A slow-release multi-mineral feed additive and a preparation method thereof

Abstract

The present application relates to a kind of slow-release multi-mineral feed additive and its preparation method applied to the technical field of feed additive, the additive is microsphere with three concentric ball structures, from outside to inside, in turn: outermost layer, include selenium and / or iodine, carrier is enterase sensitive polymer;Middle layer, include zinc and manganese, carrier is the pH-sensitive polymer modified by quaternary ammonium salt;Nucleus, include copper, carrier is slow-release skeleton material.The total particle size of microsphere is 100-200 μm, the thickness ratio of three layers is 1:(1.8-2.2):(1.8-2.2).Its preparation method uses "multi-stage atomization-layer-by-layer self-assembly-ladder temperature drying" integrated process, three layers of slurry are pumped out by coaxial three-channel atomizing nozzle, and are formed by ladder temperature zone drying and solidification.The present application realizes the directional gradient sequential release of mineral elements in the digestive tract of poultry, solves the antagonism problem among minerals, significantly improves the bioavailability, and the middle layer has antibacterial function simultaneously, can improve intestinal health, and is suitable for poultry feed such as laying hens.

Description

Technical Field

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

[0002] Minerals are essential nutrients for poultry growth, development, reproduction, and production performance. For example, selenium and iodine participate in metabolic regulation, zinc and manganese affect bone development and immune function, and copper participates in enzyme activity regulation. Multimineral additives are widely used in laying hen feed, but current technologies suffer from the following core deficiencies:

[0003] Severe mineral element antagonism: Traditional multi-mineral additives are mostly mixed powders or single-layer particles. Elements such as copper, zinc, and selenium are released simultaneously in the digestive tract, which easily lead to chemical reactions to form insoluble complexes (such as copper competing with zinc for absorption sites, and selenium forming precipitates with iodine), resulting in a significant reduction in mineral utilization (usually less than 50%). Furthermore, unabsorbed minerals are excreted with feces, causing environmental pollution.

[0004] Release characteristics do not match digestive tract physiology: The digestive tract of laying hens is divided into the stomach, duodenum, jejunum, ileum, and posterior intestinal tract. Significant differences exist in pH and enzyme composition between these sections (e.g., stomach pH 2.0-3.5, containing pepsin; intestinal pH 6.0-7.0, containing pancreatic enzymes and bile salts). Existing additives lack targeted release design; outer layer minerals are rapidly released in the stomach, while inner layer minerals are insufficiently released in the posterior intestinal tract, failing to precisely supply minerals according to their absorption sites (e.g., selenium and iodine are mainly absorbed in the duodenum, zinc and manganese in the jejunum-ileum, and copper in the ileum and posterior intestinal tract).

[0005] Insufficient protection of gut health: During the peak egg production period, the gut microbiota of laying hens is prone to imbalance, with harmful bacteria such as E. coli proliferating, leading to intestinal inflammation and digestive disorders. Traditional multi-mineral additives have no antibacterial function, and the excessive release of some mineral ions (such as copper ions) can even damage the intestinal mucosa.

[0006] The preparation process is complex and the stability is poor: existing multilayer sustained-release particles mostly adopt the "stepwise encapsulation method" (first prepare the core, and then encapsulate the middle layer and the outer layer in sequence), which has problems such as weak interlayer bonding force, uneven structure, and low production efficiency. Moreover, the sustained-release effect is easily affected by processing and storage conditions.

[0007] To address the aforementioned issues, there is an urgent need in this field to develop a multi-mineral feed additive with precise targeted release characteristics, the ability to eliminate mineral antagonism, and the ability to protect intestinal health, as well as an efficient and stable preparation process. Summary of the Invention

[0008] To address the shortcomings of existing technologies, the present invention aims to provide a slow-release multi-mineral feed additive, its preparation method, and its application. Through the design of "three-layer concentric sphere structure + sensitive carrier matching + quaternization modification", the mineral elements are released sequentially in different sections of the laying hen's digestive tract, eliminating antagonism and improving utilization. At the same time, the middle layer is endowed with antibacterial function to protect intestinal health. And the integrated preparation process ensures product stability and production efficiency.

