A method for preparing and purifying cefuroxime sodium

Abstract

The present application relates to the technical field of cefuroxime sodium medicine, and relates to a preparation and purification method of cefuroxime sodium, which comprises the following steps: dissolving cefuroxime acid in an aqueous acetone solution, adding a sodium acetate aqueous ethanol solution to stir and react, to obtain a mixed solution; pumping the mixed solution into a nanofiltration assembly containing a bacterial cellulose nanofiltration membrane to perform nanofiltration concentration, to obtain a concentrated solution; adjusting the pH of the concentrated solution, adding an ethanol acetone mixed solution, uniformly mixing, adding cefuroxime sodium crystal seeds, controlling the temperature, stirring to perform primary crystallization, after constant-speed cooling, performing secondary crystallization, to obtain a crystallization product; filtering and drying the crystallization product, to obtain cefuroxime sodium crystals. The preparation method significantly improves the purity and colority of the cefuroxime sodium product, and the purity can reach more than 99.7%. The present application uses biodegradable bacterial cellulose nanofiltration membrane as a separation medium, avoids the environmental pollution problem caused by traditional petroleum-based polymer membranes, and conforms to the principle of green chemistry.

Description

Technical Field

[0001] This invention relates to the field of cefuroxime sodium pharmaceutical technology, and specifically to a method for preparing and purifying cefuroxime sodium. Background Technology

[0002] Cefuroxime sodium is an important second-generation cephalosporin antibiotic with broad-spectrum antibacterial activity, widely used in the treatment of clinical infectious diseases. Its preparation typically uses cefuroxime acid as a raw material, proceeding through neutralization, crystallization, and drying to obtain the final product. However, during the synthesis of cefuroxime sodium, unreacted cefuroxime acid, intermediate byproducts, and organic solvent impurities often remain in the reaction system. Without effective separation and purification, these residues can affect the purity, yield, and color of the final product.

[0003] Traditional purification methods often combine activated carbon adsorption decolorization with recrystallization. For example, patent CN200910162867 describes dissolving cefuroxime axetine in sodium bicarbonate, followed by activated carbon adsorption decolorization and recrystallization. However, this method suffers from poor adsorption selectivity, unstable decolorization, and cumbersome operation steps. Furthermore, activated carbon treatment generates a large amount of solid waste, impacting environmental protection requirements. To improve purity and recovery rate, some methods attempt to use supercritical fluid extraction (e.g., patent CN201610709544.4). While this can improve purity to some extent, it requires extremely precise temperature and pressure control, resulting in expensive equipment and complex operation, making it unsuitable for large-scale industrial applications. Other methods use petroleum-based polymer nanofiltration membranes (such as fully aromatic polyamide APA membranes) to concentrate and remove impurities from the reaction solution before crystallization (CN202411471577.0). However, these membrane materials are non-degradable, and long-term use can easily lead to membrane fouling and waste disposal problems. Existing purification methods for cefuroxime sodium generally rely on non-degradable petroleum-based polymer membranes or energy-intensive physical extraction processes, which often require activated carbon decolorization. These methods are not only complex and energy-intensive, but also have a significant environmental impact, hindering the improvement of key quality indicators such as product purity and color, and are not in line with the development trend of green chemistry. Summary of the Invention

[0004] To overcome the deficiencies described in the prior art, the present invention provides a method for preparing and purifying cefuroxime sodium.

[0005] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows: A method for preparing and purifying cefuroxime sodium includes the following steps: S1. Dissolve cefuroxime acid in an aqueous acetone solution, add sodium acetate ethanol aqueous solution to the above solution, stir to react, and obtain a mixture; S2. The mixture is pumped into a nanofiltration module containing a bacterial cellulose nanofiltration membrane for nanofiltration concentration to obtain a concentrate; S3. Adjust the pH of the concentrate, add the ethanol-acetone mixture, mix well, add the cefuroxime sodium seed crystals, control the temperature at 18~20℃, stir for initial crystallization for 0.5~1 hour, cool down at a constant rate to 8~12℃, and carry out secondary crystallization for 2~3 hours to obtain the crystalline product. S4. Filter and dry the crystallized product to obtain cefuroxime sodium crystals.

[0006] Preferably, the mass ratio of cefuroxime acid to acetone aqueous solution in step S1 is 1:(9~11), and the mass percentage of acetone in the acetone aqueous solution is 85%~95%.

