阅读说明：本技术 饲料添加剂及其制备方法和其在饲料中的应用以及替抗饲料 (Feed additive, preparation method thereof, application of feed additive in feed and anti-feed ) 是由 张宇婷 孙铁虎 马增强 张晓琳 李勇 李桂冠 唐诗 于 2020-06-09 设计创作，主要内容包括：本发明涉及动物饲料领域,公开了一种饲料添加剂及其制备方法和其在饲料中的应用以及替抗饲料。该饲料添加剂由芯材和包裹芯材的肠溶包衣组成；其中,所述芯材含有载体以及负载在所述载体上的活性组分；所述活性组分为植物精油和/或饲用酸化剂,所述载体为二氧化硅；其中,所述肠溶包衣含有淀粉基聚合物。本发明通过将植物精油和/或饲用酸化剂活性组分负载到作为载体的二氧化硅上,以其作为芯材,并在其上包裹作为肠溶包衣的淀粉基聚合物,由此提供了一种饲料添加剂。通过对该饲料添加剂进行溶出效果体外评价,显示,该饲料添加剂在胃模拟环境下,具有优良的抗酸腐蚀性,在肠道模拟环境下,具有优良的活性组分释放性。(The invention relates to the field of animal feed, and discloses a feed additive, a preparation method thereof, application of the feed additive in feed and a substitute antibiotic feed. The feed additive consists of a core material and an enteric coating wrapping the core material; wherein the core material contains a carrier and an active component loaded on the carrier; the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide; wherein the enteric coating comprises a starch-based polymer. The invention provides a feed additive by loading active components of plant essential oil and/or feeding acidifier on silicon dioxide as a carrier, taking the silicon dioxide as a core material and coating a starch-based polymer as an enteric coating on the silicon dioxide. The in-vitro evaluation of the dissolution effect of the feed additive shows that the feed additive has excellent acid corrosion resistance in a stomach simulation environment and excellent active component release performance in an intestinal simulation environment.)

1. A feed additive is characterized in that the feed additive consists of a core material and an enteric coating wrapping the core material;

wherein the core material contains a carrier and an active component loaded on the carrier;

the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide;

wherein the enteric coating comprises a starch-based polymer.

2. The feed additive according to claim 1, wherein the carrier is contained in an amount of 60 to 120 parts by weight and the enteric coating is contained in an amount of 25 to 70 parts by weight, based on 100 parts by weight of the active ingredient.

3. The feed additive of claim 1 or 2, wherein the plant essential oil is at least one of cinnamaldehyde, eucalyptol, menthol, eugenol, anethole, and oregano oil; and/or

The feeding acidifier is prepared from organic acid and/or inorganic acid;

preferably, the organic acid is at least one of L-lactic acid, citric acid, fumaric acid, formic acid, acetic acid, propionic acid, butyric acid, sorbic acid, malic acid, tartaric acid and benzoic acid; and/or

The inorganic acid is phosphoric acid and/or hydrochloric acid.

4. The feed additive according to any one of claims 1 to 3, wherein the starch in the starch-based polymer is at least one of corn starch, potato starch, wheat starch, sweet potato starch and mung bean starch;

preferably, the starch-based polymer is a corn starch-based polymer;

preferably, the starch-based polymer is starch octenyl succinate;

preferably, the preparation method of the starch octenyl succinate ester comprises the following steps:

(1) carrying out ultrasonic treatment on starch at the temperature of 100-125 ℃ in the presence of calcium salt to obtain pretreated starch;

(2) mixing the pretreated starch with water to obtain a starch slurry having a starch content of 50-60 wt%;

(3) adding a mixture of octenyl succinic anhydride and alcohol into the starch slurry, and carrying out esterification reaction at 35-45 ℃ and pH7.5-9.5 to obtain a product containing octenyl succinic acid starch ester;

(4) purifying and drying the product containing octenyl succinic acid starch ester in sequence to obtain octenyl succinic acid starch ester;

preferably, in step (1), the calcium salt is used in an amount of 1 to 3 parts by weight in terms of calcium element, relative to 100 parts by weight of starch on a dry basis;

preferably, in the step (3), the alcohol is C2-C4 alcohol;

preferably, the volume ratio of octenyl succinic anhydride to alcohol is 1: 3-5;

preferably, the octenyl succinic anhydride is used in an amount of 2 to 4 parts by weight, relative to 100 parts by weight of starch on a dry weight basis.

