Omeprazole enteric capsule and preparation method thereof

Abstract

The invention provides an omeprazole enteric capsule and a preparation method thereof, the omeprazole enteric capsule comprises an omeprazole enteric pellet and a capsule shell, and the omeprazole enteric pellet sequentially comprises a blank medicine core layer, a first protective layer, a medicine carrying layer, a second protective layer, an isolating layer and an enteric layer from inside to outside. According to the prepared omeprazole enteric capsule, due to the introduction of the first protective layer, the second protective layer, the basifier and the like, the medicine has good stability and release property.

Description

Technical Field

[0001] The invention belongs to pharmaceutical technology, and in particular relates to omeprazole enteric-coated capsules and a preparation method thereof. Background Art

[0002] Omeprazole is a proton pump inhibitor, which is commonly used in clinical treatment of intestinal ulcers, gastric ulcers and esophagitis. Omeprazole is weakly alkaline and does not dissolve in gastric acid environment. Therefore, omeprazole enteric-coated capsules need to ensure that they do not dissolve under acidic conditions and completely dissolve under alkaline conditions, so as to achieve better clinical effects.

[0003] The existing method for preparing omeprazole enteric-coated microcapsules is usually to prepare drug-loaded microcapsules by extrusion spheronization, and then coat the drug-loaded microcapsules with an isolation layer and an enteric layer respectively. However, in this process, the distance from the outlet of the spray gun to the surface of the substrate is long, resulting in a long drying process, an increase in the viscosity of the drug-loaded layer, and a poor stability.

[0004] In order to solve the above problems, some other technologies purchase blank pill cores and directly coat the drug-loading layer on the blank pill cores. However, the blank pill cores will also have an adverse effect on the stability of the drug in the drug-loading layer.

[0005] Finally, in order to solve problems such as excipient compatibility and product uniformity, various excipients such as adhesives are added to the drug-carrying layer. However, improper addition and proportion of excipients will not only affect product stability, but will also affect the release of the product. Summary of the invention

[0006] The purpose of the present invention is to provide an olamezole enteric-coated capsule and a preparation method thereof, so as to solve the problems of poor stability and poor release of the existing olamezole enteric-coated capsules, and to provide an olamezole enteric-coated capsule with good stability, good release and uniform appearance and a preparation method thereof.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] An omeprazole enteric-coated capsule comprises an omeprazole enteric-coated micro-pellet and a capsule shell. The omeprazole enteric-coated micro-pellet comprises, from the inside to the outside, a blank drug core layer, a first protective layer, a drug-carrying layer, a second protective layer, an isolation layer and an enteric-coated layer.

[0009] Wherein, the component of the blank drug core layer is selected from any one of sucrose, starch or cellulose;

[0010] The first protective layer comprises a binder and an alkaline agent;

[0011] The components of the drug-carrying layer include omeprazole raw material, hydroxymethyl chitosan, adhesive, alkaline agent, stabilizer and filler;

[0012] The components of the second protective layer include a binder and an alkaline agent;

[0013] The component of the isolation layer is selected from oil-soluble cellulose;

[0014] The components of the enteric layer include enteric materials, lubricants and anti-adhesive agents.

[0015] Wherein, in the first protective layer, the mass ratio of the adhesive to the alkaline agent is 1:0.5-2;

[0016] In the drug-carrying layer, the mass ratio of omeprazole raw material, hydroxymethyl chitosan, binder, alkaline agent, stabilizer and filler is: 1: (0.1-0.2): (0.05-0.07): (0.05-0.07): (0.06-0.08): (0.3-0.6);

[0017] In the second protective layer, the mass ratio of the adhesive to the alkaline agent is 1:0.5-2;

[0018] In the enteric layer, the mass ratio of the enteric material, the lubricant and the anti-adhesive agent is: 1: (0.05-0.1): (0.02-0.05).