[0007] Preferably, the mass ratio of sodium acetate, ethanol, and water in the sodium acetate-ethanol aqueous solution in step S1 is (0.8~1.2):4:5. Preferably, the mass ratio of sodium acetate, ethanol, and water in the sodium acetate-ethanol aqueous solution in step S1 is (0.9~1.1):4:5. Preferably, the mass ratio of the acetone aqueous solution to the sodium acetate ethanol aqueous solution in step S1 is 1:(0.9~1.1).

[0008] Preferably, the nanofiltration assembly described in step S2 includes a bacterial cellulose nanofiltration membrane as the core separation layer. It is preferably a plate-type assembly structure, with the membrane installed in a sealable plate module. It has an inlet, a concentrated water outlet, and a permeate outlet, which can achieve stable nanofiltration concentration operation.

[0009] Preferably, the nanofiltration concentration conditions in step S2 are as follows: the mass of the filtrate is 30% to 40% of the mass of the mixture, the operating pressure of nanofiltration concentration is 1.0 to 1.2 MPa, and the temperature of nanofiltration concentration is 24 to 26°C.

[0010] In this invention, the mass of the filtrate is controlled at 40% to 50% of the mass of the mixture, allowing cefuroxime axetine and other impurities to pass through, while cefuroxime sodium is enriched in the concentrate, improving its crystallization purity and yield, and also maintaining a good balance between throughput, operating pressure and recovery rate.

[0011] Preferably, the seed crystals in step S3 are 0.1% to 0.15% of the mass of cefuroxime acid.

[0012] Preferably, the stirring speed in step S3 is 80~100 rpm.

[0013] Preferably, the pH of the concentrate in step S3 is adjusted to 5.6-6.4.

[0014] Preferably, the pH of the concentrate in step S3 is adjusted to 6.0.

[0015] Preferably, the mass of the ethanol-acetone mixture added in step S3 is 8 times that of the concentrate, and the mass ratio of ethanol to acetone in the ethanol-acetone mixture is 1:(0.9~1.1).

[0016] Preferably, the cooling rate of the constant-rate cooling in step S3 is 0.4~0.6℃ / min.

[0017] The bacterial cellulose nanofiltration membrane is prepared by the following steps: (1) Prepare bacterial cellulose film-forming solution.

[0018] (2) Adjust the pH of the bacterial cellulose membrane preparation solution and filter the bacterial cellulose membrane preparation solution into a primary bacterial cellulose membrane using vacuum filtration.

[0019] (3) Dry the primary bacterial cellulose membrane into a film.

[0020] (4) Place the dried primary bacterial cellulose membrane at 70-90℃ for 2-3 hours, then soak it in an acetone aqueous solution, and then dry it again to form a membrane, thus obtaining a bacterial cellulose nanofiltration membrane.

[0021] The bacterial cellulose film-forming solution is prepared from bacterial cellulose, cefuroxime acid, acetone, ethanol, and water; wherein, bacterial cellulose is 1-3 parts by weight (dry weight), cefuroxime acid is 1-3 parts by weight, acetone is 10-20 parts by weight, ethanol is 30-50 parts by weight, and water is 30-50 parts by weight.

[0022] In this invention, a sacrificial template strategy is used to selectively regulate bacterial cellulose nanofiltration membranes. Cefuroxime acid is creatively introduced as a pore-forming agent into the primary bacterial cellulose membrane matrix, so that the pore-forming agent is evenly distributed within the membrane structure.

[0023] Preferably, in the bacterial cellulose film-forming solution, the mass ratio of bacterial cellulose (dry weight) to cefuroxime acid is 1:1.

[0024] Preferably, the mass ratio of acetone to ethanol in the bacterial cellulose film-forming solution is (1~3):5.

[0025] Preferably, the mass ratio of acetone to ethanol in the bacterial cellulose film-forming solution is 2:5.

[0026] Preferably, the pH of the bacterial cellulose film-forming solution prepared in step (2) is adjusted to 4-6.

[0027] More preferably, the pH of the bacterial cellulose film-forming solution prepared in step (2) is adjusted to 5.

[0028] In this invention, adjusting the pH of the bacterial cellulose membrane-forming solution to 4-6 results in a bacterial cellulose nanofiltration membrane with good nanofiltration separation performance.

