Preparation method and application of magnesium L-threonate
By reacting L-ascorbic acid with magnesium hydroxide and alkaline magnesium carbonate, and purifying hydrogel with temperature-sensitive molecular blotting and crystallization of aqueous ethanol solution, the problem of low purity and yield in the existing preparation methods of L-threonate was solved, and high-purity and high-yield magnesium L-threonate was prepared and applied to sustained-release antidepressant drugs.
Patent Information
- Application Number
- CN202411937318.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-26
- Publication Date
- 2025-03-21
AI Technical Summary
Among the existing preparation methods for magnesium threonate, the product has low purity and low yield, which is not suitable for industrial production.
Reacting L-ascorbic acid with magnesium hydroxide and alkaline magnesium carbonate, adding hydrogen peroxide dropwise, heating and stirring, and then purifying by temperature-sensitive molecular blotting hydrogel and crystallizing aqueous ethanol solution to produce high purity and high yield of magnesium L-threonate.
The purity and yield of L-threonate was improved, and the low-toxic and biocompatible sustained release form was prepared, which was suitable for the preparation of antidepressants.
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Figure CN119661345A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of medical technology, and in particular to a preparation method of magnesium L-threonate and application thereof. Background Art
[0002] L-threonate is widely present in plants, human gastric acid and uric acid. It is a degradation product of L-ascorbic acid. Magnesium is one of the essential elements for the survival of living organisms. Mg is very important for the activities of many enzyme functions. During normal metabolism in cells, the catalytic activity of several enzymes must rely on Mg. Magnesium L-threonate can be used as a Mg supplement, as a laxative and choleretic, and its injection can also be used as an anticonvulsant.
[0003] The synthesis technology of magnesium L-threonate includes the following: Chinese patent document CN1301691A "New L-threonic acid derivatives" reports: In a water system, vitamin C is used as a raw material, basic magnesium carbonate is added, hydrogen peroxide is added as an oxidant under controlled low temperature conditions, activated carbon is added as a catalyst after sufficient stirring, and hydrogen peroxide is decomposed under high temperature conditions. The L-threonic acid magnesium product obtained by this method has low purity and low yield because the generated magnesium oxalate is slightly soluble in water and difficult to remove, and is not suitable for industrial production.
[0004] Chinese patent document CN102875362A "A method for preparing L-threonic acid or its salt" reports. Vitamin C is used as raw material, hydrogen peroxide is used as oxidant, magnesium hydroxide is added to form salt, synthesized in a pure water system, and crystallized at room temperature using ethanol aqueous solution. Because the generated magnesium oxalate is slightly soluble in water and difficult to remove, the product purity is not high and the yield is not high.
[0005] Chinese patent document CN104961636A "L-threonate magnesium synthesis method" reported that vitamin C is used as raw material, hydrogen peroxide is used as oxidant, remade magnesium carbonate is added, synthesized in a water system, and the product is obtained by crystallization of ethanol aqueous solution. The process has been optimized to improve the purity and yield, and the obtained product has a higher bulk density, which is more in line with the market demand for L-threonate magnesium. Summary of the invention
[0006] The purpose of the present invention is to provide a preparation method of L-magnesium threonate and application thereof. The preparation method is simple, high in purity and high in yield. At the same time, a sustained-release L-magnesium threonate is prepared, which has low toxicity, good biocompatibility, large drug loading capacity, low economic cost and good drug efficacy, and has broad application prospects in the preparation of antidepressant drugs.
[0007] The technical solution of the present invention is achieved in this way: The invention provides a preparation method of magnesium L-threonate. The method comprises the following steps: dissolving L-ascorbic acid in water, adding magnesium hydroxide and alkaline magnesium carbonate and stirring, dropping hydrogen peroxide, heating and stirring for reaction, filtering a product, purifying the product by passing it through a thermosensitive molecular imprinting hydrogel while it is hot, concentrating the product, adding an ethanol aqueous solution to the concentrated solution, standing the concentrated solution for crystallization, filtering, washing, and drying the concentrated solution to obtain magnesium L-threonate. The adsorbed thermosensitive molecular imprinting hydrogel is cooled to room temperature, washed, and reused.
