A method for preparing potassium L-aspartate using an ion-exchange membrane reactor

Abstract

This invention belongs to the field of pharmaceutical manufacturing technology, specifically proposing a method for preparing L-aspartate potassium using an ion-exchange membrane reactor. The method comprises the following steps: arranging the membrane stacks in the ion-exchange membrane reactor according to a predetermined pattern; based on the membrane stack arrangement, introducing L-aspartate ammonium solution and potassium sulfate solution into raw material chamber 1 and raw material chamber 2 respectively, introducing deionized water into product chambers 1 and 2, and introducing potassium sulfate solution into the anode and cathode chambers; applying direct current to both ends of the ion-exchange membrane reactor and reacting according to a predetermined pattern; and obtaining the target product L-aspartate potassium in product chamber 1 after the reaction. This method achieves the exchange of anions and cations in two different salt solutions, allowing different ions to recombine to generate the target compound L-aspartate potassium. This method is highly efficient, low in energy consumption, and can realize a displacement reaction that cannot spontaneously occur under conventional conditions.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical production technology, and specifically relates to a method for preparing potassium L-aspartate using an ion-exchange membrane reactor. Background Technology

[0002] Potassium is an essential mineral element for maintaining normal life activities in the human body, exhibiting a variety of biological functions. L-Aspartate potassium (L-ASP-K) is a pharmaceutical intermediate used as a food additive and biochemical research preparation. It has significant efficacy in regulating myocardial function and electrophysiology, and in treating cardiovascular and cerebrovascular diseases, hypokalemia, various arrhythmias, hepatitis, and liver dysfunction. The combined use of L-aspartate potassium and L-aspartate magnesium is common and widely used to treat cardiovascular diseases such as arrhythmias, angina pectoris, chronic ischemic heart failure with ventricular premature beats, acute myocardial infarction, hypertension, and viral myocarditis; and central nervous system diseases such as pulmonary encephalopathy, acute cerebral infarction, and hepatic encephalopathy. In addition, it is used for chronic hepatitis B; diabetic neuropathy; and pediatric wheezing disorders, in various dosage forms.

[0003] The existing production process for potassium L-aspartate utilizes L-aspartic acid and potassium-containing inorganic substances (such as potassium carbonate or potassium hydroxide) as raw materials for synthesis. L-Aspartic acid, as one of the raw materials for the synthesis of potassium L-aspartate, 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-aspartate 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 product, potassium L-aspartate. A method for preparing potassium L-aspartate from L-aspartic acid, as proposed in patent publication CN102875403A, involves using potassium carbonate or potassium hydroxide as raw materials and reacting in water at 70-80℃. After the reaction, the pH of the reaction solution is adjusted to 6.0-7.5. The reaction solution is then decolorized, filtered, and concentrated to supersaturation to obtain a saturated solution. The cooled saturated solution is then dried using a vacuum dryer to obtain the finished product. This type of preparation method first requires the preparation of L-aspartic acid, which is then used as a raw material to prepare potassium L-aspartate. However, the entire preparation process of L-aspartic acid involves long reaction steps and cumbersome operations. The addition of strong acid to precipitate L-aspartic acid also causes some corrosion to the equipment. Secondly, the production of potassium L-aspartate requires heating to 70-80℃, resulting in high energy consumption and increased costs, which does not conform to the concept of green production.

[0004] Therefore, it is particularly important to propose a clean method that can directly convert L-aspartic ammonium to prepare L-aspartic potassium. Summary of the Invention

[0005] To address the above problems, this invention discloses a method for preparing L-aspartate potassium 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, L-aspartic acid ammonium solution and potassium sulfate solution are respectively introduced into raw material chamber 1 and raw material chamber 2, deionized water is introduced into product chamber 1 and product chamber 2, and potassium sulfate solution is introduced into anode chamber and cathode chamber;

[0008] A 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, potassium L-aspartate, is obtained in product chamber 1.

[0009] Furthermore, the membrane stack arrangement in the ion exchange membrane reactor is configured as follows: anode - anode chamber - [cation exchange membrane - product chamber 1 - anion exchange membrane - feed chamber 1 - cation exchange membrane - product chamber 2 - anion exchange membrane - feed chamber 2] n -Cation exchange membrane-cathode chamber;

[0010] Where n is the number of repeating units, and n is 1-1000.

[0011] Furthermore, the products also include ammonium sulfate, a byproduct obtained in product chamber 2.

[0012] Furthermore, the concentration of the L-aspartic ammonium solution is 0.1-1.0 mol / L.

[0013] Furthermore, the concentration of potassium sulfate solution introduced into the raw material chamber 2, the anode chamber, and the cathode chamber is 0.1-0.6 mol / L.

[0014] 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 .

[0015] Furthermore, the ion-exchange membrane reactor is terminated when the conductivity of the raw material chamber 1 drops to ≤8.0 mS / cm.

[0016] Furthermore, the cation exchange membrane is a CIS cation exchange membrane; the anion exchange membrane is an AIS anion exchange membrane.

