A sustained-release capsule for treating gastric ulcer and a preparation method thereof

Abstract

The present application relates to the technical field of pharmaceutical preparation, in particular to a sustained-release capsule for treating gastric ulcer and a preparation method thereof; the present application takes the traditional formula of Weike Ning as the basis and improves it, uses aluminum magnesium carbonate to replace the traditional white vitriol, the release amount of aluminum ions in the aluminum magnesium carbonate is much lower than that of the white vitriol, and most of the aluminum ions will form insoluble complexes in the intestinal tract and be discharged out of the body, so that the risk of accumulation in the body is extremely low, thereby reducing the side effects on the nervous system and the skeletal system; and the medicine is also subjected to gastric floating and sustained-release treatment, so that the medicine can float above the gastric juice, prolong the residence time of the medicine in the stomach and release slowly, thereby realizing the slow release of the medicine in the stomach and avoiding the defect that the medicine needs to be taken multiple times.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, specifically to a sustained-release capsule for treating gastric ulcers and its preparation method. Background Technology

[0002] Weikening is a classic traditional Chinese medicine. Its formula uses ingredients such as celandine, cuttlebone, phellodendron bark, alum, and menthol as raw materials. Clinically, it is often used to improve symptoms caused by gastric diseases such as gastric ulcers, duodenal ulcers, and chronic gastritis. Its core clinical efficacy focuses on four aspects: pain relief, acid inhibition, mucosal protection, and anti-inflammation. Among them, the calcium carbonate in cuttlebone can directly neutralize gastric acid and reduce the acidity in the stomach. The alkaloids in phellodendron bark and celandine can indirectly inhibit the secretion of gastric acid by gastric parietal cells and reduce the stimulation of gastric acid on the ulcer surface, thereby effectively relieving typical symptoms such as excessive gastric acid, stomach pain, bloating, heartburn, and acid reflux. It is especially suitable for patients with the syndrome of "disharmony between liver and stomach and damp-heat obstruction" in traditional Chinese medicine.

[0003] However, traditional antacids are mostly in the form of ordinary tablets, which disintegrate rapidly in the gastrointestinal tract after oral administration and quickly enter the intestines as the stomach empties. The short gastric retention time results in only moderate bioavailability, and the blood drug concentration rises and falls rapidly over time, leading to rapid decline in efficacy and the need for frequent dosing. This results in poor patient compliance and is especially unsuitable for busy people or elderly patients. Gastric floating formulations, as a modern pharmaceutical product, have the characteristic of significantly prolonging the gastric retention time, enabling long-acting and stable administration. Therefore, it is necessary to improve antacids to avoid the pain point of needing to take them frequently. Summary of the Invention

[0004] The purpose of this invention is to provide a sustained-release capsule for treating gastric ulcers and a method for preparing the same, in order to solve the problems raised in the prior art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0006] S1. Preparation of gastric floating capsule shells;

[0007] S11. Disperse carbomer in purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.5~7.0, and let it stand to swell for 1~1.5h to form a gel-like solution;

[0008] S12. Disperse hydroxypropyl methylcellulose in purified water, heat to 40~45℃, stir and disperse evenly, let stand for 2~3 hours, add the gel solution from step S11 and glycerol, stir and mix at a rate of 1000~1500 rpm for 30~45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0009] S13. Preheat the capsule mold to 32~35℃, immerse it in the capsule glue solution to dip it in the glue, dry it at 33~35℃ and then peel off the mold to obtain the gastric floating capsule shell;

[0010] S2. Preparation of gastric floating sustained-release microspheres;

[0011] S21. After uniformly mixing cuttlefish sheath powder, celandine powder, berberine hydrochloride, magnesium aluminum carbonate and menthol, microcrystalline cellulose and E5 type hydroxypropyl methylcellulose are added and mixed evenly. Then, 20-35% of purified water by dry weight is added dropwise to prepare microsphere soft material. After extruding and spheroidizing with a spheroidizer, microsphere cores with a particle size of 0.8-1.2 mm are obtained.

[0012] S22. Ethyl cellulose is mixed with PEOz-TK-MAL and polyethylene glycol, and then dissolved in an ethanol aqueous solution with a concentration of 75~80wt%. After stirring and mixing evenly, a coating solution is obtained.