[0029] Preferably, the drying film-forming temperature in step (3) is 35~45℃ and the humidity is 40%~60%.

[0030] More preferably, the drying film-forming temperature in step (3) is 40°C and the humidity is 50%.

[0031] In this invention, when the drying film-forming temperature in step (3) is 35~45℃ and the humidity is 40%~60%, it is beneficial to control the pore size of the nanofiltration membrane and the preparation and purification of cefuroxime sodium are better.

[0032] Preferably, the mass percentage of acetone in the acetone aqueous solution in step (4) is 60% to 80%.

[0033] Preferably, the soaking time in step (4) is at least 24 hours.

[0034] In this invention, a specific solvent and treatment method are used to selectively dissolve cefuroxime acid, forming nanoscale pores with molecular recognition function inside the membrane, thereby improving the selective permeation of cefuroxime acid by the nanofiltration membrane and enhancing the overall nanofiltration effect.

[0035] Preferably, the thickness of the bacterial cellulose nanofiltration membrane in step (4) is 20~30μm.

[0036] In this invention, the thickness of the bacterial cellulose nanofiltration membrane is controlled at 20~30μm, which is beneficial to achieve high nanofiltration flux and molecular selective retention effect while ensuring membrane structure stability.

[0037] This invention innovatively proposes using bacterial cellulose as the membrane substrate material and introducing a specific ratio of organic solvent system to co-construct a nanofiltration membrane structure with drug template molecules. Traditional nanofiltration membrane preparation commonly employs polymer or surface modification methods to control the membrane structure. However, this invention uses cefuroxime acid as a sacrificial template molecule, dispersing it together with bacterial cellulose in a composite solvent system composed of acetone, ethanol, and water in a specific mass ratio. By controlling the mass ratio of acetone and ethanol, pH, and heating treatment at 70–90°C, a highly controllable microporous network is imparted to the membrane structure, enabling the dissolution of cefuroxime acid through solvent extraction and thermal degradation, forming confined nanochannels with molecular recognition effects within the membrane.

[0038] The method of this invention not only endows nanofiltration membranes with good size repulsion selectivity, but also effectively achieves molecular-level separation of cefuroxime sodium and cefuroxime acid. In particular, the precise optimization of the ratio between bacterial cellulose, organic solvent and pore-forming agent in the membrane-forming solution formula ensures the synergistic unity of membrane structure stability and functionality, and has high technical originality and application value.

[0039] Compared with the prior art, the beneficial effects of the technical solution of the present invention are: The method for preparing and purifying cefuroxime sodium of the present invention utilizes a nanofiltration module comprising a bacterial cellulose nanofiltration membrane, achieving selective permeation of cefuroxime acid and efficient retention of cefuroxime sodium in the reaction system. This effectively controls the composition of the mother liquor and the crystallization environment during crystallization, which is beneficial for directional nucleation and pure crystal growth. Experimental results show that the purity of cefuroxime sodium obtained using the preferred preparation process of the present invention can reach over 99.7%, with a yield exceeding 99%, and the product color is significantly improved to the Y-1 level.

[0040] This invention uses renewable bacterial cellulose as a matrix and combines it with sacrificial template molecule cefuroxime acid for structural regulation, avoiding the potential environmental pollution caused by traditional petroleum-based polymer membranes during synthesis and disposal. It has good environmental friendliness and sustainability, and is in line with the concept of green chemistry and clean production.

[0041] This invention is innovative not only in the selection of membrane materials and the method of structural control, but also shows excellent separation efficiency and product quality improvement potential in the purification of cephalosporin drugs, and has broad industrial application prospects. Attached Figure Description

[0042] Figure 1 This is an electron microscope image of the bacterial cellulose nanofiltration membrane of Example 1 of the present invention. Detailed Implementation

[0043] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0044] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0045] The bacterial cellulose dispersion was prepared by the inventor. The bacterial cellulose wet film was purchased from Hainan Yide Food Co., Ltd. The bacterial cellulose wet film was cut into rectangular pieces (4 cm × 4 cm) and stirred at 80°C with a 0.5 mol / L NaOH aqueous solution at 500 rpm for 3 hours, followed by treatment with 3 wt% hydrogen peroxide at 80°C for 3 hours. The treated bacterial cellulose wet film was rinsed with deionized water and then soaked in deionized water for 24–48 hours to remove residual NaOH and hydrogen peroxide. After pulverizing the bacterial cellulose, it was homogenized in a high-pressure homogenizer for 20–30 minutes to obtain dispersed bacterial cellulose.

