A capsule wall material for improving the stability of ursodeoxycholic acid and its preparation method

Abstract

This invention relates to a capsule wall material for improving the stability of ursodeoxycholic acid and its preparation method, belonging to the field of capsule wall material preparation technology. Specifically, it includes the following steps: acylation modification of soybean protein followed by preparation of a moisture-proof layer material with an enteric coating material; mixing gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone, sugars, and metal salts, adding water, and stirring to form a capsule base; molding hollow capsule shells using a mold; uniformly spraying the moisture-proof layer material onto the capsule shell surface, followed by low-temperature drying and curing to form a composite wall material with both light-shielding properties and high mechanical strength. By introducing a moisture-proof layer material prepared from modified soybean protein and an enteric coating material, moisture can be prevented from eroding the drug inside the capsule, further ensuring the stability and shelf life of the drug. The resulting capsule wall material effectively protects ursodeoxycholic acid, preventing its degradation or inactivation during storage and use, thereby improving the stability and efficacy of the drug.

Description

Technical Field

[0001] This application relates to the field of capsule wall material preparation technology, and more specifically, it relates to a capsule wall material for improving the stability of ursodeoxycholic acid and a method for preparing the same. Background Technology

[0002] In the field of pharmaceutical formulations, ursodeoxycholic acid is a core drug for treating cholestatic liver disease, cholesterol gallstones, and other conditions. The stability of its oral formulation directly affects its efficacy and safety, and its stability and shelf life are crucial for achieving the desired therapeutic effect. However, existing capsule wall material preparation technologies suffer from a series of problems and shortcomings, severely restricting the stability and efficacy of ursodeoxycholic acid.

[0003] Traditional hard capsule shells often use gelatin or hydroxypropyl methylcellulose (HPMC) as the base material. However, gelatin is prone to absorbing moisture and softening, and while HPMC has some moisture-proof properties, it is still difficult to prevent moisture penetration in high-humidity environments. Although some soft capsules use vegetable oil to improve stability, hard capsules lack a similar protective mechanism, causing ursodeoxycholic acid to easily absorb moisture and clump or hydrolyze and become ineffective during storage. In addition, conventional light-blocking agents (such as titanium dioxide) only block light through physical shielding and cannot synergistically improve moisture-proof performance; increasing their usage will reduce the flexibility of the capsule shell, leading to increased brittleness.

[0004] Furthermore, in existing technologies, the complexation of polysaccharides and proteins mostly relies on physical mixing, without enhancing interfacial bonding through chemical cross-linking. For example, unmodified natural soybean protein, due to its high hydroxyl content, easily binds to water molecules, leading to the failure of the moisture barrier; while excessive acylation, although improving hydrophobicity, will destroy amino activity and hinder covalent cross-linking with polysaccharides.

[0005] In summary, existing capsule wall materials have significant shortcomings in terms of moisture resistance, light blocking, mechanical strength, and process adaptability, necessitating a solution that balances multiple properties while being processed gently. Therefore, this application provides a capsule wall material for improving the stability of ursodeoxycholic acid and its preparation method. Summary of the Invention

[0006] To address the problems mentioned in the background art, this application provides a capsule wall material for improving the stability of ursodeoxycholic acid and a method for preparing the same.

[0007] The technical solution adopted in this application is as follows:

[0008] A method for preparing a capsule wall material that improves the stability of ursodeoxycholic acid includes the following steps:

[0009] S1. Modified soybean protein is prepared by using an acylation reagent; the modified soybean protein and enteric material are mixed in deionized water to prepare a moisture-proof layer material.

[0010] S2. Mix gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone, sugars and metal salts to obtain capsule base material; add deionized water to capsule base material, raise the system temperature to 40-50℃, stir and use a mold to prepare hollow capsule shells;

[0011] S3. Using a spray coating machine, spray the moisture-proof layer material obtained in step S1 onto the surface of the hollow capsule shell obtained in step S2, and then dry and cure the hollow capsule shell to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

[0012] Furthermore, a method for preparing a capsule wall material that improves the stability of ursodeoxycholic acid includes the following steps:

[0013] S1. Modified soybean protein was prepared by using an acylation reagent; the modified soybean protein and enteric material were mixed in deionized water with a mass-to-volume ratio of (8-12) g: 100 mL and stirred evenly to prepare a moisture-proof layer material.

