A method for preparing thin sheet-like lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasonic technology

Abstract

The application discloses a preparation method of thin sheet four-water lanthanum carbonate powder crystal based on microwave / ultrasonic technology, which comprises the following steps: (1) preparation of eight-water lanthanum carbonate, slowly drop sodium bicarbonate solution into lanthanum chloride solution, fully react for 2-5 hours at a reaction temperature of 30 DEG C; then, the final product is washed with water, filtered and dried to prepare eight-water lanthanum carbonate powder; (2) preparation of thin sheet four-water lanthanum carbonate powder crystal, the eight-water lanthanum carbonate powder prepared in the step (1) is placed in a solvent medium at room temperature, different microwave intensities are regulated to carry out rapid dehydration treatment; then, the product is peeled by means of high-frequency ultrasonic vibration, centrifuged and dried to obtain four-water lanthanum carbonate powder crystal product. The four-water lanthanum carbonate is prepared by means of microwave / ultrasonic technology, which can avoid the generation of basic lanthanum carbonate impurities, and the obtained four-water lanthanum carbonate is thin sheet and uniform in dispersion, and the purity is more than 99.5%.

Description

Technical Field

[0001] This invention relates to lanthanide compounds used to treat hyperphosphatemia, specifically a method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology. Background Technology

[0002] Hyperphosphatemia is a common complication in patients with chronic kidney disease. Due to decreased kidney function, patients have difficulty excreting ingested phosphates, resulting in serum phosphorus levels exceeding normal levels. Furthermore, hyperphosphatemia is often accompanied by hypocalcemia, cardiovascular disease, and other risks, significantly increasing patient mortality. Therefore, taking measures to lower serum phosphorus levels is crucial. Oral phosphate binders are currently an important clinical treatment for hyperphosphatemia. In these binders, the trivalent lanthanum ion of lanthanum carbonate tetrahydrate binds to phosphates in food to form an insoluble lanthanum phosphate precipitate, thus preventing absorption and excretion. Compared to traditional phosphate binders, lanthanum carbonate tetrahydrate has advantages such as fewer toxic side effects, better efficacy, higher binding rate, and better tolerability, and is widely used clinically.

[0003] There is limited research on lanthanum carbonate tetrahydrate as a phosphorus-lowering drug in China. Currently, the preparation methods for lanthanum carbonate tetrahydrate primarily involve first synthesizing lanthanum carbonate octahydrate, followed by dehydration treatment to obtain lanthanum carbonate tetrahydrate. The main methods are as follows:

[0004] Patent CN111620363A discloses a method for preparing lanthanum carbonate tetrahydrate. The method involves reacting lanthanum oxide, acetic acid, potassium carbonate, potassium bicarbonate, or ammonium bicarbonate to synthesize lanthanum carbonate octahydrate, followed by high-temperature drying of the lanthanum carbonate octahydrate to obtain lanthanum carbonate tetrahydrate.

[0005] Patent CN114477265A synthesizes lanthanum carbonate octahydrate by adding carbonate or bicarbonate solution dropwise to lanthanum chloride solution and then refluxing in methanol, ethanol, isopropanol, n-butanol, ethylene glycol, toluene, acetone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, and N-methylpyrrolidone solvents to obtain lanthanum carbonate tetrahydrate.

[0006] Lanthanum carbonate tetrahydrate can be prepared by methods such as high-temperature drying and reflux crystallization in organic solvents. However, high-temperature and high-humidity environments easily generate the impurity lanthanum carbonate (basic lanthanum carbonate). The presence of basic lanthanum carbonate in the sample is detrimental to the absorption of phosphate by drugs; therefore, the formation of basic lanthanum carbonate impurities must be avoided during production. Summary of the Invention

[0007] The purpose of this invention is to provide a method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology, which avoids the generation of impurity phases under high temperature and high humidity conditions, and obtains thin-film samples with high purity and uniform dispersion, with a yield of over 90%.

[0008] To solve the above technical problems, the following technical solution is adopted:

[0009] A method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology, characterized by comprising the following steps:

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

[0011] (2) Preparation of thin-film lanthanum carbonate tetrahydrate powder crystals: The lanthanum carbonate octahydrate powder prepared in step (1) is placed in a solvent medium at room temperature, and different microwave intensities are adjusted for rapid dehydration treatment; then, the powder is peeled off by high-frequency vibration of ultrasound, and after centrifugation and drying, lanthanum carbonate tetrahydrate powder crystal products are obtained.

