Composite antibacterial agent and its application in feed

Abstract

The application discloses a kind of composite antibacterial agent and its application in feed, it is related to the technical field of feed additive.A kind of composite antibacterial agent, by mass parts, include the following components: antibacterial active substance 5-10 parts, natural plant extract 10-20 parts, organic acid 10-25 parts, antibacterial synergist 1-5 parts, carrier 45-65 parts, stabilizer 1-5 parts.The application realizes the widening of antibacterial spectrum and the enhancement of antibacterial activity by the synergistic cooperation of core antibacterial active substance and natural plant extract, can form effective inhibition to a variety of common pathogenic bacteria, fundamentally avoids the problem of drug resistance caused by traditional antibiotics, and there is no drug residue risk, meet the demand of green and healthy development of animal husbandry.

Description

Technical Field

[0001] This invention relates to the field of feed additive technology, specifically to a compound antibacterial agent and its application in feed. Background Technology

[0002] In the livestock farming sector, antibacterial products in feed additives are a key component in ensuring the health of farmed animals and improving farming efficiency. Traditional farming relies heavily on antibiotics to achieve antibacterial and bacteriostatic effects, but the long-term use of these products has exposed many prominent problems: On the one hand, the overuse of antibiotics can easily lead to the development of drug-resistant strains in farmed animals, which not only reduces the effectiveness of subsequent antibacterial treatments but may also be transmitted to humans through the food chain, posing a public health and safety hazard; on the other hand, these antibacterial agents are prone to forming drug residues in animals, affecting the quality and safety of livestock and poultry products, while also causing certain pollution to the farming environment.

[0003] To address these issues, the industry has gradually explored the use of natural plant extracts as alternatives to antibacterial agents. However, the application of single natural plant extracts also has significant drawbacks: their antibacterial spectrum is narrow, making it difficult to effectively inhibit various pathogenic bacteria and harmful microorganisms in the breeding environment; their antibacterial activity is weak, and their effectiveness is easily reduced by environmental factors during feed processing and animal digestion; furthermore, their inherent stability is insufficient, easily affected by factors such as temperature and pH, leading to changes in their composition and an inability to sustain antibacterial effects, thus failing to meet the needs of large-scale, modern livestock farming. In addition, the intestinal function of young livestock such as piglets is not yet fully developed, and the intestinal microecological balance is easily disrupted, requiring higher standards for the safety, effectiveness, and compatibility of antibacterial agents in feed. Existing antibacterial products either pose safety risks or have poor antibacterial effects, failing to simultaneously address both antibacterial effects and the need for intestinal microecological regulation.

[0004] Therefore, developing a compound antibacterial agent with a broad antibacterial spectrum, strong antibacterial activity, no drug resistance, and no drug residue to replace traditional antibiotic antibacterial agents has become an urgent need to promote the green and healthy development of animal husbandry. Summary of the Invention

[0005] The purpose of this invention is to address the problems of traditional antibiotic antibacterial agents in the prior art, such as drug resistance, drug residues, low safety, and narrow antibacterial spectrum and weak activity of single natural plant extracts. This invention provides a compound antibacterial agent and its application in feed. This compound antibacterial agent has the characteristics of broad antibacterial spectrum and strong antibacterial activity. It can also effectively regulate the intestinal microecology of animals, replace traditional antibiotics, and promote the green and healthy development of animal husbandry.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: An antibacterial active ingredient, wherein the antibacterial active ingredient is a compound represented by Formula 1: Formula 1: .

[0007] Furthermore, in Formula 1, the substituent R1 is selected from any one of methyl, phenyl, methyl ester, and chlorine.

[0008] Furthermore, the application of an antibacterial active ingredient in the preparation of a composite antibacterial agent.

[0009] A compound antibacterial agent, by weight, comprises the following components: 5-10 parts of antibacterial active ingredient, 10-20 parts of natural plant extract, 10-25 parts of organic acid, 1-5 parts of antibacterial synergist, 45-65 parts of carrier, and 1-5 parts of stabilizer. The antibacterial active ingredient is a compound with the structure shown above.

