Nanometer magnesium oxide and preparation method and application of enteric-coated preparation of nanometer magnesium oxide

Abstract

The invention discloses nano magnesium oxide and a preparation method and application of an enteric-coated preparation of the nano magnesium oxide, and belongs to the technical field of feed additives. The preparation method comprises the following steps: preparing high-purity nano magnesium oxide powder through a hydrothermal precipitation-calcination technical route in combination with precise process parameter regulation and control, and coating the high-purity nano magnesium oxide through a coating technology to obtain the enteric-coated preparation. The pH response material adopted during coating has pH responsiveness, and the nano magnesium oxide is protected from being damaged by strong acidic conditions of gastric juice, so that the stability and the bioavailability of the nano magnesium oxide are improved; chitosan quaternary ammonium salt serves as a stabilizer and is good in biocompatibility and adhesiveness, positive charges carried by chitosan quaternary ammonium salt can interact with negative charges of an intestinal mucous layer, the retention time of nano magnesium oxide in the mucous layer can be prolonged, accurate release of magnesium ions in the intestinal tract is achieved, and the antibacterial performance of the nano magnesium oxide is improved.

Description

Technical Field

[0001] This invention relates to the field of feed additive technology, and more specifically to a method for preparing and applying nano-magnesium oxide and its enteric-coated formulation. Background Technology

[0002] In the field of feed additives, the application of antibacterial agents is crucial for ensuring animal health and improving breeding efficiency. While traditional feed antibacterial agents such as zinc oxide and copper preparations have certain antibacterial effects, they have many limitations in practical application. Zinc oxide, as a commonly used feed additive, can inhibit bacterial growth and improve intestinal health through various mechanisms. However, ordinary zinc oxide reacts with gastric acid in the stomach to generate excessive zinc ions, leading to insufficient gastric acid, affecting protein digestion, and inhibiting the absorption of divalent ions such as copper and iron, causing anemia and coat problems in piglets. Furthermore, its high acid-binding capacity increases the acid-binding capacity of the diet, increasing the risk of undigested protein fermentation in the hindgut and causing diarrhea. Excessive zinc ion emissions also cause environmental pollution. Long-term use of copper preparations can easily lead to bacterial resistance, and the accumulation of copper ions in the body may produce toxicity.

[0003] With the development of nanotechnology, the application of nano-magnesium oxide in feed additives has gradually attracted attention. Nano-magnesium oxide possesses unique physicochemical properties, such as high specific surface area and strong antibacterial properties. It can inhibit bacterial growth through various mechanisms, including generating reactive oxygen free radicals, dissociating magnesium ions, and directly disrupting bacterial cell membranes, exhibiting high inhibition rates against Staphylococcus aureus and Escherichia coli. Simultaneously, appropriate addition of nano-magnesium oxide can significantly improve daily weight gain in animals, reduce feed conversion ratio, improve intestinal health, and reduce diarrhea rates. Furthermore, its dosage is only about one-tenth that of traditional zinc oxide, which can significantly reduce feed costs and decrease heavy metal residues in animals and environmental pollution. However, ordinary nano-magnesium oxide also faces challenges such as the premature and excessive release of magnesium ions in the acidic environment of the stomach, affecting its antibacterial effect and the absorption and utilization of nutrients by animals.

[0004] To address the issue of premature release of nanoparticles in the acidic environment of the stomach, enteric coating technology was developed. Enteric coating allows nanoparticles to remain stable in the stomach, ensuring precise release upon reaching the intestines and improving bioavailability. Currently, enteric coating technology has been applied in drug delivery, such as tilmicosin enteric-coated granules, which improve bioavailability by over 40% through coating technology, solving palatability issues. However, in the feed additive field, there is a lack of formulations specifically designed for enteric-coated nano-magnesium oxide.

