Stomach-passing acid-resistant intestinal slow-release coating preparation as well as preparation method and application thereof

Abstract

The invention relates to the technical field of coating preparations, and particularly discloses a stomach-passing acid-resistant intestinal slow-release coating preparation as well as a preparation method and application thereof. The coating preparation is prepared from 15 to 30 parts of polyacrylic resin III, 10 to 20 parts of hydroxypropyl methyl cellulose phthalate, 10 to 20 parts of cellulose acetate phthalate, 20 to 50 parts of absolute ethyl alcohol, 5 to 20 parts of methanol and 15 to 30 parts of acetone. Mixing polyacrylic resin III with absolute ethyl alcohol to form a swelling substance; mixing the hydroxypropyl methyl cellulose with the phthalate and a mixture of methanol and acetone to form a swelled substance; mixing cellulose acetate phthalate with acetone to form a swelling substance; and uniformly mixing the three swelling substances to obtain the stomach-passing acid-resistant intestinal slow-release coating preparation. The prepared coating preparation has the advantages of good coating effect, good stomach passing effect and high small intestine release rate, the mechanical parameters of the obtained coating film are reasonable, and the bridging phenomenon of the coating particles is avoided.

Description

Technical Field

[0001] The present invention relates to the technical field of coating preparations, in particular to a gastric acid-resistant intestinal sustained-release coating preparation and a preparation method and application thereof. Background Art

[0002] Film coating involves evenly applying a relatively stable polymer coating to the surface of a solid pharmaceutical preparation via spraying, forming a plastic film several microns thick. Acid-resistant intestinal sustained-release coatings are suitable for drugs that disintegrate in the intestines. The material must remain stable in digestive fluids such as gastric juice (pH 2-4) while rapidly releasing the drug in digestive fluids such as the small intestine (pH 6-8). This effectively prevents release in the stomach and other areas without affecting dissolution time in the small intestine.

[0003] At present, various acid-resistant coating premixes mainly include fat coating materials and macromolecular polymer coating materials. Fat coating materials do not have a good gastric protection effect, so a large amount of coating materials needs to be used, and the general amount should be greater than 30% to have a certain gastric effect. Commonly used macromolecular polymer coating materials include polyacrylic acid resin. Due to its alcohol-soluble properties, a large amount of ethanol (the amount of ethanol is much greater than the amount of polyacrylic acid resin) must be used to dissolve it during use. Moreover, the components are single and cannot be well sustained-released in the intestine after passing through gastric acid. This will increase the risk in the production process and waste a lot of ethanol.

[0004] In view of this, it is urgent to develop a coating preparation with low cost, good gastric protection effect and sustained release in the intestine. Summary of the Invention

[0005] In order to improve the gastric protection effect and the sustained-release effect in the intestine of the coating preparation, the present application provides a gastric acid-resistant intestinal sustained-release coating preparation and its preparation method and application.

[0006] In the first aspect, the present application provides a gastric acid-resistant intestinal sustained-release coating preparation, which adopts the following technical solution:

[0007] A gastric acid-resistant intestinal sustained-release coating preparation comprises the following raw materials in parts by weight: 15-30 parts of polyacrylic resin III, 10-20 parts of hydroxypropyl methylcellulose phthalate, 10-20 parts of cellulose acetate phthalate, 20-50 parts of anhydrous ethanol, 5-20 parts of methanol, and 15-30 parts of acetone.

