A method for biophysical degradation of antibiotics in a drug residue

Abstract

The present application relates to the technical field of dregs of medicine antibiotic degradation, specifically to a method for antibiotic biological and physical degradation in dregs of medicine, comprising the following steps: step S1, dregs of medicine pretreatment; step S2, strain activation and mixing; step S3, sectional temperature control fermentation; step S4, ultraviolet irradiation; step S5, post-treatment. The present application not only degrades part of antibiotics through early fermentation, but also changes the microstructure of dregs of medicine through microbial metabolism, releases antibiotics from organic matrix, and reduces the energy consumption demand of subsequent irradiation through self-heating. Late ultraviolet-ozone synergistic irradiation not only completely degrades residual antibiotics, but also slightly modifies the organic matter of dregs of medicine using the weak oxidizing property of ozone, thereby improving the nutrient release efficiency when used as organic fertilizer.

Description

Technical Field

[0001] This invention relates to the field of antibiotic degradation technology in pharmaceutical residues, specifically a method for the biological and physical degradation of antibiotics in pharmaceutical residues. Background Technology

[0002] The pharmaceutical industry generates tens of millions of tons of antibiotic-containing waste residue annually. If this waste is discharged directly without proper treatment, antibiotic residues will seep into the soil and water, inducing the growth of drug-resistant bacteria in the environment, threatening ecological security and human health. It falls under the category of hazardous solid waste explicitly listed in the "National Hazardous Waste List." Current mainstream treatment technologies have significant shortcomings and cannot meet the industry's demands for "high efficiency, low consumption, no secondary pollution, and resource recovery." Existing technologies suffer from the following problems: Chemical degradation methods, which employ ozone oxidation, acid-base neutralization, or advanced oxidation technologies, can rapidly degrade antibiotics, but they have two major problems: First, the reaction process easily generates toxic intermediates such as chlorophenols and nitro compounds. GC-MS analysis shows that some of these byproducts are more toxic than the original antibiotics, and chemical residues can contaminate the residue, rendering it unusable. Second, the cost is high, with the purchase of chemical reagents and wastewater treatment accounting for more than 35% of the total treatment cost. Processing 10 tons of residue per day requires an additional investment of 20,000 to 30,000 yuan, making it unsuitable for small and medium-sized enterprises.

[0003] Single physical degradation methods include high-temperature incineration and simple ultraviolet irradiation. High-temperature incineration requires temperatures above 800℃, which can completely destroy antibiotics, but it also carbonizes more than 80% of the organic matter in the residue, completely eliminating its resource value. Furthermore, the dioxins produced by incineration require additional desulfurization and denitrification equipment for treatment, posing a high risk of secondary pollution. Simple ultraviolet irradiation relies on high-power equipment, and the deep antibiotic degradation rate is less than 60%, which cannot meet the requirement of "antibiotic residue <10mg / kg" in GB4284~2018 "Standard for Pollutant Control of Agricultural Sludge".

[0004] Single biodegradation method: Fermentation using pure EM bacteria or yeast is environmentally friendly, but antibiotics have a strong inhibitory effect on microorganisms. When the concentration of antibiotics in the residue is >50mg / kg, the activity of the microbial community decreases by more than 60%, the degradation cycle is as long as 12 to 15 days, and the final degradation rate is only 40 to 50%. Moreover, it cannot inactivate harmful bacteria in the residue, and there are safety risks in subsequent use.

[0005] In summary, to address the aforementioned problems, we propose a method for the biological and physical degradation of antibiotics in pharmaceutical residues. Summary of the Invention

[0006] The purpose of this invention is to provide a method for the biological and physical degradation of antibiotics in medicinal residues, so as to solve the problems mentioned in the background art.

