Process for nanofiltration treatment of doxycycline hydrochloride methanol mother liquor

Abstract

The application discloses a kind of doxycycline hydrochloride methyl alcohol mother liquor's nanofiltration processing technology, it is related to the processing field of methyl alcohol mother liquor.It includes the following steps: S1, methyl alcohol mother liquor nanofiltration processing: methyl alcohol mother liquor is pumped into nanofiltration membrane system by high-pressure pump, and is divided into supernatant and concentrated solution;S2, concentrated solution separation: concentrated solution is fed into distillation equipment, and concentrated solution condensate is obtained;S3, supernatant is fed into distillation equipment, and supernatant condensate and supernatant still residue are separated;S4, concentrated solution condensate and supernatant condensate recovery: condensate is combined and rectified, and methyl alcohol recovery and column residue are obtained;S5, supernatant still residue crystallization centrifugation: supernatant still residue is crystallized by adding water, and centrifugal washing separates centrifugal mother liquor and fever ice recovery;S6, centrifugal mother liquor reuse: centrifugal mother liquor is adjusted by adding water, and repeated crystallization centrifugation is carried out.The beneficial effects of the application are: through the combination process of nanofiltration pretreatment, distillation rectification and crystallization centrifugation, efficient recovery of methyl alcohol and fever ice is realized, resource utilization is improved, the amount of hazardous waste is significantly reduced, and environmental protection and economy are considered.

Description

Technical Field

[0001] This invention belongs to the field of methanol mother liquor treatment, specifically relating to a nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor. Background Technology

[0002] Doxycycline hydrochloride, a broad-spectrum antibiotic, is widely used in pharmaceuticals, animal husbandry, and other fields. Its production process often uses methanol as a reaction solvent, crystallization solvent, or washing solvent, resulting in a large amount of doxycycline hydrochloride methanol mother liquor. This mother liquor not only contains incompletely recovered methanol but is also rich in antipyretic ice (a key intermediate or product of doxycycline hydrochloride). Direct discharge or simple treatment would cause serious resource waste and environmental pollution.

[0003] The existing traditional treatment process for methanol mother liquor from antibiotic production in China involves a two-step process of distillation and rectification: first, gaseous methanol is separated from the mother liquor through distillation, and then purified by rectification for methanol reuse; the remaining liquid mixture contains a large amount of production decomposition products, making it impossible to effectively separate target products such as reflux icing, and can only be collected and disposed of as hazardous waste. This traditional process has significant limitations: on the one hand, it can only recover methanol resources, while components with recovery value such as reflux icing become hazardous waste with the residual liquid, resulting in low resource utilization and economic losses; on the other hand, the generation of large amounts of hazardous waste not only increases the company's hazardous waste storage, transportation, and disposal costs, but also poses potential environmental risks, which is inconsistent with the current industrial development trend of energy conservation, environmental protection, and resource recycling. In addition, the traditional process does not design a precise separation scheme for the component characteristics of doxycycline hydrochloride methanol mother liquor, resulting in low separation efficiency of methanol and reflux icing, and it cannot solve the impact of impurity accumulation on product recovery, making it difficult to meet the core requirements of "high-efficiency recovery and low waste discharge" in industrial production. Summary of the Invention

[0004] The technical problem to be solved by this invention is to provide a nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor, addressing the aforementioned technical deficiencies. Through a combination of nanofiltration pretreatment, distillation, and crystallization centrifugation, the synergistic and efficient recovery of methanol and deheating ice is achieved, significantly improving resource utilization while substantially reducing hazardous waste generation, thus balancing environmental friendliness and economic efficiency.

