content in magnesium citrate in the examples and comparative examples.

[0073] Weigh approximately 200 mg of the dried sample to constant weight, accurate to 0.0001 g, and place it in a 250 mL Erlenmeyer flask. Add 25 mL of water to dissolve the sample, add 10 mL of ammonia-ammonium chloride buffer solution, add 2 drops of Eriochrome Black T indicator solution, and titrate with disodium ethylenediaminetetraacetate standard titration solution until the solution changes from purple-red to pure blue as the endpoint.

[0074] Simultaneously prepare a blank solution. The blank sample solution should contain the same types and amounts of reagents as the sample solution, except for the absence of the sample solution (excluding standard titration solutions). Prepare two parallel determinations and take the average result. The absolute difference between the two parallel determinations should not exceed 0.3%.

[0075] Calculation formula: Magnesium (calculated as Mg) content X1 is expressed as mass fraction % and is calculated according to the following formula.

[0076]

[0077] In the formula: V: the numerical value of the volume of EDTA standard titration solution consumed by the sample, in milliliters (mL);

[0078] V0: The numerical value of the volume of EDTA standard titration solution consumed in the blank test, in milliliters (mL);

[0079] c: Concentration of EDTA standard solution, in moles per liter (mol / L);

[0080] M: The numerical value of the molar mass of magnesium, in grams per mole (g / mol) [M(magnesium) = 24];

[0081] m: The numerical value of the sample mass, in mg;

[0082] Test Example 4

[0083] This experimental example illustrates the determination of the Mg chelation rate of magnesium citrate in the examples and comparative examples.

[0084] Method for determining magnesium content: EDTA titration. Take the test solution, add 5 mL of ammonia-ammonium chloride buffer (pH = 10.0) and 5 drops of 0.5% Eriochrome Black T solution, and immediately titrate with 0.05 mol / L EDTA-Na2 until the solution changes from purple-red to sky blue. Perform three parallel titrations and record the volume of titrant used.

[0085] The formula for calculating the chelation rate is as follows:

[0086] Chelation rate (%) = (Mm) / M × 100%

[0087] In the formula, M represents the total amount of magnesium, and m represents the amount of free magnesium.

[0088] The results showed that, compared with the traditional method for extracting magnesium citrate, this method not only greatly shortened the reaction time but also improved the magnesium chelation rate and reaction efficiency.

[0089] Table 1. Yield, purity, magnesium content, and chelation rate for each example.

[0090] Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Yield 95.8％ 97.7％ 96.7％ 93.2％ 95.4％ 75.4％ purity 97.5％ 98.8％ 97.8％ 97.3％ 97.8％ 67.3％ magnesium content 16.0％ 16.19％ 16.15％ 16.1％ 16.07％ 15.36％ Magnesium chelation rate 74.4％ 74.9％ 74.1％ 73.9％ 73.3％ 42.7％

[0091] According to Table 1 and Figure 4 , Figure 5 The data shows that the yield and purity of magnesium citrate prepared by microfluidic technology are significantly higher than those prepared by traditional methods, and the magnesium content and chelation rate are also increased. Furthermore, the yield, purity, magnesium content and chelation rate vary among different microchannels. Among them, the yield, purity, magnesium content and chelation rate of magnesium citrate prepared by microfluidic technology with Y-shaped cross-flow geometry channels are the best.

[0092] Experimental Example 5

[0093] This experimental example illustrates the relationship between the chelation rate, yield, and purity of the magnesium citrate solution in Example 2.

[0094] The 0.5 mol / L citric acid solution and 0.5 mol / L magnesium sulfate solution prepared in Example 2 were introduced into the Y-shaped crossflow geometry channel of the microfluidic chip at different flow rates (5 ml / min, 10 ml / min, 20 ml / min, 40 ml / min, 60 ml / min, 80 ml / min, 100 ml / min, and 120 ml / min) using a peristaltic pump. The temperature of the reaction region of the microfluidic chip was controlled at 60°C, and the reaction time was 20 min. After the reaction was completed, the magnesium citrate solution was collected by filtration through a membrane with a pore size of 0.1–0.45 mm and then transferred to a microfluidic crystallizer (dual-pulse platform). Slow crystallization was carried out at 10°C for 3 hours to facilitate more accurate detection of crystal nucleation and eliminate heterogeneous nucleation sites (e.g., impurities). The crystal size was set to 10 μm. A microfluidic biosensor was used to rapidly and sensitively detect whether the content of Salmonella typhimurium, Staphylococcus aureus, molds, and yeasts in the food sample exceeded the limits for pathogenic bacteria. After meeting the national food safety standards, the magnesium citrate crystals were centrifuged at 2000 r / min and then dried with hot air at 85°C for 8 hours. The product was collected to obtain the magnesium citrate product. The effects of different flow rates on the chelation rate, yield, and purity of the magnesium citrate solution were studied according to the methods of Experiments 2 and 3. The results are as follows: Figure 9 and Figure 11 As shown.