[0007] To achieve the above objectives, the present invention provides the following technical solution: A method for the biological and physical degradation of antibiotics in pharmaceutical residues includes the following steps: Step S1, Pretreatment of drug residue: Remove impurities from antibiotic drug residue, and then coarsely crush it to a particle size of 2-5 mm using a jaw crusher, dry it with forced air at 50-60℃ to a moisture content of 30-35%, and finely pulverize it to a particle size of 0.1-0.3 mm using a planetary ball mill to obtain pretreated drug residue; Step S2, Strain Activation and Mixing: Mix EM bacteria and Bifidobacterium longum ATCC15707 at a mass ratio of 4:1, inoculate LB medium at a 1% inoculum, and culture at 37℃ and 180 r / min for 12-16 h until the bacterial concentration reaches 10. 8 ~10 9 CFU / mL; Mix the activated bacterial solution with the pretreated drug residue at a mass ratio of 1:11 to 1:13 and stir at 30 to 40 r / min for 15 to 20 min; Step S3, segmented temperature-controlled fermentation: First, aerobic fermentation is carried out at 26℃ and an aeration rate of 0.6~1.0L / (L・min) for 72h. Then, the aeration is stopped, and the temperature is naturally raised to 68~72℃ by utilizing the heat generated by microbial metabolism. After stirring at 20~25r / min for 5~8min, the temperature is maintained for another 48h. Step S4, Ultraviolet Irradiation: Spread the fermented residue to a thickness of 1-2 cm, and irradiate it continuously for 8 hours under the conditions of wavelength 254 nm and irradiation intensity of 15-20 mW / cm². Step S5, Post-processing: The irradiated residue is vacuum dried at 60-70℃ and -0.08MPa to a moisture content of 10-12%, and then ultra-finely pulverized to a particle size of 50-100μm to obtain the degraded residue product.

[0008] Preferably, the antibiotic residue in step S1 is waste residue generated during the pharmaceutical manufacturing process of cephalosporins, penicillins, or macrolides.

[0009] Preferably, the viable count of EM bacteria in step S2 is ≥10¹. 0 CFU / g, viable count of Bifidobacterium longum ≥10 9 CFU / g, stirred using a twin-helix stirrer.

[0010] Preferably, the stirring in step S3 is done with a paddle mixer, and the fermentation process does not require external heating.

[0011] Preferably, the irradiation in step S4 is carried out in a continuous ultraviolet irradiation chamber equipped with a stainless steel conveying device, with a conveying speed of 0.5 m / min.

[0012] Compared with the prior art, the beneficial effects of the present invention are: This invention not only degrades some antibiotics through early fermentation, but also alters the microstructure of the drug residue through microbial metabolism, allowing antibiotics to be released from the organic matrix. At the same time, self-heating reduces the energy consumption requirement for subsequent irradiation. In the later stage, ultraviolet-ozone synergistic irradiation not only completely degrades residual antibiotics, but also uses the weak oxidizing properties of ozone to slightly modify the organic matter of the drug residue, improving its nutrient release efficiency when used as organic fertilizer.

[0013] This invention requires no external heating and utilizes the self-heating of microorganisms to achieve a temperature jump, which saves energy, inactivates harmful bacteria through high temperature, and enhances the activity of degrading enzymes.

[0014] This invention achieves the highest hydroxyl radical yield under a combination of ultraviolet and ozone parameters, while avoiding the oxidation of organic matter caused by excessive ozone, thus improving the antibiotic degradation rate compared to simple ultraviolet irradiation. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the process of the present invention. Detailed Implementation

[0016] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0017] like Figure 1 As shown, a method for the biological and physical degradation of antibiotics in drug residues includes the following steps: Step S1, Pretreatment of medicinal residue: Step S11, Targeted removal of impurities: Select raw material residue containing antibiotics and remove impurities such as stones, plastic particles, and metal scraps by passing it through a 10mm aperture vibrating screen to avoid impurities hindering subsequent mixing and ensure that the fungal residue is mixed evenly. Step S12, graded crushing: First-stage crushing: A jaw crusher is used to crush the dregs to 2-5mm at a speed of 200r / min, breaking the blocky agglomeration structure and reducing the energy consumption of subsequent fine grinding; Second-stage pulverization: A planetary ball mill is used with a ball-to-material ratio of 5:1 and a rotation speed of 300 r / min to pulverize the coarsely crushed drug residue to 0.1-0.3 mm, which increases the specific surface area of ​​the drug residue by 4-6 times and significantly increases the contact area between the bacteria and the antibiotics. Step S13, Drying: The pulverized medicinal residue is placed in a forced-air drying oven at 50-60℃ and dried to a moisture content of 30-35%. This moisture content satisfies the water requirements for microbial fermentation, avoids the dormancy of the microbial community due to excessively low moisture content, and prevents anaerobic putrefaction due to excessively high moisture content. It also avoids the destruction of organic matter such as polysaccharides and proteins in the medicinal residue by high temperature.

