A production process for enteric-coated plant hollow capsules

Abstract

The present invention relates to the technical field of hollow capsules, and specifically to a production process of enteric-coated plant hollow capsules. First, the present invention uses hypromellose as the main material, and carrageenan, Tween 80, and sodium alginate as auxiliary materials. After mixing the main material, auxiliary materials and water, hollow capsules are obtained through processes such as dipping, forming, drying, demolding, and cutting; the present invention also modifies chitosan with sodium palmitate to obtain chitosan-palmitate with hydrophobic properties; a coating solution is prepared by mixing chitosan-palmitate and hypromellose acetate succinate, and the hollow capsules are coated to obtain the finished product. The enteric-coated plant hollow capsules prepared by the present invention have a high finished product rate, a low moisture absorption rate, a long disintegration time in gastric acid, ensure the release of effective components in the upper part of the small intestine, and increase the absorption efficiency.

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:

[0006] Step 1:

[0007] 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;

[0008] Step 2:

[0009] 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.

[0010] 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.

[0011] Further, in step 1, drying is carried out in an environment with a temperature of 65 - 75°C and a relative humidity of 20 - 30%.

[0012] Further, in step 2, the coating time is 10 - 15 s.

[0013] Further, in step 2, drying is carried out in an environment with a temperature of 60 - 70°C and a relative humidity of 20 - 30%.

[0014] Further, in step 2, the preparation method of the coating solution includes the following steps:

[0015] S1: By weight, add 0.5 - 1 part of glacial acetic acid to 2 - 3 parts of chitosan, and grind to obtain chitosan - acetate 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 min, let it stand, filter by suction, and then wash, filter by suction, grind, and dry with deionized water and ethanol at 60 - 70°C respectively to obtain chitosan - palmitate powder;

[0016] S2: Take chitosan - palmitate powder and disperse it in an acetic acid solution with a mass fraction of 2 - 3% and heat to 60 - 65°C to obtain component A; disperse hypromellose acetate succinate powder in a mixed solution of ethanol and dichloromethane and stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, and react at 25 - 35°C in a nitrogen environment for 48 h to obtain the coating solution.

[0017] Further, in S1, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:(0.6 - 0.8).

[0018] Further, in S2, the preparation method of hypromellose acetate succinate powder is as follows: Dry hypromellose by blowing air for 2 - 3 h. By weight, take 10 parts of hypromellose and disperse it in 250 - 280 parts of glacial acetic acid, control the temperature at 75 - 85°C and stir until completely dissolved, keep warm and add 4 - 5 parts of acetic anhydride, 2 - 3 parts of succinic anhydride and 5 - 6 parts of anhydrous sodium acetate, and react for 3 - 5 h; after the reaction ends, add 15 - 20 parts of deionized water and 2 - 3 parts of concentrated hydrochloric acid to terminate the reaction, add the reactants to deionized water at 50 - 60°C, stir until white flocculates appear, filter the white flocculates, wash with deionized water until the pH value is 5.5 - 6, vacuum - dry and grind the washed product to obtain hypromellose acetate succinate powder.

[0019] Further, in S2, in the coating solution, the mass ratio of chitosan - palmitate to hypromellose acetate succinate is 1:(4 - 9).

[0020] 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-coated plant hollow capsules. The present invention uses hydroxypropyl methylcellulose as the main raw material, and carrageenan, Tween 80, and sodium alginate as auxiliary materials. Among them, Tween 80 has an emulsifying effect, effectively preventing the caking of hydroxypropyl methylcellulose and playing a good dispersing role; while sodium alginate and carrageenan, as coagulants, are beneficial to maintaining the stability of the initially coagulated raw materials. The main raw material, auxiliary materials and water are mixed to form a paste-like glue solution, and then subjected to the processes of dipping, forming, drying, demolding, and cutting to obtain hollow capsules.

