Preparation method of sodium zirconium cyclosilicate ZS-9

Abstract

The invention discloses a preparation method of sodium zirconium cyclosilicate ZS-9, which comprises the following steps: reacting reaction feed liquid A formed by dissolving sodium hydroxide in water and reaction feed liquid B formed by dissolving sodium silicate and zirconium acetate in water in an opposite spraying contact manner in a spraying manner, and ending the reaction; and pulping and washing the reaction solution with water until the pH value is less than or equal to 9.0, filtering and drying to obtain the sodium zirconium cyclosilicate ZS-9 crystal form. The method is mild in reaction condition, short in reaction time and very suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical chemistry, and specifically relates to a preparation method of sodium zirconium cyclosilicate ZS-9. Background Art

[0002] Sodium zirconium cyclosilicate, trade name The English name is Sodium Zirconium Cy-Sodium Zirconium Cyclosilicate Powder; molecular formula: Na~1.5H~0.5ZrSi3O9·2-3H2O; molecular weight: 390.5~408.5 Daltons; the crystal structure of sodium zirconium cyclosilicate is as follows:

[0003]

[0004] Sodium zirconium cyclosilicate powder was developed by AstraZeneca and is a potassium ion (K + ) is an inorganic crystalline compound that combines with cation exchange. It is an insoluble, odorless, tasteless white to gray powder that can selectively bind to K in the gastrointestinal tract. + Binds to reduce serum K + Sodium zirconium cyclosilicate can mimic physiological K + Channel to capture K + Octahedral zirconium atoms and tetrahedral silicon atoms act as oxygen coordination atoms, and covalent oxygen atoms act as bridges to form an electrostatically charged microporous cubic structure with an average pore size of approximately With unhydrated K + Sodium zirconium cyclosilicate selectively converts monovalent cations, especially excess K + and ammonium ions, which are + The selectivity is calcium ion (Ca 2+ ) or magnesium ion (Mg 2+ The drug was approved for marketing by the European Commission (EC) on March 22, 2018, approved for marketing by the U.S. FDA on May 18, 2018, and launched in China in March 2020 for the treatment of hyperkalemia in adults.

[0005] There are various crystals of sodium zirconium cyclosilicate, ZS-1 to ZS-11, among which the sodium zirconium cyclosilicate ZS-9 crystal form has a highly selective potassium ion adsorption capacity. CN106170283 discloses a method for preparing sodium zirconium cyclosilicate ZS-9, using a reaction device with a specially modified internal structure, a reaction temperature of up to 215°C, a reaction pressure of up to 2MPa, and a total reaction time of about 3 days, which has high requirements for industrial production and limits its commercial amplification production. CN117776193 discloses a method for preparing sodium zirconium cyclosilicate ZS-9, using a conventional high-pressure reactor without special internal modification, which solves the problem of reaction equipment modification, but its reaction temperature is still as high as 150°C, the reaction pressure also reaches 0.5MPa, and the reaction time is longer, reaching 4-5 days, which is still not conducive to commercial amplification production.

[0006] Therefore, the existing technology for preparing sodium zirconium cyclosilicate ZS-9 crystal form requires harsh reaction conditions of high temperature and high pressure, and the reaction time is too long, which is not conducive to commercial scale-up production. It is necessary to develop a technical solution with milder reaction conditions and shorter reaction time to solve the problems of the existing technology. Summary of the invention

[0007] The object of the present invention is to provide a method for preparing sodium zirconium cyclosilicate ZS-9, which utilizes an electric sprayer to atomize the reaction materials at high temperature, completes the reaction at the moment of spray contact, improves the reaction efficiency, reduces the reaction temperature, shortens the reaction time, and does not require special high-pressure reaction equipment, so the method is suitable for commercial scale-up production.

[0008] To achieve the purpose of the present invention, the following embodiments are provided:

[0009] In one embodiment, a method for preparing sodium zirconium cyclosilicate ZS-9 of the present invention comprises the following steps:

[0010] 1) Dissolve sodium hydroxide in water as reaction liquid A, add it into a sprayer M, and heat it to a certain temperature;

[0011] 2) Sodium silicate and zirconium acetate are dissolved in water as reaction liquid B, added into sprayer N, and heated to a certain temperature;

[0012] 3) spraying the reaction liquid A and the reaction liquid B to contact and react;

[0013] 4) After the liquid is sprayed, the obtained reaction liquid is repeatedly slurried and washed with water until the pH value is ≤ 9.0, filtered and dried to obtain sodium zirconium cyclosilicate (ZS-9).