[0010] Furthermore, the natural plant extract is at least one of thymol, chlorogenic acid, and forsythoside.

[0011] Furthermore, the organic acid is at least one of citric acid, malic acid, lactic acid, and acetic acid, with a purity ≥98%.

[0012] Furthermore, the antibacterial synergist is a mixture of glyceryl monolaurate and glyceryl butyrate, with a mass ratio of 1:1.

[0013] Furthermore, the carrier is at least one of corn starch, wheat bran, and zeolite powder.

[0014] Furthermore, the stabilizer is at least one of vitamin E and disodium ethylenediaminetetraacetate.

[0015] Furthermore, the antibacterial active ingredient is any one of the following compounds: ; .

[0016] A method for preparing a composite antibacterial agent includes the following steps: S1. Pretreatment: The carrier is placed in a constant temperature drying oven and dried until the moisture content is ≤8%, then pulverized and passed through an 80-100 mesh sieve for later use; the natural plant extract and antibacterial active ingredient are pulverized to a 100-120 mesh sieve for later use. S2. Mixing: First, add the pretreated carrier to a high-speed mixer, adjust the speed to 1500-2000 r / min, stir for 5-10 min, then add the antibacterial active ingredient, natural plant extract, organic acid, and antibacterial synergist in sequence, and continue stirring for 15-20 min to obtain the premixed material; S3. Stabilization treatment: Add the stabilizer to the premixed material, adjust the mixer speed to 1200-1500 r / min, stir for 8-12 min to obtain the mixture; S4. Post-processing: The mixture is granulated, and the particle size is controlled at 0.8-1.2 mm. After granulation, it is placed in a constant temperature drying oven at 50-60℃ and dried until the moisture content is ≤5%. After cooling to room temperature, it is sieved to obtain a composite antibacterial agent.

[0017] Furthermore, the drying temperature in step S1 is 60-80℃.

[0018] Furthermore, in step S2, the temperature inside the mixer is controlled at 25-30℃ during the stirring process to avoid the antibacterial active ingredients and natural plant extracts becoming ineffective due to high temperatures.

[0019] Application of a compound antibacterial agent in piglet feed.

[0020] This invention, through the precise proportions and synergistic effects of its various formulation components, fundamentally solves the technical problems of drug resistance and residues in traditional antibiotic antibacterial agents, as well as the narrow antibacterial spectrum, weak activity, and insufficient stability of single natural plant extracts. The core antibacterial active ingredient, relying on a specific structure, possesses potent and broad-spectrum antibacterial activity, laying the foundation for its antibacterial effect. The natural plant extract and the antibacterial active ingredient form an antibacterial complement, further broadening the antibacterial spectrum and effectively inhibiting various pathogenic bacteria and harmful microorganisms in the breeding environment, thus solving the problem of the limited antibacterial range of single natural extracts. High-purity organic acids can regulate the acid-base environment of the animal's intestines, enhancing the antibacterial efficacy of both the antibacterial active ingredient and the natural plant extracts, while also promoting the proliferation of beneficial intestinal bacteria. The antibacterial synergist significantly improves the overall antibacterial activity, compensating for the weakness of single natural extracts. Furthermore, this synergist... The synergistic effect of the active ingredient system and organic acids better maintains the balance of the intestinal microecology in piglets, which is not yet fully developed, while taking into account both antibacterial and intestinal regulation needs. The stabilizer effectively resists the influence of environmental factors such as temperature and pH during feed processing, storage, and digestion in the animal's body, preventing changes in the composition and loss of activity of antibacterial active ingredients and natural plant extracts, thus solving the problem of insufficient stability of natural extracts. The carrier ensures the uniform dispersion and effective carrying of each antibacterial component, allowing the antibacterial components to exist stably in the feed and play a precise role in the animal's body. Moreover, the entire formula system contains no antibiotic components, avoiding the generation of drug-resistant strains and drug residues in the animal's body from the source. At the same time, all components are adapted to the intestinal digestive characteristics of piglets and will not cause additional stimulation to the intestines of young livestock and poultry. It not only meets the antibacterial needs of large-scale modern animal husbandry, but also realizes the green and healthy development of animal husbandry.