[0019] Wherein, the binders in the first protective layer, the drug-carrying layer and the second protective layer are all selected from any one or more of hydroxypropyl methylcellulose, polyvinyl pyrrolidine, povidone and sodium carboxymethyl cellulose;

[0020] The alkaline agents in the first protective layer, the drug-carrying layer and the second protective layer are all selected from any one or more of magnesium carbonate, magnesium hydroxide and sodium carbonate;

[0021] The stabilizer is selected from any one or more of sodium hydroxide, sodium dihydrogen phosphate, disodium hydrogen phosphate, anhydrous sodium carbonate and sodium phosphate;

[0022] The filler is selected from any one or more of microcrystalline cellulose, mannitol, casein, dextrin and starch;

[0023] The enteric material is selected from any one or more of acrylic resin, hypromellose phthalate and methacrylic resin;

[0024] The lubricant is selected from any one or more of magnesium stearate, micro powder silica gel and hydrogenated vegetable oil;

[0025] The anti-adhesive agent is selected from one or both of talc and glyceryl stearate.

[0026] Wherein, the adhesive in the first protective layer and the second protective layer is different from the adhesive in the drug-carrying layer.

[0027] Wherein, the weight gains of the first protective layer, drug-carrying layer, second protective layer, isolation layer and enteric layer are: (2%-5%), (120%-150%), (2%-5%), (10%-15%), (20%-25%) respectively.

[0028] Wherein, the hydroxymethyl chitosan is subjected to radiation treatment.

[0029] Wherein, the particle size D90 of the omeprazole bulk drug is 20-50 microns.

[0030] The present invention further provides a method for preparing omeprazole enteric-coated capsules, comprising the following steps:

[0031] Step S1, first protective layer coating: dissolving a binder and an alkaline agent in an organic solvent, stirring evenly to obtain a first protective layer coating solution, spraying the first protective layer coating solution onto the blank drug core by fluidized bed coating technology, drying to a moisture content of the pellets less than 5% after the spraying, cooling, discharging, and sieving to obtain first protective layer coated pellets;

[0032] Step S2, drug-loaded layer coating: dissolving the prescribed amount of omeprazole API, hydroxymethyl chitosan, binder, alkaline agent, stabilizer and filler in an organic solvent, stirring evenly to obtain a drug-loaded layer coating solution, spraying the drug-loaded layer coating solution onto the first protective layer coated pellets by fluidized bed coating technology, drying to a moisture content of the pellets less than 5% after the spraying, cooling, discharging and sieving to obtain drug-loaded layer coated pellets;

[0033] Step S3, coating the second protective layer: dissolving the binder and the alkaline agent in an organic solvent, stirring evenly to obtain a second protective layer coating solution, spraying the second protective layer coating solution onto the drug-supporting layer coated pellets by fluidized bed coating technology, drying the pellets to a moisture content of less than 5% after spraying, cooling, discharging, and sieving to obtain second protective layer coated pellets;

[0034] Step S4, isolation layer coating: dissolving oil-soluble cellulose in an organic solvent, stirring evenly to obtain an isolation layer coating solution, spraying the isolation layer coating solution onto the second protective layer coated pellets by fluidized bed coating technology, drying after the spraying to a moisture content of the pellets less than 5%, cooling, discharging, and sieving to obtain isolation layer coated pellets;

[0035] Step S5, enteric layer coating: dissolving the enteric material, lubricant and anti-adherent agent in an organic solvent, stirring evenly to obtain an enteric layer coating solution, spraying the enteric layer coating solution onto the isolation layer coated pellets by fluidized bed coating technology, drying after the spraying to a moisture content of the pellets less than 5%, cooling, discharging, and sieving to obtain omeprazole enteric coated pellets;

[0036] Step S6, filling omeprazole enteric-coated micropellets into hollow capsules according to required specifications to obtain omeprazole enteric-coated capsules.

