A method for concentrated reduction treatment of antibiotic bacterial residue

Abstract

The application provides a concentrated volume reduction treatment method of antibiotic bacterial residue, and belongs to the technical field of biological pharmaceutical separation and purification and hazardous waste resource utilization. The concentrated volume reduction treatment method comprises the following steps: (1) antibiotic fermentation liquor is subjected to solid-liquid separation to obtain wet bacterial residue, and the wet bacterial residue is diluted with an aqueous solution to obtain a feed liquid; (2) the feed liquid obtained in the step (1) is pumped into a membrane separation device capable of generating shearing force to perform cross-flow filtration, and concentrated liquid after volume reduction and dialysate separated out are obtained. The concentrated volume reduction method can greatly improve the concentration multiple of high-bacterial-concentration erythromycin bacterial residue under the conditions of low energy consumption and low cost, reduce the subsequent disposal volume, reduce the treatment cost, and improve the resource utilization efficiency of solid waste. Meanwhile, the dialysate obtained by concentration can be recycled and utilized, and the yield of erythromycin product is improved. In addition, the concentrated membrane cleaning scheme can make the membrane flux recovery rate be greater than or equal to 96%. The application provides a good operation method for industrialized production of antibiotic products.

Description

Technical Field

[0001] This invention belongs to the field of biopharmaceutical separation and purification and hazardous waste resource utilization technology, specifically relating to a method for concentrating and reducing the volume of antibiotic bacterial residue. Background Technology

[0002] Erythromycin is a macrolide antibiotic produced by the fermentation of *Streptomyces rubrum* and is widely used in clinical anti-infective treatment. During the fermentation production of erythromycin, a large amount of highly concentrated and viscous bacterial residue is generated after solid-liquid separation. This residue contains residual culture medium, bacterial protein, metabolites, and small amounts of residual antibiotics, and is characterized by its large volume, high water content, and difficulty in treatment. With increasingly stringent environmental protection requirements and the inclusion of antibiotic bacterial residue in hazardous waste management, how to efficiently reduce the volume of this residue, lower subsequent disposal costs, and achieve resource utilization of byproducts has become a pressing technical problem for the erythromycin production industry.

[0003] Currently, the existing technologies for treating fermentation broths and bacterial residues of antibiotics such as erythromycin mainly include the following solutions: (I) Integrated process of ceramic ultrafiltration membrane and nanofiltration membrane: Patent application CN104262431A discloses a method and apparatus for extracting erythromycin thiocyanate, which adopts a two-stage process integrating ceramic ultrafiltration membrane and nanofiltration membrane, mainly used for the preliminary clarification of fermentation broth and the deep concentration of filtrate. The nanofiltration unit needs to operate under high temperature (50℃) and high pressure (1.4MPa) conditions. The shortcomings of this solution are: its process focuses on the clarification of fermentation broth and the concentration of filtrate, and does not involve the subsequent concentration treatment of high viscosity and high biomass bacterial residues generated after solid-liquid separation; at the same time, high pressure nanofiltration has high requirements for the pressure resistance and energy consumption of equipment, and is not suitable for treating bacterial residues with high solid content and high viscosity. Patent application CN111217837A discloses a method and apparatus for purifying antibiotic fermentation broth, which also adopts an integrated process of ceramic membrane and nanofiltration membrane. The improvement lies in returning the dialysis solution produced by nanofiltration to be used as dialysis water for the ceramic membrane, realizing water circulation within the system. The shortcomings of this scheme are: it still does not solve the problem of deep concentration of high-concentration bacterial residue; the utilization of dialysis solution is only limited to low-value reuse within the system, and it fails to be used as an effective resource for the high-value-added main product extraction process at the front end, thus failing to improve the overall product yield. (II) Static ceramic membrane treatment process: There are already practices in the industry of using static ceramic membranes (such as 50nm pore size) to treat erythromycin fermentation broth, with an average flux of about 120-130 LMH. However, when processing viscous bacterial residue concentrate with extremely high solid content (or bacterial concentration), the flux will drop sharply to below 10 LMH in a very short time (less than 30 minutes) due to severe membrane concentration polarization and membrane fouling. It is impossible to achieve stable concentration of more than 1.3 times, and membrane cleaning and recovery are difficult, which cannot meet the deep reduction requirements for continuous and economical industrial operation.

