Production process of enteric plant empty capsule

Abstract

The invention relates to the technical field of empty capsules, in particular to a production process of enteric plant empty capsules. The preparation method comprises the following steps: firstly, taking hydroxypropyl methylcellulose as a main material, taking carrageenan, Tween 80 and sodium alginate as auxiliary materials, mixing the main material, the auxiliary materials and water, and carrying out glue dipping, forming, drying, demolding and cutting processes to obtain an empty capsule; the preparation method comprises the following steps: modifying chitosan by adopting sodium palmitate, so as to obtain chitosan-palmitate with hydrophobic property; and mixing the chitosan-palmitate with the hydroxypropyl methylcellulose acetate succinate to prepare a coating solution, and coating the hollow capsule to obtain a finished product. The prepared enteric plant empty capsule is high in yield, low in moisture absorption rate and long in disintegration time in gastric acid, it is ensured that effective components are released on the upper portion of the small intestine, and the absorption efficiency is improved.

Description

Technical Field

[0001] The invention relates to the technical field of hollow capsules, in particular to a production process of enteric-coated plant hollow capsules. Background Art

[0002] Enteric-coated capsules are capsules that can only be dissolved and absorbed in the human intestine. They are made of enteric-coated materials. Enteric-coated materials are insoluble in gastric juice, but can disintegrate in intestinal juice to release active ingredients. Therefore, enteric-coated capsules are mainly used for some drugs that are sensitive to gastric juice or irritating to the stomach.

[0003] Hydroxypropyl methylcellulose (2-hydroxypropyl ether methylcellulose) is derived from plant fibers. It is a non-ionic water-soluble polymer obtained by etherifying cotton linters or wood pulp fibers with propylene oxide, chlorinated alkali cellulose and alkali cellulose after alkalization. Hydroxypropyl methylcellulose can be safely absorbed by the human body, and using it as a raw material to prepare capsules can greatly improve safety. Hydroxypropyl methylcellulose contains a large number of hydroxyl groups, which can be modified to improve its tolerance to gastric acid. In addition, in order to improve the storage performance of hollow capsules, it is also necessary to make them hydrophobic to avoid the occurrence of active components failing due to moisture absorption by the capsule material. Summary of the invention

[0004] The purpose of the present invention is to provide a production process of enteric-coated plant hollow capsules to solve the problems raised in the above background technology.

[0005] In order to solve the above technical problems, the present invention provides the following technical solution: a production process of enteric-coated plant hollow capsules, comprising the following steps: Step 1: Mix hydroxypropyl methylcellulose and deionized water, add carrageenan and Tween 80, continue to stir evenly, and let stand for 2-3 hours; then add sodium alginate after vacuum drying, and then ultrasonically disperse in an ice water bath for 30-60 minutes to obtain a paste-like glue solution; then dip in glue, shape, dry, demould, and cut to obtain hollow capsules; Step 2: The hollow capsules are immersed in the coating liquid for coating; after being taken out, they are dried to obtain enteric-coated plant hollow capsules.

[0006] Furthermore, in step 1, the amounts of the components used, by weight, are 16 to 20 parts of hydroxypropyl methylcellulose, 100 parts of deionized water, 1 to 2 parts of carrageenan, 0.8 to 1 part of Tween 80, and 4 to 7 parts of sodium alginate.

[0007] Furthermore, in step 1, drying is performed at 65-75° C. and a relative humidity of 20-30%.

[0008] Furthermore, in step 2, the coating time is 10 to 15 seconds.

[0009] Furthermore, in step 2, drying is performed at 60-70° C. and a relative humidity of 20-30%.

[0010] Furthermore, in step 2, the method for preparing the coating solution comprises the following steps: S1: Add 0.5-1 part of glacial acetic acid to 2-3 parts of chitosan by weight, grind to obtain chitosan-acetic acid powder; take 1 part of chitosan-acetate powder and add it to 100 parts of deionized water, add sodium palmitate, stir and react at 25-35°C for 30-60 minutes, let stand, filter, then wash with 60-70°C deionized water and ethanol, filter, grind, and dry to obtain chitosan-palmitate powder; S2: Disperse chitosan-palmitate powder in 2-3% acetic acid solution by mass, heat to 60-65°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react for 48 hours in a nitrogen environment at 25-35°C to obtain a coating solution.

[0011] Furthermore, in S1, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:(0.6~0.8).

