Slow-release multi-mineral feed additive and preparation method thereof

Abstract

The invention relates to a slow-release multi-mineral feed additive and a preparation method thereof, which are applied to the technical field of feed additives, the additive is a microsphere with a three-layer concentric sphere structure, and from outside to inside, the outermost layer comprises selenium and / or iodine, and a carrier is an intestinal enzyme sensitive polymer; the middle layer comprises zinc and manganese, and the carrier is a quaternary ammonium salt modified pH sensitive polymer; the inner core contains copper, and the carrier is a sustained-release framework material. The total particle size of the microspheres is 100-200 [mu] m, and the wall thickness ratio of the three layers is 1: (1.8-2.2): (1.8-2.2). The preparation method adopts an integrated process of'multi-stage atomization-layer-by-layer self-assembly-stepped variable-temperature drying ', three layers of slurry are pumped out through a coaxial three-channel atomization nozzle, and the slurry is dried and cured in a stepped temperature zone. The directional gradient sequential release of mineral elements in digestive tracts of poultry is realized, the problem of antagonism among minerals is solved, the bioavailability is remarkably improved, meanwhile, the middle layer has an antibacterial function, the intestinal health can be improved, and the feed is suitable for poultry such as laying hens.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of feed additives, in particular to a slow-release multi-mineral feed additive, a preparation method and application thereof BACKGROUND

[0002] Minerals are essential nutrients for the growth and development, reproduction and performance of poultry. For example, selenium and iodine are involved in metabolic regulation, zinc and manganese affect bone development and immune function, and copper is involved in enzyme activity regulation. In the feed of laying hens, the application of multi-mineral additives is extremely common, but the existing technology has the following core defects:

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

[0004] Release characteristics do not match the physiology of the digestive tract: the digestive tract of laying hens is divided into the stomach, duodenum, jejunum, ileum and the rear end of the intestine, and there are significant differences in pH and enzyme composition in different sections (such as pH 2.0-3.5 in the stomach containing pepsin, and pH 6.0-7.0 in the intestine containing pancreatic enzymes and bile salts). The existing additives lack targeted release design, and the outer layer of minerals is quickly released in the stomach, and the inner layer of minerals is insufficiently released in the rear end of the intestine, which cannot accurately supply different minerals according to their absorption sites (such as selenium and iodine being mainly absorbed in the duodenum, zinc and manganese being absorbed in the jejunum-ileum, and copper being absorbed in the ileum and the rear end of the intestine).

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

[0006] Complex preparation process and poor stability: the existing multi-layer slow-release particles mostly use the "step-by-step wrapping method" (first prepare the core, then wrap the middle layer and the outer layer in turn), which has the problems of weak interlayer bonding force, uneven structure, low production efficiency, and the slow-release effect is easily affected by processing and storage conditions.

[0007] To solve the above problems, there is an urgent need in the field to develop a multi-mineral feed additive with precise targeted release characteristics, which can eliminate mineral antagonism and protect intestinal health, as well as an efficient and stable preparation process. SUMMARY

[0008] In view of the defects of the prior art, the present application aims to provide a slow-release multi-mineral feed additive as well as a preparation method and application thereof, by means of the design of "three-layer concentric ball structure + sensitive carrier matching + quaternary ammonium salt modification", the sequential release of mineral elements in different sections of the digestive tract of laying hens is realized, antagonism is eliminated, and the utilization rate is improved; at the same time, the middle layer is endowed with antibacterial function, and the intestinal health is protected; and the product stability and production efficiency are ensured through the integrated preparation process.

[0009] To achieve the above-mentioned purposes, the present application adopts the following technical solutions:

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

[0011] The outermost layer contains one or both of selenium and iodine, and the carrier thereof is an enterase-sensitive polymer; wherein 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 enterase-sensitive polymer is preferably one or both of cross-linked amylose and a specific peptide segment (such as glutamine oligopeptide), which can be degraded under the action of enterase (such as amylase and peptidase) in the duodenum and the anterior jejunum of laying hens, realizing the rapid release of selenium and / or iodine and matching the demand of the main absorption site.