[0046] TEMPO oxidized cellulose nanoparticles were purchased from SenseTime.

[0047] Example 1 (I) Preparation of bacterial cellulose nanofiltration membrane: Prepare a bacterial cellulose membrane-forming solution containing the following components by weight: 2g bacterial cellulose (dry weight), 2g cefuroxime axetine, 16g acetone, 40g ethanol, and 40g distilled water (acetone to ethanol mass ratio 2:5). After thorough mixing, the bacterial cellulose membrane-forming solution has a pH of 5. Use this solution to prepare a primary bacterial cellulose membrane through a vacuum filtration device (membrane pore size 0.22μm). Dry the primary bacterial cellulose membrane at 40℃ and 50% humidity, then treat it at 80℃ for 2.5 hours, and then soak it in a 70% acetone aqueous solution for 24 hours. After post-treatment, dry the membrane at 45℃ to obtain a bacterial cellulose nanofiltration membrane with a thickness of 25μm.

[0048] (II) Purification of cefuroxime sodium, including the following steps: S1. Dissolve 10g of cefuroxime acid in 100g of acetone aqueous solution (acetone mass percentage 90%), add 100g of sodium acetate ethanol aqueous solution (mass ratio of sodium acetate, ethanol and water 1:4:5) to the above solution, stir and react at 25℃ for 60min to obtain a mixed solution.

[0049] S2. The mixed liquor is pumped into a nanofiltration module containing a bacterial cellulose nanofiltration membrane for nanofiltration concentration, so that the filtrate is 40% of the original mixed liquor mass, and a concentrated liquid is obtained; the operating pressure of nanofiltration concentration is 1.1 MPa, and the temperature of nanofiltration concentration is 25℃.

[0050] S3. Adjust the pH of the concentrate to 6.0, add 8 times the weight of the concentrate in an ethanol-acetone mixture (ethanol to acetone mass ratio of 1:1), mix well, add 0.01g of cefuroxime sodium seed crystals, control the temperature at 18℃, and carry out primary crystallization at a stirring speed of 80rpm for 30 minutes. Then, cool down to 8℃ at a constant rate of 0.4℃ / min and carry out secondary crystallization for 2 hours to obtain the crystalline product.

[0051] S4. Filter and dry the crystallized product to obtain cefuroxime sodium crystals.

[0052] Example 2 (I) Preparation of bacterial cellulose nanofiltration membrane: Prepare a bacterial cellulose membrane-forming solution containing the following parts by weight: 2g bacterial cellulose (dry weight), 1g cefuroxime axetine, 10g acetone, 50g ethanol, and 40g distilled water (acetone to ethanol mass ratio 1:5). After thorough mixing, the bacterial cellulose membrane-forming solution should have a pH of 4. Use this solution to prepare a primary bacterial cellulose membrane through a vacuum filtration device (membrane pore size 0.22μm). Dry the primary bacterial cellulose membrane at 35℃ and 40% humidity, then treat it at 80℃ for 3 hours, followed by immersion in a 70% acetone aqueous solution for 24 hours. After post-treatment, dry the membrane at 45℃ to obtain a bacterial cellulose nanofiltration membrane with a thickness of 25μm.

[0053] (II) Purification of cefuroxime sodium, including the following steps: S1. Dissolve 10g of cefuroxime acid in 100g of acetone aqueous solution (acetone mass percentage 90%), add 100g of sodium acetate ethanol aqueous solution (mass ratio of sodium acetate, ethanol and water 1:4:5) to the above solution, stir and react at 25℃ for 60min to obtain a mixed solution.

[0054] S2. The mixed liquor is pumped into a nanofiltration module containing a bacterial cellulose nanofiltration membrane for nanofiltration concentration, so that the filtrate is 30% of the original mixed liquor mass, and a concentrated liquid is obtained; the operating pressure of nanofiltration concentration is 1.1 MPa, and the temperature of nanofiltration concentration is 25℃.

