An enteric plant capsule and a method of making the same

Abstract

The application relates to the technical field of pharmaceutical auxiliaries, and particularly discloses an enteric plant capsule and a preparation method thereof. The enteric plant capsule comprises a film-forming material, an enteric coating mixed solution and an ethyl cellulose aqueous solution; the enteric coating mixed solution comprises 50-120 parts of hydroxypropyl methyl cellulose acetate succinate, 50-120 parts of hydroxypropyl methyl cellulose phthalate and 200-500 parts of a sodium hydroxide aqueous solution; the mass concentration of the sodium hydroxide aqueous solution is 0.04-0.4 mg / L; and the preparation method is as follows: the prepared enteric coating mixed solution is added into the prepared film-forming material, vacuum extraction is carried out at 60-70 DEG C and a vacuum degree of 0.065-0.092 MPa for 15-30 min, the prepared ethyl cellulose aqueous solution is added, and a glue solution is obtained; the glue solution is subjected to glue melting and glue dipping forming, and then drying, so that the enteric plant capsule with low water content, stable properties and high storage stability is obtained.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical excipients technology, and more specifically, to an enteric-coated plant capsule and a method for preparing the same. Background Technology

[0002] Capsules are the second largest oral dosage form after tablets. Because the contents of capsules can be powder, particles, microspheres, or even fluids or semi-fluids, capsules have a wide range of applications in the pharmaceutical, health product, and functional food industries.

[0003] Based on how the capsule releases its contents at a specific site in the body, capsules can be divided into enteric-coated capsules and gastric-coated capsules. Compared to gastric-coated capsules, enteric-coated capsules avoid irritating the stomach tissue with their contents, protecting the safe and effective release of the contents within the intestines. An enteric coating refers to a raw material that does not disintegrate or dissolve in simulated gastric juice but rapidly disintegrates or dissolves in simulated intestinal juice. The preparation method for enteric-coated capsules typically involves coating, spraying, or film-coating the surface of the gastric-coated capsule to form an acid-resistant polymer layer, thereby improving the capsule's stability in the stomach.

[0004] Currently, the commonly used enteric coating is cellulose acetate phthalate, a white, free-flowing, hygroscopic powder. Because it is insoluble in water and ethanol, but soluble in acetone or a mixture of ethanol and acetone, cellulose acetate ester is usually dissolved in an ethanol-acetone mixture before coating, spraying, or film-coating the gastric-coated capsules. However, ethanol and acetone are organic solvents that easily volatilize during the preparation process, causing environmental pollution. Furthermore, their residues in the capsules can cause harm to the human body, reducing the safety of the capsules. Summary of the Invention

[0005] To improve the safety of enteric-coated capsules, this application provides an enteric-coated plant capsule and a method for preparing the same.

[0006] In a first aspect, this application provides an enteric-coated plant-based capsule, employing the following technical solution:

[0007] An enteric-coated plant capsule comprising a film-forming material, an enteric coating mixture, and an aqueous solution of ethyl cellulose;

[0008] The enteric coating mixture comprises the following components in parts by weight:

[0009] 50-120 parts of hydroxypropyl methylcellulose succinate acetate;

[0010] 50-120 parts of hydroxypropyl methylcellulose phthalate;

[0011] 200-500 parts of sodium hydroxide aqueous solution;

[0012] The mass concentration of the sodium hydroxide aqueous solution is 0.04-0.4 mg / L.

[0013] The film-forming material can be any of the conventional raw materials used in the preparation of plant capsules.

[0014] An aqueous solution of ethyl cellulose is a mixture of ethyl cellulose and pure water.

[0015] Hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate are enteric film coating materials that are insoluble in water but soluble in organic solvents.

[0016] By adopting the above technical solution, on the one hand, after mixing hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate and sodium hydroxide aqueous solution with a mass concentration of 0.04-0.4 mg / L, hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate dissolve, which avoids the use of organic solvents as solvents and improves the safety of enteric-coated plant capsules.

[0017] On the other hand, film-forming materials can form capsule shells, and aqueous solutions of ethyl cellulose can increase the toughness of the capsule shells. In enteric-coated plant capsules prepared by mixing film-forming materials, enteric coating mixtures, and aqueous solutions of ethyl cellulose, the enteric raw materials obtained by compounding hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate in sodium hydroxide solution of the above-mentioned mass concentration have strong acid resistance and high plasticity, which can reduce the use of plasticizers and improve the safety and gastric stability of the final enteric-coated plant capsules.

[0018] Meanwhile, hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate contain stable acetyl groups, which have strong anti-sticking properties and are beneficial to improving the storage stability of the final enteric-coated plant capsules.