[0012] The middle layer contains zinc and manganese, and the carrier thereof is a pH-sensitive polymer; wherein 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 sodium alginate-chitosan composite gel, and after the composite gel is modified by quaternary ammonium salt, it can permanently endow positive electricity and antibacterial property. Further, this layer swells and degrades under the neutral pH environment (pH 6.0-7.0) in the middle and posterior jejunum and ileum, releasing zinc and manganese to match the optimal absorption window, and the positive electric group can destroy the cell membrane of harmful bacteria, exerting antibacterial effect.

[0013] The core contains copper, and the carrier thereof is a slow-release skeleton material; wherein the copper source is preferably one or both of copper sulfate and copper oxide; the slow-release skeleton material is preferably one or both of ethyl cellulose and glycerol monostearate, which can gradually degrade in the slow digestion environment of the ileum and the posterior intestinal tract, realizing the sustained release of copper and adapting to its slow absorption characteristics.

[0014] Preferably, the total particle size of the microspheres is 100 μm to 200 μm, more preferably 150 μm ± 50 μm; this particle size range can ensure that the residence time of the microspheres in the digestive tract of laying hens matches the release requirements, while having good fluidity, easy mixing with feed, and not affecting the feeding of poultry. Further preferably, the ratio of the wall thickness of the outermost layer, the intermediate layer and the core is 1: (1.8-2.2): (1.8-2.2); this ratio is optimized through a large number of fluid dynamics simulations and in vitro release experiments, and can accurately regulate the release rate of each layer to achieve the sequential release effect of "fast release of the outer layer, medium release of the middle layer, and slow release of the core".

[0015] Further, the quaternary ammonium salt modification process of the intermediate layer is specifically: realizing in-situ polymerization grafting of cationic monomers onto the sodium alginate-chitosan composite gel network, wherein the cationic monomer is preferably methacryloyloxyethyl trimethylammonium chloride (DMC); during preparation of the intermediate layer slurry, DMC and a thermal initiator (potassium persulfate or ammonium persulfate, added in an amount of 0.5%-2% of the total mass of the intermediate layer slurry) are synchronously added, and in-situ polymerization is triggered at a low temperature zone (60°C to 80°C) of the stepwise temperature drying to graft cationic groups to the composite gel network, forming a permanent positive structure. Tests show that the modified intermediate layer has a 24h in-vitro inhibition rate of harmful bacteria such as Escherichia coli of ≥30%, which can effectively improve intestinal health.

[0016] Further, the additive of the present application has clear in-vitro sequential release characteristics, and when determined according to the following method, its release performance meets the following requirements: an appropriate amount of microspheres is placed in a simulated gastric juice environment (pH 2.0-3.5, temperature 37°C, containing 0.1% by mass fraction of pepsin, stirring speed 50r / min), and sampled for determination at 2h; the release rate of selenium and / or iodine in the outermost layer is ≥80% (the release rate is the cumulative release amount of the mineral elements contained in the corresponding layer, expressed as a percentage of the initial mass of the mineral content in the layer); then the remaining sample is transferred to a simulated jejunum liquid environment (pH 6.0-6.5, temperature 37°C, containing 0.1% by mass fraction of pancreatin, stirring speed 50r / min), and continues to be determined, and sampled at 6h from the start of the determination as the timing starting point; the cumulative release rate of zinc and manganese in the intermediate layer is ≥70%; finally, the remaining sample is transferred to a simulated ileum liquid environment (pH 6.5-7.0, temperature 37°C, containing 0.1% by mass fraction of pancreatin and 0.05% by mass fraction of bile salts, stirring speed 50r / min), and continues to be determined, and sampled at 14h from the start of the determination as the timing starting point; the cumulative release rate of copper in the core is ≥60%.

