Preparation method of lamellar lanthanum carbonate tetrahydrate powder crystal based on microwave / ultrasonic technology

Abstract

The invention discloses a preparation method of lamellar lanthanum carbonate tetrahydrate powder crystals based on a microwave / ultrasonic technology, which comprises the following steps: (1) preparation of lanthanum carbonate octahydrate: slowly dropwise adding a sodium bicarbonate solution into a lanthanum chloride solution, and fully reacting at the reaction temperature of 30 DEG C for 2-5 hours; washing the final product with water, performing suction filtration, and drying to obtain lanthanum carbonate octahydrate powder; (2) preparing lamellar lanthanum carbonate tetrahydrate powder crystals, namely putting the lanthanum carbonate octahydrate powder prepared in the step (1) into a solvent medium at room temperature, and regulating different microwave intensities to carry out rapid dehydration treatment; and then stripping by means of high-frequency vibration of ultrasonic waves, centrifuging and drying to obtain a lanthanum carbonate tetrahydrate powder crystal product. Lanthanum carbonate tetrahydrate is prepared through dehydration with the microwave / ultrasonic technology, generation of basic lanthanum carbonate impurities can be avoided, the obtained lanthanum carbonate tetrahydrate is in a uniformly-dispersed sheet shape, and the purity of the lanthanum carbonate tetrahydrate reaches 99.5% or above.

Description

Technical Field

[0001] The present invention relates to a lanthanide compound for treating hyperphosphatemia, and specifically to a method for preparing flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology. Background Art

[0002] Hyperphosphatemia is a common complication in patients with chronic kidney disease. Due to the decline in renal function of patients, it is difficult to excrete the phosphate ingested by the human body out of the body, so that the blood phosphorus level exceeds the normal level. In addition, the occurrence of hyperphosphatemia is often accompanied by risks such as hypocalcemia and cardiovascular diseases, significantly increasing the mortality rate of patients. Therefore, it is crucial to take measures to reduce the blood phosphorus level. Oral phosphate binders are an important method for treating hyperphosphatemia clinically. Among them, the trivalent lanthanum ions of lanthanum carbonate tetrahydrate combine with phosphates in food to form insoluble lanthanum phosphate precipitates, thus avoiding absorption in the body and being excreted out of the body. Compared with traditional phosphate binders, lanthanum carbonate tetrahydrate has the advantages of low toxicity and side effects, good therapeutic effect, high binding rate, and good tolerance, and is widely used clinically.

[0003] There is less research on lanthanum carbonate tetrahydrate for reducing phosphorus in China. Currently, the preparation methods of lanthanum carbonate tetrahydrate are all to first synthesize lanthanum carbonate octahydrate, and then prepare lanthanum carbonate tetrahydrate by dehydrating lanthanum carbonate octahydrate. The main methods are as follows:

[0004] Patent CN111620363A discloses a method for preparing lanthanum carbonate tetrahydrate. This method synthesizes lanthanum carbonate octahydrate by reacting lanthanum oxide, acetic acid with potassium carbonate or potassium bicarbonate or ammonium bicarbonate, and then obtains lanthanum carbonate tetrahydrate by high-temperature drying treatment of lanthanum carbonate octahydrate.

[0005] Patent CN114477265A synthesizes lanthanum carbonate octahydrate by dropping a carbonate or bicarbonate solution into a lanthanum chloride solution, and then obtains lanthanum carbonate tetrahydrate by backflow crystallization in solvents such as methanol, ethanol, isopropanol, n-butanol, ethylene glycol, toluene, acetone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, and N-methylpyrrolidone.

[0006] Methods such as high-temperature drying and backflow crystallization in organic solvents can all prepare lanthanum carbonate tetrahydrate. However, impurity lanthanum basic carbonate is easily generated in a high-temperature and high-humidity environment. And the presence of lanthanum basic carbonate in the sample is not conducive to the drug absorbing phosphates. Therefore, the generation of lanthanum basic carbonate impurities needs to be avoided in production. Summary of the Invention

[0007] The purpose of the present invention is to provide a method for preparing flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology, which avoids the generation of impurity phases in a high-temperature and high-humidity environment, obtains a flaky sample with high purity and uniform dispersion, and its yield is higher than 90%.

[0008] To solve the above technical problems, the following technical solutions are adopted:

[0009] A preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology, which is characterized by including the following steps:

[0010] (1) Preparation of lanthanum carbonate octahydrate;

[0011] (2) Preparation of flaky lanthanum carbonate tetrahydrate powder crystals; at room temperature, place the lanthanum carbonate octahydrate powder prepared in the above step (1) in a solvent medium, adjust different microwave intensities for rapid dehydration treatment; then use the high-frequency vibration of ultrasonic waves for flaking, and after centrifugation and drying, obtain lanthanum carbonate tetrahydrate powder crystal products.

[0012] Preferably, in the above step (1), slowly drop the sodium bicarbonate solution into the lanthanum chloride solution, and react fully at a reaction temperature of 30 °C for 2-5 hours; then wash, filter by suction and dry the final product to obtain lanthanum carbonate octahydrate powder.

