An antibacterial benzoic acid preparation and its preparation method

Abstract

This invention belongs to the field of feed additive technology and discloses an antibacterial benzoic acid preparation and its preparation method. The preparation consists of a benzoic acid core and a protective layer surrounding the core. The core includes benzoic acid and a molding agent, while the protective layer includes a wax-based coating material and a fumaric acid efficacy enhancer. The preparation method includes: mixing benzoic acid and the molding agent, followed by rolling and granulation to obtain the core; melting the wax material and adding fumaric acid to prepare a suspension coating solution; spraying the coating solution onto the core surface using a fluidized bed coating process, and then sieving to obtain the finished product. This invention utilizes the acidic microenvironment provided by the dissociation of fumaric acid at the posterior end of the intestine to form a release channel, enabling benzoic acid to be efficiently released at the target intestinal site while maintaining its molecular shape, significantly improving the antibacterial effect; simultaneously, it effectively masks odor, prevents clumping, improves product stability and animal feed intake, and can replace ordinary benzoic acid granules at a 1:3 ratio, demonstrating significant economic and application value.

Description

Technical Field

[0001] This invention belongs to the field of feed additive technology, specifically relating to an antibacterial benzoic acid preparation and its preparation method, and in particular to a benzoic acid coated granule with intestinal targeted release function and its application in animal feed. Background Technology

[0002] Benzoic acid is the simplest aromatic acid, appearing as lustrous white monoclinic platy crystals with a melting point of 122°C. It sublimates at 100°C, and its vapor is highly irritating, easily causing coughing upon inhalation. Furthermore, the sublimated vapor recrystallizes upon cooling. Benzoic acid is sparingly soluble in water but has strong hygroscopic properties. At around 25°C, its pKa value is 4.2, classifying it as a monoprotic weak acid, but its acidity is stronger than that of fatty acids.

[0003] Benzoic acid molecules have a broad-spectrum antibacterial / bactericidal effect and are widely used in livestock and poultry feed. The purpose is to inhibit and kill harmful bacteria such as Escherichia coli, Salmonella, Clostridium perfringens, and Staphylococcus aureus in the intestines, regulate the balance of intestinal flora, and maintain intestinal health. Its antibacterial / bactericidal mechanism mainly has two aspects: (1) Undissociated benzoic acid molecules are lipid-soluble and can act on the cell membrane of bacteria, thereby destroying the integrity of the bacterial cell membrane, causing changes in bacterial morphology and death; (2) When benzoic acid enters the cells of harmful bacteria, it dissociates into H+ due to the high pH. + Harmful bacteria in order to H + They were transported out, consuming a large amount of energy before dying.

[0004] Currently, there are several problems with the use of benzoic acid: (1) The posterior end of the animal duodenum is a place where harmful bacteria accumulate in large numbers. The pH of the posterior end of the duodenum is close to neutral. When pH > 5, more than 80% of benzoic acid molecules are dissociated. The dissociated benzoic acid has no antibacterial / bactericidal effect. Therefore, benzoic acid needs to be at pH < 5 to exert the strongest antibacterial / bactericidal effect. (2) Because benzoic acid sublimates at high temperature and recrystallizes at low temperature, and because of its strong hygroscopicity, benzoic acid is prone to clumping during storage and transportation. At the same time, it will react with other nutrients in the feed (alkaline substances, vitamins, etc.), which brings great inconvenience to the feed workers. (3) Benzoic acid has an irritating odor. A high amount added will affect the animal's feed intake; a low amount added will not achieve the desired effect. (4) Benzoic acid is absorbed in large quantities in the animal's stomach and duodenum, resulting in very little benzoic acid reaching the posterior end of the intestine.

[0005] Currently, in order to solve the problems existing in the application of benzoic acid in feed, the main approach is to mix benzoic acid or benzoic acid with other organic acids, add some excipients, and then perform hot melt mixing and granulation (CN 118235819A), or cold granulation (CN116473165A), or tableting and granulation + coating (CN 109043145A) to obtain sustained-release benzoic acid granules. After microencapsulation or coating treatment, the irritating odor of benzoic acid can be masked, and the animal's feed intake can be increased; at the same time, it can ensure that most of the benzoic acid is not released in the animal's stomach and duodenum, but is released to exert its effect only after reaching the end of the intestine. However, there are still problems with this method: (1) When the benzoic acid reaches the end of the intestine and is released, most of the benzoic acid molecules dissociate into H+ when they encounter a near-neutral pH environment. + To provide the pH environment in which benzoic acid molecules exert their strongest effect, this will result in a large waste of benzoic acid. At this time, even if other organic acids are compounded in the granulation formula, benzoic acid will be released and dissociated along with other organic acids after entering the end of the intestine. (2) These methods do not use effective methods to solve the problem of benzoic acid easily clumping during storage and transportation. Summary of the Invention