[0005] In summary, while nano-magnesium oxide offers advantages in feed additives such as antibacterial and growth-promoting properties, its application is limited by the acidic environment of the stomach. Enteric coating technology offers a potential solution, but currently, there is a lack of dedicated enteric-coated nano-magnesium oxide formulations for feed additives. Therefore, developing an enteric-coated nano-magnesium oxide formulation to achieve precise release of magnesium ions in the intestines, reducing stomach acid consumption and environmental pollution, has become a pressing technical challenge in the feed additive industry. Summary of the Invention

[0006] In view of this, the present invention provides a method for preparing nano-magnesium oxide and its enteric-coated formulation, as well as its application. High-purity nano-magnesium oxide is prepared by using a hydrothermal precipitation-calcination technique combined with precise process parameter control. Furthermore, a coating technique is used to coat the high-purity nano-magnesium oxide, which prevents the nano-magnesium oxide core from being decomposed in gastric juice and ensures that the core can disintegrate or dissolve in the intestine.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] A method for preparing nano-magnesium oxide includes the following steps:

[0009] (1) First, add urea and deionized water into a homogenizing tank and stir continuously at room temperature; then slowly add magnesium sulfate solution through a constant flow pump and continue stirring to form a homogenous mixed solution of urea and magnesium sulfate.

[0010] (2) Transfer the mixed solution in step (1) to a hydrothermal reactor, with the filling degree controlled at 60%~80%, and raise the temperature to 160~200℃ at a heating rate of 4~8℃ / min. Maintain the constant temperature for 4~10h, the reaction pressure is 0.5~1.5MPa, and the rotation speed is 600~1500rpm / min. After the reaction is completed, cool it to room temperature and then transfer it to the reaction liquid storage tank.

[0011] (3) The white precipitate was collected by centrifugation of the reaction solution. The precipitate was then transferred to a washing tank, deionized water was added, and ultrasonic dispersion was used to assist washing until the pH value of the washing solution reached 7.0~8.0. Finally, the precipitate was washed with ethanol, centrifuged, and dried to obtain magnesium carbonate powder. The reaction centrifuge liquid and the washing liquid were combined and recycled.

[0012] (4) The dried magnesium carbonate powder is sieved and calcined to obtain nano magnesium oxide powder.

[0013] Preferably, the magnesium sulfate solution in step (1) is obtained by treating magnesite roasted to produce light-burned magnesium oxide using the sulfuric acid method. The magnesium sulfate solution is purified to a concentration of 40-44 °Bé, pH=5-6, and temperature not lower than 60℃. The feeding rate of the magnesium sulfate solution is 30-180 mL / min. The mass concentration of the urea is 50-75%. The mixture is made by mixing the magnesium sulfate solution and the urea solution at a volume ratio of 1:0.6-2.5. The stirring speed is 200-500 rpm / min. The homogenization stirring time is 1.5-3 h.

[0014] Preferably, the centrifugal separation parameters in step (3) are: centrifugal speed of 2000~5000 rpm / min, centrifugation time of 5~20 min; the ultrasonic dispersion-assisted washing is: ultrasonic power of 100~300W, ultrasonic time of 10~30 min; the deionized water washing process is repeated 3~5 times, and centrifugation is performed after each washing.

[0015] Preferably, the drying process in step (3) is as follows: the washed precipitate is dried by a two-stage vibrating fluidized bed, wherein the inlet temperature of the two-stage vibrating fluidized bed is controlled at 165-190℃ and the outlet temperature is controlled at 110-145℃.

[0016] Preferably, the fineness of the powder after sieving in step (4) is not less than 300 mesh; the calcination is carried out at a heating rate of 2~5℃ / min to 550~1000℃ and kept at a constant temperature for 1~2h.

[0017] Another object of the present invention is to provide a method for preparing an enteric-coated formulation, comprising the following steps:

[0018] S1. The nano magnesium oxide powder obtained above is mixed with excipients and stabilizers, and then spherical particles of 30-40 mesh are formed by a polishing machine to serve as the inner core. The pH-responsive material is dissolved in edible alcohol to serve as the coating material.

[0019] S2. Add the rounded inner core into the fluidized bed coating machine, start the coating machine, introduce air, and dry the inner core. Take online samples to test the moisture content, which should not exceed 3%.

