Capsule wall material for improving stability of ursodesoxycholic acid and preparation method thereof

Abstract

The invention relates to a capsule wall material for improving the stability of ursodesoxycholic acid and a preparation method thereof, and belongs to the technical field of preparation of capsule wall materials, and the preparation method specifically comprises the following steps: performing acylation modification on soybean protein, and then preparing a damp-proof layer material from the modified soybean protein and an enteric-coated material; the preparation method comprises the following steps: mixing gelatin, carboxymethylcellulose, glycerol, polyvinylpyrrolidone, saccharides and metal salt, adding water, stirring to form a capsule base material, and forming a hollow capsule shell by a mold; the moisture-proof layer material is uniformly sprayed on the surface of the capsule shell, and is dried and cured at low temperature to form the composite wall material with shading property and high mechanical strength. And a moisture-proof layer material prepared by mixing modified soybean protein and an enteric-coated material is introduced, so that erosion of water to medicines in the capsule is prevented, and the stability and the validity period of the medicines are further guaranteed. The prepared capsule wall material can effectively protect ursodesoxycholic acid and prevent ursodesoxycholic acid from being degraded or inactivated in the storage and use processes, so that the stability and curative effect of the medicine are improved.

Description

Technical Field

[0001] The present application relates to the technical field of capsule wall material preparation, and more specifically, to a capsule wall material for improving the stability of ursodeoxycholic acid and a preparation method thereof. Background Art

[0002] In the field of pharmaceutical preparations, ursodeoxycholic acid is a core drug for the treatment of cholestatic liver disease, cholesterol stones and other diseases. The stability of its oral preparation directly affects the efficacy and safety, and its stability and shelf life are crucial to the efficacy of the drug. However, there are a series of problems and deficiencies in the existing capsule wall material preparation technology, which seriously restricts the stability and efficacy of ursodeoxycholic acid drugs.

[0003] Traditional hard capsule shells mostly use gelatin or hydroxypropyl methylcellulose (HPMC) as the base material, but gelatin easily absorbs moisture and softens. Although HPMC has a certain degree of moisture resistance, it is still difficult to block moisture penetration in a high humidity environment. Although some soft capsules are wrapped in vegetable oil to improve stability, hard capsules lack a similar protection mechanism, causing ursodeoxycholic acid to easily absorb moisture and agglomerate or hydrolyze and become ineffective during storage. In addition, conventional sunscreens (such as titanium dioxide) only block light through physical shielding and cannot synergistically improve moisture resistance; if their usage is increased, the flexibility of the capsule shell will be reduced, resulting in increased brittleness.

[0004] In addition, in the prior art, the composite of polysaccharides and proteins mostly relies on physical mixing, and chemical cross-linking is not used to enhance the interfacial bonding strength. For example, unmodified natural soy protein is easy to combine with water molecules due to its high hydroxyl content, resulting in the failure of the moisture barrier; while over-acylation improves hydrophobicity, it will destroy the activity of the amino group and hinder the covalent cross-linking with the polysaccharide.

[0005] In summary, existing capsule wall materials have significant shortcomings in terms of moisture resistance, light shielding, mechanical strength and process adaptability, and a solution that takes into account multiple performances and has a mild process is urgently needed. Based on this, the present application provides a capsule wall material that improves the stability of ursodeoxycholic acid and a preparation method thereof. Summary of the invention

[0006] In order to solve the problems raised in the background technology, the present application provides a capsule wall material for improving the stability of ursodeoxycholic acid and a preparation method thereof.