[0004] In summary, existing technologies lack a dedicated, efficient, stable, and low-energy-consumption treatment scheme for deep volume reduction of high-concentration, high-viscosity erythromycin bacterial residue. Furthermore, they fail to utilize the byproducts (dialysis fluid) generated during the volume reduction process for high-value resource recovery. Therefore, it is necessary to provide a method for concentrating and reducing the volume of antibiotic bacterial residue that overcomes the aforementioned shortcomings. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a method for concentrating and reducing the volume of antibiotic bacterial residue.

[0006] The present invention provides a method for concentrating and reducing the volume of antibiotic bacterial residue, comprising the following steps: (1) The antibiotic fermentation broth was separated into solid and liquid to obtain wet bacterial residue, which was then diluted with an aqueous solution to obtain a feed liquid; (2) The feed liquid obtained in step (1) is pumped into a membrane separation device that can generate shear force for cross-flow filtration to obtain a reduced volume concentrate and a separated dialysate.

[0007] Furthermore, in step (1), the solid-liquid separation method is plate and frame filtration, centrifugal separation, or static membrane separation; And / or, in step (1), the liquid is obtained by diluting wet bacterial residue with water, the centrifuged bacterial concentration of the liquid is 65%-78%, and the total solid content is 10%-18%.

[0008] Furthermore, in step (2), the membrane separation device capable of generating shear force is a rotary dynamic ceramic membrane; Preferably, in step (2), the pore size of the rotating dynamic ceramic membrane is 50-100 nm.

[0009] Furthermore, in step (2), the inlet pressure during cross-flow filtration is 1.5-2.5 Bar, and the tangential velocity of the membrane surface is 5.0-8.0 m / s.

[0010] Furthermore, in step (2), the inlet pressure during cross-flow filtration is 1.8-2.2 Bar, and the tangential velocity of the membrane surface is 7.0-8.0 m / s; Preferably, in step (2), the inlet pressure during cross-flow filtration is 2.0 Bar.

[0011] Furthermore, in step (2), no external cooling or external heating is performed during the cross-flow filtration.

[0012] Furthermore, in step (2), the separated dialysis fluid can be used as process water for antibiotic extraction.

[0013] The antibiotic of this invention is erythromycin.

[0014] The present invention also provides a method for cleaning the aforementioned membrane separation device capable of generating shear force, comprising the following steps: (A) Acid washing: The membrane separation equipment that can generate shear force after filtration is cleaned in nitric acid solution, and then rinsed with water until neutral. (B) Alkaline oxidation washing: The membrane separation equipment after cleaning in step (A) is cleaned in a mixed cleaning solution containing sodium hydroxide and hydrogen peroxide. After cleaning, it is rinsed with water until neutral.

[0015] Furthermore, In step (A), the nitric acid solution is an aqueous nitric acid solution with a volume percentage of 0.8%-1.2%; And / or, in step (A), the cleaning method is to perform cyclic cleaning at a temperature of 50-55°C for 30-45 minutes; And / or, in step (A), after cleaning, rinse with water until the pH value is 6.5-7.5; And / or, in step (B), the mixed cleaning solution containing sodium hydroxide and hydrogen peroxide is an aqueous solution containing 1.5%-2.5% sodium hydroxide and 0.5%-1.5% hydrogen peroxide by mass volume; And / or, in step (B), the cleaning method is to perform cyclic cleaning at a temperature of 45-55°C for 30-50 minutes; And / or, in step (B), rinse with water after cleaning until the pH value is 6.5-7.5.

[0016] Furthermore, In step (A), the nitric acid solution is a 1.0% (v / v) aqueous nitric acid solution; And / or, in step (A), the cleaning method is to perform a cyclic cleaning at 52°C for 40 minutes; And / or, in step (B), the mixed cleaning solution containing sodium hydroxide and hydrogen peroxide is an aqueous solution containing 2.0% sodium hydroxide and 1.0% hydrogen peroxide by mass volume. And / or, in step (B), the cleaning method is to perform a cyclic cleaning at 50°C for 45 minutes; Preferably, in step (A), the membrane separation device that can generate shear force is a rotary dynamic ceramic membrane.

[0017] The innovations of this invention are reflected in the following aspects: (1) Precise positioning of the process object and innovative discovery of the problem: For the first time, this invention systematically identified the pre-treatment deep reduction of "high bacterial concentration (65%-78%), medium and low solid content (10%-18%) erythromycin bacterial residue" as the core technical problem, which is different from the existing technology that focuses on "fermentation liquid treatment" or "terminal disposal of bacterial residue".

