Protective bacteriostatic acidifier and preparation method thereof

Abstract

The invention relates to the technical field of feed additives, in particular to a protective bacteriostatic acidifier and a preparation method thereof. The acidifying agent is prepared by the method. The method comprises the following steps: crushing benzoic acid to a target particle size; uniformly mixing fumaric acid with benzoic acid with a target particle size to obtain a mixture; uniformly mixing the mixture, an auxiliary agent and water to prepare prefabricated particles; rolling the prefabricated particles to obtain spherical particles; carrying out drying treatment on the spherical particles; screening the dried spherical particles, and selecting the spherical particles with the required particle size as pellet cores; and coating the pellet core with the hot-melted coating material to prepare the protective antibacterial acidifying agent. The problem that the titer of benzoic acid cannot be improved due to the fact that existing coated benzoic acid is not protected by other acidifying agents can be solved.

Description

Technical Field

[0001] The invention relates to the technical field of feed additives, and in particular to a protective antibacterial acidifier and a preparation method thereof. Background Art

[0002] The mechanism of antibacterial acidifiers in feed additives is as follows: antibacterial acidifiers enter microbial cells in molecular form, change their intracellular pH value, and interfere with the structure and activity of various enzymes in the cells, thereby causing the death of microorganisms. Benzoic acid is a broad-spectrum antibacterial acidifier. Because its dissociation constant pKa value is 4.2, which is higher than that of general organic acidifiers, and the benzene ring structure in its molecule enhances its lipophilicity, it is easier to penetrate the phospholipid bilayer and enter the microbial cell membrane, so its antibacterial effect is better than that of general organic acidifiers. However, in animals, there are many limiting factors for the antibacterial effect of benzoic acid. One is that most of the untreated benzoic acid entering the animal body is absorbed in the foregut, and only a small part enters the hindgut to exert an antibacterial effect; the second is that the environmental pH value of the hindgut is above 6, which is higher than the dissociation constant pKa value of benzoic acid of 4.2, causing the benzoic acid that enters the hindgut to be dissociated again and unable to exert an antibacterial effect. Therefore, in practical applications, it is usually necessary to increase the amount of addition to achieve the desired effect. Not only is the cost of use high, but the pungent smell of benzoic acid will also affect the feeding of animals.

[0003] In order to increase the potency of the antibacterial acidifier benzoic acid and reduce the pungent smell of benzoic acid, benzoic acid is usually coated. The coated antibacterial acidifiers prepared in the prior art are mostly directly coated with benzoic acid, that is, the coated benzoic acid is not protected by other acidifiers, so that benzoic acid is easily dissociated when released in the intestine after delivery, and it is difficult to maintain a molecular state. Therefore, the coated antibacterial acidifiers prepared in the prior art still need to maintain a high amount of benzoic acid to exert the antibacterial effect, and the potency of benzoic acid cannot be increased.

[0004] In summary, it is necessary to provide a protective antibacterial acidifier and a preparation method thereof to solve the problem that the existing coated benzoic acid is not protected by other acidifiers, resulting in the inability to increase the potency of benzoic acid. Summary of the invention

[0005] The object of the present invention is to provide a protective antibacterial acidifier and a preparation method thereof. The specific technical scheme is as follows:

[0006] In a first aspect, the present invention provides a method for preparing a protective antibacterial acidifier, comprising:

[0007] Step S1, crushing: crushing benzoic acid to a target particle size;

[0008] Step S2, mixing; mixing the fumaric acid and benzoic acid of target particle size to obtain a mixture;

[0009] Step S3, granulation: the mixture, the auxiliary agent and water are mixed to form prefabricated granules;

[0010] Step S4, rolling: rolling the prefabricated particles to obtain spherical particles;

[0011] Step S5, drying: drying the spherical particles;

[0012] Step S6, screening: screening the dried spherical particles to select spherical particles of a desired particle size as pellet cores;

[0013] Step S7, coating: coating the pellet core with the hot-melt coating material to obtain a protective antibacterial acidifier.

[0014] Optionally, in the mixture, the weight proportion of the benzoic acid is 50 to 70 parts; the weight of the fumaric acid is 15% to 50% of the weight of the benzoic acid.

[0015] Optionally, the target particle size is below 40 mesh, preferably below 60 mesh.

[0016] Optionally, the drying temperature used in the drying treatment is 45-60° C., preferably 50-55° C.; the moisture content of the spherical particles after the drying treatment is less than 10%.

