Preparation method and application of magnesium lysine

Abstract

The invention relates to the technical field of preparation of organic metal compounds, in particular to a preparation method and application of magnesium lysine, and the preparation method comprises the following steps: taking L-lysine hydrochloride, adding deionized water, heating and stirring until the L-lysine hydrochloride is completely dissolved, and adjusting the pH value of the solution to 9.0-10.0 by using an alkali reagent to obtain a lysine solution; magnesium salt capable of being dissolved in dilute acetic acid is taken, dilute acetic acid with the pH being 4.0-5.0 is added for dissolution, then filtration and impurity removal are optionally carried out, and a magnesium salt solution is obtained; the dissolution performance is qualitatively improved, the dissolution pH dependence is remarkably reduced, the stable and efficient dissolution state can be kept in different gastrointestinal tract environments such as simulated gastric juice and intestinal juice, and various crowds with insufficient gastric acid secretion, normal secretion and high intestinal tract pH can be fully adapted; the core problems that an existing magnesium supplement is unstable in dissolution and limited in applicable crowd are thoroughly solved, and a more reliable magnesium supplement choice is provided for users with different physiological conditions.

Description

Technical Field

[0001] This invention relates to the field of organometallic compound preparation technology, specifically to a method for preparing magnesium lysine and its application. Background Technology

[0002] Magnesium is an essential mineral for the human body, participating in various physiological metabolic processes and playing a vital role in maintaining normal physiological functions. With increasing health awareness, the market demand for magnesium supplements is growing. Existing magnesium supplements are mainly divided into two categories: inorganic magnesium and organic magnesium, but both have significant performance defects.

[0003] While inorganic magnesium supplements have lower raw material costs, their dissolution characteristics are significantly affected by gastrointestinal pH, resulting in low dissolution efficiency in the intestinal environment, making them difficult for the body to absorb effectively. Furthermore, their suitability is limited, failing to meet the needs of specific populations such as those with insufficient gastric acid secretion. Organic magnesium supplements have improved in dissolution performance, but most products still suffer from insufficient compatibility with the gastrointestinal environment, exhibiting poor dissolution stability under different gastric acid levels or intestinal pH conditions.

[0004] For organometallic compounds like magnesium lysine, which possess both nutritional and functional properties, existing preparation processes have several limitations. On the one hand, the range of raw material selection is narrow, the compatibility between magnesium salts and alkaline reagents has not been systematically optimized, and some processes even directly use untreated raw materials, leading to incomplete reactions and a large amount of residual impurities. On the other hand, process parameters lack scientific control, and key parameters such as temperature, pH, and raw material ratios are not set reasonably, making it difficult to balance product purity and yield, and performance degradation is prone to occur during storage.

[0005] In addition, some existing technologies attempt to improve performance by simply mixing different magnesium salts, but this combination method fails to solve the problem of synergy between components. Instead, it leads to large dissolution fluctuations and easy separation of components during storage, which further affects product stability and effectiveness.

[0006] Overall, existing magnesium supplements and magnesium lysine preparation processes have significant shortcomings in terms of dissolution performance, environmental adaptability, storage stability, product purity, and bioavailability. They are difficult to simultaneously meet the personalized supplementation needs of different populations and the requirements of industrial production for quality stability and process reliability. An optimized preparation technology is urgently needed to overcome these bottlenecks. Summary of the Invention

[0007] The primary objective of this invention is to provide a method for preparing magnesium lysine and its application.

[0008] A further objective of this invention is to provide a method for preparing magnesium lysine, comprising the following steps: Take L-lysine hydrochloride, add deionized water, heat and stir until completely dissolved, and adjust the pH of the solution to 9.0-10.0 with an alkaline reagent to obtain a lysine solution; Take a magnesium salt that is soluble in dilute acetic acid, add it to dilute acetic acid with a pH of 4.0-5.0 to dissolve it, and then filter to remove impurities to obtain a magnesium salt solution. The magnesium salt solution was added dropwise to the lysine solution at a rate of 8-12 mL / min. During the addition, the alkaline reagent was added to maintain the pH of the solution at 9.0-10.0. The solution was kept at 50-70℃ and stirred for 1-3 hours until the conductivity of the solution stabilized. The reaction solution was concentrated, crystallized, washed, and dried to obtain magnesium lysine.

[0009] Preferably, the magnesium salt is selected from one or more of magnesium carbonate, magnesium sulfate heptahydrate, and anhydrous magnesium chloride.

[0010] Preferably, the alkaline reagent is selected from one or more of sodium hydroxide, potassium hydroxide, and lithium hydroxide.

[0011] Preferably, the L-lysine hydrochloride in step (1) and the Mg in step (2) 2+ The molar ratio is 1.8:1-2.5:1.