5. The method of any one of claims 1-4, wherein the enteric coating further comprises magnesium stearate.

6. A method of preparing a feed additive, the method comprising:

(a) loading an active component on a carrier to obtain a core material;

(b) dissolving the enteric coating in water to obtain an enteric coating suspension;

(c) coating the enteric coating suspension onto the core material to obtain the feed additive;

wherein the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide;

wherein the enteric coating comprises a starch-based polymer.

7. The preparation method according to claim 6, wherein in the step (b), the enteric coating is dissolved in water at 60-80 ℃; and/or

In step (c), applying the enteric coating suspension to the core material at a temperature below 35 ℃; and/or

In step (c), the coating is carried out in a coating pan or a fluidized bed.

8. A feed additive prepared by the method of claim 6 or 7.

9. Use of a feed additive according to any one of claims 1-5 and 8 in feed.

10. A feed substitute comprising the feed additive according to any one of claims 1 to 5 and 8 as a component for substitute antibody.

Technical Field

The invention relates to the field of animal feed, in particular to a feed additive, a preparation method of the feed additive, the feed additive prepared by the method, application of the feed additive in feed and a substitute anti-feed.

Background

With the continuous and deep research of researchers on novel antibiotic substitutes in livestock and poultry production, plant essential oil, acidifier and the like are found to have the characteristics of antibiosis, antivirus, no residue, multifunctionality, stress resistance, inoxidizability and the like, so that the plant essential oil, acidifier and the like can be used as a partial or complete antibiotic substitute when being applied to the livestock and poultry production, accord with the development direction of healthy breeding of livestock and poultry, effectively substitute antibiotics, promote the growth of animals, improve the feed conversion efficiency and reduce the disease incidence, and are safe, efficient and green feed additives.

However, the additive has the characteristics of instability and volatility, so that the additive has the problems of easy loss, difficult stomach passing and the like in the process of passing through the digestive tract of animals in the feed processing process, and is difficult to realize industrialization and popularization as a novel feed additive.

Disclosure of Invention

The present invention aims to overcome the problems of the prior art and provide a feed additive, a preparation method of the feed additive, the feed additive prepared by the method, the application of the feed additive in feed, and a substitute anti-feed. The feed additive provided by the invention has higher over-stomach rate and intestinal release rate.

In order to achieve the above objects, the present invention provides, in one aspect, a feed additive comprising a core material and an enteric coating surrounding the core material;

wherein the core material contains a carrier and an active component loaded on the carrier;

the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide;

wherein the enteric coating comprises a starch-based polymer.

In a second aspect, the present invention provides a method for preparing a feed additive, the method comprising:

(a) loading an active component on a carrier to obtain a core material;

(b) dissolving the enteric coating in water to obtain an enteric coating suspension;

(c) coating the enteric coating suspension onto the core material to obtain the feed additive;

wherein the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide;

wherein the enteric coating comprises a starch-based polymer.

In a third aspect the present invention provides a feed additive prepared by the method as described above.

In a fourth aspect the invention provides the use of a feed additive as described above in a feed.

A fifth aspect of the present invention provides a feed substitute comprising the feed additive as described above as a component of the substitute antibiotic.

The invention provides a feed additive by loading active components of plant essential oil and/or feeding acidifier on silicon dioxide as a carrier, taking the silicon dioxide as a core material and coating a starch-based polymer as an enteric coating on the silicon dioxide. The in-vitro evaluation of the dissolution effect of the feed additive shows that the feed additive has excellent acid corrosion resistance in a stomach simulation environment and excellent active component release performance in an intestinal simulation environment.

Detailed Description

The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.

In a first aspect, the invention provides a feed additive, which consists of a core material and an enteric coating wrapping the core material;

wherein the core material contains a carrier and an active component loaded on the carrier;

the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide;

wherein the enteric coating comprises a starch-based polymer.