[0014] S2. Mix gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone, sugars and metal salts to obtain capsule base material; add deionized water to capsule base material, the mass ratio of capsule base material to deionized water is 10:(3-4), raise the system temperature to 40-50℃, stir for 20-30 minutes, and then use a hollow capsule shell mold to prepare hollow capsule shells.

[0015] S3. Using a spray coating machine, 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.

[0016] Furthermore, in step S1, the modified soy protein is specifically prepared by the following steps:

[0017] Add soy protein to phosphate buffer and stir for 10-20 minutes. Then add acylation reagent to the system and raise the reaction temperature to 30-40℃. Maintain the pH of the system at 8.0-9.0 during the process. After reacting for 2-4 hours, allow the system to return to room temperature naturally. Adjust the pH of the system to 4.5-5.0. After dialysis, centrifuge, collect the precipitate, and freeze-dry it to obtain modified soy protein.

[0018] Furthermore, in step S1, the modified soy protein is specifically prepared by the following steps:

[0019] Soy protein was added to a phosphate buffer solution with a pH of 8.0-9.0 at a concentration of 5-10% (w / v). The system was then stirred at 30-90 rpm for 10-20 minutes at room temperature. An acylation reagent was then added to the system, and the reaction temperature was increased to 30-40°C, while maintaining the pH of the system at 8.0-9.0. After reacting for 2-4 hours, the system was allowed to return to room temperature naturally. The pH of the system was then adjusted to 4.5-5.0 using 0.1 mol / L HCl solution. The system was dialyzed at 4°C for 48 hours, followed by centrifugation at 10000×g for 10-20 minutes. The precipitate was collected and freeze-dried to obtain modified soy protein.

[0020] In the above reaction process, soy protein is treated with an acylation reagent. By controlling the reaction environment to be alkaline, the deprotonation process of hydroxyl groups is promoted, the nucleophilicity of hydroxyl groups is enhanced, and the nucleophilic substitution reaction is promoted. Subsequently, the acyl group on the acylation reagent and the hydroxyl group on the soy protein molecule are combined through the acylation reaction to prepare modified soy protein.

[0021] Furthermore, the acylation reagent used is at least one of acetic anhydride, succinic anhydride, maleic anhydride, acetyl chloride, and benzoyl chloride.

[0022] Furthermore, the mass ratio of soybean protein to acylation reagent is (3-5)g:(1-1.2)g.

[0023] Further, in step S2, the mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinylpyrrolidone, sugars and metal salts is (50-60):(1-3):(10-15):(2-4):(5-10):(0.01-0.05).

[0024] Furthermore, in step S2, the sugar is at least one of pentose sugars and aldoses.

[0025] Preferably, the pentose sugar is at least one of arabinose and xylose.

[0026] Preferably, the aldose is glucose.

[0027] Furthermore, in step S2, the metal salt is at least one of an iron salt and a copper salt.

[0028] Furthermore, in step S3, during the spraying operation, the inlet air temperature is set to 60-70℃, the outlet air temperature to 40-60℃, the atomization pressure to 0.8-1.5 bar, the spray gun distance to 20-30 cm, the spray rate to 5-10 mL / min, and the spraying time to 15-20 minutes.

[0029] Furthermore, in step S3, the temperature for drying and curing the hollow capsule shell after spraying is 20-40℃.

[0030] A method for preparing capsule wall material that improves the stability of ursodeoxycholic acid.