[0021] Compared with the prior art, the beneficial effects of the present invention are: 1. Significantly enhanced antibacterial performance, effectively replacing traditional antibiotics: This invention achieves a broadened antibacterial spectrum and enhanced antibacterial activity through the synergistic combination of core antibacterial active ingredients and natural plant extracts. It can effectively inhibit a variety of common pathogens, fundamentally avoiding the drug resistance problem caused by traditional antibiotics, and has no risk of drug residues, meeting the needs of green and healthy development of animal husbandry.

[0022] 2. It takes into account the regulation of intestinal microecology and is adapted to the physiological characteristics of young livestock and poultry: The organic acids and antibacterial synergists in the formula work synergistically to enhance the antibacterial effect while effectively regulating the acid-base environment of the animal's intestines, promoting the proliferation of beneficial bacteria in the intestines, and maintaining the intestinal microecological balance of young livestock and poultry such as piglets that have not yet fully developed, thus achieving the dual functions of antibacterial and intestinal health care.

[0023] 3. Significantly improved stability, ensuring storage and application effectiveness: Through the addition of stabilizers and scientific preparation processes, the compound antibacterial agent of this invention can effectively resist the influence of environmental factors such as temperature and pH during feed processing, storage, and digestion in animals, preventing the loss of active ingredients and ensuring the continuous effectiveness of the product during storage and use. Attached Figure Description

[0024] Figure 1 This is the NMR spectrum of the antibacterial active ingredient 1 described in this invention. Detailed Implementation

[0025] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely 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.

[0026] Example 1 Preparation of antibacterial active ingredient 1: ; CAS number of compound 1: 122-04-3; CAS number of compound 2: 7305-71-7; Under nitrogen protection, 3.38 g of compound 2, 7.51 mL of triethylamine, and 0.33 g of DMAP were added sequentially to a reaction flask, followed by 80 mL of anhydrous dichloromethane. Stirring was initiated to form a homogeneous solution. The reaction flask was placed in an ice-water bath until the internal temperature dropped to 0°C. 5.00 g of compound 1 was dissolved in 20 mL of anhydrous dichloromethane and transferred to a constant-pressure dropping funnel. While stirring at 0°C, the solution was added dropwise to the reaction mixture at approximately 1 drop / second, with the internal temperature monitored to ensure it did not exceed 5°C during the addition. After the addition was complete, the ice-water bath was removed, and the reaction mixture was allowed to naturally rise to room temperature. The mixture was then stirred continuously at room temperature for 4 hours. After the reaction was complete, the reaction mixture was returned to an ice bath for cooling. 50 mL of saturated ammonium chloride aqueous solution was slowly added dropwise to quench the reaction. After stirring for 10 minutes, the mixture was transferred to a separatory funnel to separate the lower organic phase. The aqueous phase was subjected to a second extraction with dichloromethane. All organic phases were combined and washed successively with 0.5M dilute hydrochloric acid to remove residual alkali, followed by washing with saturated sodium bicarbonate aqueous solution, and finally washing with saturated brine. The washed organic phases were transferred to an Erlenmeyer flask, anhydrous sodium sulfate solid was added and dried for 30 minutes, filtered under reduced pressure through a Buchner funnel, and the filter cake was washed with dichloromethane. The filtrate was concentrated under reduced pressure on a rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography using a gradient elution with a mixed solution of petroleum ether and ethyl acetate. The fraction containing the target was collected, concentrated under reduced pressure, and then recrystallized by slurrying in anhydrous ethanol. The mixture was filtered and washed with ice-cold ethanol, and finally dried in a vacuum drying oven to obtain 5.31 g of intermediate 1.