[0019] Preferably, the film-forming material comprises the following components in parts by weight:

[0020] 620-740 parts of hydroxypropyl methylcellulose;

[0021] 2500-4900 portions of water;

[0022] 50-100 parts pectin;

[0023] 5-35 parts gellan gum;

[0024] 0-35 parts of carrageenan;

[0025] 1-10 parts of coagulant aid;

[0026] 1-8 parts glycerin;

[0027] 1-12 parts of polyethylene glycol;

[0028] The aqueous solution of ethyl cellulose comprises the following components in parts by weight:

[0029] 30-60 parts of ethyl cellulose;

[0030] 200-300 parts water.

[0031] By employing the above technical solution, hydroxypropyl cellulose is used as the main film-forming substance for plant-based capsules, while pectin, gellan gum, and carrageenan are used as gelling agents. With the aid of potassium chloride, pectin, gellan gum, and carrageenan are promoted to form a gel within the hydroxypropyl cellulose. Then, an aqueous solution of ethyl cellulose and a mixture of enteric coatings are added, resulting in enteric-coated plant-based capsules that are resilient and not easily broken. Furthermore, the enteric-coated plant-based capsules have a stable molecular structure and low water content, making them more suitable for filling oxygen-sensitive and fast-release ingredients. These characteristics enhance the safety of the contents and improve the efficacy of the product. In addition, the enteric-coated plant-based capsules prepared using cellulose in this application have higher safety and applicability compared to animal-derived gelatin capsules.

[0032] Preferably, the weight ratio of the film-forming material, the enteric coating mixture, and the ethyl cellulose aqueous solution is 1:(0.0752-0.1105):(0.0489-0.0712).

[0033] By employing the above technical solution, film-forming materials, enteric coating mixture, and ethyl cellulose aqueous solution were mixed in the aforementioned proportions to prepare enteric-coated plant capsules. Disintegration time tests were conducted according to the relevant operational requirements of the Chinese Pharmacopoeia (2020 edition). The test results showed that the enteric-coated plant capsules exhibited a high disintegration time of 124-150 minutes in simulated gastric fluid and a low disintegration time of 4.0-6.3 minutes in simulated intestinal fluid, indicating that the enteric-coated plant capsules possess good acid resistance and enteric solubility.

[0034] Preferably, the weight ratio of hydroxypropyl methylcellulose succinate to hydroxypropyl methylcellulose phthalate is 1:(1-2).

[0035] By adopting the above technical solution, the hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate have good compatibility in sodium hydroxide aqueous solution, and the resulting enteric coating mixture has stronger acid resistance, which is beneficial to improving the acid resistance and enteric properties of the final enteric plant capsule.

[0036] Preferably, the film-forming material comprises the following components in parts by weight:

[0037] 700 parts of hydroxypropyl methylcellulose;

[0038] 4092 portions of water;

[0039] 50 parts pectin;

[0040] 10 parts gellan gum;

[0041] 6 parts carrageenan;

[0042] 8 parts of coagulant aid;

[0043] 4 parts glycerin;

[0044] 8 parts polyethylene glycol;

[0045] The enteric coating mixture comprises the following components in parts by weight:

[0046] 50 parts of hydroxypropyl methylcellulose succinate acetate;

[0047] 75 parts of hydroxypropyl methylcellulose phthalate;

[0048] 250 parts of sodium hydroxide aqueous solution;

[0049] The mass concentration of the sodium hydroxide aqueous solution is 0.22 mg / L;

[0050] The aqueous ethyl cellulose solution comprises the following components in parts by weight:

[0051] 47 parts of ethyl cellulose;

[0052] 200 portions of water.

[0053] Enteric-coated plant capsules prepared using the above-described technical solution and the above-described proportions of components were subjected to disintegration time tests according to the relevant operational requirements of the Chinese Pharmacopoeia (2020 edition). The test results showed that the enteric-coated plant capsules exhibited a disintegration time of up to 150 minutes in simulated gastric fluid and as low as 4.0 minutes in simulated intestinal fluid.

[0054] Preferably, the viscosity of the ethyl cellulose is 4-8 mp·s.

[0055] By adopting the above technical solution, ethyl cellulose of the above viscosity is mixed with water to prepare an ethyl cellulose aqueous solution of a certain viscosity, which has a good toughening effect on capsules and reduces capsule breakage.

[0056] Secondly, this application provides a method for preparing enteric-coated plant capsules, using the following technical solution:

[0057] A method for preparing enteric-coated plant capsules includes the following preparation steps:

[0058] S1 Preparation: The components of the film-forming material, enteric coating mixture, and ethyl cellulose aqueous solution are mixed separately to prepare the film-forming material, enteric coating mixture, and ethyl cellulose aqueous solution;

[0059] S2 sol: Add the enteric coating mixture to the film-forming material, and after vacuuming for 15-30 minutes at 60-70℃ and a vacuum degree of 0.065-0.092MPa, add it to an aqueous solution of ethyl cellulose to obtain the sol.

