Method for concentrating medical mother liquor by membrane method

Abstract

The invention provides a method for concentrating medical mother liquor by a membrane process, which belongs to the technical field of medical waste liquid treatment and comprises the following steps: S1, treating the medical mother liquor by a self-cleaning filter to obtain first filtrate; s2, treating the first filtrate through a security filter to obtain a second filtrate; s3, treating the second filtrate by using a nanofiltration membrane system to obtain a permeate and a concentrated solution; and S4, returning the concentrated liquid to the step S3, repeatedly treating the concentrated liquid by using the nanofiltration membrane until the concentrated liquid reaches a preset concentration degree, and merging permeate liquid obtained by nanofiltration membrane treatment each time. The method for concentrating the medical mother liquor can solve the problem that toxic and harmful waste gas is generated when the medical mother liquor is concentrated at high temperature.

Description

Technical Field

[0001] The present invention relates to the treatment of pharmaceutical mother liquor, and particularly to a method for concentrating pharmaceutical mother liquor by membrane method, belonging to the technical field of pharmaceutical waste liquid treatment. Background Art

[0002] In the process of pharmaceutical production, the mother liquor storage tank in a pharmaceutical factory stores the remaining solution after chemical reactions, namely pharmaceutical mother liquor. The mother liquor usually contains unreacted raw materials, intermediates, products, and various solvents, etc.; and the mother liquor has high organic matter content but small molecular weight, and contains a large amount of sodium ions, chloride ions, and sulfate ions. The discharge of unreacted raw materials, intermediates, products, various solvents, etc. contained in the pharmaceutical mother liquor will not only pollute the environment but also waste the recyclable components in the mother liquor. Based on this, concentrating the mother liquor and specifically recovering the recyclable components can achieve the purpose of environmentally friendly treatment of pharmaceutical mother liquor and at the same time improve the added value of the pharmaceutical mother liquor.

[0003] However, during the storage process of pharmaceutical mother liquor, due to its own volatility and possible chemical reactions, a certain amount of waste gas will be generated. The waste gas components in the mother liquor storage tank of a pharmaceutical factory are complex and diverse, which may include organic solvents (such as methanol, ethanol, acetone, dichloromethane, etc.), volatile organic compounds (VOCs), acidic gases (such as hydrogen chloride, hydrogen sulfide, etc.), alkaline gases (such as ammonia, etc.), and some organic substances with special odors and toxicity. The organic substances such as VOCs in the waste gas produced by pharmaceutical mother liquor will participate in photochemical reactions in the atmosphere, forming secondary pollutants such as ozone and fine particulate matter, resulting in a decline in air quality and exacerbating the formation of haze weather. Acidic and alkaline gases may cause environmental problems such as acid rain, damaging the soil, water bodies, and ecological systems. Many waste gas components are irritating, toxic, and carcinogenic. For example, organic solvents can cause respiratory irritation, central nervous system damage, etc.; long-term exposure to certain toxic organic substances may lead to serious diseases such as gene mutations and cancer.

[0004] Therefore, simply concentrating pharmaceutical mother liquor by high-temperature evaporation not only consumes more energy but also causes more serious waste gas pollution. Summary of the Invention

[0005] In view of the above problems, the present invention provides a method for concentrating pharmaceutical mother liquor by membrane method to effectively concentrate the mother liquor at low temperature.

[0006] To achieve the above object, the technical solution of the present invention is: A method for concentrating pharmaceutical mother liquor by membrane method, comprising the following steps: Step S1, the pharmaceutical mother liquor is processed by a self-cleaning filter to obtain a first filtrate; Step S2, the first filtrate is processed by a security filter to obtain a second filtrate; Step S3: The second filtrate is processed by a nanofiltration membrane system to obtain a permeate and a concentrate. Step S4: The concentrate is returned to Step S3 for repeated treatment by the nanofiltration membrane system until the obtained concentrate reaches a predetermined concentration. Each permeate obtained from the treatment by the nanofiltration membrane system is combined for treatment.

[0007] Further, the temperature of the traditional Chinese medicine mother liquor in Step S1 is 0 - 40°C.

[0008] Further, the filtration accuracy of the security filter in Step S2 is 50μm.