[0018] (2) "Low pressure-high temperature-high shear" synergistic process innovation: creatively combining the high shear force of the rotating dynamic membrane with the "allowable temperature rise" (50-60℃) strategy for high viscosity materials, a stable deep concentration of more than 1.8 times for high viscosity bacterial residue was achieved under ultra-low operating pressure (≤2.2 Bar), breaking through the technical limit of static membrane (<1.3 times).

[0019] (3) Innovative cleaning solution for complex contamination: A two-step cleaning method of "nitric acid dissociation-hydrogen peroxide alkaline solution oxidation" was developed for the complex contamination of mycelium, protein and inorganic salt in erythromycin residue, which effectively restored membrane performance.

[0020] (4) Innovative resource utilization pathway design: A high-value resource utilization closed loop of “membrane reduction-dialysis fluid-main product extraction” was established, which transformed the dialysis fluid from low-value recycled water into raw material for the extraction process, directly contributing to the improvement of the main product yield.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) Excellent volume reduction performance: The volume concentration ratio of high-concentration erythromycin bacterial residue is increased from 1.3 times, which is difficult to surpass by static membranes, to more than 1.8 times (up to about 2.1 times), which reduces the volume of subsequent treatment sections by 35%-45%, solving the technical bottleneck in the industry.

[0022] (2) Significantly reduced operating energy consumption: When operating at a low pressure of ≤2.2 Bar, no evaporation phase change is required. The power consumption per ton of liquid is about 2.0-2.5 kWh, which is more than 60% lower than that of high pressure nanofiltration and more than 40% lower than that of direct spray drying.

[0023] (3) Outstanding resource recycling and economic benefits: The reuse of dialysis fluid can increase the total yield of erythromycin from fermentation broth to finished product by 1.5%-2.5%, while reducing the amount of high-concentration organic wastewater by 20%-30%, thus achieving both environmental and economic benefits.

[0024] (4) Stable operation and low maintenance cost: High shear force effectively inhibits pollution, and the matching special cleaning solution makes the membrane flux recovery rate ≥96%, extends the membrane service life, and the system can operate stably for a long time.

[0025] In summary, this invention provides a method for concentrating and reducing the volume of antibiotic bacterial residue. This specific concentration and volume reduction method can significantly increase the concentration ratio of high-concentration erythromycin bacterial residue under low energy consumption and low cost conditions, reducing subsequent treatment volume, lowering treatment costs, and improving the efficiency of solid waste resource utilization. Simultaneously, during the concentration of high-concentration erythromycin bacterial residue, the dialysis fluid obtained from the concentration can be recovered and reused, increasing the yield of erythromycin products. Furthermore, this invention provides a specific membrane cleaning scheme, achieving a membrane flux recovery rate of ≥96%, extending membrane lifespan, and ensuring long-term stable system operation. This invention provides a good operating method for the industrial production of antibiotic products and has promising application prospects.

[0026] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0027] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Detailed Implementation

[0028] Unless otherwise specified, the raw materials and equipment used in the specific embodiments of the present invention are all known products and were obtained by purchasing commercially available products.

[0029] Taking erythromycin as an example, the process steps and process conditions range for each step in the concentration and volume reduction treatment method for antibiotic bacterial residue of the present invention are as follows: Step 1: Pretreatment of the feed liquid Collect the wet bacterial residue after preliminary separation of erythromycin fermentation broth by plate and frame, centrifugation or static membrane, add water or filtrate to adjust to a suitable concentration. After adjustment, the centrifuged bacterial concentration (volume ratio) of the liquid is 65%-78%, the total solids content (weight ratio) is 10%-18%, and the pH is natural (about 6.5-8.0).

[0030] Step 2: Rotating dynamic ceramic membrane for deep volume reduction and concentration The pretreated feed solution is pumped into a rotary dynamic ceramic membrane system for cross-flow filtration, continuously separating the dialysate until the concentrate reaches the target volume. The core equipment uses a rotary dynamic ceramic membrane with a preferred pore size of 50nm or 100nm, an operating pressure (inlet pressure) of 1.8-2.2 Bar, and a membrane tangential velocity of 7.0-8.0 m / s. A "permissible temperature rise" strategy is adopted to address the characteristics of the bacterial residue, meaning no external cooling is performed, allowing the feed solution to naturally heat up due to circulation pumping and membrane shear friction. The operating temperature is controlled at 50-60℃ (i.e., the temperature should not exceed 50-60℃, and normal operation typically does not exceed 60℃). The concentration endpoint is indicated by the volumetric concentration factor. Under optimal conditions, the concentration endpoint is controlled at 1.7-2.0 times (corresponding to a bacterial concentration ≥92%). By optimizing parameters such as the membrane tangential velocity, the volumetric concentration factor can be stably increased to over 1.8 times, and can reach a maximum of approximately 2.0 times. The concentration endpoint refers to the critical state under specific process conditions where continued concentration will result in loss of fluidity due to a sharp increase in material viscosity, uncontrollable equipment operation risks, or loss of operational feasibility due to unit energy consumption costs exceeding economic benefits.