According to the invention, the content of the components in the feed additive can vary within wide limits, preferably the carrier is present in an amount of 60 to 120 parts by weight, for example 60 parts by weight, 70 parts by weight, 80 parts by weight, 90 parts by weight, 100 parts by weight, 110 parts by weight, 120 parts by weight, more preferably 80 to 100 parts by weight, based on 100 parts by weight of the active component; the content of the enteric coating is 25 to 70 parts by weight, and for example, may be 25 parts by weight, 30 parts by weight, 35 parts by weight, 40 parts by weight, 45 parts by weight, 50 parts by weight, 55 parts by weight, 60 parts by weight, 65 parts by weight, 70 parts by weight, and more preferably 40 to 50 parts by weight.

According to the present invention, the plant essential oil may be any of various existing plant essential oils having antibacterial, antiviral, residue-free, multifunctional, anti-stress or antioxidant properties, and may include, for example, but not limited to, at least one of cinnamaldehyde, eucalyptol, menthol, eugenol, anethole, and oregano oil. According to a preferred embodiment of the present invention, the plant essential oil is at least one of cinnamaldehyde, cineole and menthol, and is further preferably a mixed essential oil of cinnamaldehyde, cineole and menthol (preferably in a ratio of 10-20:30-50:10, and more preferably 12-18:35-45: 10). In this preferred embodiment, the feed additive has not only an excellent substitution effect but also better acid corrosion resistance and enteric dissolution resistance.

According to the invention, the feeding acidifier can be various existing feeding acidifiers with the characteristics of antibiosis, antivirus, no residue, multifunction, stress resistance or oxidation resistance and the like, and can be prepared from organic acid and/or inorganic acid.

Wherein, examples of the organic acid may include, but are not limited to, at least one of L-lactic acid, citric acid, fumaric acid, formic acid, acetic acid, propionic acid, butyric acid, sorbic acid, malic acid, tartaric acid, and benzoic acid. According to a preferred embodiment of the present invention, the organic acid is at least one of acetic acid, propionic acid and butyric acid.

Wherein, the inorganic acid may include, but is not limited to, phosphoric acid and/or hydrochloric acid.

According to the invention, the active component may be at least one of a plant essential oil, may be at least one of a feeding acidifier, or may be a combination of at least one of a plant essential oil and at least one of a feeding acidifier.

According to the present invention, the starch-based polymer may be a polymer obtained by denaturing various starches, examples of which may include, but are not limited to, at least one of corn starch, potato starch, wheat starch, sweet potato starch, and mung bean starch. According to a most preferred embodiment of the invention, the starch-based polymer is a corn starch-based polymer. In this preferred embodiment, the feed additive has better acid corrosion resistance and intestinal dissolution resistance.

Further preferably, the starch-based polymer is starch octenyl succinate.

Wherein, the starch octenyl succinate can be prepared by a conventional method, and in order to further improve the acid corrosion resistance and the intestinal tract dissolution property of the feed additive prepared by the starch octenyl succinate, the preparation method preferably comprises the following steps:

(1) carrying out ultrasonic treatment on starch at the temperature of 100-125 ℃ in the presence of calcium salt to obtain pretreated starch;

(2) mixing the pretreated starch with water to obtain a starch slurry having a starch content of 50-60 wt%;

(3) adding a mixture of octenyl succinic anhydride and alcohol into the starch slurry, and carrying out esterification reaction at 35-45 ℃ and pH7.5-9.5 to obtain a product containing octenyl succinic acid starch ester;

(4) and purifying and drying the product containing the octenyl succinic acid starch ester in sequence to obtain the octenyl succinic acid starch ester.

According to the present invention, in step (1), the calcium salt may be any conventional calcium salt, preferably a soluble calcium salt, more preferably calcium chloride, calcium sulfate, calcium phosphate or the like.

According to the present invention, in step (1), the starch is preferably dry starch. The dry starch refers to dry starch with the water content less than or equal to 5 weight percent.

According to the invention, the amount of said calcium salt used in step (1) may vary within wide limits, preferably from 1 to 3 parts by weight, for example 1, 1.4, 1.8, 2.2, 2.6, 3 parts by weight, calculated as calcium element, with respect to 100 parts by weight of starch on a dry weight basis.

According to the present invention, in the step (1), the conditions of the ultrasound are not particularly limited, and preferably, the power of the ultrasound is 100- & lt 300 & gt W, and the time of the ultrasound is 2-6 hours; more preferably, the power of the ultrasonic wave is 150-250W, and the time of the ultrasonic wave is 3.5-4.5 hours.