[0031] In summary, this application has the following beneficial effects:

[0032] 1. In the technical solution of this invention, during the preparation of the capsule wall material, a moisture-proof layer material prepared by mixing modified soybean protein and enteric-coating materials is introduced, which significantly enhances the moisture-proof performance of the capsule. This helps prevent moisture from eroding the drug inside the capsule, further ensuring the stability and shelf life of the drug. Through a specific preparation method, the resulting capsule wall material can effectively protect ursodeoxycholic acid, preventing its degradation or inactivation during storage and use, thereby improving the stability and efficacy of the drug.

[0033] 2. In the technical solution of this invention, by adding metal salt ions to the hollow capsule shell and selecting suitable polysaccharides, the Maillard reaction in the thermal spraying process is promoted, avoiding conventional high-temperature methods to promote the Maillard reaction. This maintains the shape of the hollow capsule shell while ensuring uniform coverage of the moisture-proof layer material. By controlling the acylation modification of soybean protein, its hydrophobic properties are retained while its amino groups are preserved. These amino groups can react with the polysaccharides on the hollow capsule shell to form melanin-like brown substances, improving the bonding stability between the hollow capsule shell and the moisture-proof layer. This also imparts good light-blocking properties to the capsule wall material, further improving the storage stability of ursodeoxycholic acid. Simultaneously, the metal ions stabilize the polysaccharide-protein network through chelation, further enhancing the mechanical strength of the capsule wall material. Detailed Implementation

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

[0035] The raw materials involved in the specific embodiments of this application are analytical grade. Additionally:

[0036] The mold used was a No. 0 capsule shell mold;

[0037] The enteric coating material used was the commercially available Eudragit-L100 product;

[0038] The ursodeoxycholic acid raw material used has a purity of 99.0% and a residue on ignition of ≤0.1%.

[0039] Example 1

[0040] A method for preparing a capsule wall material that improves the stability of ursodeoxycholic acid includes the following steps:

[0041] S1. Modified soybean protein was prepared by using an acylation reagent; the modified soybean protein and enteric material were mixed in deionized water at a mass-to-volume ratio of 8g:100mL and stirred evenly to prepare a moisture-proof layer material.

[0042] The modified soy protein is prepared by the following steps:

[0043] Soy protein was added to a phosphate buffer solution with a pH of 8.0 at a concentration of 5% (w / v). The system was then stirred at 30 rpm for 10 minutes at room temperature. An acylation reagent was then added, and the reaction temperature was increased to 30°C, maintaining the pH at 8.0 throughout the process. After 2 hours of reaction, the mixture was allowed to return to room temperature. The pH was adjusted to 4.5 using 0.1 mol / L HCl solution. The system was dialyzed at 4°C for 48 hours, followed by centrifugation at 10000 × g for 15 minutes. The precipitate was collected and freeze-dried to obtain modified soy protein. The mass ratio of soy protein to acylation reagent was 3 g:1 g, and the acylation reagent used was acetic anhydride.

[0044] S2. Mix gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone and metal salt to obtain capsule base material; add deionized water to capsule base material, the mass ratio of capsule base material to deionized water is 10:3, raise the system temperature to 40℃, stir for 20 minutes and then inject into hollow capsule shell mold, use a rotary molding machine to form a cylindrical shell in the mold, cool to room temperature, and cut off the excess edge part to prepare hollow capsule shell;

[0045] The mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinylpyrrolidone, sugars and metal salts is 50:1:10:2:5:0.01.

[0046] The carbohydrate is glucose.

[0047] The metal salt is copper sulfate.

[0048] 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 at 20°C to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

[0049] During the spraying operation, the inlet air temperature was set to 60℃, the outlet air temperature to 40℃, the atomization pressure to 0.8 bar, the spray gun distance to 20 cm, the spray rate to 5 mL / min, and the spraying time to 15 minutes.

[0050] Example 2

[0051] A method for preparing a capsule wall material that improves the stability of ursodeoxycholic acid includes the following steps:

[0052] S1. Modified soybean protein was prepared by using an acylation reagent; the modified soybean protein and enteric material were mixed in deionized water at a mass-to-volume ratio of 10g:100mL and stirred evenly to prepare a moisture-proof layer material.