[0027] ; Under nitrogen protection, 5.31 g of intermediate 1 and 3.24 g of ammonium chloride were added to the reaction flask. Then, 80 mL of anhydrous ethanol and 20 mL of deionized water were mixed and added to the reaction flask. Stirring was started to disperse the solids. 6.76 g of iron powder was added to the reaction solution in three batches. After the addition was complete, it was ensured that all solids were suspended in the solvent. The reaction flask was then placed in a pre-set temperature-controlled oil bath. The temperature of the oil bath was slowly raised to 80°C, and stirring was maintained for 3 hours. After the reaction was completed, the reaction apparatus was removed from the oil bath and allowed to cool naturally to room temperature. The reaction mixture was filtered through a funnel lined with diatomaceous earth. The reaction flask and filter cake were thoroughly washed with hot ethyl acetate. The filtrate was collected and concentrated under reduced pressure in a rotary evaporator to remove most of the solvent. 100 mL of ethyl acetate and 30 mL of saturated sodium bicarbonate solution were added to the remaining aqueous suspension. The mixture was transferred to a separatory funnel and shaken vigorously. After standing and separating the layers, the organic phase was collected. The aqueous phase was extracted again with ethyl acetate. All organic layers were combined and washed once with saturated brine. Then, anhydrous sodium sulfate was added and the mixture was dried for 30 minutes. The desiccant was removed by filtration. The filtrate was concentrated to dryness under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography using a gradient elution with a mixed solution of dichloromethane and methanol. The fraction containing the target was collected, concentrated under reduced pressure, and dried overnight in a vacuum drying oven to obtain 3.40 g of intermediate 2.

[0028] ; CAS number of compound 3: 102-92-1; Under nitrogen protection, 3.40 g of intermediate 2 and 0.18 g of DMAP were added to a reaction flask, followed by 60 mL of anhydrous dichloromethane. Stirring was started to disperse the solids, and 5.08 mL of N,N-diisopropylethylamine was added using a syringe. The reaction flask was then cooled to 0°C in an ice-water bath. 2.67 g of compound 3 was pre-dissolved in 10 mL of anhydrous dichloromethane and placed in a constant-pressure dropping funnel. Under stirring at 0°C, the solution was slowly added dropwise to the main reaction system at a rate of approximately 1 drop / second, with the system temperature closely monitored to ensure it did not exceed 5°C. After the addition was complete, the ice-water bath was removed, and the reaction mixture was allowed to naturally rise to room temperature. The reaction was then stirred continuously at room temperature for 4 hours. After the reaction was complete, the reaction solution was cooled to 0°C, and 20 mL of saturated sodium bicarbonate aqueous solution was added to quench any residual acyl chlorides in the system. The mixture was transferred to a separatory funnel to separate the lower organic phase. The aqueous phase was then... Extracted again with dichloromethane, all organic layers were combined and washed sequentially with 1N hydrochloric acid aqueous solution, saturated ammonium chloride aqueous solution, and saturated brine. The washed organic phase was transferred to an Erlenmeyer flask, dried with anhydrous sodium sulfate for 30 minutes, filtered through a Buchner funnel to remove the desiccant, and the filtrate was concentrated under reduced pressure using a rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography using a gradient elution with a mixed solution of petroleum ether and ethyl acetate. The fraction containing the target was collected, concentrated under reduced pressure, and then recrystallized by slurrying in a small amount of hexane. The mixture was filtered and washed with cold hexane, and finally dried in a vacuum drying oven to obtain 4.10 g of antibacterial active ingredient 1.

[0029] Structural assessment: NMR of antibacterial active ingredient 1 1 HNMR(Chloroform-d)δ9.55(s,1H),7.96-7.86(m,2H),7.72-7.62(m,2H),7.62-7.52(m,3H),7.41-7.24(m,4H),6.80(d,1H),2.47(s,3H).

[0030] Examples 2-4 In Examples 2-4, antibacterial active ingredients 2-4 were prepared sequentially, following the preparation method in Example 1, except that compound 2 was replaced, and the rest remained the same as in Example 1. For details, please refer to Table 1.

[0031] Table 1. Structures and data involved in Examples 2-4 Performance testing: inhibition zone experiment: The indicator bacteria used in the experiment were *Escherichia coli*, *Salmonella*, and *Staphylococcus aureus*. LB agar was used as the culture medium. The test samples were antibacterial active ingredients 1, 2, 3, and 4 obtained in Preparation Examples 1-4; thymol was used as a control sample; and dimethyl sulfoxide (DMSO) was used as a solvent control. All test samples were dissolved in DMSO and diluted to prepare a 10.0 mg / mL sample solution.

