Method for recovering the active ingredient as a whole from the crystallization acetone mother liquor of ceftriaxone sodium
By recovering the solvent and active ingredients from the acetone mother liquor of ceftriaxone sodium crystallization using distillation and nanofiltration concentration technologies, the problems of environmental pollution and resource waste have been solved, achieving efficient resource recovery and environmental protection goals.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SHANXI WEIQIDA PHARMA IND
- Filing Date
- 2023-06-05
- Publication Date
- 2026-05-15
AI Technical Summary
During the production of ceftriaxone sodium, the solvent, residual ceftriaxone sodium, triethylamine, and sodium acetate in the acetone mother liquor from crystallization were not effectively recovered, resulting in environmental pollution and resource waste.
The solvent, triethylamine acetate, and ceftriaxone sodium in the acetone mother liquor were recovered by distillation, nanofiltration concentration, and crystallization. Effective separation and recovery were achieved by adjusting the pH value and using nanofiltration membranes with different molecular weights.
It achieves the overall recycling of solvents, residual ceftriaxone sodium and sodium acetate, reduces pollution from organic matter and salts, meets environmental protection requirements, and improves production yield.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical technology and relates to a method for the overall recovery of active ingredients in the acetone mother liquor of ceftriaxone sodium crystallization, which can realize the overall recovery and utilization of solvent, residual ceftriaxone sodium, triethylamine and sodium acetate in the mother liquor. Background Technology
[0002] Ceftriaxone sodium, chemically named (6R,7R)-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thio-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid disodium salt trihexahydrate, has the following structural formula:
[0003]
[0004] Ceftriaxone sodium is a third-generation cephalosporin antibiotic with broad-spectrum and high efficacy. It is used for diseases caused by susceptible pathogens, such as urinary tract infections, biliary tract infections, lower respiratory tract infections, pelvic infections, abdominal infections, bone and joint infections, skin and soft tissue infections, sepsis, and meningitis.
[0005] The main method for producing ceftriaxone sodium is as follows: 7-ACA is used as the main raw material and condensed with triazine to generate 7-ACT intermediate. 7-ACT and AE active ester undergo a condensation reaction in a methanol-dichloromethane system catalyzed by triethylamine, while 2-mercaptobenzothiazole (M) is produced as a byproduct. Water and sodium acetate are added to the reaction solution to carry out the salt formation reaction of ceftriaxone sodium. After standing and separating the layers, the aqueous layer undergoes the crystallization process of ceftriaxone sodium, and the organic layer is the dichloromethane mother liquor, in which the main components are M 3wt%~5wt%, triethylamine 3wt%~4wt%, dichloromethane 91wt%~94wt%, and impurities. In this phase separation process, byproduct M, 40% of the triethylamine in the feed, and most organic impurities can be carried away through the organic phase, i.e., the dichloromethane mother liquor. The aqueous phase is crystallized by adding alcohol as a dispersant and then adding acetone to obtain ceftriaxone sodium product. Therefore, the ceftriaxone sodium obtained in this way has low impurity content, high purity, and a molar yield of ceftriaxone sodium of approximately 92.5%-94%.
[0006] In the aforementioned production process of ceftriaxone sodium, two main types of waste liquid are generated: First, the organic layer after settling and stratification, which is the dichloromethane mother liquor. The applicant's Chinese patent CN109053627B, "Comprehensive Recovery Method of 2-Mercaptobenzothiazole, Triethylamine, and Dichloromethane from Ceftriaxone Sodium Dichloromethane Mother Liquor," can achieve comprehensive recovery of 2-mercaptobenzothiazole, triethylamine, and dichloromethane, maximizing the recovery and utilization of organic matter and reducing environmental pollution. Second, acetone is added to the aqueous phase for crystallization. The crystallization mother liquor after separating ceftriaxone sodium mainly contains 80-85% acetone. The mother liquor contains 5-8% v / v of methanol and 8-10% v / v of water (based on all solvents), approximately 7-9 g / L of triethylamine acetate, approximately 2-3 g / L of sodium acetate, and approximately 1-1.5 g / L of ceftriaxone sodium. The residual ceftriaxone sodium accounts for approximately 3% of the total ceftriaxone sodium product. The mother liquor is generally treated by simple atmospheric distillation to recover acetone and methanol solvents. The recovered residue is discharged into the sewage system as saline wastewater. Therefore, the acetate, triethylamine, and residual ceftriaxone sodium in the mother liquor pollute the environment, causing harm and waste.