[0053] The modified soy protein is prepared by the following steps:

[0054] Soy protein was added to a phosphate buffer solution with a pH of 9.0 at a concentration of 8% (w / v). The system was then stirred at 60 rpm for 20 minutes at room temperature. An acylation reagent was then added, and the reaction temperature was increased to 40°C, maintaining the pH at 9.0 throughout the process. After 3 hours of reaction, the mixture was allowed to return to room temperature. The pH was then adjusted to 5.0 using 0.1 mol / L HCl solution. The system was dialyzed at 4°C for 48 hours, followed by centrifugation at 10000 × g for 15 minutes. The precipitate was collected and freeze-dried to obtain modified soy protein. The mass ratio of soy protein to acylation reagent was 4 g:1.1 g, and the acylation reagent used was acetic anhydride.

[0055] S2. Mix gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone and metal salt to obtain capsule base material; add deionized water to capsule base material, the mass ratio of capsule base material to deionized water is 10:3.5, raise the system temperature to 45℃, stir for 25 minutes and then inject into hollow capsule shell mold, use a rotary molding machine to make the system form a cylindrical shell in the mold, cool to room temperature, and cut off the excess edge part to prepare hollow capsule shell;

[0056] The mass ratio of gelatin, carboxymethyl cellulose, glycerol, polyvinylpyrrolidone, sugars and metal salts is 55:2:13:3:7:0.03.

[0057] The carbohydrate is glucose.

[0058] The metal salt is copper sulfate.

[0059] 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 at 30°C to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

[0060] During the spraying operation, the inlet air temperature was set to 65℃, the outlet air temperature to 50℃, the atomization pressure to 1.2 bar, the spray gun distance to 25 cm, the spray rate to 8 mL / min, and the spraying time to 18 minutes.

[0061] Example 3

[0062] A method for preparing a capsule wall material that improves the stability of ursodeoxycholic acid includes the following steps:

[0063] S1. Modified soybean protein was prepared by using an acylation reagent; the modified soybean protein and enteric material were mixed in deionized water at a mass-to-volume ratio of 12g:100mL and stirred evenly to prepare a moisture-proof layer material.

[0064] The modified soy protein is prepared by the following steps:

[0065] Soy protein was added to a phosphate buffer solution with a pH of 9.0 at a concentration of 10% (w / v). The system was then stirred at 90 rpm for 20 minutes at room temperature. An acylation reagent was then added, and the reaction temperature was increased to 40°C, maintaining the pH at 9.0 throughout the process. After 4 hours of reaction, the mixture was allowed to return to room temperature naturally. The pH was then adjusted to 5.0 using 0.1 mol / L HCl solution. The system was dialyzed at 4°C for 48 hours, followed by centrifugation at 10000×g for 20 minutes. The precipitate was collected and freeze-dried to obtain modified soy protein. The mass ratio of soy protein to acylation reagent was 5 g:1.2 g, and the acylation reagent used was succinic anhydride.

[0066] S2. Mix gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone and metal salt to obtain capsule base material; add deionized water to capsule base material, the mass ratio of capsule base material to deionized water is 10:4, raise the system temperature to 50°C, stir for 30 minutes and then inject into a hollow capsule shell mold, use a rotary molding machine to form a cylindrical shell in the mold, cool to room temperature, and cut off the excess edge parts to prepare hollow capsule shell;

[0067] The mass ratio of gelatin, carboxymethyl cellulose, glycerin, polyvinylpyrrolidone, sugars and metal salts is 60:3:15:4:10:0.05.

[0068] The sugar is arabinose.

[0069] The metal salt is ferrous sulfate.

[0070] 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 at 30°C to obtain a capsule wall material that improves the stability of ursodeoxycholic acid.

[0071] During the spraying operation, the inlet air temperature was set to 70℃, the outlet air temperature to 60℃, the atomization pressure to 1.5 bar, the spray gun distance to 30 cm, the spray rate to 10 mL / min, and the spraying time to 20 minutes.

[0072] Comparative Example 1

[0073] The difference between this comparative example and Example 1 is that in step S2, the sugar used is mannose.