[0037] Among them, in step S1-step S5, the operating parameters of the fluidized bed coating technology are as follows:

[0038] Step S1: Material temperature 30-40 degrees Celsius, spray speed 2-4mL / min, air volume 30-40m 3 / h, atomization pressure (1-2) × 10 5 Pa;

[0039] Step S2: Material temperature 40-60 degrees Celsius, spray speed 8-10mL / min, air volume 50-60m 3 / h, atomization pressure (1-2) × 10 5 Pa;

[0040] Step S3: Material temperature 30-40 degrees Celsius, spray speed 2-4mL / min, air volume 30-40m 3 / h, atomization pressure (1-2) × 10 5 Pa;

[0041] Step S4: Material temperature 40-60 degrees Celsius, spray speed 4-6mL / min, air volume 40-50m 3 / h, atomization pressure (1-2) × 10 5 Pa;

[0042] Step S5: Material temperature 40-50 degrees Celsius, spray speed 4-6mL / min, air volume 40-50m 3 / h, atomization pressure (1-2) × 10 5 Pa.

[0043] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0044] 1. In order to prevent the main drug component from contacting with the components in the blank drug core and the isolation layer, which may lead to the degradation and damage of the components, the present invention considers setting a protective layer between the blank drug core and the drug-carrying layer, and between the drug-carrying layer and the isolation layer. The inventors selected from the common auxiliary materials of the drug-carrying layer and found that the adhesive and alkalizer that can be used to prepare the drug-carrying layer will not damage the main drug component, and the coating process will not affect the appearance and uniformity of the product, especially when the material of the adhesive is different from the material in the drug-carrying layer, the protective effect is more obvious; therefore, the present invention prepares the protective layer with the components of the adhesive and alkalizer that can be used to prepare the drug-carrying layer, and ensures that the material selection of the adhesive in the protective layer is different from the material selection of the adhesive in the drug-carrying layer, the adhesive and the alkalizer will not damage the main drug component, and can prevent the main drug component from directly contacting with the components in the blank drug core or the isolation layer, thereby increasing the stability of the drug;

[0045] 2. In order to prevent the auxiliary materials in the drug-carrying layer from damaging the stability of the main drug component, the present invention attempts to set an alkaline agent in the drug-carrying layer where the main drug component is located and in the protective layer that may be in contact with the main drug component, considering the insolubility of the main drug under acidic conditions. Experiments have confirmed that the alkaline agent can indeed reduce the rupture of the drug during the coating process and increase the stability of the drug;

[0046] 3. The present invention provides adhesives in the drug-carrying layer where the main component is located and in the protective layer that may be in contact with the main drug component. The adhesive can avoid the incompleteness of the drug surface and ensure the appearance and uniformity of the finished drug. At the same time, the present invention finds that when the adhesive in the drug-carrying layer and the adhesive in the protective layer in contact with the drug-carrying layer are selected from different components, it can be more conducive to the stability of the drug. The reason may be that the functional groups of the adhesives of different components are different, which can ensure that the adjacent coated pills are more firmly wrapped during the coating process.

[0047] 4. In the drug-carrying layer of the present invention, in order to promote the compatibility, adsorption and stability of each auxiliary material, the hydroxymethyl chitosan is irradiated to break its hydrogen bonds, so as to wrap each component in the structural network, absorb water and swell, promote disintegration, and ensure good drug release. On this basis, it is unexpectedly found that in addition to improving the drug release, it can also synergistically increase the drug stability. The reason is that the hydrogen bonds are broken to form a network structure, which improves the wrapping effect of the auxiliary materials and avoids the rupture of the main drug component;

[0048] 5. The present invention controls the weight gain of the isolation layer and the enteric layer within a reasonable range, takes into account the stability and release of the drug, and ensures the acid resistance of the product at the same time; if the weight gain is too large, it is not conducive to the release of the internal main drug component and affects the efficacy of the drug; if the weight gain is too small, it cannot play a good coating protection role for the main drug component, and the enteric layer is prone to aging, affecting the stability. Combined with the metabolic environment of the intestine where omeprazole is located, the inventor sets the weight gain of the isolation layer and the enteric layer to (10%-15%) and (20%-25%) respectively through optimization experiments; in this weight gain range, it can ensure that omeprazole is completely released within one hour after entering the intestine, and will not affect the stability of the main drug component;

[0049] 6. The present invention controls the particle size of the omeprazole raw material within a reasonable range to take into account both the release and the uniformity of the appearance. If the particle size is too small, the release is good and it is easy to agglomerate, but the product appearance is poor and the uniformity is not good. If the particle size is too large, it is difficult to mix, the uniformity is poor, and the release is poor. DETAILED DESCRIPTION