[0007] As the country intensifies its efforts in environmental governance to improve environmental quality, people's environmental awareness is also increasing. Therefore, it is necessary to conduct in-depth research and treatment on the acetone mother liquor of ceftriaxone sodium crystallization in order to achieve the overall recovery and utilization of solvents, residual ceftriaxone sodium, triethylamine, and sodium acetate in the mother liquor, maximize the recovery and utilization of organic matter, and reduce organic pollution of the environment. Summary of the Invention
[0008] Therefore, the purpose of this invention is to provide a method for the overall recovery of the active ingredients in the acetone mother liquor of ceftriaxone sodium crystallization, which can realize the overall recovery and utilization of solvent, residual ceftriaxone sodium, triethylamine and sodium acetate in the mother liquor, maximize the recovery and utilization of organic matter and salt, and reduce the environmental pollution caused by organic matter and salt.
[0009] To address the aforementioned technical problems of this invention, this invention provides a method for the overall recovery of active ingredients from the acetone mother liquor of ceftriaxone sodium crystallization, the method comprising the following steps:
[0010] (1) Recovering solvent
[0011] The acetone mother liquor from ceftriaxone sodium crystallization was distilled to recover a mixed solvent of methanol and acetone.
[0012] (2) Recovery of triethylamine
[0013] The mother liquor from step (1) above, after solvent removal, is filtered to obtain a clear filtrate and triethylamine acetate solid. The clear filtrate is then concentrated by nanofiltration using a nanofiltration membrane with a molecular weight cutoff of 200-300 Daltons to obtain a primary nanofiltration concentrate and a primary nanofiltration dilute solution. The triethylamine acetate solid obtained above is added to the primary nanofiltration dilute solution, and the pH is adjusted to 12-13 using sodium hydroxide to dissolve the triethylamine acetate. The solution is then distilled to collect crude triethylamine and an aqueous solution of sodium acetate alkaline solution after removing triethylamine.
[0014] (3) Recovery of sodium acetate
[0015] The pH of the sodium acetate alkaline aqueous solution obtained in step (2) above was adjusted to 8.5-9.2 using acetic acid, and then evaporated and concentrated to obtain sodium acetate.
[0016] (4) Recovery of ceftriaxone sodium
[0017] Add 0.5 to 2.5 times the volume of water to the primary nanofiltration concentrate obtained in step (2) above, and then use a nanofiltration membrane with a molecular weight cutoff of 400 to 800 Daltons to concentrate the dilution by nanofiltration. Repeat this process once or more to collect secondary nanofiltration concentrate and secondary nanofiltration dilution, wherein the ceftriaxone sodium content in the secondary nanofiltration concentrate is less than 5 mg / ml.
[0018] Then, the obtained secondary nanofiltration solution was concentrated to the minimum volume using a nanofiltration membrane with a molecular weight cutoff of 150-200 Daltons to obtain a concentrated ceftriaxone sodium solution. 0.5-1.2 times the volume of dichloromethane was added to the solution for washing and phase separation to obtain an aqueous phase. Acetone was added to the aqueous phase for crystallization to obtain ceftriaxone sodium crystals.
[0019] The following describes in more detail the method for the overall recovery of the active ingredient in the acetone mother liquor of ceftriaxone sodium crystallization according to the present invention.
[0020] In step (1) of solvent recovery, the acetone mother liquor of ceftriaxone sodium crystals is distilled to recover a mixed solvent of methanol and acetone.