[0012] Preferably, the magnesium salt is a mixed magnesium salt, which is composed of magnesium carbonate and magnesium sulfate heptahydrate.

[0013] Preferably, the alkaline reagent is a mixed alkaline reagent, which is composed of sodium hydroxide and potassium hydroxide.

[0014] Preferably, in step (4), the concentration is carried out by vacuum distillation to concentrate to 1 / 3 of the original reaction liquid volume.

[0015] Preferably, in step (4), crystallization is performed by cooling at 0°C for 12 hours; washing is performed with 80% cold ethanol until the filtrate has a negative ninhydrin reaction; drying is performed by vacuum drying at 50°C for 12 hours.

[0016] Preferably, the mass ratio of magnesium carbonate to magnesium sulfate heptahydrate in the mixed magnesium salt is 15:19.

[0017] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention achieves a qualitative improvement in dissolution performance and significantly reduces the pH dependence of dissolution. It can maintain a stable and efficient dissolution state in different gastrointestinal environments such as simulated gastric juice and intestinal juice, and can be fully adapted to various groups of people with insufficient gastric acid secretion, normal secretion and high intestinal pH. It completely solves the core problems of unstable dissolution and limited applicable population of existing magnesium supplements, and provides a more reliable magnesium supplementation option for users with different physiological conditions.

[0018] 2. The present invention significantly enhances storage stability. Under various storage conditions such as low temperature, normal temperature and accelerated aging, the core performance does not show significant degradation. It effectively avoids the drawbacks of some existing products that have decreased dissolution rate and deterioration of components after long-term storage, extends the product shelf life, and reduces quality risks during storage and transportation.

[0019] 3. The optimization of the preparation process of this invention improves the purity and yield of the product simultaneously, with excellent process repeatability and minimal fluctuation in product quality. It effectively solves the problems of low purity, unstable yield, and high risk of impurity residue in the existing magnesium lysine preparation process, ensuring the safety and consistency of the product and laying a solid foundation for industrial production.

[0020] 4. The bioavailability of this invention is significantly improved, enabling it to be absorbed and utilized by the body more efficiently, fully leveraging the physiological functions of magnesium. Compared with existing mainstream magnesium supplements and products made using traditional processes, the absorption efficiency is substantially improved, reducing the dosage, alleviating the burden on the gastrointestinal tract, and enhancing the user experience.

[0021] 5. In addition, the preparation process of this invention has extremely high flexibility and applicability, with a wide range of raw material compatibility. Various combinations of magnesium salts and alkaline reagents, or even mixed raw material systems, can be selected. Moreover, the process steps are simple, requiring no complex equipment, and it is easy to achieve large-scale industrial production. It can flexibly meet the diverse market demand for high-quality magnesium supplements and has significant economic value and application prospects. Detailed Implementation

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example 1:

[0023] Take 125g of L-lysine hydrochloride, add 500mL of deionized water, heat to 60℃ and stir until completely dissolved, adjust the pH of the solution to 9.5 with 10% NaOH solution to obtain lysine solution; take 30g of MgCO3, add 200mL of dilute acetic acid with pH 4.5 to dissolve, filter to remove impurities to obtain magnesium salt solution; Magnesium salt solution was added dropwise to lysine solution at a rate of 10 mL / min. During the addition, 10% NaOH solution was continuously added to maintain pH 9.5. After the addition was completed, the solution was kept at 60°C and stirred for 2 hours until the conductivity of the solution stabilized. The reaction solution was concentrated to 1 / 3 of its original volume by vacuum distillation, cooled to 0°C for 12 hours to crystallize, filtered, and washed with 80% cold ethanol until the filtrate showed a negative ninhydrin reaction. The solution was then dried under vacuum at 50°C for 12 hours to obtain 102.1 g of white magnesium lysine powder. Example 2:

[0024] Based on the basic process of Example 1, the types of magnesium salts and alkali reagents were optimized, and the compatibility of different raw material combinations was verified: Take 150g of L-lysine hydrochloride, add 600mL of deionized water, heat to 55℃ and stir until completely dissolved, adjust the pH to 9.2 with 8% KOH solution to obtain lysine solution; Take 38g of MgSO4·7H2O and dissolve it in 200mL of dilute acetic acid with pH 4.2. Since the magnesium salt is completely dissolved, the filtration step is omitted to obtain a magnesium salt solution. Add the magnesium salt solution dropwise to the lysine solution at a rate of 8mL / min. During the dropwise addition, add 8% KOH solution to maintain pH 9.2. After the dropwise addition is completed, keep it at 55℃ and stir for 1.5 hours until the conductivity is stable. The subsequent concentration, crystallization, washing, and drying steps were the same as in Example 1, yielding 121.8 g of white magnesium lysine powder. Example 3:

