Preparation method of sodium zirconium cyclosilicate ZS-9 and application thereof

Abstract

The application belongs to the technical field of inorganic materials, and particularly relates to a preparation method of sodium zirconium cyclosilicate ZS-9 and application thereof. The preparation method comprises the following steps: reacting a silicon salt, an alkali and a zirconium-containing compound, adjusting pH, and filtering, so as to obtain the sodium zirconium cyclosilicate ZS-9, wherein the molar ratio of the silicon salt, the alkali and the zirconium-containing compound is 3.8-4.2:4-4.5:1. The preparation method of the sodium zirconium cyclosilicate ZS-9 is relatively mild in reaction condition, does not need special high-pressure reaction equipment, and is easy to realize industrialization. Compared with the prior art, the obtained sodium zirconium cyclosilicate ZS-9 has higher purity, yield and potassium ion exchange capacity.

Description

Technical Field

[0001] This invention belongs to the field of inorganic materials technology, specifically relating to a method for preparing sodium zirconium cyclosilicate ZS-9 and its application. Background Technology

[0002] Hyperkalemia refers to a condition where the level of potassium ions (K) in the blood is too high. + Hyperkalemia is a pathological condition characterized by abnormally elevated potassium levels. Normally, blood potassium levels remain within a relatively stable range; hyperkalemia indicates that blood potassium levels exceed the normal range. Chronic kidney disease (CKD) has a high incidence worldwide, and elevated blood potassium can accelerate disease progression in CKD patients, leading to adverse consequences such as emergency hospitalization and increasing the risk of death. Therefore, commonly used medications for treating hyperkalemia include sodium polystyrene sulfonate and diuretics such as furosemide. Sodium zirconium cyclosilicate is an inorganic crystalline drug that has been marketed in the last five years, launched in the US and China in 2018 and 2019 respectively. It has a unique cubic crystal structure with a high binding affinity for potassium ions. After administration, it binds to potassium ions in the gastrointestinal tract and is excreted in feces, thereby lowering blood potassium levels.

[0003] Sodium zirconium cyclosilicate was first disclosed in patent US5891417, and it has different crystal forms from ZS-1 to ZS-11.

[0004] Chinese invention patent CN106170283A discloses various crystal forms of sodium zirconium silicate, ZS-1 to ZS-11. Among them, sodium zirconium silicate ZS-9 is a novel highly selective potassium ion adsorption resin, whose main component is sodium zirconium silicate. This resin can selectively adsorb potassium ions, effectively reducing the potassium concentration in the blood and treating hyperkalemia. The resin has a cyclic structure, which is more selective for adsorbing potassium ions than linear resins. It also has good gastrointestinal compatibility, is safe for the human body, and has strong reusability, being able to re-adsorb potassium ions after elution. However, during the preparation of sodium zirconium silicate ZS-9, other undesirable crystal forms may be formed, and the product is insoluble in all solvents, making further processing difficult. Therefore, it is essential to control the formation of unwanted forms during the manufacturing process. The patent CN106170283A also discloses a method for preparing ZS-9—through a hydrothermal crystallization reaction: a mixed solution of sodium silicate, sodium hydroxide, and zirconium acetate is reacted at a temperature above 200°C and a pressure above 2.5 MPa to obtain ZS-9. However, the reaction conditions of this invention are quite harsh, and the reaction equipment needs to be specially modified. A baffle-like structure related to the stirrer needs to be used in the crystallization container and correctly positioned relative to the stirrer. A serpentine coil that meanders along the inner wall of the reactor tube is also used.

[0005] Indian patents IN202041056388 and IN201941046191, in order to find a more economical method for preparing pure sodium zirconium cyclosilicate, also disclosed an improved method for preparing sodium zirconium cyclosilicate ZS-9. In a specially designed reaction apparatus, sodium silicate, sodium hydroxide and zirconium acetate are mixed and reacted at 210-230°C under 20-30 kg nitrogen pressure to obtain sodium zirconium cyclosilicate ZS-9.

