A slow-release feed additive and a preparation method thereof

Abstract

The application relates to the technical field of feed additives, in particular to a slow-release feed additive and a preparation method thereof, which comprises chitosan, sodium alginate, an effective component, calcium chloride, Tween-80 and water, and forms pH-responsive interpenetrating network microspheres. The release rate of the microspheres in gastric juice is less than 10% in 2 hours, and the release rate in intestinal juice is greater than 90% in 24 hours. The preparation method adopts a W / O emulsion method, and the microsphere structure is constructed through ionic crosslinking. The application can realize the gastric protection and intestinal uniform release of acid-sensitive nutritional ingredients, improve the utilization rate of vitamins or amino acids by animals, and has good stability and biocompatibility.

Description

Technical Field

[0001] This invention belongs to the field of feed additive technology, specifically a slow-release feed additive and its preparation method. Background Technology

[0002] To improve the bioavailability of nutrients, the development of slow-release feed additives has become an important direction. An ideal slow-release additive needs to possess both gastric stability and targeted intestinal release characteristics to protect acid-sensitive active ingredients (such as vitamins, amino acids, and plant extracts) from gastric acid degradation and achieve continuous and controllable release under specific intestinal pH conditions. Currently, existing technologies attempt to construct slow-release systems using natural or synthetic materials, but there is still room for improvement in release kinetics regulation, material biocompatibility, and cost control.

[0003] For example, patent CN102524536B discloses an application of theaflavins as a feed additive. The technical solution involves directly adding theaflavins to conventional feed formulations at a dosage of 0.015% to 0.045% of the total feed weight. This additive can enhance the immunity and antioxidant capacity of farmed animals, avoiding the use of antibiotics and chemical antioxidants. However, this solution does not perform any form of encapsulation or sustained-release treatment on the theaflavins. The active ingredient is exposed to a highly acidic environment in the stomach along with the feed matrix, which may cause some theaflavins to degrade before reaching the absorption site, affecting their effective concentration and duration of action in the intestines.

[0004] Patent CN101884366B also discloses a feed additive containing pollen extract and cysteine, used to replace exogenous hormones and promote animal growth. This additive is prepared by physical mixing and, while showing some growth-promoting effects in practical applications, it also does not employ sustained-release carrier technology. Both the active polyphenols in the pollen extract and cysteine ​​are acid-sensitive and may undergo structural changes or inactivation under low pH conditions in the stomach. Furthermore, their release depends on the natural disintegration of the feed in the digestive tract, making it difficult to achieve a uniform and continuous release in the intestines, potentially leading to excessively rapid initial release followed by insufficient supply later.

[0005] Therefore, while preserving the efficacy of natural active ingredients, constructing a carrier system that can remain stable in the stomach and achieve controlled sustained release under intestinal pH conditions has become a key technological path to improve the effectiveness of feed additives. The "chitosan-alginate interpenetrating network microsphere" sustained-release system proposed in this invention aims to optimize release kinetics and improve bioavailability through the synergistic response mechanism of the two natural polysaccharides. Summary of the Invention

[0006] This application provides a slow-release feed additive and its preparation method, which aims to achieve gastric protection and uniform intestinal release of acid-sensitive active ingredients by constructing a microsphere carrier with an interpenetrating network structure of chitosan and sodium alginate, and utilizing the response characteristics of the two natural polysaccharides under different pH conditions.

[0007] In a first aspect, the present invention provides a slow-release feed additive, made from the following raw materials in the indicated weight percentages: 2.0% to 2.5% chitosan, 1.5% to 2.0% sodium alginate, 1.0% to 2.0% active ingredient, 1.0% to 1.5% calcium chloride, 0.5% to 1.0% Tween-80, with the balance being water; the additive is in the form of microspheres with an average particle size of 100 to 200 micrometers, and has a release rate of less than 10% in simulated gastric fluid at pH 1.2 after 2 hours, and a release rate of greater than 90% in simulated intestinal fluid at pH 6.8 after 24 hours.

[0008] Preferably, the degree of deacetylation of the chitosan is not less than 90%, and the weight-average molecular weight of the sodium alginate is 150 to 200 kDa.

[0009] Preferably, the active ingredient is a complex vitamin, wherein the mass ratio of vitamin E, vitamin B12 and folic acid is 5:2:1; or the active ingredient is an amino acid, wherein the mass ratio of lysine and methionine is 3:1.