[0009] Further, in the nanofiltration membrane system (i.e., the NXF membrane system) in Step S3, the nanofiltration membrane is a hollow fiber nanofiltration membrane, and it is an internal pressure filtration with an operating pressure of 3 - 4 bar.

[0010] Further, the predetermined concentration in Step S4 is 3 - 5 times the concentration of the solution before entering the nanofiltration membrane system.

[0011] Further, the concentrate that reaches the predetermined concentration in Step S4 is transferred to a storage tank for temporary storage to be used for subsequent extraction of various components in the concentrate, and the permeate is discharged after passing the post-treatment up to the standard.

[0012] Further, the concentrate that reaches the predetermined concentration in Step S4 is subjected to post-treatment to meet the emission standard, and the permeate is temporarily stored in a storage tank for subsequent extraction of various components in the permeate.

[0013] Further, before the traditional Chinese medicine mother liquor in Step S1 enters the self-cleaning filter for treatment, modified chitosan is added to the traditional Chinese medicine mother liquor and stirred evenly.

[0014] Further, the modified chitosan is β-cyclodextrin modified chitosan, and the added mass to the volume ratio of the traditional Chinese medicine mother liquor is 3 - 5 g / L. After adding the modified chitosan, the pH value of the traditional Chinese medicine mother liquor is adjusted to 7.5 - 8.0.

[0015] Further, the preparation method of β-cyclodextrin modified chitosan is as follows: First, chitosan is swollen in a 0.1 mol / L sodium hydroxide solution for 8 h, then a sodium hydroxide solution dissolved with β-cyclodextrin is added dropwise, and the reaction is carried out at 60°C for 4 h. After filtration, the solid is washed with distilled water until neutral, and dried to obtain a light yellow solid, which is β-cyclodextrin modified chitosan.

[0016] The beneficial effects of a membrane method for concentrating traditional Chinese medicine mother liquor of the present invention are as follows: The concentration method of the present invention can achieve the efficient concentration of the traditional Chinese medicine mother liquor, providing a good material basis for subsequent extraction of various components in the mother liquor.

[0017] When concentrating the pharmaceutical mother liquor of the present invention, it is first treated with a self-cleaning filter. A self-cleaning filter is a precision device that directly intercepts impurities in water using a filter screen, removes suspended solids and particulate matter in the water body, reduces turbidity, purifies water quality, reduces the generation of system fouling, bacteria, algae, rust, etc., so as to purify water quality and protect the normal operation of other equipment in the system. Water enters the self-cleaning filter body from the water inlet. Due to the intelligent (PLC) design, the system can automatically identify the degree of impurity deposition and give a signal to the drain valve for automatic full drainage; it can achieve automatic cleaning, and the system does not require manual cleaning of the filter residue.

[0018] After the pharmaceutical mother liquor of the present invention is treated with a self-cleaning filter, it is then treated with a security filter. A precision filter (security filter) is generally installed before the pressure vessel to remove fine particles with a turbidity of more than 1 degree to meet the requirements of the subsequent process for the influent water; sometimes it is also installed at the end of the entire water treatment system to prevent fine particles (such as broken resin) from entering the finished water.

[0019] The present invention adopts the NXF nanofiltration membrane separation system, which can save the investment in pretreatment without the need for ultrafiltration as a pretreatment process; the NXF nanofiltration membrane operates under normal pressure (3 - 4 bar) with low energy consumption; the present invention realizes the concentration of the pharmaceutical mother liquor at low temperature (0 - 40 °C), solving the problems of easy decomposition and easy volatilization and vaporization at high temperature.

[0020] The NXF nanofiltration membrane of the present invention can intercept that part of the small molecular weight organic matter that passes through the ultrafiltration membrane and can also dialyze the inorganic salts intercepted by the reverse osmosis membrane, that is, it can make "concentration" and desalination proceed simultaneously, which is very beneficial for the concentration and recovery of organic matter in the pharmaceutical mother liquor and the reduction of the salt content in the mother liquor, and helps to realize the resource utilization and subsequent treatment of the pharmaceutical mother liquor.