[0008] As a further improvement of the present invention, the preparation method of the thermosensitive molecular imprinted hydrogel is as follows: dissolving oxalic acid, a monomer composition, and a crosslinking agent in water, adding an initiator, heating and stirring to react, filtering while hot, cooling the solid to room temperature, washing, and drying to obtain a thermosensitive molecular imprinted hydrogel.
[0009] As a further improvement of the present invention, the monomer composition is N-isopropylacrylamide, methyl acrylate, and butyl methacrylate, and the mass ratio is 12-17:10-15:7-10.
[0010] As a further improvement of the present invention, the mass ratio of the oxalic acid, the monomer composition, the crosslinking agent, and the initiator is 4-6:20-30:1-2:0.2-0.3, the crosslinking agent is N,N'-methylenebisacrylamide, and the initiator is selected from at least one of sodium persulfate, potassium persulfate, and ammonium persulfate; the temperature of the heating and stirring reaction is 80-90°C, and the time is 3-5h.
[0011] As a further improvement of the present invention, 35-45 parts by weight of L-ascorbic acid are dissolved in 200 parts by weight of water, the temperature is raised to 20-30° C., 4-7 parts by weight of magnesium hydroxide and 25-30 parts by weight of alkaline magnesium carbonate are added and stirred, 50-70 parts by weight of 22-25wt% hydrogen peroxide are added dropwise, the temperature is heated to 70-80° C., the reaction is stirred for 2-4 hours, the product is filtered, purified by a thermosensitive molecular imprinting hydrogel while hot, concentrated to a relative density of 1.07-1.1, 80-90wt% of an ethanol aqueous solution is added to the concentrated solution, the solution is allowed to stand for 2-4 hours, crystallized, filtered, washed, and dried to obtain magnesium L-threonate, and the thermosensitive molecular imprinting hydrogel after adsorption is cooled to room temperature, washed, and reused.
[0012] The present invention further protects a method for preparing sustained-release magnesium L-threonate, comprising the following steps: S1. Preparation of modified polyvinyl alcohol: dissolving polyvinyl alcohol in water, adding polydopamine and a catalyst, heating and stirring to react, dialyzing, and drying the dialyzate to obtain modified polyvinyl alcohol; S2. Preparation of sustained-release magnesium L-threonate: Dissolve the silk fibroin peptide and the modified polyvinyl alcohol obtained in step S1 in water, add magnesium L-threonate, adjust the pH value to 6.4-6.6 to obtain a gel, freeze-dry, and pulverize to obtain sustained-release magnesium L-threonate.
[0013] As a further improvement of the present invention, the mass ratio of polyvinyl alcohol, polydopamine and catalyst in step S1 is 14-18:4-7:0.5-1, the catalyst is a Tris-HCl solution with a pH of 8.5-9.5, the temperature of the heating and stirring reaction is 40-50°C, the time is 1-3h, the pore size of the dialysis bag used for dialysis is 1-2kDa, and the dialysis time is 18-24h.
[0014] As a further improvement of the present invention, the mass ratio of the silk fibroin peptide, modified polyvinyl alcohol, and magnesium L-threonate in step S2 is 10-15:7-12:8-10.
[0015] The present invention further protects a sustained-release magnesium L-threonate prepared by the above-mentioned preparation method.
[0016] The present invention further protects the use of the sustained-release magnesium L-threonate in the preparation of antidepressant drugs.
[0017] The present invention has the following beneficial effects: The invention adopts hydrogen peroxide to oxidize L-ascorbic acid, and reacts with magnesium carbonate and magnesium hydroxide to obtain magnesium oxalate precipitate and L-magnesium threonate. The reaction yield is high, but the obtained magnesium oxalate is slightly soluble in water, which reduces the reaction purity.