[0018] Step S2, Strain Activation and Mixing: Step S21, Selection of bacterial strains and compounding ratio: EM bacteria and Bifidobacterium longum were mixed at a mass ratio of 4:1. The EM bacteria contained lactic acid bacteria, yeast, and actinomycetes, with a viable count ≥ CFU / g, viable count of Bifidobacterium longum ≥ CFU / g, strain number ATCC15707. Experiments have verified that at this ratio, the extracellular polysaccharide secreted by Bifidobacterium can encapsulate the actinomycetes in EM bacteria, reducing the inhibitory effect of antibiotics on actinomycetes; the organic acids produced by EM bacteria metabolism can promote the proliferation of Bifidobacterium, forming a "mutually promoting symbiotic" bacterial community, which has a higher antibiotic resistance than a single-strain bacteria. Step S22, Strain Activation: Culture medium preparation: sterile LB medium; The method for preparing sterile LB culture medium includes the following steps: Preparation before preparation: Basic reagents: peptone, yeast extract, sodium chloride, distilled water; pH adjustment reagents: 1 mol / L sodium hydroxide solution, 1 mol / L hydrochloric acid solution; Consumables: 1L volumetric flask, 2L beaker, glass rod, pipette, pH meter, autoclave, sterile conical flask.

[0019] The specific preparation steps are as follows: Step 1: Calculate the reagent usage (based on 1L of culture medium): Accurately weigh the following reagents according to the concentration requirements of "10g / L, 5g / L, 10g / L": Peptone: 10.0g; Yeast extract: 5.0g; NaCl: 10.0g.

[0020] Step 2, Dissolve the reagent: Add the weighed peptone, yeast extract, and NaCl to a 2L clean beaker in sequence; Add about 800 mL of distilled water to the beaker and stir slowly in the same direction with a glass rod; Place on a thermostatic magnetic stirrer at room temperature and stir at a speed of 150-200 r / min until all solid reagents are completely dissolved. Avoid local overheating that could cause reagent denaturation.

[0021] Step 3: Adjust the pH value: Stop stirring, immerse the pH meter probe in the culture medium solution, and record the initial pH after the reading stabilizes; If pH < 6.8: Slowly add 1 mol / L NaOH solution dropwise with a pipette, stirring gently with a glass rod as you add. Pause after each 0.5 mL drop, and wait for the pH meter reading to stabilize before continuing until the pH reaches 7.0–7.2. If pH > 7.2: Slowly add 1 mol / L HCl solution dropwise using a pipette, adjusting as above, until the pH reaches 7.0–7.2; After adjustment, rinse the pH meter probe with distilled water and dry it for later use.

[0022] Step 4, Volume Adjustment: Transfer the pH-adjusted culture medium solution to a 1L volumetric flask; Rinse the beaker and glass rod 2-3 times with a small amount of distilled water, and pour all the rinsing solution into the volumetric flask. Add distilled water to the volumetric flask until the liquid level is about 1-2 cm below the graduation mark; Use a dropper to add distilled water. Look at the graduation mark at eye level and align the lowest point of the concave meniscus with the 1L mark. Tighten the stopper of the volumetric flask and shake it 3-5 times to ensure uniform solution concentration.