[0012] Furthermore, in S2, the preparation method of hydroxypropyl methylcellulose acetate succinate powder is as follows: blast-dry hydroxypropyl methylcellulose for 2 to 3 hours, dispersing 10 parts of hydroxypropyl methylcellulose in 250 to 280 parts of glacial acetic acid by weight, controlling the temperature to 75 to 85°C and stirring until completely dissolved, adding 4 to 5 parts of acetic anhydride, 2 to 3 parts of succinic anhydride and 5 to 6 parts of anhydrous sodium acetate while keeping warm, and reacting for 3 to 5 hours; after the reaction is completed, adding 15 to 20 parts of deionized water and 2 to 3 parts of concentrated hydrochloric acid to terminate the reaction, adding the reactant to deionized water at 50 to 60°C, stirring until white flocs appear, filtering the white flocs, washing with deionized water to a pH value of 5.5 to 6, vacuum drying the washed product, grinding and crushing it to obtain hydroxypropyl methylcellulose acetate succinate powder.

[0013] Furthermore, in S2, in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:(4~9).

[0014] Compared with the prior art, the beneficial effects achieved by the present invention are as follows: the present invention provides a production process for enteric plant hollow capsules. The present invention uses hydroxypropyl methylcellulose as the main material, carrageenan, Tween 80 and sodium alginate as auxiliary materials, wherein Tween 80 has an emulsifying effect, effectively prevents hydroxypropyl methylcellulose from agglomerating, and plays a good dispersing role; and sodium alginate and carrageenan as coagulants are beneficial to maintaining the stability of the primary coagulation raw materials. The main material, auxiliary materials and water are mixed to form a paste-like glue liquid, and then the glue dipping, molding, drying, demoulding and cutting processes are carried out to obtain hollow capsules.

[0015] Since enteric-coated capsules are required to be insoluble in gastric juice and dissolve in intestinal juice, hollow capsules are coated to improve the acid resistance of their surface. The present invention selects the derivative of hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, to prepare the coating solution. The chemical stability of hydroxypropyl methylcellulose acetate succinate is better, and the pH value of dissolution is low, which is conducive to prolonging the disintegration time of the capsule in gastric acid, ensuring release in the upper part of the small intestine, and increasing the absorption efficiency. However, considering that hydroxypropyl methylcellulose acetate succinate has poor water permeability and has certain hygroscopicity, it is not conducive to the long-term storage of the capsule in the medicine, therefore, the present invention uses sodium palmitate to modify chitosan to obtain chitosan-palmitate, and chitosan-palmitate is mixed with hydroxypropyl methylcellulose acetate succinate to prepare the coating solution, and after adding chitosan-palmitate, the hygroscopicity of the coating material is reduced.

[0016] When preparing chitosan-palmitate, the inventors found that controlling the molar ratio of the ammonium ions of chitosan to the carboxylate ions of sodium palmitate to 1: (0.6~0.8) not only can sufficient hydrophobic segments be grafted onto chitosan to give it good hydrophobicity, but the amino groups that do not participate in the reaction can also react with hydroxypropyl methylcellulose acetate succinate to form a film. At the same time, during the coating process, since sodium alginate in the hollow capsule is a polyanionic polysaccharide with a negative charge, it produces an electrostatic adsorption effect with the positively charged chitosan, which is beneficial to improve the coating encapsulation rate. In addition, in the process of preparing the coating solution, the mass ratio of chitosan-palmitate and hydroxypropyl methylcellulose acetate succinate needs to be controlled to 1: (4~9). If the amount of chitosan-palmitate is too low, the water absorption rate will increase, while if the amount of chitosan-palmitate is too high, the disintegration time in an acidic environment will be shortened. DETAILED DESCRIPTION

[0017] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative work shall fall within the scope of protection of the present invention.

[0018] Materials and sources used in the present invention: Hydroxypropyl methylcellulose comes from Anhui Shanhe Pharmaceutical Excipients Co., Ltd., pharmaceutical grade, batch number 170826; carrageenan (fine gelatin) comes from Zhaoqing Haixing Biotechnology Co., Ltd., pharmaceutical grade, batch number 1005; chitosan comes from Aladdin Reagent (Shanghai) Co., Ltd., with a deacetylation degree of 95% and a relative molecular mass (Mw) of 50,000; sodium alginate comes from Qingdao Jingyan Biological Products Co., Ltd., medical grade; in the EDC / NHS coupling agent, EDC is 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, and NHS is N-hydroxysuccinimide; MES buffer is pH=5.0 aqueous morpholineethanesulfonic acid (MES) solution, and EDC, NHS, and MES are all from Shanghai Covalent Chemical Technology Co., Ltd.