[0060] S3 Dissolving agent: Let the adhesive solution stand at 50-60℃ for 2-4 hours to obtain the dissolving agent solution;

[0061] S4 Dipping and Molding: Dip the molten adhesive at 50-60℃, and then mold it at 25-35℃ to obtain a blank;

[0062] S5 Drying: Dry the raw material until the moisture content is less than 8% to obtain enteric-coated plant capsules.

[0063] By adopting the above technical solution, the preparation method of this application is simple. It only requires sol-gelling the film-forming material, enteric coating mixture and ethyl cellulose aqueous solution under the above conditions, followed by melting, dipping and molding, and then drying to obtain enteric-coated plant capsules with low water content, stable properties and high storage stability, which are suitable for large-scale production.

[0064] Preferably, in the preparation of the enteric coating mixture in S1, the steps are as follows: hydroxypropyl methylcellulose succinate is added to an aqueous sodium hydroxide solution, stirred and mixed, and then hydroxypropyl methylcellulose phthalate is added and stirred and mixed to obtain the enteric coating mixture.

[0065] By adopting the above technical solution, hydroxypropyl methylcellulose acetate succinate is first dissolved in sodium hydroxide aqueous solution, and then hydroxypropyl methylcellulose phthalate is dissolved, which increases the compatibility of hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate, thereby improving the toughness, acid stability and enteric solubility of enteric-coated plant capsules.

[0066] In summary, this application has the following beneficial effects:

[0067] 1. This application uses sodium hydroxide with a mass concentration of 0.04-0.4 mg / L to dissolve hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate, which not only reduces the use of organic solvents and plasticizers and improves the safety of enteric-coated plant capsules, but also increases the acid resistance, enteric solubility and storage stability of enteric-coated plant capsules.

[0068] 2. Ethyl cellulose aqueous solution can not only increase the smoothness, gloss, transparency and softness of the capsule surface, but also increase the cold resistance and anti-sticking properties of the capsule, which is beneficial to obtaining enteric-coated plant capsules with low water content, stable properties and high storage stability.

[0069] 3. The preparation method of the enteric-coated plant capsules in this application has few process steps, is simple to operate, and is suitable for large-scale production. Detailed Implementation

[0070] The present application will be further described in detail below with reference to the embodiments.

[0071] Unless otherwise specified below, all raw materials used in the embodiments of this application are commercially available.

[0072] Hydroxypropyl methylcellulose acetate succinate, general grade L, purchased from Shin-Etsu;

[0073] Hydroxypropyl methylcellulose phthalate, model 55S, and hydroxypropyl methylcellulose, model SH-E6, were both purchased from Anhui Shanhe.

[0074] Pectin, with the molecular formula C5H 10 O5, gellan gum, brand name CG-HA, was purchased from CPKelcogel;

[0075] Glycerin and polyethylene glycol were both purchased from Hunan Ercon.

[0076] Ethyl cellulose, brand name ECD-RA(C), was purchased from Tianjin Hongri.

[0077] Performance testing

[0078] The enteric-coated plant capsules obtained in the embodiments of this application and the enteric-coated capsules obtained in the comparative examples were tested for friability, disintegration time, and stability. The testing methods are as follows:

[0079] Friability test: 50 enteric-coated plant capsules obtained in the examples or the comparative examples (hereinafter referred to as capsules) were soaked in a saturated magnesium nitrate solution at 25℃±1℃ for 24 hours. First, a glass tube (inner diameter 24mm, length 200mm) was placed upright on a wooden board (thickness 2cm). Then, the soaked capsules were placed into the glass tube one by one. Finally, a cylindrical weight (made of polytetrafluoroethylene, diameter 22mm, weight 20g±0.1g) was dropped freely from the opening of the glass tube. The capsules were visually inspected for breakage. If any capsule was broken, no more than one capsule should be broken.

[0080] Disintegration time limit test: In accordance with the relevant operating requirements of the Chinese Pharmacopoeia (2020 edition), the disintegration of the enteric-coated plant capsules obtained in the example or the enteric-coated capsules obtained in the comparative example was tested in artificial gastric fluid and artificial intestinal fluid.

[0081] Stability testing: In accordance with the requirements of Appendix XIX C "Guiding Principles for Drug Stability Testing" of Part II of the 2010 edition of the Pharmacopoeia of the People's Republic of China, the influencing factor experiment and accelerated experiment were conducted on the enteric-coated plant capsules obtained in the examples of this application and the enteric-coated capsules obtained in the comparative example.