[0007] This application adopts the following technical solutions: A method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid comprises the following steps: S1. Modifying soybean protein with an acylating agent to obtain modified soybean protein; mixing the modified soybean protein and an enteric material in deionized water to obtain a moisture-proof layer material; S2, mixing gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt to obtain a capsule base; adding deionized water to the capsule base, raising the system temperature to 40-50° C., stirring and using a mold to prepare a hollow capsule shell; S3, using a spray coating machine to spray the moisture-proof layer material obtained in step S1 onto the surface of the hollow capsule shell obtained in step S2, and then drying and curing the hollow capsule shell to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

[0008] Furthermore, a method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid comprises the following steps: S1. Modifying soybean protein with an acylating agent to obtain modified soybean protein; mixing the modified soybean protein and the enteric material in deionized water, setting the mass volume ratio to (8-12) g:100 mL, and stirring evenly to obtain a moisture-proof layer material; S2, mixing gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt to obtain a capsule base; adding deionized water to the capsule base, the mass ratio of the capsule base to the deionized water is 10:(3-4), raising the system temperature to 40-50° C., stirring for 20-30 minutes and then using a hollow capsule shell mold to prepare a hollow capsule shell; S3. Use a spray coating machine to spray the moisture-proof layer material obtained in step S1 onto the surface of the hollow capsule shell obtained in step S2. The hollow capsule shell does not need to be dried before spraying. After spraying, the hollow capsule shell is dried and cured to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

[0009] Furthermore, in step S1, the modified soy protein is prepared by the following steps: Add soybean protein to phosphate buffer and stir for 10-20 minutes. Then add acylation reagent to the system and increase the reaction temperature to 30-40°C. During the process, maintain the pH value of the system at 8.0-9.0. After reacting for 2-4 hours, naturally return to room temperature. Adjust the pH value of the system to 4.5-5.0. After dialyzing, centrifuge, collect the precipitate and freeze-dry to obtain modified soybean protein.

[0010] Furthermore, in step S1, the modified soy protein is prepared by the following steps: The soy protein was added to a phosphate buffer with a pH value of 8.0-9.0 and the concentration was set to 5-10% (w / v). The system was then stirred at 30-90 rpm for 10-20 minutes at room temperature. An acylation agent was then added to the system and the reaction temperature was increased to 30-40°C. The pH value of the system was maintained at 8.0-9.0 during the process. After reacting for 2-4 hours, the system was naturally restored to room temperature. A 0.1 mol / L HCl solution was used to adjust the pH value of the system to 4.5-5.0. The system was dialyzed at 4°C for 48 hours and then centrifuged at 10000×g for 10-20 minutes. The precipitate was collected and freeze-dried to obtain modified soy protein.

[0011] In the above reaction process, the soy protein is treated with an acylating agent. By controlling the reaction environment to be alkaline, the deprotonation process of the hydroxyl group is promoted, the nucleophilicity of the hydroxyl group is enhanced, and the nucleophilic substitution reaction is promoted. Subsequently, the acyl group on the acylating agent and the hydroxyl group on the soy protein molecule are combined through an acylation reaction to prepare a modified soy protein.

[0012] Furthermore, the acylating agent used is at least one of acetic anhydride, succinic anhydride, maleic anhydride, acetyl chloride and benzoyl chloride.

[0013] Furthermore, the mass ratio of soybean protein to acylating agent is (3-5) g:(1-1.2) g.

[0014] Furthermore, in step S2, the mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt is (50-60):(1-3):(10-15):(2-4):(5-10):(0.01-0.05).

[0015] Furthermore, in step S2, the sugar is at least one of pentose and aldose.

[0016] Preferably, the pentose is at least one of arabinose and xylose.

[0017] Preferably, the aldose is glucose.

[0018] Furthermore, in step S2, the metal salt is at least one of an iron salt and a copper salt.

[0019] Furthermore, in step S3, during the spraying operation, the air inlet temperature is set to 60-70°C, the air outlet temperature is set to 40-60°C, the atomization pressure is set to 0.8-1.5 bar, the spray gun distance is set to 20-30 cm, the spray rate is set to 5-10 mL / min, and the spraying time is set to 15-20 minutes.

[0020] Furthermore, in step S3, the temperature at which the hollow capsule shell is dried and cured after spraying is 20-40°C.

[0021] A method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid to obtain a capsule wall material.

[0022] In summary, this application has the following beneficial effects: 1. In the technical solution of the present invention, in the process of preparing the capsule wall material, the moisture-proof layer material prepared by mixing modified soybean protein and enteric material is introduced, which significantly enhances the moisture-proof performance of the capsule. This helps to prevent moisture from eroding the drug inside the capsule, and further ensures the stability and shelf life of the drug. Through a specific preparation method, the obtained capsule wall material can effectively protect ursodeoxycholic acid and prevent it from being degraded or inactivated during storage and use, thereby improving the stability and efficacy of the drug.