[0009] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0010] In a first aspect, the present invention provides a slow-release multi-mineral feed additive, wherein the additive is a microsphere with a three-layer concentric spherical structure, consisting of an outermost layer, a middle layer, and a core layer from the outside to the inside, and the structure of each layer and the core parameters are as follows:

[0011] The outermost layer contains one or both of selenium and iodine, and its carrier is an intestinal enzyme-sensitive polymer. The selenium source is preferably one or both of sodium selenite and yeast selenium, and the iodine source is preferably one or both of potassium iodide and calcium iodate. The intestinal enzyme-sensitive polymer is preferably one or both of cross-linked linear starch and specific peptides (such as glutamine oligopeptides). It can be degraded by intestinal enzymes (such as amylase and peptidase) in the duodenum and prejejunum of laying hens to achieve rapid release of selenium and / or iodine, matching the needs of their main absorption sites.

[0012] The intermediate layer contains zinc and manganese, and its carrier is a pH-sensitive polymer. The zinc source is preferably one or both of zinc sulfate and zinc oxide, and the manganese source is preferably one or both of manganese sulfate and manganese oxide. The pH-sensitive polymer is preferably a sodium alginate-chitosan composite gel, which, after quaternization modification, can permanently acquire positive charge and antibacterial properties. Furthermore, this layer swells and degrades in the neutral pH environment (pH 6.0-7.0) of the mid-to-late jejunum and ileum, releasing zinc and manganese to match their optimal absorption window. Simultaneously, the positively charged groups can disrupt the cell membranes of harmful bacteria, exerting an antibacterial effect.

[0013] The core contains copper, and its carrier is a slow-release matrix material. The copper source is preferably one or two of copper sulfate and copper oxide. The slow-release matrix material is preferably one or two of ethyl cellulose and glyceryl monostearate, which can be gradually degraded in the slow digestive environment of the ileum and posterior intestinal tract to achieve continuous release of copper and adapt to its slow absorption characteristics.

[0014] Preferably, the total particle size of the microspheres is 100μm to 200μm, more preferably 150μm ± 50μm; this particle size range ensures that the residence time of the microspheres in the digestive tract of laying hens matches the release requirements, while also possessing good flowability, making them easy to mix with feed and not affecting poultry consumption. More preferably, the wall thickness ratio of the outermost layer, the middle layer, and the core is 1:(1.8-2.2):(1.8-2.2); this ratio was determined through extensive fluid dynamics simulations and in vitro release experiments, enabling precise control of the release rate of each layer and achieving a sequential release effect of "rapid release from the outer layer, moderate release from the middle layer, and sustained release from the core."

[0015] Furthermore, the quaternization modification process of the intermediate layer specifically involves grafting a cationic monomer onto a sodium alginate-chitosan composite gel network through in-situ polymerization. The preferred cationic monomer is methacryloyloxyethyltrimethylammonium chloride (DMC). During the preparation of the intermediate layer slurry, DMC and a thermal initiator (potassium persulfate or ammonium persulfate, added at 0.5%-2% of the total mass of the intermediate layer slurry) are simultaneously added. Thermal initiation of in-situ polymerization is triggered in a low-temperature zone (60°C to 80°C) during stepped temperature drying, causing the composite gel network to graft cationic groups and form a permanent positively charged structure. Testing showed that the modified intermediate layer exhibited a 24-hour in vitro inhibition rate of ≥30% against harmful bacteria such as Escherichia coli, effectively improving intestinal health.

[0016] Furthermore, the additive of the present invention has a clear in vitro sequential release characteristic. When measured according to the following method, its release performance meets the following requirements: A suitable amount of microspheres are placed in a simulated gastric fluid environment (pH 2.0-3.5, temperature 37°C, containing 0.1% pepsin by mass, stirring speed 50 r / min). Samples are taken after 2 hours, and the release rate of selenium and / or iodine in the outermost layer is ≥80% (the release rate is the mass percentage of the cumulative release of the corresponding mineral elements to the initial mineral content of that layer). The remaining sample is then transferred to a simulated jejunal fluid environment (pH 6.0-6.5, temperature 37°C, containing 0.1% pancreatin by mass, stirring speed 50 r / min), and the measurement continues. Samples are taken after a total time of 6 hours from the start of the measurement, and the cumulative release rate of zinc and manganese in the middle layer is ≥70%. Finally, the remaining sample is transferred to a simulated ileal fluid environment (pH 6.0-6.5, temperature 37°C, containing 0.1% pancreatin by mass, stirring speed 50 r / min). 6.5-7.0, temperature 37℃, containing 0.1% trypsin and 0.05% bile salts by mass, stirring speed 50r / min), continue the measurement, and take samples at a total time of 14h. The cumulative release rate of core copper is ≥60%.