[0082] Influencing factors and experimental conditions:

[0083] Under conditions of high temperature (40℃±2℃), high humidity (RH75%±5%), light (4500Lx±500Lx), low temperature (10℃±2℃), and low humidity (RH10%±5%), the capsules were placed for 10 days, and samples were taken at 0, 5, and 10 days to test the capsule's properties, friability, and viscosity.

[0084] Accelerated experimental conditions:

[0085] Under conditions of 30℃±2℃ and RH60%±5% (saturated NaNO2 solution), the capsules were left to stand for 6 months, and samples were taken at 1, 2, 3 and 6 months to test the capsule's appearance, friability and viscosity.

[0086] Example Example 1

[0087] An enteric-coated plant capsule, the components of which and their corresponding weights (kg) are shown in the table below.

[0088]

[0089] The preparation method of the above-mentioned enteric-coated plant capsules includes the following preparation steps:

[0090] S1 Preparation: The components of the film-forming material, enteric coating mixture and ethyl cellulose aqueous solution are mixed separately to prepare the film-forming material, enteric coating mixture and ethyl cellulose aqueous solution.

[0091] The preparation steps of the above film-forming material are as follows: potassium chloride, polyethylene glycol, and glycerin are added to pure water at 80-90℃ (85℃ in this application example). After stirring and mixing at 6000r / min for 3-5min (4min in this application example), hydroxypropyl methylcellulose is added first and stirred and mixed for 10min. Then, pectin and gellan gum are added and stirred and mixed for 3-5min (4min in this application example). Finally, carrageenan is added and stirred and mixed for 3-5min (4min in this application example). The mixture is then cooled to 50-60℃ (55℃ in this application example) to obtain the film-forming material.

[0092] In this embodiment, the polyethylene glycol is PEG400.

[0093] The coagulant is potassium chloride.

[0094] The preparation steps of the enteric coating mixture are as follows: hydroxypropyl methylcellulose succinate is added to an aqueous sodium hydroxide solution, and stirred at 6000 r / min for 10-20 min (15 min in this application example). Then, the temperature is raised to 50-60℃ (55℃ in this application example), and hydroxypropyl methylcellulose phthalate is added. The mixture is stirred at 6000 r / min for 10-20 min (15 min in this application example) to obtain the enteric coating mixture.

[0095] In this embodiment, the mass concentration of the sodium hydroxide aqueous solution is 0.22 mg / L.

[0096] The preparation steps of the ethyl cellulose aqueous solution are as follows: pure water at 20-30℃ is added to ethyl cellulose, and the mixture is stirred at 6000r / min for 3-5min (4min in the example of this application) to obtain the ethyl cellulose aqueous solution.

[0097] In the embodiments of this application, the viscosity of ethyl cellulose is 4-8 mp·s, and the grade is ECD-RA(C).

[0098] S2 sol: The enteric coating mixture is added to the film-forming material, and after being evacuated for 20 minutes at 65°C and a vacuum degree of 0.0785MPa, it is added to an aqueous solution of ethyl cellulose to obtain the sol.

[0099] S3 Dissolving agent: The adhesive solution is left to stand at 50-60℃ (50℃ in this application example) for 2-4 hours (2 hours in this application example) to obtain the dissolving agent solution;

[0100] S4 Dipping and Molding: Dip the molten adhesive at 50-60℃ (50℃ in this embodiment) and then mold it at 25-35℃ to obtain a blank;

[0101] S5 Drying: Dry the raw material until the moisture content is less than 8% to obtain enteric-coated plant capsules.

[0102] Examples 2-5

[0103] An enteric-coated plant capsule, which differs from Example 1 in that the components and their corresponding weights are shown in the table below.

[0104]

[0105] The enteric-coated plant capsules obtained in Examples 1-5 of this application were tested for friability and disintegration time. The test results are shown in the table below.

[0106]

[0107] Data analysis of the table above shows that the enteric-coated plant capsules obtained in Examples 1-5 have a low friability of 0-2 capsules, a high disintegration time of 120-150 minutes in simulated gastric fluid, and a low disintegration time of 4.0-7.0 minutes in simulated intestinal fluid. This indicates that the enteric-coated plant capsules obtained in Examples 1-5 of this application have high toughness, strong acid resistance, and good enteric properties.

[0108] Further analysis of the table above shows that, compared to Examples 4 and 5, Examples 1-3 exhibit significantly reduced friability, significantly increased disintegration time of the artificial gastric fluid, and significantly reduced disintegration time of the artificial intestinal fluid. Furthermore, Examples 1-3 contain less glycerol and polyethylene glycol compared to Example 5. This indicates that, in the total raw materials for preparing the enteric-coated plant capsules of this application, when the weight ratio of the film-forming material, the enteric coating mixture, and the ethyl cellulose aqueous solution is 1:(0.0752-0.1105):(0.0489-0.0712), the toughness, acid resistance, enteric solubility, and safety of the enteric-coated plant capsules can be improved.