[0008] By adopting the above technical solution, polyacrylic acid resin III, when mixed with anhydrous ethanol, can fully absorb the ethanol and swell, forming a polyacrylic acid resin III swellable product. Hydroxypropyl methylcellulose phthalate, when mixed with methanol and acetone, can form a hydroxypropyl methylcellulose phthalate swellable product. Cellulose acetate phthalate, when mixed with acetone, can form a cellulose acetate phthalate swellable product. The three swellable products are then evenly mixed to produce a liquid dispersion for a gastric acid-resistant intestinal sustained-release coating. This liquid dispersion can be directly used for fluidized bed coating or spray coating without the need for additional granulation or drying steps. Since polyacrylic acid resin III is insoluble in gastric fluid (pH 1-3), it ionizes and dissolves at intestinal pH (≥5.5). The solubility threshold of hydroxypropyl methylcellulose phthalate is pH 5.0-5.5, forming a pH-responsive gradient with polyacrylic acid resin III, which helps enhance membrane integrity in the presence of gastric acid. Cellulose acetate phthalate dissolves at pH ≥6.0, serving as a third line of defense against gastric acid penetration. Acetone acts as a co-solvent to promote the compatibility of hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate, and reduce local defects caused by phase separation. Therefore, the present application adopts the above-mentioned ratio of polyacrylic resin III, hydroxypropyl methylcellulose phthalate, and cellulose acetate phthalate to fully mix, dissolve and disperse, and the prepared coating preparation has a good coating effect, good gastric effect, high small intestine release rate, reasonable mechanical parameters of the obtained coating film, and no bridging phenomenon occurs in the coated particles. Moreover, the prices of polyacrylic resin III, hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate are relatively low. The combination of the three can reduce the use of a single high-priced material. Moreover, no large amount of organic reagents or water is required for dissolution, and the sustained release effect in the intestine after gastric passage is very good. Anhydrous ethanol, methanol and acetone are all common low-boiling point solvents, which are easy to volatilize and have mature recovery processes, making the gastric acid-resistant intestinal sustained-release coating preparation low-cost, short production cycle, easy to implement GMP standard management, and suitable for large-scale production.

[0009] In a specific embodiment, the invention further comprises 5-15 parts of other excipients, wherein the other excipients include any one or more of zinc stearate, magnesium stearate, calcium oxide, talc, and polyethylene glycol.

[0010] By adopting the above technical solution and adding the above excipients, the mechanical parameters of the coating film prepared from the gastric acid-resistant intestinal sustained-release coating preparation can be adjusted, so that the coating film is evenly colored, smooth and beautiful.

[0011] In a second aspect, the present application provides a method for preparing a gastric acid-resistant intestinal sustained-release coating preparation, which adopts the following technical solution:

[0012] A method for preparing a gastric acid-resistant intestinal sustained-release coating preparation comprises the following steps:

[0013] Mixing polyacrylic acid resin III with anhydrous ethanol in proportion to obtain a polyacrylic acid resin III swollen product;

[0014] Divide acetone into two parts, mix methanol with the first part of acetone, add hydroxypropyl methylcellulose phthalate, and mix well to obtain HPCP swelling material;

[0015] mixing the cellulose acetate phthalate with a second portion of acetone to obtain a cellulose acetate phthalate swellable product;

[0016] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are uniformly mixed to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0017] By adopting the above technical solution, the gastric coating preparation obtained has a fine finished product, various components are interconnected, the viscosity is moderate, and the film-forming property is good. When used to coat solid materials, the coating layer of the resulting finished product is firmly bonded to the core of the solid material, tightly wrapped, with uniform thickness, uniform coloring, smooth and beautiful appearance, and can reduce the occurrence of surface wear, film edge cracking, peeling or adhesion of the coated product. At the same time, the coating film has good density, reducing the generation of bubbles, surface roughness and wrinkling, and can better meet the various needs of solid material film coating.

[0018] In a third aspect, the present application provides an application of a gastric acid-resistant intestinal sustained-release coating preparation as an animal feed additive, which adopts the following technical solution:

[0019] An application of a gastric acid-resistant intestinal sustained-release coating preparation, wherein the gastric acid-resistant intestinal sustained-release coating preparation is applied as an animal feed additive.

[0020] In a specific embodiment, the animal feed additive includes a zearalenone-degrading enzyme.

[0021] By adopting the above technical scheme, the coating preparation of the present application can be used in animal feed additives, especially for coating additives such as zearalenone-degrading enzymes that degrade zearalenone toxins in large quantities in the intestine, and has a good intestinal sustained-release effect.

[0022] In summary, this application has the following beneficial effects:

[0023] 1. The present application adopts the above-mentioned ratio of polyacrylic resin III, hydroxypropyl methylcellulose phthalate, and cellulose acetate phthalate to fully mix, dissolve and disperse, and the prepared coating preparation has a good coating effect, a good gastric effect, a high small intestine release rate, and the mechanical parameters of the obtained coating film are reasonable, and the coated particles will not have a bridging phenomenon.

[0024] 2. The method of the present application produces a fine gastric coating preparation, with various ingredients interconnected, moderate viscosity, good film-forming properties, uniform coloring, smooth and beautiful appearance, and can reduce the occurrence of surface wear, film edge cracking, peeling or adhesion of the coated product.