[0050] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0051] Examples 1-5

[0052] This embodiment provides a method for preparing olamezole enteric-coated capsules, comprising the following steps:

[0053] Step S1: coating the first protective layer: dissolving the binder and the alkaline agent in an organic solvent, stirring evenly to obtain a first protective layer coating solution, spraying the first protective layer coating solution onto the blank drug core by fluidized bed coating technology, drying to a moisture content of the pellets of 1.37% after the spraying, cooling, discharging, and sieving to obtain first protective layer coated pellets;

[0054] Step S2, drug-loaded layer coating: dissolving the prescribed amount of omeprazole API, radiation-treated hydroxymethyl chitosan (absorbed dose rate of 55 Gy / min, irradiation time of 7 hours), adhesive, alkaline agent, stabilizer and filler in an organic solvent, stirring evenly to obtain a drug-loaded layer coating liquid, spraying the drug-loaded layer coating liquid onto the first protective layer coated pellets by fluidized bed coating technology, drying to a moisture content of 1.92% after spraying, cooling, discharging, sieving, obtaining drug-loaded layer coated pellets, lifting, and the particle size D90 of the omeprazole API is 30 microns;

[0055] Step S3, second protective layer coating: dissolving the binder and the alkaline agent in an organic solvent, stirring evenly to obtain a second protective layer coating solution, spraying the second protective layer coating solution onto the drug-carrying layer coated pellets by fluidized bed coating technology, drying to a moisture content of 1.57% after spraying, cooling, discharging, and sieving to obtain second protective layer coated pellets;

[0056] Step S4, isolation layer coating: dissolving the binder and the alkaline agent in an organic solvent, stirring evenly to obtain an isolation layer coating liquid, spraying the isolation layer coating liquid onto the second protective layer coated pellets by fluidized bed coating technology, drying to a moisture content of the pellets of 1.93% after the spraying, cooling, discharging, and sieving to obtain isolation layer coated pellets;

[0057] Step S5, enteric layer coating: dissolving the enteric material, lubricant and anti-adherent agent in an organic solvent, stirring evenly to obtain an enteric layer coating solution, spraying the enteric layer coating solution onto the isolation layer coated pellets by fluidized bed coating technology, drying to a moisture content of the pellets of 1.27% after the spraying, cooling, discharging and sieving to obtain omeprazole enteric coated pellets;

[0058] Step S6, filling omeprazole enteric-coated micropellets into hollow capsules according to required specifications to obtain omeprazole enteric-coated capsules.

[0059] In the above embodiments, the selection and proportion of each component in each drug, the weight gain of each layer and the fluidized bed process parameters are shown in Tables 1 to 3 respectively.

[0060] Table 1: Ingredient selection and ratio of Examples 1-5

[0061]

[0062]

[0063]

[0064] Among them, hydroxypropyl methylcellulose was purchased from Merck's official website, product number H7509, molecular weight 86kDa, viscosity 2600-5600cP;

[0065] Polyvinylpyrrolidine was purchased from Merck’s official website, product number 77627, particle size 110 μm;

[0066] Povidone was purchased from Merck’s official website, product number P2472;

[0067] Sodium carboxymethyl cellulose was purchased from Merck’s official website, product number 419338, relative molecular mass 700000;

[0068] Hydroxymethyl chitosan was purchased from Merck’s official website, product number 912123, and the specific structure is N, N, N-trimethyl chitosan;

[0069] Microcrystalline cellulose was purchased from Merck’s official website, product number 1.02330, with a particle size of 5–40 μm;

[0070] Mannitol was purchased from Merck’s official website, product number 100494, molecular weight 182;

[0071] Casein was purchased from Merck’s official website, product number C7078;

[0072] Dextrin was purchased from Merck’s official website, product number D2006, degree of polymerization 50-100;

[0073] Starch was purchased from Merck official website, product number 33615, degree of polymerization 50-100;

[0074] The oil-soluble cellulose is specifically hydroxypropyl cellulose, purchased from the official website of Merck, product number 1329822;