[0019] Embodiment 1: A production process of enteric-coated plant hollow capsules, comprising the following steps: Step 1: 20g of hydroxypropyl methylcellulose and 100g of deionized water were mixed, 2g of carrageenan and 1g of Tween 80 were added, and the mixture was stirred evenly and allowed to stand for 2h. Then, 5g of sodium alginate was added after vacuum drying, and then ultrasonically dispersed in an ice water bath for 30min to obtain a paste-like glue solution. Then, the mixture was dipped in glue and formed, and dried at 65°C and a relative humidity of 20%, and then demolded and cut to obtain hollow capsules. Step 2: S1: Dry the hydroxypropyl methylcellulose with air for 2 hours, take 10g of hydroxypropyl methylcellulose and disperse it in 250g of glacial acetic acid, control the temperature to 75°C and stir until it is completely dissolved, add 4g of acetic anhydride, 2g of succinic anhydride and 5g of anhydrous sodium acetate while keeping warm, and react for 3 hours; after the reaction is completed, add 15g of deionized water and 2g of concentrated hydrochloric acid to terminate the reaction, add the reactant to 50°C deionized water, stir until white flocs appear, filter the white flocs, wash with deionized water until the pH value is 5.5, vacuum dry the washed product, grind and crush to obtain hydroxypropyl methylcellulose acetate succinate powder; S2: Add 0.5g of glacial acetic acid to 2g of chitosan, grind to obtain chitosan-acetic acid powder; take 1g of chitosan-acetate powder and add it to 100g of deionized water, add sodium palmitate, stir and react at 25°C for 30min, let stand, filter, then wash with 60°C deionized water and ethanol, filter, grind and dry to obtain chitosan-palmitate powder; wherein the molar ratio of ammonium ions of chitosan to carboxylate ions of sodium palmitate is 1:0.8; S3: Disperse chitosan-palmitate powder in 3% acetic acid solution, heat to 60°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react for 48 hours at 25°C in a nitrogen environment to obtain a coating solution; in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:4; Step 3: The hollow capsules are immersed in the coating liquid for coating for 10 seconds; after being taken out, they are dried at 65° C. and 20% relative humidity to obtain enteric-coated plant hollow capsules.

[0020] Embodiment 2: A production process of enteric-coated plant hollow capsules, comprising the following steps: Step 1: 20g of hydroxypropyl methylcellulose and 100g of deionized water were mixed, 2g of carrageenan and 1g of Tween 80 were added, and the mixture was stirred evenly and allowed to stand for reaction for 2.5h; 5g of sodium alginate was added after vacuum drying, and then ultrasonically dispersed in an ice water bath for 45min to obtain a paste-like glue solution; then the mixture was dipped in glue and formed, and dried at 70°C and a relative humidity of 25%, and then demolded and cut to obtain hollow capsules; Step 2: S1: Dry the hydroxypropyl methylcellulose with air for 2.5 hours, take 10g of hydroxypropyl methylcellulose and disperse it in 250g of glacial acetic acid, control the temperature to 80°C and stir until it is completely dissolved, add 4g of acetic anhydride, 2g of succinic anhydride and 5g of anhydrous sodium acetate while keeping warm, and react for 4 hours; after the reaction is completed, add 15g of deionized water and 2g of concentrated hydrochloric acid to terminate the reaction, add the reactant to 55°C deionized water, stir until white flocs appear, filter the white flocs, wash with deionized water until the pH value is 5.5, vacuum dry the washed product, grind and crush to obtain hydroxypropyl methylcellulose acetate succinate powder; S2: Add 0.5g of glacial acetic acid to 2g of chitosan, grind to obtain chitosan-acetic acid powder; take 1g of chitosan-acetate powder and add it to 100g of deionized water, add sodium palmitate, stir and react at 30°C for 45min, let stand, filter, then wash with 65°C deionized water and ethanol, filter, grind and dry to obtain chitosan-palmitate powder; wherein the molar ratio of ammonium ions of chitosan to carboxylate ions of sodium palmitate is 1:0.8; S3: Disperse chitosan-palmitate powder in 3% acetic acid solution, heat to 63°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react at 30°C in a nitrogen environment for 48 hours to obtain a coating solution; in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:7; Step 3: The hollow capsules are immersed in the coating liquid for coating for 13 seconds; after being taken out, they are dried at 70° C. and 25% relative humidity to obtain enteric-coated plant hollow capsules.