[0013] S23. Set the inlet air temperature to 35~40℃, the material temperature to 30~35℃, and the atomization pressure to 0.2~0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 8~10 hours to obtain gastric floating sustained-release microcapsules.

[0014] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0015] Furthermore, in step S1, the amount of each component added, by weight, is 16-20 parts carbomer, 90-100 parts hydroxypropyl methylcellulose, 18-22 parts glycerol and 780-820 parts purified water.

[0016] Furthermore, in step S1, the mass ratio of purified water in step S11 to purified water in step S12 is 3:5 by weight.

[0017] Furthermore, in step S1, the carbomer is any one or more of the 971P or 974P type carbomer; the hydroxypropyl methylcellulose is K15M type hydroxypropyl methylcellulose.

[0018] Furthermore, in step S21, the amount of each component added, by weight, is 70-80 parts cuttlefish skin powder, 5-10 parts celandine powder, 0.05-0.3 parts berberine hydrochloride, 20-30 parts magnesium aluminum carbonate, 1-2 parts menthol, 25-30 parts microcrystalline cellulose and 10-15 parts E5 hydroxypropyl methylcellulose.

[0019] Furthermore, in step S22, the amount of each component added, by weight, is 10 parts ethyl cellulose and 0.5~1.5 parts PEOz-TK-MAL, 2~3 parts polyethylene glycol and 100~120 parts ethanol aqueous solution.

[0020] Furthermore, in step S22, the polyethylene glycol is either polyethylene glycol 4000 or polyethylene glycol 6000.

[0021] Furthermore, a sustained-release capsule for treating gastric ulcers is prepared by the above method.

[0022] Compared with the prior art, the beneficial effects of the present invention are:

[0023] This invention prepares a sustained-release capsule for treating gastric ulcers. The components are based on the traditional formula of Weikening, but with improvements. This invention retains the components of cuttlefish sheath, celandine, and menthol, and uses berberine hydrochloride as the active ingredient to replace phellodendron bark. It also uses magnesium aluminum carbonate to replace traditional alum. The aluminum ion release from magnesium aluminum carbonate is much lower than that from alum, and most of the aluminum ions will form insoluble complexes in the intestines and be excreted from the body, resulting in a very low risk of accumulation in the body, thereby reducing the side effects on the nervous and skeletal systems.

[0024] Furthermore, based on this, the present invention also performs gastric floating and sustained-release treatment on the drug; the present invention first uses a compound system of high viscosity hydroxypropyl cellulose and carbomer as the capsule shell component. This component will quickly absorb water, swell and disintegrate in the stomach, thereby forming a viscous gel material to cover the internal microspheres. Due to the density angle of the gel material, it can initially drive the contents to float above the gastric juice.

[0025] The gastric floating sustained-release microspheres prepared in this invention contain cuttlefish sheath components, primarily composed of calcium carbonate. In gastric acid, these components generate a large amount of gas, which is then coated with an external gel, further maintaining the drug's floating state in the stomach and prolonging its residence time. Furthermore, this invention further enhances the sustained-release properties of the gastric floating sustained-release microspheres by forming a sustained-release coating using ethyl cellulose and polyethylene glycol, achieving a sustained-release effect. Additionally, this invention further incorporates PEOz-TK-MAL as a specific degradation agent into the sustained-release coating. EOz-TK-MAL is a block polymer containing poly(2-ethyl-2-oxazoline), thioketal bonds, and maleimide groups. The thioketal bonds are highly sensitive to reactive oxygen species (ROS). When gastric ulcers are inflamed, the body's immune cells, such as neutrophils and macrophages, clear pathogens, generating a large amount of ROS. The large amount of ROS in these cells attacks the thioketal bonds, thereby accelerating the disintegration of the sustained-release capsule and accelerating drug release. This allows for rapid drug delivery to the ulcer site, increases drug concentration, and forms a protective film, thus accelerating the healing of ulcer tissue. Detailed Implementation

[0026] Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] In this invention, both cuttlefish shell powder and celandine powder used are passed through a 120-mesh sieve; the ethyl cellulose used is ECN100 type ethyl cellulose; and the PEOz-TK-MAL used is provided by Xi'an Ruixi Biotechnology Co., Ltd.