[0031] Step 3: Membrane System Cleaning and Regeneration The membrane after step two was cleaned using a two-step "acid-base oxidation" cleaning method. The first step, acid washing, used a 0.8%-1.2% (v / v) nitric acid aqueous solution and circulated it for 30-45 minutes at 50-55℃, followed by rinsing with water until the pH was neutral (pH 6.5-7.5). The second step, base oxidation washing, used a mixed cleaning solution (water as solvent) containing 1.5%-2.5% (w / v) sodium hydroxide and 0.5%-1.5% (w / v) hydrogen peroxide and circulated it for 30-50 minutes at 45-55℃, followed by rinsing with water until the pH was neutral (pH 6.5-7.5), thus obtaining the cleaned membrane.

[0032] Step 4: Resource recycling of dialysis fluid After collecting the clarified dialysis solution (transmittance > 99%) produced in step two, it is used as process water to supplement the erythromycin solvent extraction workshop. The preferred reuse point is the back-extraction solution preparation section or the top washing section of the extraction tower, replacing 10%-30% of the pure water used in these sections.

[0033] The method for concentrating and reducing the volume of antibiotic bacterial residue of the present invention is applicable to the treatment of wet bacterial residue after filtration of antibiotic fermentation broth obtained by various methods in the art. The erythromycin wet bacterial residue used in the embodiments of the present invention is prepared by the following conventional method: Erythromycin Streptomyces spores are activated by slant culture and subjected to three-stage seed culture, then inoculated into the fermentation medium at an inoculum rate of 10%~20%, and cultured at 32~34℃ for 7~10 days to obtain erythromycin fermentation broth; the fermentation broth is then separated by plate and frame filtration or centrifugation, and the solid portion is collected to obtain the erythromycin wet bacterial residue.

[0034] Example 1: Concentration and Volume Reduction Treatment Method for Antibiotic Microbial Residue of the Present Invention Step 1: Pretreatment of the feed solution: The wet bacterial residue obtained from the erythromycin fermentation broth through plate and frame filtration is mixed with purified water at a volume ratio of approximately 1:1. The mixture is stirred at 200-500 rpm for 15-30 minutes to prepare the slurry. After preparation, the slurry is centrifuged at 3500-4500 rpm for 10-30 minutes. The precipitate is collected, and purified water is added to adjust the centrifuged bacterial concentration to 75.2%, with a total solids content of 15.5%. This yields the pretreated solution, with a viscosity of 72 mPa·s. Centrifuged bacterial concentration refers to the percentage of the volume of the precipitated wet bacterial cells (bacterial sludge) relative to the total volume of the centrifuged system after centrifugation.

[0035] Step 2: Rotating dynamic ceramic membrane for deep volume reduction and concentration A rotating dynamic ceramic membrane with a pore size of 50 nm was used. The pretreated feed solution was pumped into the rotating dynamic ceramic membrane for cross-flow filtration, continuously separating the dialysate. During filtration, the operating pressure (inlet pressure) was 2.0 Bar, and the membrane tangential velocity was 7.0 m / s. The temperature rose naturally during concentration without external cooling, but was controlled to remain below 60°C; under normal operation, the temperature typically did not exceed 60°C. Filtration lasted for 165 minutes to reach the concentration endpoint, with a final concentration factor of 1.81 times (final bacterial concentration of 95.3%), yielding the concentrated solution.

[0036] Step 3: Membrane System Cleaning and Regeneration The membrane after step two is cleaned. The first step, acid washing, uses a 1.0% (v / v) nitric acid aqueous solution to circulate and wash at 52°C for 40 minutes, and then rinses with water until neutral (pH 6.5-7.5). The second step, alkaline oxidation washing, uses a mixed aqueous solution containing 2.0% (w / v) sodium hydroxide and 1.0% (w / v) hydrogen peroxide to circulate and wash at 50°C for 45 minutes, and finally rinses with water until neutral (pH 6.5-7.5), thus obtaining the cleaned membrane.