[0023] Step 5: Dispensing and Sterilization Dispense the culture medium solution after it has been brought to a final volume into sterile Erlenmeyer flasks. The amount dispensed into each flask should not exceed 2 / 3 of the volume of the Erlenmeyer flask. Wrap the mouth of the flask with a cotton plug made of two layers of sterile gauze. Place the conical flasks into the autoclave, arranging them neatly. Ensure that all cold air inside the autoclave is expelled. After closing the exhaust valve, wait for the pressure to rise to 0.05 MPa, then open the exhaust valve to expel all the cold air before closing it again. Set the sterilization parameters: temperature 121℃, pressure 103.4kPa, sterilization time 20min; After sterilization, turn off the power to the sterilizer. When the pressure inside the sterilizer naturally drops to 0 MPa and the temperature drops to below 80°C, slowly open the exhaust valve, remove the conical flask, and place it on a sterile operating table to cool to room temperature for later use.

[0024] Step 6, Aseptic verification: Take 10 mL of cooled sterile LB medium, pour it into a sterile petri dish to make a plate, and incubate it in a 37℃ constant temperature incubator for 24 h; if no colonies grow on the plate, it means that the medium is sterile and can be used for bacterial activation; if colonies appear, it needs to be prepared again.

[0025] Activation conditions: Inoculate the culture medium with the compound bacterial strain at a 1% inoculation rate and incubate at 37℃ and 180 rpm for 12–16 h until the bacterial concentration reaches the target value. This ensures a sufficient number of microorganisms in the early stages of fermentation.

[0026] Uniform mixing of bacterial residue: Add the activated bacterial solution and pretreated medicinal residue to a stainless steel fermenter at a mass ratio of 1:12. Stir for 16-20 minutes using a double helix stirrer at a speed of 30-40 r / min. The double helix structure can prevent bacterial residue from agglomerating. The stirring speed has been optimized to ensure that there is no local agglomeration between the bacterial solution and the medicinal residue, and that they are in uniform contact.

[0027] Step S3, Segmented Temperature-Controlled Fermentation: Phase 1: Low-temperature propagation fermentation (26℃, 48–72 h): Sterile air is introduced into the fermenter at a rate of 0.8 L / (L·min) to maintain an aerobic environment. The microbial community uses glucose and amino acids in the drug residue as carbon and nitrogen sources to rapidly proliferate and build a dominant community. At the same time, it initially degrades low-concentration antibiotics (degradation rate of 35-40%), laying the foundation for subsequent high-temperature degradation.

[0028] Second stage: Deep fermentation at high temperature of 68-72℃ for 24-48 hours.

[0029] After the first stage is completed, ventilation is stopped, and the temperature naturally rises to 68-72°C by utilizing the heat generated by microbial metabolism (lactic acid bacteria producing lactic acid, yeast producing heat through respiration), without the need for external heating, thus saving energy. After the temperature stabilizes, use a paddle stirrer (17-25 r / min) to stir for 5-8 minutes to break the temperature and concentration gradient inside the residue and promote the release of antibiotics from deep layers.

[0030] High-temperature environments can activate actinomycetes to secrete degradation enzymes such as β-lactamase and esterase, which can efficiently destroy the active groups of antibiotics, increasing the total degradation rate of antibiotics to 85-90%. At the same time, high temperatures can inactivate most of the Escherichia coli and Salmonella in the drug residues, and the plate count method can be used to detect them, ensuring the safety of subsequent resource utilization.

[0031] Step S4, Ultraviolet Irradiation: Preparations before irradiation: The fermented residue is spread evenly in a continuous ultraviolet irradiation chamber equipped with a stainless steel conveyor. The thickness of the spread is 1-2 cm. If the thickness is too thick, the deep residue will not be able to be penetrated by ultraviolet light, and if it is too thin, the processing efficiency will be reduced. Irradiation parameters: A low-pressure mercury lamp with a wavelength of 254nm is used, with an irradiation intensity of 18mW / cm². Continuous irradiation for 8 hours is achieved, and the residue is continuously processed through a conveying device to avoid local over- or under-irradiation. Ultraviolet irradiation can directly destroy the molecular structure of residual antibiotics, improve the antibiotic degradation rate, and generate no toxic byproducts.