[0028] Example 1. A method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0029] S1. Preparation of gastric floating capsule shells;

[0030] S11. By weight, disperse 16 parts of 974P carbomer into 300 parts of purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.6, and let it stand for 1 hour to form a gel-like solution.

[0031] S12. Disperse 90 parts of K15M type hydroxypropyl methylcellulose in 500 parts of purified water, heat to 42℃, stir and disperse evenly, let stand for 2 hours, add the gel solution from step S11 and 18 parts of glycerol, stir and mix at 1200 rpm for 45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0032] S13. Preheat the capsule mold to 32°C, dip it into the capsule glue solution, dry it at 35°C and then peel off the mold to obtain the gastric floating capsule shell.

[0033] S2. Preparation of gastric floating sustained-release microspheres;

[0034] S21. By weight, 70 parts cuttlefish skin powder, 5 parts celandine powder, 0.3 parts berberine hydrochloride, 20 parts magnesium aluminum carbonate and 1 part menthol are mixed evenly. Then, 25 parts microcrystalline cellulose and 10 parts E5 hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. The microspheres are then extruded and spheroidized to obtain microsphere cores with a particle size of 0.8~1.2 mm.

[0035] S22. By weight, 10 parts of ethyl cellulose, 0.5 parts of PEOz-TK-MAL, and 2 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0036] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0037] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0038] Example 2. A method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0039] Compared with Example 1, this example increases the amount of carbomer and hydroxypropyl methylcellulose added in step S1;

[0040] S1. Preparation of gastric floating capsule shells;

[0041] S11. By weight, disperse 20 parts of 974P carbomer into 300 parts of purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.6, and let it stand for 1 hour to form a gel-like solution.

[0042] S12. Disperse 100 parts of K15M type hydroxypropyl methylcellulose in 500 parts of purified water, heat to 42°C, stir and disperse evenly, let stand for 2 hours, add the gel solution from step S11 and 18 parts of glycerol, stir and mix at 1200 rpm for 45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0043] S13. Preheat the capsule mold to 32°C, dip it into the capsule glue solution, dry it at 35°C and then peel off the mold to obtain the gastric floating capsule shell.

[0044] S2. Preparation of gastric floating sustained-release microspheres;

[0045] S21. By weight, 70 parts cuttlefish skin powder, 5 parts celandine powder, 0.3 parts berberine hydrochloride, 20 parts magnesium aluminum carbonate and 1 part menthol are mixed evenly. Then, 25 parts microcrystalline cellulose and 10 parts E5 hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. The microspheres are then extruded and spheroidized to obtain microsphere cores with a particle size of 0.8~1.2 mm.

[0046] S22. By weight, 10 parts of ethyl cellulose, 0.5 parts of PEOz-TK-MAL, and 2 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0047] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0048] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0049] Example 3. A method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0050] Compared with Example 2, this example increases the amount of cuttlefish skin powder added in step S21;

[0051] S1. Preparation of gastric floating capsule shells;

[0052] S11. By weight, disperse 20 parts of 974P carbomer into 300 parts of purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.6, and let it stand for 1 hour to form a gel-like solution.

[0053] S12. Disperse 100 parts of K15M type hydroxypropyl methylcellulose in 500 parts of purified water, heat to 42°C, stir and disperse evenly, let stand for 2 hours, add the gel solution from step S11 and 18 parts of glycerol, stir and mix at 1200 rpm for 45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0054] S13. Preheat the capsule mold to 32°C, dip it into the capsule glue solution, dry it at 35°C and then peel off the mold to obtain the gastric floating capsule shell.

[0055] S2. Preparation of gastric floating sustained-release microspheres;

[0056] S21. By weight, 80 parts of cuttlefish skin powder, 5 parts of celandine powder, 0.3 parts of berberine hydrochloride, 20 parts of magnesium aluminum carbonate and 1 part of menthol are mixed evenly. Then, 25 parts of microcrystalline cellulose and 10 parts of E5 type hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. After extrusion and spheroidization by a spheroidizer, microsphere cores with a particle size of 0.8~1.2mm are obtained.