[0017] In a second aspect, the present application provides a preparation method of the above-mentioned slow-release multi-mineral feed additive, which adopts an integrated preparation process of "multi-stage atomization-layer-by-layer self-assembly-stepwise temperature drying", including the following steps:

[0018] S1, slurry preparation:

[0019] Outer layer slurry: dissolve enteric enzyme sensitive polymer (such as cross-linked amylose) in deionized water, add selenium source and / or iodine source, stir evenly, adjust solid content to 20%-30%, ultrasonic dispersion for 15-20 min, remove air bubbles;

[0020] Middle layer slurry: dissolve sodium alginate-chitosan composite gel (preferably sodium alginate and chitosan mass ratio 1:1) in deionized water, add zinc source, manganese source, cationic monomer (DMC) and thermal initiator (potassium persulfate), stir evenly, adjust solid content to 20%-30%, ultrasonic dispersion for 15-20 min;

[0021] Inner layer slurry: dissolve sustained-release matrix material (such as ethyl cellulose) in ethanol solution (preferably ethanol and water volume ratio 3:7), add copper source, stir evenly, adjust solid content to 20%-30%, ultrasonic dispersion for 15-20 min;

[0022] Preferably, the power of ultrasonic dispersion is 100-150 W, which can ensure uniform dispersion of raw materials and avoid uneven structure caused by local high concentration;

[0023] S2, atomization and granulation:

[0024] Use a coaxial three-channel atomizing nozzle to pump out the inner layer slurry, middle layer slurry and outer layer slurry from the inside to the outside through the inner, middle and outer channels at the same time, and the pump speed ratio (outer layer channel: middle layer channel: inner layer channel) is controlled to be 1:1.5:1; through compressed air atomization (control air pressure 0.3-0.5 MPa), form a three-layer concentric structure of composite droplets. Further, the channel inner diameter of the coaxial three-channel atomizing nozzle is preferably 1 mm for the inner layer, 2 mm for the middle layer and 3 mm for the outer layer, which can ensure the stable delivery of each layer of slurry and the uniformity of the interlayer structure;

[0025] S3, stepwise variable temperature drying:

[0026] Dry and solidify the composite droplets in turn through high temperature zone, medium temperature zone and low temperature zone to form a three-layer concentric spherical structure of microspheres:

[0027] High temperature zone: temperature 150°C to 170°C, quickly remove the surface moisture of the droplets, preliminary shaping (prevent interlayer fusion);

[0028] Medium temperature zone: temperature 100°C to 120°C, gradually remove the internal moisture, enhance the interlayer bonding force (make the middle layer gel preliminary cross-linking and solidification);

[0029] Low temperature zone: temperature 60°C to 80°C, trigger the thermal initiation in-situ polymerization of the cationic monomer in the middle layer slurry, complete the quaternary ammonium salt modification, and at the same time, gently dry the inner core to form a porous structure (adapt to the demand of long-acting release).

[0030] In a third aspect, the present application provides the use of the slow-release multi-mineral feed additive as described above, in particular the addition of the additive to the feed of laying hens in an amount of 0.1-0.5% by mass of the feed. The additive is particularly suitable for use in laying hens during the egg-laying period, and can significantly improve the utilization rate of mineral elements, reduce the rate of broken eggs, improve intestinal health, and at the same time reduce the amount of mineral additives, thereby reducing the cost of breeding and environmental pollution.

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

[0032] 1. By matching the three-layer concentric ball structure and the sensitive carrier, the present application realizes the segmented and sequential release of selenium / iodine (in the duodenum), zinc / manganese (in the jejunum-ileum), and copper (in the ileum and the posterior end), avoids the simultaneous encounter of different minerals in the digestive tract, and eliminates the antagonistic effect. Through egg hen feeding experiments, the apparent digestibility of zinc is increased to more than 70%, which is significantly higher than that of traditional additives.