[0017] The beneficial effects of this invention are:

[0018] This invention employs an ion-exchange membrane reactor to produce potassium L-aspartate in a single step from L-aspartate ammonium, an intermediate product of industrial L-aspartate production. This avoids the shortcomings of existing processes that require first preparing L-aspartate and then potassium L-aspartate. The resulting potassium L-aspartate has a purity of over 99%. Simultaneously, ammonium sulfate is also obtained as a byproduct in product chamber 2, improving the economic efficiency of the process and demonstrating significant industrial application value. The ion-exchange membrane reactor 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 and generate the target compound, potassium L-aspartate. This method is highly efficient, energy-saving, and can achieve displacement reactions that cannot spontaneously occur under conventional conditions.

[0019] 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

[0020] 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.

[0021] Figure 1 A flowchart of the method for preparing potassium L-aspartate using an ion-exchange membrane reactor in an embodiment of the present invention is shown;

[0022] Figure 2 A schematic diagram illustrating the principle of preparing potassium L-aspartate using an ion-exchange membrane reactor in an embodiment of the present invention is shown. Detailed Implementation

[0023] 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.

[0024] The present invention provides a method for the clean preparation of potassium L-aspartate using an ion-exchange membrane reactor, as follows: Figure 1As shown, the method employs an ion-displacement membrane reactor and includes the following steps:

[0025] The membrane stacks in the ion exchange membrane reactor are arranged according to the predetermined arrangement.

[0026] Based on the membrane stack arrangement, L-aspartic acid ammonium solution and potassium sulfate solution are respectively introduced into raw material chamber 1 and raw material chamber 2, deionized water is introduced into product chamber 1 and product chamber 2, and potassium sulfate solution is introduced into anode chamber and cathode chamber;

[0027] 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 L-aspartate potassium is obtained in product chamber 1 and the by-product ammonium sulfate is obtained in product chamber 2.

[0028] The membrane stack arrangement in the ion exchange membrane reactor is as follows: anode - anode chamber - [cation exchange membrane - product chamber 1 - anion exchange membrane - feed chamber 1 - cation exchange membrane - product chamber 2 - anion exchange membrane - feed chamber 2] n -Cation exchange membrane-cathode chamber, n is the number of repeating units, n is 1-1000.

[0029] The concentration of the L-aspartic ammonium solution introduced into the raw material chamber 1 is 0.1-1.0 mol / L.

[0030] The concentration of potassium sulfate solution introduced into the raw material chamber 2, anode chamber and cathode chamber is 0.1-0.6 mol / L.

[0031] When the ion exchange membrane reactor is running, a constant current operation mode is adopted, and the current density is set to 5-30 mA / cm². 2 .

[0032] The ion-exchange membrane reactor operation ends when the conductivity of feed chamber 1 drops to ≤8.0 mS / cm.

[0033] The cation exchange membrane and anion exchange membrane are high-density ion exchange membranes, such as CIS cation exchange membranes and AIS anion exchange membranes.

[0034] 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.

[0035] In this invention, there are no restrictions on the amount of potassium sulfate solution, L-aspartic acid ammonium solution, and deionized water used. The above method will be described in detail below with reference to the embodiments.

[0036] Example 1

[0037] This embodiment uses, as follows: Figure 2The ion exchange membrane reactor shown has the following arrangement of ion exchange membranes: anode-anode chamber-[cation exchange membrane-product chamber 1-anion exchange membrane-feed chamber 1-cation exchange membrane-product chamber 2-anion exchange membrane-feed chamber 2] n The cation exchange membrane-cathode chamber has two repeating units. 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 manufactured by Shandong Tianwei Membrane Technology Co., Ltd., with an effective area of ​​189 cm² per membrane. 2 (9cm×21cm).

[0038] 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 potassium sulfate solution is introduced as the electrode solution. 500 mL of 0.30 mol / L L-aspartic acid ammonium solution is introduced into raw material chamber 1, and 500 mL of 0.30 mol / L potassium sulfate 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 .

[0039] During the preparation process, the process ended when the conductivity of raw material chamber 1 dropped to 8.0 mS / cm, with a running time of 22.5 minutes. Ultimately, the conversion rate of L-aspartic ammonium in raw material chamber 1 was 70.1%, the concentration of L-aspartic potassium in product chamber 1 was 0.20 mol / L, the purity of L-aspartic potassium obtained in product chamber 1 was as high as 99.1%, and the energy consumption was 0.64 kWh / kg.

[0040] Example 2

[0041] The ion exchange membrane reactor used in this example is the same as that in Example 1.

[0042] 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 potassium sulfate solution is introduced as the electrode solution. 500 mL of 0.50 mol / L L-aspartic acid ammonium solution is introduced into raw material chamber 1, and 500 mL of 0.30 mol / L potassium sulfate 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 .

[0043] During the preparation process, the process ended when the conductivity of raw material chamber 1 dropped to 8.0 mS / cm, with a running time of 91 minutes. Ultimately, the concentration of potassium L-aspartate in product chamber 1 was 0.35 mol / L, the conversion rate of ammonium L-aspartate in raw material chamber 1 was 83.8%, the purity of potassium L-aspartate obtained in product chamber 1 was as high as 99.5%, and the energy consumption was 0.18 kWh / kg.

