Method and device for clean production of l-magnesium aspartate by ion replacement membrane reactor

Abstract

The application belongs to the technical field of pharmaceutical production, and particularly relates to a method and device for cleaning preparation of L-magnesium aspartate by using an ion replacement membrane reactor. The method uses the ion replacement membrane reactor, and comprises the following steps: arranging membrane stacks in the ion replacement membrane reactor according to a set arrangement mode; based on the arrangement of the membrane stacks, feeding magnesium sulfate solution into a raw material chamber 1, feeding L-ammonium aspartate solution into a raw material chamber 2, feeding deionized water into product chambers 1 and 2, feeding sodium sulfate solution into an anode chamber and a cathode chamber; and applying direct current at both ends of the ion replacement membrane reactor to perform reaction according to a set mode, so that the target product L-magnesium aspartate is obtained in the product chamber 1 after the reaction. Meanwhile, ammonium sulfate byproduct can also be obtained in the product chamber 2, which improves the economic benefit of the process and has important industrial application value.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical production technology, and specifically relates to a method and apparatus for the clean preparation of L-aspartic acid magnesium using an ion exchange membrane reactor. Background Technology

[0002] Magnesium is an essential mineral element for maintaining normal life activities in the human body, exhibiting a variety of biological functions. It accounts for 0.05% of the human body's total composition. Of this, nearly 98% is found in bone marrow, teeth, and soft tissues, with 2% present in body fluids. British researchers have found that magnesium can significantly reduce the mortality rate of those experiencing sudden cardiac arrest. Magnesium salts can be used clinically to treat patients with hypertension, hypertensive encephalopathy, and acute myocardial infarction with heart failure. L-aspartate magnesium (L-ASP-Mg) is one such example. The combined use of L-aspartate potassium and L-aspartate magnesium is common and widely used to treat cardiovascular diseases, central nervous system disorders, chronic hepatitis B, diabetic neuropathy, and pediatric wheezing.

[0003] The existing production process for L-aspartic magnesium utilizes L-aspartic acid and magnesium-containing inorganic substances (such as magnesium carbonate, magnesium oxide, or magnesium hydroxide) as raw materials for synthesis. L-Aspartic acid, as one of the raw materials for synthesizing L-aspartic magnesium, is commonly prepared using a combination of chemical synthesis and fermentation. The method for preparing L-aspartic acid, as described in the journal *Tianjin Chemical Industry*, January 2015, Vol. 29, No. 1, pp. 13-15, uses maleic acid as a raw material, converting it to fumaric acid under inorganic catalyst and strong acid conditions. Fumaric acid reacts with ammonia to form ammonium fumarate, which is then converted to ammonium L-aspartic acid under the action of L-aspartate transaminase. Sulfuric acid is added to the reaction solution to cause isoelectric precipitation of L-aspartic acid, yielding the final L-aspartic acid product. A method for preparing magnesium L-aspartate from L-aspartic acid, proposed in patent CN102875402A, involves using magnesium carbonate, magnesium oxide, or magnesium hydroxide as raw materials, reacting them in water at 70-80℃. After the reaction, the pH of the reaction solution is adjusted to 6.0-7.5, the solution is decolorized, filtered, and concentrated to supersaturation to obtain a saturated solution. The supersaturated solution is then dried using a vacuum freeze dryer to obtain the finished product. This method first requires the preparation of L-aspartic acid, followed by the addition of a magnesium-containing inorganic salt to its aqueous solution to prepare magnesium L-aspartate. However, the entire preparation process of L-aspartic acid is lengthy and cumbersome. The addition of strong acid to precipitate L-aspartic acid also causes corrosion to the equipment. Furthermore, the production of magnesium L-aspartate requires heating to 70-80℃, resulting in high energy consumption and increased costs, which does not align with the principles of green production.