[0006] To address the aforementioned problems, this invention discloses an antibacterial benzoic acid preparation and its preparation method. This invention uses benzoic acid as the main raw material, mixed with some excipients, and granulates it using a rolling method to obtain a benzoic acid core. A wax-based substance is used as the main coating material, and fumaric acid is added to the main coating material to form a suspension coating liquid, which is used to coat the benzoic acid core. Finally, through sieving and packaging, an antibacterial benzoic acid preparation is obtained.

[0007] The objective of this invention is achieved through the following technical solution.

[0008] An antibacterial benzoic acid formulation comprises a benzoic acid core and a protective layer surrounding the core; the benzoic acid core includes benzoic acid and a molding agent; the protective layer includes a main coating material and an efficacy promoter; wherein the main coating material is a waxy substance and the efficacy promoter is fumaric acid.

[0009] The above solution has the following innovative features: (1) Unconventional applications of fumaric acid as a conventional material: Fumaric acid is a commonly used organic acid. In conventional applications, it is mixed with other organic acids such as benzoic acid for granulation to synergistically exert its antibacterial effect. This invention adds fumaric acid to the coating solution, serving three functions: ① pH adjuster: In the near-neutral pH environment of the posterior intestinal tract, it is first dissociated to release H+, providing a lower pH environment for benzoic acid to exert its antibacterial effect. ② Intestinal release agent: Because it is first dissociated in the posterior intestinal tract, it forms pores in the protective layer, providing a channel for the release of benzoic acid, promoting its slow release and exertion. ③ Anti-caking agent: Fumaric acid has an extremely high melting point (around 300℃) and is very stable and non-hygroscopic; adding it to the coating solution improves the stability of the product.

[0010] (2) Combination of two conventional materials: The choice of wax-based materials is based on their hydrophobicity and plasticity. After adding fumaric acid, no other dispersants are needed; a stable suspension coating can be formed simply through emulsification and stirring. In contrast, conventional hydrogenated aliphatic coating materials lack plasticity and are prone to cracking at low temperatures, requiring the addition of plasticizers for use.

[0011] Furthermore, in the above-mentioned antibacterial benzoic acid preparation, based on the total mass of the benzoic acid core, the mass percentage of benzoic acid is 90% to 95%, and the mass percentage of the molding agent is 5% to 10%.

[0012] Furthermore, in the above-mentioned antibacterial benzoic acid preparation, the molding agent is selected from one or more of microcrystalline cellulose, pregelatinized starch, lactose, and dicalcium phosphate.

[0013] Furthermore, in the above-mentioned antibacterial benzoic acid preparation, based on the total mass of the antibacterial benzoic acid preparation, the mass percentage of the benzoic acid core is 80% to 90%, and the mass percentage of the protective layer is 10% to 20%; wherein, based on the total mass of the protective layer, the mass percentage of the main coating material is 8% to 15%, and the mass percentage of the efficacy promoter is 2% to 5%.

[0014] Furthermore, in the above-mentioned antibacterial benzoic acid preparation, the wax substance is selected from one or more of carnauba wax, beeswax, and rice bran wax.

[0015] This invention discloses a method for preparing the above-mentioned antibacterial benzoic acid preparation, such as... Figure 1 As shown, it includes the following steps: (1) Mix benzoic acid with a molding agent to obtain a mixture; (2) The mixture is granulated by rolling to obtain benzoic acid core; (3) The waxy substance is heated and melted, fumaric acid is added, and after emulsification and stirring, a suspension coating solution is obtained; (4) Coating the benzoic acid core with the suspension coating liquid to obtain the antibacterial benzoic acid preparation.

[0016] Furthermore, in the above preparation method, the mixing time in step (1) is 3 minutes.