[0021] The NXF nanofiltration membrane of the present invention is a hollow fiber nanofiltration membrane with a small membrane pore size and high filtration accuracy; the NXF nanofiltration membrane separation system adopts cross-flow filtration, and the filtration layer is continuously flushed during operation, so that dirt is not easily deposited; the NXF nanofiltration membrane filtration adopts an internal pressure filtration method, and pollutants are on the inner side of the membrane without filtration dead spots; each membrane filament is an independent open filtration channel with uniform water distribution, and the membrane filaments are isolated from each other without adhesion, which is easy to clean; and it can be washed with strong acid and strong alkali, has strong chlorine resistance, does not require adding a reducing agent, can be chlorinated to prevent microbial fouling, and can also be backwashed.

[0022] The present invention uses β-cyclodextrin modified chitosan to adsorb and fix the organic solvents and volatile organic compounds that are prone to generate gases or volatilize at high temperature in the pharmaceutical mother liquor, as well as the acidic and alkaline gases doped in the mother liquor due to the reaction, which can ensure that no toxic and harmful gases are generated during the entire mother liquor concentration process, especially avoiding the volatilization of volatile organic compounds.

[0023] The β-cyclodextrin modified chitosan of the present invention is obtained by modifying chitosan with β-cyclodextrin. Chitosan is a linear amino polysaccharide natural polymer obtained by partial or complete deacetylation of chitin under alkaline and heating conditions. Chitosan is naturally non-toxic and has the characteristics of good biocompatibility and easy biodegradability. The lone pair electrons and empty orbitals on its amino group can make it attract other compounds or adsorb other compounds by forming hydrogen bonds through hydroxyl groups. However, chitosan is not resistant to acidic environments and is insoluble in neutral and alkaline conditions. Cyclodextrin is an oligosaccharide composed of 6-8 D-glucose units generated by enzymatic degradation of starch, also known as cyclodextrin. The most common types are α, β, and γ. β-cyclodextrin has a cyclic cavity structure, with a hydrophobic inner cavity and a hydrophilic molecular surface. β-cyclodextrin can form inclusion complexes with other molecules. The present invention uses β-cyclodextrin to modify chitosan under alkaline conditions. The obtained β-cyclodextrin modified chitosan has certain solubility in both acidic and alkaline conditions, and its adsorption performance is greatly improved compared to single β-cyclodextrin and single chitosan. It has a good adsorption effect on organic substances in pharmaceutical mother liquors, especially has a good fixation effect on volatile organic compounds. It can not only adsorb and fix non-polar volatile organic compounds, but also has a good adsorption and fixation effect on some small-molecule polar volatile organic compounds, and will not be intercepted by self-cleaning filters and security filters, ensuring that no toxic and harmful gases are generated during the entire concentration process. In addition, β-cyclodextrin modified chitosan has good biodegradability and will not cause more serious pollution to the environment.

[0024] The adsorption and fixation effect of the β-cyclodextrin modified chitosan of the present invention is best under specific pH conditions. When the pH is 7.5-8.0, it can adsorb and fix organic substances in pharmaceutical mother liquors to the greatest extent, especially volatile substances, especially volatile organic compounds. Too high or too low pH values will affect the exertion of its effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present invention will be further described in detail below with reference to the drawings and specific embodiments.

[0026] Figure 1 is a schematic flow chart of concentrating a pharmaceutical mother liquor in an embodiment of the present invention; Figure 2 is a schematic flow chart of concentrating a pharmaceutical mother liquor in another embodiment of the present invention; Figure 3 is a schematic overall structure diagram of a single membrane in the NXF membrane system of the present invention; Figure 4 is a cross-sectional view showing a membrane element of the NXF membrane system of the present invention.

[0027] DESCRIPTION OF THE REFERENCE NUMERALS 1. Outer shell; 2. A end cover; 21. Water inlet; 3. B end cover; 31. Concentrated water outlet; 4. Quick-install fastening kit; 5. Membrane element; 51. Produced water cavity; 6. Produced water conduit; 61. Produced water outlet. Detailed implementation manner

[0028] The following combines the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Many specific details are set forth in the following description in order to fully understand the present invention. However, the present invention can also be implemented in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0029] A method for membrane concentration of pharmaceutical mother liquor, characterized by comprising the following steps: Step S1, adjust the temperature of the pharmaceutical mother liquor to 0 - 40 °C. After the pharmaceutical mother liquor is treated by a self-cleaning filter, a first filtrate is obtained; the self-cleaning filter intercepts some large suspended matters, medicinal residues and other substances to protect the subsequent system; the self-cleaning filter automatically cleans itself according to the pressure difference and resumes work.