[0025] 3. The coating preparation of the present application can be used in animal feed additives, especially for coating additives such as zearalenone-degrading enzymes that degrade zearalenone toxins in large quantities in the intestine, and has a good intestinal sustained-release effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a picture of the dissolution effect of the sample of Application Example 4 of this application in a PBS buffer solution with a pH of 3.0;

[0027] Figure 2 This is a picture of the dissolution effect of the sample of Application Example 4 of this application in a PBS buffer solution with a pH of 6.5. DETAILED DESCRIPTION

[0028] It is important to note that in the following examples and comparative examples, where specific conditions are not specified, the experiments were conducted under conventional conditions or those recommended by the manufacturer. Unless otherwise specified, all instruments, materials, and reagents used in the following examples were commercially available. Polyacrylic acid resin III was purchased from Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd. Hydroxypropyl methylcellulose phthalate (HPCP) was purchased from Luofu Pharmaceutical Technology (Shanghai) Co., Ltd. Cellulose acetate phthalate (CAP) was purchased from Luofu Pharmaceutical Technology (Shanghai) Co., Ltd.

[0029] The present application is further described in detail below with reference to the following examples and comparative examples.

[0030] Example

[0031] Example 1

[0032] This embodiment provides a gastric acid-resistant intestinal sustained-release coating preparation, which includes the following raw materials: 20 kg of polyacrylic resin III, 10 kg of hydroxypropyl methylcellulose phthalate, 10 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 5 kg of methanol, and 15 kg of acetone.

[0033] The preparation method of the gastric acid-resistant intestinal sustained-release coating preparation comprises the following steps:

[0034] According to the proportion, polyacrylic acid resin III is added to anhydrous ethanol and stirred evenly to obtain a polyacrylic acid resin III swollen product.

[0035] Acetone was divided into a first portion of 5 kg acetone and a second portion of 10 kg acetone. Methanol was mixed with the first portion of acetone, and hydroxypropyl methylcellulose phthalate was added and mixed uniformly to obtain an HPCP swellable product.

[0036] The cellulose acetate phthalate is mixed evenly with the second portion of acetone to obtain a cellulose acetate phthalate swellable product.

[0037] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are uniformly mixed to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0038] Example 2

[0039] The only difference between this embodiment and embodiment 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 15 kg of polyacrylic resin III, 10 kg of hydroxypropyl methylcellulose phthalate, 10 kg of cellulose acetate phthalate, 15 kg of anhydrous ethanol, 5 kg of methanol, and 15 kg of acetone.

[0040] Example 3

[0041] The only difference between this embodiment and embodiment 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 30 kg of polyacrylic acid resin III, 20 kg of hydroxypropyl methylcellulose phthalate, 20 kg of cellulose acetate phthalate, 30 kg of anhydrous ethanol, 10 kg of methanol, and 30 kg of acetone.

[0042] Example 4

[0043] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 10 kg of hydroxypropyl methylcellulose phthalate, 10 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 5 kg of methanol, 15 kg of acetone, 3 kg of zinc stearate, 3 kg of polyethylene glycol, and 3 kg of talc.

[0044] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0045] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are mixed evenly, and then zinc stearate, polyethylene glycol and talc are added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0046] Example 5

[0047] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 10 kg of hydroxypropyl methylcellulose phthalate, 10 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 5 kg of methanol, 15 kg of acetone, 3 kg of zinc stearate, and 3 kg of polyethylene glycol.

[0048] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0049] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are mixed evenly, and then zinc stearate and polyethylene glycol are added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0050] Example 6

[0051] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 10 kg of hydroxypropyl methylcellulose phthalate, 10 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 5 kg of methanol, 15 kg of acetone, and 3 kg of zinc stearate.

[0052] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0053] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are mixed evenly, and then zinc stearate is added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0054] Example 7

[0055] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 15 kg of hydroxypropyl methylcellulose phthalate, 15 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 7.5 kg of methanol, 22.5 kg of acetone, 3 kg of zinc stearate, 3 kg of polyethylene glycol, and 3 kg of talc.

[0056] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0057] According to the proportion, polyacrylic acid resin III is added to anhydrous ethanol and stirred evenly to obtain a polyacrylic acid resin III swollen product.