[0055] S3. Adjust the pH of the concentrate to 6.0, add 8 times the weight of the concentrate in an ethanol-acetone mixture (ethanol to acetone mass ratio of 1:1), mix well, add 0.01g of cefuroxime sodium seed crystals, control the temperature at 18℃, and carry out primary crystallization at a stirring speed of 80rpm for 30 minutes. Then, cool down to 8℃ at a constant rate of 0.4℃ / min and carry out secondary crystallization for 2 hours to obtain the crystalline product.

[0056] S4. Filter and dry the crystallized product to obtain cefuroxime sodium crystals.

[0057] Example 3 (I) Preparation of bacterial cellulose nanofiltration membrane: Prepare a bacterial cellulose membrane-forming solution containing the following parts by weight: 2g bacterial cellulose (dry weight), 3g cefuroxime axetine, 18g acetone, 30g ethanol, and 40g distilled water (acetone to ethanol mass ratio 3:5). After thorough mixing, the bacterial cellulose membrane-forming solution should have a pH of 6. Then, use this solution to prepare a primary bacterial cellulose membrane through a vacuum filtration device (membrane pore size 0.22μm). Dry the primary bacterial cellulose membrane at 45℃ and 60% humidity, then treat it at 80℃ for 2 hours, and finally immerse it in a 70% acetone aqueous solution for 24 hours. After post-treatment, dry the membrane at 45℃ to obtain a bacterial cellulose nanofiltration membrane with a thickness of 25μm.

[0058] (II) Purification of cefuroxime sodium, including the following steps: S1. Dissolve 10g of cefuroxime acid in 100g of acetone aqueous solution (acetone mass percentage 90%), add 100g of sodium acetate ethanol aqueous solution (mass ratio of sodium acetate, ethanol and water 1:4:5) to the above solution, stir and react at 25℃ for 60min to obtain a mixed solution.

[0059] S2. The mixed liquor is pumped into a nanofiltration module containing a bacterial cellulose nanofiltration membrane for nanofiltration concentration, so that the filtrate is 30% of the original mixed liquor mass, and a concentrated liquid is obtained; the operating pressure of nanofiltration concentration is 1.1 MPa, and the temperature of nanofiltration concentration is 25℃.

[0060] S3. Adjust the pH of the concentrate to 6.0, add 8 times the weight of the concentrate in an ethanol-acetone mixture (ethanol to acetone mass ratio of 1:1), mix well, add 0.01g of cefuroxime sodium seed crystals, control the temperature at 20℃, and carry out primary crystallization at a stirring speed of 80rpm for 30 minutes. Then, cool down to 8℃ at a constant rate of 0.6℃ / min and carry out secondary crystallization for 2 hours to obtain the crystalline product.

[0061] S4. Filter and dry the crystallized product to obtain cefuroxime sodium crystals.

[0062] Comparative Example 1 This comparative example is similar to Example 1, except that (a) in the preparation of the bacterial cellulose nanofiltration membrane, cefuroxime acid is not added to the bacterial cellulose membrane-forming solution.

[0063] Comparative Example 2 This comparative example is similar to Example 1, except that (a) in the preparation of the bacterial cellulose nanofiltration membrane, acetone is not added to the bacterial cellulose membrane-forming solution.

[0064] Comparative Example 3 This comparative example is similar to Example 1, except that (a) in the preparation of the bacterial cellulose nanofiltration membrane, the bacterial cellulose membrane-forming solution contains 8g of acetone and 48g of ethanol, with a mass ratio of 1:6 between acetone and ethanol.

[0065] Comparative Example 4 This comparative example is similar to Example 1, except that (a) in the preparation of the bacterial cellulose nanofiltration membrane, the pH of the bacterial cellulose membrane-forming solution was adjusted to 7.

[0066] Comparative Example 5 This comparative example is similar to Example 1, except that in step (i), the primary bacterial cellulose membrane is not dried at 40°C and 50% humidity, but is directly dried at 80°C.

[0067] Comparative Example 6 This comparative example is similar to Example 1, except that the treatment at 80°C is not performed in step (i).

[0068] Comparative Example 7 This comparative example is similar to Example 1, except that in step (a), it is soaked in a 70% acetone aqueous solution for 12 hours.

[0069] Comparative Example 8 This comparative example is similar to Example 1, except that in step (II), S1, 10g of cefuroxime acid is dissolved in 150g of acetone aqueous solution (acetone mass percentage 60%), and 100g of sodium acetate ethanol aqueous solution (mass ratio of sodium acetate, ethanol, and water 1:4:5) is added to the above solution. The mixture is stirred at 25°C for 60 min to obtain a mixed solution. The mass ratio of acetone aqueous solution to sodium acetate ethanol aqueous solution is 1.5:1.