[0017] Optionally, the auxiliary agent includes 5 to 15 parts by weight of silicon dioxide, 1 to 10 parts by weight of maltodextrin, 1 to 5 parts by weight of hydroxypropylmethylcellulose sodium and 1 to 5 parts by weight of microcrystalline cellulose.

[0018] Optionally, the coating material accounts for 10% to 30% of the weight of the pellet core;

[0019] The coating material comprises hydrogenated fat and monoglyceride in a weight ratio of 10 to 25:1;

[0020] Alternatively, the coating material comprises hydrogenated fat and mono- and di-glycerides in a weight ratio of 10 to 25:1.

[0021] Optionally, the coating material comprises hydrogenated fat and monoglyceride in a weight ratio of 13 to 18:1;

[0022] Alternatively, the coating material comprises hydrogenated fat and mono- and di-glycerides in a weight ratio of 13 to 18:1.

[0023] Optionally, the hot melt temperature is 95-115°C.

[0024] Optionally, the particle size of the pellet core is 20 to 40 meshes.

[0025] In a second aspect, the present invention provides a protective antibacterial acidifier, which is prepared by the preparation method of the protective antibacterial acidifier.

[0026] The application of the technical solution of the present invention has at least the following beneficial effects:

[0027] (1) The present invention provides a method for preparing a protective antibacterial acidifier, which can solve the problem that the existing coated benzoic acid is not protected by other acidifiers, resulting in the inability to improve the potency of benzoic acid. Specifically, the present invention uses fumaric acid with a dissociation constant pKa value of 3.02 and benzoic acid with a pKa value of 4.2 to mix and granulate them before coating. Fumaric acid and benzoic acid are released simultaneously in the intestine, and the fumaric acid with a lower pKa value can provide H for benzoic acid. + , inhibiting the dissociation of benzoic acid, so that more benzoic acid remains in a molecular state in the intestine, and can better exert the antibacterial effect. Therefore, the protective antibacterial acidifier prepared by the present invention has dual protection, that is, the coating effect of the coating material protects benzoic acid from being released in the intestine, especially in the posterior intestine, after passing through the stomach; while releasing benzoic acid, more benzoic acid is in a molecular state through fumaric acid protection, thereby enhancing the antibacterial effect. Therefore, the protective antibacterial acidifier prepared by the present invention has dual protection, so that benzoic acid can achieve high titer at a low dosage, which not only reduces the negative impact of irritating odor, but also can reduce costs and create more economic value. In addition, after the benzoic acid is crushed to the target particle size, the benzoic acid can be fully mixed with the powdered fumaric acid, so that the protection effect of the fumaric acid on the benzoic acid is better; the granulation and spheronization steps can make the pill core more round, and the higher the roundness, the more uniform the coating material will be, the better the release performance will be, and the higher the proportion of benzoic acid delivered to the posterior intestine will be; the drying treatment and screening are used to obtain the pill core with stable molding and uniform particle size, which is convenient for uniform coating of the coating material.

[0028] (2) The coating material of specific composition used in the present invention can assist fumaric acid and benzoic acid to have good release performance. According to in vitro dissolution test, the proportion of benzoic acid released in the posterior intestinal tract can reach more than 50%. DETAILED DESCRIPTION

[0029] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention belong to the scope of protection of the present invention.

[0030] Embodiment 1:

[0031] A method for preparing a protective antibacterial acidifier comprises:

[0032] Step S1, crushing: crushing benzoic acid to a target particle size;

[0033] Step S2, mixing; mixing the fumaric acid and benzoic acid of target particle size to obtain a mixture;

[0034] Step S3, granulation: the mixture, the auxiliary agent and water (the weight proportion of water is 20-40 parts, specifically 30 parts) are mixed and then made into strip-shaped or spherical prefabricated granules in a granulator;

[0035] Step S4, rounding: rounding the prefabricated particles in a shot blasting machine to obtain spherical particles;

[0036] Step S5, drying: drying the spherical particles in a fluidized bed;

[0037] Step S6, screening: screening the dried spherical particles to select spherical particles of a desired particle size as pellet cores;

[0038] Step S7, coating: The hot-melt coating material is transported to a coating machine via a peristaltic pump to coat the pellet cores to obtain a protective antibacterial acidifier.

[0039] In the mixture, the weight of the benzoic acid is 50 to 70 parts (specifically 70 parts); the weight of the fumaric acid is 15% to 50% (specifically 20%) of the weight of the benzoic acid.

[0040] The target particle size is below 40 mesh (specifically below 60 mesh).

[0041] The drying temperature used in the drying process is 45-60° C. (specifically 52° C.); the moisture content of the spherical particles after the drying process is less than 10% (specifically between 5% and 6%).