[0004] Ion-exchange membrane reactors are a highly efficient, low-energy-consumption, and environmentally friendly reaction separation technology that can achieve displacement reactions that cannot spontaneously occur under conventional conditions. It comprises two feed chambers and two product chambers. Under the influence of a DC electric field, the selective permeability of the ion-exchange membrane enables the exchange of anions and cations in two different salt solutions, allowing different ions to recombine to generate the target compound. However, there are currently no reports on the conversion of L-aspartic ammonium to L-aspartic magnesium using an ion-exchange membrane reactor. Summary of the Invention

[0005] To address the above problems, this invention discloses a method for the clean preparation of L-aspartic acid magnesium using an ion-exchange membrane reactor. The method employs an ion-exchange membrane reactor and includes the following steps:

[0006] The membrane stacks in the ion exchange membrane reactor are arranged according to the predetermined arrangement.

[0007] Based on the membrane stack arrangement, magnesium sulfate solution is introduced into raw material chamber 1, L-aspartic acid ammonium solution is introduced into raw material chamber 2, deionized water is introduced into product chamber 1 and product chamber 2, and sodium sulfate solution is introduced into anode chamber and cathode chamber.

[0008] Direct current is applied to both ends of the ion-exchange membrane reactor to carry out the reaction according to the set mode. After the reaction, the target product, magnesium L-aspartate, is obtained in product chamber 1.

[0009] Furthermore, the membrane stack arrangement in the ion exchange membrane reactor is configured as follows:

[0010] Anode - Anode Chamber - [Anion Exchange Membrane - Raw Material Chamber 1 - Cation Exchange Membrane - Product Chamber 1 - Anion Exchange Membrane - Raw Material Chamber 2 - Cation Exchange Membrane - Product Chamber 2] n -Anion exchange membrane-cathode chamber;

[0011] Where n is the number of repeating units, and n is 1-1000.

[0012] Furthermore, the products also include ammonium sulfate, a byproduct obtained in product chamber 2.

[0013] Furthermore, the concentration of the magnesium sulfate solution introduced into the raw material chamber 1 is 0.1-0.6 mol / L.

[0014] Furthermore, the concentration of the L-aspartic ammonium solution introduced into the raw material chamber 2 is 0.1-1.0 mol / L.

[0015] Furthermore, the concentration of sodium sulfate solution introduced into the anode and cathode chambers is 0.1-0.6 mol / L.

[0016] Furthermore, during operation of the ion exchange membrane reactor, a constant current operation mode is adopted, with the current density set at 5-30 mA / cm². 2 .

[0017] Furthermore, the ion-exchange membrane reactor is terminated when the conductivity of the raw material chamber 2 drops to ≤5.0 mS / cm.

[0018] Furthermore, the cation exchange membrane is a CIS cation exchange membrane; the anion exchange membrane is an AIS anion exchange membrane.

[0019] On the other hand, the present invention also proposes an apparatus for the clean preparation of L-aspartic magnesium using an ion-exchange membrane reactor, the apparatus being used to prepare the L-aspartic magnesium;

[0020] The device includes an anode plate, a cathode plate, and an ion exchange membrane;

[0021] An anode chamber is formed between the anode plate and the adjacent ion exchange membrane, and a cathode chamber is formed between the cathode plate and the anion exchange membrane. The anode chamber and the cathode chamber are connected in series. An anion exchange membrane, raw material chamber 1, cation exchange membrane, product chamber 1, anion exchange membrane, raw material chamber 2, cation exchange membrane, product chamber 2 and anion exchange membrane are arranged sequentially from the anode chamber to the cathode chamber.

[0022] The beneficial effects of this invention are:

[0023] This invention utilizes L-aspartic acid ammonium, an intermediate product from the industrial production of L-aspartic acid, to produce L-aspartic acid magnesium in a single step via a novel ion-exchange membrane reactor. This avoids the shortcomings of existing processes that require first preparing L-aspartic acid and then L-aspartic acid magnesium, resulting in a high-purity L-aspartic acid magnesium product. Simultaneously, ammonium sulfate byproduct is also obtained in product chamber 2, improving the economic efficiency of the process. Therefore, the conversion of L-aspartic acid ammonium to L-aspartic acid magnesium via an ion-exchange membrane reactor is an economical, green, and environmentally friendly production method with significant industrial application value.

[0024] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of the invention may be realized and obtained by means of the structures pointed out in the description, claims and drawings. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 A flowchart of the method for preparing L-aspartic acid magnesium using an ion-exchange membrane reactor according to an embodiment of the present invention is shown.