[0070] Comparative Example 9 This comparative example is similar to Example 1, except that in step (ii), S3, the pH of the concentrate is adjusted to 7.5.

[0071] Comparative Example 10 This comparative example is similar to Example 1, except that bacterial cellulose is replaced with TEMPO oxidized nanocellulose.

[0072] Detection method: The content of cefuroxime sodium and cefuroxime acid was determined by HPLC. The color of cefuroxime sodium was determined according to the test method in the Chinese Pharmacopoeia. Flux decay was tested using a cross-flow nanofiltration cell. The feed solution was prepared according to the following mass fractions: 1 part by weight of cefuroxime acid, 500 parts by weight of acetone, and 499 parts by weight of water. The cell was continuously run at 25℃ and 1.1 MPa constant pressure for 24 h. The membrane sample was pre-pressurized at 1.1 MPa for 30 min until the flux stabilized. After discarding the first 50 mL of permeate, the volume collected for 10 min was calculated to determine the initial flux J0. The flux J0 was measured again using the same method after 24 h. 24 , according to (J0−J 24 ) / J0×100% calculates the attenuation rate.

[0073] The results are shown in the table below: Results analysis: The results of Examples 1-3 show that the bacterial cellulose nanofiltration membrane prepared using the preferred parameters of this invention exhibits excellent separation performance in the purification of cefuroxime sodium. The purity of the obtained cefuroxime sodium products is all above 99.7%, the yield is over 99%, and the color is good (Y-1), demonstrating the significant advantages of the present invention in improving product quality and purification efficiency.

[0074] As shown in Table 2, after continuous operation at a constant pressure of 1.1 MPa for 24 h, the flux of Examples 1-3 decreased by only 3.1% to 4.2%, and all were <5%. This result fully demonstrates that the bacterial cellulose nanofiltration membrane has excellent stability and long-term operational reliability under the operating conditions of this invention, providing a solid guarantee for the highly selective purification of cefuroxime sodium.

[0075] The experimental results of Examples 1 and Comparative Examples 1-3 show that when the mass fraction of the components in the bacterial cellulose membrane-forming solution is not within the preferred range of this invention, especially when cefuroxime acid is not introduced as a pore-forming template (Comparative Example 1), the prepared nanofiltration membrane lacks selective permeation performance, resulting in a significant decrease in the purity and yield of cefuroxime sodium. The product has high color, poor purity (less than 95%), low yield, and poor overall quality. When the mass ratio of acetone to ethanol in the bacterial cellulose membrane-forming solution deviates from the range set by this invention (Comparative Examples 2 and 3), it may lead to a decrease in the compatibility and dispersibility of the solvent system with bacterial cellulose and cefuroxime acid, resulting in insufficient development of the membrane pore structure. Ultimately, this leads to a cefuroxime sodium purity of less than 96% and a yield of less than 75%, indicating that the design of the solvent system has a significant impact on membrane structure regulation and separation performance.

[0076] As shown in the results of Comparative Examples 4-7, the pH of the bacterial cellulose membrane-forming solution, the drying temperature and humidity of the primary bacterial cellulose membrane, whether the treatment is carried out at 70-90℃, and the soaking time in acetone aqueous solution have a significant impact on the overall quality of the final cefuroxime sodium. These conditions directly affect the distribution and dissolution efficiency of cefuroxime acid in the membrane, thereby affecting the selectivity and permeation performance of the nanofiltration membrane. If non-preferred conditions of this invention are used, the purity and yield of the final cefuroxime sodium decrease significantly, and the product color is too high, indicating that the membrane pore structure is not ideal or the template is not sufficiently removed, leading to the deterioration of nanofiltration performance.

[0077] As can be seen from the results of Example 1 and Comparative Example 8, the mass of the acetone aqueous solution and sodium acetate ethanol aqueous solution in step S1 is not within the preferred range of the present invention. The purity of the cefuroxime sodium obtained is less than 96%, the color increases to Y-2, and the yield is only 93.2%, which is significantly lower than that of Example 1.