[0021] As described above, the acetone mother liquor for ceftriaxone sodium crystallization is obtained as follows: 7-ACT and AE active ester undergo a condensation reaction catalyzed by triethylamine in a methanol-dichloromethane system, with the byproduct 2-mercaptobenzothiazole (M) as a byproduct; water and sodium acetate are added to the reaction solution to carry out the salt formation reaction of ceftriaxone sodium, and the mixture is allowed to stand and separate into layers. The aqueous layer is separated, methanol is added as a dispersant and acetone is added to the aqueous phase to carry out ceftriaxone sodium crystallization. After separating the ceftriaxone sodium crystals, the acetone mother liquor for ceftriaxone sodium crystallization is obtained, wherein the pH is generally 8-8.7, and based on the total solvent, it contains 80%-85% (v / v) acetone, 5%-8% (v / v) methanol and 8%-10% (v / v) water. The mother liquor contains about 7-9 g / L of triethylamine acetate, about 2-3 g / L of sodium acetate and about 1-1.5 g / L of ceftriaxone sodium.
[0022] First, the pH of the acetone mother liquor from ceftriaxone sodium crystallization is adjusted to neutral using acetic acid, for example, to pH 7. Then, the acetone mother liquor from ceftriaxone sodium crystallization is distilled to recover the mixed solvent of methanol and acetone. Preferably, vacuum distillation is performed, with the distillation temperature controlled at 35℃~50℃ and the pressure at -0.080~-0.085MPa. The mixed solvent of methanol and acetone in the mother liquor is distilled off to recover the mixed solvent of methanol and acetone. This mixed solvent can be separated into finished methanol and acetone by conventional water extraction distillation, which can be reused in the production of ceftriaxone sodium. At the same time, the mother liquor after removing the solvent is collected.
[0023] In step (2) of recovering triethylamine, the mother liquor from step (1) to which the solvent was removed is filtered to obtain a clear filtrate and triethylamine acetate solid. Then, the clear filtrate is concentrated by nanofiltration using a nanofiltration membrane with a molecular weight cutoff of 200-300 Daltons to obtain a primary nanofiltration concentrate and a primary nanofiltration dilute solution. The obtained triethylamine acetate solid is added to the primary nanofiltration dilute solution, and the pH is adjusted to 12-13 using sodium hydroxide to dissolve the triethylamine acetate. The solution is then distilled to collect crude triethylamine and an aqueous solution of sodium acetate alkaline solution from which triethylamine has been removed.
[0024] In this process, the mother liquor from step (1) after solvent removal is filtered through a 0.45 μm filter membrane to obtain a clear filtrate and triethylamine acetate solid. Then, the clear filtrate is concentrated using a nanofiltration membrane with a molecular weight cutoff of 200–300 Daltons. When the nanofiltration concentration reaches its minimum volume, water (0.8–1.2 times the volume of the concentrated liquid) is added to the concentrate, and nanofiltration concentration is continued. This process of adding water and concentration can be repeated 1–2 times as needed to obtain a first-stage nanofiltration concentrate and a first-stage nanofiltration dilute solution. During the nanofiltration concentration process, the membrane pressure is controlled at 2.0–2.5 MPa, and the temperature is <25°C, for example, approximately 20°C. During the first-stage nanofiltration concentration, triethylamine acetate and sodium acetate are dialyzed into the nanofiltration dilute solution, while ceftriaxone sodium is retained in the nanofiltration concentrate, thus achieving the separation of ceftriaxone sodium from triethylamine acetate and sodium acetate.
[0025] Then, the obtained triethylamine acetate solid was added to the dilute nanofiltration solution, and the pH was adjusted to 12-13 using sodium hydroxide to dissolve the triethylamine acetate. The solution was then subjected to atmospheric distillation at 80-100°C to collect crude triethylamine and a sodium acetate alkaline aqueous solution from which triethylamine was removed. The collected crude triethylamine contains a high water content and can be subjected to phase separation at 30-60°C (triethylamine has low solubility in water at this temperature) to obtain an upper layer of triethylamine and a lower layer of water. The separated upper layer of triethylamine can be further recovered by distillation.