[0020] S3. Adjust the air inlet temperature and coat the inner core with the coating material through the coating bottom spray system; after coating, adjust the air inlet temperature and dry to obtain the enteric nano magnesium oxide preparation.

[0021] Preferably, the mass ratio of the nano-magnesium oxide powder, excipients, stabilizers and pH-responsive materials in step S1 is (7~9):(1~2):1:(6~7).

[0022] Preferably, the excipient in step S1 is methylcellulose or hydroxypropyl methylcellulose;

[0023] The stabilizer is a chitosan quaternary ammonium salt;

[0024] The pH-responsive material is polyacrylic acid resin II or hydroxypropyl methylcellulose phthalate.

[0025] Preferably, the drying temperature in step S2 is 70~80℃ and the drying time is 0.5~1.5h.

[0026] Preferably, in step S3, the first air intake temperature is 40~45℃ and the second air intake temperature is 60~70℃.

[0027] Another object of the present invention is to provide the application of the enteric-coated preparation obtained by the above-mentioned method in feed additives.

[0028] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects:

[0029] This invention uses abundant and inexpensive magnesite to prepare high-purity magnesium sulfate solution, replacing traditional high-priced magnesium salt reagents, providing a stable and low-cost raw material base for large-scale industrial production. After the reaction centrifuge liquid and washing liquid are combined and recovered, magnesium sulfate solution is added again at room temperature, and high-purity magnesium hydroxide can be prepared by direct precipitation. This enables a single production line to simultaneously produce nano-magnesium oxide, high-purity magnesium carbonate, high-purity magnesium hydroxide, and even higher value-added enteric-coated nano-magnesium oxide preparations. The production-input ratio is high, the process is simple, and the pollution is low.

[0030] The nano-magnesium oxide prepared by this invention is a spherical powder with a particle size of 30-100 nm, a specific surface area of ​​up to 101.98 m² / g, an oxygen vacancy concentration of 31.32%, a purity of up to 99.60%, and an antibacterial rate of up to 99.47% (for Escherichia coli 10). 6 (CFU / ml).

[0031] The pH-responsive material used in this invention has pH-responsive properties, protecting nano-magnesium oxide from the destruction caused by the strong acidity of gastric juice, thereby improving its stability and effectiveness. This invention uses chitosan quaternary ammonium salt as a stabilizer, which is an alkaline positively charged polysaccharide with good biocompatibility and adhesion. Its positive charge can interact with the negative charge of the intestinal mucus layer, which is beneficial to increasing the retention time of nano-magnesium oxide in the mucus layer. Attached Figure Description

[0032] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0033] Figure 1 This is a scanning electron microscope image of nano-magnesium oxide powder from Example 1. Detailed Implementation

[0034] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] This invention achieves efficient conversion from raw materials to product through a hydrothermal precipitation-calcination method in the preparation of nano-magnesium oxide. This method uses magnesium sulfate and urea as core raw materials to achieve controllable morphology synthesis of nano-magnesium oxide. The core chemical reactions are as follows:

[0036] (1) Hydrothermal precipitation reaction: CO(NH2)2 + 2H2O = (NH4)2CO3

[0037] MgSO4+ (NH4)2CO3=MgCO3↓+(NH4)2SO4

[0038] The alkaline environment created by urea hydrolysis promotes the growth of Mg. 2+ With CO3 2- The reaction produces a magnesium carbonate intermediate.

[0039] (2) High-temperature calcination decomposition: MgCO3 = MgO + CO2↑

[0040] Magnesium carbonate is thermally decomposed into nano-magnesium oxide, achieving both crystal reconstruction and morphology control.