[0032] Step S5, Post-processing: Vacuum drying: The irradiated residue was placed in a vacuum drying oven at 65℃ and -0.08MPa and dried to a moisture content of 10-12%. The vacuum environment can avoid the carbonization of organic matter caused by high temperature. The organic matter retention rate was high as detected by the potassium dichromate method. Ultrafine grinding: The dried medicinal residue is ground to 60-100μm using an ultrafine grinder to obtain the degraded medicinal residue powder. This particle size is convenient for subsequent organic fertilizer formation and can also improve nutrient release efficiency.

[0033] Specific Implementation Example 1: Processing the residue of cephalosporin-based drugs.

[0034] (1) Experimental materials: Type of residue: Residue after cefadroxil administration, initial cefadroxil concentration 125 mg / kg, moisture content 65%, organic matter content 52%; Bacterial strain: EM bacteria live count CFU / g, Bifidobacterium longum ATCC15707, viable count 1.5×10⁻⁶ 9 CFU / g; Equipment: Vibrating screen, jaw crusher, planetary ball mill, constant temperature shaking table, 1000L fermentation tank, continuous ultraviolet irradiation chamber, vacuum drying oven, ultrafine pulverizer.

[0035] (2) Specific implementation steps: Step 1, Pretreatment: The dregs are removed by a 10mm vibrating screen, coarsely crushed to 3mm by a jaw crusher, dried at 55℃ with forced air until the moisture content is 32%, and finely pulverized to 0.2mm by a planetary ball mill. Step 2, Strain Activation: EM bacteria and Bifidobacterium were mixed at a ratio of 4:1, and 1% inoculum was added to LB medium. The mixture was incubated at 37℃ and 180 rpm for 14 hours on a shaker, resulting in a bacterial concentration of 1.1 × 10⁻⁶. 9 CFU / mL; Step 3, Mixing the bacterial solution and pretreated residue: Mix the bacterial solution and pretreated residue at a ratio of 1:12 and stir with a double spiral stirrer at 35 r / min for 18 min; Step 4, Segmented fermentation: Ferment at 26℃ and 0.8L / (L・min) for 72h, then naturally raise the temperature to 70℃, stir with a paddle mixer at 22r / min for 6min, and continue fermentation for 48h; Step 5, UV irradiation: Spread the residue 1.5cm apart and irradiate with a 254nm UV lamp for 8 hours; Step 6, Post-processing: Vacuum dry at 65℃ and -0.08MPa until the moisture content is 11%, then ultrafine pulverize to 80μm.

[0036] (3) Test results: Detection methods: HPLC for antibiotics, potassium dichromate method for organic matter, and plate count method for harmful bacteria.

[0037] Cefadroxil residue: 4.8 mg / kg, degradation rate 96.2%; Organic matter content: 49.1%, retention rate: 94.4%; Escherichia coli: Not detected; The product meets the GB / T19524.1~2019 standard for organic fertilizers, with organic matter ≥45% and total nutrients ≥45%. .

[0038] Specific Implementation Example 2: Treatment of Amoxicillin Pharmaceutical Residue.

[0039] (1) Experimental materials: Drug residue type: Drug residue after amoxicillin manufacturing, initial amoxicillin concentration 110 mg / kg, moisture content 62%, organic matter content 48%; Microbial strain: Same as in Example 1; Equipment: Same as in Example 1.

[0040] (2) Specific implementation steps: Pretreatment: After removing impurities, the dregs are coarsely crushed to 2mm, dried at 50℃ to a moisture content of 30%, and then finely pulverized to 0.1mm; Activation of bacterial strain: EM bacteria and Bifidobacterium were mixed at a ratio of 4:1 and cultured for 12 hours to achieve a bacterial concentration of 1.0 × 10⁻⁶. 9 CFU / mL; Mixing of bacterial culture and medicinal residue: Mix bacterial culture and medicinal residue at a ratio of 1:11 and stir at 30 r / min for 15 min; Segmented fermentation: Ferment at 25℃ and 0.6L / (L・min) for 72 hours, then naturally raise the temperature to 68℃, stir for 5 minutes, and continue fermentation for 48 hours; Ultraviolet irradiation: Spread the drug residue in a 1cm layer and irradiate it with a 254nm ultraviolet lamp (15mW / cm²) for 8 hours; Post-processing: Vacuum dry at 60℃ until moisture content is 10%, then pulverize to 50μm.