[0010] Another aspect of the present invention provides a method for preparing a slow-release feed additive, comprising the following steps: (1) Aqueous phase preparation: Chitosan is dissolved in acetic acid solution, stirred until dissolved, active ingredients are added, and ultrasonically dispersed to form a homogeneous aqueous phase; (2) Preparation of oil phase: Liquid paraffin is mixed with Tween-80 and stirred to form an oil phase; (3) Emulsification: The aqueous phase is injected into the oil phase and stirred at high speed to form a W / O emulsion; (4) Ionic crosslinking: Add calcium chloride aqueous solution dropwise to the emulsion and stir to react, so that chitosan and sodium alginate form microspheres through ionic bonds; (5) Solidification and drying: Microspheres are collected by filtration, residual oil phase is removed by washing, and vacuum drying is performed to obtain the slow-release feed additive.

[0011] Preferably, in step (1), the concentration of the acetic acid solution is 1 wt%, and the stirring conditions are 25°C, 300 rpm, and 30 minutes; after adding the active ingredient, the ultrasonic dispersion power is 200 W and the time is 10 minutes.

[0012] Preferably, in step (2), the mass percentage of liquid paraffin in the oil phase is 95%, the mass percentage of Tween-80 is 5%, and the stirring conditions are 25°C, 200 rpm, and 15 minutes.

[0013] Preferably, in step (3), the mass ratio of the aqueous phase to the oil phase is 1:5, the stirring speed is 800 to 1200 rpm, the time is 30 to 40 minutes, and the temperature is 25°C.

[0014] Preferably, in step (4), the concentration of the calcium chloride aqueous solution is 1.0% to 1.5 wt%, and the reaction conditions after dropwise addition are 25°C, 500 rpm, and 60 minutes.

[0015] Preferably, in step (5), the washing is performed three times with petroleum ether, and the vacuum drying conditions are 40°C and 8 hours.

[0016] The beneficial effects of this invention are as follows: This invention constructs interpenetrating network microspheres with dual pH response characteristics by precisely controlling the ratio, molecular parameters, and preparation process parameters of chitosan and sodium alginate. Chitosan provides gastric stability, while sodium alginate provides intestinal swelling. The two are bridging each other with Ca²⁺ to form a synergistic structure, overcoming the limitations of single materials. The preparation process adopts the W / O emulsion method, and the particle size and release performance of the microspheres are precisely controlled by adjusting the stirring speed, phase ratio, and crosslinking conditions. All raw materials used are natural and biodegradable, with costs more than 50% lower than synthetic polymers. They are non-toxic and non-irritating, solving the technical problems of "premature gastric release" and "uncontrollable intestinal release" in existing technologies. By constructing interpenetrating network microspheres with clear pH response thresholds and release kinetic characteristics, both gastric stability and intestinal release efficiency are taken into account. Attached Figure Description

[0017] Figure 1 The graphs show the in vitro release performance of the feeds in simulated gastric juice in Example 1 and Comparative Examples 1 and 2 of the present invention. Detailed Implementation

[0018] The various embodiments or implementation schemes in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments.

[0019] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with an embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0020] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0021] As described in the background section above, acid-sensitive active ingredients in feed additives (such as vitamin B12, folic acid, and lysine) are prone to degradation or inactivation in the low pH environment of an animal's stomach, leading to a significant reduction in bioavailability. Furthermore, conventional encapsulation or physical mixing methods fail to achieve continuous and uniform release into the intestines, affecting nutrient absorption efficiency. While existing technologies have attempted to use single chitosan or sodium alginate microspheres as carriers, the former swells insufficiently in the alkaline environment of the intestines, and the latter exhibits poor stability in the stomach; neither can simultaneously meet the dual requirements of gastric protection and controlled release into the intestines.

[0022] Based on this, this application provides a slow-release feed additive and its preparation method. By constructing a microsphere carrier with an interpenetrating network structure of chitosan and sodium alginate, the differences in the ionic state changes and cross-linking behavior of the two under different pH environments are utilized to achieve gastric protection and uniform intestinal release of acid-sensitive active ingredients.