[0017] Furthermore, in the above preparation method, in step (2), the parameters of the rolling granulation include: feeding speed of 30-60 rpm, rolling pressure of 4-8 MPa, rolling speed of 6-12 rpm, and roller gap of 1.2-2 mm; and / or, step (2) also includes sieving the granulated material, with a sieve mesh size of 20 mesh for the upper layer and 40 mesh for the lower layer.

[0018] Furthermore, in the above preparation method, the temperature of the suspension coating liquid in step (3) is 100-110℃; and / or, the coating parameters in step (4) include: material temperature 55-60℃, atomization temperature 120-130℃, and atomization pressure 0.22-0.25MPa; and / or, after step (4), the coated material is further screened with a sieve mesh size of 16 mesh for the upper layer and 40 mesh for the lower layer. The present invention also discloses the use of the above-mentioned antibacterial benzoic acid preparation in the preparation of feed additives, wherein the feed additives are additives used to inhibit harmful bacteria in the animal intestines.

[0019] Compared with existing technologies, the present invention has the following advantages and beneficial effects: (1) It solves the problem of benzoic acid molecules being dissociated and wasted in the high pH environment of the lower end of the intestine: This invention uses wax-based materials as the main coating material and incorporates fumaric acid, an efficacy enhancer, as a protective layer for the benzoic acid core. This protective layer is almost undamaged in the stomach and duodenum of animals. Upon reaching the posterior end of the intestine, where the pH is near neutral, the fumaric acid in the protective layer begins to dissociate. On one hand, the dissociation of H+ ions lowers the environmental pH; on the other hand, the dissociated fumaric acid forms pores in the protective layer, providing channels for the release of benzoic acid. At this point, the internal benzoic acid begins to be slowly released. The released benzoic acid maintains its molecular form in the lower pH environment, thus exerting its antibacterial effect.

[0020] (2) It solved the problem of benzoic acid easily clumping during storage and transportation: The wax material in the protective layer of this invention has a melting point of 60-90℃, while fumaric acid has a melting point as high as about 300℃ and is stable. When these two are combined, the melting point of the protective layer is very high. The benzoic acid core coated with this protective layer achieves excellent stability during storage and transportation without the need for any anti-caking agents.

[0021] (3) It solves the problem of benzoic acid's irritating odor and release at the front end of the intestine: Benzoic acid, protected by a protective layer, has its pungent odor masked and will not affect the animal's feed intake. At the same time, it is almost never released at the front of the intestine, but is released only at the back of the intestine, which greatly enhances the antibacterial effect of benzoic acid and can replace benzoic acid granules at a ratio of 1:3. Attached Figure Description

[0022] Figure 1 The preparation process of the antibacterial benzoic acid preparation of the present invention; Figure 2 Examples 1-3, Comparative Example 1, and Comparison of dissolution rates of benzoic acid particles in simulated gastrointestinal tract; Figure 3 Stability test results of the antibacterial benzoic acid preparations prepared in Examples 1-3. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below. However, it should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of the invention. Furthermore, descriptions of well-known structures and technologies are omitted in the following description to avoid unnecessarily obscuring the concept of the invention. All raw materials (including bacterial strains, etc., are commercially available products) in the embodiments of this invention are commercially available.

[0024] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the embodiments.

[0025] Example 1 Weigh 450 kg of benzoic acid and 50 kg of microcrystalline cellulose into a mixer, turn on the mixer, and mix for 3 minutes. After mixing, the material is conveyed to a roller pelletizer via a screw feeder for pelletizing. The feeding speed is 50 rpm, the rolling pressure is 6 MPa, the rolling speed is 10 rpm, and the roller gap is 1.5 mm. After pelleting, the sample is crushed into irregular small particles by a crusher, and then sieved. The qualified particle size is the benzoic acid core, which enters the next process for coating. During sieving, the upper screen mesh is 20 mesh, and the lower screen mesh is 40 mesh.

[0026] 35 kg of carnauba wax was weighed and placed in a heating melting kettle for melting. After melting, 15 kg of fumaric acid was added, and emulsification and stirring were started to obtain a suspension coating solution. The temperature of the suspension coating solution was stabilized at around 105℃. 450 kg of the benzoic acid core obtained above was weighed and placed in a fluidized bed. The induced draft fan, air intake heating, atomization heating, and atomization were turned on to fluidize the benzoic acid core in the fluidized bed. After the material temperature reached 55℃, the peristaltic pump was turned on to spray the suspension coating solution onto the surface of the benzoic acid core to begin coating. During the coating process, the material temperature was around 57℃, the atomization temperature was around 125℃, and the atomization pressure was around 0.23 MPa. After coating, the particles were sieved, and those with qualified particle size were packaged to obtain an antibacterial benzoic acid preparation (benzoic acid content of 80.5%). The upper sieve mesh size was 16 mesh, and the lower sieve mesh size was 40 mesh.