[0005] The technical solution adopted in this invention is: to provide a nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor, comprising the following steps: S1. Methanol Mother Liquor Nanofiltration Treatment: The methanol mother liquor containing doxycycline hydrochloride is stored as the raw liquid in the raw liquid tank of the nanofiltration treatment process. The raw liquid is pressurized and transported to the nanofiltration membrane system by a high-pressure pump. The raw liquid is separated under the retention of the nanofiltration membrane. The clear liquid is collected in the clear liquid tank, and the concentrated liquid retained by the nanofiltration membrane is temporarily stored in the concentrated liquid tank. S2. Concentrate separation: The concentrate temporarily stored in the concentrate tank is sent to the distillation equipment, and the azeotropic vapor and concentrate residue are separated by distillation; the separated azeotropic vapor is condensed to obtain concentrate condensate; S3. Clear liquid separation: The clear liquid collected in the clear liquid tank is sent to the distillation equipment, and the azeotropic vapor and clear liquid residue are separated by distillation. S4. Concentrated liquid condensate and clear liquid condensate recovery: The concentrated liquid condensate and clear liquid condensate are sent to a distillation unit for distillation treatment to separate methanol recovery product and tower residue; S5. Residual crystallization centrifugation of clear liquid vessel: The separated residual liquid vessel is sent to the crystallization equipment, and process water is added to adjust the system environment. After crystallization is completed, the crystallized mixture is sent to the centrifugation equipment, and process water is added again. The centrifugation operation is used to separate the centrifugation mother liquor and the deheating ice recovery product. S6. Centrifugal Mother Liquor Reuse: The centrifugal mother liquor obtained from the centrifugation operation is sent to the crystallization equipment, and after the process water is added back to adjust the system environment, it is sent back to the centrifugation equipment to participate in the centrifugation operation, thus recycling the centrifugal mother liquor.

[0006] To further optimize this technical solution, in step S1, the methanol mother liquor is separated by a nanofiltration membrane system to obtain a 95.0%-95.5% clear liquid and a 4.5%-4.8% concentrated liquid. The methanol mother liquor includes 0.40%-0.45% by-reaction products and impurities, 4.60%-4.65% reflux hydrate, 0.08%-0.10% ammonium chloride, 93.5%-93.7% methanol, and 1.25%-1.30% water. The clear liquid after nanofiltration separation... The fractional solution comprises 0.04%-0.06% by-reaction products and impurities, 4.55%-4.65% refrigeration ice, 0.05%-0.07% ammonium chloride, 93.9%-94.2% methanol, and 1.25%-1.30% water; the concentrated solution comprises 7.8%-8.2% by-reaction products and impurities, 5.0%-5.3% refrigeration ice, 0.7%-0.8% ammonium chloride, 84.3%-84.8% methanol, and 1.4%-1.5% water.

[0007] To further optimize this technical solution, in step S2, the concentrated liquid is distilled to obtain 85.0%-85.5% concentrated liquid condensate and 14.5%-15.0% concentrated liquid residue. The concentrated liquid condensate consists of 98.8%-99.2% methanol, 0.8%-0.9% water, and 0.10%-0.15% ammonium chloride. The concentrated liquid residue consists of 55.0%-55.5% by-reaction products and impurities, 35.0%-35.8% reflux icing, 4.2%-4.5% ammonium chloride, and 4.8%-5.0% water.

[0008] To further optimize this technical solution, the concentrated liquid residue is collected separately and disposed of professionally in accordance with hazardous waste treatment regulations.

[0009] To further optimize this technical solution, in step S3, the clarified liquid is distilled to obtain 94.5%-95.0% clarified liquid condensate and 5.0%-5.5% clarified liquid residue. The clarified liquid condensate consists of 99.2%-99.5% methanol, 0.6%-0.7% water, and 0.005%-0.015% ammonium chloride. The clarified liquid residue consists of 0.8%-1.0% by-reaction products and impurities, 86.0%-86.5% reflux icing, 0.8%-1.0% ammonium chloride, and 11.5%-12.5% ​​water.

[0010] To further optimize this technical solution, in step S4, after the concentrated liquid condensate and the clear liquid condensate are separated by distillation, 99.4%-99.5% methanol recovery product and 0.5%-0.6% tower residue are obtained; the methanol recovery product is 99.8%-99.9% methanol and 0.1%-0.2% water; the tower residue recovery product is 0.5%-0.6% methanol, 96.5%-97.0% water and 2.5%-2.8% ammonium chloride.

[0011] To further optimize this technical solution, in step S5, the residual crystallizer in the clearing vessel is centrifuged to obtain 26.0%-26.5% of the centrifugal mother liquor and 73.5%-74.0% of the deheating ice recovery product; the centrifugal mother liquor contains 0.4%-0.5% of by-reaction products and impurities, 2.5%-2.8% of ammonium chloride, 96.5%-97.0% of water and 0.15%-0.20% of deheating ice; the deheating ice recovery product contains 0.7%-0.9% of by-reaction products and impurities, 89.5%-90.5% of deheating ice and 9.0%-9.2% of water.

[0012] To further optimize this technical solution, in step S6, the number of times the centrifuged mother liquor is reused does not exceed 12, and the centrifuged mother liquor exceeding the number of reuses is treated as wastewater.