[0037] Step 4: Resource recycling of dialysis fluid The clarified dialysis solution produced in step two (with a transmittance of 99.6% and tested to contain erythromycin potency) is recovered and reused.

[0038] Reuse method: In the laboratory simulation of erythromycin solvent extraction-back-extraction process, 25% of purified water was used to replace the purified water to prepare the back-extraction buffer.

[0039] Results and Effects: In a single back-extraction operation, the erythromycin transfer rate in the experimental group was 6.5% higher than that in the blank control group, which used purified water exclusively. Through full-process material balance simulation, this reuse operation is expected to increase the overall yield of erythromycin by approximately 2.3%.

[0040] This study verified that the reuse of dialysis fluid can bring direct economic benefits.

[0041] result: Final temperature: 57.8℃. The final temperature is the final temperature of step two, which is in the range of 50-60℃.

[0042] Concentration factor: 1.81 times (final bacterial concentration 95.3%).

[0043] The average flux of the filter membrane during the filtration process was 24.1 LMH, and the final flux was 18.2 LMH.

[0044] Dialysis fluid transmittance: 99.6%.

[0045] Membrane flux recovery rate after cleaning: 98.9%. The method for determining the membrane flux recovery rate is as follows: before and after cleaning, the pure water flux of the membrane is measured using deionized water under the same operating conditions (temperature 25℃, pressure 2.0 Bar, membrane surface tangential velocity 7.0 m / s), and calculated using the following formula: Membrane flux recovery rate = (pure water flux after cleaning / initial pure water flux) × 100%.

[0046] The method in Example 1 has the following advantages: (1) Excellent volume reduction performance: The volume concentration ratio of high-concentration erythromycin bacterial residue is increased from 1.3 times, which is difficult to surpass by static membranes, to more than 1.8 times, which reduces the volume of subsequent treatment sections by more than 44%, thus solving the technical bottleneck in the industry.

[0047] (2) High and stable membrane flux: The average flux was 24.1 LMH, and the final flux was still 18.2 LMH, proving that the high shear force effectively suppressed membrane fouling and overcame the technical problem of sudden drop in static membrane flux.

[0048] (3) Natural heating and energy saving: The concentration endpoint temperature is 57.8℃, which falls within the optimal operating window of 50-60℃. No external heating or cooling is required, which significantly reduces energy consumption.

[0049] (4) Excellent membrane cleaning and regeneration: The two-step method of "acid washing + alkaline oxidation washing" is adopted, and the membrane flux recovery rate reaches 98.9%, which ensures the long-term stable operation of the membrane.

[0050] (5) High-value reuse of dialysate: The dialysate has a transmittance of 99.6%. It is used to replace purified water at a ratio of 25% for back-extraction, which increases the erythromycin transfer rate by 6.5% and the total yield of the whole process is expected to increase by 2.3%, realizing the resource-based value-added of by-products.

[0051] In summary, this embodiment achieves high-concentration of high-viscosity bacterial residue, efficient cleaning, and high-value reuse of dialysis liquid through low-pressure (2.0 Bar) and low-energy operation, resulting in outstanding comprehensive economic and environmental benefits.

[0052] Example 2: Concentration and volume reduction treatment method for antibiotic bacterial residue of the present invention The raw materials and concentration / volume reduction treatment methods used in Example 2 are the same as those in Example 1. The only difference is that the membrane tangential velocity in step two of Example 1 is increased to 7.8 m / s to enhance the shear force. The filtration process lasts for 190 minutes to reach the concentration endpoint.

[0053] result: Final temperature: 58.5℃.

[0054] Concentration factor: 2.05 times (final bacterial concentration 96.2%).

[0055] The average flux of the filter membrane during filtration was 22.0 LMH, and the final flux was 15.3 LMH.

[0056] Dialysis fluid transmittance: 99.4%.

[0057] Membrane flux recovery rate after cleaning: 98.9%.

[0058] Comparative Example 1: Static ceramic membrane treatment of the same feed solution Comparative Example 1 used the same raw materials and concentration / volume reduction treatment method as Example 1, the only difference being that the 50nm rotating dynamic ceramic membrane used in step two of Example 1 was replaced with a tubular static ceramic membrane of the same material and 50nm pore size. The operating pressure (inlet pressure) during filtration was the same as in Example 1, which was 2.0 Bar.

[0059] result: The membrane flux decreased sharply from 35 LMH to 9.2 LMH within the first 15 minutes.

[0060] After 120 minutes of operation, the process was stopped because the flux had dropped to 4.8 LMH and could not be concentrated further. The final concentration factor was only 1.21 times, and the average flux was 9.0 LMH.