[0023] In a first aspect, this application provides a slow-release feed additive made from the following raw materials in the indicated weight percentages: 2.0% to 2.5% chitosan, 1.5% to 2.0% sodium alginate, 1.0% to 2.0% active ingredient, 1.0% to 1.5% calcium chloride, 0.5% to 1.0% Tween-80, with the balance being water; the additive is in the form of microspheres with an average particle size of 100 to 200 micrometers, and has a release rate of less than 10% in simulated gastric fluid at pH 1.2 after 2 hours and a release rate of greater than 90% in simulated intestinal fluid at pH 6.8 after 24 hours.

[0024] According to this application, chitosan is protonated under acidic conditions to form a cationic polymer, which weakens the electrostatic repulsion between molecular chains and results in a dense structure. This maintains the integrity of the microspheres in the low pH environment of the stomach and inhibits the premature release of the active ingredients. Sodium alginate swells under alkaline conditions with the cross-linked network formed by calcium ions, promoting the continuous diffusion of the active ingredients inside the microspheres. Through the blending and ionic cross-linking of chitosan and sodium alginate, an interpenetrating network structure is formed, enabling the microspheres to remain stable in the stomach while achieving uniform release in the intestinal pH environment.

[0025] In some embodiments, the degree of deacetylation of the chitosan is not less than 90%, and the weight-average molecular weight of the sodium alginate is 150 to 200 kDa. Chitosan with a high degree of deacetylation exhibits stronger cationic properties, enhancing its stability in acidic environments; sodium alginate within a specific molecular weight range provides suitable viscosity and crosslinking density, ensuring a balance between the mechanical strength and release kinetics of the microspheres.

[0026] In some embodiments, the active ingredient is a complex vitamin, wherein the mass ratio of vitamin E, vitamin B12, and folic acid is 5:2:1; or the active ingredient is an amino acid, wherein the mass ratio of lysine and methionine is 3:1. This formulation is designed based on animal nutritional needs and the physicochemical properties of the components. Vitamin E is a fat-soluble antioxidant, and vitamin B12 and folic acid participate in one-carbon metabolism. The synergistic effect of the three can enhance the immunity and growth performance of piglets. Lysine and methionine are limiting amino acids, and their 3:1 ratio can optimize protein synthesis efficiency.

[0027] Secondly, this application provides a method for preparing the above-mentioned slow-release feed additive, comprising the following steps: (1) Aqueous phase preparation: Chitosan is dissolved in acetic acid solution, stirred until dissolved, active ingredients are added, and ultrasonically dispersed to form a homogeneous aqueous phase; (2) Preparation of oil phase: Liquid paraffin is mixed with Tween-80 and stirred to form an oil phase; (3) Emulsification: The aqueous phase is injected into the oil phase and stirred at high speed to form a W / O emulsion; (4) Ionic crosslinking: Add calcium chloride aqueous solution dropwise to the emulsion and stir to react, so that chitosan and sodium alginate form microspheres through ionic bonds; (5) Solidification and drying: Microspheres are collected by filtration, residual oil phase is removed by washing, and vacuum drying is performed to obtain the slow-release feed additive.

[0028] According to this application, microspheres are prepared using a W / O emulsion method, with liquid paraffin as the continuous phase and Tween-80 as the emulsifier to control the size of the aqueous droplets, thereby regulating the microsphere particle size. Calcium chloride is used as a crosslinking agent, and it interacts ionicly with the carboxyl groups of sodium alginate and the amino groups of chitosan to form a double network structure, which enhances the stability of the microspheres under mechanical friction in the stomach and endows them with pH responsiveness.

[0029] In some embodiments, in step (1), the concentration of the acetic acid solution is 1 wt%, and the stirring conditions are 25°C, 300 rpm, and 30 minutes; after adding the active ingredient, the ultrasonic dispersion power is 200 W for 10 minutes. This acetic acid concentration is sufficient to dissolve chitosan without causing its degradation, the stirring speed of 300 rpm ensures that the chitosan is fully swollen and dissolved, and the 200 W ultrasonic treatment can uniformly disperse vitamins or amino acids in the aqueous phase, avoiding aggregation.

[0030] In some embodiments, in step (2), the oil phase contains 95% liquid paraffin by mass and 5% Tween-80 by mass, and the stirring conditions are 25°C, 200 rpm, and 15 minutes. Tween-80, as a nonionic surfactant, reduces the interfacial tension between the aqueous and oil phases, forming a stable W / O emulsion; the 95% proportion of liquid paraffin provides a sufficient hydrophobic environment to prevent the aqueous droplets from coalescing.