[0033] 2. Each layer of the carrier responds to the environmental signals (intestinal enzymes, pH value) of different segments of the digestive tract, realizes the precise release of mineral elements in the optimal absorption site, such as the rapid release of selenium / iodine in the duodenum to match the main absorption site, and the sustained release of copper in the posterior intestinal tract to adapt to its slow absorption characteristics, thereby maximizing the biological function of minerals.

[0034] 3. The middle layer is modified by quaternary ammonium salt and has permanent positive charge, which can destroy the cell membrane of harmful bacteria such as E. coli through electrostatic action, and the 24h in vitro inhibition rate is ≥30%; at the same time, it avoids the damage of excessive release of mineral ions to the intestinal mucosa, maintains the balance of intestinal flora, and reduces the incidence of diarrhea in laying hens.

[0035] 4. The integrated preparation process integrates "atomization granulation, layer-by-layer self-assembly, and modification and solidification" into one, and the production efficiency is increased by more than 30% compared with the traditional step-by-step wrapping method; the product structure is uniform, the storage stability is good, and it is suitable for large-scale industrial production.

[0036] 5. After being applied to the feed of laying hens, the rate of broken eggs during the peak egg-laying period of the laying hens is reduced to less than 1.0%, the eggshell strength is increased by 10-15%, and at the same time, the amount of mineral additives is reduced, thereby reducing the cost of breeding and environmental pollution. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 FIG. 1 is a schematic diagram of the cross section of the three-layer concentric ball structure of the slow-release multi-mineral feed additive of the present application;

[0038] Figure 2 FIG. 4 is a flow chart of the preparation process of the slow-release multi-mineral feed additive of the present application;

[0039] Figure 3The in-vitro sequential release curve of the slow-release multi-mineral feed additive of the present application. DETAILED DESCRIPTION

[0040] The technical solutions of the present application are described in detail below through specific examples. Those skilled in the art can make appropriate modifications and adjustments to the present application based on the description in this specification without deviating from the spirit and scope of the present application. All examples use conventional experimental methods in the art, and if specific conditions are not specified, they are performed under conventional conditions or according to the manufacturer's recommendations.

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

[0042] 1. Preparation of raw materials

[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 200-300 mPa·s), chitosan (degree of deacetylation ≥ 90%), zinc sulfate (zinc content 22%), manganese sulfate (manganese content 31%), methacryloyloxyethyl trimethyl ammonium chloride (DMC, purity ≥ 97%), potassium persulfate (initiator, purity ≥ 99%); inner layer raw materials: ethyl cellulose (viscosity 10-20 mPa·s), copper sulfate (copper content 25%); solvents: deionized water (density 1 g / mL), anhydrous ethanol (density 0.79 g / mL, purity ≥ 99.5%).

[0044] 2. Preparation of slurry

[0045] Outer layer slurry: 100 g of cross-linked amylose was dissolved in 324 g of deionized water (corresponding to 324 mL, density 1 g / mL), heated to 80°C and stirred to dissolve, cooled to room temperature, then 5 g of sodium selenite and 3 g of potassium iodide were added, stirred uniformly, and the solid content was adjusted to 25% by adding water or concentrating (solid content = total solid mass / (total solid + solvent mass) × 100%), ultrasonic dispersion for 20 min (power 120 W), remove bubbles, and reserve;

[0046] Middle layer slurry: 50 g of sodium alginate and 50 g of chitosan were dissolved in 402 g of deionized water (corresponding to 402 mL), stirred until completely dissolved, then 10 g of zinc sulfate, 8 g of manganese sulfate, 15 g of DMC and 1 g of potassium persulfate (0.8% of the total mass of the middle layer slurry) were added, stirred uniformly, the solid content was adjusted to 25% (the calculation basis is the same as before), ultrasonic dispersion for 20 min (power 120 W), and reserve;

[0047] Inner layer slurry: 100 g of ethyl cellulose was dissolved in a mixed solution of 102 mL of anhydrous ethanol (mass ≈ 80.6 g, 102 mL x 0.79 g / mL) and 238 g of deionized water (corresponding to 238 mL) (ethanol to water volume ratio 3:7, ensuring that the ethyl cellulose is fully dissolved), stirring to dissolve, adding 6 g of copper sulfate, stirring uniformly, adjusting the solid content to 25% (the calculation basis is the same as before), ultrasonic dispersion for 20 min (power 120 W), standby.