[0017] Secondly, the present invention provides a method for preparing the above-mentioned slow-release multi-mineral feed additive, which adopts an integrated preparation process of "multi-stage atomization-layer self-assembly-step temperature-variable drying", including the following steps:

[0018] S1. Slurry preparation:

[0019] Outer slurry: Dissolve the intestinal enzyme-sensitive polymer (such as cross-linked amylose) in deionized water, add selenium source and / or iodine source, stir evenly, adjust the solid content to 20%-30%, ultrasonically disperse for 15-20 minutes, and remove air bubbles;

[0020] Intermediate slurry: Dissolve sodium alginate-chitosan composite gel (preferably sodium alginate to chitosan mass ratio 1:1) in deionized water, add zinc source, manganese source, cationic monomer (DMC) and thermal initiator (potassium persulfate), stir evenly, adjust the solid content to 20%-30%, and ultrasonically disperse for 15-20 minutes;

[0021] Inner layer slurry: Dissolve the slow-release skeleton material (such as ethyl cellulose) in an ethanol solution (preferably ethanol to water volume ratio 3:7), add a copper source, stir evenly, adjust the solid content to 20%-30%, and ultrasonically disperse for 15-20 minutes;

[0022] Preferably, the ultrasonic dispersion power is 100-150W, which can ensure uniform dispersion of raw materials and avoid structural inhomogeneity caused by excessively high local concentrations.

[0023] S2, Atomization granulation:

[0024] Using a coaxial three-channel atomizing nozzle, the inner, middle, and outer layers of slurry are simultaneously pumped out from the inside to the outside through the inner, middle, and outer channels, respectively, with a pump speed ratio (outer channel: middle channel: inner channel) controlled at 1:1.5:1. Atomization is achieved using compressed air (controlled pressure 0.3-0.5 MPa), forming a three-layer concentric composite droplet structure. Furthermore, the preferred inner diameter of the channels in the coaxial three-channel atomizing nozzle is 1 mm for the inner layer, 2 mm for the middle layer, and 3 mm for the outer layer, ensuring stable delivery of each slurry layer and uniformity of the interlayer structure.

[0025] S3, stepped temperature variable drying:

[0026] The composite droplets were sequentially dried and solidified by passing them through high-temperature, medium-temperature, and low-temperature zones, ultimately forming microspheres with a three-layer concentric spherical structure.

[0027] High-temperature zone: Temperature 150°C to 170°C, quickly removes moisture from the surface of droplets and initially sets the shape (prevents interlayer fusion).

[0028] Medium temperature zone: Temperature 100°C to 120°C, gradually remove internal moisture and enhance interlayer bonding (so that the middle layer gel can be initially cross-linked and cured).

[0029] Low-temperature zone: Temperature 60°C to 80°C triggers thermal in-situ polymerization of cationic monomers in the middle layer slurry, completing quaternization modification, while the core is gently dried to form a porous structure (suitable for long-term release requirements).

[0030] Thirdly, this invention provides the application of the aforementioned slow-release multi-mineral feed additive, specifically by adding the additive to laying hen feed at a dosage of 0.1%-0.5% of the feed mass. This additive is particularly suitable for laying hens, significantly improving mineral element utilization, reducing egg breakage rate, and improving gut health, while simultaneously reducing the amount of mineral additives required, thus lowering breeding costs and environmental pollution.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. This invention achieves the segmented sequential release of selenium / iodine (duodenum), zinc / manganese (jejunum-ileum), and copper (ileum and posterior end) through the matching of a three-layer concentric sphere structure and a sensitive carrier, avoiding the simultaneous encounter of different minerals in the digestive tract and eliminating antagonistic effects; verified by feeding experiments in laying hens, the apparent digestibility of zinc is increased to over 70%, which is significantly higher than that of traditional additives.

[0033] 2. Each layer of the carrier responds to environmental signals (intestinal enzymes, pH value) in different sections of the digestive tract, enabling the precise release of mineral elements at the optimal absorption site. For example, selenium / iodine is rapidly released in the duodenum to match its main absorption site, while copper is continuously released in the posterior intestine to adapt to its slow absorption characteristics, maximizing the biological functions of minerals.