[0032] Single colonies of *Escherichia coli*, *Salmonella*, and *Staphylococcus aureus* were picked and inoculated into LB broth. The cultures were incubated at 37°C and 180 rpm with shaking for 18–24 h to allow the bacteria to enter the logarithmic growth phase. After incubation, the bacterial suspension was diluted with sterile physiological saline or sterile LB broth to adjust the concentration to approximately 1.0 × 10⁶ CFU / mL. 100 μL of this bacterial suspension was evenly spread onto the surface of an LB agar plate and allowed to stand for 10 min to allow absorption. Sterile filter paper discs with a diameter of 6 mm were used, and 20 μL of each of the following sample solutions were added: antimicrobial active ingredient 1, antimicrobial active ingredient 2, antimicrobial active ingredient 3, antimicrobial active ingredient 4, and thymol, respectively, to achieve a sample loading of 200 μg per disc. For the solvent control group, 20 μL of dimethyl sulfoxide was added to the filter paper discs. After the solvent on the filter paper discs had largely evaporated, they were attached to the surface of the LB agar plates containing indicator bacteria. Each plate was incubated in a 37℃ incubator for 24 hours. After incubation, the diameter of the transparent inhibition zone around the filter paper was measured using calipers. Measurements were taken along two mutually perpendicular directions for each inhibition zone, and the average value was recorded. Three parallel samples were set for each group, and the results are expressed as the average. If no obvious transparent inhibition zone was formed, the diameter of the filter paper was recorded as 6.0 mm. The inhibition zone experimental data are shown in Table 1.

[0033] Table 1. Antibacterial active substances 1-4 prepared in Examples 1-4 and the control sample thymol, inhibition zone test data. Application Example 1 Preparation of a composite antibacterial agent: 1. Raw material components by weight: Antibacterial active ingredient: 7.5 parts (using antibacterial active ingredient 1 prepared in Example 1); Natural plant extract: 15 parts (a mixture of thymol, chlorogenic acid, and forsythoside in a mass ratio of 1:1:1). Organic acids: 20 parts (citric acid with a purity of ≥98%) Antibacterial synergist: 3 parts (a mixture of glyceryl monolaurate and glyceryl butyrate in a 1:1 mass ratio); Carrier: 55 parts (corn starch was selected); Stabilizer: 3 parts (Vitamin E preferred).

[0034] 2. Preparation method: S1. Pretreatment: Place 55 parts of carrier in a constant temperature drying oven and dry at 70℃ until the moisture content is ≤8%. After taking it out, pulverize it and pass it through an 80-mesh sieve for later use; pulverize 15 parts of natural plant extract and 7.5 parts of antibacterial active ingredient into 100-mesh sieves for later use. S2. Mixing: Add the pretreated carrier to a high-speed mixer, adjust the speed to 1800 r / min, and stir for 8 minutes. Then, add the antibacterial active ingredient, natural plant extract, organic acid and antibacterial synergist to the mixer in sequence. After the addition is complete, continue stirring at 1800 r / min for 18 minutes. During this process, control the temperature inside the mixer to below 28℃ to avoid the active ingredients from being deactivated by high temperature, and obtain the premixed material. S3. Stabilization treatment: Add 3 parts of stabilizer to the above premixed material, adjust the mixer speed to 1300 r / min, stir for 10 minutes to make the stabilizer evenly dispersed, and obtain the mixture. S4. Post-processing: The mixture is fed into a granulator for granulation, and the particle size is controlled to be about 1.0 mm. The granulated particles are placed in a constant temperature drying oven at 55℃ and dried until the moisture content is ≤5%. After drying, the particles are taken out and cooled to room temperature. Fine powder and excessively large particles are removed by sieving to obtain a composite antibacterial agent.