[0026] In step (3) to recover sodium acetate, acetic acid is used to adjust the pH of the sodium acetate alkaline aqueous solution obtained in step (2) to 8.5-9.2, which is then evaporated and concentrated to a solution density of 1.2-1.24 g / ml, cooled to below 35°C to crystallize, and dried to obtain sodium acetate.
[0027] In step (4) of recovering ceftriaxone sodium, 0.5 to 2.5 times the volume of water is added to the primary nanofiltration concentrate obtained in step (2). Then, the diluent is concentrated using a nanofiltration membrane with a molecular weight cutoff of 400 to 800 Daltons, preferably 600 to 800 Daltons. This process mainly serves as dialysis decolorization and can be repeated once or multiple times to obtain secondary nanofiltration concentrate and secondary nanofiltration dilute solution, wherein the ceftriaxone sodium content in the secondary nanofiltration concentrate is less than 5 mg / ml. During the nanofiltration concentration process, the membrane pressure is controlled at 2.0 to 2.5 MPa, and the temperature is <25°C.
[0028] Then, the obtained secondary nanofiltration solution is concentrated to the minimum volume using a nanofiltration membrane with a molecular weight cutoff of 150-200 Daltons to obtain a ceftriaxone sodium concentrate. 0.5-1.2 times the volume of dichloromethane is added to the concentrate for washing and phase separation to obtain an aqueous phase. Acetone is added to this aqueous phase for crystallization. After filtration and drying, ceftriaxone sodium crystals are obtained with a content >92%, a purity of 99.3%-99.6%, and a color <4. Further purification can be carried out as needed.
[0029] After the above process, the final secondary nanofiltration concentrate is only 1%-2% of the volume of the acetone mother liquor from ceftriaxone sodium crystallization before treatment, minimizing pollutants. This secondary nanofiltration concentrate can be discharged into wastewater treatment.
[0030] Beneficial effects
[0031] The present invention provides a method for the overall recovery of active ingredients in the acetone mother liquor from ceftriaxone sodium crystallization. This method can achieve the overall recovery and utilization of solvent, residual ceftriaxone sodium, triethylamine, and sodium acetate in the mother liquor, maximize the recovery and utilization of organic matter and salt, reduce the pollution of the environment by organic matter and salt, thereby meeting the national requirements for environmental governance and minimizing pollutants. Detailed Implementation
[0032] The following examples illustrate the overall recovery method of the active ingredient in the acetone mother liquor of ceftriaxone sodium crystallization according to the present invention in more detail, but the scope of protection of the present invention is not limited to these examples.
[0033] Example 1
[0034] (1) Recovering solvent
[0035] Take 50L of acetone mother liquor from ceftriaxone sodium crystallization, which has a pH of 8.6 and mainly contains 84% v / v acetone, 6% v / v methanol, and 10% v / v water (based on all solvents), approximately 8g / L of triethylamine acetate, 3g / L of sodium acetate, and 1.19g / L of ceftriaxone sodium.
[0036] The pH of the mother liquor from the acetone crystallization of ceftriaxone sodium was adjusted to 7 with acetic acid. Then, vacuum distillation was carried out at -0.085 MPa and 35°C. The distillation temperature was then continuously increased to 45°C to distill off the mixed solvent of methanol and acetone in the mother liquor. 3.2 L of mother liquor with the solvent removed was collected.
[0037] (2) Recovery of triethylamine
[0038] The mother liquor from step (1) was filtered using a 0.45 μm filter membrane to obtain 3.2 L of clear filtrate and 6 g of triethylamine acetate solid.