[0006] The preparation of sodium zirconium cyclosilicate ZS-9 in existing publicly available technologies all require modified high-pressure reactors and high temperatures above 200°C, which are quite harsh and not conducive to large-scale industrialization. Therefore, there is an urgent need for a more moderate technology to achieve the industrial preparation of sodium zirconium cyclosilicate ZS-9. Summary of the Invention

[0007] This invention addresses the problems existing in the prior art by providing a method for preparing sodium zirconium cyclosilicate ZS-9 and its applications. This preparation method does not require specially modified high-pressure reaction equipment, the reaction conditions are relatively mild, it is easily industrialized, and the obtained sodium zirconium cyclosilicate ZS-9 exhibits higher purity, yield, and potassium ion exchange capacity.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] A method for preparing sodium zirconium cyclosilicate ZS-9, the method comprising reacting a silicon salt, an alkali and a zirconium-containing compound, adjusting the pH, and filtering to obtain the product.

[0010] Preferably, the molar ratio of the silicon salt, alkali and zirconium-containing compound is 3.8-4.2:4-4.5:1.

[0011] Preferably, the silicon salt is sodium silicate.

[0012] Preferably, the zirconium-containing compound is zirconium oxychloride.

[0013] Preferably, the alkali is selected from one or more of sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium methoxide, potassium ethoxide, and potassium tert-butoxide.

[0014] More preferably, the alkali is selected from any one of sodium hydroxide, potassium hydroxide, and barium hydroxide.

[0015] Preferably, the reaction involves first dissolving the silicon salt, alkali, and zirconium-containing compound in water, then mixing the silicon salt solution with the alkali solution, and finally adding the zirconium-containing compound solution.

[0016] Preferably, the silicon salt has a mass concentration of 30-45% in the aqueous solution, the zirconium-containing compound has a mass concentration of 30-40% in the aqueous solution, and the alkali has a mass concentration of 7-15% in the aqueous solution.

[0017] Preferably, the reaction temperature is 120-220℃ and the reaction time is 3-10 days.

[0018] More preferably, the reaction temperature is 170-190°C and the reaction time is 4-6 days.

[0019] Preferably, the reaction is followed by cooling, and the cooling temperature is 20-30°C.

[0020] Preferably, the pH is 7-9, and the pH-adjusting solution is selected from any one of hydrochloric acid, sulfuric acid, and acetic acid.

[0021] Preferably, the filtration is followed by pulping and drying, the solvent for pulping is water, and the drying temperature is 70-120℃.

[0022] This invention also provides the application of sodium zirconium cyclosilicate ZS-9 prepared by the above preparation method in the preparation of drugs for treating hyperkalemia.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The method for preparing sodium zirconium cyclosilicate ZS-9 provided by this invention has relatively mild reaction conditions, does not require specially modified high-pressure reaction equipment, and is easy to industrialize. Compared with the prior art, the obtained sodium zirconium cyclosilicate ZS-9 has higher purity, yield and potassium ion exchange capacity. Attached Figure Description

[0025] Figure 1 The image shows the XRD pattern of sodium zirconium cyclosilicate ZS-9 obtained according to the preparation method of Example 1.

[0026] Figure 2 The image shows the infrared (IR) spectrum of sodium zirconium cyclosilicate ZS-9 obtained according to the preparation method of Example 1.

[0027] Figure 3 This is a photograph of the internal structure of the autoclave used to prepare sodium zirconium cyclosilicate ZS-9 according to Example 1. Detailed Implementation

[0028] It is worth noting that all raw materials used in this invention are commercially available products. The Hastelloy autoclave, model HT-1000-F JC, was purchased from Shanghai Huotong Instrument Co., Ltd.; the Monel autoclave, model ZN-2000-F JM, was purchased from Shanghai Huotong Instrument Co., Ltd.; sodium silicate, analytical grade, was purchased from Aladdin Reagent Co., Ltd.; and zirconium oxychloride octahydrate, analytical grade, was purchased from Leyan Reagent.

[0029] Example 1

[0030] A method for preparing sodium zirconium cyclosilicate ZS-9 includes the following steps:

[0031] (1) First, weigh 42.6g of sodium silicate (0.349mol) and dissolve it in 70mL of water to prepare a sodium silicate solution with a concentration of 37%. Weigh 15g of sodium hydroxide (0.375mol) and dissolve it in 195mL of water to prepare a sodium hydroxide solution with a concentration of 7%. Weigh 28.2g of zirconium oxychloride octahydrate (0.088mol) and dissolve it in 60mL of water to prepare a zirconium oxychloride solution with a concentration of 32%. Then, mix the 37% sodium silicate solution and the 7% sodium hydroxide solution and stir for 30min. Add the 32% zirconium oxychloride solution dropwise and stir until homogeneous. Finally, transfer the reaction mixture to a 1L Hastelloy autoclave.