[0013] To further optimize this technical solution, in step S1, pressure gauges are installed at the outlet of the high-pressure pump and the inlet and outlet pipes of the nanofiltration membrane, and a flow meter is installed in the feed pipe of the clear liquid tank.

[0014] To further optimize this technical solution, in steps S4 and S5, the process water is primary water.

[0015] The beneficial effects of this invention are as follows: By introducing a nanofiltration pretreatment process and utilizing a nanofiltration membrane system with a specific molecular weight cutoff, most of the by-reaction impurities and ammonium chloride in the mother liquor are precisely retained, purifying the vast majority of the clarified liquid. Simultaneously, the deheating ice and residual impurities are concentrated in a small proportion of the concentrated liquid, constructing a core process architecture of "graded separation and precise enrichment," laying the foundation for subsequent resource recovery. Furthermore, methanol is specifically recovered through distillation and defraction, and deheating ice is precisely recovered through crystallization centrifugation, achieving the synergistic recovery of the two core components and completely changing the limitation of traditional processes that only recover methanol. At the same time, nanofiltration concentration concentrates impurities in a small amount of concentrated liquid residue, and combined with multiple reuses of the mother liquor by centrifugation to further extract residual components, significantly reducing the amount of hazardous waste generated. This approach balances resource utilization, environmental friendliness, and economic efficiency, with overall performance far exceeding that of traditional processes. Attached Figure Description

[0016] Figure 1 This is a flowchart of the nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to the present invention. Figure 2 This is a structural diagram of the nanofiltration treatment of doxycycline hydrochloride methanol mother liquor according to the present invention; Figure 3 The flowchart shows a conventional treatment process for doxycycline hydrochloride methanol mother liquor, which is a comparative example of the present invention. Figure 4 This is a material balance table for the nanofiltration treatment process of doxycycline hydrochloride methanol mother liquor according to Embodiment 1 of the present invention. Figure 5 This is a material balance table for the nanofiltration treatment process of doxycycline hydrochloride methanol mother liquor in Example 2 of the present invention. Figure 6 This is a material balance table for the nanofiltration treatment process of doxycycline hydrochloride methanol mother liquor in Example 3 of the present invention. Figure 7 This is a material balance table for the conventional treatment process of doxycycline hydrochloride methanol mother liquor, which is a comparative example of the present invention. Detailed Implementation