[0075] Acrylic resin was purchased from Merck’s official website, product number L9774;

[0076] Hydroxypropyl methylcellulose phthalate was purchased from Merck’s official website, product number L9774, density 0.6 g / mL;

[0077] The specific structure of methacrylic resin is methyl methacrylate, purchased from Merck official website, product number Y0001488, density 0.936 g / mL;

[0078] Micropowder silica gel was purchased from Merck’s official website, product number 1.07748, with a particle size of 5–40 μm;

[0079] Talc powder was purchased from Guangzhou Aichuan Chemical Co., Ltd., with a specification of 325 mesh;

[0080] Stearic acid glyceryl ester is 1,2-stearate glyceryl ester purchased from Merck official website, product number 43697, molecular weight 625.

[0081] Table 2: Weight gain of each coated pellet of Example 1-5 drug pellets

[0082]

[0083] Table 3: Process parameters for preparing drug pellets in Examples 1-5

[0084]

[0085]

[0086]

[0087] Comparative Example 1

[0088] The difference from Example 1 is that there is no first protective layer, and other processes, materials and proportions are the same as those in Example 1.

[0089] Comparative Example 2

[0090] The difference from Example 1 is that there is no second protective layer, and other processes, materials and proportions are the same as those in Example 1.

[0091] Comparative Example 3

[0092] The difference from Example 1 is that the hydroxymethyl chitosan is not irradiated, and other processes, materials and proportions are the same as those in Example 1.

[0093] Comparative Example 4

[0094] The difference from Example 1 is that the binders of the first protective layer, the drug-carrying layer and the second protective layer are all selected from hydroxypropyl methylcellulose, and the other processes, materials and proportions are the same as those in Example 1.

[0095] Comparative Example 5

[0096] The difference from Example 1 is that the weight of each component in the isolation layer and the enteric layer is twice that of Example 1, resulting in the weight gain of the isolation layer and the enteric layer reaching 20.1% and 39.2% respectively. Other processes, materials and proportions are the same as those in Example 1.

[0097] Comparative Example 6

[0098] The difference from Example 1 is that the weight of each component in the isolation layer and the enteric layer is half of that in Example 1, resulting in the weight gain of the isolation layer and the enteric layer reaching 6.3% and 12.4% respectively. Other processes, materials and proportions are the same as those in Example 1.

[0099] In the present invention, in the process of preparing omeprazole enteric-coated pellets, the weight gain of each coated pellet is (the total weight of the pellets after the preparation of the pellets - the total weight of the pellets before the preparation of the pellets) / the total weight of the pellets before the preparation of the pellets, such as the weight gain of the first protective layer coated pellets = (the weight of the first protective layer coated pellets - the weight of the blank drug core) / the weight of the blank drug core.

[0100] Stability effect verification:

[0101] The samples (omeprazole enteric-coated pellets not filled into hollow capsules) were placed under a light environment (4500-5000 l x), and the total impurity content was measured regularly. The results are shown in Table 4.

[0102] Table 4: Stability effect verification results

[0103]

[0104]

[0105] Among them, the total impurity content is determined by high performance liquid chromatography (General Rules 0512 of Part IV of the 2020 edition of the "Chinese Pharmacopoeia") and calculated by peak area using the external standard method. The preparation methods of the reference and test solutions refer to Method 2, General Rules 0931 of Part IV of the 2020 edition of the "Chinese Pharmacopoeia".

[0106] Combined with the stability data of Examples 1-5, it can be seen that the omeprazole enteric-coated microcapsules prepared by the present invention have good stability. After 150 days of accelerated experiment, the total impurity content has hardly increased, which can fully meet the shelf life of the product; Combined with the stability data of Comparative Example 3, it can be seen that under the premise that the hydroxymethyl chitosan is irradiated, the stability of the omeprazole enteric-coated microcapsules is slightly reduced. Analysis may be that the hydrogen bonds are not broken, the wrapping effect of the auxiliary materials is poor, and the main drug components are easily broken; Combined with the stability data of Comparative Examples 1-2 and Comparative Examples 4-6, it can be seen that: in the absence of the first protective layer, or the absence of the second protective layer, or the binder of the drug-carrying layer is the same as the first protective layer and the second protective layer, or the isolation layer and the enteric layer are not weighted enough, the stability of the omeprazole enteric-coated microcapsules is significantly reduced, which also proves the technical concept and technical effect of the present invention.