[0048] 3. Atomization and prilling

[0049] A coaxial three-channel atomizing nozzle (channel inner diameter: inner layer 1 mm, middle layer 2 mm, outer layer 3 mm) was used, and the inner layer slurry, middle layer slurry, and outer layer slurry were pumped in through the inner, middle, and outer channels, respectively, with a pump speed ratio of 1:1.5:1 (outer layer 10 mL / min, middle layer 15 mL / min, inner layer 10 mL / min), and compressed air pressure 0.4 MPa, to form composite droplets with a three-layer concentric structure by atomization. Due to the difference in shrinkage rate between the middle layer carrier (sodium alginate-chitosan composite gel) and the inner core carrier (ethyl cellulose) in the subsequent drying process (gel material shrinkage rate about 15%-20%, ethyl cellulose shrinkage rate about 5%-10%), this pump speed ratio can ensure that the final microspheres form a target wall thickness ratio of 1:2:2.

[0050] 4. Stepwise variable temperature drying

[0051] The composite droplets were passed into a continuous drying tower (by adjusting the airflow speed in the tower to match the residence time), and were sequentially dried and solidified in the high temperature zone, medium temperature zone, and low temperature zone, to finally form microspheres with a three-layer concentric sphere structure:

[0052] High temperature zone: temperature 160°C, residence time 8 seconds (airflow speed 2.5 m / s), quickly remove the surface moisture of the droplets, preliminary shaping, prevent interlayer fusion;

[0053] Medium temperature zone: temperature 110°C, residence time 25 seconds (airflow speed 1.2 m / s), gradually remove the internal moisture, enhance the interlayer bonding force, and preliminarily crosslink and solidify the middle layer gel;

[0054] Low temperature zone: temperature 70°C, residence time 90 seconds (airflow speed 0.5 m / s), trigger the thermal initiation in-situ polymerization of the cationic monomer in the middle layer slurry, complete the quaternary ammonium salt modification, and at the same time, gently dry the inner core to form a porous structure (adapted to the needs of long-acting release); after drying is completed, the microspheres are collected and sieved (100-200 μm) to obtain the target product.

[0055] Example 2: Product structure parameter test

[0056] Test purpose: verify whether the particle size and wall thickness ratio of the product meet the design target.

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

[0058] Test method and results

[0059] Particle size test: Take the product prepared in Example 1, randomly select 3 parallel samples, take 1 g from each sample, disperse in deionized water, use laser particle size analyzer to determine the particle size distribution, and take the average value ± standard deviation.

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

[0061] Wall thickness ratio test: Freeze section the sample, observe the cross-sectional structure by SEM, randomly select 10 microspheres, measure the wall thickness of each layer, and calculate the average value.

[0062] Test results: The wall thickness of the outermost layer, the middle layer and the core is 10 μm ± 1 μm, 20 μm ± 1 μm and 20 μm ± 1 μm respectively, and the wall thickness ratio is 1:2:2, reaching the design ratio of 1:(1.8-2.2):(1.8-2.2).

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

[0064] Test purpose: To verify whether the in vitro sequential release property of the product reaches the design target.

[0065] Test basis: Refer to the dissolution test method (paddle method) of Chinese Pharmacopoeia 2020 edition four general chapters 0931.

[0066] Test 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% pancreatin), simulated ileal juice (pH 6.8, containing 0.1% pancreatin and 0.05% bile salt).