[0023] 2. In the technical solution of the present invention, by adding metal salt ions to the hollow capsule shell and selecting suitable polysaccharides, the Maillard reaction in the thermal spraying process of the preparation process is promoted, the conventional high temperature means are avoided to promote the Maillard reaction, and the shape of the hollow capsule shell is maintained while promoting uniform coverage of the moisture-proof layer material. By regulating the acylation modification of soybean protein, while retaining its hydrophobic properties, the amino group thereon is retained, which can react with the polysaccharide on the hollow capsule shell to form a melanin-like brown substance, improve the bonding stability between the hollow capsule shell and the moisture-proof layer, and can give the capsule wall material good light-shielding properties, further improving the storage stability of ursodeoxycholic acid. At the same time, metal ions stabilize the polysaccharide-protein network through chelation, further improving the mechanical strength of the capsule wall material. DETAILED DESCRIPTION

[0024] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] The raw materials involved in the specific implementation of this application are of analytical grade, and: The mold used is a size 0 capsule shell mold; The enteric material used was the commercially available Eudragit-L100 product; The purity of the ursodeoxycholic acid raw material used is 99.0%, and the ignition residue is ≤0.1%.

[0026] Example 1 A method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid comprises the following steps: S1. Modifying soybean protein with an acylating agent to obtain modified soybean protein; mixing the modified soybean protein and the enteric material in deionized water, setting the mass volume ratio to 8 g:100 mL, and stirring evenly to obtain a moisture-proof layer material; Wherein, the modified soy protein is specifically prepared by the following steps: Soy protein was added to a phosphate buffer with a pH value of 8.0, and the concentration was set to 5% (w / v). The system was then stirred at 30 rpm for 10 minutes at room temperature, and then an acylating agent was added to the system and the reaction temperature was raised to 30°C. The pH value of the system was maintained at 8.0 during the process. After reacting for 2 hours, the system was naturally restored to room temperature. A 0.1 mol / L HCl solution was used to adjust the pH value of the system to 4.5. The system was dialyzed at 4°C for 48 hours and then centrifuged at 10000×g for 15 minutes. The precipitate was collected and freeze-dried to obtain modified soybean protein. The mass ratio of soybean protein to acylating agent was 3g:1g, and the acylating agent used was acetic anhydride.

[0027] S2, gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone and metal salt are mixed to obtain a capsule base; deionized water is added to the capsule base, the mass ratio of the capsule base to the deionized water is 10:3, the system temperature is increased to 40°C, and after stirring for 20 minutes, the mixture is injected into a hollow capsule shell mold, and a rotary molding machine is used to form a cylindrical shell in the mold. After cooling to room temperature, the excess edge portion is cut to prepare a hollow capsule shell; Among them, the mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt is 50:1:10:2:5:0.01.

[0028] The sugar is glucose.

[0029] The metal salt is copper sulfate.

[0030] S3, using a spray coating machine to spray the moisture-proof layer material obtained in step S1 on the surface of the hollow capsule shell obtained in step S2, the hollow capsule shell does not need to be dried before spraying, and after spraying, the hollow capsule shell is dried and cured at 20° C., thereby obtaining a capsule wall material that improves the stability of ursodeoxycholic acid; During the spraying operation, the inlet air temperature was set to 60°C, the outlet air temperature was set to 40°C, the atomization pressure was set to 0.8 bar, the spray gun distance was set to 20 cm, the spray rate was set to 5 mL / min, and the spraying time was set to 15 minutes.