[0041] (3) Test results: Amoxicillin residue: 3.9 mg / kg, degradation rate: 96.5%; Organic matter content: 43.8%, retention rate: 91.2%; Salmonella: Not detected; The product meets the standards for organic fertilizer.

[0042] Specific Implementation Example 3: Treatment of erythromycin pharmaceutical residue.

[0043] (1) Experimental materials: Type of residue: Residue after erythromycin manufacturing (initial erythromycin concentration 95 mg / kg, moisture content 68%, organic matter content 50%). Microbial strain: Same as in Example 1; Equipment: Same as in Example 1.

[0044] (2) Specific implementation steps: Step 1, Pretreatment: After removing impurities from the dregs, coarsely crush them to 5mm, dry them at 60℃ to a moisture content of 35%, and then finely pulverize them to 0.3mm; Step 2, bacterial activation: EM bacteria and Bifidobacterium are mixed at a ratio of 4:1 and cultured for 16 hours to achieve a bacterial concentration of 1.2 × 10⁻⁶. 9 CFU / mL; Step 3, Mixing the bacterial solution and the medicinal residue: Mix the bacterial solution and the medicinal residue at a ratio of 1:13 and stir at 40 r / min for 20 min; Step 4, Segmented fermentation: Ferment at 27℃ and 1.0L / (L・min) for 72h, then naturally raise the temperature to 72℃, stir for 8min, and continue fermentation for 48h; Step 5, UV irradiation: Spread the residue in a 2cm layer and irradiate with a 254nm UV lamp (20mW / cm²) for 8 hours; Step 6, Post-processing: Vacuum dry at 70℃ until the moisture content is 12%, then pulverize to 100μm.

[0045] (3) Test results: Erythromycin residue: 3.2 mg / kg, degradation rate: 96.6%; Organic matter content: 46.5%, retention rate: 93.0%; Harmful bacteria: Not detected; The product meets the standards for organic fertilizer.

[0046] Comparative experiment: A comparative experiment was conducted to verify the advantages of the invention, and a control group was designed based on the original disclosed core technology.

[0047] Experimental preparation: Experimental materials: Raw material residue: Select similar drug residue suitable for the method of this invention (such as residue containing penicillin or cephalosporin antibiotics). To ensure consistency in the experimental basis of each group, the drug residue needs to be pretreated to unify its initial state: Initial antibiotic concentration: adjusted to 100±5 mg / kg (confirmed by high performance liquid chromatography-HPLC).

[0048] Initial moisture content: adjusted to 65±2% (determined by drying method).

[0049] Initial organic matter content: ≥50% (determined by potassium dichromate method).

[0050] bacterial strains: EM bacteria: viable count ≥ 1.0 × 10¹ 0 CFU / g.

[0051] Bifidobacteria: Bifidobacterium longum (e.g., ATCC15707), viable count ≥ 1.0 × 10⁻⁶ 9 CFU / g.

[0052] Chemical reagents: Ozone: Purity ≥ 99%.

[0053] 1 mol / L hydrochloric acid (HCl) and 1 mol / L sodium hydroxide (NaOH): for pH adjustment (if needed).

[0054] Sterile water: Used for diluting and adjusting moisture content.

[0055] Sample collection: Initial samples: Before the experiment, three parallel samples (100g each) were collected from the uniformly pretreated drug residue to determine the initial antibiotic concentration, organic matter content and moisture content.

[0056] Final product samples: After each group of experiments (including parallel samples), three parallel samples (100g each) were collected from the final product for the detection of various indicators.

[0057] Experimental equipment: Constant temperature shaking incubator: used to control fermentation temperature and provide a shaking environment.

[0058] Ultraviolet irradiation device: wavelength 254nm, power adjustable.

[0059] Ozone generator: used as a chemical control group.

[0060] Muffle furnace: Used as a control group for high-temperature incineration.

[0061] High-performance liquid chromatography (HPLC): used to detect antibiotic residue concentrations.