[0027] Example 2 Weigh 475 kg of benzoic acid, 15 kg of microcrystalline cellulose, and 10 kg of pregelatinized starch into a mixer and start the mixer for 3 minutes. After mixing, the material is fed into a roller pelletizer via a screw feeder for pelletizing. The feeding speed is 40 rpm, the rolling pressure is 6 MPa, the rolling speed is 10 rpm, and the roller gap is 1.5 mm. The pelletized sample is then crushed into irregular small particles by a crusher and sieved. The qualified particle size is the benzoic acid core, which proceeds to the next process for coating. During sieving, the upper sieve mesh is 20 mesh, and the lower sieve mesh is 40 mesh.

[0028] Weigh 50 kg of beeswax and place it in a heating melting kettle for melting. After melting, add 25 kg of fumaric acid, start emulsification and stirring to obtain a suspension coating solution. The temperature of the suspension coating solution is stabilized at around 110℃. Weigh 425 kg of the obtained benzoic acid core and place it in a fluidized bed. Turn on the induced draft fan, air intake heating, atomization heating, and atomization to fluidize the benzoic acid core in the fluidized bed. After the material temperature reaches 55℃, turn on the peristaltic pump to spray the suspension coating solution onto the surface of the benzoic acid core to begin coating. During the coating process, the material temperature is around 58℃, the atomization temperature is around 125℃, and the atomization pressure is around 0.23 MPa. After coating, sieve the particles. Pack the qualified particles to obtain an antibacterial benzoic acid preparation (benzoic acid content of 80.3%). The upper sieve mesh size is 16 mesh, and the lower sieve mesh size is 40 mesh.

[0029] Example 3 Weigh 475 kg of benzoic acid, 15 kg of lactose, and 10 kg of dicalcium phosphate and place them in a mixer. Turn on the mixer and mix for 3 minutes. After mixing, the material is fed into a roller pelletizer via a screw feeder for pelletizing. The feeding speed is 40 rpm, the rolling pressure is 6 MPa, the rolling speed is 10 rpm, and the roller gap is 1.5 mm. After pelleting, the sample is crushed into irregular small particles by a crusher, and then sieved. The qualified particle size is benzoic acid core, which enters the next process for coating. During sieving, the upper sieve mesh is 20 mesh and the lower sieve mesh is 40 mesh.

[0030] 40 kg of rice bran wax was weighed and placed in a heating melting kettle for melting. After melting, 10 kg of fumaric acid was added, and emulsification and stirring were started to obtain a suspension coating solution. The temperature of the suspension coating solution was stabilized at around 110℃. 450 kg of the benzoic acid core obtained above was weighed and placed in a fluidized bed. The induced draft fan, air intake heating, atomization heating, and atomization were turned on to fluidize the benzoic acid core in the fluidized bed. After the material temperature reached 55℃, the peristaltic pump was turned on to spray the suspension coating solution onto the surface of the benzoic acid core to begin coating. During the coating process, the material temperature was around 58℃, the atomization temperature was around 125℃, and the atomization pressure was around 0.23 MPa. After coating, the particles were sieved, and those with qualified particle size were packaged to obtain an antibacterial benzoic acid preparation (benzoic acid content of 85%). The upper sieve mesh size was 16 mesh, and the lower sieve mesh size was 40 mesh.

[0031] Comparative Example 1 Weigh 475 kg of benzoic acid, 15 kg of microcrystalline cellulose, and 10 kg of pregelatinized starch into a mixer and start the mixer for 3 minutes. After mixing, the material is fed into a roller pelletizer via a screw feeder for pelletizing. The feeding speed is 40 rpm, the rolling pressure is 6 MPa, the rolling speed is 10 rpm, and the roller gap is 1.5 mm. The pelletized sample is then crushed into irregular small particles by a crusher and sieved. The qualified particle size is the benzoic acid core, which proceeds to the next process for coating. During sieving, the upper sieve mesh is 20 mesh, and the lower sieve mesh is 40 mesh.