[0034] 3. The intermediate layer, after being modified by quaternization, has permanent positive charge, which can destroy the cell membranes of harmful bacteria such as Escherichia coli through electrostatic action, with an in vitro inhibition rate of ≥30% after 24 hours; at the same time, it avoids damage to the intestinal mucosa caused by excessive release of mineral ions, maintains the balance of intestinal flora, and reduces the incidence of diarrhea in laying hens.

[0035] 4. The integrated preparation process combines "atomization granulation, layer-by-layer self-assembly, and modification curing" into one, which improves production efficiency by more than 30% compared with the traditional step-by-step encapsulation method; the product has a uniform structure, good storage stability, and is suitable for large-scale industrial production.

[0036] 5. When applied to laying hen feed, the breakage rate during the peak egg production period is reduced to below 1.0%, and the eggshell strength is increased by 10%-15%. At the same time, the amount of mineral additives added is reduced, thus lowering breeding costs and environmental pollution. Attached Figure Description

[0037] Figure 1 This is a schematic cross-sectional view of the three-layer concentric spherical structure of the slow-release multi-mineral feed additive of the present invention;

[0038] Figure 2 This is a flow chart of the preparation process of the slow-release multi-mineral feed additive of the present invention;

[0039] Figure 3This is an in vitro sequential release curve of the slow-release multi-mineral feed additive of the present invention. Detailed Implementation

[0040] The technical solutions of the present invention are described in detail below through specific embodiments. Those skilled in the art can make appropriate modifications and adjustments to the present invention based on the description herein without departing from the spirit and scope of the invention. All embodiments employ conventional experimental methods in the art; unless specific conditions are specified, conventional conditions or conditions recommended by the manufacturer are followed.

[0041] Example 1: Preparation of a slow-release multi-mineral feed additive

[0042] 1. Raw material preparation

[0043] Outer layer raw materials: cross-linked amylose (purity ≥98%), sodium selenite (selenium content 45%), potassium iodide (iodine content 76%); Middle layer raw materials: sodium alginate (viscosity 200~300mPa·s), chitosan (degree of deacetylation ≥90%), zinc sulfate (zinc content 22%), manganese sulfate (manganese content 31%), methacryloyloxyethyltrimethylammonium chloride (DMC, purity ≥97%), potassium persulfate (initiator, purity ≥99%); Inner layer raw materials: ethyl cellulose (viscosity 10~20mPa·s), copper sulfate (copper content 25%); Solvents: deionized water (density 1g / mL), anhydrous ethanol (density 0.79g / mL, purity ≥99.5%).

[0044] 2. Slurry preparation

[0045] Outer slurry: Dissolve 100g of cross-linked amylose in 324g of deionized water (corresponding to 324mL, density 1g / mL), heat to 80℃ and stir to dissolve, cool to room temperature and add 5g of sodium selenite and 3g of potassium iodide, stir evenly, and adjust the solid content to 25% by adding water or concentrating (solid content = total mass of solids / (total mass of solids + total mass of solvents) × 100%), ultrasonically disperse for 20min (power 120W) to remove air bubbles, and set aside;

[0046] Intermediate layer slurry: Dissolve 50g sodium alginate and 50g chitosan in 402g deionized water (corresponding to 402mL), stir until completely dissolved, add 10g zinc sulfate, 8g manganese sulfate, 15g DMC and 1g potassium persulfate (0.8% of the total mass of the intermediate layer slurry), stir evenly, adjust the solid content to 25% (calculation basis as before), ultrasonically disperse for 20min (power 120W), and set aside;

[0047] Inner layer slurry: Dissolve 100g of ethyl cellulose in a mixed solution of 102mL of anhydrous ethanol (mass ≈ 80.6g, 102mL × 0.79g / mL) and 238g of deionized water (corresponding to 238mL) (ethanol to water volume ratio 3:7, to ensure that ethyl cellulose is fully dissolved), stir to dissolve, add 6g of copper sulfate, stir evenly, adjust the solid content to 25% (calculation basis as before), and ultrasonically disperse for 20min (power 120W), and set aside.