[0109] Example 6

[0110] An enteric-coated plant capsule, which differs from Example 1 in that the weight ratio of hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate in the enteric coating mixture is 1:1.

[0111] Example 7

[0112] An enteric-coated plant capsule, which differs from Example 1 in that the weight ratio of hydroxypropyl methylcellulose acetate succinate to hydroxypropyl methylcellulose phthalate in the enteric coating mixture is 1:2.

[0113] The enteric-coated plant capsules obtained in Examples 6-7 of this application were tested for friability and disintegration time. The test results are shown in the table below.

[0114]

[0115] Data analysis of the table above shows that, compared to Example 1, the disintegration time of the artificial gastric fluid in Examples 6 and 7 is reduced, while the disintegration time of the artificial intestinal fluid is increased. This indicates that, in the total raw materials for preparing the enteric-coated plant capsules of this application, when the weight ratio of hydroxypropyl methylcellulose acetate succinate to hydroxypropyl methylcellulose phthalate in the enteric coating mixture is 1:1.5, the acid stability and enteric solubility of the resulting enteric-coated plant capsules can be improved.

[0116] Example 8

[0117] An enteric-coated plant capsule, which differs from Example 1 in that the mass concentration of the sodium hydroxide aqueous solution in the enteric coating mixture is 0.04 mg / L.

[0118] Example 9

[0119] An enteric-coated plant capsule, which differs from Example 1 in that the mass concentration of the sodium hydroxide aqueous solution in the enteric coating mixture is 0.4 mg / L.

[0120] The enteric-coated plant capsules obtained in Examples 8-9 of this application were tested for friability and disintegration time. The test results are shown in the table below.

[0121]

[0122] Analysis of the data in the table above shows that the enteric-coated plant capsules obtained in Examples 1, 8, and 9 have a friability of 0 capsules, a disintegration time of 135.0-150.0 min in simulated gastric fluid, and a disintegration time of 4.0-5.1 min in simulated intestinal fluid. This indicates that in the total raw materials for preparing the enteric-coated plant capsules of this application, when the mass concentration of sodium hydroxide aqueous solution in the enteric coating mixture is 0.04-0.4 mg / L, the resulting enteric-coated plant capsules exhibit good toughness, acid stability, and enteric solubility. The reason for this may be that the sodium hydroxide aqueous solution at the above-mentioned mass concentration has good solubility for hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate, allowing for thorough mixing of the two phthalates, thus improving the stability of the enteric-coated plant capsules.

[0123] Example 10

[0124] An enteric-coated plant capsule, which differs from Example 1 in that the viscosity of the ethyl cellulose is 9-11 mp·s.

[0125] Example 11

[0126] An enteric-coated plant capsule, which differs from Example 1 in that the viscosity of the ethyl cellulose is 2-3 mp·s.

[0127] The enteric-coated plant capsules obtained in Examples 10-11 of this application were tested for friability and disintegration time. The test results are shown in the table below.

[0128]

[0129] Data analysis of the table above shows that, compared to Example 1, Examples 10 and 11 exhibit increased friability, decreased disintegration time of artificial gastric fluid, and increased disintegration time of artificial intestinal fluid. This indicates that, in the total raw materials for preparing the enteric-coated plant capsules of this application, a viscosity of ethyl cellulose of 4-8 mp·s can improve the toughness, acid stability, and enteric solubility of the resulting enteric-coated plant capsules.

[0130] Example 12

[0131] An enteric-coated plant capsule differs from Example 1 in that, in the preparation step S1 of the enteric-coated plant capsule preparation method, the preparation step of the enteric coating mixture is as follows: hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate are added to an aqueous sodium hydroxide solution, stirred and mixed at 6000 r / min for 15 min, then heated to 55°C, and stirred and mixed at 6000 r / min for 15 min to obtain the enteric coating mixture.

[0132] Example 13

[0133] An enteric-coated plant capsule differs from Example 1 in that the preparation step of S2 sol in the method for preparing the enteric-coated plant capsule is as follows:

[0134] S2 sol: The enteric coating mixture is added to the film-forming material, and after being evacuated for 15 minutes at 60°C and a vacuum degree of 0.065MPa, it is added to an aqueous solution of ethyl cellulose to obtain the sol.

[0135] Example 14

[0136] An enteric-coated plant capsule differs from Example 1 in that the preparation step of S2 sol in the method for preparing the enteric-coated plant capsule is as follows:

[0137] S2 sol: The enteric coating mixture is added to the film-forming material, and after being evacuated for 30 minutes at 70°C and a vacuum degree of 0.092 MPa, it is added to an aqueous solution of ethyl cellulose to obtain the sol.