[0041] To further illustrate the implementation process and technical effects of the present invention, a detailed description is provided below in conjunction with specific embodiments and characterization data:

[0042] Example 1

[0043] This embodiment provides a method for preparing nano-magnesium oxide and its enteric-coated formulation, including the following steps:

[0044] (1) First, add 1.9t of urea and 1.0t of deionized water to a homogenizing tank and stir continuously at room temperature for 1.5h; then, slowly add a high-purity magnesium sulfate solution with pH 5.8, temperature 85℃, and concentration 42°Bé through a constant flow pump, controlling the feeding rate at 90ml / min, and mix the magnesium sulfate solution and urea solution at a volume ratio of 1:1.45; the stirring speed is 350rpm / min; the homogenization stirring time is 1h, forming a homogenized mixed solution of urea and magnesium sulfate;

[0045] (2) Transfer the mixed solution in step (1) to a hydrothermal reactor, with the filling degree controlled at 75%, raise the temperature to 180°C at a rate of 4°C / min, maintain the constant temperature for 4.5h, the reaction pressure is 1.1MPa, the stirring speed is 800rpm / min, cool to room temperature after the reaction is completed, and then transfer to the reaction liquid storage tank.

[0046] (3) The reaction solution was centrifuged at 4000 rpm / min for 15 min, and the white precipitate was collected. The precipitate was then transferred to a washing tank, and an equal volume of deionized water was added. The mixture was ultrasonically dispersed at 300 W for 10 min and washed. This process was repeated 3 times until the pH of the washing solution reached 7.3. Finally, ethanol was added to the precipitate, and it was washed once under the same conditions. After centrifugation, the precipitate was dried in a two-stage vibrating fluidized bed. The inlet temperature was set at 165℃ and the outlet temperature at 110℃ to obtain magnesium carbonate powder. The reaction centrifuge liquid and the washing liquid were combined and recycled.

[0047] (4) Pass the dried intermediate magnesium carbonate powder through a 300-mesh sieve to ensure uniform particle size, and calcine it in a muffle furnace at 5℃ / min to 800℃ for 1.5h to obtain nano magnesium oxide powder.

[0048] (5) Weigh out nano magnesium oxide powder, methylcellulose, chitosan quaternary ammonium salt and polyacrylic acid resin II in a ratio of 8:1:1:6. Mix the prepared nano magnesium oxide powder with methylcellulose and chitosan quaternary ammonium salt, and form 40-mesh spherical particles as the inner core by a rounding machine. Dissolve polyacrylic acid resin II in edible alcohol as the coating material.

[0049] (6) Add the rounded inner core into the fluidized bed coating machine, start the coating machine, introduce air at 80°C, and dry the inner core for 0.5 hours. Take online samples to test the moisture content, which should not exceed 3%.

[0050] (7) Adjust the air inlet temperature to 45°C, and apply the coating material to the inner core through the coating bottom spray system. After coating, adjust the air inlet temperature to 70°C for drying to obtain enteric nano magnesium oxide preparation.

[0051] Example 2

[0052] This embodiment provides a method for preparing nano-magnesium oxide and its enteric-coated formulation, including the following steps:

[0053] (1) First, add 1.4t of urea and 1.0t of deionized water to a homogenizing tank and stir continuously at room temperature for 1 hour; then, slowly add a high-purity magnesium sulfate solution with pH 6.0, temperature 60℃, and concentration 40°Bé through a constant flow pump, controlling the feeding rate at 60ml / min, and mix the magnesium sulfate solution and urea solution at a volume ratio of 1:2; the stirring speed is 400rpm / min; the homogenization stirring time is 2 hours, forming a homogenized mixed solution of urea and magnesium sulfate;

[0054] (2) Transfer the mixed solution in step (1) to a hydrothermal reactor, with the filling degree controlled at 80%, raise the temperature to 190°C at a rate of 8°C / min, maintain the constant temperature for 6 hours, the reaction pressure is 0.8MPa, the stirring speed is 1200rpm / min, cool to room temperature after the reaction is completed, and then transfer to the reaction liquid storage tank.