[0031] Example 2 A method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid comprises the following steps: S1. Modifying soybean protein with an acylating agent to obtain modified soybean protein; mixing the modified soybean protein and the enteric material in deionized water, setting the mass volume ratio to 10 g:100 mL, and stirring evenly to obtain a moisture-proof layer material; Wherein, the modified soy protein is specifically prepared by the following steps: Soy protein was added to a phosphate buffer with a pH value of 9.0, and the concentration was set to 8% (w / v). The system was then stirred at 60 rpm for 20 minutes at room temperature, and then an acylating agent was added to the system and the reaction temperature was raised to 40°C. The pH value of the system was maintained at 9.0 during the process. After 3 hours of reaction, the system was naturally restored to room temperature. A 0.1 mol / L HCl solution was used to adjust the pH value of the system to 5.0. The system was dialyzed at 4°C for 48 hours and then centrifuged at 10000×g for 15 minutes. The precipitate was collected and freeze-dried to obtain modified soybean protein. The mass ratio of soybean protein to acylating agent was 4g:1.1g, and the acylating agent used was acetic anhydride.

[0032] S2, gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone and metal salt are mixed to obtain a capsule base; deionized water is added to the capsule base, the mass ratio of the capsule base to deionized water is 10:3.5, the system temperature is increased to 45°C, and after stirring for 25 minutes, the mixture is injected into a hollow capsule shell mold, and a rotary molding machine is used to form a cylindrical shell in the mold. After cooling to room temperature, the excess edge portion is cut to prepare a hollow capsule shell; Among them, the mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt is 55:2:13:3:7:0.03.

[0033] The sugar is glucose.

[0034] The metal salt is copper sulfate.

[0035] S3, using a spray coating machine to spray the moisture-proof layer material obtained in step S1 on the surface of the hollow capsule shell obtained in step S2, the hollow capsule shell does not need to be dried before spraying, and after spraying, the hollow capsule shell is dried and cured at 30° C., thereby obtaining a capsule wall material that improves the stability of ursodeoxycholic acid; During the spraying operation, the inlet air temperature was set to 65°C, the outlet air temperature was set to 50°C, the atomization pressure was set to 1.2 bar, the spray gun distance was set to 25 cm, the spray rate was set to 8 mL / min, and the spraying time was set to 18 minutes.

[0036] Example 3 A method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid comprises the following steps: S1. Modifying soybean protein with an acylating agent to prepare modified soybean protein; mixing the modified soybean protein and the enteric material in deionized water, setting the mass volume ratio to 12 g:100 mL, and stirring evenly to prepare a moisture-proof layer material; Wherein, the modified soy protein is specifically prepared by the following steps: Soy protein was added to a phosphate buffer with a pH value of 9.0, and the concentration was set to 10% (w / v). The system was then stirred at 90 rpm for 20 minutes at room temperature, and then an acylating agent was added to the system and the reaction temperature was raised to 40°C. The pH value of the system was maintained at 9.0 during the process. After reacting for 4 hours, the system was naturally restored to room temperature. A 0.1 mol / L HCl solution was used to adjust the pH value of the system to 5.0. The system was dialyzed at 4°C for 48 hours and then centrifuged at 10000×g for 20 minutes. The precipitate was collected and freeze-dried to obtain modified soybean protein. The mass ratio of soybean protein to acylating agent was 5g:1.2g, and the acylating agent used was succinic anhydride.

[0037] S2, gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone and metal salt are mixed to obtain a capsule base; deionized water is added to the capsule base, the mass ratio of the capsule base to the deionized water is 10:4, the system temperature is increased to 50°C, and after stirring for 30 minutes, the mixture is injected into a hollow capsule shell mold, and a rotary molding machine is used to form a cylindrical shell in the mold. After cooling to room temperature, the excess edge portion is cut to prepare a hollow capsule shell; Among them, the mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt is 60:3:15:4:10:0.05.

[0038] The sugar is arabinose.

[0039] The metal salt is ferrous sulfate.

[0040] S3, using a spray coating machine to spray the moisture-proof layer material obtained in step S1 on the surface of the hollow capsule shell obtained in step S2, the hollow capsule shell does not need to be dried before spraying, and after spraying, the hollow capsule shell is dried and cured at 30° C., thereby obtaining a capsule wall material that improves the stability of ursodeoxycholic acid; During the spraying operation, the air inlet temperature was set to 70°C, the air outlet temperature was set to 60°C, the atomization pressure was set to 1.5 bar, the spray gun distance was set to 30 cm, the spray rate was set to 10 mL / min, and the spraying time was set to 20 minutes.