[0035] Application Examples 2-4 The preparation of a composite antibacterial agent is carried out by referring to the preparation method in Application Example 1, except that the antibacterial active ingredient is replaced with antibacterial active ingredient 2-antibacterial active ingredient 4 prepared in Examples 2-4, and the rest is the same as in Application Example 1.

[0036] Comparative Application Example 1 The preparation of a composite antibacterial agent is the same as in Application Example 1, except that no antibacterial active ingredient is added.

[0037] Comparative Application Example 2 The preparation of a compound antibacterial agent is carried out by referring to the preparation method in Application Example 1, except that the antibacterial synergist is replaced by using only glyceryl monolaurate, and the rest remains the same as in Application Example 1.

[0038] Comparative Application Example 3 The preparation of a compound antibacterial agent is carried out by referring to the preparation method in Application Example 1, except that the mass fraction of the natural plant extract is replaced with 5 parts, while the rest remains the same as in Application Example 1.

[0039] Comparative Application Example 4 The preparation of a composite antibacterial agent is the same as in Application Example 1, except that the stabilizer is not added.

[0040] Performance testing 1. Antibacterial Performance Test: The inhibitory effect of this compound antibacterial agent on common pathogenic bacteria was evaluated using an in vitro viable cell count method. *Escherichia coli*, *Salmonella*, and *Staphylococcus aureus* were selected as indicator bacteria and inoculated into LB liquid medium. After incubation at 37°C for 24 hours, the bacterial suspension concentration was adjusted to approximately 1.0 × 10⁻⁶ with sterile physiological saline. 6 CFU / mL. Weigh 1.00 g of the compound antibacterial agent sample and add it to 99 mL of sterile phosphate buffer. Shake thoroughly to disperse the sample and obtain a sample dispersion. Mix 9 mL of the sample dispersion with 1 mL of the above bacterial suspension as the experimental group. Mix 9 mL of sterile phosphate buffer with 1 mL of the bacterial suspension as the blank control group. After incubating each group at 37℃ for 24 h, perform serial dilutions and plate them on LB agar plates. After incubating at 37℃ for 24 h, count the colonies. Calculate the inhibition rate using the following formula: The inhibition rate (%) was calculated as follows: (number of colonies in the blank control group - number of colonies in the experimental group) / number of colonies in the blank control group × 100%. The results are shown in Table 2.

[0041] 2. Intestinal microecological regulation performance test: Healthy weaned piglets were selected and divided into 8 groups (fed with piglet feed supplemented with Examples 1-4 and control piglet feed supplemented with Examples 1-4, respectively). After 7 days of feeding, fresh fecal samples were aseptically collected from the piglets. The fecal samples were added to sterile physiological saline in a certain proportion, homogenized, and then serially diluted to 10. -3 -10 -6 The bacterial solutions of each dilution were spread onto modified MC medium and anaerobic cultured at 37℃ for 48 h. Lactobacillus acidophilus was identified according to GB / T20191-2006, and the number of Lactobacillus acidophilus per gram of feces (CFU / g) was calculated. The results are shown in Table 2.

[0042] 3. Thermal stability test: The composite antibacterial agent was placed in a constant temperature drying oven and heated at 80℃ for 4 hours. After cooling to room temperature, the content of antibacterial active ingredients before and after heating was determined by high performance liquid chromatography. The activity retention rate was calculated as follows: Activity retention rate = content after heating / content before heating × 100%. The results are shown in Table 2.

[0043] 4. Hygiene and safety index testing: The compound antibacterial agent was added to the basic piglet feed without antibacterial agent at an addition rate of 1.0 g / kg, and mixed thoroughly to obtain the piglet feed samples to be tested. The hygiene and safety indexes of the piglet feed samples were evaluated according to GB13078-2017. Salmonella was determined according to GB / T13091-2018, total bacterial count according to GB / T13093-2023, and total mold count according to GB / T13092-2025. The results are shown in Table 2.