[0021] Since enteric-coated capsules are required not to dissolve in gastric juice and dissolve in intestinal juice, the hollow capsules are coated to improve their acid resistance on the surface. The present invention selects the derivative of hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, to prepare the coating solution. Hydroxypropyl methylcellulose acetate succinate has better chemical stability and a lower dissolution pH value, which is beneficial 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 penetration resistance and certain hygroscopicity, which is not conducive to the long-term storage of drugs in the capsule, therefore, the present invention modifies chitosan with sodium palmitate to obtain chitosan-palmitate, and mixes chitosan-palmitate with hydroxypropyl methylcellulose acetate succinate to prepare the coating solution. After adding chitosan-palmitate, the hygroscopic property of the coating material is reduced.

[0022] When preparing chitosan-palmitate, the inventors found that controlling the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate to be 1:(0.6 - 0.8) can not only graft sufficient hydrophobic segments onto chitosan to endow it with good hydrophobicity, but also the unreacted amino groups can 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 has an electrostatic adsorption effect with positively charged chitosan, which is beneficial to improving the coating encapsulation rate. In addition, during the preparation of the coating solution, it is necessary to control the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate to be 1:(4 - 9). If the dosage of chitosan-palmitate is too low, the water absorption rate increases, while if the dosage of chitosan-palmitate is too high, the disintegration time in an acidic environment shortens. Detailed implementation mode

[0023] Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0024] Materials and their sources used in the present invention: Hydroxypropyl methylcellulose is from Anhui Shanhe Pharmaceutical Excipients Co., Ltd., pharmaceutical grade, batch number 170826; carrageenan (refined gum) is from Zhaoqing Haixing Biotechnology Co., Ltd., pharmaceutical grade, batch number 1005; chitosan is from Aladdin Reagent (Shanghai) Co., Ltd., with a degree of deacetylation of 95% and a relative molecular mass (Mw) of 50,000; sodium alginate is from Qingdao Jingyan Bioproducts Co., Ltd., medical grade; in the EDC / NHS coupling agent, EDC is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and NHS is N-hydroxysuccinimide; the MES buffer is a pH = 5.0 morpholineethanesulfonic acid (MES) solution in water, and EDC, NHS, and MES are all from Shanghai Covalent Chemical Technology Co., Ltd.

[0025] Example 1: A production process of enteric-coated plant hollow capsules, comprising the following steps:

[0026] Step 1:

[0027] Mix 20 g of hydroxypropyl methylcellulose and 100 g of deionized water, add 2 g of carrageenan and 1 g of Tween 80, continue to stir evenly, and let stand for reaction for 2 h; then vacuum dry and add 5 g of sodium alginate, and then ultrasonically disperse in an ice-water bath for 30 min to obtain a paste-like glue solution; then dip the glue and form, and dry in an environment of 65°C and a relative humidity of 20%, demold and cut to obtain hollow capsules;

[0028] Step 2:

[0029] S1: Blow-dry hydroxypropyl methylcellulose for 2 h, take 10 g of hydroxypropyl methylcellulose and disperse it in 250 g of glacial acetic acid, control the temperature at 75°C and stir until completely dissolved, keep warm and add 4 g of acetic anhydride, 2 g of succinic anhydride and 5 g of anhydrous sodium acetate, and react for 3 h; after the reaction is completed, add 15 g of deionized water and 2 g of concentrated hydrochloric acid to terminate the reaction, add the reactants to deionized water at 50°C, stir until white flocculants appear, filter the white flocculants, wash with deionized water until the pH value is 5.5, vacuum dry and grind the washed product to obtain hydroxypropyl methylcellulose acetate succinate powder;

[0030] S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan and 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 25°C for 30 min, let stand and filter, and then wash, filter, grind and dry with deionized water and ethanol at 60°C respectively to obtain chitosan-palmitate powder; among them, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:0.8;

[0031] S3: Disperse the chitosan - palmitate powder in acetic acid solution with a mass fraction of 3%, and heat it to 60 °C to obtain Component A; disperse the hypromellose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stir to obtain Component B; mix Component A and Component B, add EDC / NHS coupling agent and MES buffer, and react at 25 °C in a nitrogen environment for 48 h to obtain the coating solution; in the coating solution, the mass ratio of chitosan - palmitate to hypromellose acetate succinate is 1:4;

[0032] Step 3:

[0033] Coat the hollow capsule by dipping it into the coating solution for 10 s; after taking it out, dry it in an environment of 65 °C and a relative humidity of 20% to obtain the enteric - coated plant hollow capsule.