[0067] Test method and results:

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

[0069] Simulated gastric juice stage: Place in 200 mL of simulated gastric juice, constant temperature at 37℃, stirring at 50 r / min, take 5 mL at 2h, filter through 0.45 μm filter membrane, determine the content of selenium and iodine by ICP-OES, and calculate the release rate;

[0070] Simulated jejunal fluid stage: the remaining sample and medium are transferred to 200 mL of simulated jejunal fluid, and stirring is continued under the above conditions, and 5 mL of sample is taken at a total time of 6 h (4 h in the jejunal fluid), and the zinc and manganese contents are determined, and the cumulative release rate is calculated;

[0071] Simulated ileal fluid stage: the remaining sample and medium are transferred to 200 mL of simulated ileal fluid, and stirring is continued under the above conditions, and 5 mL of sample is taken at a total time of 14 h (8 h in the ileal fluid), and the copper content is determined, and the cumulative release rate is calculated.

[0072] Test results (average value ± standard deviation):

[0073] Detection index 2h release rate 6h 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% - Inner core (copper) cumulative release rate - - 65%±2%

[0074] The results show that the additive of the present application exhibits a clear in-vitro sequential release rule, and the release timing and release efficiency of each layer of mineral elements are consistent with the design target, so that precise targeted release of different minerals in the corresponding sections of the digestive tract of poultry can be achieved, and the physiological needs of poultry are met.

[0075] Example 4: Bacteriostatic performance test

[0076] Test purpose: verify the bacteriostatic effect of the quaternary ammonium salt modified intermediate layer.

[0077] Test method: plate counting method (referring to the 2002 edition of "Disinfection Technical Specification"), supplemented by direct characterization of the modification effect.

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

[0079] Test steps and results

[0080] Direct characterization (modification success verification): take the microspheres prepared in Example 1, grind and separate the intermediate layer powder, and use FT-IR to determine the functional groups: a characteristic absorption peak of quaternary ammonium salt group (-N -1 (CH3)3) appears near 1480 cm + , which proves that DMC is successfully grafted to the sodium alginate-chitosan composite gel network; the surface potential of the intermediate layer is measured by a Zeta potential instrument: the potential value is +25 mV ± 3 mV, which verifies that it has permanent positive electric properties.

[0081] Bacteriostatic rate test: 100 mg of the intermediate layer powder is added to 10 mL of Escherichia coli bacterial solution (concentration 10 6 CFU / mL), and cultured at 37°C for 24 h, 1 mL of the bacterial solution is gradiently diluted, spread on LB plates, and the number of surviving bacteria is counted after culture, and the bacteriostatic rate is calculated (3 parallel samples).

[0082] Test result: the antibacterial rate is 38%±2%, which reaches the design target of 30% or more, proving that the product has a significant antibacterial effect.

[0083] Example 5: laying hen feeding experiment

[0084] Purpose of the experiment: to verify the application effect of the product in the feed of laying hens.

[0085] Experiment design:

[0086] Experimental animals: 180 healthy Roman Brown laying hens (egg laying rate ≥ 85%, egg laying peak period), randomly divided into 3 groups, 60 in each group, 3 replicates in each group (20 in each 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 ordinary single-layer slow-release mineral additive;

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

[0090] Experimental period: 8 weeks, free access to feed and water, consistent environmental conditions.

[0091] Detection index and result:

[0092] After the experiment, the apparent zinc digestibility, egg breaking rate, eggshell strength, cecal E. coli count, and fecal zinc discharge (average value ± standard deviation of 3 replicates) were measured, and SPSS 26.0 was used for one-way ANOVA (ANOVA), and Duncan's multiple comparison test was used to test the significance of differences between groups:

[0093] Detection index Control group I Control group II Experimental group Significance of difference from control group I Significance of difference from control group II Zinc apparent digestibility (%) 45±2 58±2 72±3 P<0.01 P<0.01 Cracked egg 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 Coliform bacteria in cecum (log CFU / g) 6.8±0.2 6.5±0.2 5.9±0.2 P<0.01 P<0.05 Fecal zinc discharge (mg / kg) 110±5 85±4 62±3 P<0.01 P<0.01

[0094] Note: “P<0.05” in the table indicates that the difference between groups is statistically significant, “P<0.01” indicates that the difference between groups is statistically extremely significant, and both are objective judgment standards recognized in the field of biological statistics.