[0057] S22. By weight, 10 parts of ethyl cellulose, 0.5 parts of PEOz-TK-MAL, and 2 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0058] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0059] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0060] Example 4. A method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0061] Compared with Example 3, this example increases the amount of PEOz-TK-MAL added in step S22;

[0062] S1. Preparation of gastric floating capsule shells;

[0063] S11. By weight, disperse 20 parts of 974P carbomer into 300 parts of purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.6, and let it stand for 1 hour to form a gel-like solution.

[0064] S12. Disperse 100 parts of K15M type hydroxypropyl methylcellulose in 500 parts of purified water, heat to 42°C, stir and disperse evenly, let stand for 2 hours, add the gel solution from step S11 and 18 parts of glycerol, stir and mix at 1200 rpm for 45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0065] S13. Preheat the capsule mold to 32°C, dip it into the capsule glue solution, dry it at 35°C and then peel off the mold to obtain the gastric floating capsule shell.

[0066] S2. Preparation of gastric floating sustained-release microspheres;

[0067] S21. By weight, 80 parts of cuttlefish skin powder, 5 parts of celandine powder, 0.3 parts of berberine hydrochloride, 20 parts of magnesium aluminum carbonate and 1 part of menthol are mixed evenly. Then, 25 parts of microcrystalline cellulose and 10 parts of E5 type hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. After extrusion and spheroidization by a spheroidizer, microsphere cores with a particle size of 0.8~1.2mm are obtained.

[0068] S22. By weight, 10 parts of ethyl cellulose, 1.5 parts of PEOz-TK-MAL, and 2 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0069] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0070] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0071] Example 5: A method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0072] S1. Preparation of gastric floating capsule shells;

[0073] S11. By weight, disperse 20 parts of 974P carbomer into 300 parts of purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.6, and let it stand for 1 hour to form a gel-like solution.

[0074] S12. Disperse 100 parts of K15M type hydroxypropyl methylcellulose in 500 parts of purified water, heat to 42℃, stir and disperse evenly, let stand for 2 hours, add the gel solution from step S11 and 22 parts of glycerol, stir and mix at 1200 rpm for 45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0075] S13. Preheat the capsule mold to 32°C, dip it into the capsule glue solution, dry it at 35°C and then peel off the mold to obtain the gastric floating capsule shell.

[0076] S2. Preparation of gastric floating sustained-release microspheres;

[0077] S21. By weight, 80 parts of cuttlefish skin powder, 10 parts of celandine powder, 0.3 parts of berberine hydrochloride, 30 parts of magnesium aluminum carbonate and 2 parts of menthol are mixed evenly. Then, 30 parts of microcrystalline cellulose and 15 parts of E5 type hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. After extrusion and spheroidization by a spheroidizer, microsphere cores with a particle size of 0.8~1.2mm are obtained.

[0078] S22. By weight, 10 parts of ethyl cellulose, 1.5 parts of PEOz-TK-MAL, and 3 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0079] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0080] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0081] Comparative Example 1. A method for preparing gastric floating sustained-release microspheres for treating gastric ulcers, comprising the following steps:

[0082] Compared with Example 1, this comparative example only prepared gastric floating sustained-release microspheres;

[0083] S2. Preparation of gastric floating sustained-release microspheres;

[0084] S21. By weight, 70 parts cuttlefish skin powder, 5 parts celandine powder, 0.3 parts berberine hydrochloride, 20 parts magnesium aluminum carbonate and 1 part menthol are mixed evenly. Then, 25 parts microcrystalline cellulose and 10 parts E5 hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. The microspheres are then extruded and spheroidized to obtain microsphere cores with a particle size of 0.8~1.2 mm.

[0085] S22. By weight, 10 parts of ethyl cellulose, 0.5 parts of PEOz-TK-MAL, and 2 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0086] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0087] Comparative Example 2. A method for preparing a sustained-release capsule for treating gastric ulcers, comprising the following steps:

[0088] Compared to Example 1, this comparative example did not use PEOz-TK-MAL;

[0089] S1. Preparation of gastric floating capsule shells;

[0090] S11. By weight, disperse 16 parts of 974P carbomer into 300 parts of purified water, stir and mix evenly, then add triethanolamine dropwise to adjust the pH to 6.6, and let it stand for 1 hour to form a gel-like solution.