[0044] Table 2. Performance test data of application examples and comparative application examples As shown in Table 2, Application Examples 1-4 exhibited high inhibition rates against Escherichia coli, Salmonella, and Staphylococcus aureus, indicating that the antibacterial active ingredient, natural plant extract, organic acid, and antibacterial synergist described in this invention can form a synergistic antibacterial effect, simultaneously enhancing the inhibitory effect against both Gram-negative and Gram-positive bacteria. Compared to Application Example 1 without the addition of antibacterial active ingredient, the inhibition rates of all three pathogenic bacteria decreased significantly, indicating that the antibacterial active ingredient is the key component for exerting a broad-spectrum antibacterial effect. Compared to Application Example 2 using only a single antibacterial synergist, and compared to Application Example 3 with reduced natural plant extract dosage, the inhibition rate and the number of Lactobacillus acidophilus were both lower than in the Application Examples, indicating that the antibacterial synergist compound system and natural plant extract play an important role in enhancing antibacterial activity and regulating intestinal microecology. Compared to Application Example 4 without the addition of stabilizer, the decrease in inhibition rate was smaller, but the activity retention rate after treatment at 80℃ for 4 hours was significantly reduced, indicating that the stabilizer is mainly used to improve the activity retention capacity of the compound antibacterial agent during processing and storage. Salmonella was not detected in any of the piglet feed samples after the addition of the compound antibacterial agent. The total bacterial count and total mold count were at low levels, indicating that the compound antibacterial agent of the present invention will not introduce significant microbial contamination risk when applied to piglet feed, and can take into account antibacterial effect, intestinal microecological regulation effect and application safety.

[0045] Although embodiments / application examples / comparative application examples of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A composite antibacterial agent, characterized in that, By weight, it includes the following components: 5-10 parts of antibacterial active ingredient, 10-20 parts of natural plant extract, 10-25 parts of organic acid, 1-5 parts of antibacterial synergist, 45-65 parts of carrier, and 1-5 parts of stabilizer. The antibacterial active ingredient is a compound represented by Formula 1; Formula 1: ; In Formula 1, the substituent R1 is selected from any one of methyl, phenyl, methyl ester, and chlorine; The natural plant extract is at least one of thymol, chlorogenic acid, and forsythoside. The antibacterial synergist is a mixture of glyceryl monolaurate and glyceryl butyrate, with a mass ratio of 1:

1.

2. The composite antibacterial agent according to claim 1, characterized in that, The organic acid is at least one of citric acid, malic acid, lactic acid, and acetic acid, with a purity ≥98%.

3. The composite antibacterial agent according to claim 1, characterized in that, The carrier is at least one of corn starch, wheat bran, and zeolite powder.

4. The composite antibacterial agent according to claim 1, characterized in that, The stabilizer is at least one of vitamin E and disodium ethylenediaminetetraacetate.

5. A method for preparing a composite antibacterial agent according to any one of claims 1-4, characterized in that, Includes the following steps: S1. Pretreatment: The carrier is placed in a constant temperature drying oven and dried until the moisture content is ≤8%, then pulverized and passed through an 80-100 mesh sieve for later use; the natural plant extract and antibacterial active ingredient are pulverized to a 100-120 mesh sieve for later use. S2. Mixing: First, add the pretreated carrier to a high-speed mixer, adjust the speed to 1500-2000 r / min, stir for 5-10 min, then add the antibacterial active ingredient, natural plant extract, organic acid, and antibacterial synergist in sequence, and continue stirring for 15-20 min to obtain the premixed material; S3. Stabilization treatment: Add the stabilizer to the premixed material, adjust the mixer speed to 1200-1500 r / min, stir for 8-12 min to obtain the mixture; S4. Post-processing: The mixture is granulated, and the particle size is controlled at 0.8-1.2 mm. After granulation, it is placed in a constant temperature drying oven at 50-60℃ and dried until the moisture content is ≤5%. After cooling to room temperature, it is sieved to obtain a composite antibacterial agent.

6. The method for preparing the composite antibacterial agent according to claim 5, characterized in that, The drying temperature in step S1 is 60-80℃.

7. The method for preparing the composite antibacterial agent according to claim 5, characterized in that, In step S2, the temperature inside the mixer is controlled at 25-30℃ during the stirring process to avoid the antibacterial active ingredients and natural plant extracts becoming ineffective due to high temperature.

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