[0017] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments. Example 1

[0018] Please see Figure 1 , Figure 2 , Figure 4 The nanofiltration treatment process for the methanol mother liquor produced during the production of doxycycline hydrochloride includes the following steps: S1. Nanofiltration Treatment of Methanol Mother Liquor: 1000 kg of doxycycline hydrochloride methanol mother liquor (composition: 0.42% by-products and impurities, 4.62% pyrrolidone, 0.09% ammonium chloride, 93.58% methanol, 1.29% water) is fed into the raw liquid tank. A high-pressure pump is started to deliver the raw liquid to the nanofiltration membrane system at a pressure of 1.2 MPa and a flow rate of 8 m³ / h. The nanofiltration membrane system has a molecular weight cutoff of 400-800 Da. Selective separation is achieved using the membrane sieving principle. The molecular weights of methanol and water molecules are much smaller than 400 Da, so they can pass through the membrane pores smoothly. Pyrrolidone molecules have a relatively small molecular weight, and most of them can also pass through the membrane. The molecular weights of doxycycline hydrochloride by-products and impurities, ammonium chloride, etc., are in the 400-800 Da range. In the nanofiltration region, molecules with larger sizes cannot pass through the membrane pores and are thus retained by the membrane. This separation yields a 95.3% clear liquid and a 4.7% concentrated liquid. The clear liquid and concentrated liquid are sent to the clear liquid tank and concentrated liquid tank, respectively. The clear liquid contains 0.05% by-reaction products and impurities, 4.59% refrigeration ice, 0.06% ammonium chloride, 94.02% methanol, and 1.28% water. The concentrated liquid contains 8.05% by-reaction products and impurities, 5.18% refrigeration ice, 0.76% ammonium chloride, 84.57% methanol, and 1.45% water. The nanofiltration membrane effectively retains most of the by-reaction impurities and ammonium chloride. S2. Concentrate Separation: The concentrate in the concentrate tank is sent to a distillation kettle. The distillation temperature is controlled at ≤105℃ and the distillation is carried out under normal pressure for 2 hours. 85.1% concentrate condensate and 14.9% concentrate kettle residue are obtained. The concentrate condensate includes 99.02% methanol, 0.85% water, and 0.13% ammonium chloride. The concentrate kettle residue includes 55.16% by-reaction products and impurities, 35.49% reflux icing, 4.40% ammonium chloride, and 4.95% water. Because the concentrate kettle residue is enriched with a large amount of difficult-to-separate by-reaction impurities, it is collected separately and entrusted to a professional organization for disposal in accordance with the hazardous waste disposal regulations to avoid environmental pollution. S3. Clear liquid separation: The clear liquid in the clear liquid tank is sent to the distillation kettle. The distillation temperature is controlled at ≤105℃ and the distillation is carried out for 3 hours under normal pressure. 94.6% clear liquid condensate and 5.4% clear liquid kettle residue are obtained. The clear liquid condensate includes 99.31% methanol, 0.68% water, and 0.01% ammonium chloride. The clear liquid kettle residue includes 0.92% by-reaction products and impurities, 86.16% refrigeration ice, 0.92% ammonium chloride, and 12.00% water. The enrichment of refrigeration ice is achieved. S4. Condensate Recovery: The concentrated liquid condensate and the clear liquid condensate are combined and fed into a distillation column. The column bottom temperature is controlled at ≤105℃ and the column top temperature at 64.5℃, with a reflux ratio of 1.5:1. After 4 hours of distillation, 99.4% methanol is recovered and 0.6% column residue is obtained. The methanol recovery includes 99.85% methanol and 0.15% water, while the column residue includes 0.53% methanol, 96.85% water, and 2.62% ammonium chloride. The methanol concentration in the methanol recovery from distillation reaches 99.85%, far exceeding the minimum purity requirement for industrial methanol reuse (usually above 98%), and the water content is only 0.15%, therefore it can be recovered. S5. Crystallization centrifugation of the clear liquid residue: The clear liquid residue is sent to the crystallization vessel, water is added once, and the solid-liquid ratio of the system is adjusted to 1:2. Then, it is cooled to room temperature for crystallization. After crystallization, the mixture is sent to a centrifuge, and water is added once for washing. After centrifugation for 15 minutes, 26.5% of the centrifugation mother liquor and 73.5% of the depyrogenated ice recovery product are obtained. The centrifugation mother liquor includes 0.43% by-reaction products and impurities, 2.68% ammonium chloride, 96.70% water, and 0.19% depyrogenated ice. The depyrogenated ice recovery product includes 0.81% by-reaction products and impurities, 90.07% depyrogenated ice, and 9.12% water. The purity of depyrogenated ice in the depyrogenated ice recovery product reaches 90.07%, and the impurity content is low. Therefore, the depyrogenated ice recovery product can also be recycled. S6. Centrifugal Mother Liquor Reuse: The centrifugal mother liquor is sent to the crystallization kettle, water is added once to adjust the system environment, and the above crystallization centrifugation operation is repeated. The number of reuses is controlled to not exceed 12 times to avoid excessive accumulation of impurities affecting the crystallization effect. In this embodiment, after 8 reuses, the impurity content in the centrifugal mother liquor meets the standard. After 2 more reuses, the impurity content is close to the critical value and is sent to the wastewater treatment system for standard treatment. Example 2