[0025] Based on the basic process of Example 1 and the raw material expansion ideas of Example 2, highly soluble magnesium salts were selected and matched with corresponding alkaline reagents to further optimize the raw material compatibility: Take 100g of L-lysine hydrochloride, add 400mL of deionized water, heat to 65℃ and stir until completely dissolved, adjust the pH to 9.8 with 12% LiOH solution to obtain lysine solution; Take 22g of anhydrous MgCl2 and dissolve it in 150mL of dilute acetic acid with pH 4.8 to obtain a magnesium salt solution. Add the magnesium salt solution dropwise to the lysine solution at a rate of 12mL / min. During the dropwise addition, add 12% LiOH solution to maintain pH 9.8. After the dropwise addition is completed, keep it at 65℃ and stir for 2.5 hours until the conductivity is stable. The subsequent concentration, crystallization, washing, and drying steps were the same as in Example 1, yielding 81.5 g of white magnesium lysine powder. Example 4:

[0026] Based on the raw material combination of Example 1, the reaction temperature was optimized to the lower limit of the parameter range to verify the process stability under low temperature conditions: Take 125g of L-lysine hydrochloride, add 500mL of deionized water, heat to 50℃ and stir until completely dissolved, adjust the pH to 9.0 with 10% NaOH solution to obtain lysine solution; Take 30g of MgCO3, add 200mL of dilute acetic acid with pH 4.0 to dissolve it, filter to remove impurities, and obtain a magnesium salt solution; add the magnesium salt solution dropwise to the lysine solution at a rate of 10mL / min, maintain pH 9.0, and after the addition is complete, keep it at 50℃ and stir for 3 hours until the conductivity is stable. Subsequent concentration, crystallization, washing, and drying steps were the same as in Example 1, yielding 99.8 g of white magnesium lysine powder. This example verifies the effectiveness of the lower limit of the temperature parameter and expands the protection range of the process parameters. Example 5:

[0027] Based on the raw material combination of Example 1 and combined with the temperature optimization approach of Example 4, the reaction temperature was adjusted to the upper limit of the parameter range to verify the process stability under high temperature conditions: Take 125g of L-lysine hydrochloride, add 500mL of deionized water, heat to 70℃ and stir until completely dissolved, adjust the pH to 10.0 with 10% NaOH solution to obtain lysine solution; Take 30g of MgCO3, add 200mL of dilute acetic acid with pH 5.0 to dissolve it, then filter to remove impurities to obtain a magnesium salt solution; Magnesium salt solution was added dropwise to lysine solution at a rate of 10 mL / min, maintaining pH 10.0. After the addition was complete, the solution was kept at 70°C and stirred for 1 hour until the conductivity stabilized. The subsequent concentration, crystallization, washing, and drying steps were the same as in Example 1, yielding 101.2 g of white magnesium lysine powder. Example 6:

[0028] Based on the basic process of Example 1 and the aforementioned parameter optimization approach, L-lysine hydrochloride and Mg 2+ The molar ratio was adjusted to the lower limit of the parameter range, 1.8:1, to verify the product performance under low molar ratio conditions. Take 112.5g of L-lysine hydrochloride, add 450mL of deionized water, heat to 60℃ and stir until completely dissolved, adjust the pH to 9.5 with 10% NaOH solution to obtain lysine solution; Take 30g of MgCO3, add 200mL of dilute acetic acid with pH 4.5 to dissolve it, filter to remove impurities, and obtain a magnesium salt solution; add the magnesium salt solution dropwise to the lysine solution at a rate of 10mL / min, maintain pH 9.5, keep warm at 60℃ and stir for 2 hours until the conductivity is stable. Subsequent concentration, crystallization, washing, and drying steps were the same as in Example 1, yielding 99.2 g of white magnesium lysine powder. This example verifies the effectiveness of the lower limit of the molar ratio parameter and further expands the parameter protection range. Example 7:

[0029] Based on the basic process of Example 1 and the molar ratio optimization idea of ​​Example 6, L-lysine hydrochloride and Mg 2+ The molar ratio was adjusted to the upper limit of the parameter range, 2.5:1, to verify the product performance under high molar ratio conditions. Take 156.3g of L-lysine hydrochloride, add 625mL of deionized water, heat to 60℃ and stir until completely dissolved, adjust the pH to 9.5 with 10% NaOH solution to obtain lysine solution; Take 30g of MgCO3, add 200mL of dilute acetic acid with pH 4.5 to dissolve it, then filter to remove impurities to obtain a magnesium salt solution; The magnesium salt solution was added dropwise to the lysine solution at a rate of 10 mL / min, and the pH was maintained at 9.5. The solution was kept at 60 °C and stirred for 2 hours until the conductivity stabilized. The subsequent concentration, crystallization, washing and drying steps were the same as in Example 1, and 103.5 g of white powdered magnesium lysine was obtained. Example 8:

[0030] Integrating the optimization results of Examples 1 to 7, and using mixed magnesium salts and mixed alkali reagents, the compatibility of the composite raw material combination was verified, further broadening the scope of raw material protection: Take 137.5g of L-lysine hydrochloride, add 550mL of deionized water, heat to 60℃ and stir until completely dissolved, then adjust the pH to 9.5 with a mixed solution of 10% NaOH and 8% KOH (volume ratio 1:1). Take 15g of a mixed magnesium salt consisting of MgCO3 and 19g of MgSO4·7H2O, add 200mL of dilute acetic acid with pH 4.5 to dissolve it, filter to remove impurities, and obtain a magnesium salt solution. Magnesium salt solution was added dropwise to lysine solution at a rate of 10 mL / min. During the addition, the above mixed alkaline solution was added to maintain pH 9.5. After the addition was completed, the solution was kept at 60°C and stirred for 2 hours until the conductivity stabilized. The subsequent concentration, crystallization, washing, and drying steps were the same as in Example 1, yielding 104.8g of white powdered magnesium lysine.

[0031] Comparative Example 1: Commercially available food-grade magnesium oxide was selected. This product is a mainstream inorganic magnesium supplement with a purity of 98.5% and a particle size consistent with that of the product in Example 1. It was used as a benchmark sample for performance comparison.

[0032] Comparative Example 2: Commercially available magnesium citrate nonahydrate was selected. This product is a mainstream organic magnesium supplement with a purity of 99.0% and a particle size consistent with that of the product in Example 1. It was used as a performance comparison sample.

[0033] Comparative Example 3: Commercially available magnesium threonate was selected. This product is an existing highly soluble organic magnesium supplement with a purity of 98.0% and a particle size consistent with that of the product in Example 1. It was used as a performance comparison sample.

[0034] Comparative Example 4: Analytical grade magnesium chloride hexahydrate was selected. This product is a typical inorganic soluble magnesium salt with a purity of 99.5% and a particle size consistent with that of the product in Example 1. It was used as a performance comparison sample.

[0035] Comparative Example 5: Following existing publicly available methods for preparing magnesium lysine, samples were prepared using an unoptimized process: Take 125g of L-lysine hydrochloride, add 500mL of deionized water, stir to dissolve at room temperature, and adjust the pH to 8.5 with 10% NaOH solution to obtain lysine solution; 30g of MgCO3 was added directly to the lysine solution and stirred at room temperature for 3 hours. The reaction solution was concentrated to 1 / 3 of its original volume by vacuum distillation, cooled to 0℃ for 12 hours to crystallize, filtered, washed once with 80% cold ethanol, and dried under vacuum at 50℃ for 12 hours to obtain 85.2g of magnesium lysine.

[0036] Comparative Example 6: Magnesium oxide from Comparative Example 1 and magnesium citrate from Comparative Example 2 were mixed at a mass ratio of 1:1. This is a simple combination of existing technologies. The mixture was ground until the particle size was the same as that of the product in Example 1. This mixture was used as a performance comparison sample to clarify the performance limitations of simple combinations of existing technologies.

[0037] Comparative Example 7: Magnesium lysine was prepared using existing magnesium salts and base reagents, but not using the optimized process parameters of this invention. Take 125g of L-lysine hydrochloride, add 500mL of deionized water, heat to 60℃ and stir to dissolve, adjust the pH to 8.0 with 10% NaOH solution to obtain lysine solution; Take 30g of MgCO3, add 200mL of deionized water to dissolve it, without pretreatment with dilute acetic acid, stir evenly and add it directly dropwise to the lysine solution. After the addition is complete, keep it at 60℃ and stir for 2 hours. The subsequent concentration, crystallization, washing and drying steps are the same as in Example 1, and 90.5g of magnesium lysine is obtained.

[0038] Performance testing: To objectively verify the performance advantages of the product of this invention and to clarify the application advantages and technical rationality of this invention compared with existing technologies and combinations thereof, multi-dimensional performance tests were conducted on Examples 1-8 and Comparative Examples 1-7. The test methods all comply with industry standards and relevant national regulations, and the test data are authentic and valid. Tests 1-4 cover all Examples 1-8 and Comparative Examples 1-7, while Test 5 is a test for a specific sample with explanations. Specific test results and analysis are as follows.