[0034] Example 2: A production process of an enteric - coated plant hollow capsule, comprising the following steps:

[0035] Step 1:

[0036] Mix 20 g of hypromellose and 100 g of deionized water, add 2 g of carrageenan and 1 g of Tween 80, continue to stir evenly, and let it stand and react for 2.5 h; then after vacuum drying, add 5 g of sodium alginate, and then ultrasonically disperse it in an ice - water bath for 45 min to obtain a paste - like adhesive solution; then perform dipping and molding, dry it in an environment of 70 °C and a relative humidity of 25%, demold and cut to obtain the hollow capsule;

[0037] Step 2:

[0038] S1: Dry the hypromellose by blowing air for 2.5 h. Take 10 g of hypromellose and disperse it in 250 g of glacial acetic acid, control the temperature at 80 °C and stir until completely dissolved. Keep the temperature and add 4 g of acetic anhydride, 2 g of succinic anhydride and 5 g of anhydrous sodium acetate, and react for 4 h; after the reaction ends, add 15 g of deionized water and 2 g of concentrated hydrochloric acid to terminate the reaction. Add the reactants to deionized water at 55 °C, stir until white flocculants appear, filter the white flocculants, wash them with deionized water until the pH value is 5.5, and vacuum - dry and grind the washed product to obtain the hypromellose acetate succinate powder;

[0039] S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan, and grind to obtain chitosan - acetate powder; take 1 g of chitosan - acetate powder and add it to 100 g of deionized water, add sodium palmitate, stir and react at 30 °C for 45 min, let it stand, filter by suction, and then wash, filter by suction, grind and dry with deionized water and ethanol at 65 °C respectively to obtain chitosan - palmitate powder; among them, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:0.8;

[0040] S3: Disperse chitosan - palmitate powder in acetic acid solution with a mass fraction of 3%, and heat to 63 °C to obtain component A; Disperse hypromellose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stir to obtain component B; Mix component A and component B, add EDC / NHS coupling agent and MES buffer, and react at 30 °C in a nitrogen environment for 48 h to obtain a coating solution; In the coating solution, the mass ratio of chitosan - palmitate to hypromellose acetate succinate is 1:7;

[0041] Step 3:

[0042] Coat the hollow capsule by immersing it in the coating solution for 13 s; After taking it out, dry it in an environment of 70 °C and a relative humidity of 25% to obtain an enteric - coated plant hollow capsule.

[0043] Example 3: A production process of an enteric - coated plant hollow capsule, comprising the following steps:

[0044] Step 1:

[0045] Mix 20 g of hypromellose and 100 g of deionized water, add 2 g of carrageenan and 1 g of Tween 80, continue to stir evenly, and let it stand and react for 3 h; Then, after vacuum drying, add 5 g of sodium alginate, and then ultrasonically disperse it in an ice - water bath for 60 min to obtain a paste - like adhesive solution; Then perform dipping and molding, dry it in an environment of 75 °C and a relative humidity of 30%, demold and cut to obtain a hollow capsule;

[0046] Step 2:

[0047] S1: Dry hypromellose by blowing air for 3 h. Take 10 g of hypromellose and disperse it in 250 g of glacial acetic acid, control the temperature at 85 °C and stir until completely dissolved. Keep the temperature and add 4 g of acetic anhydride, 2 g of succinic anhydride and 5 g of anhydrous sodium acetate, and react for 5 h; After the reaction ends, add 15 g of deionized water and 2 g of concentrated hydrochloric acid to terminate the reaction. Add the reactants to deionized water at 60 °C, stir until white flocculants appear, filter the white flocculants, wash them with deionized water until the pH value is 5.5, and vacuum - dry and grind the washed product to obtain hypromellose acetate succinate powder;

[0048] S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan, and grind to obtain chitosan - acetate powder; Take 1 g of chitosan - acetate powder and add it to 100 g of deionized water, add sodium palmitate, and stir and react at 35 °C for 60 min, let it stand and filter by suction. Then wash, filter by suction, grind and dry it with deionized water and ethanol at 70 °C respectively to obtain chitosan - palmitate powder; Among them, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:0.8;

[0049] S3: Disperse chitosan - palmitate powder in acetic acid solution with a mass fraction of 3%, and heat to 65 °C to obtain component A; Disperse hypromellose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stir to obtain component B; Mix component A and component B, add EDC / NHS coupling agent and MES buffer, and react at 35 °C in a nitrogen environment for 48 h to obtain a coating solution; In the coating solution, the mass ratio of chitosan - palmitate to hypromellose acetate succinate is 1:9;

[0050] Step 3:

[0051] Coat the hollow capsule by immersing it in the coating solution, and the coating time is 15 s; After taking it out, dry it at 75 °C and a relative humidity of 30% to obtain enteric - coated plant hollow capsules.

[0052] Comparative Example 1: When preparing chitosan - palmitate powder, control the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate to be 1:1, and the other parameters are the same as those in Example 1.

[0053] Step 1:

[0054] Mix 20 g of hypromellose and 100 g of deionized water, add 2 g of carrageenan and 1 g of Tween 80, continue to stir evenly, and let it stand and react for 2 h; Then, after vacuum drying, add 5 g of sodium alginate, and then ultrasonically disperse it in an ice - water bath for 30 min to obtain a paste - like adhesive solution; Then dip and form, dry at 65 °C and a relative humidity of 20% environment, demold and cut to obtain hollow capsules;

[0055] Step 2:

[0056] S1: Dry hypromellose by blowing air for 2 h. Take 10 g of hypromellose and disperse it in 250 g of glacial acetic acid. Control the temperature at 75 °C and stir until completely dissolved. Keep the temperature and add 4 g of acetic anhydride, 2 g of succinic anhydride and 5 g of anhydrous sodium acetate, and react for 3 h; After the reaction is completed, add 15 g of deionized water and 2 g of concentrated hydrochloric acid to terminate the reaction. Add the reactants to deionized water at 50 °C, stir until white flocculates appear, filter the white flocculates, wash with deionized water until the pH value is 5.5, and vacuum - dry and grind the washed product to obtain hypromellose acetate succinate powder;

[0057] S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan, and grind to obtain chitosan - acetate powder; Take 1 g of chitosan - acetate powder and add it to 100 g of deionized water, add sodium palmitate, stir and react at 25 °C for 30 min, let it stand, filter by suction, and then wash, filter by suction, grind, and dry with deionized water and ethanol at 60 °C respectively to obtain chitosan - palmitate powder; Among them, the molar ratio of the ammonium ions of chitosan to the carboxylate ions of sodium palmitate is 1:1;

[0058] S3: Take the chitosan - palmitate powder and disperse it in a 3% acetic acid solution by mass, heat to 60 °C to obtain component A; Disperse the hypromellose 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, and react at 25 °C in a nitrogen environment for 48 h to obtain a coating solution; In the coating solution, the mass ratio of chitosan - palmitate to hypromellose acetate succinate is 1:4;

[0059] Step 3:

[0060] Coat the hollow capsule by immersing it in the coating solution, and the coating time is 10 s; After taking it out, dry it in an environment of 65 °C and relative humidity of 20% to obtain an enteric - coated plant hollow capsule.