[0012] After optimization, in step (1), sodium bicarbonate solution is slowly added dropwise to lanthanum chloride solution, and the reaction is carried out at a reaction temperature of 30°C for 2-5 hours; then the final product is washed with water, filtered and dried to obtain lanthanum carbonate octahydrate powder.

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

[0014] After optimization, in step (2), the solvent medium is acetonitrile, glycerol, or ethyl acetate, and more preferably acetonitrile.

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

[0016] After optimization, in step (2), the ultrasonic intensity is 10-60 W / m. 2 The ultrasonic time is 10-30 minutes, and the ultrasonic intensity is further optimized to be 60 W / m. 2 The ultrasound time was 10 minutes.

[0017] After optimization, the obtained lanthanum carbonate tetrahydrate powder is free of basic lanthanum carbonate impurities and has a crystal purity of over 99.5%.

[0018] After optimization, the obtained lanthanum carbonate tetrahydrate is in the form of uniformly dispersed flakes with a thickness of 0.5-1.5 micrometers.

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

[0020] The above technical solution has the following beneficial effects:

[0021] This invention utilizes microwave / ultrasound technology to dehydrate and prepare lanthanum carbonate tetrahydrate, which avoids the generation of basic lanthanum carbonate impurities. The obtained lanthanum carbonate tetrahydrate is in the form of uniformly dispersed flakes with a purity of over 99.5%. Attached Figure Description

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

[0023] Figure 1 XRD patterns of samples after microwave / ultrasonic treatment with different solvents as media.

[0024] Figure 2 SEM image of lanthanum carbonate tetrahydrate prepared by microwave / ultrasound technique

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

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

[0027] The present invention aims to provide a method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology, which avoids the generation of impurity phases under high temperature and high humidity conditions, and obtains thin-film samples with high purity and uniform dispersion, with a yield of over 90%.

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

[0029] Example 1

[0030] 490.52 g of lanthanum chloride powder and 504.06 g of sodium bicarbonate powder were weighed and dissolved in 1 L and 3 L of deionized water respectively to prepare 2 mol / L solutions. The reaction temperature was set at 30 °C, and the prepared sodium bicarbonate solution was added dropwise to the lanthanum chloride solution and reacted for 2 hours. After the reaction was completed, the reaction product was filtered and dried to obtain lanthanum carbonate octahydrate powder. Finally, lanthanum carbonate octahydrate was dehydrated in different solvents using microwave / ultrasound technology to prepare lanthanum carbonate tetrahydrate.

[0031] Example 2

[0032] The microwave / ultrasonic conditions in Example 1 were adjusted. Lanthanum carbonate octahydrate was placed in an ethyl acetate solution and microwaved at 2 kW for 8 min to remove the water of crystallization, followed by ultrasonic treatment at an intensity of 30 W / m. 2 After peeling for 20 minutes, the product was finally obtained by centrifugation and drying, yielding lanthanum carbonate tetrahydrate with a yield of 95%. XRD analysis showed high crystal purity and no impurities. Figure 1 .

[0033] Example 3

[0034] The microwave / ultrasonic conditions in Example 1 were adjusted. Lanthanum carbonate octahydrate was placed in a glycerol solution and microwaved at 3 kW for 7 min to remove the water of crystallization, followed by ultrasonic treatment at an intensity of 40 W / m. 2 After peeling for 15 minutes, the product was finally obtained by centrifugation and drying, yielding lanthanum carbonate tetrahydrate with a yield of 93%. XRD analysis showed high crystal purity and no impurities. Figure 1 .

[0035] Example 4

[0036] The microwave / ultrasonic conditions in Example 1 were adjusted. Lanthanum carbonate octahydrate was placed in an acetonitrile solution and microwaved at 4 kW for 6 min to remove water of crystallization, followed by ultrasonic treatment at an intensity of 50 W / m. 2 After peeling for 10 minutes, the product was finally obtained by centrifugation and drying, yielding lanthanum carbonate tetrahydrate with a yield of 96%. XRD analysis showed high crystallinity, high crystal purity, and no impurities. Figure 1 .