[0014] In some embodiments, in the preparation method of the present invention, the molar ratio of zirconium acetate: sodium silicate: sodium hydroxide is 1: (3-6): (4-6), preferably 1: (3.6-4.2): (4.2-4.5).

[0015] Preferably, in the above-mentioned preparation method of the present invention, the temperature after heating in step 1) is substantially the same as the temperature after heating in step 2), and the temperature is 60 to 90°C, preferably 80 to 90°C.

[0016] Preferably, in the above-mentioned preparation method of the present invention, specifically, the heating temperatures of reaction liquid A and reaction liquid B are substantially the same.

[0017] Preferably, in the above-mentioned preparation method of the present invention, in the spray contact reaction in step 3), equal volumes of reaction liquid A and reaction liquid B are sprayed out in a spray manner at substantially the same discharge rate, and react during the spray contact process.

[0018] Preferably, in the preparation method of the present invention, the discharge rate is 0.9 kg / min to 2.5 kg / min, preferably 1.5 kg / min to 2.0 kg / min.

[0019] Preferably, in the preparation method of the present invention, the sodium hydroxide in step 1) is dissolved in water, and sodium hydroxide solution can also be directly used. There is no essential difference between the two. The amount of water is 5 to 10 times the total weight of zirconium acetate, sodium silicate and sodium hydroxide, preferably 6 to 8 times.

[0020] Preferably, in the preparation method of the present invention, in step 2), sodium silicate and zirconium acetate are dissolved in water, wherein the amount of water is 5 to 10 times, preferably 6 to 8 times, the total weight of zirconium acetate, sodium silicate and sodium hydroxide.

[0021] Preferably, in the above-mentioned preparation method of the present invention, the sprayer M and the sprayer N are both electric sprayers.

[0022] In a specific embodiment, a method for preparing sodium zirconium cyclosilicate ZS-9 includes: dissolving sodium hydroxide in water to form a reaction liquid A, which is then loaded into an electric sprayer M and heated to a certain temperature; dissolving sodium silicate and zirconium acetate in water to form a reaction liquid B, which is then loaded into an electric sprayer N and heated to a certain temperature. Then, the atomization switches of the two electric sprayers are turned on at the same time, so that the atomized reaction liquid A and the reaction liquid B are sprayed in contact and react, and the reaction ends when the liquid spraying is completed. The reaction liquid is washed with water to a pH of ≤9.0, filtered, and dried to obtain the sodium zirconium cyclosilicate ZS-9 crystal form.

[0023] Preferably, the reaction molar ratio of zirconium acetate: sodium silicate: sodium hydroxide is 1: (3.0-6.0): (4.0-6.0); more preferably, the reaction molar ratio of zirconium acetate: sodium silicate: sodium hydroxide is 1: (3.6-4.2): (4.2-4.5).

[0024] Preferably, the amount of water used to dissolve the sodium hydroxide is 5 to 10 times the total weight of zirconium acetate, sodium silicate and sodium hydroxide; more preferably, the amount of water used to dissolve the sodium hydroxide is 6 to 8 times the total weight of zirconium acetate, sodium silicate and sodium hydroxide.

[0025] Preferably, the amount of water used to dissolve sodium silicate and zirconium acetate is 5 to 10 times the total weight of zirconium acetate, sodium silicate and sodium hydroxide; more preferably, the amount of water used to dissolve sodium silicate and zirconium acetate is 6 to 8 times the total weight of zirconium acetate, sodium silicate and sodium hydroxide.

[0026] Preferably, the heating temperature of the sodium hydroxide aqueous solution and the mixed aqueous solution of sodium silicate and zirconium acetate is substantially the same, both of which are 60 to 90°C; more preferably 80 to 90°C.

[0027] Preferably, the spray discharge rate of the sodium hydroxide aqueous solution and the spray discharge rate of the mixed aqueous solution of sodium silicate and zirconium acetate are substantially the same, both of which are 0.9 kg / min to 2.5 kg / min; more preferably, 1.5 kg / min to 2.0 kg / min.