[0030] Step S2, the first filtrate is treated by a security filter to obtain a second filtrate; the filtration accuracy of the security filter is 50 μm, further removing some fine impurities and playing a protective role for the membrane system.

[0031] Step S3, the second filtrate is treated by a nanofiltration membrane system (i.e., NXF membrane system) to obtain a permeate and a concentrated solution; the nanofiltration membrane in the nanofiltration membrane system is a hollow fiber nanofiltration membrane, and is an internal pressure filtration, and the operating pressure is 3 - 4 bar; Step S4, the concentrated solution is returned to Step S3 for repeated use of nanofiltration membrane treatment until the obtained concentrated solution reaches a predetermined concentration. Each permeate obtained by the nanofiltration membrane system treatment is combined and treated; the predetermined concentration is 3 - 5 times the concentration of the solution before entering the nanofiltration membrane (here, the concentration can also be set according to the needs of the user). Optionally, the concentrated solution reaching the predetermined concentration is transferred to a storage tank for temporary storage for subsequent extraction of each component in the concentrated solution, and the permeate is discharged after post-treatment up to the standard. Further optionally, the concentrated solution reaching the predetermined concentration is post-treated to meet the discharge standard, and the permeate is temporarily stored in a storage tank for subsequent extraction of each component in the permeate.

[0032] Preferably, before the pharmaceutical mother liquor enters the self-cleaning filter for treatment in Step S1, β-cyclodextrin modified chitosan is added to the pharmaceutical mother liquor and stirred evenly; the modified chitosan is β-cyclodextrin modified chitosan, and the added mass to the volume ratio of the pharmaceutical mother liquor is 3 - 5 g / L. After adding the modified chitosan, the pH value of the pharmaceutical mother liquor is adjusted to 7.5 - 8.0.

[0033] The preparation method of the above-mentioned β-cyclodextrin modified chitosan is as follows: First, swell chitosan in a 0.1 mol / L sodium hydroxide solution for 8 h, then dropwise add a sodium hydroxide solution dissolved with β-cyclodextrin, react at 60 °C for 4 h, filter, wash the solid with distilled water until neutral, and dry to obtain a light yellow solid, which is β-cyclodextrin modified chitosan.

[0034] The nanofiltration membrane system of the present invention (i.e., the NXF membrane system) includes multiple single membranes, and different numbers of single membranes are set according to different water volumes, and multiple single membranes can be arbitrarily connected in parallel or in series as needed. Refer to Figure 3 and Figure 4 As shown, a single membrane includes a housing 1, an A end cap 2, a B end cap 3, a quick-install fastening kit 4, a membrane element 5, and a water production conduit 6. The housing 1 is arranged in a cylindrical shape with a hollow interior and open ends at both ends. Both the A end cap 2 and the B end cap 3 are arranged in a cylindrical shape with a hollow interior and an open end at one end. The A end cap 2 is arranged at the bottom end of the housing 1, and the B end cap 3 is arranged at the top end of the housing 1. The open ends of both are fixed to the housing 1 through the quick-install fastening kit 4. An inlet 21 is fixedly provided on the side of the A end cap 2, and a concentrated water outlet 31 is fixedly provided on the side of the B end cap 3. The membrane element 5 (i.e., a hollow fiber nanofiltration membrane) is arranged along the height direction of the housing 1. The membrane element 5 is wound into a cylinder coaxial with the housing 1 and is fixedly arranged inside the housing 1, and a cavity is formed at the central position, which is the water production cavity 51. The water production cavity 51 is arranged along the height direction of the housing 1. The number of water production conduits 6 is two, which are respectively fixedly arranged at the central positions of the A end cap 2 and the B end cap 3 and are arranged along the height direction of the housing 1. The two ends of the water production conduits 6 close to the membrane element 5 extend into the water production cavity 51 and are connected to it. The end of the water production conduit 6 located in the B end cap 3 away from the membrane element 5 extends out of the B end cap 3 and is fixedly provided with a water production port 61.