[0032] (2) The reaction solution was heated to 150℃, at which point the reaction pressure reached 1.05MPa, and the reaction was maintained at this temperature and pressure for 7 days. Afterward, the reaction solution was cooled to 30℃, and 6M hydrochloric acid solution was added dropwise to adjust the pH of the reaction solution to 8.5. The solution was filtered to obtain a filter cake, which was then mixed with 900mL of purified water, filtered again, and the filter cake was placed in a vacuum oven and dried under reduced pressure at 100℃ to constant weight to obtain 30g of sodium zirconium cyclosilicate.

[0033] Figure 1 The image shows the XRD pattern of sodium zirconium cyclosilicate ZS-9 prepared in Example 1. Figure 2 The infrared (IR) image of sodium zirconium cyclosilicate ZS-9 prepared in Example 1 is shown. The crystal form of the obtained sodium zirconium cyclosilicate is ZS-9, as determined by XRD and IR analysis.

[0034] Example 2

[0035] A method for preparing sodium zirconium cyclosilicate ZS-9 includes the following steps:

[0036] (1) First, weigh 85.2g of sodium silicate (0.698mol) and dissolve it in 199mL of water to prepare a 30% sodium silicate solution. Weigh 30g of sodium hydroxide (0.75mol) and dissolve it in 270mL of water to prepare a 10% sodium hydroxide solution. Weigh 56.4g of zirconium oxychloride octahydrate (0.175mol) and dissolve it in 132mL of water to prepare a 30% zirconium oxychloride solution. Then, mix the 30% sodium silicate solution and the 10% sodium hydroxide solution and stir for 20min. Add the 30% zirconium oxychloride solution dropwise and stir until homogeneous. Finally, transfer the reaction mixture to a 2L Monel alloy autoclave.

[0037] (2) The reaction solution was heated to 190℃, at which point the reaction pressure reached 1.38MPa, and the reaction was maintained at this temperature and pressure for 3 days. Afterward, the reaction solution was cooled to 20℃, and 3M sulfuric acid solution was added dropwise to adjust the pH of the reaction solution to 8.5. The solution was filtered to obtain a filter cake, which was then mixed with 1500mL of purified water, filtered again, and the filter cake was placed in a vacuum oven and dried under reduced pressure at 95℃ to constant weight to obtain 60g of sodium zirconium cyclosilicate.

[0038] Example 3

[0039] A method for preparing sodium zirconium cyclosilicate ZS-9 includes the following steps:

[0040] (1) First, weigh 25.6g of sodium silicate (0.210mol) and dissolve it in 60mL of water to prepare a 30% sodium silicate solution. Weigh 38.5g of barium hydroxide (0.225mol) and dissolve it in 347mL of water to prepare a 10% barium hydroxide solution. Weigh 9.81g of zirconium oxychloride octahydrate (0.050mol) and dissolve it in 23mL of water to prepare a 30% zirconium oxychloride solution. Then, mix the 30% sodium silicate solution and the 10% barium hydroxide solution for 40min. Add the 30% zirconium oxychloride solution dropwise and stir until homogeneous. Finally, transfer the reaction mixture to a 1L Hastelloy autoclave.

[0041] (2) The reaction solution was heated to 220℃, at which point the reaction pressure reached 1.01 MPa, and the reaction was maintained at this temperature and pressure for 3 days. Afterward, the reaction solution was cooled to 30℃, and 6M acetic acid solution was added dropwise to adjust the pH of the reaction solution to 9. The mixture was filtered to obtain a filter cake, which was then mixed with 900 mL of purified water, filtered again, and placed in a vacuum oven to dry under reduced pressure at 70℃ to constant weight, yielding 10.4 g of sodium zirconium cyclosilicate.