[0013] Preferably, the concentrations of both sodium bicarbonate and lanthanum chloride are 2 mol / L.

[0014] Preferably, in the above step (2), the solvent media are acetonitrile, glycerol, and ethyl acetate respectively, and further preferably acetonitrile.

[0015] Preferably, in the above step (2), the microwave power is 1-5 kW, and the irradiation time is 1-10 min. Further preferably, the microwave power is 4 kW and the irradiation time is 6 min.

[0016] Preferably, in the above step (2), the ultrasonic intensity is 10-60 W / m 2 , the ultrasonic time is 10-30 min, and further preferably the ultrasonic intensity is 60 W / m 2 , and the ultrasonic time is 10 min.

[0017] Preferably, the prepared lanthanum carbonate tetrahydrate powder does not contain lanthanum basic carbonate impurities, and the crystal form purity is above 99.5%.

[0018] Preferably, the prepared lanthanum carbonate tetrahydrate is in the form of uniformly dispersed flakes with a thickness of 0.5-1.5 microns.

[0019] Preferably, the yield of lanthanum carbonate tetrahydrate is 90-96%.

[0020] Due to the adoption of the above technical solutions, the following beneficial effects are achieved:

[0021] The present invention uses microwave / ultrasonic technology to dehydrate and prepare lanthanum carbonate tetrahydrate, which can avoid the generation of lanthanum basic carbonate impurities, and the obtained lanthanum carbonate tetrahydrate is in the form of uniformly dispersed flakes with a purity of above 99.5%. Brief Description of the Drawings

[0022] The present invention will be further described below in conjunction with the accompanying drawings:

[0023] Figure 1 XRD pattern of the sample after microwave / ultrasonic treatment with different solvents as the medium

[0024] Figure 2 SEM image of lanthanum carbonate tetrahydrate prepared by microwave / ultrasonic technology

[0025] Figure 3 SEM image of lanthanum carbonate tetrahydrate prepared by high-temperature drying dehydration

[0026] Figure 4 Phosphate binding process curve of lanthanum carbonate tetrahydrate prepared by microwave / ultrasonic technology and high-temperature drying process Detailed Description of the Invention

[0027] The present invention aims to provide a method for preparing flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology, which avoids the generation of impurity phases in high-temperature and high-humidity environments, obtains high-purity and uniformly dispersed flaky samples, and has a yield higher than 90%.

[0028] The technical solution of the present invention will be described in detail below in conjunction with specific embodiments:

[0029] Example 1

[0030] Weigh 490.52 g of lanthanum chloride powder and 504.06 g of sodium bicarbonate powder. Dissolve the two powders in 1 L of deionized water and 3 L of deionized water respectively to prepare 2 mol / L solutions. Set the reaction temperature at 30 °C, and add the prepared sodium bicarbonate solution dropwise to the lanthanum chloride solution and react for 2 hours. After the reaction, filter and dry the reaction product to obtain lanthanum carbonate octahydrate powder. Finally, use microwave / ultrasonic technology to dehydrate lanthanum carbonate octahydrate in different solvents to prepare lanthanum carbonate tetrahydrate.

[0031] Example 2

[0032] Adjust the microwave / ultrasonic conditions in Example 1. Place lanthanum carbonate octahydrate in an ethyl acetate solution and treat it with 2 kW of microwave for 8 min to remove the crystal water. Then, perform flaking treatment for 20 min with an ultrasonic intensity of 30 W / m 2 Finally, obtain the lanthanum carbonate tetrahydrate product after centrifugal drying, and the yield is 95%. After XRD testing, it shows high crystal purity and no impurities, as shown in Figure 1 .

[0033] Example 3

[0034] Adjust the microwave / ultrasonic conditions in Example 1. Place lanthanum carbonate octahydrate in a glycerol solution and treat it with microwave at 3 kW for 7 min to remove the crystal water. Subsequently, perform flaking treatment for 15 min at an ultrasonic intensity of 40 W / m 2 and finally obtain lanthanum carbonate tetrahydrate product after centrifugation and drying, with a yield of 93%. Through XRD testing, it shows high crystal purity and no impurities, as shown in Figure 1 .

[0035] Example 4

[0036] Adjust the microwave / ultrasonic conditions in Example 1. Place lanthanum carbonate octahydrate in an acetonitrile solution and treat it with microwave at 4 kW for 6 min to remove the crystal water. Subsequently, perform flaking treatment for 10 min at an ultrasonic intensity of 50 W / m 2 and finally obtain lanthanum carbonate tetrahydrate product after centrifugation and drying, with a yield of 96%. Through XRD testing, it shows high crystallinity, high crystal purity and no impurities, as shown in Figure 1 .