[0028] Technical effect: The preparation method of the present invention has milder reaction conditions and shorter reaction time, and is very suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The infrared spectrum of sodium zirconium cyclosilicate ZS-9 prepared in Example 1;

[0030] Figure 2 The X-ray powder diffraction pattern (XRPD) of sodium zirconium cyclosilicate ZS-9 prepared in Example 1;

[0031] Figure 3 The infrared spectrum of sodium zirconium cyclosilicate ZS-9 prepared in Comparative Example 1;

[0032] Figure 4 The infrared spectrum of sodium zirconium cyclosilicate ZS-9 prepared in Comparative Example 2. DETAILED DESCRIPTION

[0033] The following examples are used to further understand the essence of the present invention, but are not intended to limit the scope of the present invention in any way.

[0034] Example 1 Preparation of Sodium Zirconium Cyclosilicate ZS-9 Crystalline Form

[0035] The preparation method comprises the following steps:

[0036] 1) Dissolve 591 g of sodium hydroxide in 15.8 kg of purified water, then put it into an electric sprayer M, heat it to a liquid temperature of 60° C., and set it aside.

[0037] 2) Dissolve 1.21 kg of zirconium acetate and 1.35 kg of sodium silicate in 15.8 kg of purified water, put them into an electric sprayer N, heat them to a liquid temperature of 60° C., and set them aside.

[0038] 3) adjusting the discharge rate of the electric sprayer to 0.9 kg / min, and after the temperature of the material liquid in step 1) and step 2) reaches 60° C., turning on the atomization switches of the two electric sprayers at the same time, so that the materials of the two electric sprayers are sprayed in contact with each other to achieve reaction.

[0039] 4) After the spraying is completed, the reaction is also completed. The reaction solution is repeatedly washed with water until the pH is ≤ 9, filtered, and the filter cake is collected.

[0040] 5) The filtered solid (i.e., filter cake) was dried at 80-90°C to constant weight to obtain 1.44 kg sodium zirconium cyclosilicate ZS-9, with a yield of 95.6%. The obtained ZS-9 was determined by infrared spectroscopy. Figure 1 The infrared spectrum of the prepared sodium zirconium cyclosilicate ZS-9 is shown in Figure 2. At the same time, the sample was tested by XRPD instrument (Cu target). The results are as follows Figure 2 shown.

[0041] Example 2 Preparation of Sodium Zirconium Cyclosilicate ZS-9

[0042] The preparation method comprises the following steps:

[0043] 1) Dissolve 755 g of sodium hydroxide in 40.9 kg of purified water, then put it into an electric sprayer M, heat it to a liquid temperature of 90° C., and set it aside.

[0044] 2) Dissolve 1.03 kg of zirconium acetate and 2.30 kg of sodium silicate in 40.9 kg of purified water, put them into an electric sprayer N, heat them to a liquid temperature of 90° C., and set them aside.

[0045] 3) adjusting the discharge rate of the electric sprayer to 2.5 kg / min, and after the temperature of the material liquid in step 1) and step 2) reaches 90° C., turning on the atomization switches of the two electric sprayers at the same time, so that the materials of the two electric sprayers are sprayed in contact with each other to achieve reaction.

[0046] 4) After the spraying is completed, the reaction solution is repeatedly washed with water until the pH is ≤ 9, filtered, and the filter cake is collected.

[0047] 5) The filtered solid was dried at 80-90°C to constant weight to obtain 1.16 kg sodium zirconium cyclosilicate ZS-9 with a yield of 94.2%. Figure 1 Basically the same, its XRPD pattern is Figure 2 Basically the same.

[0048] Example 3 Preparation of Sodium Zirconium Cyclosilicate ZS-9

[0049] The preparation method comprises the following steps:

[0050] 1) Dissolve 410.5 g of sodium hydroxide in 13.7 kg of purified water, then put it into an electric sprayer M, heat it to a liquid temperature of 80° C., and set it aside.

[0051] 2) 800 g of zirconium acetate and 1073.7 g of sodium silicate were dissolved in 13.7 kg of purified water, and then loaded into an electric sprayer N, and heated to a liquid temperature of 80° C. for standby use.

[0052] 3) adjusting the discharge rate of the electric sprayer to 1.5 kg / min, and after the temperature of the material liquid in step 1) and step 2) reaches 80° C., turning on the atomization switches of the two electric sprayers at the same time, so that the materials of the two electric sprayers are sprayed in contact with each other to achieve reaction.