[0048] 3. Atomized granulation

[0049] Using a coaxial three-channel atomizing nozzle (channel inner diameter: inner layer 1mm, middle layer 2mm, outer layer 3mm), the inner, middle, and outer slurries are pumped in through the inner, middle, and outer channels respectively, with a pump speed ratio of 1:1.5:1 (outer layer 10mL / min, middle layer 15mL / min, inner layer 10mL / min), and compressed air pressure of 0.4MPa, atomizing to form a three-layer concentric composite droplet structure. Because the shrinkage rates of the middle layer carrier (sodium alginate-chitosan composite gel) and the core carrier (ethyl cellulose) differ during the subsequent drying process (gel material shrinkage rate approximately 15%-20%, ethyl cellulose shrinkage rate approximately 5%-10%), this pump speed ratio ensures that the final microspheres form the target wall thickness ratio of 1:2:2.

[0050] 4. Stepped temperature drying

[0051] The composite droplets are passed into a continuous drying tower (the residence time is matched by adjusting the airflow velocity in the tower), and are dried and solidified sequentially through a high-temperature zone, a medium-temperature zone, and a low-temperature zone, ultimately forming microspheres with a three-layer concentric spherical structure:

[0052] High-temperature zone: temperature 160℃, residence time 8 seconds (airflow velocity 2.5m / s), quickly removes moisture from the surface of droplets, preliminarily sets the shape, and prevents interlayer fusion;

[0053] Medium temperature zone: temperature 110℃, residence time 25 seconds (airflow speed 1.2m / s), gradually remove internal moisture, enhance interlayer bonding, and allow the middle layer gel to initially cross-link and solidify;

[0054] Low-temperature zone: Temperature 70℃, residence time 90 seconds (airflow velocity 0.5m / s), triggering thermal in-situ polymerization of cationic monomers in the middle layer slurry, completing quaternization modification, while gently drying the core to form a porous structure (to meet the requirements of long-term release); after drying, collect the microspheres and sieve (100~200μm) to obtain the target product.

[0055] Example 2: Product structural parameter testing

[0056] Test objective: To verify whether the particle size and wall thickness ratio of the product meets the design target.

[0057] Testing instruments: Malvern Mastersizer 3000 laser particle size analyzer, ZEISS Sigma 300 scanning electron microscope (SEM).

[0058] Test methods and results

[0059] Particle size test: Take the product prepared in Example 1, randomly select 3 parallel samples, take 1g of each sample, disperse in deionized water, and use a laser particle size analyzer to determine the particle size distribution. The results are taken as mean ± standard deviation.

[0060] Test results: The total particle size of the microspheres was 150μm±10μm, which is within the design range of 100~200μm.

[0061] Wall thickness ratio test: The sample was frozen and sectioned, and the cross-sectional structure was observed using SEM. Ten microspheres were randomly selected, and the wall thickness of each layer was measured and the average value was calculated.

[0062] Test results: The wall thicknesses of the outermost layer, the middle layer, and the core are 10μm±1μm, 20μm±1μm, and 20μm±1μm, respectively, with a wall thickness ratio of 1:2:2, achieving the design ratio of 1:(1.8~2.2):(1.8~2.2).

[0063] Example 3: In vitro sequential release characteristic test

[0064] Test objective: To verify whether the product's in vitro sequential release characteristics meet the design objectives.

[0065] Test basis: Refer to the Dissolution Test Method (Paddle Method) of General Chapter 0931, Part IV, Chinese Pharmacopoeia 2020 Edition.

[0066] Testing instruments and reagents: intelligent dissolution tester, ICP-OES inductively coupled plasma spectrometer, simulated gastric juice (pH 2.5, containing 0.1% pepsin), simulated jejunal juice (pH 6.3, containing 0.1% pancreatic enzyme), and simulated ileal juice (pH 6.8, containing 0.1% pancreatic enzyme and 0.05% bile salts).

[0067] Test methods and results:

[0068] Accurately weigh 1.0 g of the microsphere sample prepared in Example 1 (3 parallel samples) and perform a release test according to the following steps:

[0069] Simulated gastric fluid stage: The sample was placed in 200 mL of simulated gastric fluid, kept at 37 °C, stirred at 50 r / min, and 5 mL was taken after 2 h. The sample was filtered through a 0.45 μm filter membrane, and the selenium and iodine contents were determined by ICP-OES. The release rate was then calculated.