[0027] Figure 2 A schematic diagram illustrating the principle of preparing L-aspartic acid magnesium using the ion-exchange membrane reactor of the present invention is shown. Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, 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.

[0029] The present invention proposes a method for the clean preparation of L-aspartic acid magnesium using an ion-exchange membrane reactor, such as... Figure 1 As shown, the method employs an ion-displacement membrane reactor and includes the following steps:

[0030] The membrane stacks in the ion exchange membrane reactor are arranged according to a predetermined pattern; the membrane stack arrangement in the ion exchange membrane reactor is as follows: anode - anode chamber - [anion exchange membrane - feed chamber 1 - cation exchange membrane - product chamber 1 - anion exchange membrane - feed chamber 2 - cation exchange membrane - product chamber 2] n -Anion exchange membrane-cathode chamber, n is the number of repeating units, n is 1-1000.

[0031] Based on the membrane stack arrangement, a magnesium sulfate solution is introduced into the feed chamber 1, an L-aspartic acid ammonium solution is introduced into the feed chamber 2, deionized water is introduced into the product chambers 1 and 2, and a sodium sulfate solution is introduced into the anode and cathode chambers; wherein the concentration of the magnesium sulfate solution is 0.1-0.6 mol / L, the concentration of the L-aspartic acid ammonium solution is 0.1-1.0 mol / L, and the concentration of the sodium sulfate solution is 0.1-0.6 mol / L;

[0032] A direct current is applied to both ends of the ion-exchange membrane reactor, and the reaction proceeds according to a set mode. After the reaction, the target product, L-aspartic acid magnesium, is obtained in product chamber 1. During operation, the ion-exchange membrane reactor operates in a constant current mode, with a current density set to 5-30 mA / cm². 2 The ion exchange membrane reactor operation ends when the conductivity of raw material chamber 2 drops to ≤5.0mS / cm.

[0033] In this invention, there are no restrictions on the amount of magnesium sulfate solution, L-aspartic acid ammonium solution, deionized water, and sodium sulfate solution used. The above method will be described in detail below with reference to the embodiments.

[0034] Example 1

[0035] This embodiment uses, as follows: Figure 2 The ion exchange membrane reactor shown has membrane stacks arranged as follows: anode-anode chamber-[anion exchange membrane-feed chamber 1-cation exchange membrane-product chamber 1-anion exchange membrane-feed chamber 2-cation exchange membrane-product chamber 2] n - Anion exchange membrane - Cathode chamber, with a repeating unit number of 2. In the diagram, the anion membrane represents the anion exchange membrane, and the cation membrane represents the cation exchange membrane. The anode and cathode materials in the membrane stack are corrosion-resistant titanium coated with ruthenium. Each compartment between adjacent ion exchange membranes is composed of a mesh with flow channels, and the thickness of a single mesh is 0.8 mm. The ion exchange membranes used in the membrane stack are CIS cation exchange membranes and AIS anion exchange membranes produced by Shandong Tianwei Membrane Technology Co., Ltd., with an effective area of ​​189 cm² per membrane. 2 (9cm×21cm).

[0036] The anode and cathode plates form an anode chamber and a cathode chamber respectively with the adjacent ion exchange membrane. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is circulated as the electrode solution. 500 mL of 0.30 mol / L magnesium sulfate solution is circulated into raw material chamber 1, and 500 mL of 0.30 mol / L L-aspartic acid ammonium solution is circulated into raw material chamber 2. 500 mL of deionized water is circulated into product chambers 1 and 2. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operation mode is used, with a current density of 10 mA / cm². 2 .

[0037] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 25 minutes. Ultimately, the conversion rate of L-aspartic acid ammonium in raw material chamber 2 was 80.0%, the concentration of L-aspartic acid magnesium in product chamber 1 was 0.12 mol / L, the purity of L-aspartic acid magnesium obtained in product chamber 1 was as high as 99.1%, and the energy consumption was 1.27 kWh / kg.

[0038] Example 2

[0039] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0040] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is introduced as the electrode solution. 500 mL of 0.30 mol / L magnesium sulfate solution is introduced into raw material chamber 1, and 500 mL of 0.50 mol / L L-aspartic acid ammonium solution is introduced into raw material chamber 2. 500 mL of deionized water is introduced into product chambers 1 and 2. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 10 mA / cm². 2 .