The starch treated under the condition of the step (1) can be more effectively subjected to esterification reaction with octenyl succinic anhydride, so that the obtained octenyl succinic acid starch ester can better protect active components in a gastric acid environment and release the active components in an intestinal environment.

According to the invention, in step (2), the pretreated starch is mixed with water with or without temperature reduction treatment to obtain the starch slurry, and the starch slurry is preferably mixed with water after being cooled to room temperature.

According to the invention, in step (3), the alcohol is a C2-C4 alcohol, for example, ethanol, propanol or butanol, preferably propanol.

Preferably, the volume ratio of octenyl succinic anhydride to alcohol is 1:3 to 5, and may be, for example, 1:3, 1:3.4, 1:3.8, 1:4.2, 1:4.6, 1: 5.

Preferably, the octenyl succinic anhydride is used in an amount of 2 to 4 parts by weight, for example, 2 parts by weight, 2.4 parts by weight, 2.8 parts by weight, 3.2 parts by weight, 3.6 parts by weight, or 4 parts by weight, based on 100 parts by weight of starch on a dry weight basis.

According to the present invention, in the step (3), the temperature of the esterification reaction may be 35 ℃, 37 ℃, 39 ℃, 41 ℃, 43 ℃, 45 ℃; the pH may be 7.5, 7.8, 8, 8.3, 8.5, 8.7, 9, 9.3, 9.5; preferably, the temperature of the esterification reaction is 38-42 ℃ and the pH is 8-9.

According to the present invention, in the step (4), the purification may be performed by a conventional water washing centrifugation method.

According to the present invention, in the step (4), before the drying, it is preferable that the pH of the purified octenyl succinate starch ester is adjusted to 3 to 7 by adding water.

According to the invention, in the step (4), the drying may be a conventional drying method, for example, spray drying, the inlet air temperature is controlled at 210-.

According to the invention, the enteric coating also preferably contains magnesium stearate. More preferably, the enteric coating consists of a starch-based polymer and magnesium stearate. More preferably, the magnesium stearate is present in an amount of 10 to 20 parts by weight, preferably 13 to 18 parts by weight, relative to 100 parts by weight of starch-based polymer on a dry weight basis. Under this preferred condition, the feed additive has better acid corrosion resistance and intestinal dissolution resistance.

In a second aspect, the present invention provides a method for preparing a feed additive, the method comprising:

(a) loading an active component on a carrier to obtain a core material;

(b) dissolving the enteric coating in water to obtain an enteric coating suspension;

(c) coating the enteric coating suspension onto the core material to obtain the feed additive;

wherein the active component is plant essential oil and/or feeding acidifier, and the carrier is silicon dioxide;

wherein the enteric coating comprises a starch-based polymer.

The selection and amounts of the components of the preparation process according to the invention have been described in detail in the first aspect, and are not described here again in order to avoid unnecessary repetition.

According to the present invention, in the step (a), the carrier may be loaded in a mixer, and then the active ingredient may be uniformly sprayed in the mixer filled with the carrier to allow the active ingredient to be uniformly adsorbed on the carrier, thereby obtaining the core material.

The inventor of the invention finds that when the active component is a composition of a plurality of components, an endothermic phenomenon occurs in the process, the temperature of the raw material mixed liquid is lower, and volatilization loss caused by high temperature can be avoided. According to a preferred embodiment of the present invention, the plant essential oil is a mixed essential oil of cinnamaldehyde, eucalyptol and menthol (preferably in a ratio of 10-20:30-50:10, more preferably 12-18:35-45: 10).

According to the present invention, in step (b), the enteric coating is dissolved in water, preferably at 60 to 80 ℃, preferably 65 to 75 ℃, to obtain an enteric coating suspension.

More preferably, the starch-based polymer is dissolved in water at 60-80 deg.C (preferably 65-75 deg.C) and homogenized by stirring (e.g., with a propeller stirrer or diffuser), then magnesium stearate is added and stirring is continued for 40-50min, during which time the temperature is maintained at 60-80 deg.C (preferably 65-75 deg.C).

According to the present invention, in step (c), the enteric coating suspension is sprayed onto the core material, preferably at a temperature below 35 ℃. More preferably, in step (c), the spraying is carried out in a coating pan or in a fluidised bed, even more preferably a fluidised bed. In this preferred case, the heat stability and gastric acid resistance of the active ingredient, as well as the enteric dissolution properties, can be further improved.