[0091] S12. Disperse 90 parts of K15M type hydroxypropyl methylcellulose in 500 parts of purified water, heat to 42℃, stir and disperse evenly, let stand for 2 hours, add the gel solution from step S11 and 18 parts of glycerol, stir and mix at 1200 rpm for 45 minutes, and after vacuum degassing, obtain capsule gel solution.

[0092] S13. Preheat the capsule mold to 32°C, dip it into the capsule glue solution, dry it at 35°C and then peel off the mold to obtain the gastric floating capsule shell.

[0093] S2. Preparation of gastric floating sustained-release microspheres;

[0094] S21. By weight, 70 parts cuttlefish skin powder, 5 parts celandine powder, 0.3 parts berberine hydrochloride, 20 parts magnesium aluminum carbonate and 1 part menthol are mixed evenly. Then, 25 parts microcrystalline cellulose and 10 parts E5 hydroxypropyl methylcellulose are added and mixed evenly. Then, purified water of 30% of the dry weight of the material is added dropwise to prepare microspheres. The microspheres are then extruded and spheroidized to obtain microsphere cores with a particle size of 0.8~1.2 mm.

[0095] S22. By weight, 10 parts of ethyl cellulose and 2 parts of polyethylene glycol 6000 are mixed and then dissolved in 100 parts of an 80 wt% aqueous ethanol solution. After stirring and mixing evenly, a coating solution is obtained.

[0096] S23. Set the inlet air temperature to 38℃, the material temperature to 32℃, and the atomization pressure to 0.3MPa. Spray the coating liquid onto the inner core of the microcapsules. After the coating weight increases by 8~10%, stop spraying and dry and age the microcapsules in a 40℃ oven for 10 hours to obtain gastric floating sustained-release microcapsules.

[0097] S3. Fill the gastric floating sustained-release microspheres into the gastric floating capsule shell, seal the opening, and obtain a sustained-release capsule for the treatment of gastric ulcers.

[0098] Testing: According to the method for determining dissolution and release in the General Chapter of Part IV of the 2020 Chinese Pharmacopoeia, a hydrochloric acid solution containing 0.5% Tween 80 and with a pH of 1.2 was prepared as the release medium. The paddle method was used at 50 rpm and a temperature of 37 ± 0.5 °C. The release behavior of sustained-release capsules prepared in Examples 1-5 and Comparative Examples 1-2 on berberine hydrochloride was determined, and the drift time was also determined.

[0099] Another inflammation simulation group was set up. According to the dissolution and release determination method in the General Chapter of Part IV of the 2020 Chinese Pharmacopoeia, a hydrochloric acid solution containing 0.5% Tween 80 and with a pH of 1.2 was prepared as the release medium. The paddle method was used at 50 rpm and the temperature was 37±0.5℃. Hydrogen peroxide was added to the release medium to make its concentration 100 μmol / L to simulate the gastric fluid near the wound of a gastric ulcer. During the test, the concentration of hydrogen peroxide was monitored and replenished at any time to keep its concentration stable at 100±10 μmol / L. The release behavior of sustained-release capsules prepared in Examples 1-5 and Comparative Examples 1-2 on berberine hydrochloride was tested again.

[0100] The test results are shown in the table below;

[0101]

[0102] As shown in the table above, a comparison of the data from Examples 1, 2, and 5 with Comparative Example 1 reveals that increasing the content of hydroxymethyl cellulose and carbomer in the capsule shell effectively improves the sustained-release function of the drug. After entering the gastric juice, the capsule shell preferentially forms a gel-like substance that coats the surface of the contents of the microspheres, thereby achieving the first-layer sustained-release effect. A comparison of the data from Examples 2 and 3 shows that adding cuttlefish powder further increases the gas content in the gel due to the calcium carbonate component, thus prolonging the floating time of the drug gel in the gastric juice. The data from Example 4 and Comparative Example 2 show that after adding PEOz-TK-MAL, the TK bonds in PEOz-TK-MAL break when facing the increased ROS caused by the inflammatory environment in the human body, thereby accelerating the release of the contents of the microspheres and achieving a rapid increase in drug concentration at the site of ulcer inflammation. Furthermore, the cuttlefish and magnesium aluminum carbonate components contained therein can also achieve rapid coating of the ulcer site, thereby reducing further damage to the ulcer wound by gastric acid.