[0041] Comparative Example 1 The difference between this comparative example and Example 1 is that in step S2, the sugar used is mannose.

[0042] Comparative Example 2 The difference between this comparative example and Example 1 is that in step S1, soybean protein is used instead of modified soybean protein.

[0043] Comparative Example 3 The difference between this comparative example and Example 1 is that in step S1, the modified soybean protein is prepared by the following steps: Soy protein was added to deionized water, stirred at 30 rpm for 10 minutes at room temperature, 0.1 mol / L NaOH solution was used to adjust the pH value of the system to 7.5, then an acylating agent was added to the system and the reaction temperature was increased to 30°C, and the reaction was naturally restored to room temperature after 60 minutes, and 0.1 mol / L HCl solution was used to adjust the pH value of the system to neutral, and the system was dialyzed at 4°C for 48 hours to remove the residual acylating agent, and then freeze-dried to obtain modified soy protein. The amount of soy protein, deionized water and acylating agent used was 3g:20mL:1g.

[0044] Comparative Example 4 The difference between this comparative example and Example 1 is that in step S2, the metal salt used is magnesium sulfate.

[0045] Comparative Example 5 The difference between this comparative example and Example 1 is that in the spraying operation of step S3, the inlet air temperature is set to 80°C, the outlet air temperature is set to 40°C, the atomization pressure is set to 0.8 bar, the spray gun distance is set to 20 cm, the spray rate is set to 5 mL / min, and the spraying time is set to 30 minutes.

[0046] Performance Testing The performance of the capsule wall materials prepared in Examples 1-3 and Comparative Examples 1-5 of the present application is now tested.

[0047] Mechanical strength: The tensile strength of the capsules prepared in different groups was tested using a universal material testing machine. The tensile rate was set to 80 mm / min. Each sample was tested 10 times and the average value was recorded.

[0048] Light-shielding performance: The transmittance was determined by UV-visible spectrophotometry, measuring the transmittance of the capsule at 600 nm.

[0049] The specific test results are shown in Table 1: Table 1

[0050] The ursodeoxycholic acid raw material is crushed and sieved, and then filled into the capsule wall materials prepared in different groups to obtain ursodeoxycholic acid capsules.

[0051] Among them, the ursodeoxycholic acid raw materials specifically include the following raw materials by weight: 83.3 parts of ursodeoxycholic acid, 10 parts of microcrystalline cellulose, 5 parts of lactose, 1 part of povidone K30, 0.5 parts of magnesium stearate, and 0.05 parts of silicon dioxide. Ursodeoxycholic acid in the raw materials is passed through an 80-mesh sieve to control the particle size D90≤50μm; microcrystalline cellulose and lactose are passed through a 60-mesh sieve; and the remaining components are passed through a 20-mesh sieve.

[0052] The specific preparation method is: Dissolve povidone K30 in purified water to prepare a 4% solution (temperature 40℃±2℃); then put all the raw materials into a high-speed shear granulator and set the stirring rate to 200rpm. The shear blade speed is 1500rpm, spray the povidone solution, the spray rate is 15mL / min, and the end point control torque value is 10N·m. Then dry the obtained wet granules at 50℃ in a fluidized bed until the moisture content is ≤2% to obtain dry granules; pass the dry granules through a 30-mesh sieve, then mix with magnesium stearate and silicon dioxide for 30 minutes at a mixing rate of 15rpm, and finally fill them into capsule shells with a filling amount of 250mg.

[0053] Moisture-proof performance test: The prepared capsules were stored at 25°C and 75% RH for 72 hours, and the moisture absorption and weight gain rate was measured. Each sample was tested 10 times and the average value was recorded.

[0054] Friability test: Use a capsule friability tester to test and count the breakage rate of 200 capsules.

[0055] Stability test: The samples prepared in different groups were stored at 40℃±2℃ and 75%RH±5% for 6 months. The increase in total impurities in the capsule contents was then statistically analyzed using chromatography. Each sample was tested 10 times and the average value was recorded.