[0058] Acetone was divided into a first portion of 7.5 kg acetone and a second portion of 15 kg acetone. Methanol was mixed with the first portion of acetone, and hydroxypropyl methylcellulose phthalate was added and mixed uniformly to obtain an HPCP swellable product.

[0059] The cellulose acetate phthalate is mixed evenly with the second portion of acetone to obtain a cellulose acetate phthalate swellable product. The polyacrylic acid resin III swellable product, the HPCP swellable product, and the cellulose acetate phthalate swellable product are mixed evenly, and then zinc stearate, polyethylene glycol, and talc are added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0060] Example 8

[0061] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 10 kg of hydroxypropyl methylcellulose phthalate, 15 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 5 kg of methanol, 20 kg of acetone, 3 kg of zinc stearate, 3 kg of polyethylene glycol, and 3 kg of talc.

[0062] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0063] According to the proportion, polyacrylic acid resin III is added to anhydrous ethanol and stirred evenly to obtain a polyacrylic acid resin III swollen product.

[0064] Acetone was divided into a first portion of 5 kg acetone and a second portion of 15 kg acetone. Methanol was mixed with the first portion of acetone, and hydroxypropyl methylcellulose phthalate was added and mixed uniformly to obtain an HPCP swellable product.

[0065] The cellulose acetate phthalate is mixed evenly with the second portion of acetone to obtain a cellulose acetate phthalate swellable product.

[0066] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are mixed evenly, and then zinc stearate, polyethylene glycol and talc are added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0067] Example 9

[0068] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 15 kg of hydroxypropyl methylcellulose phthalate, 10 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 7.5 kg of methanol, 17.5 kg of acetone, 3 kg of zinc stearate, 3 kg of polyethylene glycol, and 3 kg of talc.

[0069] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0070] According to the proportion, polyacrylic acid resin III is added to anhydrous ethanol and stirred evenly to obtain a polyacrylic acid resin III swollen product.

[0071] Acetone was divided into a first portion of 7.5 kg acetone and a second portion of 10 kg acetone. Methanol was mixed with the first portion of acetone, and hydroxypropyl methylcellulose phthalate was added and mixed uniformly to obtain an HPCP swellable product.

[0072] The cellulose acetate phthalate is mixed evenly with the second portion of acetone to obtain a cellulose acetate phthalate swellable product.

[0073] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are mixed evenly, and then zinc stearate, polyethylene glycol and talc are added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0074] Example 10

[0075] The only difference between this embodiment and Example 1 is that the gastric acid-resistant intestinal sustained-release coating preparation includes the following raw materials: 20 kg of polyacrylic resin III, 20 kg of hydroxypropyl methylcellulose phthalate, 20 kg of cellulose acetate phthalate, 20 kg of anhydrous ethanol, 10 kg of methanol, 20 kg of acetone, 3 kg of zinc stearate, 3 kg of polyethylene glycol, and 3 kg of talc.

[0076] In the preparation method of the gastric acid-resistant intestinal sustained-release coating preparation:

[0077] According to the proportion, polyacrylic acid resin III is added to anhydrous ethanol and stirred evenly to obtain a polyacrylic acid resin III swollen product.

[0078] Acetone was divided into a first portion of 10 kg acetone and a second portion of 10 kg acetone. Methanol was mixed with the first portion of acetone, and hydroxypropyl methylcellulose phthalate was added and mixed uniformly to obtain an HPCP swellable product.

[0079] The cellulose acetate phthalate is mixed evenly with the second portion of acetone to obtain a cellulose acetate phthalate swellable product.

[0080] The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are mixed evenly, and then zinc stearate, polyethylene glycol and talc are added and stirred evenly to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

[0081] Comparative Example

[0082] Comparative Example 1

[0083] The only difference between this comparative example and Example 1 is that in the raw materials and preparation method of the gastric acid-resistant intestinal sustained-release coating preparation, an equal amount of polyacrylic acid resin III is used to replace hydroxypropyl methylcellulose phthalate.

[0084] Comparative Example 2

[0085] The only difference between this comparative example and Example 1 is that an equal amount of polyacrylic acid resin III is used to replace cellulose acetate phthalate in the raw materials and preparation method of the gastric acid-resistant intestinal sustained-release coating preparation.