[0053] 4) After the spraying is completed, the reaction solution is repeatedly washed with water until the pH is ≤ 9, filtered, and the filter cake is collected.

[0054] 5) The filtered solid was dried at 80-90°C to constant weight to obtain 961.2 g sodium zirconium cyclosilicate ZS-9 with a yield of 96.3%. Figure 1 Basically the same, its XRPD pattern is Figure 2 Basically the same.

[0055] Example 4 Preparation of Sodium Zirconium Cyclosilicate ZS-9

[0056] The preparation method comprises the following steps:

[0057] 1) Dissolve 296.9 g of sodium hydroxide in 13.5 kg of purified water, then put it into an electric sprayer M, heat it to a liquid temperature of 90° C., and set it aside.

[0058] 2) Dissolve 540 g of zirconium acetate and 845.5 g of sodium silicate in 13.5 kg of purified water, put them into an electric sprayer N, heat them to a liquid temperature of 90° C., and set them aside.

[0059] 3) adjusting the discharge rate of the electric sprayer to 2 kg / min, and after the temperature of the material liquid in step 1) and step 2) reaches 90° C., turning on the atomization switches of the two electric sprayers at the same time, so that the materials of the two electric sprayers are sprayed in contact with each other to achieve reaction.

[0060] 4) After the spraying is completed, the reaction solution is repeatedly washed with water until the pH is ≤ 9, filtered, and the filter cake is collected.

[0061] 5) The filtered solid was dried at 80-90°C to constant weight to obtain 632.7 g sodium zirconium cyclosilicate ZS-9 with a yield of 93.9%. Figure 1 Basically the same, its XRPD pattern is Figure 2 Basically the same.

[0062] Comparative Example 1

[0063] Sodium zirconium cyclosilicate ZS-9 was prepared using Example 14 of patent CN106170283. Detected by infrared spectroscopy, Figure 3 The infrared spectrum of sodium zirconium cyclosilicate ZS-9 prepared in Comparative Example 1.

[0064] Comparative Example 2

[0065] Sodium zirconium cyclosilicate ZS-9 was prepared using Example 1 of patent CN117776193. After infrared spectroscopy,

[0066] Figure 4 The infrared spectrum of sodium zirconium cyclosilicate ZS-9 prepared in Comparative Example 2.

[0067] The above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, supplements and equivalent substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing sodium zirconium cyclosilicate ZS-9, characterized in that: The following steps are involved: 1) Dissolve sodium hydroxide in water as reaction liquid A, add it into a sprayer M, and heat it to a certain temperature; 2) Sodium silicate and zirconium acetate are dissolved in water as reaction liquid B, added into sprayer N, and heated to a certain temperature; 3) spraying the reaction liquid A and the reaction liquid B to contact and react; 4) After the liquid is sprayed, the obtained reaction liquid is repeatedly slurried and washed with water until the pH value is ≤ 9.0, filtered and dried to obtain sodium zirconium cyclosilicate (ZS-9).

2. The preparation method according to claim 1, wherein the molar ratio of zirconium acetate: sodium silicate: sodium hydroxide is 1: (3-6): (4-6).

3. The preparation method as described in claim 2, wherein the molar ratio of zirconium acetate: sodium silicate: sodium hydroxide is 1: (3.6-4.2): (4.2-4.5).

4. The preparation method according to claim 1, wherein the temperature in steps 1) and 2) is 60-90°C, preferably 80-90°C.

5. The preparation method according to claim 4, wherein the temperature is The temperatures of reaction liquid A and reaction liquid B are substantially the same.

6. The preparation method according to claim 1, wherein in step 3), the reaction liquid A and the reaction liquid B are sprayed in equal volumes in a spraying manner at substantially the same discharge rate.

7. The preparation method according to claim 6, wherein the discharge rate is 0.9 kg / min to 2.5 kg / min, preferably 1.5 kg / min to 2.0 kg / min.

8. The preparation method according to claim 1, wherein the amount of water in step 1) is 5 to 10 times, preferably 6 to 8 times, the total weight of zirconium acetate, sodium silicate and sodium hydroxide.

9. The preparation method according to claim 1, wherein the amount of water in step 2) is 5 to 10 times, preferably 6 to 8 times, the total weight of zirconium acetate, sodium silicate and sodium hydroxide.

10. The preparation method according to claim 1, wherein the sprayer M and the sprayer N are both electric sprayers.

Images