[0055] (3) The reaction solution was centrifuged at 3000 rpm / min for 10 min, and the white precipitate was collected. The precipitate was then transferred to a washing tank, and an equal volume of deionized water was added. The mixture was ultrasonically dispersed at 300 W for 10 min and washed. This process was repeated three times until the pH of the washing solution reached 7.6. Finally, ethanol was added to the precipitate, and it was washed once under the same conditions. After centrifugation, the precipitate was dried in a two-stage vibrating fluidized bed. The inlet temperature was set at 190℃ and the outlet temperature at 145℃ to obtain magnesium carbonate powder. The reaction centrifuge liquid and the washing liquid were combined and recycled.

[0056] (4) Pass the dried intermediate magnesium carbonate powder through a 300-mesh sieve to ensure uniform particle size, heat it to 700°C in a muffle furnace at 3°C / min, and calcine it at a constant temperature for 2 hours to obtain nano magnesium oxide powder.

[0057] (5) Weigh out nano magnesium oxide powder, hydroxypropyl methylcellulose, chitosan quaternary ammonium salt and hydroxypropyl methylcellulose phthalate in a ratio of 9:2:1:7. Mix the prepared nano magnesium oxide powder with cellulose and chitosan quaternary ammonium salt, and form 30-mesh spherical particles as the inner core using a rounding machine. Dissolve polyacrylic acid resin II in edible alcohol as the coating material.

[0058] (6) Add the rounded inner core into the fluidized bed coating machine, start the coating machine, introduce air at 70°C, and dry the inner core for 1.5 hours. Take online samples to test the moisture content, which should not exceed 3%.

[0059] (7) Adjust the air inlet temperature to 40°C, and apply the coating material to the inner core through the coating bottom spray system. After coating, adjust the air inlet temperature to 60°C for drying to obtain enteric nano magnesium oxide preparation.

[0060] Example 3

[0061] This embodiment provides a method for preparing nano-magnesium oxide and its enteric-coated formulation, including the following steps:

[0062] (1) First, add 1.62t of urea and 0.6t of deionized water to a homogenizing tank and stir continuously at room temperature for 2.5h. Then, slowly add a high-purity magnesium sulfate solution with pH 5.8, temperature 80℃, and concentration 44°Bé through a constant flow pump, controlling the feeding rate at 50mL / min. The magnesium sulfate solution and urea solution are mixed at a volume ratio of 1:0.8. The stirring speed is 350rpm / min. The homogenization stirring time is 2.5h to form a homogenized mixed solution of urea and magnesium sulfate.

[0063] (2) Transfer the mixed solution in step (1) to a hydrothermal reactor, with the filling degree controlled at 75%, and raise the temperature to 170°C at a rate of 5°C / min. Maintain the constant temperature for 4 hours, with a reaction pressure of 1.3MPa and a stirring speed of 1500rpm / min. After the reaction is completed, cool to room temperature and then transfer to the reaction liquid storage tank.

[0064] (3) The reaction solution was centrifuged at 3000 rpm / min for 10 min, and the white precipitate was collected. The precipitate was then transferred to a washing tank, and an equal volume of deionized water was added. The mixture was ultrasonically dispersed at 300 W for 10 min and washed. This process was repeated 3 times until the pH of the washing solution reached 7.8. Finally, ethanol was added to the precipitate, and it was washed once under the same conditions. After centrifugation, the precipitate was dried in a two-stage vibrating fluidized bed. The inlet temperature was set at 180℃ and the outlet temperature at 130℃ to obtain magnesium carbonate powder. The reaction centrifuge liquid and the washing liquid were combined and recycled.

[0065] (4) Pass the dried intermediate magnesium carbonate powder through a 300-mesh sieve to ensure uniform particle size, and calcine it in a muffle furnace at a temperature of 6℃ / min to 650℃ for 2 hours to obtain nano magnesium oxide powder.

[0066] (5) Weigh out nano magnesium oxide powder, methylcellulose, chitosan quaternary ammonium salt and polyacrylic acid resin II in a ratio of 7:1:1:7. Mix the prepared nano magnesium oxide powder with methylcellulose and chitosan quaternary ammonium salt, and form 30-mesh spherical particles as the inner core by a rounding machine. Dissolve polyacrylic acid resin II in edible alcohol as the coating material.