[0042] The auxiliary agent includes 5 to 15 parts by weight (specifically 10 parts) of silicon dioxide, 1 to 10 parts by weight (specifically 3 parts) of maltodextrin, 1 to 5 parts by weight (specifically 1.5 parts) of hydroxypropylmethylcellulose sodium and 1 to 5 parts by weight (specifically 1.5 parts) of microcrystalline cellulose.

[0043] The coating material accounts for 10% to 30% (specifically 24%) of the weight of the pellet core;

[0044] The coating material comprises hydrogenated fat and monoglyceride in a weight ratio of 10 to 25:1 (specifically 10:1).

[0045] The temperature of the hot melt is 95-115° C. (specifically 100° C.).

[0046] The particle size of the pellet core is 20 to 40 meshes.

[0047] Embodiment 2:

[0048] The difference from Example 1 is that the weight of the benzoic acid is 50 parts; the weight of the fumaric acid is 15% of the weight of the benzoic acid.

[0049] Embodiment 3:

[0050] The difference from Example 1 is that the weight of the benzoic acid is 60 parts; the weight of the fumaric acid is 30% of the weight of the benzoic acid.

[0051] Comparative Example 1:

[0052] The difference from Example 1 is that the weight of the benzoic acid is 50 parts; the weight of the fumaric acid is 13% of the weight of the benzoic acid.

[0053] Comparative Example 2:

[0054] The difference from Example 1 is that the weight of the benzoic acid is 50 parts; the weight of the fumaric acid is 52% of the weight of the benzoic acid.

[0055] Comparative Example 3:

[0056] The commercially available antibacterial acidifier coated with benzoic acid but not fumaric acid was purchased, the core component of which was benzoic acid; the coating material component was hydrogenated fat, and the benzoic acid content in the product was ≥84%.

[0057] Comparative Example 4:

[0058] The commercially available antibacterial acidifier coated with benzoic acid but not fumaric acid was purchased, the core component of which was benzoic acid; the coating material component was palm oil, etc., and the benzoic acid content in the product was ≥84%.

[0059] Comparative Example 5:

[0060] Purchase commercially available antibacterial acidifiers coated with benzoic acid but not fumaric acid, the core ingredients of which are benzoic acid and lactic acid; the coating material ingredients are hydrogenated fat, etc., and the benzoic acid content in the product is ≥40%.

[0061] Comparative Example 6:

[0062] A commercially available antibacterial acidifier coated with benzoic acid but not fumaric acid was purchased, the core component of which was benzoic acid; the composition of the coating material was unknown, and the benzoic acid content in the product was ≥50%.

[0063] Each antibacterial acidifier in Examples 1-3 and Comparative Examples 1-6 was sampled for in vitro dissolution release test, and the test results are shown in Table 1. The test method was completed in accordance with the in vitro dissolution release test method specified in the 2020 version of the "Chinese Pharmacopoeia", and the test was performed using a drug intelligent dissolution instrument model RCZ-6C3.

[0064] Table 1 In vitro dissolution release test results (expressed as the benzoic acid content retained in the antibacterial acidifier)

[0065]

[0066] From the data in Table 1, it can be seen that compared with Comparative Examples 2-6, the proportion of benzoic acid released in the posterior intestinal tract by each antibacterial acidifier prepared by Examples 1-3 of the present invention can reach more than 50%, showing better release performance. In addition, by comparing Examples 1-3 with Comparative Example 1, it can be seen that when the dosage of fumaric acid is adjusted to too low, it will basically not affect the proportion of benzoic acid released in the posterior intestinal tract, but it will reduce the antibacterial effect, see the data in Table 2.

[0067] Each antibacterial acidifier prepared in Examples 1-3 and Comparative Examples 1-6 was sampled and tested for minimum inhibitory concentration (MIC) in a pH 6.8 environment simulating the hind intestine, and the test results are shown in Table 2. The test method is the minimum inhibitory concentration (MIC) method.