[0035] During use, the pharmaceutical mother liquor treated by the security filter will enter from the inlet 21 of the A end cap 2. The mother liquor will enter the membrane element 5. After being filtered by the membrane element 5, it is divided into two parts. One part is the permeate, which enters the water production cavity 51 and is discharged from the water production port through the water production conduit 6 for collection. The other part is the concentrated solution (i.e., the concentrated liquid). The concentrated solution enters the B end cap 3 and is discharged from the concentrated water outlet 31. The A end cap 2 and the B end cap 3 can be interchanged.

[0036] The method for concentrating pharmaceutical mother liquor by membrane method of the present invention is applicable to the concentration of various mother liquors in pharmaceutical factories. Using the method of the present invention, effective concentration of various pharmaceutical mother liquors (especially pharmaceutical mother liquors that need to separate organic substances and inorganic ions) can be achieved, and the overflow of toxic and harmful gases caused by high temperature can be avoided; after adding the β-cyclodextrin modified chitosan prepared by the present invention to various mother liquors, the overflow of toxic and harmful gases can be further avoided, and it will continue to play a role in the downstream component extraction or reprocessing stage after the mother liquor is concentrated. The following is an example to illustrate the specific application process of the method of the present invention in the concentration of pharmaceutical mother liquor: Example 1

[0037] In this example, the pharmaceutical mother liquor refers to the erythromycin crystallization mother liquor. Existing erythromycin manufacturers mainly obtain erythromycin by converting thiocyanate erythromycin or erythromycin lactate. After conversion and centrifugation, there are still erythromycin molecules dissolved in the mother liquor formed by water and acetone. Acetone is a volatile VOC substance. The method for recovering erythromycin molecules in the mother liquor is generally to first pretreat the mother liquor, that is, first transfer the erythromycin molecules in the mother liquor to the butyl acetate phase that is easy to carry out salt-forming reaction. Specifically, add sufficient butyl acetate to the mother liquor for extraction, stir and heat to about 50°C after adding butyl acetate, adjust the pH of the mother liquor to 9.8 - 10.0 with 20% sodium hydroxide solution, let it stand for 1 h, add solid sodium chloride and stir, and then let it stand to separate the aqueous phase and impurities to obtain the extract after the mother liquor is transformed; under the condition of about 30°C, slowly add 30% (v / v) lactic acid-butyl acetate solution to the transformed extract while continuing to stir and control the pH to 4.0 - 4.3, then cool down, let it stand and filter, and at the same time supplement with a small amount of butyl acetate for rinsing to obtain erythromycin lactate.

[0038] Concentrating the erythromycin crystallization mother liquor can effectively recover the erythromycin in it, improve the recovery efficiency and save energy consumption; specifically, as shown in Figure 1 , according to the method for concentrating the pharmaceutical mother liquor of the present invention, first filter the normal-temperature erythromycin crystallization mother liquor through a self-cleaning filter, and then through a security filter ( Figure 1 The pretreatment herein refers to the filtration through the self-cleaning filter and the security filter), the obtained solution is filtered by the NXF nanofiltration membrane system, and the obtained concentrated solution is repeatedly passed through the nanofiltration membrane system until the concentration of the final concentrated solution is 3 - 5 times the concentration of the solution obtained after being treated by the security filter. Here, the content of erythromycin in the solution is used as the calculation standard for the concentration. The content of erythromycin can be determined by any known method in the prior art (for example, it can be detected by high-performance liquid chromatography. The specific chromatographic conditions are: using octadecylsilane-bonded silica gel as the stationary phase, using 0.1 mol / L ammonium dihydrogen phosphate solution (adjusted to pH 6.5 with triethylamine)-acetonitrile (70:30); flow rate 1.0 ml / min; detection wavelength 210 nm); the concentrated erythromycin solution recovers erythromycin according to the above method for converting erythromycin lactate. Compared with the method of directly converting erythromycin lactate without concentration, the energy consumption is saved by 60 - 70%, and the usage amounts of substances such as sodium hydroxide and butyl acetate are all reduced to a certain extent.