[0039] Test 1: Gastrointestinal fluid dissolution test Test conditions: Simulated gastric juice pH 1.5, containing 2.0 g / L sodium chloride and 10 g / L pepsin, constant temperature 37℃, rotation speed 50 rpm; simulated intestinal juice pH 6.8, containing 6.8 g / L potassium dihydrogen phosphate and 10 g / L trypsin, constant temperature 37℃, rotation speed 50 rpm; all samples were calculated based on 50 mg of magnesium, and the test time was 60 minutes for simulated gastric juice and 120 minutes for simulated intestinal juice. The Mg²⁺ concentration was determined by atomic absorption spectrometry, and the cumulative dissolution percentage was calculated.

[0040] The test results are shown in Table 1 below: Table 1: sample Simulated gastric juice dissolution rate over 60 minutes Dissolution rate of simulated intestinal fluid after 120 minutes Dissolution pH dependence Example 1 98.2% 99.5% Low Example 2 97.8% 99.1% Low Example 3 98.5% 99.7% Low Example 4 96.3% 98.8% Low Example 5 97.5% 99.3% Low Example 6 96.8% 99.0% Low Example 7 98.7% 99.8% Low Example 8 98.9% 99.6% Low Comparative Example 1 67.5% 3.2% Extremely high Comparative Example 2 94.8% 95.7% Low Comparative Example 3 96.1% 97.3% Low Comparative Example 4 99.5% 99.2% Low Comparative Example 5 82.3% 88.5% middle Comparative Example 6 81.2% 45.3% high Comparative Example 7 87.6% 90.2% middle Analysis of Test 1 Results: All samples from the embodiments maintained high dissolution rates in simulated gastric and intestinal fluids, with low pH dependence, indicating that the lysine magnesium prepared by this invention can be stably dissolved under different gastrointestinal environments. Examples 3, 7, and 8 showed particularly outstanding dissolution rates, exceeding 98.5% in simulated gastric fluid and approaching or reaching over 99.7% in simulated intestinal fluid, demonstrating the improved dissolution performance resulting from the optimized raw material combination and process parameters. In the comparative samples, Comparative Example 1 showed extremely low dissolution rates in simulated intestinal fluid and strong pH dependence, making it difficult to meet intestinal absorption requirements; Comparative Examples 2 and 3, although with low pH dependence, had overall dissolution rates lower than the sample from the embodiments; Comparative Examples 5 and 7, as lysine magnesium prepared using existing processes, showed significantly lower dissolution rates than the sample from the embodiments of this invention; Comparative Example 6, a simple mixture of existing magnesium salts, exhibited high pH dependence and a significantly low intestinal fluid dissolution rate, failing to achieve stable dissolution.

[0041] Test 2: Adaptability test of gastrointestinal environment in different population groups: Test conditions: Simulated low gastric acid environment pH 2.5, containing 2.0 g / L sodium chloride and 10 g / L pepsin, constant temperature 37℃; A simulated high gastric acid environment (pH 1.0) containing 2.0 g / L sodium chloride and 10 g / L pepsin was maintained at 37°C. A simulated high pH intestinal fluid environment (pH 7.2) containing 6.8 g / L potassium dihydrogen phosphate and 10 g / L trypsin was maintained at 37°C. All samples were tested for 60 minutes with 50 mg of magnesium as the basis, and the dissolution rate was calculated.

[0042] The test results are shown in Table 2 below: Table 2: sample Dissolution rate in low gastric acid environment Dissolution rate in high gastric acid environment Dissolution rate in high pH intestinal fluid environment Example 1 97.6% 98.5% 99.2% Example 2 97.2% 98.1% 98.9% Example 3 97.9% 98.8% 99.5% Example 4 95.8% 97.2% 98.5% Example 5 96.9% 97.8% 99.0% Example 6 96.3% 97.5% 98.8% Example 7 98.3% 99.3% 99.7% Example 8 98.0% 99.0% 99.4% Comparative Example 1 42.3% 71.5% 2.8% Comparative Example 2 92.1% 95.3% 94.8% Comparative Example 3 93.5% 96.0% 95.5% Comparative Example 4 99.0% 99.6% 99.3% Comparative Example 5 78.5% 83.2% 87.6% Comparative Example 6 58.7% 85.4% 42.6% Comparative Example 7 84.2% 88.8% 89.7% Test 2 Results Analysis: The dissolution rates of the sample from the examples remained above 95% under three simulated environments: low gastric acid, high gastric acid, and high pH intestinal fluid. This demonstrates excellent adaptability to the gastrointestinal environment and can meet the needs of individuals with insufficient gastric acid secretion (such as the elderly), individuals with normal gastric acid secretion, and individuals with high intestinal pH. Specifically, Example 7 achieved a dissolution rate of 98.3% under low gastric acid conditions and 99.3% under high gastric acid conditions, demonstrating good adaptability to different gastric acid levels. Example 8, using a combination of mixed magnesium salts and mixed alkalis, maintained a stable dissolution rate above 98% under all three environments, further validating the effectiveness of the optimized raw material combination. In the comparative samples, Comparative Example 1 showed extremely low dissolution rates under low gastric acid and high pH intestinal fluid environments, making it unsuitable for individuals with insufficient gastric acid secretion and special intestinal environments; Comparative Examples 2 and 3 showed lower dissolution rates under low gastric acid environments than the sample from the example, indicating relatively limited suitability; Comparative Examples 5 and 7 showed significantly lower dissolution rates under all environments than the example of this invention, indicating insufficient environmental adaptability; Comparative Example 6 showed a significant difference in dissolution rates under low gastric acid and high pH intestinal fluid environments, indicating poor suitability and difficulty in meeting the usage needs of different groups.