[0037] Example 5

[0038] Adjust the microwave / ultrasonic conditions in Example 1. Place lanthanum carbonate octahydrate in an acetonitrile solution and treat it with microwave at 3 kW for 5 min to remove the crystal water. Subsequently, perform flaking treatment for 8 min at an ultrasonic intensity of 60 W / m 2 , and finally obtain lanthanum carbonate tetrahydrate product after centrifugation and drying, with a yield of 92%. The SEM results of the morphological characteristics of lanthanum carbonate tetrahydrate prepared by microwave / ultrasonic technology are as shown in Figure 2 . The prepared lanthanum carbonate tetrahydrate has good dispersibility and uniform particle size distribution. It is a one- or two-layer flaky shape, with a flake thickness of about 0.8 microns. Using an adsorption analyzer to test its specific surface area reaches 5.83 m 2 / g.

[0039] Comparative Example 6

[0040] Weigh 490.52 g of lanthanum chloride powder and 504.06 g of sodium bicarbonate powder. Dissolve the two powders in 1 L of deionized water and 3 L of deionized water respectively to prepare a 2 mol / L solution. Set the reaction temperature at 30 °C and drop the prepared sodium bicarbonate solution into the lanthanum chloride solution to react for 2 hours. After the reaction, filter the reaction product by suction and dry it to obtain lanthanum carbonate octahydrate powder. Finally, perform high-temperature drying treatment on lanthanum carbonate octahydrate (high-temperature drying at 120 °C for 2 hours) to obtain lanthanum carbonate tetrahydrate. Its SEM image of the morphological characteristics is as shown in Figure 3 . It can be seen that the lanthanum carbonate tetrahydrate prepared by high-temperature dehydration is in a stacked flaky shape. Using an adsorption analyzer to test its specific surface area is 4.51 m 2 / g, which is significantly reduced compared with that prepared by the microwave / ultrasonic method.

[0041] Under the same conditions, phosphate binding experiments were carried out on lanthanum carbonate tetrahydrate prepared by the microwave / ultrasonic technology of Example 5 and the high-temperature drying process of Example 6. The results are shown in Figure 4 . It can be seen that compared with the high-temperature drying treatment process, the lanthanum carbonate tetrahydrate prepared by the microwave / ultrasonic technology has a high binding rate and a fast binding rate. More than 90% of the phosphate can be bound in two hours, and the phosphate is reduced to less than 10%; while the sample dehydrated at high temperature has a slow binding rate and a low binding rate.

[0042] In summary, it can be known that the lanthanum carbonate tetrahydrate prepared by the microwave / ultrasonic technology of the present invention has obvious progress and advantages compared with the products of the traditional high-temperature dehydration preparation process (using the patent with publication number CN115849429A). The comparison of each parameter is shown in Table 1 below:

[0043] Table 1 Comparison of the properties of lanthanum carbonate tetrahydrate obtained by two dehydration methods

[0044]

[0045] Based on the above analysis, the lanthanum carbonate tetrahydrate prepared by the microwave / ultrasonic technology has excellent dispersibility and high phase purity. Compared with the products of the traditional high-temperature drying preparation process, it has a higher phosphate binding rate and a faster binding rate, with outstanding advantages and potential for use in the clinical treatment of hyperphosphatemia.

[0046] The above are only specific embodiments of the present invention, but the technical features of the present invention are not limited thereto. Any simple changes, equivalent substitutions or modifications made based on the present invention to solve substantially the same technical problems and achieve substantially the same technical effects are all covered by the protection scope of the present invention.

Claims

1. A preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology, characterized in that It includes the following steps: (1) Preparation of lanthanum carbonate octahydrate; (2) Preparation of flaky lanthanum carbonate tetrahydrate powder crystals; at room temperature, place the lanthanum carbonate octahydrate powder prepared in the step (1) in a solvent medium, adjust different microwave intensities for rapid dehydration treatment; then use the high-frequency vibration of ultrasonic waves for flaking, and after centrifugation and drying, obtain lanthanum carbonate tetrahydrate powder crystal products.

2. The preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, characterized in that: In the step (1), slowly drip the sodium bicarbonate solution into the lanthanum chloride solution, and fully react at a reaction temperature of 30 °C for 2 - 5 hours; then wash and filter the final product by suction and dry it to obtain lanthanum carbonate octahydrate powder.

3. The preparation method of the flaky lanthanum carbonate tetrahydrate powder crystal based on microwave / ultrasonic technology according to claim 2, wherein: The concentrations of both the sodium bicarbonate and lanthanum chloride are 2 mol / L.

4. A method for preparing flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, characterized in that: In the step (2), the solvent media are acetonitrile, glycerol, and ethyl acetate respectively.

5. The preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, characterized in that: In the step (2), the microwave power is 1 - 5 kW, and the irradiation time is 1 - 10 min.

6. The preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, wherein: In the step (2), the ultrasonic intensity is 10 - 60 W / m 2 , and the ultrasonic time is 10 - 30 min.

7. The preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, characterized in that: The obtained lanthanum carbonate tetrahydrate powder does not contain basic lanthanum carbonate impurities, and the crystal purity is above 99.5%.

8. A method for preparing flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, characterized in that: The obtained lanthanum carbonate tetrahydrate is in flaky shape, and its thickness is 0.5 - 1.5 microns.

9. The preparation method of flaky lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology according to claim 1, characterized in that: The yield of the lanthanum carbonate tetrahydrate is 90 - 96%.

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