[0068] Table 2 Minimum inhibitory concentration (MIC) test results

[0069] Grouping Staphylococcus aureus (mg / L) Escherichia coli (mg / L) Salmonella(mg / L) Example 1 1280 640 320 Example 2 1280 640 640 Example 3 1280 640 640 Comparative Example 1 1280 1280 640 Comparative Example 2 2560 1280 640 Comparative Example 3 5120 2560 2560 Comparative Example 4 5120 2560 2560 Comparative Example 5 2560 1280 640 Comparative Example 6 >5120 5120 5120

[0070] From the data in Table 2, it is known that compared with Comparative Examples 3-6, the MIC values ​​of each antibacterial acidifier prepared by Examples 1-3 of the present invention are lower, and the antibacterial effect is stronger. This shows that each antibacterial acidifier prepared by Examples 1-3 uses benzoic acid and fumaric acid in a compounded form, and more benzoic acid is in a molecular state through fumaric acid protection, thereby enhancing the antibacterial effect. Compared with Example 1, Comparative Example 1 uses too low a dosage of fumaric acid, and the protective effect on benzoic acid is weak, which reduces the antibacterial effect. Compared with Example 1, Comparative Example 2 uses too high a dosage of fumaric acid, so that the content of benzoic acid in the antibacterial acidifier is relatively reduced, thereby reducing the antibacterial effect.

[0071] The protective antibacterial acidifier prepared in Example 1 was used to test the growth performance of piglets. The test results are shown in Table 3 ("d" in Table 3 represents days). The test method is as follows:

[0072] 153 healthy Duroc Changda three-way piglets (average weight of about 11.5 kg) were selected and randomly divided into three treatment groups, namely Group A, Group B and Group C. Group A was the control group 1, i.e. the basic diet group; Group B was the control group 2, i.e. the basic diet + 3kg / t benzoic acid raw powder group (3kg benzoic acid raw powder was added to each ton of the basic diet); Group C was the experimental group, i.e. the basic diet + 1kg / t protective antibacterial acidifier prepared in Example 1 group (1kg protective antibacterial acidifier prepared in Example 1 was added to each ton of the basic diet). Each treatment group had 3 replicates, and the initial weight of the piglets in each treatment group was adjusted to make the initial average weight similar. The experiment lasted for 14 days. The basic diet was a combination of corn and soybean meal, and the nutritional standard was based on NRC2012.

[0073] Table 3 Results of growth performance test of piglets

[0074]

[0075]

[0076] From the data in Table 3, it can be seen that compared with the control group 1 (i.e., group A) and the control group 2 (i.e., group B), the test group (i.e., group C) increased the average daily weight gain of piglets, reduced the feed-to-meat ratio and diarrhea rate, and improved the growth performance of piglets. This shows that the protective antibacterial acidifier prepared by the present invention can achieve high titer of benzoic acid at a low dosage due to its dual protection.

[0077] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a protective antibacterial acidifier, characterized in that: include: Step S1, crushing: crushing benzoic acid to a target particle size; Step S2, mixing; mixing fumaric acid and benzoic acid of target particle size to obtain a mixture; Step S3, granulation: the mixture, the auxiliary agent and water are mixed to form prefabricated granules; Step S4, rolling: rolling the prefabricated particles to obtain spherical particles; Step S5, drying: drying the spherical particles; Step S6, screening: screening the dried spherical particles to select spherical particles of a desired particle size as pellet cores; Step S7, coating: coating the pellet core with the hot-melt coating material to obtain a protective antibacterial acidifier.

2. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: In the mixture, the weight proportion of the benzoic acid is 50 to 70 parts; the weight of the fumaric acid is 15% to 50% of the weight of the benzoic acid.

3. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: The target particle size is below 40 mesh.

4. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: The drying temperature used in the drying process is 45-60° C.; the moisture content of the spherical particles after the drying process is less than 10%.

5. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: The auxiliary agent comprises 5 to 15 parts by weight of silicon dioxide, 1 to 10 parts by weight of maltodextrin, 1 to 5 parts by weight of sodium hydroxypropylmethylcellulose and 1 to 5 parts by weight of microcrystalline cellulose.

6. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: The coating material accounts for 10% to 30% of the weight of the pellet core; The coating material comprises hydrogenated fat and monoglyceride in a weight ratio of 10 to 25:1; Alternatively, the coating material comprises hydrogenated fat and mono- and di-glycerides in a weight ratio of 10 to 25:

1.

7. The method for preparing the protective antibacterial acidifier according to claim 6, characterized in that: The coating material comprises hydrogenated fat and monoglyceride in a weight ratio of 13 to 18:1; Alternatively, the coating material comprises hydrogenated fat and mono- and di-glycerides in a weight ratio of 13 to 18:

1.

8. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: The temperature of the hot melt is 95-115°C.

9. The method for preparing the protective antibacterial acidifier according to claim 1, characterized in that: The particle size of the pellet core is 20 to 40 meshes.

10. A protective antibacterial acidifier, characterized in that: The protective antibacterial acidifier is prepared by the preparation method of any one of claims 1 to 9.

Images