[0095] The results show that:

[0096] The product of the application not only significantly outperforms the traditional mixed additive (control group I), but also outperforms the existing slow-release technology (control group II), and can significantly improve mineral utilization, reduce egg breaking rate, and enhance eggshell strength;

[0097] The cecal E. coli count is extremely significantly reduced, directly verifying the antibacterial function of the intermediate layer of quaternary ammonium salt modification; the fecal zinc discharge is significantly reduced by 43.6% (compared with control group I), which reflects the significant environmental advantage;

[0098] In the experimental group, the addition amount (0.3%) is reduced by 25% compared with the control group I (traditional multi-mineral additive, 0.4%) and is lower than the control group II (commercial ordinary single-layer slow-release mineral additive, 0.4%), and better technical effects are still achieved, which not only reflects the efficiency advantage of the application, but also significantly reduces the breeding cost, and the application value is outstanding.

[0099] Example 6: Optimization of preparation process parameters

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

[0101] Optimization experiment 1: optimization of pump speed ratio

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

[0103] Test results:

[0104] Pump speed ratio (outer: intermediate: inner) Wall thickness ratio (outer: intermediate: inner) Target wall thickness ratio adaptability 1:1.5:1 1:2:2 Adapted 1:1:1 1:1.2:1.2 Not adapted 1:2:1 1:2.5:2.5 Not adapted

[0105] Conclusion: the 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 spherical structure.

[0106] Optimization experiment 2: optimization of low-temperature zone temperature

[0107] Experimental design: set the low-temperature zone temperature to 60℃, 70℃, 80℃ respectively, and other conditions are the same as in Example 1. After preparing the product, the bacteriostatic rate (3 parallel samples) is measured;

[0108] Test results:

[0109] Low temperature zone temperature (°C) Bacteriostatic rate (%) Bacteriostatic effect adaptability 60 30±2 Adapted 70 38±2 Adapted (optimal) 80 39±2 Adapted

[0110] Conclusion: the low-temperature zone temperature of 60-80℃ can meet the bacteriostatic requirements, and 70℃ takes into account the bacteriostatic effect and energy consumption, which is the optimal parameter selection for industrial production.

[0111] Example 7: Product storage stability test

[0112] Test purpose: verify the storage stability of the product and support industrial practicability.

[0113] Test conditions: the product prepared in Example 1 is stored for 6 months in two environments respectively:

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

[0115] Environment 2: 40℃ / RH 75% (accelerated aging condition).

[0116] Detection index and result:

[0117] The in vitro release characteristics (2h outer layer selenium release rate, 6h middle layer zinc release rate, 14h inner core copper release rate) and bacteriostatic rate were determined every month, and the results showed that:

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

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

[0120] Conclusion: The product has good storage stability, can maintain the core functional characteristics under the conditions of conventional circulation and storage, meets the needs of large-scale industrial production and market application, and has good industrial practicability.

[0121] In combination with the current actual demand, the protection scope of the above-mentioned embodiments of the application is not limited thereto, various changes made within the knowledge range of those skilled in the art without departing from the concept of the application still fall within the protection scope of the application.

Claims

1. A slow-release multi-mineral feed additive, characterized in that, The additive is a microsphere with a three-layer concentric sphere structure, from outside to inside: The outermost layer contains one or both of selenium and iodine, and the carrier is an enterase-sensitive polymer; The intermediate layer contains zinc and manganese, and the carrier is a pH-sensitive polymer; The inner core contains copper, and the carrier is a sustained-release matrix material; The total particle size of the microsphere is 100-200 μm, and the wall thickness ratio of the outermost layer, intermediate layer and inner 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 enterase-sensitive polymer is cross-linked amylose or a specific peptide segment, the pH-sensitive polymer is a sodium alginate-chitosan composite gel, and the sustained-release matrix material is ethyl cellulose and / or glycerol monostearate.