[0032] 75 kg of beeswax was weighed and placed in a heating melting kettle for melting to obtain a coating solution. The temperature of the coating solution was stabilized at around 110℃. 425 kg of the obtained benzoic acid core was weighed and placed in a fluidized bed. The induced draft fan, inlet air heating, atomization heating, and atomization were activated to fluidize the benzoic acid core in the fluidized bed. Once the material temperature reached 55℃, the peristaltic pump was turned on to spray the coating solution onto the surface of the benzoic acid core, initiating the coating process. During the coating process, the material temperature was around 58℃, the atomization temperature was around 125℃, and the atomization pressure was around 0.23 MPa. After coating, the particles were sieved, and those meeting the acceptable particle size were packaged to obtain an antibacterial benzoic acid preparation (benzoic acid content of 80.3%). The upper sieve mesh size was 16 mesh, and the lower sieve mesh size was 40 mesh.

[0033] Test case 1. Simulated pig gastrointestinal digestion experiment Refer to the relevant methods for dissolution and release testing in Chinese Pharmacopoeia (2020 Edition) 0931.

[0034] (1) Simulated gastric juice dissolution determination Preparation of simulated gastric juice: Take 32.8 mL of dilute hydrochloric acid, add 1600 mL of water and shake well, then add 20 g of pepsin and bring the volume to 2000 mL for later use.

[0035] Experimental Method: Accurately weigh 0.5000g of benzoic acid granules from Examples 1-3 and Comparative Example 1 for later use. Take 400mL of simulated gastric fluid from each of the five groups and inject it into five dissolution vessels. Heat the solution and maintain the temperature at 39℃. Add the weighed samples to the dissolution baskets. Set the stirring speed to 100r / min. After 2 hours, take 10mL of gastric fluid and detect the benzoic acid content in the gastric fluid (the initial content of the sample also needs to be detected). Calculate the dissolution rate of the sample in the simulated gastric fluid.

[0036] (2) Determination of the dissolution rate of simulated intestinal fluid Preparation of simulated intestinal fluid: Weigh 13.6g of potassium dihydrogen phosphate, dissolve in 1000mL of water, and adjust the pH to 6.8 with 0.1mol / L sodium hydroxide; separately weigh 20g of pancreatic enzyme, 40mg of soybean lecithin, and 32g of bile salts, dissolve in 400mL of water, mix the two solutions, shake well, and dilute with water to 2000mL.

[0037] Experimental Method: Samples were removed from gastric fluid, and 400 mL of simulated intestinal fluid was measured and injected into five dissolution vessels. The solutions were heated and kept at a stable temperature of 39°C. The samples from the simulated gastric fluid were then transferred into the simulated intestinal fluid. The stirring speed was set to 100 r / min, and 10 mL of intestinal fluid was collected at 2 h, 4 h, 6 h, and 8 h to detect the benzoic acid content and calculate the dissolution rate of the samples in the simulated intestinal fluid.

[0038] (3) Experimental results: like Figure 2 As shown, the antibacterial benzoic acid preparations prepared in Examples 1-3 have very low release rates in the stomach and foregut, but begin to gradually release benzoic acid to exert their antibacterial effect upon reaching the hindgut. In Comparative Example 1, because the efficacy enhancer fumaric acid was not added, the benzoic acid was overprotected, resulting in very low release at the posterior end of the intestine.

[0039] 2. Animal experiments (1) Experimental Methods: 120 weaned piglets aged 34 days were selected and divided into two groups: an experimental group (Example 2, Comparative Example 1) and a control group (benzoic acid granules). Each group was replicated twice, with 20 weaned piglets in each replicate. The experimental group was fed 1.5 kg / t of the antibacterial benzoic acid preparation prepared in Example 2 and Comparative Example 1 to their basal diet, while the control group was fed 4.5 kg / t of benzoic acid granules to their basal diet. The feeding period was 21 days. After the experiment, the effects of the experimental and control groups on the production performance and diarrhea rate of weaned piglets were statistically analyzed.

[0040] (3) Experimental results: Table 1

[0041] As shown in Table 1, adding 1.5 kg / t of the antibacterial benzoic acid preparation prepared in Example 2 to the basal diet can improve the average daily weight gain of weaned piglets, reduce the feed conversion ratio, and decrease the diarrhea rate. Compared to Example 1, which showed the same addition amount, the effect on the production performance and diarrhea rate of weaned piglets was significantly reduced due to overprotection. Furthermore, the effect of adding 4.5 kg / t of benzoic acid granules was also inferior to that of Example 2.