[0018] The present invention combines the template molecule oxalic acid with the functional monomer, copolymerizes under the action of a cross-linking agent to obtain a solid medium, and then elutes the template molecule to obtain a molecular imprinting polymer with a binding site that matches the spatial configuration of the target molecule and the arrangement of functional groups. However, the molecular imprinting polymer obtained by the traditional method relies on a high degree of crosslinking to maintain the rigidity of its imprinted structure, and often has a crosslinking degree that reduces the swelling property when it is too high, resulting in difficulty in adsorption and desorption of the template molecule in the polymer. The thermosensitive molecular imprinting hydrogel prepared by the present invention can respond to changes in ambient temperature, so that the molecular imprinting polymer has temperature controllability in recognizing the template molecule oxalate. When the temperature is lower than the lower critical solution temperature, the hydrogel exhibits a swelling property, so that the template molecule is desorbed and eluted, and when the temperature is higher than the lower critical solution temperature, the hydrogel exhibits a shrinking property, so that the oxalate can be well adsorbed, so that a small amount of oxalate in the reaction solution can be adsorbed and removed, so that the product is highly purified, and the purity of the product L-threonase is greatly improved. At the same time, the thermosensitive molecular imprinting hydrogel can be used repeatedly, thereby improving its applicability.
[0019] The invention prepares a sustained-release magnesium L-threonate, which not only greatly improves the bioavailability of magnesium L-threonate in an organism, but also has good intestinal sustained-release effect and prolongs the drug effect. The sustained-release magnesium L-threonate adopts a self-crosslinking hydrogel as a carrier. The hydrogel uses polydopamine to modify polyvinyl alcohol, which can construct a hydrogel network based on non-covalent interaction (hydrogen bond and hydrophobic interaction) physical crosslinking with silk protein peptides, realizes physical crosslinking without a crosslinking agent, has good mechanical properties, low toxicity, good biocompatibility, large drug loading, low economic cost, can realize sustained-release of magnesium L-threonate, improve drug effect, and has broad application prospects in the preparation of antidepressant drugs.
[0020] The preparation method of the magnesium L-threonate is simple, high in purity and high in yield, and a sustained-release magnesium L-threonate is prepared at the same time, which has low toxicity, good biocompatibility, large drug loading capacity, low economic cost and good drug efficacy, and has broad application prospects in the preparation of antidepressant drugs. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.
[0022] Figure 1 The equilibrium swelling ratio of each group of thermosensitive molecular imprinting hydrogels in Test Example 1 of the present invention varies with temperature. DETAILED DESCRIPTION
[0023] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0024] Preparation Example 1 Preparation of Thermosensitive Molecularly Imprinted Hydrogel The method is as follows: 4 g oxalic acid, 20 g monomer composition, and 1 g cross-linking agent N,N'-methylenebisacrylamide are dissolved in 150 mL water, 0.2 g sodium persulfate is added, heated to 80°C, stirred for reaction for 3 h, filtered while hot, the solid is cooled to room temperature, washed, and dried to obtain a thermosensitive molecularly imprinted hydrogel; The monomer composition is N-isopropylacrylamide, methyl acrylate and butyl methacrylate, and the mass ratio is 12:10:7.
[0025] Preparation Example 2 Preparation of Thermosensitive Molecularly Imprinted Hydrogel The method is as follows: 6 g of oxalic acid, 30 g of the monomer composition, and 2 g of the cross-linking agent N,N'-methylenebisacrylamide are dissolved in 150 mL of water, 0.3 g of potassium persulfate is added, heated to 90°C, stirred for reaction for 5 hours, filtered while hot, the solid is cooled to room temperature, washed, and dried to obtain a thermosensitive molecularly imprinted hydrogel; The monomer composition is N-isopropylacrylamide, methyl acrylate and butyl methacrylate, and the mass ratio is 17:15:10.