3. The slow-release multi-mineral feed additive according to claim 2, characterized in that, The pH-sensitive polymer of the intermediate layer is modified by quaternary ammonium salt, which permanently gives it positive charge and antibacterial properties.

4. The slow-release multi-mineral feed additive according to claim 3, characterized in that, The quaternary ammonium salt modification is achieved by in-situ polymerization grafting of cationic monomers onto the sodium alginate-chitosan composite gel network; The cationic monomer is methacryloyloxyethyl trimethylammonium chloride.

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

6. The slow-release multi-mineral feed additive according to claim 1, characterized in that, When determined according to the following method, its in-vitro sequential release characteristics meet: The microsphere is placed in a simulated gastric juice environment, pH 2.0-3.5, temperature 37°C, containing 0.1% by mass pepsin, stirring speed 50 r / min, sample is taken at 2h for determination, the release rate of selenium and / or iodine in the outermost layer is ≥80%; then the remaining sample is transferred to a simulated jejunum liquid environment, pH 6.0-6.5, temperature 37°C, containing 0.1% by mass trypsin, stirring speed 50 r / min, continues to be determined, sample is taken at a total time of 6h, the cumulative release rate of the intermediate layer is ≥70%; finally, the remaining sample is transferred to a simulated ileum liquid environment, pH 6.5-7.0, temperature 37°C, containing 0.1% by mass trypsin and 0.05% by mass choline salt, stirring speed 50 r / min, continues to be determined, sample is taken at a total time of 14h, the cumulative release rate of the inner core is ≥60%; The release rate is the cumulative release amount of the mineral elements contained in the corresponding layer relative to the initial mineral content of the layer.

7. A process for the preparation of the slow-release multi-mineral feed additive according to any one of claims 1 to 6, characterized in that, Comprising the following steps: S1, slurry preparation: prepare the outer layer slurry, the intermediate layer slurry and the inner layer slurry respectively, wherein the solid content of the outer layer slurry, the intermediate layer slurry and the inner layer slurry is controlled at 20-30%; S2, atomization granulation: use a coaxial three-channel atomizing nozzle, the inner layer slurry, the intermediate layer slurry and the outer layer slurry are pumped out from the inside to the outside through the inner channel, the middle channel and the outer channel respectively to form composite droplets; S3, stepwise temperature drying: the composite droplets are sequentially dried and solidified through high temperature zone, medium temperature zone and low temperature zone to form the microsphere with a three-layer concentric sphere structure.

8. The method of claim 7, wherein the slow-release multi-mineral feed additive is prepared by mixing the mineral compound with the carrier in a ratio of 1 : 1 to 1 :

10. In step S1, when preparing the intermediate layer slurry, cationic monomers and thermal initiators are added, the thermal initiator is potassium persulfate or ammonium persulfate, and the addition amount is 0.5-2% of the total mass of the intermediate layer slurry; In the low temperature zone drying stage of step S3, the temperature is controlled at 60-80°C to trigger the thermal initiation in-situ polymerization of the cationic monomers, so that the intermediate layer is modified by quaternary ammonium salt.

9. The method of claim 7, wherein the slow-release multi-mineral feed additive is prepared by mixing the mineral compound with the carrier in a ratio of 1: 1 to 1:

5. In step S2, the pump speed ratio of the coaxial three-channel atomizing nozzle is 1:1.5:1 for the outer channel, the middle channel and the inner channel. 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.

10. Use of the slow-release multi-mineral feed additive according to any one of claims 1 to 6 in layer feed, characterized in that, The additive is added in the feed in an amount of 0.1%-0.5% of the mass of the feed.

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