[0095] from Figure 9 and Figure 11It can be seen that as the flow rate increases, the chelation rate, yield, and purity of magnesium citrate first increase and then decrease and gradually stabilize. The chelation rate, yield, and purity of magnesium citrate are the highest when the flow rate is 20 ml / min. This may be because as the flow rate increases, some reactants do not react in time, and there is the presence of raw material encapsulation and excess.

[0096] Experimental Example 6

[0097] This experimental example illustrates the stability of the magnesium citrate aqueous solution in Example 1.

[0098] Accurately weigh 200g (accurate to 0.0001g) of magnesium citrate into a 1000ml volumetric flask, dissolve in water and dilute to the mark. Store in a sealed container in a constant temperature water bath and conduct stability tests using the classical isothermal method. Test temperatures were room temperature, 40℃, 45℃, 50℃, 55℃, and 60℃, with sampling intervals of one day at each temperature. The pH and transmittance of the solution were measured, and the results are as follows: Figure 12 and Figure 13 As shown.

[0099] from Figure 12 and Figure 13 It can be seen that as the storage temperature increases, the pH generally tends to increase slightly, while the transmittance generally tends to remain stable; the changes in these two indicators are not significant.

[0100] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Such modifications or substitutions also fall within the protection scope defined by the appended claims.

Claims

1. A method for preparing magnesium citrate, characterized in that, Includes the following steps: Step (1) Solution preparation: Prepare citric acid solution and magnesium salt solution; in step (1), the concentration of the citric acid solution is limited to the range of 0.1-1.0 mol / L, and the concentration of the magnesium salt solution is limited to the range of 0.1-1.0 mol / L. Step (2) Solution introduction: The citric acid solution and magnesium salt solution prepared in step (1) are introduced into the microfluidic channel of the microfluidic chip; the microfluidic chip is provided with a microfluidic channel, which is selected from one of the following: T-shaped cross-flow geometry channel, Y-shaped cross-flow geometry channel and continuous flow channel; Step (3) Reaction control: By setting the channel structure of the microfluidic chip and the flow rate of the solution in the microfluidic chip, the two solutions are fully mixed and react efficiently in the reaction area of ​​the microfluidic chip, thereby forming a pure liquid reaction system to prepare magnesium citrate solution; in step (3), the flow rates of the citric acid solution and magnesium salt in the microfluidic chip are both controlled at 10-40 mL / min; the temperature of the reaction area of ​​the microfluidic chip is limited to the range of 30-70℃; the pressure of the reaction area of ​​the microfluidic chip is controlled at 0.1 kPa-50 kPa; the reaction time of step (3) is 10-30 min; Step (4) Product post-processing: After the reaction is carried out in the microfluidic chip according to the preset conditions, the magnesium citrate solution generated in step (3) is filtered, collected, crystallized, centrifuged and dried to obtain the magnesium citrate product.

2. The method for preparing magnesium citrate according to claim 1, characterized in that, In step (1), the concentration of the citric acid solution is limited to the range of 0.3-0.7 mol / L, and the concentration of the magnesium salt solution is limited to the range of 0.3-0.7 mol / L.

3. The method for preparing magnesium citrate according to claim 2, characterized in that, The magnesium salt solution used in step (1) is a magnesium chloride solution or a magnesium sulfate solution.

4. The method for preparing magnesium citrate according to claim 3, characterized in that, In step (2), the channel structure of the microfluidic chip is a Y-shaped cross-flow geometry channel.

5. The method for preparing magnesium citrate according to claim 4, characterized in that, In step (3), the flow rates of the citric acid solution and magnesium salt in the microfluidic chip are both controlled at 20 mL / min.

6. The method for preparing magnesium citrate according to claim 5, characterized in that, In step (3), the temperature of the reaction area of ​​the microfluidic chip is in the range of 45-65℃.

7. The method for preparing magnesium citrate according to claim 6, characterized in that, In step (3), the pressure in the reaction area of ​​the microfluidic chip is controlled at 15 kPa.

8. The method for preparing magnesium citrate according to claim 6, characterized in that, In step (4), after the reaction is completed in the microfluidic chip, the magnesium citrate solution after the reaction in step (3) is filtered and collected through a filter membrane with a pore size of 0.1-0.45 mm and introduced into a microfluidic crystallizer for crystallization under specific conditions. The crystallization conditions are: temperature 10℃, slow stirring for 3 hours, crystal size set at 10 μm, and subsequent centrifugation at 2000 r / min. The drying is hot air drying at 85℃ for 8 hours.

9. The method for preparing magnesium citrate according to claim 1, characterized in that, The method for preparing magnesium citrate described above has excellent repeatability. Through repeated preparation experiments, the deviation of the prepared magnesium citrate product in key indicators such as purity and magnesium content can be precisely controlled within 2%, which fully demonstrates the stability and reliability of the preparation method of the present invention.

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