[0103] Finally, it should be noted that the above descriptions are merely 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, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a sustained-release capsule for treating gastric ulcer, characterized by, Comprise the following steps: S1. Prepare the stomach floating capsule shell; S11. Disperse carbomer into purified water, after stirring and mixing evenly, add triethanolamine dropwise to adjust the pH value to 6.5~7.0, then stand for 1~1.5h to form a gel-like solution; S12. Disperse hydroxypropyl methyl cellulose into purified water, heat to 40~45℃, after stirring and dispersing evenly, stand for 2~3h, then add the gel-like solution of step S11 and glycerol to it, stir and mix at a speed of 1000~1500rpm for 30~45min, then vacuum degassing treatment to obtain a capsule glue solution; S13. Preheat the capsule mold to 32~35℃, dip it into the capsule glue solution for coating, dry and shape at 33~35℃, then peel off the mold to obtain the stomach floating capsule shell; S2. Prepare the stomach floating sustained-release pellets; S21. Mix evenly the cuttlefish bone powder, white chelidonium powder, berberine hydrochloride, and aluminum magnesium carbonate with menthol, then add microcrystalline cellulose and E5 type hydroxypropyl methyl cellulose to it, continue to mix evenly, then add purified water accounting for 20~35% of the dry material mass to prepare a soft material for the pellets, then extrude and round them in a pelletizer to obtain pellets with a particle size of 0.8~1.2mm; Wherein, the adding amount of each component is 70~80 parts of cuttlefish bone powder, 5~10 parts of white chelidonium powder, 0.05~0.3 parts of berberine hydrochloride, 20~30 parts of aluminum magnesium carbonate, 1~2 parts of menthol, 25~30 parts of microcrystalline cellulose, and 10~15 parts of E5 type hydroxypropyl methyl cellulose, by weight fraction; S22. Mix ethyl cellulose and PEOz-TK-MAL, polyethylene glycol, then dissolve them in an ethanol aqueous solution with a concentration of 75~80wt%, stir and mix evenly to obtain a coating solution; S23. Set the inlet air temperature to 35~40℃, the material temperature to 30~35℃, and the atomization pressure to 0.2~0.3MPa, spray the coating solution onto the pellets, stop spraying when the coating weight increases by 8~10%, then dry and age in a 40℃ oven for 8~10h to obtain the stomach floating sustained-release pellets; S3. Fill the stomach floating sustained-release pellets into the stomach floating capsule shell, seal, to obtain the sustained-release capsules for treating gastric ulcer.

2. The method of claim 1, wherein the method is for preparing a sustained release capsule for treating gastric ulcer. In step S1, the adding amount of each component is 16~20 parts of carbomer, 90~100 parts of hydroxypropyl methyl cellulose, 18~22 parts of glycerol, and 780~820 parts of purified water, by weight fraction.

3. The method of claim 1, wherein the method is for preparing a sustained release capsule for treating gastric ulcer. In step S1, the mass ratio of purified water in step S11 to purified water in step S12 is 3:5, by weight fraction.

4. The method of claim 1, wherein the method is for preparing a sustained release capsule for treating gastric ulcer. In step S1, the carbomer is any one or more of carbomer 971P or 974P; the hydroxypropyl methyl cellulose is K15M type hydroxypropyl methyl cellulose.

5. The method of claim 1, wherein the method is for preparing a sustained release capsule for treating gastric ulcer. In step S22, the adding amount of each component is 10 parts of ethyl cellulose, 0.5~1.5 parts of PEOz-TK-MAL, 2~3 parts of polyethylene glycol, and 100~120 parts of ethanol aqueous solution, by weight fraction.

6. The method of claim 1, wherein the method is for preparing a sustained release capsule for treating gastric ulcer. In step S22, the polyethylene glycol is any one of polyethylene glycol 4000 or polyethylene glycol 6000.

7. A sustained release capsule for the treatment of gastric ulcer prepared by the process as claimed in any one of claims 1 to 6.

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