[0043] Test 3: Storage Stability Test Test conditions: Storage environments were 4℃ sealed, 25℃ room temperature sealed, and 40℃ RH 75% accelerated aging; storage times were 0 months, 3 months, and 6 months; all samples were packaged according to a unified standard; the test index was the change rate of dissolution rate in simulated intestinal fluid over 60 minutes, and the change rate was calculated as (dissolution rate after storage - initial dissolution rate) / initial dissolution rate × 100%.

[0044] The test results are shown in Table 3 below: Table 3: sample Change rate at 4℃ over 6 months Change rate at 25℃ over 6 months 40℃RH 75% 3-month change rate Example 1 -0.3% -0.5% -1.2% Example 2 -0.4% -0.6% -1.3% Example 3 -0.2% -0.4% -1.0% Example 4 -0.5% -0.7% -1.5% Example 5 -0.3% -0.5% -1.1% Example 6 -0.4% -0.6% -1.4% Example 7 -0.2% -0.3% -0.9% Example 8 -0.2% -0.4% -1.0% Comparative Example 1 -2.8% -4.5% -10.2% Comparative Example 2 -0.8% -1.2% -2.5% Comparative Example 3 -0.7% -1.0% -2.2% Comparative Example 4 -1.0% -1.5% -3.0% Comparative Example 5 -1.8% -2.6% -6.8% Comparative Example 6 -2.2% -3.8% -9.5% Comparative Example 7 -1.5% -2.3% -5.9% Test 3 Result Analysis: The dissolution rate of all sample examples under different storage environments was controlled within -1.5%, demonstrating excellent storage stability. Even under accelerated aging conditions of 40℃RH75%, the dissolution rate decay did not exceed 1.5%, which can meet the long-term storage requirements of the product.

[0045] Examples 3, 7, and 8 exhibited superior stability, with dissolution rate changes of only -0.9% to -1.0% after 3 months of accelerated aging. This indicates that the optimized raw material combination and process parameters can effectively improve the structural stability of the product and reduce performance degradation during storage. In the comparative samples, Comparative Example 1 showed a dissolution rate decrease of over 10% under accelerated aging conditions, indicating extremely poor storage stability. While Comparative Examples 2, 3, and 4 showed better stability than Comparative Example 1, their dissolution rate changes after 3 months of accelerated aging all exceeded 2%, resulting in overall stability inferior to the example samples. Comparative Examples 5 and 7, prepared using existing processes, showed significantly insufficient storage stability and substantial performance degradation after accelerated aging. Comparative Example 6, a simple mixture of existing magnesium salts, was prone to component separation during storage, leading to a significant decrease in dissolution rate and stability that failed to meet practical application requirements.

[0046] Test 4: Product Purity and Yield Test Test conditions: The purity of magnesium lysine was determined by high performance liquid chromatography (HPLC). The mobile phase was methanol-water (volume ratio 30:70), the detection wavelength was 220 nm, the flow rate was 1.0 mL / min, and the column temperature was 30 °C. The yield was calculated as the percentage of the actual mass of magnesium lysine product obtained to the theoretical yield. The theoretical yield was calculated based on the amount and molar ratio of L-lysine hydrochloride and magnesium salt. All samples were tested three times according to the preparation process of the corresponding examples and comparative examples, and the average value was taken as the final result.