[0067] (6) Add the rounded inner core into the fluidized bed coating machine, start the coating machine, introduce air at 75°C, and dry the inner core for 1 hour. Take online samples to test the moisture content, which should not exceed 3%.

[0068] (7) Adjust the air inlet temperature to 45°C, and apply the coating material to the inner core through the coating bottom spray system. After coating, adjust the air inlet temperature to 60°C for drying to obtain enteric nano magnesium oxide preparation.

[0069] Quantitative evaluation of antibacterial properties of nano-magnesium oxide

[0070] Using Escherichia coli and Staphylococcus aureus as targets, the antibacterial rate of the samples was calculated by colony counting at a concentration of 600 μg / ml of nano-magnesium oxide. The antibacterial efficiency of both samples reached over 97%.

[0071]

[0072] Evaluation of pH stability and disintegration in simulated gastric and intestinal fluids of enteric-coated nano-magnesium oxide formulations

[0073] The samples prepared in Examples 1, 2, and 3 were placed in simulated gastric fluid (pH 1.2) and stirred at 37°C for 2 hours. Then, the samples were transferred to simulated intestinal fluid (pH 6.8) and kept at 37°C. A disintegration apparatus was activated, and the time it took for the samples to completely disintegrate and pass through a sieve was recorded (n=6). Examples 1, 2, and 3 did not dissolve in gastric fluid (pH 1.2) but rapidly disintegrated in intestinal fluid (pH 6.8), ensuring precise release of the enteric-coated nano-magnesium oxide formulation into the intestine.

[0074]

[0075] Solubility evaluation of enteric-coated nano-magnesium oxide formulations in simulated intestinal fluid

[0076] The samples obtained in Examples 1, 2, and 3 were poured into prepared simulated intestinal fluid (pH 7.5), and centrifuged after 1 hour and 3 hours, respectively. The supernatant was then collected, and the content of Mg was determined. Within 3 hours, the samples from Examples 1, 2, and 3 were completely dissolved in the simulated intestinal fluid, with a solubility rate of over 95%.

[0077]

[0078] Verification of the efficacy of chicken enteritis treatment

[0079] A single-factor experiment was conducted. 360 7-day-old AA white-feathered broiler chickens with near-healthy body condition were selected, with an equal number of males and females, and were administered 10 doses daily via gavage. 9CFU of Escherichia coli induced enteritis for 3 consecutive days, and fecal occult blood tests were positive in all cases. Chickens were randomly assigned to 3 treatment groups, with 6 replicates per group and 20 chickens per replicate. Experimental group: basal diet + 0.2% enteric-coated nano-magnesium oxide (Example 1); control group: basal diet + 0.2% uncoated nano-magnesium oxide (Example 1); blank group: basal diet (no additives). The experimental period was 42 days. Feed intake per replicate was recorded daily during the experimental period. Each replicate was weighed on day 1 and day 42. Fecal samples were collected at the end of day 42 for E. coli testing. The results showed that the basal diet + 0.2% enteric-coated nano-magnesium oxide (Example 1) significantly reduced the number of E. coli in chicken excrement after 42 days, and significantly increased both average daily feed intake and average daily weight gain.

[0080]

[0081] Note: Different lowercase letters in the same row indicate significant differences (P < 0.05), while the same lowercase letter or no letter indicates no significant differences (P > 0.05).

[0082] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since they correspond to the methods disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to the method section.

[0083] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing nano-magnesium oxide, characterized in that, Includes the following steps: (1) First, add urea and deionized water into a homogenizing tank and stir continuously at room temperature; then slowly add magnesium sulfate solution through a constant flow pump and continue stirring to form a homogenous mixed solution of urea and magnesium sulfate. (2) Transfer the mixed solution in step (1) to a hydrothermal reactor, with the filling degree controlled at 60%~80%, and raise the temperature to 160~200℃ at a heating rate of 4~8℃ / min. Maintain the constant temperature for 4~10h, the reaction pressure is 0.5~1.5MPa, and the rotation speed is 600~1500rpm / min. After the reaction is completed, cool it to room temperature and then transfer it to the reaction liquid storage tank. (3) The white precipitate was collected by centrifugation of the reaction solution. The precipitate was then transferred to a washing tank, deionized water was added, and ultrasonic dispersion was used to assist washing until the pH value of the washing solution reached 7.0~8.