[0070] Simulated jejunal fluid stage: Transfer the remaining sample and medium to 200mL of simulated jejunal fluid, continue stirring under the above conditions, and take 5mL of sample after a total time of 6h (4h in jejunal fluid) to determine the zinc and manganese content and calculate the cumulative release rate;

[0071] Simulated ileal fluid stage: Transfer the remaining sample and medium to 200 mL of simulated ileal fluid, continue stirring under the above conditions, and take a 5 mL sample after a total time of 14 h (8 h in ileal fluid) to determine the copper content and calculate the cumulative release rate.

[0072] Test results (mean ± standard deviation):

[0073] detection indicators 2h release rate 6-hour cumulative release rate 14h cumulative release rate Outermost layer (selenium) release rate 85%±2% - - Outermost layer (iodine) release rate 82%±2% - - Intermediate layer (zinc) cumulative release rate - 75%±3% - Intermediate layer (manganese) cumulative release rate - 72%±3% - Core (copper) cumulative release rate - - 65%±2%

[0074] The results show that the additive of the present invention exhibits a clear in vitro sequential release pattern. The release timing and release efficiency of mineral elements in each layer are consistent with the design target. It can achieve precise targeted release of different minerals in the corresponding sections of the poultry digestive tract, and adapt to the digestive physiological needs of poultry.

[0075] Example 4: Antibacterial Performance Test

[0076] Test objective: To verify the antibacterial effect of the intermediate layer after quaternization modification.

[0077] Test method: Plate count method (refer to the 2002 edition of "Disinfection Technical Specifications"), and supplemented by direct characterization of modification effect.

[0078] Test materials: Escherichia coli (ATCC 25922), LB medium, Fourier transform infrared spectrometer (FT-IR), Zeta potential meter.

[0079] Test steps and results

[0080] Direct characterization (verification of successful modification): The microspheres prepared in Example 1 were ground and the intermediate layer powder was separated. The functional groups were determined by FT-IR: at 1480 cm⁻¹ -1 Quaternary ammonium salt groups (-N) appear nearby + The characteristic absorption peak of (CH3)3) proves that DMC was successfully grafted into the sodium alginate-chitosan composite gel network; the surface potential of the intermediate layer was measured by Zeta potentiometer: the potential value is +25mV±3mV, which verifies that it has permanent positive charge.

[0081] Antibacterial rate test: 100 mg of intermediate layer powder was added to 10 mL of Escherichia coli bacterial solution (concentration 10). 6 In a culture medium of CFU / mL, the bacterial culture was incubated at 37℃ for 24 h. 1 mL of the bacterial culture was serially diluted, spread on LB plates, and the number of surviving colonies was counted after incubation. The inhibition rate was calculated (3 parallel samples).

[0082] Test results: The antibacterial rate was 38% ± 2%, reaching the design target of over 30%, proving that the product has a significant antibacterial effect.

[0083] Example 5: Laying hen feeding experiment

[0084] Experimental objective: To verify the effectiveness of the product in laying hen feed.

[0085] Experimental Design:

[0086] Experimental animals: 180 healthy Lohmann Brown chickens (egg production rate ≥85%, peak egg production period) were randomly divided into 3 groups of 60 chickens each, with 3 replicates per group (20 chickens per replicate).

[0087] Control group I: basal diet + 0.4% traditional multi-mineral feed additive (ordinary inorganic mixture);

[0088] Control group II: basal diet + 0.4% commercially available single-layer slow-release mineral additive;

[0089] Experimental group: basal diet + 0.3% of the product prepared in Example 1 of this invention;

[0090] Experiment duration: 8 weeks, with free access to food and water, and consistent environmental conditions.

[0091] Detection indicators and results:

[0092] After the experiment, apparent zinc digestibility, egg breakage rate, eggshell strength, cecal Escherichia coli count, and fecal zinc excretion were measured (mean ± standard deviation of three replicates). One-way ANOVA was performed using SPSS 26.0, and Duncan's multiple comparison test was used to determine the significance of differences between groups.

[0093] detection indicators Control Group I Control Group II experimental group Significant difference compared to control group I Significant difference compared to control group II Apparent digestibility of zinc (%) 45±2 58±2 72±3 P<0.01 P<0.01 Egg breakage rate (%) 2.3±0.2 1.5±0.2 0.8±0.1 P<0.05 P<0.05 Eggshell strength (N) 32±1 34±1 36±1 P<0.05 P<0.05 Cecal Escherichia coli count (log CFU / g) 6.8±0.2 6.5±0.2 5.9±0.2 P<0.01 P<0.05 Fecal zinc emissions (mg / kg) 110±5 85±4 62±3 P<0.01 P<0.01

[0094] Note: In the table, "P<0.05" indicates that the difference between groups is statistically significant, and "P<0.01" indicates that the difference between groups is highly statistically significant. Both are recognized objective criteria in the field of biostatistics.