[0061] After cleaning with the same formula, the membrane flux recovery rate was 83.5%.

[0062] Comparison of Example 1 and Comparative Example 1: The technical solution of Example 1 of the present invention achieves a concentration factor of 1.81 times, which is approximately 1.5 times the concentration factor of Comparative Example 1 (1.21 times); the technical solution of Example 2 of the present invention achieves a concentration factor of 2.05 times, which is approximately 1.7 times the concentration factor of Comparative Example 1 (1.21 times). Furthermore, the embodiments of the present invention have significant advantages over Comparative Example 1 in terms of flux stability and cleaning recovery effect.

[0063] The following specific experimental examples demonstrate the beneficial effects of the present invention.

[0064] Experimental Example 1: The Effect of Operating Pressure on Concentration Effect Based on the method described in Example 1, the process conditions were fixed: membrane tangential velocity of 7.0 m / s, natural temperature rise during concentration, and temperature controlled below 60°C. Only the operating pressure during filtration was varied to 1.5 Bar, 2.0 Bar, and 2.5 Bar. The concentration endpoint was defined as a flux below 10 LMH or a running time exceeding 3 hours. The results are shown in Table 1.

[0065] Table 1. Effects of different operating pressures on concentration efficiency Results analysis: When the pressure increased from 1.5 Bar to 2.0 Bar, the concentration factor increased significantly from 1.45 to 1.81, and the average flux increased by 49%. When the pressure continued to rise to 2.5 Bar, the increase in concentration factor and flux was not significant, and the final flux decreased slightly, indicating that excessive pressure would increase the membrane fouling rate. It has been demonstrated that the optimal pressure range of 1.8-2.2 Bar can achieve the best concentration effect with lower energy consumption.

[0066] Experimental Example 2: The Effect of Temperature Strategy on Flux Stability Based on the method described in Example 1, with fixed process conditions: pressure 2.0 Bar, membrane tangential velocity 7.0 m / s, only the temperature control method during concentration was changed, including forced cooling (using external 9°C cooling water during concentration), natural temperature rise (same as in Example 1), and external heating (using steam heating during concentration). The process was continued until the concentration factor was ≥1.7 or the flux decreased to less than 40% of the initial value. The results are shown in Table 2.

[0067] Table 2. Results of the impact of temperature strategy on flux stability Results analysis: When forced cooling occurs (≤40℃), the viscosity of the feed liquid is too high, the throughput decreases rapidly, and the concentration factor is only 1.32. When the temperature is naturally raised to 50-60℃, the viscosity of the liquid decreases, the diffusion coefficient increases, the throughput stabilizes, and the concentration factor reaches 1.81. Although external heating (>65℃) results in a higher initial throughput, it may lead to increased protein denaturation and contamination, thus reducing the concentration effect. This demonstrates that the "allowable temperature rise" strategy (50-60℃) is key to achieving high concentration.

[0068] Experimental Example 3: Effect of membrane tangential velocity on concentration factor Based on the method described in Example 1, the process conditions were kept constant: pressure 2.0 Bar, natural temperature rise. Only the membrane tangential velocity was varied to 4.5 m / s, 7.0 m / s, and 7.8 m / s. The process was continued until the flux was below 15 LMH or the concentration factor was ≥1.8. The results are shown in Table 3.

[0069] Table 3. Effect of different membrane tangential velocities on concentration factor Results analysis: At a linear velocity of 4.5 m / s, the shear force is insufficient, concentration polarization is severe, and the concentration factor is only 1.38. At a linear velocity of 7.0 m / s, high shear effectively suppresses contamination, with a concentration factor of 1.81. When the linear velocity is increased to 7.8 m / s, although the average flux decreases slightly (due to operating at a higher concentration), the concentration factor increases to 2.05, reaching an industry-leading level. It has been proven that a membrane surface linear velocity ≥ 7.0 m / s is a necessary condition for achieving depth reduction, with the preferred range being 7.0-8.0 m / s.

[0070] Experimental Example 4: The Effect of Cleaning Scheme on Membrane Flux Recovery The fouled membrane (initial flux approximately 120 LMH) after operation in Example 1 was cleaned according to the following procedure: 4-1 (Rinse with clean water): Use deionized water to circulate and clean for 40 minutes at 50℃. After draining, rinse with deionized water until neutral (pH value is 6.5-7.5).