[0039] Since the erythromycin crystallization mother liquor contains acetone, the VOC content during the concentration process and the process of converting erythromycin lactate to base after concentration was tracked and detected. Specifically, a fixed online multi-functional TVOC detector of Shenzhen Jishunan Technology Co., Ltd. was used, with the specification of JK50-TVOC. This detector is used for continuous online monitoring of the concentration of multi-functional TVOC detectors at the site for 24 hours and the measurement of temperature and humidity. It can detect the concentrations of multiple gases and temperature and humidity simultaneously, display the concentration on-site and give an audible and visual alarm for exceeding the standard, and transmit data remotely. JK50 can detect the TVOC concentration in pipelines or confined spaces. The TVOC concentrations at the liquid outlet of the self-cleaning filter, the liquid outlet of the security filter, and the concentrated water outlet of the NXF nanofiltration membrane were detected using this detector. The temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, the security filter, and the NXF nanofiltration membrane system was normal temperature, and trace concentrations of TVOC were detected. The TVOC concentrations at the three places were 1.21 mg / m², 1.32 mg / m², and 1.03 mg / m² respectively; in the subsequent pretreatment stage of the erythromycin crystallization mother liquor, the detected TVOC concentration was 2.16 mg / m². The increase in the TVOC concentration value here may be due to the pretreatment temperature reaching 50 °C, resulting in an increase in the concentration of related waste gases. The NXF nanofiltration membrane of the present invention can concentrate the pharmaceutical mother liquor under normal temperature conditions without heating and high-temperature concentration, and can avoid the generation of more pharmaceutical waste gases at high temperatures. Example 2

[0040] On the basis of Example 1, it was further optimized according to the method of the present invention. Before treating the erythromycin crystallization mother liquor with the self-cleaning filter, 4 g / L of the β-cyclodextrin-modified chitosan of the present invention was first added to the erythromycin crystallization mother liquor, and the pH value of the mother liquor was adjusted to 7.5 - 8.0, and stirred evenly. Then, it was successively concentrated by the self-cleaning filter, the security filter, and the NXF nanofiltration membrane system, and finally erythromycin was recovered according to the method of converting erythromycin lactate to base; the TVOC concentrations at the liquid outlet of the self-cleaning filter, the liquid outlet of the security filter, and the concentrated water outlet of the NXF nanofiltration membrane were also detected using the above detector. The temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, the security filter, and the NXF nanofiltration membrane system was normal temperature, and no TVOC was detected; in the subsequent pretreatment stage of the erythromycin crystallization mother liquor, the detected TVOC concentration was 0.26 mg / m², indicating that the addition of β-cyclodextrin-modified chitosan to the mother liquor can inhibit the volatilization of volatile organic compounds, and still has a good inhibitory effect at higher temperatures.

[0041] The detection of TVOC at each position of the above self-cleaning filter, security filter and NXF nanofiltration membrane system can be carried out by detecting the air inside the equipment after the solution in each equipment is emptied, or by taking the effluent from each place and placing it in a closed space for a period of time to detect the internal air. Due to the different sizes of the environmental space, the values may vary, but the trend of value change is the same, which is consistent with the data results of Examples 1 and 2 above.

[0042] Comparative Examples 1-4 Comparative Examples 1-4 were carried out on the basis of Example 2. Specifically, the addition amount of β-cyclodextrin modified chitosan in Comparative Example 1 was 2 g / L, the addition amount of β-cyclodextrin modified chitosan in Comparative Example 2 was 6 g / L, the pH value of the pharmaceutical mother liquor was adjusted to 7.0 in Comparative Example 3, and the pH value of the pharmaceutical mother liquor was adjusted to 8.5 in Comparative Example 4. Other conditions were the same as those in Example 2. Results: In Comparative Example 1, the temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, security filter and NXF nanofiltration membrane system was normal temperature, and the TVOC concentrations at the three places were 0.65 mg / m², 0.57 mg / m², and 0.55 mg / m² respectively; during the subsequent pretreatment stage of the erythromycin crystallization mother liquor, the detected TVOC concentration was 0.96 mg / m²; In Comparative Example 2, the temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, security filter and NXF nanofiltration membrane system was normal temperature, and the TVOC concentrations at the three places were 0, that is, not detected; during the subsequent pretreatment stage of the erythromycin crystallization mother liquor, the detected TVOC concentration was 0.24 mg / m²; In Comparative Example 3, the temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, security filter and NXF nanofiltration membrane system was normal temperature, and the TVOC concentrations at the three places were 1.01 mg / m², 0.96 mg / m², and 0.98 mg / m² respectively; during the subsequent pretreatment stage of the erythromycin crystallization mother liquor, the detected TVOC concentration was 1.35 mg / m²; In Comparative Example 4, the temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, security filter and NXF nanofiltration membrane system was normal temperature, and the TVOC concentrations at the three places were 0.94 mg / m², 0.91 mg / m², and 0.88 mg / m² respectively; during the subsequent pretreatment stage of the erythromycin crystallization mother liquor, the detected TVOC concentration was 0.95 mg / m²; From the above comparative examples, it can be seen that the β-cyclodextrin modified chitosan of the present invention can effectively adsorb and fix organic substances in the mother liquor, especially volatile VOC organic compounds, under specific dosage and pH environmental conditions, which can ensure the air safety during the mother liquor treatment process; the change of environmental pH will weaken the exertion of its effect. Example 3