[0095] The results show that:

[0096] The product of this invention is not only significantly superior to traditional mixed additives (control group I), but also superior to existing slow-release technology (control group II), and can significantly improve mineral utilization, reduce egg breakage rate, and enhance eggshell strength;

[0097] The number of Escherichia coli in the cecum was significantly reduced, directly confirming the antibacterial function of the quaternization modification of the intermediate layer; fecal zinc emissions were reduced by 43.6% (compared to control group I), demonstrating significant environmental advantages;

[0098] Despite the experimental group having a 25% lower addition rate (0.3%) compared to control group I (traditional multi-mineral additive, 0.4%) and lower than control group II (commercially available ordinary single-layer slow-release mineral additive, 0.4%), it still achieved superior technical results. This demonstrates the efficiency advantage of the invention and significantly reduces breeding costs, highlighting its application value.

[0099] Example 6: Optimization of Preparation Process Parameters

[0100] Optimization objective: To verify the rationality of key parameters in the preparation process.

[0101] Optimization Experiment 1: Pump Speed ​​Ratio Optimization

[0102] Experimental design: The pump speed ratio (outer:middle:inner) was set to 1:1.5:1, 1:1:1, and 1:2:1 respectively, and other conditions were the same as in Example 1. After the product was prepared, the wall thickness ratio was measured (3 parallel samples).

[0103] Test results:

[0104] Pump speed ratio (outer:middle:inner) Wall thickness ratio (outer:middle:inner) Target wall thickness ratio adaptability 1:1.5:1 1:2:2 adaptation 1:1:1 1:1.2:1.2 Incompatible 1:2:1 1:2.5:2.5 Incompatible

[0105] Conclusion: A pump speed ratio of 1:1.5:1 is the optimal parameter, which can stably obtain the target wall thickness ratio and meet the design requirements of the three-layer concentric sphere structure.

[0106] Optimization Experiment 2: Temperature Optimization in the Low-Temperature Region

[0107] Experimental design: The low temperature zone was set at 60℃, 70℃ and 80℃ respectively, and other conditions were the same as in Example 1. The antibacterial rate was measured after the product was prepared (3 parallel samples).

[0108] Test results:

[0109] Temperature in the low-temperature zone (°C) Antibacterial rate (%) Antibacterial effect adaptability 60 30±2 adaptation 70 38±2 Optimal fit 80 39±2 adaptation

[0110] Conclusion: Temperatures of 60–80℃ in the low-temperature zone can meet the antibacterial requirements, while 70℃ balances antibacterial effect and energy consumption, making it the optimal parameter selection for industrial production.

[0111] Example 7: Product Storage Stability Test

[0112] Test objective: To verify the product's storage stability and support its industrial applicability.

[0113] Test conditions: The product prepared in Example 1 was stored in two different environments for 6 months:

[0114] Environment 1: 25℃ / 60% relative humidity (RH) (normal storage conditions);

[0115] Environment 2: 40℃ / RH75% (accelerated aging conditions).

[0116] Detection indicators and results:

[0117] Monthly sampling was conducted to determine in vitro release characteristics (2h outer selenium release rate, 6h middle zinc release rate, and 14h core copper release rate) and antibacterial rate. The results showed:

[0118] After 6 months of normal storage, the release rate of each layer changed by ≤5%, and the antibacterial rate was 36%±2% (≥30%).

[0119] After 6 months of accelerated aging, the release rate of each layer changed by ≤8%, and the antibacterial rate was 32%±2% (≥30%).

[0120] Conclusion: The product exhibits good storage stability and can maintain its core functional characteristics under normal circulation and storage conditions, meeting the needs of large-scale industrial production and market applications, and demonstrating good industrial applicability.

[0121] In light of current practical needs, the above-described embodiments of this invention are not limited to these. Any changes made within the scope of knowledge possessed by those skilled in the art without departing from the concept of this invention still fall within the protection scope of this invention.