[0138] The enteric-coated plant capsules obtained in Examples 12-14 of this application were tested for friability and disintegration time. The test results are shown in the table below.

[0139]

[0140] Analysis of the data in the table above shows that, compared to Example 1, Example 12 exhibits increased friability, decreased disintegration time of the artificial gastric fluid, and increased disintegration time of the artificial intestinal fluid. This indicates that in the preparation method of the enteric-coated plant capsules of this application, first dissolving hydroxypropyl methylcellulose acetate succinate in an aqueous sodium hydroxide solution, and then dissolving hydroxypropyl methylcellulose phthalate, can improve the toughness, acid stability, and enteric solubility of the resulting enteric-coated plant capsules. The reason for this may be that hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate have different solubilities in an aqueous sodium hydroxide solution. Dissolving hydroxypropyl methylcellulose acetate succinate first, and then dissolving hydroxypropyl methylcellulose phthalate, increases the compatibility between the two, thereby improving the toughness, acid stability, and enteric solubility of the enteric-coated plant capsules.

[0141] The enteric-coated plant capsules obtained in Examples 1, 13, and 14 exhibited a low friability (0 capsules per capsule), a high disintegration time of 147.0-150.0 min in simulated gastric fluid, and a low disintegration time of 4.0-4.2 min in simulated intestinal fluid. This demonstrates that, in the preparation method of the enteric-coated plant capsules of this application, by controlling the temperature, vacuum level, and time during the S2 sol process, the resulting enteric-coated plant capsules all possess good toughness, acid stability, and enteric solubility.

[0142] Comparative Example 1

[0143] An enteric-coated capsule, which differs from Example 1 in that an equal weight of hydroxypropyl methylcellulose acetate succinate is used instead of hydroxypropyl methylcellulose phthalate.

[0144] Comparative Example 2

[0145] An enteric-coated capsule, which differs from Example 1 in that an equal weight of hydroxypropyl methylcellulose phthalate is used instead of hydroxypropyl methylcellulose acetate succinate.

[0146] Comparative Example 3

[0147] An enteric-coated capsule, which differs from Example 1 in that an equal weight of acetone is used instead of an aqueous solution of sodium hydroxide.

[0148] Comparative Example 4

[0149] An enteric-coated capsule, which differs from Example 1 in that it uses an aqueous sodium hydroxide solution with a mass concentration of 0.01 mg / L.

[0150] Comparative Example 5

[0151] An enteric-coated capsule, which differs from Example 1 in that it uses an aqueous sodium hydroxide solution with a mass concentration of 0.5 mg / L.

[0152] Comparative Examples 6-7

[0153] An enteric-coated capsule differs from Example 1 in that the components of the enteric coating mixture and their corresponding weights (kg) are shown in the table below.

[0154]

[0155] The enteric-coated capsules obtained in Comparative Examples 1-7 of this application were tested for friability and disintegration time. The test results are shown in the table below.

[0156]

[0157] Data analysis of the table above shows that, compared to Example 1, Comparative Examples 1 and 2 exhibit significantly increased friability, significantly decreased disintegration time of artificial gastric fluid, and significantly increased disintegration time of artificial intestinal fluid. This indicates that, in the preparation of the enteric-coated plant capsules of this application, using an enteric coating mixture prepared from a mixture of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, and sodium hydroxide aqueous solution to coat the plant capsules can improve the toughness, acid stability, and enteric solubility of the enteric-coated plant capsules.

[0158] Compared to Example 1, the disintegration time of the artificial gastric fluid in Comparative Example 3 was slightly reduced, while the disintegration time of the artificial intestinal fluid was slightly increased. This indicates that, in the total raw materials for preparing the enteric-coated plant capsules of this application, using sodium hydroxide aqueous solution instead of organic solvents to dissolve hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate results in an enteric coating mixture that improves the toughness, acid stability, and enteric solubility of the enteric-coated plant capsules, while reducing the use of organic solvents and improving the safety of the enteric-coated plant capsules.

[0159] Compared to Example 1, Comparative Examples 4 and 5 showed increased friability, decreased disintegration time of artificial gastric fluid, and increased disintegration time of artificial intestinal fluid. This indicates that, in the total raw materials for preparing the enteric-coated plant capsules of this application, using a sodium hydroxide aqueous solution with a mass concentration of 0.04-0.4 mg / L to dissolve hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate, the resulting enteric coating mixture can improve the toughness, acid stability, and enteric solubility of the enteric-coated plant capsules.