[0021] Embodiment 3: A production process of enteric-coated plant hollow capsules, comprising the following steps: Step 1: 20g of hydroxypropyl methylcellulose and 100g of deionized water were mixed, 2g of carrageenan and 1g of Tween 80 were added, and the mixture was stirred evenly and allowed to stand for reaction for 3h; 5g of sodium alginate was added after vacuum drying, and then ultrasonically dispersed in an ice water bath for 60min to obtain a paste-like glue solution; then the mixture was dipped in glue, formed, dried at 75°C and a relative humidity of 30%, demolded, and cut to obtain hollow capsules; Step 2: S1: Dry the hydroxypropyl methylcellulose with air for 3 hours, take 10g of hydroxypropyl methylcellulose and disperse it in 250g of glacial acetic acid, control the temperature to 85°C and stir until it is completely dissolved, add 4g of acetic anhydride, 2g of succinic anhydride and 5g of anhydrous sodium acetate while keeping warm, and react for 5 hours; after the reaction is completed, add 15g of deionized water and 2g of concentrated hydrochloric acid to terminate the reaction, add the reactant to deionized water at 60°C, stir until white flocs appear, filter the white flocs, wash with deionized water until the pH value is 5.5, vacuum dry the washed product, grind and crush to obtain hydroxypropyl methylcellulose acetate succinate powder; S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan, grind to obtain chitosan-acetic acid powder; take 1 g of chitosan-acetate powder and add it to 100 g of deionized water, add sodium palmitate, stir and react at 35°C for 60 min, let stand, filter, then wash with 70°C deionized water and ethanol, filter, grind, and dry to obtain chitosan-palmitate powder; wherein the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:0.8; S3: Disperse chitosan-palmitate powder in 3% acetic acid solution, heat to 65°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react at 35°C in a nitrogen environment for 48 hours to obtain a coating solution; in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:9; Step 3: The hollow capsules are immersed in the coating liquid for coating for 15 seconds; after being taken out, they are dried at 75° C. and 30% relative humidity to obtain enteric-coated plant hollow capsules.

[0022] Comparative Example 1: When preparing chitosan-palmitate powder, the molar ratio of the ammonium ions of chitosan to the carboxylate ions of sodium palmitate was controlled to be 1:1, and the other parameters were the same as those in Example 1.

[0023] Step 1: 20g of hydroxypropyl methylcellulose and 100g of deionized water were mixed, 2g of carrageenan and 1g of Tween 80 were added, and the mixture was stirred evenly and allowed to stand for 2h. Then, 5g of sodium alginate was added after vacuum drying, and then ultrasonically dispersed in an ice water bath for 30min to obtain a paste-like glue solution. Then, the mixture was dipped in glue and formed, and dried at 65°C and a relative humidity of 20%, and then demolded and cut to obtain hollow capsules. Step 2: S1: Dry the hydroxypropyl methylcellulose with air for 2 hours, take 10g of hydroxypropyl methylcellulose and disperse it in 250g of glacial acetic acid, control the temperature to 75°C and stir until it is completely dissolved, add 4g of acetic anhydride, 2g of succinic anhydride and 5g of anhydrous sodium acetate while keeping warm, and react for 3 hours; after the reaction is completed, add 15g of deionized water and 2g of concentrated hydrochloric acid to terminate the reaction, add the reactant to 50°C deionized water, stir until white flocs appear, filter the white flocs, wash with deionized water until the pH value is 5.5, vacuum dry the washed product, grind and crush to obtain hydroxypropyl methylcellulose acetate succinate powder; S2: Add 0.5g of glacial acetic acid to 2g of chitosan, grind to obtain chitosan-acetic acid powder; take 1g of chitosan-acetate powder and add it to 100g of deionized water, add sodium palmitate, stir and react at 25°C for 30min, let stand, filter, then wash with 60°C deionized water and ethanol, filter, grind and dry to obtain chitosan-palmitate powder; wherein the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:1; S3: Disperse chitosan-palmitate powder in 3% acetic acid solution, heat to 60°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react for 48 hours at 25°C in a nitrogen environment to obtain a coating solution; in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:4; Step 3: The hollow capsules are immersed in the coating liquid for coating for 10 seconds; after being taken out, they are dried at 65° C. and 20% relative humidity to obtain enteric-coated plant hollow capsules.