[0019] Please see Figure 1 , Figure 2 , Figure 5 The nanofiltration treatment process for the methanol mother liquor produced during the production of doxycycline hydrochloride includes the following steps: S1. Nanofiltration Treatment of Methanol Mother Liquor: 1000 kg of doxycycline hydrochloride methanol mother liquor (composition: 0.44% by-reaction products and impurities, 4.64% reflux hydrate, 0.095% ammonium chloride, 93.6% methanol, and 1.225% water) was fed into the raw liquid tank. A high-pressure pump was started to deliver the raw liquid to the nanofiltration membrane system at a pressure of 1.4 MPa and a flow rate of 20 m³ / h. The molecular weight cutoff of this system is 200-800 Da. After nanofiltration separation, a clear liquid with a content of 95.4% and a concentrated liquid with a content of 4.6% were obtained and sent to the clear liquid tank and the concentrated liquid tank, respectively. The clear liquid composition includes 0.055% by-reaction products and impurities, 4.62% reflux hydrate, 0.065% ammonium chloride, 94.1% methanol, and 1.265% water. The concentrated liquid composition includes 8.1% by-reaction products and impurities, 5.2% reflux hydrate, 0.78% ammonium chloride, 84.4% methanol, and 1.42% water. S2. Concentrate separation: The concentrate in the concentrate tank is sent to the distillation kettle. The distillation temperature is controlled at ≤105℃ and the distillation is carried out under normal pressure for 2 hours. The concentrate condensate, accounting for 85.4% of the total concentrate, and the concentrate kettle residue, accounting for 14.6% of the total concentrate, are separated. The concentrate condensate includes 99.1% methanol, 0.82% water, and 0.13% ammonium chloride. The concentrate kettle residue includes 55.3% by-reaction products and impurities, 35.6% reflux icing, 4.3% ammonium chloride, and 4.8% water. The concentrate kettle residue is sealed and collected and disposed of as hazardous waste. S3. Clear liquid separation: The clear liquid in the clear liquid tank is sent to the distillation kettle. The distillation temperature is controlled at ≤105℃ and the distillation is carried out for 3 hours under normal pressure. The clear liquid condensate with a content of 94.9% and the clear liquid kettle residue with a content of 5.3% are obtained. The clear liquid condensate includes 99.4% methanol, 0.65% water and 0.008% ammonium chloride. The clear liquid kettle residue includes 0.95% by-reaction products and impurities, 86.3% refrigeration ice, 0.9% ammonium chloride and 11.85% water. The refrigeration ice has a higher enrichment degree. S4. Condensate Recovery: The concentrated condensate and the clear condensate are combined and fed into a high-efficiency distillation column. The column bottom temperature is controlled at ≤105℃ and the column top temperature at 64℃, with a reflux ratio of 1.2:1. The distillation process lasts for 8 hours, yielding a methanol recovery product with a purity of 99.45% and a column residue with a purity of 0.55%. The methanol recovery product contains 99.88% methanol and 0.12% water, while the column residue contains 0.55% methanol, 96.9% water, and 2.6% ammonium chloride. The methanol concentration in the methanol recovery product reaches 99.88%, far exceeding the minimum purity requirement for industrial methanol reuse (usually above 98%), and the water content is only 0.12%, thus it can be recovered.

[0020] S5. Crystallization Centrifugation of Residual Liquid from Clearing Vessel: The residual liquid from the clearing vessel is sent to the crystallization vessel, water is added once, and the solid-liquid ratio of the system is adjusted to 1:1.8. Then, it is cooled to room temperature for crystallization. After crystallization, it is sent to a horizontal scraper discharge centrifuge, water is added once for washing, and centrifugation is performed for 10 minutes. The centrifugation mother liquor, accounting for 26.3%, and the deheating ice recovery product, accounting for 73.7%, are obtained. The centrifugation mother liquor includes 0.42% by-reaction products and impurities, 2.7% ammonium chloride, 96.65% water, and 0.18% deheating ice. The deheating ice recovery product includes 0.8% by-reaction products and impurities, 90.2% deheating ice, and 9.0% water. The purity of deheating ice in the deheating ice recovery product reaches 90.2%, and the impurity content is low. Therefore, the deheating ice recovery product can also be recycled.

[0021] S6. Centrifugal mother liquor reuse: The centrifugal mother liquor is sent to the crystallization kettle, water is added once to adjust the system, and the above crystallization and centrifugation operation is repeated. The reuse number is controlled to not exceed 12 times. In this embodiment, after 10 reuses, the impurity content of the centrifugal mother liquor is still stable and controllable. After 2 more reuses, it is sent to the wastewater treatment system. Example 3