[0026] Preparation Example 3 Preparation of Thermosensitive Molecularly Imprinted Hydrogel The method is as follows: 5 g of oxalic acid, 25 g of the monomer composition, and 1.5 g of the cross-linking agent N,N'-methylenebisacrylamide are dissolved in 150 mL of water, 0.25 g of ammonium persulfate is added, heated to 85°C, stirred for reaction for 4 hours, filtered while hot, the solid is cooled to room temperature, washed, and dried to obtain a thermosensitive molecularly imprinted hydrogel; The monomer composition is N-isopropylacrylamide, methyl acrylate and butyl methacrylate, and the mass ratio is 15:12:8.
[0027] Test Example 1 The equilibrium swelling ratio Rs of the hydrogel in distilled water at different temperatures was determined by weighing method. The thermosensitive molecular imprinting hydrogel prepared in Preparation Example 1-3 was weighed and placed in 10 mL of distilled water at different temperatures (20, 25, 30, 35, 40, 45, 50°C) for 24 hours. The temperature condition was controlled by a constant temperature water bath. After reaching swelling equilibrium, the surface moisture of the gel was wiped with filter paper, and the equilibrium mass m of the hydrogel at each temperature was recorded. 24h , and the measurements were performed three times in parallel to calculate the equilibrium swelling ratio Rs.
[0028] Rs=(m 24h -m0) / m0×100% Where: m 24h is the mass of the hydrogel at 24 hours, and m0 is the mass of the gel when it is dried to a constant weight at the initial moment.
[0029] The results are shown in the table Figure 1 As can be seen from the figure, at about 35°C, the slope of the swelling rate curve has a sudden jump, which shows that 35°C is the lower critical solution temperature (LCST) value of the hydrogel. Below this temperature, the thermosensitive molecular imprinting hydrogel swells, and at this time, the template oxalate is easy to desorb. At a temperature higher than this, the thermosensitive molecular imprinting hydrogel shrinks, which has a good adsorption effect on oxalate.
[0030] Example 1 The present embodiment provides a method for preparing magnesium L-threonate, wherein 35 g of L-ascorbic acid is dissolved in 200 mL of water, the temperature is raised to 20° C., 4 g of magnesium hydroxide and 25 g of alkaline magnesium carbonate are added and stirred, 50 g of 22 wt % hydrogen peroxide is added dropwise, the mixture is heated to 70° C., stirred and reacted for 2 h, the product is filtered, and the product is purified by the thermosensitive molecular imprinting hydrogel prepared in Preparation Example 1 while hot, and concentrated to a relative density of 1.07, 80 wt % of ethanol aqueous solution is added to the concentrated solution, the solution is allowed to stand for 2 h, crystallized, filtered, washed, and dried to obtain magnesium L-threonate, with a mass yield of 62.2% and a purity of 99.94%. The temperature of the adsorbed thermosensitive molecular imprinting hydrogel is cooled to room temperature, washed, and reused.
[0031] Example 2 The present embodiment provides a method for preparing magnesium L-threonate, wherein 45 g of L-ascorbic acid is dissolved in 200 mL of water, the temperature is raised to 30° C., 7 g of magnesium hydroxide and 30 g of alkaline magnesium carbonate are added and stirred, 70 g of 25 wt % hydrogen peroxide is added dropwise, the mixture is heated to 80° C., stirred and reacted for 4 hours, the product is filtered, and the product is purified by the thermosensitive molecular imprinting hydrogel prepared in Preparation Example 2 while hot, and concentrated to a relative density of 1.1, 90 wt % of ethanol aqueous solution is added to the concentrated solution, the solution is allowed to stand for 4 hours, crystallized, filtered, washed, and dried to obtain magnesium L-threonate with a mass yield of 60.9% and a purity of 99.92%. The temperature-sensitive molecular imprinting hydrogel after adsorption is cooled to room temperature, washed, and reused.