[0042] Example 4

[0043] A method for preparing sodium zirconium cyclosilicate ZS-9 includes the following steps:

[0044] (1) First, weigh 23.19g of sodium silicate (0.190mol) and dissolve it in 28.3mL of water to prepare a sodium silicate solution with a concentration of 45%. Weigh 11.22g of potassium hydroxide (0.200mol) and dissolve it in 63.4mL of water to prepare a potassium hydroxide solution with a concentration of 15%. Weigh 9.81g of zirconium oxychloride octahydrate (0.050mol) and dissolve it in 14.7mL of water to prepare a zirconium oxychloride solution with a concentration of 40%. Then, mix the 45% sodium silicate solution and the 15% potassium hydroxide solution for 20min, add the 40% zirconium oxychloride solution dropwise, stir evenly, and finally transfer the reaction mixture to a 1L Monel alloy autoclave.

[0045] (2) The reaction solution was heated to 120℃, at which point the reaction pressure reached 1.10 MPa, and the reaction was maintained at this temperature and pressure for 10 days. Afterward, the reaction solution was cooled to 20℃, and 3M acetic acid solution was added dropwise to adjust the pH of the reaction solution to 7. The mixture was filtered to obtain a filter cake, which was then mixed with 1500 mL of purified water, filtered again, and the filter cake was placed in a vacuum oven and dried under reduced pressure at 120℃ to constant weight to obtain 10.2 g of sodium zirconium cyclosilicate.

[0046] Comparative Example 1

[0047] Sodium zirconium cyclosilicate ZS-9 was prepared according to Example 12 of Chinese Invention Patent CN106170283A.

[0048] Comparative Example 2

[0049] Sodium zirconium cyclosilicate ZS-9 was prepared according to Example 14 of Chinese Invention Patent CN106170283A.

[0050] Comparative Example 3

[0051] Sodium zirconium cyclosilicate ZS-9 was prepared according to Example 1 of Patent IN201941046191.

[0052] Comparative Example 4

[0053] A method for preparing sodium zirconium cyclosilicate ZS-9 includes the following steps:

[0054] (1) First, weigh 18.3g of sodium silicate (0.150mol) and dissolve it in 70mL of water to prepare a 21% sodium silicate solution. Weigh 6.6g of sodium hydroxide (0.165mol) and dissolve it in 103mL of water to prepare a 6% sodium hydroxide solution. Weigh 9.81g of zirconium oxychloride octahydrate (0.050mol) and dissolve it in 60mL of water to prepare a 14% zirconium oxychloride solution. Then, mix the 21% sodium silicate solution and the 6% sodium hydroxide solution and stir for 30min. Add the 14% zirconium oxychloride solution dropwise and stir until homogeneous. Finally, transfer the reaction mixture to a 1L Hastelloy autoclave.

[0055] (2) The reaction solution was heated to 150℃, at which point the reaction pressure reached 1.05MPa, and the reaction was maintained at this temperature and pressure for 7 days. Afterward, the reaction solution was cooled to 30℃, and 6M hydrochloric acid solution was added dropwise to adjust the pH of the reaction solution to 8.5. The solution was filtered to obtain a filter cake, which was then mixed with 900mL of purified water, filtered again, and the filter cake was placed in a vacuum oven and dried under reduced pressure at 100℃ to constant weight to obtain 5.5g of sodium zirconium cyclosilicate.

[0056] Comparative Example 5

[0057] A method for preparing sodium zirconium cyclosilicate ZS-9 includes the following steps:

[0058] (1) First, weigh 42.6g of sodium silicate (0.349mol) and dissolve it in 70mL of water to prepare a sodium silicate solution with a concentration of 37%. Weigh 15g of sodium hydroxide (0.375mol) and dissolve it in 195mL of water to prepare a sodium hydroxide solution with a concentration of 7%. Weigh 28.2g of zirconium oxychloride octahydrate (0.088mol) and dissolve it in 60mL of water to prepare a zirconium oxychloride solution with a concentration of 32%. Then, mix the 37% sodium silicate solution and the 7% sodium hydroxide solution and stir for 30min. Add the 32% zirconium oxychloride solution dropwise and stir until homogeneous. Finally, transfer the reaction mixture to a 1L Hastelloy autoclave.