[0024] Comparative Example 2: Chitosan-palmitate was not added to the coating solution, and the other parameters were the same as those in Example 2.

[0025] Step 1: 20g of hydroxypropyl methylcellulose and 100g of deionized water were mixed, 2g of carrageenan and 1g of Tween 80 were added, and the mixture was stirred evenly and allowed to stand for reaction for 2.5h; 5g of sodium alginate was added after vacuum drying, and then ultrasonically dispersed in an ice water bath for 45min to obtain a paste-like glue solution; then the mixture was dipped in glue and formed, and dried at 70°C and a relative humidity of 25%, and then demolded and cut to obtain hollow capsules; Step 2: S1: Dry the hydroxypropyl methylcellulose with air for 2.5 hours, take 10g of hydroxypropyl methylcellulose and disperse it in 250g of glacial acetic acid, control the temperature to 80°C and stir until it is completely dissolved, add 4g of acetic anhydride, 2g of succinic anhydride and 5g of anhydrous sodium acetate while keeping warm, and react for 4 hours; after the reaction is completed, add 15g of deionized water and 2g of concentrated hydrochloric acid to terminate the reaction, add the reactant to 55°C deionized water, stir until white flocs appear, filter the white flocs, wash with deionized water until the pH value is 5.5, vacuum dry the washed product, grind and crush to obtain hydroxypropyl methylcellulose acetate succinate powder; S2: dispersing hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stirring to obtain a coating solution; Step 3: The hollow capsules are immersed in the coating liquid for coating for 13 seconds; after being taken out, they are dried at 70° C. and 25% relative humidity to obtain enteric-coated plant hollow capsules.

[0026] Comparative Example 3: The amount of chitosan-palmitate in the coating solution was increased, and the other parameters were the same as those in Example 3.

[0027] Step 1: 20g of hydroxypropyl methylcellulose and 100g of deionized water were mixed, 2g of carrageenan and 1g of Tween 80 were added, and the mixture was stirred evenly and allowed to stand for reaction for 3h; 5g of sodium alginate was added after vacuum drying, and then ultrasonically dispersed in an ice water bath for 60min to obtain a paste-like glue solution; then the mixture was dipped in glue, formed, dried at 75°C and a relative humidity of 30%, demolded, and cut to obtain hollow capsules; Step 2: S1: Dry the hydroxypropyl methylcellulose with air for 3 hours, take 10g of hydroxypropyl methylcellulose and disperse it in 250g of glacial acetic acid, control the temperature to 85°C and stir until it is completely dissolved, add 4g of acetic anhydride, 2g of succinic anhydride and 5g of anhydrous sodium acetate while keeping warm, and react for 5 hours; after the reaction is completed, add 15g of deionized water and 2g of concentrated hydrochloric acid to terminate the reaction, add the reactant to deionized water at 60°C, stir until white flocs appear, filter the white flocs, wash with deionized water until the pH value is 5.5, vacuum dry the washed product, grind and crush to obtain hydroxypropyl methylcellulose acetate succinate powder; S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan, grind to obtain chitosan-acetic acid powder; take 1 g of chitosan-acetate powder and add it to 100 g of deionized water, add sodium palmitate, stir and react at 35°C for 60 min, let stand, filter, then wash with 70°C deionized water and ethanol, filter, grind, and dry to obtain chitosan-palmitate powder; wherein the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:0.8; S3: Disperse chitosan-palmitate powder in 3% acetic acid solution, heat to 65°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react at 35°C in a nitrogen environment for 48 hours to obtain a coating solution; in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:3; Step 3: The hollow capsules are immersed in the coating liquid for coating for 15 seconds; after being taken out, they are dried at 75° C. and 30% relative humidity to obtain enteric-coated plant hollow capsules.

[0028] Experiment: The performance of the enteric-coated plant hollow capsules prepared in Examples 1 to 3 and Comparative Examples 1 to 3 was tested.

[0029] Coating encapsulation rate: 20 samples were randomly selected from each group, and defective samples with irregular morphology such as bubbles, wrinkles, and damage were eliminated. The percentage of good quality capsules with good morphology to the test prepared capsules was expressed as the coating encapsulation rate; Coating encapsulation rate = number of good products / total number of test samples in each group × 100%.

[0030] Moisture absorption rate: Take 20 samples from each group and place them in a watch glass, weigh them accurately and record them as W0, place them in a drug stability box at 25℃ and 75% relative humidity for 24 hours, take them out, weigh them accurately and record them as W1, and calculate the moisture absorption rate; Moisture absorption rate % = (W1-W0) / W0×100%.