In a third aspect, the present invention provides a feed additive prepared by the method as described above.

In a fourth aspect, the present invention provides the use of a feed additive as described above in a feed.

In a fifth aspect, the present invention provides a replacement feed comprising a feed additive as described above as a replacement component.

Wherein, the feed additive can partially or completely replace antibiotic components in the feed.

The present invention will be described in detail below by way of examples.

Preparation example 1

For illustration of starch octenyl succinate

(1) Based on 100 parts by weight of corn starch (water content. ltoreq.5 wt%), 2 parts by weight of calcium chloride in terms of calcium ion was added thereto, and then the resulting mixture was sonicated at 110 ℃ for 200W for 4 hours to obtain pretreated starch.

(2) Mixing the pretreated starch obtained in step (1) with water to obtain a starch slurry with a starch content of 55 wt%.

(3) Naturally cooling the starch slurry obtained in the step (2) to room temperature, and then adding a mixed solution of octenyl succinic anhydride and propanol in a volume ratio of 1:4 into the starch slurry, wherein the adding amount of the mixed solution is 3 parts by weight relative to 100 parts by weight of starch. The obtained system is mixed evenly and then esterification reaction is carried out at 40 ℃ and pH8.5, thus obtaining the product containing the octenyl succinic acid starch ester.

(4) And washing the product containing octenyl succinic starch ester with water and centrifuging to obtain purified octenyl succinic starch ester, then adding water into the purified octenyl succinic starch ester to adjust the pH value to 5, carrying out spray drying, controlling the air inlet temperature at 180-210 ℃, controlling the air outlet temperature at 80-95 ℃, then entering a boiling furnace at 120-160 ℃, drying for 4 hours, and cooling to obtain the target product, namely octenyl succinic starch ester A1.

Preparation example 2

For illustration of starch octenyl succinate

Preparation of starch octenylsuccinate was carried out in the same manner as in preparation example 1, except that corn starch was replaced with an equal amount of potato starch. The target product, octenyl succinic acid starch ester A2, is obtained.

Preparation example 3

For illustration of starch octenyl succinate

(1) Placing corn starch with the water content less than or equal to 5% in a negative pressure horizontal converter at the temperature of 145 ℃ for 4 hours to obtain the pretreated starch.

(2) Mixing the pretreated starch obtained in step (1) with water to obtain a starch slurry with a starch content of 55 wt%.

(3) Same as in preparation example 1, except that propanol was replaced with ethanol.

(4) The same as in preparation example 1.

The target product, octenyl succinic acid starch ester A3, is obtained.

Examples 1 to 5

Feed additive illustrating the invention and method for preparing the same

(1) Mixing the raw materials, weighing the components in the active ingredient raw materials according to the proportion shown in the table 1, and uniformly stirring to obtain the active ingredient.

(2) And (3) carrier adsorption, namely spraying the active components into a mixer filled with silicon dioxide at a constant speed according to the dosage shown in the table 1, and uniformly adsorbing the active components onto the silicon dioxide carrier to prepare the core material.

(3) Preparation of packaging Material according to the amounts shown in Table 1, starch octenyl succinate A1 prepared in preparation example 1 was added to a vessel containing water while stirring with a propeller stirrer, magnesium stearate was added, and the suspension was stirred while the temperature was kept constant. Wherein the coating material comprises starch octenyl succinate A1 and magnesium stearate.

(4) And (4) coating and spraying, namely spraying the coating material on the surface of the core material by adopting a Mini type fluidized bed coating granulator. The material temperature is normal temperature, the air inlet temperature is less than 35 ℃, the rotating speed of a fan is 2000rpm, and the rotating speed of a peristaltic pump is 12.0 rpm. Then the coated particles are dried and pass through a vibrating screen, the particle size of the product particles is controlled within 10-30 meshes, and a Transmission Electron Microscope (TEM) shows that the obtained product has a coating structure.

TABLE 1

Example 6

Feed additive illustrating the invention and method for preparing the same

The preparation of the feed additive was carried out according to the procedure of example 1, except that the starch octenyl succinate A1 was replaced by an equal amount of starch octenyl succinate A2, and the resulting product was shown to have a coating structure by Transmission Electron Microscopy (TEM).