[0107] Release effect verification:

[0108] Referring to the release determination method in the second method of Part IV General Rules 0931 of the 2020 edition of the "Chinese Pharmacopoeia": prepare a hydrochloric acid solution with a pH of 1-1.5, soak and rotate the prepared sample (omeprazole enteric-coated microcapsules not filled into hollow capsules) in the acidic solution for 2 hours, then adjust the solution pH to 6.5-7.0 with sodium hydroxide, continue to rotate for 1 hour, take samples at the time intervals in the table below, and determine the dissolution amount of each embodiment, as shown in Table 5.

[0109] Table 5: Release effect verification results

[0110]

[0111]

[0112] From the data in the above table, it can be seen that under the environment of simulated intestinal drug release, the omeprazole enteric-coated capsules provided by the present invention can achieve a release rate of more than 90% in 15 minutes, and is basically completely released in 60 minutes, with a good release effect; combined with the data of Example 1, Comparative Example 1 and Comparative Example 2, it can be seen that the addition of the first protective layer and the second protective layer does not affect the release of the drug; combined with the data of Example 1 and Comparative Example 3, it can be seen that hydroxymethyl chitosan without radiation treatment will reduce the release of the drug; combined with the data of Example 1 and Comparative Example 5, it can be seen that the weight gain of the isolation layer and the enteric layer is too heavy, which will affect the release of the drug.

[0113] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An omeprazole enteric-coated capsule, characterized in that: The method comprises omeprazole enteric-coated micropellets and a capsule shell, wherein the omeprazole enteric-coated micropellets sequentially comprise: a blank drug core layer, a first protective layer, a drug-carrying layer, a second protective layer, an isolation layer and an enteric-coated layer from the inside to the outside; Wherein, the components of the first protective layer include an adhesive and an alkaline agent; The components of the drug-carrying layer include omeprazole raw material, hydroxymethyl chitosan, adhesive, alkaline agent, stabilizer and filler; The components of the second protective layer include a binder and an alkaline agent.

2. The omeprazole enteric-coated capsule according to claim 1, characterized in that: The component of the blank drug core layer is selected from any one of sucrose, starch or cellulose; The component of the isolation layer is selected from oil-soluble cellulose; The components of the enteric layer include enteric materials, lubricants and anti-adhesive agents.

3. The omeprazole enteric-coated capsule according to claim 2, characterized in that: In the first protective layer, the mass ratio of the adhesive to the alkaline agent is 1:0.5-2; In the drug-carrying layer, the mass ratio of omeprazole raw material, hydroxymethyl chitosan, binder, alkaline agent, stabilizer and filler is: 1: (0.1-0.2): (0.05-0.07): (0.05-0.07): (0.06-0.08): (0.3-0.6); In the second protective layer, the mass ratio of the adhesive to the alkaline agent is 1:0.5-2; In the enteric layer, the mass ratio of the enteric material, the lubricant and the anti-adhesive agent is: 1: (0.05-0.1): (0.02-0.05).

4. The omeprazole enteric-coated capsule according to claim 2, characterized in that: The binders in the first protective layer, the drug-carrying layer and the second protective layer are all selected from any one or more of hydroxypropyl methylcellulose, polyvinyl pyrrolidine, povidone and sodium carboxymethyl cellulose; The alkaline agents in the first protective layer, the drug-carrying layer and the second protective layer are all selected from any one or more of magnesium carbonate, magnesium hydroxide and sodium carbonate; The stabilizer is selected from any one or more of sodium hydroxide, sodium dihydrogen phosphate, disodium hydrogen phosphate, anhydrous sodium carbonate and sodium phosphate; The filler is selected from any one or more of microcrystalline cellulose, mannitol, casein, dextrin and starch; The enteric material is selected from any one or more of acrylic resin, hypromellose phthalate and methacrylic resin; The lubricant is selected from any one or two or more of magnesium stearate, micro powder silica gel and hydrogenated vegetable oil; The anti-adhesive agent is selected from one or both of talc and glyceryl stearate.