[0061] Comparative Example 2: Do not add chitosan - palmitate to the coating solution, and the other parameters are the same as those in Example 2.

[0062] Step 1:

[0063] Mix 20 g of hypromellose and 100 g of deionized water, add 2 g of carrageenan and 1 g of Tween 80, continue to stir evenly, and let it react for 2.5 h; Then dry under vacuum and add 5 g of sodium alginate, and then ultrasonically disperse in an ice - water bath for 45 min to obtain a paste - like adhesive solution; Then perform dipping and molding, dry at 70 °C and relative humidity of 25% environment, demold and cut to obtain hollow capsules;

[0064] Step 2:

[0065] S1: Dry the hypromellose by blowing air for 2.5 h, take 10 g of hypromellose and disperse it in 250 g of glacial acetic acid, control the temperature at 80 °C and stir until completely dissolved, keep warm and add 4 g of acetic anhydride, 2 g of succinic anhydride and 5 g of anhydrous sodium acetate, and react for 4 h; After the reaction is completed, add 15 g of deionized water and 2 g of concentrated hydrochloric acid to terminate the reaction, add the reactants to deionized water at 55 °C, stir until white flocculates appear, filter the white flocculates, wash with deionized water until the pH value is 5.5, vacuum - dry and grind the washed product to obtain hypromellose acetate succinate powder;

[0066] S2: Disperse the hypromellose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stir to obtain a coating solution;

[0067] Step 3:

[0068] Immerse the hollow capsule in the coating solution for coating with the coating solution for 13 s; after taking out, dry it in an environment of 70 °C and relative humidity of 25% to obtain an enteric-coated plant hollow capsule.

[0069] Comparative Example 3: Increase the dosage of chitosan palmitate in the coating solution, and the other parameters are the same as those in Example 3.

[0070] Step 1:

[0071] Mix 20 g of hypromellose and 100 g of deionized water, add 2 g of carrageenan and 1 g of Tween 80, continue to stir evenly, and let stand for reaction for 3 h; then after vacuum drying, add 5 g of sodium alginate, and then ultrasonically disperse in an ice-water bath for 60 min to obtain a paste-like adhesive solution; then dip and form, dry in an environment of 75 °C and relative humidity of 30%, demold and cut to obtain a hollow capsule;

[0072] Step 2:

[0073] S1: Dry the hypromellose by blowing air for 3 h, take 10 g of hypromellose and disperse it in 250 g of glacial acetic acid, control the temperature at 85 °C and stir until completely dissolved, keep warm and add 4 g of acetic anhydride, 2 g of succinic anhydride and 5 g of anhydrous sodium acetate, and react for 5 h; after the reaction is completed, add 15 g of deionized water and 2 g of concentrated hydrochloric acid to terminate the reaction, add the reactant to deionized water at 60 °C, stir until white flocculates appear, filter the white flocculates, wash with deionized water until the pH value is 5.5, vacuum dry and grind the washed product to obtain hypromellose acetate succinate powder;

[0074] S2: Add 0.5 g of glacial acetic acid to 2 g of chitosan, and grind to obtain chitosan-acetate 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 and filter, and then wash, filter, grind and dry with deionized water and ethanol at 70 °C respectively to obtain chitosan palmitate powder; among them, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:0.8;

[0075] S3: Disperse chitosan - palmitate powder in acetic acid solution with a mass fraction of 3%, and heat to 65 °C to obtain component A; Disperse hypromellose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stir to obtain component B; Mix component A and component B, add EDC / NHS coupling agent and MES buffer, and react at 35 °C in a nitrogen environment for 48 h to obtain a coating solution; In the coating solution, the mass ratio of chitosan - palmitate to hypromellose acetate succinate is 1:3;

[0076] Step 3:

[0077] Coat the hollow capsules with the coating solution by immersing them in the coating solution for 15 s; After taking them out, dry them in an environment of 75 °C and a relative humidity of 30% to obtain enteric - coated plant hollow capsules.