[0031] In some embodiments, in step (3), the mass ratio of the aqueous phase to the oil phase is 1:5, the stirring speed is 800 to 1200 rpm, the time is 30 to 40 minutes, and the temperature is 25°C. This phase ratio ensures that the aqueous phase is fully dispersed into tiny droplets, the stirring speed of 800 to 1200 rpm controls the droplet diameter to be in the range of 100 to 200 micrometers, and the emulsification time of 30 to 40 minutes makes the droplet distribution tend to be uniform.

[0032] In some embodiments, in step (4), the concentration of the calcium chloride aqueous solution is 1.0% to 1.5 wt%, and the reaction conditions after dropwise addition are 25°C, 500 rpm, and 60 minutes. Within this range, the calcium chloride concentration provides sufficient Ca²⁺ to bind with the G units of sodium alginate, while simultaneously forming weak ion pairs with the -NH3⁺ of chitosan. The 500 rpm stirring speed ensures uniform crosslinking, and the 60-minute reaction time allows the microsphere structure to fully solidify.

[0033] In some embodiments, in step (5), the washing is performed three times with petroleum ether, and the vacuum drying conditions are 40°C and 8 hours. Petroleum ether can effectively dissolve and remove the liquid paraffin adhering to the surface of the microspheres, and the three washings ensure that the oil phase residue is below the detection limit; vacuum drying at 40°C avoids thermal degradation of the active ingredients, and the 8-hour drying time reduces the moisture content of the microspheres to below 5%, which is convenient for long-term storage.

[0034] Thirdly, this application provides the application of the above-mentioned slow-release feed additive in the preparation of animal feed, wherein the additive is used in mammalian feed to improve the intestinal release rate of the active ingredient and the digestibility of the animal.

[0035] According to this application, the microsphere additive is mixed into the basal feed at a ratio of 0.1% to 0.5% and fed to piglets or broilers. The microspheres remain intact in the stomach at a pH of 1.2 to 3.0, with a release rate of less than 10% within 2 hours and an effective ingredient retention rate of over 90%. After entering the intestines, the pH rises to 6.8 to 7.4, the sodium alginate network swells, chitosan deprotonates, and the microsphere pores expand. The effective ingredient is released uniformly over 24 hours, with a release rate exceeding 90%. The release curve shows a linear trend: 25% to 30% is released in the first 6 hours, 30% to 35% in 6 to 12 hours, and 35% to 40% in 12 to 24 hours, meeting the continuous nutritional needs of animals.

[0036] In some embodiments, the mammal is a weaned piglet, aged 21 to 28 days. At this stage, piglets have high gastric acid secretion, a pH value as low as 1.2 to 2.0, insufficient digestive enzyme activity, and a high demand for acid-sensitive vitamins and amino acids. After adding the microspheres of this invention, the actual absorption of vitamin B12 in the intestine increases by more than 40%, and the feed conversion ratio decreases by 0.15 to 0.20.

[0037] In some embodiments, the additive is used in combination with other functional ingredients such as phytase and probiotics. The microsphere structure does not interfere with the activity of other ingredients and can prevent phytase from being inactivated in the stomach, thereby improving its catalytic efficiency in the small intestine.

[0038] The following describes embodiments of this application. The embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Reagents or instruments used, unless otherwise specified, are all conventional products that can be obtained commercially. Example 1

[0039] Aqueous phase preparation: Weigh 2.2 g of chitosan with a degree of deacetylation of 92% (weight average molecular weight of approximately 300 kDa), add it to 97.8 g of 1 wt% acetic acid aqueous solution, stir at 300 rpm for 30 minutes at 25°C until the chitosan is completely dissolved, add 1.5 g of complex vitamins (vitamin E: vitamin B12: folic acid = 5:2:1, i.e., containing 0.9375 g of vitamin E, 0.375 g of vitamin B12, and 0.1875 g of folic acid), and sonicate at 200 W for 10 minutes to form a uniform and transparent aqueous phase.

[0040] Oil phase preparation: Weigh 95 g of liquid paraffin and 5 g of Tween-80, stir at 200 rpm for 15 minutes at 25°C to form a clear oil phase.

[0041] Emulsification: The aqueous phase was slowly injected into the oil phase, and the mass ratio of the aqueous phase to the oil phase was controlled at 1:5. The mixture was stirred at 1000 rpm for 35 minutes at 25°C to form a stable W / O type emulsion. The droplets were spherical, and the average particle size observed under a microscope was about 150 micrometers.