[0032] Example 3 The present embodiment provides a method for preparing magnesium L-threonate, wherein 40 g of L-ascorbic acid is dissolved in 200 mL of water, the temperature is raised to 25° C., 5.5 g of magnesium hydroxide and 27 g of alkaline magnesium carbonate are added and stirred, 60 g of 22 wt % hydrogen peroxide is added dropwise, the mixture is heated to 75° C., stirred and reacted for 3 h, the product is filtered, and the product is purified by the thermosensitive molecular imprinting hydrogel prepared in Preparation Example 3 while hot, and concentrated to a relative density of 1.08, 85 wt % of ethanol aqueous solution is added to the concentrated solution, the solution is allowed to stand for 3 h, crystallized, filtered, washed, and dried to obtain magnesium L-threonate with a mass yield of 64.7% and a purity of 99.98%. The temperature of the adsorbed thermosensitive molecular imprinting hydrogel is cooled to room temperature, washed, and reused.
[0033] Comparative Example 1 Compared with Example 3, the difference is that the product is not purified by thermosensitive molecular imprinting hydrogel, the mass yield is 62.0%, and the purity is 92.1%.
[0034] Example 4 This embodiment provides a method for preparing sustained-release magnesium L-threonate, comprising the following steps: S1. Preparation of modified polyvinyl alcohol: 14 g of polyvinyl alcohol was dissolved in 200 mL of water, 4 g of polydopamine and 0.5 g of a catalyst were added, the mixture was heated to 40° C., the reaction was stirred for 1 h, the dialysis bag used had a pore size of 1 kDa, and the dialyzate was dried to obtain modified polyvinyl alcohol; The catalyst is a Tris-HCl solution with a pH of 8.5; S2. Preparation of sustained-release magnesium L-threonate: 10 g of silk fibroin peptide and 7 g of modified polyvinyl alcohol prepared in step S1 were dissolved in 200 mL of water, 8 g of magnesium L-threonate prepared in Example 1 was added, the pH value was adjusted to 6.4, a gel was obtained, freeze-dried, and crushed to obtain sustained-release magnesium L-threonate. Loose bulk density 0.82 g / cm 3 , compact packing density 1.10g / cm 3 .
[0035] Example 5 This embodiment provides a method for preparing sustained-release magnesium L-threonate, comprising the following steps: S1. Preparation of modified polyvinyl alcohol: 18 g of polyvinyl alcohol was dissolved in 200 mL of water, 7 g of polydopamine and 1 g of catalyst were added, the mixture was heated to 50° C., the mixture was stirred for 3 h, the dialysis bag used had a pore size of 2 kDa and the mixture was dialyzed for 24 h, and the dialyzate was dried to obtain modified polyvinyl alcohol; The catalyst is a Tris-HCl solution with a pH of 9.5; S2. Preparation of sustained-release magnesium L-threonate: 15 g of silk fibroin peptide and 12 g of modified polyvinyl alcohol prepared in step S1 were dissolved in 200 mL of water, 10 g of magnesium L-threonate prepared in Example 2 was added, the pH value was adjusted to 6.6, a gel was obtained, freeze-dried, and crushed to obtain sustained-release magnesium L-threonate. Loose bulk density 0.84 g / cm 3 , compact packing density 1.13g / cm 3 .
[0036] Example 6 This embodiment provides a method for preparing sustained-release magnesium L-threonate, comprising the following steps: S1. Preparation of modified polyvinyl alcohol: 16 g of polyvinyl alcohol was dissolved in 200 mL of water, 6 g of polydopamine and 0.7 g of catalyst were added, the mixture was heated to 45°C, stirred and reacted for 2 h, and dialyzed for 21 h using a dialysis bag with a pore size of 1.5 kDa. The dialyzate was dried to obtain modified polyvinyl alcohol; The catalyst is a Tris-HCl solution with a pH of 9; S2. Preparation of sustained-release magnesium L-threonate: 12 g of silk fibroin peptide and 10 g of modified polyvinyl alcohol prepared in step S1 were dissolved in 200 mL of water, 9 g of magnesium L-threonate prepared in Example 3 was added, the pH value was adjusted to 6.5, a gel was obtained, freeze-dried, and crushed to obtain sustained-release magnesium L-threonate. Loose bulk density 0.85 g / cm 3 , compact packing density 1.14g / cm 3 .