[0074] Comparative Example 2

[0075] The difference between this comparative example and Example 1 is that, in step S1, soy protein is used instead of modified soy protein.

[0076] Comparative Example 3

[0077] The difference between this comparative example and Example 1 is that, in step S1, the modified soy protein is prepared by the following steps:

[0078] Soy protein was added to deionized water and stirred at 30 rpm for 10 minutes at room temperature. The pH of the system was adjusted to 7.5 using 0.1 mol / L NaOH solution. Then, an acylation reagent was added, and the reaction temperature was raised to 30°C. After reacting for 60 minutes, the mixture was allowed to return to room temperature. The pH of the system was then adjusted to neutral using 0.1 mol / L HCl solution. The system was dialyzed at 4°C for 48 hours to remove residual acylation reagent, and then freeze-dried to obtain modified soy protein. The ratio of soy protein, deionized water, and acylation reagent used was 3 g: 20 mL: 1 g.

[0079] Comparative Example 4

[0080] The difference between this comparative example and Example 1 is that, in step S2, the metal salt used is magnesium sulfate.

[0081] Comparative Example 5

[0082] The difference between this comparative example and Example 1 is that in step S3, the inlet air temperature is set to 80°C, the outlet air temperature to 40°C, the atomization pressure to 0.8 bar, the spray gun distance to 20 cm, the spray rate to 5 mL / min, and the spraying time to 30 minutes.

[0083] Performance testing

[0084] The performance of the capsule wall materials prepared in Examples 1-3 and Comparative Examples 1-5 of this application will now be tested.

[0085] Mechanical strength: The tensile strength of capsules prepared in different groups was tested using a universal testing machine. The tensile rate was set to 80 mm / min, and each sample was tested 10 times. The average value was recorded.

[0086] Light-blocking performance: Transmittance was determined by ultraviolet-visible spectrophotometry, measuring the transmittance of the capsule at 600 nm.

[0087] The specific test results are shown in Table 1:

[0088] Table 1

[0089]

[0090] After pulverizing and sieving the ursodeoxycholic acid raw material, it is filled into the capsule wall material prepared in different groups to obtain ursodeoxycholic acid capsules.

[0091] The ursodeoxycholic acid raw material specifically includes the following parts by weight:

[0092] The raw materials consist of 83.3 parts ursodeoxycholic acid, 10 parts microcrystalline cellulose, 5 parts lactose, 1 part povidone K30, 0.5 parts magnesium stearate, and 0.05 parts silicon dioxide. The ursodeoxycholic acid in the raw materials was sieved through an 80-mesh sieve, with the particle size D90 ≤ 50 μm controlled; the microcrystalline cellulose and lactose were sieved through a 60-mesh sieve; and the remaining components were sieved through a 20-mesh sieve.

[0093] The specific preparation method is as follows:

[0094] Povidone K30 was dissolved in purified water to prepare a 4% solution (temperature 40℃±2℃). Then, all raw materials were fed into a high-speed shear granulator with a stirring speed of 200 rpm. The shear blade rotated at 1500 rpm, and the povidone solution was sprayed in at a spray rate of 15 mL / min. The endpoint torque was controlled at 10 N·m. The resulting wet granules were then dried in a fluidized bed at 50℃ until the moisture content was ≤2%, yielding dry granules. The dry granules were passed through a 30-mesh sieve and then mixed with magnesium stearate and silica for 30 minutes at a mixing rate of 15 rpm. Finally, the mixture was filled into capsule shells with a filling amount of 250 mg.

[0095] Moisture resistance test: The prepared capsules were stored at 25℃ and 75%RH for 72 hours, and the moisture absorption weight gain rate was measured. Each sample was tested 10 times, and the average value was recorded.

[0096] Friability test: A capsule friability meter was used to test the friability of 200 capsules and the breakage rate was recorded.

[0097] Stability test: Samples prepared in different groups were stored at 40℃±2℃ and 75%RH±5% for 6 months. Then, the increase in total impurities in the capsule contents was statistically analyzed by chromatography. Each sample was tested 10 times and the average value was recorded.