[0042] Ionic crosslinking: A 1.2 wt% calcium chloride aqueous solution (containing 1.3 g of calcium chloride and 107 g of water) was added dropwise to the above emulsion at a rate of 1 drop per second. After the addition was completed, the mixture was stirred at 25 °C and 500 rpm for 60 minutes. During this time, chitosan and sodium alginate formed interpenetrating network microspheres under the bridging effect of Ca²⁺.

[0043] Solidification and drying: After the reaction was completed, the microspheres were collected by vacuum filtration, rinsed three times with deionized water, and then washed three times with petroleum ether (50 ml each time) to completely remove residual liquid paraffin. The washed microspheres were placed in a vacuum drying oven and dried at 40°C for 8 hours to obtain a white to pale yellow microspherical slow-release feed additive with a moisture content of 4.2%. Example 2

[0044] Except that the active ingredient is amino acids, the rest of the operation is the same as in Example 1. Specifically, 1.6 g of an amino acid mixture (lysine:methionine = 3:1, i.e., containing 1.2 g of L-lysine hydrochloride and 0.4 g of DL-methionine) was added to the aqueous phase, while the parameters of the other steps remained unchanged. The final microspheres had an average particle size of 165 μm and a water content of 4.5%. Example 3

[0045] The chitosan content was adjusted to 2.0%, sodium alginate to 2.0%, active ingredient to 1.0% complex vitamins (same ratio as in Example 1), calcium chloride to 1.5%, Tween-80 to 0.8%, and the remainder to be water. In the aqueous phase preparation, the acetic acid concentration remained 1 wt%, and the stirring and ultrasonic conditions were unchanged. In the oil phase, liquid paraffin was 95.2%, and Tween-80 was 4.8%. The emulsification stirring speed was 1200 rpm for 30 minutes; the calcium chloride solution concentration was 1.5 wt%, and the crosslinking reaction was carried out for 60 minutes. The drying conditions remained unchanged. The resulting microspheres had an average particle size of 110 μm and a narrower particle size distribution (PDI = 0.18). Example 4

[0046] The chitosan content was 2.5%, sodium alginate was 1.5%, the active ingredient was 2.0% amino acids (same ratio as in Example 2), calcium chloride was 1.0%, and Tween-80 was 1.0%. The emulsification stirring speed was 800 rpm for 40 minutes; the calcium chloride solution concentration was 1.0 wt%. The resulting microspheres had an average particle size of 195 micrometers, and the mechanical strength was tested by oscillation (simulating gastrointestinal peristalsis), and the integrity retention rate was over 95%.

[0047] Comparative Example 1 Only chitosan (2.2%) and the active ingredient (1.5% multivitamin) were used; sodium alginate and calcium chloride were not included. The remaining steps were performed as in Example 1. The resulting particles showed a release rate of only 65% ​​in simulated intestinal fluid at pH 6.8 after 24 hours, and the release curve exhibited a burst release pattern, with 50% released in the first 2 hours.

[0048] Comparative Example 2 Only sodium alginate (1.8%) and the active ingredient (1.5% multivitamin) were used; chitosan was not included, and the cross-linking agent was 1.2% calcium chloride. The remaining steps were the same as in Example 1. The resulting microspheres exhibited a 35% release rate in simulated gastric juice at pH 1.2 after 2 hours, but showed poor in-gastric stability.

[0049] Comparative Example 3 An O / W emulsion method was used instead of the W / O method: the oil phase (containing the active ingredient dissolved in vegetable oil) was dropwise into the aqueous phase (containing chitosan and sodium alginate), followed by cross-linking. The resulting microspheres had a wide particle size distribution (80 to 300 micrometers) and an active ingredient encapsulation rate of less than 70%.

[0050] The samples obtained from the above examples and comparative examples were subjected to in vitro release performance tests: the release rate was measured by sampling in simulated gastric fluid (pH 1.2, containing 0.2% NaCl, 37℃) for 2 hours; subsequently, the samples were transferred to simulated intestinal fluid (pH 6.8, containing phosphate buffer, 37℃) for continued release for 24 hours, with samples taken at regular intervals. The release rate was calculated by determining the vitamin B12 or lysine content using high-performance liquid chromatography (HPLC). The results are shown in Table 1.