[0160] Compared to Example 1, Comparative Examples 6 and 7 showed a significant increase in friability, a significant decrease in the disintegration time of the artificial gastric fluid, and a significant increase in the disintegration time of the artificial intestinal fluid. This indicates that in the total raw materials for preparing the enteric-coated plant capsules of this application, the enteric coating mixture, composed of 50-120 parts of hydroxypropyl methylcellulose acetate succinate, 50-120 parts of hydroxypropyl methylcellulose phthalate, and 200-300 parts of sodium hydroxide aqueous solution, can improve the resulting enteric coating mixture and enhance the toughness, acid stability, and enteric solubility of the enteric-coated plant capsules.

[0161] The stability of the enteric-coated plant capsules obtained in Examples 1-14 of this application was tested, and the results of the influencing factors experiment and the accelerated test are as follows.

[0162] Experimental results of influencing factors:

[0163] The enteric-coated plant capsules obtained in Examples 1-14 were placed under high temperature (40℃±2℃), high humidity (RH75%±5%), light (4500Lx±500Lx), low temperature (10℃±2℃), and low humidity (RH10%±5%) conditions for 10 days. On day 0, day 5, and day 10, the capsules were smooth, uniform in color, and without deformation.

[0164] The enteric-coated plant capsules obtained in Examples 1-14, after being placed under high temperature (40℃±2℃), high humidity (RH75%±5%), light (4500Lx±500Lx), low temperature (10℃±2℃), and low humidity (RH10%±5%) conditions for 10 days, showed a friability of 0 on days 0, 5, and 10.

[0165] The enteric-coated plant capsules obtained in Examples 1-14 were placed under high temperature (40℃±2℃), high humidity (RH75%±5%), light (4500Lx±500Lx), low temperature (10℃±2℃), and low humidity (RH10%±5%) conditions for 10 days. The viscosity of the capsules on day 0 was 0.0059-0.0062 Pa·s, and the viscosity changes on days 5 and 10 were 0-0.0001 Pa·s.

[0166] Accelerated experimental results:

[0167] The enteric-coated plant capsules obtained in Examples 1-14, after being stored for 6 months at a temperature of 30℃±2℃ and a humidity of RH60%±5% (saturated NaNO2 solution), showed that the capsules were smooth, uniform in color, and without deformation at the 1st, 2nd, 3rd, and 6th months.

[0168] The enteric-coated plant capsules obtained in Examples 1-14, after being stored for 6 months at a temperature of 30℃±2℃ and a humidity of RH60%±5% (saturated NaNO2 solution), had a viscosity of 0.0059-0.0062 Pa·s on day 0, and a viscosity change of 0-0.0002 Pa·s in months 1, 2, 3, and 6.

[0169] The enteric-coated plant capsules obtained in Examples 1-3, 6-9, and 13-14, after being stored for 6 months at a temperature of 30℃±2℃ and a humidity of RH60%±5% (saturated NaNO2 solution), showed a friability of 0 in the 1st, 2nd, 3rd, and 6th months.

[0170] The enteric-coated plant capsules obtained in Examples 4, 5, 10, 11, and 12 were stored at a temperature of 30℃±2℃ and a humidity of RH 60%±5% (NaNO2 saturated solution) for 6 months. The friability at 1, 2, 3, and 6 months is shown in the table below.

[0171]

[0172] Analysis of the stability test results of the enteric-coated plant capsules obtained in Examples 1-14 of this application shows that the enteric-coated plant capsules obtained in Examples 1-14 of this application have high structural stability, low hygroscopicity, and good toughness under conditions of high temperature, high humidity, light, low temperature, and low humidity.

[0173] The enteric-coated capsules obtained in Comparative Examples 1-7 of this application were subjected to stability testing. The results of the influencing factors experiment and the accelerated testing are as follows.

[0174] Experimental results of influencing factors:

[0175] The enteric-coated capsules obtained in Comparative Examples 1-7 were placed under high temperature (40℃±2℃), high humidity (RH75%±5%), light (4500Lx±500Lx), low temperature (10℃±2℃), and low humidity (RH10%±5%) conditions for 10 days. On day 0, the capsules were all smooth, uniform in color, and without deformation. On day 5 and day 10, the capsules in the high humidity (RH75%±5%) environment were deformed, while the capsules in other environments were smooth, uniform in color, and without deformation.

[0176] The enteric-coated capsules obtained in Comparative Examples 1-7 were placed under conditions of high temperature (40℃±2℃), high humidity (RH75%±5%), light (4500Lx±500Lx), low temperature (10℃±2℃), and low humidity (RH10%±5%) for 10 days. The viscosity of the capsules on day 0 was 0.0060-0.0063 Pa·s, and the viscosity changes on days 5 and 10 were 0.0003-0.0004 Pa·s.