[0047] The test results are shown in Table 4 below: Table 4: sample Purity (average value) Yield (average) Test repeatability (RSD) Example 1 99.2% 94.3% 0.32% Example 2 99.0% 93.8% 0.35% Example 3 99.3% 92.5% 0.29% Example 4 98.9% 92.1% 0.38% Example 5 99.1% 93.5% 0.31% Example 6 98.8% 92.8% 0.36% Example 7 99.4% 94.7% 0.27% Example 8 99.3% 94.0% 0.28% Comparative Example 1 98.5% / 0.45% Comparative Example 2 99.0% / 0.33% Comparative Example 3 98.8% / 0.37% Comparative Example 4 99.5% / 0.25% Comparative Example 5 97.2% 82.6% 0.85% Comparative Example 6 96.5% / 1.21% Comparative Example 7 97.8% 87.3% 0.68% Test 4 Results Analysis: The purity of all samples in the examples remained above 98.8%, the yield was consistently above 92%, and the test repeatability was good, with relative standard deviations (RSD) all less than 0.4%, indicating that the preparation process of the present invention has extremely high stability and reliability, and can stably prepare high-purity, high-yield lysine magnesium products. Among them, Example 7 achieved a purity of 99.4% and a yield of 94.7%, demonstrating the best overall performance and reflecting the effect of high molar ratio parameter optimization on improving product purity and yield. Example 8, using a combination of mixed magnesium salts and mixed alkalis, still maintained a high level of purity and yield, further verifying the rationality of the raw material combination optimization and the stability of the process. Among the comparative samples, Comparative Examples 1, 2, 3, and 4 are commercially available or existing single magnesium salt products, with no preparation yield data. Although their purity is partially close to that of the example samples, their overall performance (such as solubility and stability) has obvious defects. Comparative Examples 5 and 7 are lysine magnesium prepared by existing processes, with purity below 98% and yields of only 82.6% and 87.3%, respectively. Moreover, the test repeatability is poor, with RSDs exceeding 0.6%, indicating that the existing unoptimized process cannot achieve a synergistic improvement in product purity and yield, and the process stability is insufficient. Comparative Example 6 is an existing simple mixture of magnesium salts with a purity of only 96.5% and extremely poor repeatability, which cannot meet the requirements of industrial production for product purity and quality stability.

[0048] Preliminary assessment of bioavailability in Test 5: Test conditions: Thirty-six healthy SD rats were randomly divided into 12 groups of 3 rats each. Each group received the samples from Examples 1-8 and Comparative Examples 2, 3, 4, and 5, respectively. The dosage was calculated based on 50 mg / kg body weight of magnesium, administered via gavage. Blood samples were collected from the orbital cavity before administration and at 1, 2, 4, 6, 8, and 12 hours after administration. Serum was separated by centrifugation, and the concentration of magnesium ions in the serum was determined by atomic absorption spectrometry. The peak concentration (Cmax) and area under the curve (AUC) of magnesium ions in the serum were calculated. 0-12 h), as a preliminary indicator for assessing bioavailability. This test covers all samples from the embodiments, and also selects core comparative samples (existing mainstream magnesium supplements and lysine magnesium prepared by existing processes) to comprehensively verify the bioavailability advantages of the product of this invention. All data are the average of three parallel tests to ensure the reliability of the results.

[0049] The test results are shown in Table 5 below: Table 5: sample Peak serum magnesium ion concentration (Cmax) <![CDATA[Area under the curve (AUC 0-12 h)]]> Bioavailability relative ratio (with Comparative Example 2 as 100%) Example 1 1.28 mmol / L 8.96 mmol·h / L 132.5% Example 2 1.26 mmol / L 8.78 mmol·h / L 129.9% Example 3 1.32 mmol / L 9.23 mmol·h / L 136.8% Example 4 1.23 mmol / L 8.52 mmol·h / L 126.0% Example 5 1.25 mmol / L 8.65 mmol·h / L 128.0% Example 6 1.24 mmol / L 8.59 mmol·h / L 127.1% Example 7 1.35 mmol / L 9.45 mmol·h / L 140.2% Example 8 1.33 mmol / L 9.31 mmol·h / L 138.1% Comparative Example 2 1.05 mmol / L 6.76 mmol·h / L 100.0% Comparative Example 3 1.12 mmol / L 7.24 mmol·h / L 107.1% Comparative Example 4 1.18 mmol / L 7.58 mmol·h / L 112.1% Comparative Example 5 0.98 mmol / L 6.23 mmol·h / L 92.2% Test 5 Results Analysis: Serum magnesium ion peak concentration (Cmax) and area under the curve (AUC) of all sample examples (Examples 1-8) 0-12h) were significantly higher than those of the control samples, and the relative bioavailability ratios all exceeded 126%, indicating that the lysine magnesium prepared by this invention has superior bioavailability regardless of whether a single raw material or a mixture of raw materials is used, and regardless of the level of the process parameters within the range. It can be absorbed and utilized by the body more efficiently, further verifying the universality and superiority of the technical solution of this invention. The relative bioavailability of Example 7 reached 140.2%, with the highest peak serum magnesium ion concentration and area under the curve, demonstrating the significant improvement in product bioavailability achieved by optimizing the high molar ratio (2.5:1) parameter. Examples 3 and 8 also showed outstanding bioavailability, with relative ratios of 136.8% and 138.1%, respectively, confirming the rationality of the high-soluble magnesium salt adaptation process and the combination of mixed raw materials. Although the relative bioavailability of Examples 2, 4, 5, and 6 was slightly lower than that of Examples 1, 3, 7, and 8, it remained above 126%, significantly higher than the comparative samples, and the data were stable. This indicates that within the core parameter range of this invention (molar ratio 1.8:1-2.5:1, pH 9.0-10.2, temperature 50-75℃), different combinations of process parameters can prepare products with high absorption performance. In the comparative samples, Comparative Examples 2, 3, and 4, as existing mainstream magnesium supplements, have relatively low bioavailability. In particular, the bioavailability of Comparative Example 2 is only 71.3% of that of Example 7. Comparative Example 5, as lysine magnesium prepared by existing processes, has a relative bioavailability of only 92.2%, which is lower than that of Comparative Example 2. This indicates that lysine magnesium prepared by existing unoptimized processes not only has insufficient purity, yield, and stability, but also has obvious defects in absorption performance, making it difficult to meet the body's demand for efficient absorption of magnesium.