Example 7

Feed additive illustrating the invention and method for preparing the same

The preparation of the feed additive was carried out according to the procedure of example 1, except that the starch octenyl succinate A1 was replaced by an equal amount of starch octenyl succinate A3, and the resulting product was shown to have a coating structure by Transmission Electron Microscopy (TEM).

Example 8

Feed additive illustrating the invention and method for preparing the same

The preparation of the feed supplement was carried out according to the method of example 1, except that magnesium stearate was not used in the preparation of the coating material, and 45 parts by weight of starch octenylsuccinate A1 was used directly, as shown by Transmission Electron Microscopy (TEM) to show that the resulting product had a coating structure.

Example 9

Feed additive illustrating the invention and method for preparing the same

The preparation of the feed additive was carried out according to the method of example 1, except that the fluidized bed was replaced with a coating pan and Transmission Electron Microscopy (TEM) showed that the resulting product had a coating structure.

Example 10

Feed additive illustrating the invention and method for preparing the same

The preparation of the feed supplement was carried out as in example 1, except that cinnamaldehyde was replaced with an equal amount of terpineol, and Transmission Electron Microscopy (TEM) showed that the resulting product had a coating structure.

Comparative example 1

Feed additive illustrating the invention and method for preparing the same

The preparation of the feed additive was carried out according to the method of example 1, except that the silica was replaced by porous starch and the resulting product had a coating structure as shown by Transmission Electron Microscopy (TEM).

Comparative example 2

Feed additive illustrating the invention and method for preparing the same

The feed supplement was prepared as in example 1 except that the enteric coating was palmitic acid and Transmission Electron Microscopy (TEM) showed that the resulting product had a coated structure.

Test example

In vitro dissolution effect simulation experiment:

(1) release amount in acid: taking a proper amount of the product of the above examples and comparative examples, measuring the release amount in acid of the coated product by reference release measuring method (0931 of the first part of 2015 pharmacopoeia of China), measuring 900mL of 0.001mol/L hydrochloric acid solution as a test dissolution medium according to the requirement, putting the dissolution medium into a dissolution cup by standard operation until the temperature of the dissolution medium reaches 37 +/-0.5 ℃, and keeping the temperature in the range constant. Weighing a proper amount of sample, putting the sample into a dissolving-out cup, starting an instrument to reach the specified rotating speed of 50r/min, 0, 1.0 and 2.0 hours, respectively sucking 1mL of solution at the specified sampling point, complementing the corresponding volume after each time of taking, filtering the solution by a filter into a 15mL centrifuge tube, sealing the centrifuge tube by a cover, and storing the sample at 4 ℃ for later use. The collected sample is added with methanol or ethyl acetate with 1-3 times volume for extraction, the content of active substances is detected, and the dissolution rate in acid is calculated according to the following formula, and the result is shown in table 2.

Dissolution in acid (%) ═ active substance release amount/total active substance amount × 100%.

Table 2 dissolution in acid: unit (%)

(2) Release amount in buffer: the release amount in buffer solution of the coated products of the above examples and comparative examples was measured by reference to the release rate measurement method (0931 part of the national veterinary pharmacopoeia 2015 edition), the acid solution in each dissolution cup was discarded, 900mL of phosphate buffer solution (ph6.86) at 37 ℃. + -. 0.5 ℃ was immediately added at 50r/min, the operation was continued for 4.0h, 1mL of solution was taken at a predetermined sampling point, the corresponding volume was filled after each taking, the filter was filtered into a 15mL centrifuge tube, the centrifuge tube was sealed with a cover, and the product was stored at 4 ℃ for further use. The collected sample is added with methanol or ethyl acetate with 1-3 times volume for extraction, the content of the active substance is detected, the dissolution rate in the buffer solution is calculated according to the following formula, and the result is shown in table 3.

Dissolution rate (%) in acid, active substance release amount/remaining amount of active substance × 100%;

wherein the remaining amount of active substance refers to the amount of active substance remaining after release from the acid.

Table 3 dissolution in buffer: unit (%)

Note: calculation of amount released in buffer

Experiments show that the coated additive prepared by the method has the gastric-passing rate of over 84 percent at most and the small intestine release rate of over 90 percent at most.

The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.