[0039] Then, a nanofiltration membrane with a molecular weight cutoff of 200 Daltons was used, with the membrane pressure controlled at 2.3 MPa and the temperature at 20°C. The obtained clarified filtrate was concentrated by nanofiltration. When the nanofiltration concentration reached the minimum volume, 1 L of water was added to the concentrate, and nanofiltration concentration was continued. This process of adding water and concentration was repeated once to obtain 0.9 L of concentrated nanofiltration solution and 4.3 L of diluted nanofiltration solution.
[0040] Add 6g of the obtained triethylamine acetate solid to 4.3L of primary nanofiltration dilute solution, adjust the pH to 12.5 with sodium hydroxide, dissolve the triethylamine acetate, and gradually raise the temperature from 82℃ to 95℃ for atmospheric distillation. Collect 0.6L of crude triethylamine and 3.6L of sodium acetate alkaline aqueous solution with triethylamine removed.
[0041] The collected crude triethylamine, containing 73% (v / v) triethylamine, was subjected to phase separation treatment at 35°C to obtain 0.45 L of upper triethylamine.
[0042] (3) Recover sodium acetate
[0043] The pH of 3.6 L of the sodium acetate alkaline aqueous solution obtained in step (2) above was adjusted to 9.2 using acetic acid, and then the solution was heated and distilled until the liquid density was 1.21 g / cm³. 3 When heating was stopped, 145 ml of concentrated solution was obtained. The solution was cooled to 35 °C to crystallize and dried at 120 °C for 5 h to obtain 276.5 g of sodium acetate.
[0044] (4) Recovery of ceftriaxone sodium
[0045] Add 1L of reverse osmosis water to 0.9L of the primary nanofiltration concentrate obtained in step (2) above, and then concentrate the diluted solution using a nanofiltration membrane with a molecular weight cutoff of 800 Daltons. After concentrating to the minimum volume of concentrate, add 2L of reverse osmosis water to the nanofiltration concentrate and continue concentrating to the minimum volume of concentrate. Collect 0.7L of secondary nanofiltration concentrate and 3.2L of secondary nanofiltration dilute solution, wherein the ceftriaxone sodium content in the secondary nanofiltration concentrate is approximately 4.5mg / ml. During the nanofiltration concentration process, the membrane pressure is controlled at 2.3MPa and the temperature at 20℃.
[0046] Then, the obtained secondary nanofiltration solution was concentrated to the minimum volume using a nanofiltration membrane with a molecular weight cutoff of 150 Daltons, yielding 0.6 L of ceftriaxone sodium concentrate. 0.4 L of dichloromethane was added to this concentrate for washing and phase separation, resulting in an aqueous phase. 4 L of acetone was added to this aqueous phase for crystallization. After filtration and drying, 46 g of ceftriaxone sodium crystals were obtained, with a content of 92.4% and a purity of 99.3%. The yield was 46 ÷ (50 * 1.19) = 77%, which can increase the production yield by 77% × 3% = 2.3%.
[0047] Example 2
[0048] (1) Recovering solvent
[0049] Take 50L of acetone mother liquor from ceftriaxone sodium crystallization, which has a pH of 8.6 and mainly contains 84% v / v acetone, 6% v / v methanol, and 10% v / v water (based on all solvents), approximately 8g / L of triethylamine acetate, 3g / L of sodium acetate, and 1.19g / L of ceftriaxone sodium.
[0050] The pH of the acetone mother liquor from ceftriaxone sodium crystallization was adjusted to 7 with acetic acid. Then, vacuum distillation was carried out at -0.085 MPa and 35°C. The distillation temperature was then continuously increased to 43°C to distill off the mixed solvent of methanol and acetone in the mother liquor. 3.6 L of the solvent-free mother liquor was collected.
[0051] (2) Recovery of triethylamine
[0052] The mother liquor from step (1) was filtered using a 0.45 μm filter membrane to obtain 3.55 L of clear filtrate and 5.6 g of triethylamine acetate solid.