[0056] The specific performance test results are shown in Table 2: Table 2

[0057] It can be seen from the results shown in Table 1 and Table 2 above that the comprehensive performance of the capsule wall materials prepared in Examples 1-3 of the present application, including mechanical properties, light-shielding properties and storage stability, is significantly better than that of the products prepared in Comparative Examples 1-5, that is, within the technical solution defined in the present application, the comprehensive performance of the prepared capsule wall materials is excellent.

[0058] It can be seen from the results in Comparative Examples 1 and 4 that the use of pentose and suitable metal salts to strengthen the capsule shell material can promote crosslinking and bonding in the capsule shell components, thereby improving the mechanical properties of the product. At the same time, it can be used as a promoter for protein-sugar composite reactions, increase the production of colored substances in capsule wall materials, and improve the light-shielding properties of the product and the storage stability of the contents. It can also be seen from the results in the comparative examples that metal salts such as magnesium salts will inhibit the production of light-shielding substances in capsule wall materials, resulting in increased product transmittance and decreased stability of the contents.

[0059] From the results of Comparative Examples 2 and 3, it can be seen that acylation modification of protein can open the structure of protein, expose more internal hydrophobic structure, reduce the hydroxyl content and introduce hydrophobic acyl groups, further improving the hydrophobic barrier performance of the material. In addition, by regulating the type of acylation reaction, the amino functional group on the protein is retained, making it easier to react with the carbonyl group on the sugar to form a complex, thereby improving the light-shielding property while improving the bonding effect between the moisture-proof layer and the hollow capsule shell.

[0060] It can be seen from the results in Comparative Example 5 that the method of increasing the spraying temperature and spraying time to promote bonding, while improving the shading effect, will lead to a decrease in the mechanical properties of the product; and due to the change in the component structure, the breakage rate of the capsule shell is increased.

[0061] In the description of the specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0062] The above contents are merely examples and explanations of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the invention or exceed the scope defined by the claims, they shall all fall within the protection scope of the present invention.

Claims

1. A method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid, characterized in that: The method comprises the following preparation steps: S1. Modifying soybean protein with an acylating agent to obtain modified soybean protein; mixing the modified soybean protein and an enteric material in deionized water to obtain a moisture-proof layer material; S2, mixing gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt to obtain a capsule base; adding deionized water to the capsule base, raising the system temperature to 40-50° C., stirring and using a mold to prepare a hollow capsule shell; S3, using a spray coating machine to spray the moisture-proof layer material obtained in step S1 onto the surface of the hollow capsule shell obtained in step S2, and then drying and curing the hollow capsule shell to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

2. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: In step S1, the modified soy protein is prepared by the following steps: Add soybean protein to phosphate buffer and stir for 10-20 minutes. Then add acylation reagent to the system and increase the reaction temperature to 30-40°C. During the process, maintain the pH value of the system at 8.0-9.

0. After reacting for 2-4 hours, naturally return to room temperature. Adjust the pH value of the system to 4.5-5.

0. After dialyzing, centrifuge, collect the precipitate and freeze-dry to obtain modified soybean protein.

3. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 2, characterized in that: The acylating agent used is at least one of acetic anhydride, succinic anhydride, maleic anhydride, acetyl chloride and benzoyl chloride.

4. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: The mass ratio of soybean protein to acylating agent is (3-5):(1-1.2).

5. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: In step S2, the mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinyl pyrrolidone, sugar and metal salt is (50-60):(1-3):(10-15):(2-4):(5-10):(0.01-0.05).

6. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: In step S2, the sugar is at least one of pentose and aldose.

7. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: In step S2, the metal salt is at least one of an iron salt and a copper salt.

8. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: In step S3, during the spraying operation, the air inlet temperature is set to 60-70°C, the air outlet temperature is set to 40-60°C, the atomization pressure is set to 0.8-1.5 bar, the spray gun distance is set to 20-30 cm, the spray rate is set to 5-10 mL / min, and the spraying time is set to 15-20 minutes.

9. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized in that: In step S3, the temperature of drying and curing the hollow capsule shell after spraying is 20-40°C.

10. A capsule wall material obtained by the method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid as claimed in any one of claims 1 to 9.

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