[0086] Comparative Example 3

[0087] The only difference between this comparative example and Example 1 is that, in the method for preparing the acid-resistant intestinal sustained-release coating preparation, anhydrous ethanol, acetone and methanol are mixed in proportion, and then polyacrylic acid resin III, hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate are added and mixed evenly to obtain the acid-resistant intestinal sustained-release coating preparation.

[0088] Comparative Example 4

[0089] The only difference between this comparative example and Example 1 is that in the preparation method of the acid-resistant intestinal sustained-release coating preparation, anhydrous ethanol, acetone and methanol are mixed in proportion, and then polyacrylic acid resin III, hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate are added in sequence. After each addition of the raw materials, they are mixed evenly before adding the next raw material to obtain the acid-resistant intestinal sustained-release coating preparation.

[0090] Performance testing

[0091] For Examples 1-10 and Comparative Examples 1-4, the following performance tests were performed:

[0092] The gastric acid-resistant intestinal sustained-release coating preparations prepared in each example and comparative example were respectively applied to an animal feed additive, wherein the animal feed additive was a zearalenone-degrading enzyme, and the method specifically comprised the following steps:

[0093] Core material preparation method: ① Select zearalenone-degrading enzyme powder that has passed quality inspection and can be sieved to ensure that there are no foreign matter in it; ② For each batch of 1kg of zearalenone-degrading enzyme powder, add 1.5kg of starch for preliminary mixing, add water to the material until the moisture content is 12-15%, and mix for 20 minutes; ③ Shot blast with a 1.5mm swing particle machine screen to make the particles smooth and compact; then sieve and select 16-30 mesh particles for core material, with a yield of ≥90%.

[0094] Using a fluidized bed coater, the core material is spray-coated with the gastric acid-resistant, intestinal sustained-release coating formulation. After coating, the coating is cooled to room temperature and sieved to prevent sticking. The product is sieved through a 10-30 mesh screen to obtain a gastric-coated product. The gastric-coated products obtained using the gastric acid-resistant, intestinal sustained-release coating formulations of Examples 1-10 are referred to as Application Examples 1-10. The gastric-coated products obtained using the gastric acid-resistant, intestinal sustained-release coating formulations of Comparative Examples 1-4 are referred to as Comparative Application Examples 1-4.

[0095] The zeatinase system degradation enzyme activity content in the gastric coated products of Application Examples 1-10 and Comparative Application Examples 1-4 was determined by HPLC, which was recorded as the effective zeatinase enone degradation enzyme activity of the product. The test results are shown in Table 1.

[0096] The in vitro method was used to determine the gastric permeability and small intestinal enzyme activity of the gastric coating products of Application Examples 1-10 and Comparative Application Examples 1-4. The operation was as follows:

[0097] 1 g of each of the gastric-coated products from Application Examples 1-10 and Comparative Application Examples 1-4 was placed in 80 mL of PBS buffer solution (pH 3.0). The mixture was shaken at 37°C and 200 rpm for 2 hours. The pH was then adjusted to 6.5 to allow for complete dissolution. The mixture was then reacted with zearalenone toxin, and the zearalenone enzyme activity was determined by HPLC. This was recorded as the enzyme activity after acid-resistant treatment. The test results are shown in Table 1.

[0098] The enzyme activity after artificial gastric passage was calculated from the peracid enzyme loss rate calculated as: (product effective zearalenone-degrading enzyme activity - enzyme activity after acid-resistant treatment) / product effective zearalenone-degrading enzyme activity × 100%. The peracid enzyme loss rate was used to calculate the enzyme activity after artificial gastric passage. The test results are shown in Table 1.

[0099] Table 1

[0100]

[0101]

[0102] Combining Application Example 1 with Comparative Application Examples 1-4 and Table 1, it can be seen that compared to Application Example 1, the effective zearalenone-degrading enzyme activity of the products of Comparative Application Examples 1-4 did not change much, but after acid-resistant treatment, the enzyme activity was significantly reduced, and the peracid enzyme activity loss rate was significantly increased. This indicates that the raw material ratio and preparation method of Example 1 help improve the stability of the coating preparation in a gastric acid-like environment with a pH of 3.0.