[0037] Example 5

[0038] The microwave / ultrasonic conditions in Example 1 were adjusted. Lanthanum carbonate octahydrate was placed in an acetonitrile solution and microwaved at 3 kW for 5 min to remove water of crystallization, followed by ultrasonic treatment at an intensity of 60 W / m. 2 The sample was peeled for 8 minutes, and then centrifuged and dried to obtain lanthanum carbonate tetrahydrate, with a yield of 92%. The morphological characteristics of lanthanum carbonate tetrahydrate prepared by microwave / ultrasonic techniques were shown in the SEM results. Figure 2 As shown, the prepared lanthanum carbonate tetrahydrate exhibits good dispersibility and uniform particle size distribution, forming one or two thin flakes with a layer thickness of approximately 0.8 micrometers. Its specific surface area, measured using an adsorption analyzer, reaches 5.83 m². 2 / g.

[0039] Comparative Example 6

[0040] 490.52 g of lanthanum chloride powder and 504.06 g of sodium bicarbonate powder were weighed and dissolved in 1 L and 3 L of deionized water, respectively, to prepare 2 mol / L solutions. The reaction temperature was set at 30 °C, and the prepared sodium bicarbonate solution was added dropwise to the lanthanum chloride solution for 2 hours. After the reaction was complete, the reaction product was filtered and dried to obtain lanthanum carbonate octahydrate powder. Finally, the lanthanum carbonate octahydrate was dried at high temperature (120 °C for 2 hours) to obtain lanthanum carbonate tetrahydrate. Its morphological characteristics are shown in the SEM image below. Figure 3 As shown, the lanthanum carbonate tetrahydrate prepared by high-temperature dehydration exhibits a layered, stacked structure. Its specific surface area, measured using an adsorption analyzer, is 4.51 m². 2 / g, a significant reduction compared to preparations by microwave / ultrasound methods.

[0041] Under the same conditions, phosphate binding experiments were conducted on lanthanum carbonate tetrahydrate prepared by microwave / ultrasonic technology in Example 5 and high-temperature drying process in Example 6. The results are shown in [Figure Number]. Figure 4 It is evident that, compared to high-temperature drying, microwave / ultrasonic technology produces lanthanum carbonate tetrahydrate with a higher binding rate and faster binding speed, achieving over 90% phosphate binding within two hours, reducing phosphate content to below 10%; while samples dehydrated at high temperatures exhibit slower binding rates and lower binding rates.

[0042] In summary, the lanthanum carbonate tetrahydrate prepared by microwave / ultrasonic technology in this invention has significant improvements and advantages over the traditional high-temperature dehydration preparation process (using patent publication number CN115849429A). The parameters are compared in Table 1 below.

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

[0044]

[0045] Based on the above analysis, the microwave / ultrasound technique for preparing lanthanum carbonate tetrahydrate exhibits excellent dispersibility and high phase purity. Compared to traditional high-temperature drying processes, the product demonstrates higher phosphate binding rates and faster binding speeds, showing significant advantages and potential for clinical treatment of hyperphosphatemia.

[0046] The above are merely 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 essentially the same technical problems and achieve essentially the same technical effects are all covered within the protection scope of the present invention.

Claims

1. A method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology, characterized in that... Includes the following steps: (1) Preparation of lanthanum carbonate octahydrate powder; (2) Preparation of thin-film lanthanum carbonate tetrahydrate powder crystals; at room temperature, the lanthanum carbonate octahydrate powder prepared in step (1) is placed in a solvent medium, and rapid dehydration is performed by adjusting different microwave intensities. The microwave power is 1-5 kW and the irradiation time is 1-10 min; then, the powder is peeled off by high-frequency ultrasonic vibration with an ultrasonic intensity of 10-60 W / m. 2 The ultrasonic treatment time is 10-30 min; after centrifugation and drying, thin flake-shaped lanthanum carbonate tetrahydrate powder crystals are obtained with a thickness of 0.5-1.5 micrometers; the solvent medium is acetonitrile, glycerol or ethyl acetate; the obtained lanthanum carbonate tetrahydrate powder crystals do not contain basic lanthanum carbonate impurities and have a purity of more than 99.5%; the yield of lanthanum carbonate tetrahydrate is 90-96%.

2. The method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology according to claim 1, characterized in that: In step (1), sodium bicarbonate solution is slowly added dropwise to lanthanum chloride solution, and the reaction is carried out at a reaction temperature of 30 °C for 2-5 hours. Then the final product is washed with water, filtered, and dried to obtain lanthanum carbonate octahydrate powder.

3. The method for preparing thin-film lanthanum carbonate tetrahydrate powder crystals based on microwave / ultrasound technology according to claim 2, characterized in that: The concentrations of sodium bicarbonate and lanthanum chloride were both 2 mol / L.

Images