[0051] Table 1 Sample Intragastric 2h release rate (%) Intestinal 24h release rate (%) Mean particle size (μm) Encapsulation rate (%) Example 1 7.2 93.5 152 96.8 Example 2 6.8 92.1 165 95.3 Example 3 8.1 94.0 110 97.2 Example 4 9.3 91.7 195 94.6 Comparative Example 1 5.5 65.2 148 89.4 Comparative Example 2 35.6 88.9 155 91.0 Comparative Example 3 12.4 85.3 180 68.7 From Table 1 and Figure 1 As can be seen, Examples 1 to 4 of this application all meet the technical requirements of a gastric release rate of less than 10% within 2 hours and an intestinal release rate of greater than 90% within 24 hours, and exhibit high encapsulation efficiency and controllable particle size. Comparative Example 1, lacking a sodium alginate network, resulted in incomplete intestinal release; Comparative Example 2, lacking chitosan protection, resulted in excessively rapid gastric release; Comparative Example 3, due to improper emulsification methods, resulted in low encapsulation efficiency and uneven particle size.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A slow-release feed additive, characterized in that, It is made from the following raw materials in weight percentages: chitosan 2.0% to 2.5%, sodium alginate 1.5% to 2.0%, active ingredient 1.0% to 2.0%, calcium chloride 1.0% to 1.5%, Tween-80 0.5% to 1.0%, with the balance being water; the additive is in the form of microspheres with an average particle size of 100 to 200 micrometers, and has a release rate of less than 10% in simulated gastric fluid at pH 1.2 after 2 hours and a release rate of greater than 90% in simulated intestinal fluid at pH 6.8 after 24 hours.

2. The slow-release feed additive according to claim 1, characterized in that, The degree of deacetylation of the chitosan is not less than 90%, and the weight-average molecular weight of the sodium alginate is 150 to 200 kDa.

3. The slow-release feed additive according to claim 1, characterized in that, The active ingredient is a complex vitamin, wherein the mass ratio of vitamin E, vitamin B12 and folic acid is 5:2:1; or the active ingredient is an amino acid, wherein the mass ratio of lysine and methionine is 3:

1.

4. A method for preparing a slow-release feed additive as described in any one of claims 1 to 3, characterized in that, Includes the following steps: (1) Aqueous phase preparation: Chitosan is dissolved in acetic acid solution, stirred until dissolved, active ingredients are added, and ultrasonically dispersed to form a homogeneous aqueous phase; (2) Preparation of oil phase: Liquid paraffin is mixed with Tween-80 and stirred to form an oil phase; (3) Emulsification: The aqueous phase is injected into the oil phase and stirred at high speed to form a W / O emulsion; (4) Ionic crosslinking: Add calcium chloride aqueous solution dropwise to the emulsion and stir to react, so that chitosan and sodium alginate form microspheres through ionic bonds; (5) Solidification and drying: Microspheres are collected by filtration, residual oil phase is removed by washing, and vacuum drying is performed to obtain the slow-release feed additive.

5. The preparation method according to claim 4, characterized in that, In step (1), the concentration of the acetic acid solution is 1 wt%, and the stirring conditions are 25°C, 300 rpm, and 30 minutes; after adding the active ingredient, the ultrasonic dispersion power is 200 W and the time is 10 minutes.

6. The preparation method according to claim 4, characterized in that, In step (2), the mass percentage of liquid paraffin in the oil phase is 95%, the mass percentage of Tween-80 is 5%, and the stirring conditions are 25°C, 200 rpm, and 15 minutes.

7. The preparation method according to claim 4, characterized in that, In step (3), the mass ratio of the aqueous phase to the oil phase is 1:5, the stirring speed is 800 to 1200 rpm, the time is 30 to 40 minutes, and the temperature is 25°C.

8. The preparation method according to claim 4, characterized in that, In step (4), the concentration of the calcium chloride aqueous solution is 1.0% to 1.5 wt%, and the reaction conditions after dropwise addition are 25°C, 500 rpm, and 60 minutes.

9. The preparation method according to claim 4, characterized in that, In step (5), the washing is performed three times with petroleum ether, and the vacuum drying conditions are 40°C and 8 hours.

10. An animal feed, characterized in that, The feed additive comprises any one of claims 1 to 3, wherein the additive is added to the feed at a ratio of 0.1% to 0.5%.

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