[0078] Experiment: Conduct performance tests on the enteric - coated plant hollow capsules prepared in Examples 1 - 3 and Comparative Examples 1 - 3.

[0079] Coating encapsulation rate: Randomly select 20 samples in each group, eliminate defective products with irregular shapes such as bubbles, wrinkled skins, and damages, and express it as the percentage of the number of good - shaped capsules in the total number of capsules prepared in the test, that is, the coating encapsulation rate;

[0080] Coating encapsulation rate = number of good products / total number of test samples in each group × 100%.

[0081] Moisture absorption rate: Take 20 samples in each group and place them in a petri dish, accurately weigh and record as W0, take them out after placing them in a drug stability chamber at 25 °C and a relative humidity of 75% for 24 h, accurately weigh and record as W1, and calculate the moisture absorption rate;

[0082] Moisture absorption rate % = (W1 - W0) / W0 × 100%.

[0083] Stability in the stomach and disintegration in the intestine: Load talc powder into the samples (all the samples used are good products), and determine according to the method in the "Disintegration Time Limit of Enteric - Coated Capsules" item in General Chapter 0921 of the Fourth Part of the Chinese Pharmacopoeia 2015 Edition, and record the disintegration time in environments of pH = 1 and pH = 7.2 respectively.

[0084] The test results are shown in Table 1.

[0085] Table 1. Performance test results of enteric - coated plant hollow capsules

[0086]

[0087] 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 the 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 hypromellose acetate succinate cannot crosslink, the coating encapsulation rate is low, and the coating effect is not good. Therefore, the disintegration rate is fast in the environments of pH = 1 and pH = 7.2. The data of Example 2 and Comparative Example 2 show that without adding chitosan-palmitate, the coating encapsulation rate decreases slightly, and the moisture absorption rate of the capsules is relatively large, which is not conducive to the storage of drugs. The data of Example 3 and Comparative Example 3 show that increasing the dosage of chitosan-palmitate in the coating solution shortens the disintegration time of the hollow capsules in the environment of pH = 1.

[0088] Finally, it should be noted that the above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, 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 reaction for 2 to 3 hours; then add sodium alginate after vacuum drying, and then ultrasonically disperse in an ice water bath for 30 to 60 minutes to obtain a paste-like glue solution; then dip in glue, shape, dry, demould, and cut to obtain hollow capsules; Step 2: immersing the hollow capsules in the coating liquid for coating; taking them out and drying them to obtain enteric-coated plant hollow capsules; wherein the preparation method of the coating liquid comprises the following steps: S1: adding glacial acetic acid to chitosan and grinding to obtain chitosan-acetic acid powder; taking chitosan-acetate powder and adding it to deionized water, adding sodium palmitate, stirring and reacting at 25-35°C for 30-60 minutes, standing, filtering, then washing with 60-70°C deionized water and ethanol, filtering, grinding, and drying to obtain chitosan-palmitate powder; S2: Disperse chitosan-palmitate powder in acetic acid solution with a mass fraction of 2-3%, and heat to 60-65°C to obtain component A; disperse hydroxypropyl methylcellulose acetate succinate powder in a mixed solution of ethanol and dichloromethane, and stir to obtain component B; mix component A and component B, add EDC / NHS coupling agent and MES buffer, and react in a nitrogen environment at 25-35°C for 48 hours to obtain a coating solution; In S1, the molar ratio of the ammonium ion of chitosan to the carboxylate ion of sodium palmitate is 1:(0.6-0.8); in S2, in the coating solution, the mass ratio of chitosan-palmitate to hydroxypropyl methylcellulose acetate succinate is 1:(4-9).

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 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.

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 contents of the components in the chitosan-acetic acid powder are, 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 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.

8. Enteric-coated plant hollow capsules prepared by the production process according to any one of claims 1 to 7.

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