[0078] As can be seen from the results of Comparative Example 9, when the pH of the concentrate was adjusted to 7.5 in step S3, the yield and purity of the prepared cefuroxime sodium were 93.1%, and the color Y-8 was only 65.1%, which affected the crystal purity and the overall quality of the product.

[0079] As can be seen from the results of Comparative Example 10, using TEMPO-oxidized nanocellulose instead of the preferred method of this invention (bacterial cellulose) resulted in a cefuroxime sodium yield of 94.2%, a purity of 92.2%, and a higher color intensity (Y-8) for cefuroxime sodium, indicating a poorer overall quality.

[0080] This invention uses unmodified bacterial cellulose as the membrane material, significantly improving the membrane formation efficiency during the membrane fabrication process. Compared with TEMPO-oxidized nanocellulose, the bacterial cellulose nanofiltration membrane prepared by this invention has the advantages of fast membrane formation and simple operation. Specifically, under the conditions of Example 1, the bacterial cellulose membrane-forming solution can complete membrane formation in only about 2 minutes through vacuum filtration, while TEMPO-oxidized nanocellulose requires up to 5 hours to form a stable membrane layer under the same equipment and conditions. This superior performance is attributed to the good dispersibility of bacterial cellulose itself, combined with the innovative bacterial cellulose membrane-forming solution component system and pH conditions of this invention, enabling it to form a rapid and uniform membrane during the membrane formation process.

[0081] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing and purifying cefuroxime sodium, characterized in that, The steps include the following: S1. Dissolve cefuroxime acid in an aqueous acetone solution, add sodium acetate ethanol aqueous solution to the above solution, stir to react, and obtain a mixture; S2. The mixture is pumped into a nanofiltration module containing a bacterial cellulose nanofiltration membrane as the core separation layer for nanofiltration concentration to obtain a concentrate; S3. Adjust the pH of the concentrate, add the ethanol-acetone mixture, mix well, add the cefuroxime sodium seed crystals, control the temperature at 18~20℃, stir for initial crystallization for 0.5~1 hour, cool down at a constant rate to 8~12℃, and carry out secondary crystallization for 2~3 hours to obtain the crystalline product. S4. Filter and dry the crystallized product to obtain cefuroxime sodium crystals; The pH of the concentrate described in step S3 is adjusted to 5.6-6.4; The bacterial cellulose nanofiltration membrane described in step S2 is prepared by the following steps: (1) Preparation of bacterial cellulose film-forming solution; (2) Adjust the pH of the bacterial cellulose membrane-forming solution and filter the bacterial cellulose membrane-forming solution into a primary bacterial cellulose membrane using vacuum filtration. (3) Dry the primary bacterial cellulose membrane into a film; (4) Place the dried primary bacterial cellulose membrane at 70-90℃ for 2-3 hours, then soak it in an acetone aqueous solution, and then dry it again to form a membrane, thus obtaining a bacterial cellulose nanofiltration membrane. The bacterial cellulose film-forming solution is prepared from bacterial cellulose, cefuroxime acid, acetone, ethanol, and water; wherein, bacterial cellulose is 1-3 parts by weight, cefuroxime acid is 1-3 parts by weight, acetone is 10-20 parts by weight, ethanol is 30-50 parts by weight, and water is 30-50 parts by weight. In the bacterial cellulose film-forming solution, the mass ratio of acetone to ethanol is (1~3):5; In step (2), the pH of the bacterial cellulose film-forming solution is adjusted to 4-6. The drying film-forming temperature in step (3) is 35~45℃, and the humidity is 40%~60%; The soaking time in step (4) is at least 24 hours.

2. The method for preparing and purifying cefuroxime sodium according to claim 1, characterized in that, The mass ratio of sodium acetate, ethanol and water in the sodium acetate-ethanol aqueous solution in step S1 is (0.8~1.2):4:5; the mass ratio of acetone aqueous solution to sodium acetate-ethanol aqueous solution in step S1 is 1:(0.9~1.1).

3. The method for preparing and purifying cefuroxime sodium according to claim 1, characterized in that, The operating pressure for nanofiltration concentration in step S2 is 1.0~1.2MPa, and the temperature for nanofiltration concentration is 24~26℃.

4. The method for preparing and purifying cefuroxime sodium according to claim 1, characterized in that, In step S3, the mass ratio of ethanol to acetone in the ethanol-acetone mixed solution is 1:(0.9~1.1).

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