[0031] Stability in the stomach and disintegration in the intestine: talcum powder was added to the sample (all samples used were good quality products), and the disintegration time was measured according to the method of item 0921 "Disintegration time of enteric-coated capsules" in the general rules of Part IV of the 2015 edition of the Chinese Pharmacopoeia, and the disintegration time was recorded under pH=1 and pH=7.2 respectively.

[0032] The test results are shown in Table 1.

[0033] Table 1. Performance test results of enteric-coated plant hollow capsules

[0034] Conclusion: The data of Examples 1 to 3 show that the enteric-coated plant hollow capsules prepared by the present invention have good performance. The data of Example 1 and Comparative Example 1 show that when preparing chitosan-palmitate powder, when the molar ratio of the ammonium ions of chitosan to the carboxylate ions of sodium palmitate is 1:1, chitosan-palmitate and hydroxypropyl methylcellulose acetate succinate cannot be cross-linked, the coating encapsulation rate is low, and the coating effect is poor, so the disintegration speed is fast under pH=1 and pH=7.2. The data of Example 2 and Comparative Example 2 show that without the addition of chitosan-palmitate, the coating encapsulation rate decreases slightly, and the moisture absorption rate of the capsule is large, which is not conducive to the storage of medicines. The data of Example 3 and Comparative Example 3 show that the disintegration time of the hollow capsule under pH=1 is shortened by increasing the amount of chitosan-palmitate in the coating solution.

[0035] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A production process of enteric-coated plant hollow capsules, characterized in that: The following steps are involved: Step 1: Mix hydroxypropyl methylcellulose and deionized water, add carrageenan and Tween 80, continue to stir evenly, and let stand for 2-3 hours; then add sodium alginate after vacuum drying, and then ultrasonically disperse in an ice water bath for 30-60 minutes to obtain a paste-like glue solution; then dip in glue, shape, dry, demould, and cut to obtain hollow capsules; Step 2: The hollow capsules are immersed in the coating liquid for coating; after being taken out, they are dried to obtain enteric-coated plant hollow capsules; wherein the preparation method of the coating liquid comprises the following steps: S1: Add glacial acetic acid to chitosan and grind to obtain chitosan-acetic acid powder; add chitosan-acetate powder to deionized water, add sodium palmitate, stir and react at 25-35°C for 30-60 minutes, let stand, filter, then wash with 60-70°C deionized water and ethanol, filter, grind, and dry to obtain chitosan-palmitate powder; S2: Disperse chitosan-palmitate powder in 2-3% acetic acid solution by mass, heat to 60-65°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, react for 48 hours in a nitrogen environment at 25-35°C to obtain a coating solution.

2. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In step 1, the amount of each component, by weight, is 16-20 parts of hydroxypropyl methylcellulose, 100 parts of deionized water, 1-2 parts of carrageenan, 0.8-1 parts of Tween 80, and 4-7 parts of sodium alginate.

3. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In step 1, drying is performed at 65-75° C. and a relative humidity of 20-30%.

4. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In step 2, the coating time is 10 to 15 seconds.

5. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In step 2, drying is performed at 60-70°C and a relative humidity of 20-30%.

6. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In S1, the content of each component in the chitosan-acetic acid powder is, by weight, 2 to 3 parts of chitosan and 0.5 to 1 part of glacial acetic acid.

7. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In S1, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:(0.6~0.8).

8. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In S2, the preparation method of hydroxypropyl methylcellulose acetate succinate powder is as follows: hydroxypropyl methylcellulose is air-dried for 2 to 3 hours and then dispersed in glacial acetic acid, the temperature is controlled to be 75 to 85°C and stirred until completely dissolved, acetic anhydride, succinic anhydride and anhydrous sodium acetate are added while keeping warm, and the reaction is carried out for 3 to 5 hours; after the reaction is completed, deionized water and concentrated hydrochloric acid are added to terminate the reaction, the reactant is added to deionized water at 50 to 60°C, stirred until white flocs appear, the white flocs are filtered, and then washed with deionized water until the pH value is 5.5 to 6, and the washed product is vacuum dried and ground to obtain hydroxypropyl methylcellulose acetate succinate powder.

9. The production process of an enteric-coated plant hollow capsule according to claim 1, characterized in that: In S2, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate in the coating solution is 1:(4~9).

10. Enteric-coated plant hollow capsules prepared according to the production process of any one of claims 1 to 9.

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