[0043] The pharmaceutical mother liquor in this embodiment refers to the zinc-containing mother liquor in the production process of cephalosporin C zinc salt. The production of cephalosporin C zinc salt mainly includes steps such as fermentation, extraction, and cleavage. First, cephalosporin C is obtained through microbial fermentation, then the side chain of CPC is cleaved by chemical or enzymatic methods to prepare 7-ACA (7-aminocephalosporanic acid), and finally cephalosporin C zinc salt is prepared through appropriate processes; various organic solvents such as toluene, methanol, ethyl acetate, isopropanol, petroleum ether, triethylamine, acetone, etc. are used in the preparation process; the zinc-containing mother liquor is generally first distilled to recover the organic solvents, and the concentration of zinc ions in the remaining mother liquor is about 0.5% by complexometric titration. The zinc ions can be precipitated by adding an appropriate amount of sodium carbonate, stirring for 4 hours, centrifuging and filtering, and the filtrate is further treated by the ion exchange method. The precipitate is zinc carbonate.

[0044] The concentration of zinc ions in the zinc-containing mother liquor is low, and the energy consumption for evaporating and recovering organic solvents is relatively high. According to the concentration method of the present invention, it is first concentrated to remove the organic solvents, and then sodium carbonate is added to the remaining solution containing zinc ions to recover the zinc ions; specifically, as shown in Figure 2 First, the zinc-containing mother liquor at room temperature is filtered through a self-cleaning filter, and then through a security filter ( Figure 2 The pretreatment herein refers to the filtration through the self-cleaning filter and the security filter). The obtained solution is filtered by the NXF nanofiltration membrane system. The obtained concentrated solution is repeatedly passed through the nanofiltration membrane system until the concentration of the final concentrated solution is 3-5 times that of the solution obtained after being treated by the security filter. When the volume of the concentrated solution is reduced to 20-30% of the initial mother liquor volume, it is considered that the concentration degree reaches the predetermined requirement. The concentrated solution contains various organic substances, while the zinc ions have been transferred into the permeate, realizing the separation of zinc ions in the mother liquor and the concentration of organic substances; compared with the method of removing organic solvents by evaporation, the energy consumption is saved by 70-80%; nearly 98.9% of the zinc ions in the mother liquor are transferred into the NXF nanofiltration membrane permeate, facilitating the efficient recovery of zinc ions. The concentration of zinc ions is determined by the EDTA complexometric titration method and the atomic absorption spectrophotometry method (reference: Zhou Bensheng, Industrial Water Treatment Technology [M]. Beijing: Chemical Industry Press; Analytical Chemistry Handbook (Chemical Analysis) [M]. Beijing: Chemical Industry Press).

[0045] Same as in Examples 1 and 2, the TVOC concentrations at the outlet of the self-cleaning filter, the outlet of the security filter, and the concentrated water outlet of the NXF nanofiltration membrane are detected. The temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, the security filter, and the NXF nanofiltration membrane system is all at room temperature. TVOC with a certain concentration is detected. The TVOC concentrations at the three places are 3.56 mg / m², 3.68 mg / m², and 3.49 mg / m² respectively; the TVOC concentration during the process of recovering zinc ions is 0, that is, not detected, because the volatile organic compounds have all been transferred into the concentrated solution. The TVOC in the environment where the concentrated solution is located is detected, and the concentration is 5.76 mg / m². Example 4