[0059] (2) The reaction solution was heated to 150℃, at which point the reaction pressure reached 1.05MPa, and the reaction was maintained at this temperature and pressure for 7 days. Afterward, the reaction solution was cooled to 30℃, and 6M hydrochloric acid solution was added dropwise to adjust the pH of the reaction solution to 10. The mixture was filtered to obtain a filter cake, which was then mixed with 900mL of purified water, filtered again, and the filter cake was placed in a vacuum oven and dried under reduced pressure at 100℃ to constant weight, yielding 29.8g of sodium zirconium cyclosilicate.

[0060] Experiment 1: Determination of the potassium exchange capacity (KEC) of sodium zirconium cyclosilicate ZS-9 of the present invention

[0061] 1. Instruments and reagents

[0062] 1.1 Instrument: Dionex ICS-5000IC ion chromatograph.

[0063] 1.2 Reagents:

[0064] Preparation of reference solution: Potassium ion reference stock solution (5000ppm K) + Prepare an aqueous solution of potassium chloride (9.53 mg / mL) accurately using deionized water; prepare a potassium ion standard solution (50 ppm K). + A potassium chloride aqueous solution (0.0953 mg / mL) was accurately prepared using deionized water.

[0065] Preparation of sample solution: Accurately weigh 500 mg of sodium zirconium cyclosilicate samples prepared in Examples 1-2 and Comparative Examples 1-5, and place them in a 50 mL centrifuge tube. Add 40 mL of potassium reference stock solution (5000 ppm K) to the centrifuge tube. + Mix thoroughly for 3 hours. Filter the sample solution through a 0.45 μm filter, take 1.0 mL of the filtrate and place it in a 100 mL volumetric flask, dilute to the mark with deionized water and mix well.

[0066] Preparation of blank solution: Deionized water was used as the blank.

[0067] 2. Chromatographic conditions: as shown in Table 1.

[0068] Table 1 Chromatographic conditions

[0069]

[0070] 3. Results Analysis

[0071] The potassium ion exchange capacity of sodium zirconium cyclosilicate prepared in Examples 1-2 and Comparative Examples 1-5 was determined using a Dionex ion chromatograph, and the results are shown in Table 2.

[0072] Table 2 Summary of the yield, purity, and potassium ion exchange capacity of sodium zirconium cyclosilicate.

[0073]

[0074] As shown in Table 2, the sodium zirconium cyclosilicate ZS-9 prepared using the method provided by this invention has a pure ZS-9 crystal form and a higher potassium ion exchange capacity. Furthermore, it requires no special process conditions or reaction equipment, is low in cost, and is easier to scale up for production.

[0075] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing sodium zirconium cyclosilicate ZS-9, characterized in that, The preparation method includes reacting a silicon salt, an alkali, and a zirconium-containing compound, adjusting the pH, and filtering to obtain the product. The molar ratio of the silicon salt, alkali, and zirconium-containing compound is 3.8-4.2:4-4.5:

1. The silicon salt is sodium silicate, the zirconium-containing compound is zirconium oxychloride, and the alkali is selected from one or more of sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium methoxide, potassium ethoxide, and potassium tert-butoxide. In the reaction, the silicon salt, alkali, and zirconium-containing compound are first dissolved in water, then the silicon salt solution and the alkali solution are mixed, and finally the zirconium-containing compound solution is added. The pH is 7-9.

2. The preparation method according to claim 1, characterized in that, The alkali is selected from any one of sodium hydroxide, potassium hydroxide, and barium hydroxide.

3. The preparation method according to claim 1, characterized in that, The silicon salt has a mass concentration of 30-45% in the aqueous solution, the zirconium-containing compound has a mass concentration of 30-40% in the aqueous solution, the alkali has a mass concentration of 7-15% in the aqueous solution, and the mixture is stirred for 20-40 minutes.

4. The preparation method according to claim 1, characterized in that, The reaction temperature is 120-220℃, the reaction time is 3-10 days, and the reaction is cooled afterward at a temperature of 20-30℃.

5. The preparation method according to claim 1, characterized in that, The pH-adjusting solution is selected from any one of hydrochloric acid, sulfuric acid, and acetic acid.

6. The preparation method according to claim 1, characterized in that, The filtration process involves pulping and drying, with water as the solvent for pulping, and the drying temperature being 70-120℃.

7. The use of sodium zirconium cyclosilicate ZS-9 prepared by the preparation method according to any one of claims 1-6 in the preparation of drugs for treating hyperkalemia.

Images