[0044] Example 3

[0045] The ion exchange membrane reactor used in this example is the same as that in Example 1.

[0046] 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 potassium sulfate solution is introduced as the electrode solution. 500 mL of 0.30 mol / L L-aspartic acid ammonium aqueous solution is introduced into raw material chamber 1, and 500 mL of 0.30 mol / L potassium sulfate 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 20 mA / cm². 2 .

[0047] During the preparation process, the process ended when the conductivity of raw material chamber 1 dropped to 8.0 mS / cm, with a running time of 46.8 minutes. Ultimately, the concentration of potassium L-aspartate in product chamber 1 was 0.35 mol / L, the conversion rate of ammonium L-aspartate in raw material chamber 1 was 83.6%, the purity of potassium L-aspartate obtained in product chamber 1 was as high as 99.1%, and the energy consumption was 0.33 kWh / kg.

[0048] Example 4

[0049] The ion exchange membrane reactor used in this example is the same as that in Example 1.

[0050] 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 0.60 mol / L potassium sulfate solution is introduced as the electrode solution. Raw material chamber 1 is supplied with 500 mL of 0.80 mol / L L-aspartic acid ammonium solution, and raw material chamber 2 is supplied with 500 mL of 0.60 mol / L potassium sulfate 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 .

[0051] During the preparation process, the process ended when the conductivity of raw material chamber 1 dropped to 8.0 mS / cm, with a running time of 64.5 minutes. Ultimately, the concentration of potassium L-aspartate in product chamber 1 was 0.62 mol / L, the conversion rate of ammonium L-aspartate in raw material chamber 1 was 89.4%, the purity of potassium L-aspartate obtained in product chamber 1 was as high as 99.7%, and the energy consumption was 0.35 kWh / kg.

[0052] Comparative Example 1

[0053] The ion exchange membrane reactor used in this example is the same as that in Example 1.

[0054] 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 potassium sulfate solution is introduced as the electrode solution. Raw material chamber 1 is supplied with 500 mL of 0.50 mol / L L-aspartic acid ammonium aqueous solution, and raw material chamber 2 is supplied with 500 mL of 0.30 mol / L potassium sulfate 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 40 mA / cm². 2 .

[0055] During the preparation process, the process ended when the conductivity of raw material chamber 1 dropped to 8.0 mS / cm, with a running time of 24 minutes. Ultimately, the concentration of potassium L-aspartate in product chamber 1 was 0.35 mol / L, the conversion rate of ammonium L-aspartate in raw material chamber 1 was 83.2%, the purity of potassium L-aspartate obtained in product chamber 1 was as high as 95.4%, and the energy consumption was 0.65 kWh / kg.

[0056] Comparative Example 2

[0057] The ion exchange membrane reactor used in this example is the same as that in Example 1.

[0058] 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 potassium sulfate solution is introduced as the electrode solution. 500 mL of 0.50 mol / L L-aspartic acid ammonium aqueous solution is introduced into raw material chamber 1, and 500 mL of 0.30 mol / L potassium sulfate 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 50 mA / cm². 2 .

[0059] During the preparation process, the process ended when the conductivity of raw material chamber 1 dropped to 8.0 mS / cm, with a running time of 19.5 minutes. Ultimately, the concentration of potassium L-aspartate in product chamber 1 was 0.35 mol / L, the conversion rate of ammonium L-aspartate in raw material chamber 1 was 83%, the purity of potassium L-aspartate obtained in product chamber 1 was as high as 91.1%, and the energy consumption was 0.77 kWh / kg.

[0060] The results of preparing potassium L-aspartate using an ion-exchange membrane reactor in Examples 1-4 and Comparative Examples 1-2 are shown in Table 1:

[0061] Table 1. Reaction results of each embodiment.

[0062]

[0063] 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 preparing potassium L-aspartate 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 stacks in the ion exchange membrane reactor are arranged sequentially as follows: anode - anode chamber - [cation exchange membrane - product chamber 1 - anion exchange membrane - raw material chamber 1 - cation exchange membrane - product chamber 2 - anion exchange membrane - raw material chamber 2] n - cation exchange membrane - cathode chamber; 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, L-aspartic acid ammonium solution and potassium sulfate solution are respectively introduced into raw material chamber 1 and raw material chamber 2, deionized water is introduced into product chamber 1 and product chamber 2, and potassium sulfate solution is introduced into anode chamber and cathode chamber; the concentration of L-aspartic acid ammonium solution is 0.1-1.0 mol / L; the concentration of potassium sulfate solution introduced into raw material chamber 2, anode chamber and cathode chamber is 0.1-0.6 mol / L; A 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, potassium L-aspartate, is obtained in product chamber 1. When the ion exchange membrane reactor is running, a constant current operation mode is adopted, and the current density is set to 10-20 mA / cm2. The ion exchange membrane reactor stops running when the conductivity of raw material chamber 1 drops to ≤8.0 mS / cm.

2. The method for preparing L-aspartate potassium 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.

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