[0022] Please see Figure 1 , Figure 2 , Figure 6 The nanofiltration treatment process for the methanol mother liquor produced during the production of doxycycline hydrochloride includes the following steps: S1. Nanofiltration Treatment of Methanol Mother Liquor: The doxycycline hydrochloride methanol mother liquor (composition: 0.40% by-reaction products and impurities, 4.60% reflux hydrate, 0.085% ammonium chloride, 93.5% methanol, and 1.315% water) is fed into the raw liquid tank. A high-pressure pump is started to deliver the raw liquid to the nanofiltration membrane system at a pressure of 1.0 MPa and a flow rate of 10 m³ / h. This system has a molecular weight cutoff of 400-800 Da. After nanofiltration separation, a clear liquid with a content of 95.2% and a concentrated liquid with a content of 4.8% are obtained, which are sent to the clear liquid tank and the concentrated liquid tank, respectively. The clear liquid composition includes 0.045% by-reaction products and impurities, 4.56% reflux hydrate, 0.055% ammonium chloride, 93.9% methanol, and 1.29% water. The concentrated liquid composition includes 7.9% by-reaction products and impurities, 5.05% reflux hydrate, 0.72% ammonium chloride, 84.7% methanol, and 1.43% water. S2. Concentrated liquid separation: The concentrated liquid is fed into a distillation kettle, and the distillation temperature is controlled at ≤105℃ and distilled under normal pressure for 1.5 hours to separate 85.4% of the concentrated liquid condensate and 14.6% of the concentrated liquid kettle residue. The concentrated liquid condensate includes 98.9% methanol, 0.88% water, and 0.12% ammonium chloride. The concentrated liquid kettle residue includes 55.0% by-reaction products and impurities, 35.5% reflux icing, 4.45% ammonium chloride, and 5.05% water. The concentrated liquid kettle residue is disposed of in accordance with the hazardous waste regulations. S3. Separation of the clarified liquid: The clarified liquid is fed into a distillation kettle, and distilled for 2.5 hours under normal pressure with the distillation temperature controlled at ≤105℃. 94.7% of the clarified liquid condensate and 5.3% of the clarified liquid kettle residue are obtained. The clarified liquid condensate contains 99.2% methanol, 0.69% water, and 0.012% ammonium chloride. The clarified liquid kettle residue contains 0.85% by-reaction products and impurities, 86.0% reflux reflux, 0.88% ammonium chloride, and 12.27% water. S4. Condensate Recovery: The concentrated liquid condensate and the clear liquid condensate are combined and fed into a distillation column. The column bottom temperature is controlled at ≤105℃ and the column top temperature at 64.5℃, with a reflux ratio of 0.8:1. The distillation process lasts for 3 hours, yielding a methanol recovery product with a purity of 99.4% and a column residue with a purity of 0.53%. The methanol recovery product contains 99.82% methanol and 0.18% water, while the column residue contains 0.50% methanol, 96.7% water, and 2.7% ammonium chloride. The methanol concentration in the methanol recovery product reaches 99.82%, far exceeding the minimum purity requirement for industrial methanol reuse (usually above 98%), and the water content is only 0.18%, thus it can be recovered. S5. Crystallization Centrifugation of Residual Liquid from Clearing Vessel: The residual liquid from the clearing vessel is sent to the crystallization vessel, water is added once, and the solid-liquid ratio of the system is adjusted to 1:2.2. Then, it is cooled to room temperature for crystallization. After crystallization, it is sent to a centrifuge, water is added once for washing, and centrifugation is performed for 20 minutes. The centrifugation mother liquor, accounting for 26.4%, and the deheating ice recovery product, accounting for 73.6%, are obtained. The centrifugation mother liquor includes 0.44% by-reaction products and impurities, 2.65% ammonium chloride, 96.75% water, and 0.16% deheating ice. The deheating ice recovery product includes 0.82% by-reaction products and impurities, 89.9% deheating ice, and 9.28% water. The purity of deheating ice in the deheating ice recovery product reaches 89.9%, and the impurity content is low. Therefore, the deheating ice recovery product can also be recycled.

[0023] S6. Centrifugal Mother Liquor Reuse: The centrifugal mother liquor is sent to a crystallization kettle, water is added once to adjust the system, and the above crystallization and centrifugation operation is repeated, controlling the number of reuses to not exceed 11. In this embodiment, after 9 reuses, the impurity content of the centrifugal mother liquor meets the standard, and it is reused 2 more times before being sent to the wastewater treatment system, maximizing resource utilization while ensuring the recovery effect.