[0041] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 96.9 minutes. Ultimately, the conversion rate of L-aspartic ammonium in raw material chamber 2 was 89.3%, the concentration of L-aspartic magnesium in product chamber 1 was 0.19 mol / L, the purity of L-aspartic magnesium obtained in product chamber 1 was as high as 99.4%, and the energy consumption was 0.57 kWh / kg.

[0042] Example 3

[0043] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0044] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is introduced as the electrode solution. Raw material chamber 1 is supplied with 500 mL of 0.30 mol / L magnesium sulfate solution, and raw material chamber 2 is supplied with 500 mL of 0.50 mol / L L-aspartic acid ammonium solution. Product chambers 1 and 2 are supplied with 500 mL of deionized water. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 20 mA / cm². 2 .

[0045] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 49.3 minutes. Ultimately, the conversion rate of L-aspartic acid ammonium in raw material chamber 2 was 89.3%, the concentration of L-aspartic acid magnesium in product chamber 1 was 0.19 mol / L, the purity of L-aspartic acid magnesium obtained in product chamber 1 was as high as 99.4%, and the energy consumption was 0.52 kWh / kg.

[0046] Example 4

[0047] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0048] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is introduced as the electrode solution. Raw material chamber 1 is supplied with 500 mL of 0.60 mol / L magnesium sulfate solution, and raw material chamber 2 is supplied with 500 mL of 0.80 mol / L L-aspartic acid ammonium solution. Product chambers 1 and 2 are supplied with 500 mL of deionized water. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 20 mA / cm². 2 .

[0049] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 74.2 minutes. Ultimately, the conversion rate of L-aspartic ammonium in raw material chamber 2 was 93.5%, the concentration of L-aspartic magnesium in product chamber 1 was 0.31 mol / L, the purity of L-aspartic magnesium obtained in product chamber 1 was as high as 99.6%, and the energy consumption was 0.59 kWh / kg.

[0050] Example 5

[0051] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0052] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is introduced as the electrode solution. 500 mL of 0.30 mol / L magnesium sulfate solution is introduced into raw material chamber 1, and 500 mL of 0.50 mol / L L-aspartic acid ammonium solution is introduced into raw material chamber 2. 500 mL of deionized water is introduced into product chambers 1 and 2. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 30 mA / cm². 2 .

[0053] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 33.6 minutes. Ultimately, the conversion rate of L-aspartic acid ammonium in raw material chamber 2 was 89.2%, the concentration of L-aspartic acid magnesium in product chamber 1 was 0.19 mol / L, the purity of L-aspartic acid magnesium obtained in product chamber 1 was as high as 98.9%, and the energy consumption was 0.64 kWh / kg.

[0054] Comparative Example 1

[0055] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0056] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is circulated as the electrode solution. 500 mL of 0.30 mol / L magnesium sulfate solution is circulated into raw material chamber 1, and 500 mL of 0.50 mol / L L-aspartic acid ammonium solution is circulated into raw material chamber 2. 500 mL of deionized water is circulated into product chambers 1 and 2. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 40 mA / cm². 2 .

[0057] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 26.5 minutes. Ultimately, the conversion rate of L-aspartic acid ammonium in raw material chamber 2 was 89.3%, the concentration of L-aspartic acid magnesium in product chamber 1 was 0.19 mol / L, the purity of L-aspartic acid magnesium obtained in product chamber 1 was as high as 97.6%, and the energy consumption was 0.71 kWh / kg.

[0058] Comparative Example 2

[0059] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0060] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is circulated as the electrode solution. Raw material chamber 1 is circulated with 500 mL of 0.30 mol / L magnesium sulfate solution, and raw material chamber 2 is circulated with 500 mL of 0.50 mol / L L-aspartic acid ammonium solution. Product chambers 1 and 2 are circulated with 500 mL of deionized water. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 50 mA / cm². 2 .

[0061] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 5.0 mS / cm, with a running time of 21.3 minutes. Ultimately, the conversion rate of L-aspartic acid ammonium in raw material chamber 2 was 89.3%, the concentration of L-aspartic acid magnesium in product chamber 1 was 0.19 mol / L, the purity of L-aspartic acid magnesium obtained in product chamber 1 was 95.1%, and the energy consumption was 0.78 kWh / kg.