[0037] Comparative Example 2 Compared with Example 6, the difference is that L-magnesium threonate is prepared from Comparative Example 1. Loose bulk density 0.78 g / cm 3 , compact packing density 0.97g / cm 3 .
[0038] Comparative Example 3 Compared with Example 6, the difference is that step S1 is not performed.
[0039] The details are as follows: Preparation of sustained-release magnesium L-threonate: 12 g of silk fibroin peptide and 10 g of polyvinyl alcohol were dissolved in 200 mL of water, 9 g of magnesium L-threonate prepared in Example 3 was added, the pH value was adjusted to 6.5, a gel was obtained, freeze-dried, and crushed to obtain sustained-release magnesium L-threonate. Loose bulk density 0.52 g / cm 3 , compact packing density 0.61g / cm 3 .
[0040] Test Example 2 120 mice were randomly divided into 12 groups (n=10): control group, model group, Example 1-6 group, Comparative Example 1-3 group, fluoxetine treatment group, and all animals except the control group mice were subjected to 60-day depression model (CUMS) stress. The mice were subjected to two different stimulations every day, and the same stimulation could not be given for two consecutive days, and the stress stimulation lasted for 60 days. The CUMS method includes unpredictable mild stimulation: fasting (24h), water deprivation (24h), restraint (12h), wet cage (12h), tail clamping (5min), 45° tilt (6h), shaking (5min), ice water swimming (5min), day and night reversal, etc.
[0041] Administration method: The Example 1-6 group and the Comparative Example 1-3 group were given the corresponding drug at a dosage of 0.25 g / kg, the fluoxetine treatment group was given 0.015 g / kg, and the control group and the model group were given 0.9% sodium chloride solution. The dosage of all groups was 5 mg / kg·d. The administration was continued for 14 days.
[0042] 1. Sugar water preference test After 14 days of treatment, a sugar water preference test was conducted. 48 hours before the sugar water preference test, the rats were trained to adapt to 1% sucrose water by mass fraction. On the first day, two bottles of 1% sucrose water by mass fraction were placed in the mice. On the second day, one bottle of 1% sucrose solution by mass fraction and one bottle of pure drinking water by mass fraction were replaced. The two bottles had the same mass. After the adaptation, water and food were deprived for 24 hours. The mice were given two bottles of water that were quantitatively measured in advance: one bottle of 1% sucrose water by mass fraction and one bottle of pure drinking water. The volume of 1% sucrose water and pure water consumed by the mice within 2 hours was recorded, with a time interval of 7 days. The sugar water preference rate was calculated as follows: Sugar water preference rate (%) = sugar water consumption / total liquid consumption × 100% 2. Test for 5-hydroxytryptamine (5-HT) content in the brain After completing the sugar water preference test, the mice were killed, the brains were dissected, washed, homogenized, centrifuged, and the supernatant was taken. The 5-HT content in the mouse brain was measured by enzyme-linked immunosorbent assay according to the instructions of the kit.
[0043] The results are shown in Table 1.
[0044] Table 1
[0045] Note: * compared with the control group, P < 0.05; # compared with the model group, P < 0.05.
[0046] As can be seen from the above table, the sustained-release magnesium L-threonate prepared in Examples 4-6 of the present invention can significantly increase the sugar water preference rate of mice and increase the 5-HT content in the brain of mice.
[0047] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims
1. A method for preparing magnesium L-threonate, characterized in that: Dissolve L-ascorbic acid in water, add magnesium hydroxide and alkaline magnesium carbonate and stir, add hydrogen peroxide dropwise, heat and stir to react, filter the product, purify it while hot through a thermosensitive molecular imprinting hydrogel, concentrate it, add ethanol aqueous solution to the concentrate, let it stand for crystallization, filter it, wash it, dry it, and obtain magnesium L-threonate. The thermosensitive molecular imprinting hydrogel after adsorption is cooled to room temperature, washed, and reused.