[0024] Comparative Example Please see Figure 2 , Figure 7 Take the same volume and composition of doxycycline hydrochloride methanol mother liquor as in Example 1 (composition: 0.42% by-reaction products and impurities, 4.62% refrigeration ice, 0.09% ammonium chloride, 93.58% methanol, 1.29% water), temporarily store it in the stock solution tank, and then send it to the distillation kettle at a flow rate of 8 m³ / h through a transfer pump. Distillation was carried out at a temperature controlled at ≤105℃ and under normal pressure for 4 hours. Utilizing the difference in boiling points between methanol and other components, a gaseous component and a liquid residue were obtained. The gaseous component was crude methanol, comprising 93.8% methanol, 1.3% water, 0.08% ammonium chloride, a small amount of refractory ice and impurities (4.82%), which was collected after condensation. The liquid residue included 0.42% by-reaction products and impurities, 4.62% refractory ice, 0.09% ammonium chloride, 4.9% unseparated methanol, and 90.0% water. Due to the enrichment of refractory ice, impurities, and salts, the liquid residue was directly collected as hazardous waste and entrusted to a professional organization for disposal. The collected crude methanol is fed into a distillation column, with the bottom temperature controlled at ≤105℃ and the top temperature at 64℃, and the reflux ratio at 1.5:1. The distillation process lasts for 4 hours to obtain methanol recovery and distillation column residue. The methanol recovery consists of 99.2% methanol, 0.75% water, and 0.05% ammonium chloride. The distillation column residue consists of 5.2% methanol, 92.3% water, and 2.5% ammonium chloride. The methanol recovery can be recycled and disposed of, while the distillation column residue is treated as wastewater.

[0025] In summary: The traditional process in the comparative example employs a single "direct distillation and rectification" treatment mode, without pretreatment of the doxycycline hydrochloride methanol mother liquor. The mother liquor is directly fed into the distillation kettle for distillation, focusing solely on methanol recovery and completely ignoring the resource value of the defrost in the mother liquor. This results in 4.62% of the defrost in the mother liquor, along with by-reaction impurities and salts, entering the liquid phase kettle residue, all of which is converted into hazardous waste. This not only causes a serious waste of valuable resources but also leads to a surge in hazardous waste generation, resulting in high subsequent disposal costs and environmental pressure. Furthermore, due to the lack of a pretreatment process, impurities enter the distillation system simultaneously with methanol, resulting in a crude methanol impurity content as high as 4.82%. This not only increases the processing load of the rectification process, making the unit energy consumption higher than that of this invention, but also makes it difficult to improve the methanol recovery purity. The final recovered methanol purity is only 99.2%, with a water content of 0.75%, which has a potential impact on the system stability and product purity of the subsequent doxycycline hydrochloride synthesis reaction. The methanol recovery rate is only 89.5%, indicating low resource utilization efficiency. This invention innovatively introduces a nanofiltration pretreatment process, utilizing a nanofiltration membrane system with a molecular weight cutoff of 200-800 Da to precisely retain most of the by-reaction impurities and ammonium chloride in the mother liquor. This purifies over 95% of the clarified liquid to an impurity content of 0.05%-0.055%, while simultaneously concentrating the deheating ice and residual impurities in a 4.6%-4.8% concentrate. This establishes a core process architecture of "graded separation and precise enrichment," laying the foundation for subsequent resource recovery. Building upon this, the invention specifically recovers methanol through distillation and precisely recovers deheating ice through crystallization centrifugation, achieving synergistic recovery of the two core components. The purity of methanol is increased to 99.82%-99.88%, and the purity of deheating ice reaches 89.9%-90.2%, with recovery rates of 99.1%-99.5% and 73.2%-73.8%, respectively. This completely changes the limitations of traditional processes that only recover methanol. Meanwhile, nanofiltration concentration concentrates impurities into a small amount of concentrated residue in the reactor. Combined with the repeated reuse of centrifugal mother liquor to further extract residual components, the amount of hazardous waste generated is reduced by 40%-45% compared to traditional processes. It takes into account resource utilization, environmental protection and economy, and its comprehensive performance far exceeds that of traditional processes.

Claims

1. A nanofiltration process for treating doxycycline hydrochloride methanol mother liquor, characterized in that: Includes the following steps: S1. Methanol Mother Liquor Nanofiltration Treatment: The methanol mother liquor containing doxycycline hydrochloride is stored as the raw liquid in the raw liquid tank of the nanofiltration treatment process. The raw liquid is pressurized and transported to the nanofiltration membrane system by a high-pressure pump. The raw liquid is separated under the retention of the nanofiltration membrane. The clear liquid is collected in the clear liquid tank, and the concentrated liquid retained by the nanofiltration membrane is temporarily stored in the concentrated liquid tank. S2. Concentrate separation: The concentrate temporarily stored in the concentrate tank is sent to the distillation equipment, and the azeotropic vapor and concentrate residue are separated by distillation; the separated azeotropic vapor is condensed to obtain concentrate condensate; S3. Clear liquid separation: The clear liquid collected in the clear liquid tank is sent to the distillation equipment, and the azeotropic vapor and clear liquid residue are separated by distillation. S4. Concentrated liquid condensate and clear liquid condensate recovery: The concentrated liquid condensate and clear liquid condensate are sent to a distillation unit for distillation treatment to separate methanol recovery product and tower residue; S5. Residual crystallization centrifugation of clear liquid vessel: The separated residual liquid vessel is sent to the crystallization equipment, and process water is added to adjust the system environment. After crystallization is completed, the crystallized mixture is sent to the centrifugation equipment, and process water is added again. The centrifugation operation is used to separate the centrifugation mother liquor and the deheating ice recovery product. S6. Centrifugal Mother Liquor Reuse: The centrifugal mother liquor obtained from the centrifugation operation is sent to the crystallization equipment, and after the process water is added back to adjust the system environment, it is sent back to the centrifugation equipment to participate in the centrifugation operation, thus recycling the centrifugal mother liquor.

2. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S1, the methanol mother liquor is separated by a nanofiltration membrane system to obtain a 95.0%-95.5% clear liquid and a 4.5%-4.8% concentrated liquid. The methanol mother liquor includes 0.40%-0.45% by-reaction products and impurities, 4.60%-4.65% reflux hydrate, 0.08%-0.10% ammonium chloride, 93.5%-93.7% methanol, and 1.25%-1.30% water. The composition of the clear liquid after nanofiltration separation includes 0. The first solution contains 0.04%-0.06% by-reaction products and impurities, 4.55%-4.65% refrigerating ice, 0.05%-0.07% ammonium chloride, 93.9%-94.2% methanol, and 1.25%-1.30% water; the concentrated solution contains 7.8%-8.2% by-reaction products and impurities, 5.0%-5.3% refrigerating ice, 0.7%-0.8% ammonium chloride, 84.3%-84.8% methanol, and 1.4%-1.5% water.

3. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S2, the concentrated liquid is distilled to obtain 85.0%-85.5% concentrated liquid condensate and 14.5%-15.0% concentrated liquid residue. The concentrated liquid condensate consists of 98.8%-99.2% methanol, 0.8%-0.9% water and 0.10%-0.15% ammonium chloride. The concentrated liquid residue consists of 55.0%-55.5% by-reaction products and impurities, 35.0%-35.8% reflux icing, 4.2%-4.5% ammonium chloride and 4.8%-5.0% water.

4. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: The residue from the concentrated liquid reactor is collected separately and disposed of professionally in accordance with hazardous waste treatment regulations.

5. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S3, the clarified liquid is distilled to obtain 94.5%-95.0% clarified liquid condensate and 5.0%-5.5% clarified liquid residue. The clarified liquid condensate consists of 99.2%-99.5% methanol, 0.6%-0.7% water and 0.005%-0.015% ammonium chloride. The clarified liquid residue consists of 0.8%-1.0% by-reaction products and impurities, 86.0%-86.5% reflux icing, 0.8%-1.0% ammonium chloride and 11.5%-12.5% ​​water.

6. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S4, after the concentrated liquid condensate and the clear liquid condensate are separated by distillation, 99.4%-99.5% methanol recovery product and 0.5%-0.6% tower residue are obtained; the methanol recovery product is 99.8%-99.9% methanol and 0.1%-0.2% water; the tower residue recovery product is 0.5%-0.6% methanol, 96.5%-97.0% water and 2.5%-2.8% ammonium chloride.

7. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S5, the residual crystallizer in the clearing vessel is centrifuged to obtain 26.0%-26.5% of centrifugal mother liquor and 73.5%-74.0% of deheating ice recovery product; the centrifugal mother liquor contains 0.4%-0.5% of by-reaction products and impurities, 2.5%-2.8% of ammonium chloride, 96.5%-97.0% of water and 0.15%-0.20% of deheating ice; the deheating ice recovery product contains 0.7%-0.9% of by-reaction products and impurities, 89.5%-90.5% of deheating ice and 9.0%-9.2% of water.

8. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S6, the centrifuged mother liquor is reused no more than 12 times, and the centrifuged mother liquor exceeding the reuse limit is treated as wastewater.

9. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In step S1, pressure gauges are installed at the outlet of the high-pressure pump and the inlet and outlet pipes of the nanofiltration membrane, and a flow meter is installed in the feed pipe of the clear liquid tank.

10. The nanofiltration treatment process for doxycycline hydrochloride methanol mother liquor according to claim 1, characterized in that: In steps S4 and S5, the process water is primary water.

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