[0062] Potassium dichromate method apparatus: used to detect organic matter content.

[0063] pH meter: Used to monitor pH changes during fermentation.

[0064] Analytical balance: accuracy 0.0001g.

[0065] Forced-air drying oven: Used for drying samples.

[0066] Clean bench: Used for handling microbial cultures to ensure sterility.

[0067] Gas chromatography-mass spectrometry (GC-MS): used to detect potential toxic byproducts.

[0068] Test items and methods: Antibiotic residue concentration: Detected by HPLC.

[0069] Organic matter content: determined by potassium dichromate oxidation-external heating method.

[0070] Harmful bacteria count: Plate count method was used to detect Escherichia coli, Salmonella, etc.

[0071] Toxic byproducts: GC-MS analysis was used to detect chlorophenols, nitro compounds, dioxins, etc.

[0072] The experiment consisted of one experimental group and four control groups. Each experiment was repeated three times in parallel to ensure the reliability of the results.

[0073] Experimental group 1: The "biological + physical" synergistic degradation method of the present invention was adopted.

[0074] Control group 1: A single biological method (EM fermentation only) was used.

[0075] Control group 2: A single physical method (ultraviolet irradiation only) was used.

[0076] Control group 3: Chemical oxidation method (ozone treatment) was used.

[0077] Control group 4: Biological + traditional physical method (EM bacteria fermentation + high temperature incineration).

[0078] Experimental group 1: The specific steps are as follows: Mixing: Weigh 1.0 kg of the uniformly pretreated residue and place it in a sterile 5L fermenter. Add 5.0 g of EM bacteria and 5.0 g of Bifidobacterium. Adjust the moisture content of the mixture to 65% precisely with sterile water.

[0079] Staged fermentation: Phase 1: Place the fermenter in a constant temperature incubator, set the temperature to 26℃, and ferment for 72 hours. Stir manually every 12 hours to ensure uniform fermentation.

[0080] Second stage: After 72 hours, stop stirring and allow the system to naturally warm to approximately 70°C using heat generated by microbial metabolism. When the temperature reaches 70°C, stir manually for 5 minutes. Then continue fermentation at this temperature for 48 hours.

[0081] Ultraviolet irradiation: After fermentation, remove the material and spread it evenly on a stainless steel tray to a thickness of 2cm. Place it in an ultraviolet irradiator, set the wavelength to 254nm, the irradiation intensity to 15mW / cm², and irradiate for 8 hours.

[0082] Post-processing: The irradiated material was placed in a forced-air drying oven and dried at 60°C until the moisture content reached 12%. After removal, it was pulverized using a pulverizer, passed through a 100-mesh sieve, and the sample was collected for testing.

[0083] Control group 1 (fermentation with single EM bacteria): Mixing: Weigh 1.0 kg of uniformly pretreated residue and add 10.0 g of EM bacteria (total bacterial count consistent with the experimental group). The remaining operations are the same as step 1 of the experimental group.

[0084] Fermentation: The fermentation was carried out exactly according to the "segmented fermentation" parameters in step 2 of experimental group 1.

[0085] Post-processing: After fermentation, proceed directly to step 4 of experimental group 1, skipping the UV irradiation step. Collect samples for testing.

[0086] Control group 2 (single UV irradiation): Preparation: Weigh 1.0 kg of uniformly pretreated medicinal residue, without adding any inoculum.

[0087] Ultraviolet irradiation: Ultraviolet irradiation was carried out directly according to the parameters in step 3 of experimental group 1.

[0088] Post-processing: After irradiation, perform the "post-processing" step 4 of Experimental Group 1. Collect samples for testing.

[0089] Control group 3 (chemical oxidation method (ozone)): Preparation: Weigh 1.0 kg of uniformly pretreated medicinal residue, without adding any inoculum.

[0090] Ozone treatment: Spread the drug residue to a thickness of 2cm and place it in a sealed ozone reaction chamber. Turn on the ozone generator and maintain the ozone concentration at 50mg / m³ for 8 hours (the same as the ultraviolet irradiation time).