[0071] 4-2 (0.5% nitric acid cleaning + water washing): Use a 0.5% (v / v) nitric acid aqueous solution to circulate and clean for 40 minutes at 52℃. After draining, rinse with deionized water until neutral (pH value is 6.5-7.5).

[0072] 4-3 (1.0% nitric acid cleaning + water washing): Use a 1.0% (v / v) nitric acid aqueous solution to circulate and clean for 40 minutes at 52℃. After draining, rinse with deionized water until neutral (pH value is 6.5-7.5).

[0073] 4-4 (1.0% nitric acid + 2.0% NaOH cleaning): First, use a 1.0% (v / v) nitric acid aqueous solution to circulate and clean at 52°C for 40 minutes, then rinse with water until neutral (pH 6.5-7.5); then use a 2.0% (w / v) sodium hydroxide aqueous solution to circulate and clean at 50°C for 45 minutes, and finally rinse with deionized water until neutral (pH 6.5-7.5).

[0074] 4-5 (1.0% nitric acid + 2.0% NaOH + 1.0% H2O2 washing): Same as Example 1 (first 1.0% nitric acid, 52℃ / 40min, water washing; then 2.0% NaOH + 1.0% H2O2, 50℃ / 45min, water washing).

[0075] 4-6 (1.0% nitric acid + 2.0% NaOH + 2.0% H2O2 cleaning): First, use a 1.0% (v / v) nitric acid aqueous solution to circulate and clean at 52℃ for 40 minutes, then rinse with water until neutral (pH 6.5-7.5); then use a mixed aqueous solution containing 2.0% (w / v) sodium hydroxide and 2.0% (w / v) hydrogen peroxide to circulate and clean at 50℃ for 45 minutes, and finally rinse with deionized water until neutral (pH 6.5-7.5). The results are shown in Table 4.

[0076] Table 4. Results of the impact of cleaning scheme on membrane flux recovery rate Results analysis: Simple water or acid washing cannot effectively remove organic pollutants, with a recovery rate of <85%; alkaline washing can remove some protein, but leaves serious residues; alkaline oxidation washing with the addition of 1.0% H2O2 can synergistically remove protein and mycelial residues, with a recovery rate of 98.9%; however, excessively high concentrations of H2O2 (2.0%) do not significantly improve the recovery rate, but instead increase costs and safety risks.

[0077] The results show that the two-step method of "nitric acid dissociation-hydrogen peroxide alkaline oxidation" works best in the H2O2 concentration range of 0.5-1.5%.

[0078] Experimental Example 5: Comparison of effects with static membrane process Comparison of the filtration effects of Embodiment 1, Embodiment 2 and Comparative Example 1 of the present invention.

[0079] Table 5. Comparison of filtration effects of Examples 1, 2 and Comparative Example 1 of the present invention Results analysis: When treating high-viscosity bacterial residue with static membranes, the flux decreases sharply within 15 minutes, making industrial-scale deep volume reduction impossible. The technical solution of Example 1 of this invention achieves a concentration factor of 1.81 times, approximately 1.5 times that of Comparative Example 1 (1.21 times); the technical solution of Example 2 of this invention achieves a concentration factor of 2.05 times, approximately 1.7 times that of Comparative Example 1 (1.21 times). Furthermore, the embodiments of this invention show significant advantages over Comparative Example 1 in terms of flux stability and cleaning recovery effect.

[0080] The above experimental results show that: (1) Operating pressure: 1.8-2.2 Bar is the optimal window. Below 1.8 Bar, the effect is poor. Above 2.2 Bar, the energy consumption increases but the effect is not significantly improved.

[0081] (2) Temperature strategy: Naturally heating to 50-60℃ (allowable temperature rise) is the key to achieving high concentration; too low or too high is not conducive. (3) Membrane surface tangential velocity: ≥7.0 m / s can effectively suppress fouling, with a preferred range of 7.0-8.0 m / s; (4) Cleaning method: The two-step method of "nitric acid dissociation-hydrogen peroxide alkaline oxidation" works best in the range of H2O2 concentration of 0.5-1.5%; (5) Overall effect: Within the preferred parameter range, the technical solution of the present invention can stably increase the concentration multiple of high viscosity bacterial residue to more than 1.8 times, and up to 2.05 times, which is about 1.7 times higher than the static membrane process. The membrane flux recovery rate is ≥98%, and the dialysis liquid can be reused at high value.