[0046] On the basis of Example 3, further optimize according to the method of the present invention. Before treating the zinc-containing mother liquor with a self-cleaning filter, first add 5 g / L of the β-cyclodextrin-modified chitosan described in the present invention to the zinc-containing mother liquor, adjust the pH value of the mother liquor to 7.5 - 8.0, stir evenly, and then successively conduct concentration treatment through a self-cleaning filter, a security filter, and an NXF nanofiltration membrane system. Finally, recover zinc ions according to the method in Example 3; similarly, use the above detector to detect the TVOC concentration at the outlet position of the self-cleaning filter, the outlet position of the security filter, and the concentrated water outlet position of the NXF nanofiltration membrane. The temperature of the pharmaceutical mother liquor during the operation of the self-cleaning filter, the security filter, and the NXF nanofiltration membrane system is normal temperature, and no TVOC is detected; no TVOC is detected in the subsequent zinc ion recovery stage liquid, and the TVOC concentration detected in the concentrated liquid storage container is 0.36 mg / m², indicating that the addition of β-cyclodextrin-modified chitosan to the mother liquor can inhibit the volatilization of volatile organic compounds.

[0047] Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without creative efforts fall within the scope of protection of the present invention.

Claims

1. A method for concentrating pharmaceutical mother liquor by membrane method, characterized in that, It includes the following steps: Step S1: The pharmaceutical mother liquor is processed by a self-cleaning filter to obtain a first filtrate; Step S2: The first filtrate is processed by a security filter to obtain a second filtrate; Step S3: The second filtrate is processed by a nanofiltration membrane system to obtain a permeate and a concentrate; Step S4: The concentrate is returned to Step S3 for repeated treatment by the nanofiltration membrane system until the obtained concentrate reaches a predetermined concentration. Each permeate obtained from the treatment by the nanofiltration membrane system is combined for treatment.

2. The method for membrane concentration of pharmaceutical mother liquor according to claim 1, characterized in that, In Step S1, the temperature of the pharmaceutical mother liquor is 0 - 40°C.

3. The method for membrane concentration of pharmaceutical mother liquor according to claim 1, characterized in that, In Step S2, the filtration accuracy of the security filter is 50μm.

4. A method for membrane concentration of pharmaceutical mother liquor according to claim 1, characterized in that, In Step S3, the nanofiltration membrane in the nanofiltration membrane system is a hollow fiber nanofiltration membrane, and it is an internal pressure type filtration with an operating pressure of 3 - 4 bar.

5. A method for concentrating pharmaceutical mother liquor by membrane method according to claim 1, characterized in that, In Step S4, the predetermined concentration is 3 - 5 times the concentration of the solution before entering the nanofiltration membrane system.

6. A method for concentrating pharmaceutical mother liquor by membrane method according to claim 1, characterized in that, In Step S4, the concentrate that reaches the predetermined concentration is transferred to a storage tank for temporary storage to be used for subsequent extraction of various components in the concentrate, and the permeate is discharged after post-treatment to meet the standards.

7. A method for membrane concentration of pharmaceutical mother liquor according to claim 1, characterized in that, In Step S4, the concentrate that reaches the predetermined concentration undergoes post-treatment to meet the discharge standards, and the permeate is temporarily stored in a storage tank to be used for subsequent extraction of various components in the permeate.

8. A method for membrane concentration of pharmaceutical mother liquor according to claim 1, characterized in that, Before the pharmaceutical mother liquor in Step S1 enters the self-cleaning filter for treatment, β-cyclodextrin modified chitosan is first added to the pharmaceutical mother liquor and stirred evenly.

9. A method for concentrating pharmaceutical mother liquor by membrane method according to claim 1, characterized in that, The β-cyclodextrin modified chitosan is β-cyclodextrin modified chitosan, and the mass ratio of the added amount to the volume of the pharmaceutical mother liquor is 3 - 5 g / L. After adding the β-cyclodextrin modified chitosan, the pH value of the pharmaceutical mother liquor is adjusted to 7.5 - 8.

0.

10. A method for membrane concentration of pharmaceutical mother liquor according to claim 9, characterized in that, The preparation method of β-cyclodextrin modified chitosan is as follows: First, chitosan is swollen in a 0.1 mol / L sodium hydroxide solution for 8 h, then a sodium hydroxide solution dissolved with β-cyclodextrin is added dropwise, and the reaction is carried out at 60°C for 4 h. After filtration, the solid is washed with distilled water until neutral, and then dried to obtain a light yellow solid, which is β-cyclodextrin modified chitosan.

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