[0103] Combined with application examples 1-10 and Table 1 and Figure 1-2 As can be seen, the effective zearalenone-degrading enzyme activity of the products in Application Examples 1-10 did not change much, with the peracidase activity loss rate all being less than 10%. Dissolution was poor in a PBS buffer solution with a pH of 3.0, but excellent in a PBS buffer solution with a pH of 6.5. Among them, the peracidase activity loss rate in Application Example 2 was the highest, reaching 9.92%, while the peracidase activity loss rate in Application Example 4 was the lowest, at only 0.2%.

[0104] This demonstrates that changes in the composition of the coating formulations of this application have little impact on the effective enzyme activity of the 2-hour gastric transgastric coated product. The coating formulations obtained using the raw material ratios and preparation methods of Examples 1-10, when used in animal feed additives, exhibit a strong bond between the coating layer and the nutrient core, providing a tight coating, uniform thickness, even coloration, and a smooth, aesthetically pleasing appearance, effectively meeting the diverse coating formulation requirements of zearalenone-degrading enzymes.

[0105] However, the ratio of polyacrylic acid resin III, hydroxypropyl methylcellulose phthalate, and cellulose acetate phthalate in the coating formulation affects the stability of the gastric-coated product in a gastric fluid-like (pH 3.0) environment. Specifically, with the raw material ratio in Example 2, the gastric-coated product experienced the greatest loss of enzyme activity after treatment with a pH 3.0 PBS buffer. With the raw material ratio in Example 4, the enzyme activity loss was minimal.

[0106] Moreover, in combination with Application Examples 1-10 and Table 1, the present applicant found that when preparing the coating solution of the coating preparation, the addition of zinc stearate, polyethylene glycol, and talc mainly affects the viscosity and fluidity of the coating solution, and has little effect on the enzyme activity of the gastric coated product after treatment with PBS buffer at pH 3.0. At the same time, the present applicant found that only a small amount of other excipients is added to adjust the mechanical parameters of the coating film prepared by the acid-resistant coating preparation, so that the coating film is evenly colored, smooth and beautiful.

[0107] From the comparison of Application Examples 5-8 with Table 1, it can be seen that the dosage ratio of polyacrylic acid resin III, hydroxypropyl methylcellulose phthalate, and cellulose acetate phthalate in the coating preparation will affect the enzyme activity of the acid-resistant gastric-coated product after treatment with PBS buffer at pH 3.0. Taking into account the economic cost, the weight ratio of polyacrylic acid resin III: hydroxypropyl methylcellulose phthalate: cellulose acetate phthalate in this application is preferably 2:1:1.

[0108] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A gastric acid-resistant intestinal sustained-release coating preparation, characterized in that: The invention comprises the following raw materials in parts by weight: 15-30 parts of polyacrylic resin III, 10-20 parts of hydroxypropyl methylcellulose phthalate, 10-20 parts of cellulose acetate phthalate, 20-50 parts of anhydrous ethanol, 5-20 parts of methanol and 15-30 parts of acetone.

2. The gastric acid-resistant intestinal sustained-release coating preparation according to claim 1, characterized in that: The invention also includes 5-15 parts of other auxiliary materials, which include any one or more of zinc stearate, magnesium stearate, calcium oxide, talc, and polyethylene glycol.

3. A method for preparing the gastric acid-resistant intestinal sustained-release coating preparation according to any one of claims 1 to 2, characterized in that: The steps include: Mixing polyacrylic acid resin III with anhydrous ethanol in proportion to obtain a polyacrylic acid resin III swollen product; Divide acetone into two parts, mix methanol with the first part of acetone, add hydroxypropyl methylcellulose phthalate, and mix well to obtain HPCP swelling material; mixing the cellulose acetate phthalate with a second portion of acetone to obtain a cellulose acetate phthalate swellable product; The polyacrylic acid resin III swollen product, the HPCP swollen product and the cellulose acetate phthalate swollen product are uniformly mixed to obtain a gastric acid-resistant intestinal sustained-release coating preparation.

4. An application of the gastric acid-resistant intestinal sustained-release coating preparation according to any one of claims 1 to 2, characterized in that: The gastric acid-resistant intestinal sustained-release coating preparation is used as an animal feed additive.

5. The gastric acid-resistant intestinal sustained-release coating preparation according to claim 4, characterized in that: The animal feed additive includes a zearalenone-degrading enzyme.

Images