[0053] Then, a nanofiltration membrane with a molecular weight cutoff of 200 Daltons was used, with the membrane pressure controlled at 2.3 MPa and the temperature at 18°C. The obtained clarified filtrate was concentrated by nanofiltration. When the nanofiltration concentration reached the minimum volume, 1 L of water was added to the concentrate, and nanofiltration concentration was continued. This process of adding water and concentration was repeated twice to obtain 1.05 L of concentrated nanofiltration solution and 5.5 L of diluted nanofiltration solution.
[0054] 5.6 g of the obtained triethylamine acetate solid was added to 5.5 L of primary nanofiltration dilute solution. The pH was adjusted to 12.5 with sodium hydroxide to dissolve the triethylamine acetate. The temperature was gradually increased from 82 °C to 95 °C and distilled at atmospheric pressure. 0.7 L of crude triethylamine and 4.65 L of sodium acetate alkaline aqueous solution with triethylamine removed were collected.
[0055] The collected crude triethylamine, containing 72% (v / v) triethylamine, was subjected to phase separation at 40°C to obtain 425 mL of upper triethylamine.
[0056] (3) Recover sodium acetate
[0057] The pH of 4.65 L of the sodium acetate alkaline aqueous solution obtained in step (2) above was adjusted to 8.5 using acetic acid, and then distilled at a temperature until the liquid density reached 1.20 g / cm³. 3 Stop heating, cool to 35℃ for crystallization, and dry at 120℃ for 5 hours to obtain 296.3g of sodium acetate.
[0058] (4) Recovery of ceftriaxone sodium
[0059] Add 1L of reverse osmosis water to 1.05L of the primary nanofiltration concentrate obtained in step (2) above, and then concentrate the diluted solution using a nanofiltration membrane with a molecular weight cutoff of 600 Daltons. After concentrating to the minimum volume of concentrate, add 2L of reverse osmosis water to the nanofiltration concentrate and continue concentrating to the minimum volume of concentrate. Collect 0.48L of secondary nanofiltration concentrate and 3.55L of secondary nanofiltration dilute solution, wherein the ceftriaxone sodium content in the secondary nanofiltration concentrate is approximately 4.9mg / ml. During the nanofiltration concentration process, the membrane pressure is controlled at 2.5MPa and the temperature at 20℃.
[0060] Then, the obtained secondary nanofiltration solution was concentrated to the minimum volume using a nanofiltration membrane with a molecular weight cutoff of 150 Daltons, yielding 0.75 L of ceftriaxone sodium concentrate. 0.75 L of dichloromethane was added to this concentrate for washing and phase separation, resulting in an aqueous phase. 5.8 L of acetone was added to this aqueous phase for crystallization. After filtration and drying, 41.6 g of ceftriaxone sodium crystals were obtained, with a content of 92.8% and a purity of 99.6%. The yield was 41.6 ÷ (50 * 1.19) = 69.9%, which can increase the production yield by 69.9% × 3% = 2.09%.
Claims
1. A method for the overall recovery of active ingredients from acetone mother liquor of ceftriaxone sodium crystallization, the method comprising the following steps: (1) Recovering solvent The acetone mother liquor from ceftriaxone sodium crystallization was distilled to recover a mixed solvent of methanol and acetone. (2) Recovery of triethylamine The mother liquor from step (1) above, after solvent removal, is filtered to obtain a clear filtrate and triethylamine acetate solid. The clear filtrate is then concentrated by nanofiltration using a nanofiltration membrane with a molecular weight cutoff of 200-300 Daltons to obtain a primary nanofiltration concentrate and a primary nanofiltration dilute solution. The triethylamine acetate solid obtained above is added to the primary nanofiltration dilute solution, and the pH is adjusted to 12-13 using sodium hydroxide to dissolve the triethylamine acetate. The solution is then distilled to collect crude triethylamine and an aqueous solution of sodium acetate alkaline solution after removing triethylamine. (3) Recover sodium acetate The pH of the sodium acetate alkaline aqueous solution obtained in step (2) above was adjusted to 8.5-9.2 using acetic acid, and then evaporated and concentrated to obtain sodium