[0177] Accelerated experimental results:

[0178] The enteric-coated capsules obtained in Comparative Examples 1-7 were placed at a temperature of 30℃±2℃ and a humidity of RH60%±5% (saturated NaNO2 solution) for 6 months. The capsules showed deformation in the 1st, 2nd, 3rd and 6th months, and in the 3rd month.

[0179] The enteric-coated capsules obtained in Comparative Examples 1-7, after being stored for 6 months at a temperature of 30℃±2℃ and a humidity of RH60%±5% (saturated NaNO2 solution), had a viscosity of 0.0059-0.0062 Pa·s on day 0, and a viscosity change of 0.0005-0.0007 Pa·s on months 1, 2, 3, and 6.

[0180] The results of the friability tests of the enteric-coated capsules obtained in Comparative Examples 1-7, including the influencing factor test and the accelerated test, are shown in the table below.

[0181]

[0182] By comparing the stability test results of the enteric-coated plant capsules obtained in Examples 1-14 of this application with the stability test results of the enteric-coated capsules obtained in Comparative Examples 1-7, it can be seen that the enteric-coated plant capsules obtained in Examples 1-14 of this application have higher structural stability, lower hygroscopicity, and better toughness under conditions of high temperature, high humidity, light, low temperature, and low humidity.

[0183] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. An enteric plant capsule, characterized in that, The film-forming material, the enteric coating mixed solution and the ethyl cellulose aqueous solution; The enteric coating mixed solution comprises the following components in parts by weight: Hydroxypropyl methyl cellulose acetate succinate 50-120 parts; Hydroxypropyl methyl cellulose phthalate 50-120 parts; Sodium hydroxide aqueous solution 200-500 parts; The mass concentration of the sodium hydroxide aqueous solution is 0.04-0.4 mg / L; The film-forming material comprises the following components in parts by weight: Hydroxypropyl methyl cellulose 620-740 parts; Water 2500-4900 parts; Pectin 50-100 parts; Gellan gum 5-35 parts; Carrageenan 0-35 parts; Coagulant 1-10 parts; Glycerol 1-8 parts; Polyethylene glycol 1-12 parts; The ethyl cellulose aqueous solution comprises the following components in parts by weight: Ethyl cellulose 30-60 parts; Water 200-300 parts; The preparation method of the enteric plant capsule comprises the following steps: S1: the components included in the film-forming material, the enteric coating mixed solution and the ethyl cellulose aqueous solution are mixed respectively to prepare the film-forming material, the enteric coating mixed solution and the ethyl cellulose aqueous solution; S2: the enteric coating mixed solution is added to the film-forming material, vacuum is drawn for 15-30 min under the condition of 60-70 ℃ and vacuum degree of 0.065-0.092 MPa, and then the ethyl cellulose aqueous solution is added to obtain a glue solution; S3: the glue solution is placed at 50-60 ℃ for 2-4 h to obtain a molten glue solution; S4: the molten glue solution is dipped at 50-60 ℃ and then formed at 25-35 ℃ to obtain a blank; S5: the blank is dried until the water content is less than 8% to obtain the enteric plant capsule; In the S1, the preparation steps of the enteric coating mixed solution are as follows: hydroxypropyl methyl cellulose acetate succinate is added to sodium hydroxide aqueous solution, and then hydroxypropyl methyl cellulose phthalate is added after stirring and mixing to obtain the enteric coating mixed solution.

2. The enteric plant capsule according to claim 1, wherein, The weight ratio of the film-forming material, the enteric coating mixed solution and the ethyl cellulose aqueous solution is 1:(0.0752-0.1105):(0.0489-0.0712).

3. The enteric plant capsule of claim 2, wherein, The weight ratio of the hydroxypropyl methyl cellulose acetate succinate and the hydroxypropyl methyl cellulose phthalate is 1:(1-2).

4. The enteric plant capsule of claim 3, wherein, The film-forming material comprises the following components in parts by weight: Hydroxypropyl methyl cellulose 700 parts; Water 4092 parts; Pectin 50 parts; Gellan gum 10 parts; Carrageenan 6 parts; Coagulant 8 parts; Glycerol 4 parts; Polyethylene glycol 8 parts; The enteric coating mixed solution comprises the following components in parts by weight: Hydroxypropyl methyl cellulose acetate succinate 50 parts; Hydroxypropyl methyl cellulose phthalate 75 parts; Sodium hydroxide aqueous solution 250 parts; The mass concentration of the sodium hydroxide aqueous solution is 0.22 mg / L; The ethyl cellulose aqueous solution comprises the following components in parts by weight: Ethyl cellulose 47 parts; Water 200 parts.

5. The enteric plant capsule of claim 1, wherein, The viscosity of the ethyl cellulose is 4-8 mp•s.

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