[0042] 3. Stability test (1) Experimental method: The antibacterial benzoic acid preparations prepared in Examples 1-3 were packaged in 25kg bags, with each bag weighing 1t. Then, 1t of material was placed on top of each bag. The samples were stored in a warehouse for three months from July to September (maximum temperature 40℃, maximum humidity 95%) to observe the stability of the bottom layer samples.

[0043] (2) Experimental results: The antibacterial benzoic acid preparations prepared in Examples 1-3, after being subjected to a pressure of 2 tons and stored for three months during the summer months of July to September, showed the following results: Figure 3 As shown, the sample has good flowability and does not clump, and benzoic acid does not crystallize out.

[0044] In summary, Examples 1-3 successfully prepared three antibacterial benzoic acid formulations using different molding agents (microcrystalline cellulose, pregelatinized starch, lactose, and dicalcium phosphate) and different wax coating materials (carnauba wax, beeswax, and rice bran wax) through roller granulation and fluidized bed coating processes. The benzoic acid content in the products of each example ranged from 80.3% to 85%, and the preparation process parameters were clearly defined and reproducible. Simulated digestion experiments showed that the formulation of this invention had a low release rate in the stomach and foregut but was precisely released in the hindgut. Animal experiments showed that it could significantly improve the daily weight gain of piglets, reduce the feed conversion ratio, and decrease the diarrhea rate. Stability experiments confirmed that it maintained good flowability under high temperature, high humidity, and pressure, without clumping or crystallization. Comparative Example 1, without the addition of fumaric acid, resulted in over-protection of the coating layer and insufficient release, confirming the key role of fumaric acid in regulating release and enhancing antibacterial effects.

[0045] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Therefore, any changes and modifications made to the embodiments described herein based on the innovative concept of the present invention, or equivalent structural or procedural transformations made using the content of the present invention specification, directly or indirectly applying the above technical solutions to other related technical fields, are all included within the scope of protection of the present invention patent.

Claims

1. A benzoic acid preparation with antibacterial properties, characterized in that, It consists of a benzoic acid core and a protective layer surrounding the core; the benzoic acid core is composed of benzoic acid and a molding agent; the protective layer is composed of a main coating material and an efficacy enhancer. The main coating material is a wax-based substance, and the efficacy enhancer is fumaric acid. Based on the total mass of the antibacterial benzoic acid preparation, the benzoic acid core accounts for 80% to 90% of the mass, and the protective layer accounts for 10% to 20% of the mass. The main coating material comprises 8% to 15% by mass, and the efficacy enhancer comprises 2% to 5% by mass. The molding agent is microcrystalline cellulose and pregelatinized starch; The waxy substance is beeswax; The preparation method of the above-mentioned antibacterial benzoic acid preparation includes the following steps: (1) Mix benzoic acid with a molding agent to obtain a mixture; (2) The mixture is granulated by rolling to obtain benzoic acid core; (3) The waxy substance is heated and melted, fumaric acid is added, and after emulsification and stirring, a suspension coating solution is obtained; (4) Coating the benzoic acid core with the suspension coating liquid to obtain the antibacterial benzoic acid preparation.

2. The antibacterial benzoic acid preparation according to claim 1, characterized in that, The mixing time in step (1) is 3 minutes.

3. The antibacterial benzoic acid preparation according to claim 1, characterized in that, In step (2), the parameters of the rolling granulation method include: feeding speed 30-60 rpm, rolling pressure 4-8 MPa, rolling speed 6-12 rpm, and roller gap 1.2-2 mm; step (2) also includes screening the granulated material, with a screening mesh of 20 mesh for the upper layer and 40 mesh for the lower layer.

4. The antibacterial benzoic acid preparation according to claim 1, characterized in that, The temperature of the suspension coating liquid in step (3) is 100-110℃; the parameters of the coating treatment in step (4) include: material temperature 55-60℃, atomization temperature 120-130℃, and atomization pressure 0.22-0.25MPa; step (4) also includes screening the coated material with a screening mesh of 16 mesh for the upper layer and 40 mesh for the lower layer.

5. The use of the antibacterial benzoic acid preparation according to any one of claims 1-4 in the preparation of feed additives, wherein the feed additive is an additive used to inhibit harmful bacteria in the animal intestine.

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