acetate. (4) Recovery of ceftriaxone sodium Add 0.5 to 2.5 times the volume of water to the primary nanofiltration concentrate obtained in step (2) above, and then use a nanofiltration membrane with a molecular weight cutoff of 600 to 800 Daltons to concentrate the dilution by nanofiltration. Repeat this process once or more to collect secondary nanofiltration concentrate and secondary nanofiltration dilution, wherein the ceftriaxone sodium content in the secondary nanofiltration concentrate is less than 5 mg / ml. The secondary nanofiltration solution obtained above was then concentrated to a minimum volume using a nanofiltration membrane with a molecular weight cutoff of 150–200 Daltons, yielding a concentrated ceftriaxone sodium solution. This solution was then washed and separated with 0.5–1.2 times its volume of dichloromethane to obtain an aqueous phase. Acetone was added to this aqueous phase to induce crystallization, yielding ceftriaxone sodium crystals. in, The pH of the acetone mother liquor for ceftriaxone sodium crystallization is 8–8.7; based on the total solvent, it contains 80%–85% acetone, 5%–8% methanol, and 8%–10% water, by volume percentage; the acetone mother liquor for ceftriaxone sodium crystallization contains 7–9 g / L triethylamine acetate, 2–3 g / L sodium acetate, and 1–1.5 g / L ceftriaxone sodium. In step (1) of solvent recovery, the pH of the acetone mother liquor of ceftriaxone sodium crystallization is adjusted to neutral with acetic acid, and then the acetone mother liquor of ceftriaxone sodium crystallization is subjected to vacuum distillation, with the distillation temperature controlled at 35℃~50℃ and the pressure at -0.080~-0.085MPa.
2. The overall recycling method according to claim 1, characterized in that, in In step (2) to recover triethylamine, the mother liquor from step (1) to which the solvent was removed is filtered through a 0.45 μm filter membrane to obtain a clear filtrate and triethylamine acetate solid.
3. The overall recycling method according to claim 1, characterized in that, in In step (2) of recovering triethylamine, the obtained clarified filtrate is concentrated by nanofiltration using a nanofiltration membrane with a molecular weight cutoff of 200-300 Daltons. When the nanofiltration concentration reaches the minimum volume, water with a volume of 0.8-1.2 times the concentration is added to the concentrate, and nanofiltration concentration is continued. The water addition and concentration can be repeated 1-2 times as needed to obtain a nanofiltration concentrate and a nanofiltration dilute solution. During the nanofiltration concentration process, the membrane pressure is controlled at 2.0-2.5 MPa and the temperature is <25℃.
4. The overall recycling method according to claim 1, characterized in that, in In step (2) of recovering triethylamine, the collected crude triethylamine is subjected to phase separation treatment at 30℃~60℃ to obtain upper triethylamine and lower water.
5. The overall recycling method according to claim 1, characterized in that, in In step (3) to recover sodium acetate, the pH value of the sodium acetate alkaline aqueous solution obtained in step (2) is adjusted to 8.5-9.2 using acetic acid, and then evaporated and concentrated to a solution density of 1.2-1.24 g / ml. The solution is then cooled to below 35°C to crystallize and dried to obtain sodium acetate.
6. The overall recycling method according to claim 1, characterized in that, in In step (4), during the recovery of ceftriaxone sodium, the membrane pressure is controlled at 2.0-2.5 MPa and the temperature is <25℃ during nanofiltration concentration.
7. The overall recycling method according to claim 1, characterized in that, in In step (4), the recovered ceftriaxone sodium solution is concentrated to a minimum volume using a nanofiltration membrane with a molecular weight cutoff of 150-200 Daltons to obtain a concentrated ceftriaxone sodium solution. 0.5-1.2 times the volume of dichloromethane is added to the solution for washing and phase separation to obtain an aqueous phase. Acetone is added to this aqueous phase for crystallization. After filtration and drying, ceftriaxone sodium crystals are obtained, with a content >92%, purity 99.3%-99.6%, and color <4.