[0082] In summary, this invention provides a method for concentrating and reducing the volume of antibiotic bacterial residue. This specific concentration and volume reduction method can significantly increase the concentration ratio of high-concentration erythromycin bacterial residue under low energy consumption and low cost conditions, reducing subsequent treatment volume, lowering treatment costs, and improving the efficiency of solid waste resource utilization. Simultaneously, during the concentration of high-concentration erythromycin bacterial residue, the dialysis fluid obtained from the concentration can be recovered and reused, increasing the yield of erythromycin products. Furthermore, this invention provides a specific membrane cleaning scheme, achieving a membrane flux recovery rate of ≥96%, extending membrane lifespan, and ensuring long-term stable system operation. This invention provides a good operating method for the industrial production of antibiotic products and has promising application prospects.

Claims

1. A method for concentrating and reducing the volume of antibiotic bacterial residue, characterized in that: Includes the following steps: (1) The antibiotic fermentation broth was separated into solid and liquid to obtain wet bacterial residue, which was then diluted with an aqueous solution to obtain a feed liquid; (2) The feed liquid obtained in step (1) is pumped into a membrane separation device that can generate shear force for cross-flow filtration to obtain a reduced volume concentrate and a separated dialysate.

2. The concentration and volume reduction method according to claim 1, characterized in that: In step (1), the solid-liquid separation method is plate and frame filtration, centrifugal separation or static membrane separation; And / or, in step (1), the liquid is obtained by diluting wet bacterial residue with water, the centrifuged bacterial concentration of the liquid is 65%-78%, and the total solid content is 10%-18%.

3. The concentration and volume reduction method according to claim 1, characterized in that: In step (2), the membrane separation device that can generate shear force is a rotary dynamic ceramic membrane; Preferably, in step (2), the pore size of the rotating dynamic ceramic membrane is 50-100 nm.

4. The concentration and volume reduction method according to claim 1, characterized in that: In step (2), the inlet pressure of the membrane during cross-flow filtration is 1.5-2.5 Bar, and the tangential velocity of the membrane surface is 5.0-8.0 m / s.

5. The concentration and volume reduction method according to claim 4, characterized in that: In step (2), the inlet pressure of the membrane during cross-flow filtration is 1.8-2.2 Bar, and the tangential velocity of the membrane surface is 7.0-8.0 m / s; Preferably, in step (2), the inlet pressure during cross-flow filtration is 2.0 Bar.

6. The concentration and volume reduction method according to claim 1, characterized in that: In step (2), no external cooling or external heating is performed during the cross-flow filtration.

7. The concentration and volume reduction method according to claim 1, characterized in that: In step (2), the separated dialysis fluid can be used as process water for antibiotic extraction.

8. A method for cleaning the membrane separation device capable of generating shear force as described in any one of claims 1 to 7, characterized in that: Includes the following steps: (A) Pickling: The membrane separation device capable of generating shear force after filtration according to any one of claims 1 to 7 is cleaned in a nitric acid solution, and then rinsed with water until neutral; (B) Alkaline oxidation washing: The membrane separation equipment after cleaning in step (A) is cleaned in a mixed cleaning solution containing sodium hydroxide and hydrogen peroxide. After cleaning, it is rinsed with water until neutral.

9. The method according to claim 8, characterized in that: In step (A), the nitric acid solution is an aqueous nitric acid solution with a volume percentage of 0.8%-1.2%; And / or, in step (A), the cleaning method is to perform cyclic cleaning at a temperature of 50-55°C for 30-45 minutes; And / or, in step (A), after cleaning, rinse with water until the pH value is 6.5-7.5; And / or, in step (B), the mixed cleaning solution containing sodium hydroxide and hydrogen peroxide is an aqueous solution containing 1.5%-2.5% sodium hydroxide and 0.5%-1.5% hydrogen peroxide by mass volume; And / or, in step (B), the cleaning method is to perform cyclic cleaning at a temperature of 45-55°C for 30-50 minutes; And / or, in step (B), rinse with water after cleaning until the pH value is 6.5-7.

5.

10. The method according to claim 9, characterized in that: In step (A), the nitric acid solution is a 1.0% (v / v) aqueous nitric acid solution; And / or, in step (A), the cleaning method is to perform a cyclic cleaning at 52°C for 40 minutes; And / or, in step (B), the mixed cleaning solution containing sodium hydroxide and hydrogen peroxide is an aqueous solution containing 2.0% sodium hydroxide and 1.0% hydrogen peroxide by mass volume. And / or, in step (B), the cleaning method is to perform a cyclic cleaning at 50°C for 45 minutes; Preferably, in step (A), the membrane separation device that can generate shear force is a rotary dynamic ceramic membrane.

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