2. The preparation method according to claim 1, characterized in that: The preparation method of the thermosensitive molecular imprinted hydrogel is as follows: dissolving oxalic acid, a monomer composition and a crosslinking agent in water, adding an initiator, heating and stirring to react, filtering while hot, cooling the solid to room temperature, washing and drying to obtain the thermosensitive molecular imprinted hydrogel.
3. The preparation method according to claim 2, characterized in that: The monomer composition is N-isopropylacrylamide, methyl acrylate and butyl methacrylate, and the mass ratio is 12-17:10-15:7-10.
4. The preparation method according to claim 2, characterized in that: The mass ratio of the oxalic acid, the monomer composition, the crosslinking agent and the initiator is 4-6:20-30:1-2:0.2-0.3, the crosslinking agent is N,N'-methylenebisacrylamide, and the initiator is selected from at least one of sodium persulfate, potassium persulfate and ammonium persulfate; the temperature of the heating and stirring reaction is 80-90°C and the time is 3-5h.
5. The preparation method according to claim 1, characterized in that: 35-45 parts by weight of L-ascorbic acid are dissolved in 200 parts by weight of water, the temperature is raised to 20-30° C., 4-7 parts by weight of magnesium hydroxide and 25-30 parts by weight of alkaline magnesium carbonate are added and stirred, 50-70 parts by weight of 22-25wt% hydrogen peroxide are added dropwise, the temperature is heated to 70-80° C., the reaction is stirred for 2-4 hours, the product is filtered, purified by a thermosensitive molecular imprinting hydrogel while hot, and concentrated to a relative density of 1.07-1.1, 80-90wt% of an ethanol aqueous solution is added to the concentrated solution, the solution is allowed to stand for 2-4 hours, crystallized, filtered, washed, and dried to obtain L-magnesium threonate, and the thermosensitive molecular imprinting hydrogel after adsorption is cooled to room temperature, washed, and reused.
6. A method for preparing sustained-release magnesium L-threonate, characterized in that: The following steps are involved: S1. Preparation of modified polyvinyl alcohol: dissolving polyvinyl alcohol in water, adding polydopamine and a catalyst, heating and stirring to react, dialyzing, and drying the dialyzate to obtain modified polyvinyl alcohol; S2. Preparation of sustained-release magnesium L-threonate: Dissolve the silk fibroin peptide and the modified polyvinyl alcohol obtained in step S1 in water, add magnesium L-threonate, adjust the pH value to 6.4-6.6 to obtain a gel, freeze-dry, and pulverize to obtain sustained-release magnesium L-threonate.
7. The preparation method according to claim 6, characterized in that: The mass ratio of polyvinyl alcohol, polydopamine and catalyst in step S1 is 14-18:4-7:0.5-1, the catalyst is a Tris-HCl solution with a pH of 8.5-9.5, the temperature of the heating and stirring reaction is 40-50°C, the time is 1-3h, the pore size of the dialysis bag used for dialysis is 1-2kDa, and the dialysis time is 18-24h.
8. The preparation method according to claim 6, characterized in that: The mass ratio of the silk fibroin peptide, modified polyvinyl alcohol, and magnesium L-threonate in step S2 is 10-15:7-12:8-10.
9. A sustained-release magnesium L-threonate prepared by the preparation method according to any one of claims 6 to 8.
10. Use of the sustained-release magnesium L-threonate according to claim 9 in the preparation of antidepressant drugs.
Citation Information
Patent Citations
Preparation method of L-threonic acid or salts thereof
CN102875362A
Synthesis method of magnesium L-threonate
CN104961636A
New L-threonic acid derivatives
CN1301691A
Cited By
Method for biosynthesizing high-purity magnesium L-threonate
CN122303339A
A method for biosynthesis of high-purity magnesium L-threptonate
CN122303339B