Claims

1. A slow-release multi-mineral feed additive, characterized in that, The additive is a microsphere with a three-layer concentric spherical structure, from the outside to the inside as follows: The outermost layer contains one or both of selenium and iodine, and its carrier is an intestinal enzyme-sensitive polymer. The intermediate layer contains zinc and manganese, and its carrier is a pH-sensitive polymer modified by quaternization. The core contains copper, and its carrier is a slow-release framework material; The total particle size of the microspheres is 100 μm to 200 μm, and the wall thickness ratio of the outermost layer, the middle layer and the core is 1:(1.8-2.2):(1.8-2.2).

2. The slow-release multi-mineral feed additive according to claim 1, characterized in that, The intestinal enzyme-sensitive polymer is cross-linked linear starch or glutamine oligopeptide, the pH-sensitive polymer is sodium alginate-chitosan composite gel, and the sustained-release matrix material is ethyl cellulose and / or glyceryl monostearate.

3. The slow-release multi-mineral feed additive according to claim 2, characterized in that, The quaternization modification is achieved by in-situ polymerization of cationic monomers and grafting them onto the sodium alginate-chitosan composite gel network. The cationic monomer is methacryloyloxyethyltrimethylammonium chloride.

4. The slow-release multi-mineral feed additive according to claim 1, characterized in that, The total particle size of the microspheres is 150 μm ± 50 μm.

5. The slow-release multi-mineral feed additive according to claim 1, characterized in that, When measured according to the following method, its in vitro sequential release characteristics are satisfied: The microspheres were placed in a simulated gastric fluid environment at pH 2.0-3.5, temperature 37°C, containing 0.1% pepsin, and a stirring speed of 50 r / min. Samples were taken after 2 hours, and the release rate of selenium and / or iodine in the outermost layer was ≥80%. The remaining sample was then transferred to a simulated jejunal fluid environment at pH 6.0-6.5, temperature 37°C, containing 0.1% pancreatin, and a stirring speed of 50 r / min. Measurements were continued, and samples were taken after 6 hours, showing a cumulative release rate of ≥70% in the middle layer. Finally, the remaining sample was transferred to a simulated ileal fluid environment at pH 6.5-7.0, temperature 37°C, containing 0.1% pancreatin and 0.05% bile salts, and a stirring speed of 50 r / min. Measurements were continued, and samples were taken after 14 hours, showing a cumulative release rate of ≥60% in the inner core. The release rate is the percentage by mass of the cumulative release of mineral elements contained in the corresponding layer relative to the initial mineral content of that layer.

6. A method for preparing a slow-release multi-mineral feed additive according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Slurry preparation: Prepare outer layer slurry, middle layer slurry and inner layer slurry separately, wherein the solid content of the outer layer slurry, middle layer slurry and inner layer slurry is controlled at 20%-30%; S2, Atomization granulation: Using a coaxial three-channel atomizing nozzle, the inner layer slurry, middle layer slurry, and outer layer slurry are simultaneously pumped out from the inside to the outside through the inner channel, middle channel, and outer channel, respectively, to form composite droplets; S3. Stepped temperature drying: The composite droplets are sequentially dried and solidified by passing them through a high-temperature zone, a medium-temperature zone, and a low-temperature zone to form microspheres with the three-layer concentric spherical structure.

7. The method for preparing the slow-release multi-mineral feed additive according to claim 6, characterized in that, In step S1, when preparing the intermediate layer slurry, a cationic monomer and a thermal initiator are added. The thermal initiator is potassium persulfate or ammonium persulfate, and its addition amount is 0.5%-2% of the total mass of the intermediate layer slurry. In the low-temperature drying stage of step S3, the temperature is controlled at 60°C to 80°C to trigger the thermally initiated in-situ polymerization of the cationic monomer, thereby modifying the intermediate layer by quaternization.

8. The method for preparing the slow-release multi-mineral feed additive according to claim 7, characterized in that, In step S2, the pump speed ratio of the coaxial three-channel atomizing nozzle, outer channel: middle channel: inner channel, is 1:1.5:1; In step S3, the temperature of the high-temperature zone is 150°C to 170°C, the temperature of the medium-temperature zone is 100°C to 120°C, and the temperature of the low-temperature zone is 60°C to 80°C.

9. The application of the slow-release multi-mineral feed additive according to any one of claims 1-5 in laying hen feed, characterized in that, The additive is added to the feed at a rate of 0.1%-0.5% of the feed mass.

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