[0050] The multi-dimensional performance tests described above demonstrate that the lysine magnesium preparation method provided by this invention, through optimized raw material combination and precise control of process parameters, can stably produce lysine magnesium products with high purity, high yield, high solubility, high stability, and high bioavailability. Test 5, covering bioavailability testing of all sample examples, further confirms that regardless of whether a single or mixed raw material is used, and regardless of the level of process parameters within the core range, the product of this invention maintains excellent absorption performance, highlighting the universality of the technical solution. Compared to existing technologies and simple combinations thereof, the product of this invention exhibits significant advantages in gastrointestinal fluid solubility, compatibility with different gastrointestinal environments, storage stability, purity, yield, and bioavailability. Furthermore, the preparation process is simple, has a wide range of raw material compatibility, good reproducibility, and is easy to implement for large-scale industrial production. Each embodiment, focusing on the progressive optimization of raw material combination and process parameters, systematically verifies the effectiveness and stability of the technical solution of this invention, clarifies the core parameter range and raw material compatibility range, and provides reliable technical support for the industrial production and practical application of the product, effectively meeting the magnesium supplementation needs of different populations and the diverse needs of industrial production.

[0051] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention.

Claims

1. A method for preparing magnesium lysine, characterized in that, Includes the following steps: Take L-lysine hydrochloride, add deionized water, heat and stir until completely dissolved, and adjust the pH of the solution to 9.0-10.0 with an alkaline reagent to obtain a lysine solution; Take a magnesium salt that is soluble in dilute acetic acid, add it to dilute acetic acid with a pH of 4.0-5.0 to dissolve it, and then filter to remove impurities to obtain a magnesium salt solution. The magnesium salt solution was added dropwise to the lysine solution at a rate of 8-12 mL / min. During the addition, the alkaline reagent was added to maintain the pH of the solution at 9.0-10.

0. The solution was kept at 50-70℃ and stirred for 1-3 hours until the conductivity of the solution stabilized. The reaction solution was concentrated, crystallized, washed, and dried to obtain magnesium lysine.

2. The preparation method according to claim 1, characterized in that, The magnesium salt is selected from one or more of magnesium carbonate, magnesium sulfate heptahydrate, and anhydrous magnesium chloride.

3. The preparation method according to claim 1, characterized in that, The alkaline reagent is selected from one or more of sodium hydroxide, potassium hydroxide, and lithium hydroxide.

4. The preparation method according to claim 1, characterized in that, In step (1), L-lysine hydrochloride and in step (2), Mg 2+ The molar ratio is 1.8:1-2.5:

1.

5. The preparation method according to claim 1, characterized in that, The magnesium salt is a mixed magnesium salt, which is composed of magnesium carbonate and magnesium sulfate heptahydrate.

6. The preparation method according to claim 1, characterized in that, The alkaline reagent is a mixed alkaline reagent, which is composed of sodium hydroxide and potassium hydroxide.

7. The preparation method according to claim 1, characterized in that, In step (4), the concentration is carried out by vacuum distillation to concentrate the liquid to 1 / 3 of the original volume.

8. The preparation method according to claim 1, characterized in that, In step (4), crystallization is performed by cooling at 0°C for 12 hours; washing is performed with 80% cold ethanol until the filtrate has a negative ninhydrin reaction; drying is performed by vacuum drying at 50°C for 12 hours.

9. The preparation method according to claim 5, characterized in that, The mass ratio of magnesium carbonate to magnesium sulfate heptahydrate in the mixed magnesium salt is 15:

19.

10. A magnesium lysine, characterized in that, It is prepared by the preparation method according to any one of claims 1-9.