[0098] The specific performance test results are shown in Table 2 below:

[0099] Table 2

[0100]

[0101] As can be seen from the results shown in Tables 1 and 2 above, the comprehensive performance of the capsule wall material prepared in Examples 1-3 of this application, including mechanical properties, light-blocking properties and storage stability, is significantly better than that of the products prepared in Comparative Examples 1-5. That is, within the technical solution limited by this application, the comprehensive performance of the capsule wall material prepared is excellent.

[0102] The results from Comparative Examples 1 and 4 show that reinforcing the capsule shell material with pentoses and suitable metal salts can promote cross-linking and bonding within the capsule shell components, thereby improving the product's mechanical properties. Simultaneously, it can act as a promoter of protein-carbohydrate complexation reactions, increasing the production of colored substances in the capsule wall material and improving the product's light-blocking properties and storage stability of the contents. The results from the comparative examples also show that metal salts such as magnesium salts inhibit the production of light-blocking substances in the capsule wall material, leading to increased product light transmittance and decreased content stability.

[0103] The results from Comparative Examples 2 and 3 show that acylation modification of proteins can open up the protein structure, exposing more internal hydrophobic structures, while reducing the hydroxyl content and introducing hydrophobic acyl groups, further improving the hydrophobic barrier properties of the material. Furthermore, by controlling the type of acylation reaction, the amino functional groups on the protein are preserved, making it easier for them to react with carbonyl groups on sugars to form complexes. This improves the bonding effect between the moisture-proof layer and the hollow capsule shell, while also enhancing light-blocking properties.

[0104] The results in Comparative Example 5 show that while increasing the spraying temperature and spraying time to promote bonding improves the light-blocking effect, it also leads to a decrease in the mechanical properties of the product; and due to the change in the component structure, the breakage rate of the resulting capsule shell increases.

[0105] In the description of this specification, the references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0106] The above description is merely an example and illustration of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described, or use similar methods to replace them, as long as they do not deviate from the invention or exceed the scope defined in the claims, all of which should 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 by, The preparation steps include: S1, soybean protein is added into phosphate buffer solution, stirred for 10-20 minutes, then acylation reagent is added into the system and the reaction temperature is increased to 30-40℃, the pH value of the system is maintained at 8.0-9.0 during the process, the system is naturally restored to room temperature after reaction for 2-4 hours, the pH value of the system is adjusted to 4.5-5.0, centrifuged after dialysis, the precipitate is collected and freeze-dried to obtain modified soybean protein; The modified soybean protein and enteric material are mixed in deionized water to prepare the moisture-proof layer material; the enteric material is Eudragit-L100; S2, gelatin, carboxymethyl cellulose, glycerol, polyvinylpyrrolidone, sugar and metal salt are mixed to obtain a capsule base; deionized water is added into the capsule base, the temperature of the system is increased to 40-50℃, and the hollow capsule shell is prepared after stirring using a mold; the sugar is at least one of arabinose, xylose and glucose, and the metal salt is at least one of iron salt and copper salt; S3, the moisture-proof layer material obtained in S1 is sprayed on the surface of the hollow capsule shell obtained in S2 using a spray coating machine, and the hollow capsule shell is dried and solidified to obtain a capsule wall material for improving the stability of ursodeoxycholic acid; in the spraying operation, the inlet air temperature is set to 60-70℃, the outlet air temperature is 40-60℃, the atomization pressure is 0.8-1.5 bar, the spray gun distance is 20-30 cm, the spray rate is 5-10 mL / min, and the spraying time is 15-20 minutes.

2. The method for preparing a capsule wall material for improving the stability of ursodeoxycholic acid according to claim 1, characterized by, The acylation reagent used is at least one of acetic anhydride, succinic anhydride, maleic anhydride, acetyl chloride and benzoyl chloride.

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

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

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

6. A capsule wall material for improving the stability of ursodeoxycholic acid prepared by the preparation method of any one of claims 1-5.

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