[0062] Comparative Example 3

[0063] The ion exchange membrane reactor used in this embodiment is the same as that in Embodiment 1.

[0064] The anode and cathode plates, along with adjacent membranes, form an anode chamber and a cathode chamber, respectively. These chambers are connected in series and 500 mL of 0.30 mol / L sodium sulfate solution is introduced as the electrode solution. 500 mL of 0.30 mol / L magnesium sulfate solution is introduced into raw material chamber 1, and 500 mL of 0.50 mol / L L-aspartic acid ammonium solution is introduced into raw material chamber 2. 500 mL of deionized water is introduced into product chambers 1 and 2. During the experiment, the linear velocity of the solution flow in each chamber is 3 cm / s, and a constant current operating mode is used, with a current density of 30 mA / cm². 2 .

[0065] During the preparation process, the experiment ended when the conductivity of raw material chamber 2 dropped to 7.0 mS / cm, with a running time of 46.1 minutes. Ultimately, the conversion rate of L-aspartic acid ammonium in raw material chamber 2 was 82.1%, the concentration of L-aspartic acid magnesium in product chamber 1 was 0.17 mol / L, the purity of L-aspartic acid magnesium obtained in product chamber 1 was 99.0%, and the energy consumption was 0.52 kWh / kg.

[0066] The reaction results in Examples 1-5 and Comparative Examples 1-3 are shown in Table 1:

[0067] Table 1. Reaction results of each embodiment.

[0068]

[0069] As can be seen from the results of Example 5 and Comparative Example 3, the experiment ended when the conductivity dropped to 7.0 mS / cm and 5.0 mS / cm, respectively. The purity of the obtained L-aspartic acid magnesium was not much different, but the conversion rate was much different. Therefore, the conductivity was chosen to end the experiment at a value less than or equal to 5.0 mS / cm.

[0070] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for the clean preparation of L-aspartic acid magnesium using an ion-exchange membrane reactor, characterized in that, The method employs an ion-displacement membrane reactor and includes the following steps: The membrane stacks in the ion exchange membrane reactor are arranged according to a predetermined pattern; the membrane stack arrangement in the ion exchange membrane reactor is as follows: anode - anode chamber - [anion exchange membrane - feed chamber 1 - cation exchange membrane - product chamber 1 - anion exchange membrane - feed chamber 2 - cation exchange membrane - product chamber 2] n - Anion exchange membrane - Cathode chamber - Cathode; where n is the number of repeating units, n is 1-1000; the cation exchange membrane is a CIS cation exchange membrane; the anion exchange membrane is an AIS anion exchange membrane; Based on the membrane stack arrangement, a magnesium sulfate solution is introduced into raw material chamber 1, an L-aspartic acid ammonium solution is introduced into raw material chamber 2, deionized water is introduced into product chambers 1 and 2, and a sodium sulfate solution is introduced into the anode and cathode chambers; the concentration of the magnesium sulfate solution introduced into raw material chamber 1 is 0.1-0.6 mol / L; the concentration of the L-aspartic acid ammonium solution introduced into raw material chamber 2 is 0.1-1.0 mol / L. A direct current is applied to both ends of the ion-exchange membrane reactor to carry out the reaction according to a set mode. After the reaction, the target product, L-aspartic acid magnesium, is obtained in product chamber 1. During operation of the ion-exchange membrane reactor, a constant current operation mode is adopted, and the current density is set to 5-30 mA / cm². 2 The ion-exchange membrane reactor operation ends when the conductivity of the raw material chamber 2 drops to ≤5.0 mS / cm.

2. The method for clean preparation of L-aspartic acid magnesium using an ion-exchange membrane reactor according to claim 1, characterized in that, The products also include ammonium sulfate, a byproduct obtained in product chamber 2.

3. The method for clean preparation of L-aspartic acid magnesium using an ion-exchange membrane reactor according to claim 1, characterized in that, The concentration of sodium sulfate solution introduced into the anode and cathode chambers is 0.1-0.6 mol / L.

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