0. Finally, the precipitate was washed with ethanol, centrifuged, and dried to obtain magnesium carbonate powder. The reaction centrifuge liquid and the washing liquid were combined and recycled. (4) The dried magnesium carbonate powder is sieved and calcined to obtain nano magnesium oxide powder.

2. The method for preparing nano-magnesium oxide according to claim 1, characterized in that, The magnesium sulfate solution mentioned in step (1) is obtained by treating magnesite roasted to produce light-burned magnesium oxide using the sulfuric acid method. The magnesium sulfate solution is purified to a concentration of 40-44 °Bé, pH=5-6, and temperature not lower than 60℃. The feeding rate of the magnesium sulfate solution is 30-180 mL / min. The mass fraction of the urea solution is 50-75%. The mixed solution is made by mixing the magnesium sulfate solution and the urea solution at a volume ratio of 1:0.6-2.

5. The stirring speed is 200-500 rpm / min. The homogenization stirring time is 1.5-3 h.

3. The method for preparing nano-magnesium oxide according to claim 1, characterized in that, The parameters for centrifugation in step (3) are: centrifugation speed of 2000~5000 rpm / min and centrifugation time of 5~20 min; the ultrasonic dispersion-assisted washing is: ultrasonic power of 100~300W and ultrasonic time of 10~30 min; the washing process is repeated with deionized water 3~5 times, and centrifugation is performed after each washing. The drying process involves drying the washed precipitate through a two-stage vibrating fluidized bed, with the inlet temperature of the two-stage vibrating fluidized bed controlled at 165-190℃ and the outlet temperature controlled at 110-145℃.

4. The method for preparing nano-magnesium oxide according to claim 1, characterized in that, The fineness of the powder after sieving in step (4) shall not be less than 300 mesh; the calcination shall be carried out at a heating rate of 2~5℃ / min to 550~1000℃ and kept at a constant temperature for 1~2h.

5. A method for preparing an enteric-coated formulation, characterized in that, Includes the following steps: S1. The nano magnesium oxide powder prepared by the method of any one of claims 1-4 is mixed with excipients and stabilizers, and then spherical particles of 30-40 mesh are formed by a spherical polishing machine as the inner core. The pH-responsive material is dissolved in edible alcohol as the coating material. S2. Add the rounded inner core into the fluidized bed coating machine, start the coating machine, introduce air, and dry the inner core. Take online samples to test the moisture content, which should not exceed 3%. S3. Adjust the air inlet temperature and coat the inner core with the coating material through the coating bottom spray system; after coating, adjust the air inlet temperature and dry to obtain the enteric preparation.

6. The method for preparing an enteric-coated formulation according to claim 5, characterized in that, The mass ratio of the nano-magnesium oxide powder, excipients, stabilizers and pH-responsive materials in step S1 is (7~9):(1~2):1:(6~7).

7. The method for preparing an enteric-coated formulation according to claim 5, characterized in that, The excipients mentioned in step S1 are methylcellulose or hydroxypropyl methylcellulose; The stabilizer is a chitosan quaternary ammonium salt; The pH-responsive material is polyacrylic acid resin II or hydroxypropyl methylcellulose phthalate.

8. The method for preparing an enteric-coated formulation according to claim 5, characterized in that, The drying temperature in step S2 is 70~80℃, and the drying time is 0.5~1.5h.

9. The method for preparing an enteric-coated formulation according to claim 5, characterized in that, In step S3, the first air intake temperature is 40~45℃, and the second air intake temperature is 60~70℃.

10. The use of the enteric-coated formulation prepared by the method of any one of claims 5-9 in feed additives.

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