[0091] Post-processing: After the initial processing, perform the "post-processing" step 4 of the experimental group. Collect samples for testing.

[0092] Control group 4 (fermentation + high-temperature incineration): Mixing and fermentation: Follow steps 1 and 2 exactly as in control group 1 (single EM fermentation).

[0093] High-temperature incineration: After fermentation, the material is placed in a crucible and then placed in a muffle furnace. The temperature is set to 800℃ and incinerated for 30 minutes.

[0094] Post-processing: After the incineration product is cooled, it is taken out, crushed, passed through a 100-mesh sieve, and the sample is collected for testing.

[0095] Data recording: Record in detail the processing time, energy consumption (electricity, gas), and reagent usage for each group of experiments for cost accounting.

[0096] Data calculation: Antibiotic degradation rate (%) = [(initial concentration - final concentration) / initial concentration] × 100% Organic matter retention rate (%) = (Final organic matter content / Initial organic matter content) × 100% The cefadroxil residue from Example 1 was selected, and four control groups were set up to compare the degradation effect and cost:

[0097] This invention utilizes a synergistic bio-physical process, resulting in a significantly higher antibiotic degradation rate than single methods. It also features a shorter treatment cycle, higher organic matter retention, no toxic byproducts, and a cost that is only 45% of that of chemical methods, demonstrating clear comprehensive advantages.

[0098] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for the biological and physical degradation of antibiotics in medicinal residues, characterized in that, Includes the following steps: Step S1, Pretreatment of drug residue: Remove impurities from antibiotic drug residue, and then coarsely crush it to a particle size of 2-5 mm using a jaw crusher, dry it with forced air at 50-60℃ to a moisture content of 30-35%, and finely pulverize it to a particle size of 0.1-0.3 mm using a planetary ball mill to obtain pretreated drug residue; Step S2, Strain Activation and Mixing: Mix EM bacteria and Bifidobacterium longum ATCC15707 at a mass ratio of 4:1, inoculate LB medium at a 1% inoculum, and culture at 37℃ and 180 r / min for 12-16 h until the bacterial concentration reaches 10. 8 ~10 9 CFU / mL; Mix the activated bacterial solution with the pretreated drug residue at a mass ratio of 1:11 to 1:13, and stir at 30 to 40 r / min for 15 to 20 min; Step S3, segmented temperature-controlled fermentation: First, aerobic fermentation is carried out at 26℃ and an aeration rate of 0.6~1.0L / (L・min) for 72h. Then, the aeration is stopped, and the temperature is naturally raised to 68~72℃ by utilizing the heat generated by microbial metabolism. After stirring at 20~25r / min for 5~8min, the temperature is maintained for another 48h. Step S4, Ultraviolet Irradiation: Spread the fermented residue to a thickness of 1-2 cm, and irradiate it continuously for 8 hours under the conditions of wavelength 254 nm and irradiation intensity of 15-20 mW / cm². Step S5, Post-processing: The irradiated residue is vacuum dried at 60-70℃ and -0.08MPa to a moisture content of 10-12%, and then ultra-finely pulverized to a particle size of 50-100μm to obtain the degraded residue product.

2. The method for biological and physical degradation of antibiotics in medicinal residues according to claim 1, characterized in that, The antibiotic residue mentioned in step S1 is waste residue generated during the pharmaceutical manufacturing process of cephalosporins, penicillins, or macrolides.

3. The method for biological and physical degradation of antibiotics in medicinal residues according to claim 1, characterized in that, In step S2, the viable count of EM bacteria is ≥10¹. 0 CFU / g, viable count of Bifidobacterium longum ≥10 9 CFU / g, stirred using a twin-helix stirrer.

4. The method for biological and physical degradation of antibiotics in medicinal residues according to claim 1, characterized in that, The stirring in step S3 uses a paddle mixer, and the fermentation process does not require external heating.

5. The method for biological and physical degradation of antibiotics in medicinal residues according to claim 1, characterized in that, The irradiation in step S4 is carried out in a continuous ultraviolet irradiation chamber equipped with a stainless steel conveying device at a conveying speed of 0.5 m / min.

Images