5. The omeprazole enteric-coated capsule according to claim 2, characterized in that: The adhesive in the first protective layer and the second protective layer is different from the adhesive in the drug-carrying layer.

6. The omeprazole enteric-coated capsule according to claim 2, characterized in that: The weight gains of the first protective layer, drug-carrying layer, second protective layer, isolation layer and enteric layer are: (2%-5%), (120%-150%), (2%-5%), (10%-15%), (20%-25%) respectively.

7. The omeprazole enteric-coated capsule according to claim 2, characterized in that: The hydroxymethyl chitosan is irradiated.

8. The omeprazole enteric-coated capsule according to claim 2, characterized in that: The particle size D90 of the omeprazole bulk drug is 20-50 microns.

9. The method for preparing the omeprazole enteric-coated capsules according to any one of claims 2 to 8, characterized in that: The steps include: Step S1, first protective layer coating: dissolving a binder and an alkaline agent in an organic solvent, stirring evenly to obtain a first protective layer coating solution, spraying the first protective layer coating solution onto the blank drug core by fluidized bed coating technology, drying to a moisture content of the pellets less than 5% after the spraying, cooling, discharging, and sieving to obtain first protective layer coated pellets; Step S2, drug-loaded layer coating: dissolving the prescribed amount of omeprazole API, hydroxymethyl chitosan, binder, alkaline agent, stabilizer and filler in an organic solvent, stirring evenly to obtain a drug-loaded layer coating solution, spraying the drug-loaded layer coating solution onto the first protective layer coated pellets by fluidized bed coating technology, drying to a moisture content of the pellets less than 5% after the spraying, cooling, discharging and sieving to obtain drug-loaded layer coated pellets; Step S3, coating the second protective layer: dissolving the binder and the alkaline agent in an organic solvent, stirring evenly to obtain a second protective layer coating solution, spraying the second protective layer coating solution onto the drug-supporting layer coated pellets by fluidized bed coating technology, drying the pellets to a moisture content of less than 5% after spraying, cooling, discharging, and sieving to obtain second protective layer coated pellets; Step S4, isolation layer coating: dissolving oil-soluble cellulose in an organic solvent, stirring evenly to obtain an isolation layer coating solution, spraying the isolation layer coating solution onto the second protective layer coated pellets by fluidized bed coating technology, drying after the spraying to a moisture content of the pellets less than 5%, cooling, discharging, and sieving to obtain isolation layer coated pellets; Step S5, enteric layer coating: dissolving the enteric material, lubricant and anti-adherent agent in an organic solvent, stirring evenly to obtain an enteric layer coating solution, spraying the enteric layer coating solution onto the isolation layer coated pellets by fluidized bed coating technology, drying after the spraying to a moisture content of the pellets less than 5%, cooling, discharging, and sieving to obtain omeprazole enteric coated pellets; Step S6, filling omeprazole enteric-coated micropellets into hollow capsules according to required specifications to obtain omeprazole enteric-coated capsules.

10. The method for preparing omeprazole enteric-coated capsules according to claim 9, characterized in that: In step S1 to step S5, the operating parameters of the fluidized bed coating technology are as follows: Step S1: Material temperature 30-40 degrees Celsius, spray speed 2-4mL / min, air volume 30-40m 3 / h, atomization pressure (1-2) × 10 5 Pa; Step S2: Material temperature 40-60 degrees Celsius, spray speed 8-10mL / min, air volume 50-60m 3 / h, atomization pressure (1-2) × 10 5 Pa; Step S3: Material temperature 30-40 degrees Celsius, spray speed 2-4mL / min, air volume 30-40m 3 / h, atomization pressure (1-2) × 10 5 Pa; Step S4: Material temperature 40-60 degrees Celsius, spray speed 4-6mL / min, air volume 40-50m 3 / h, atomization pressure (1-2) × 10 5 Pa; Step S5: Material temperature 40-50 degrees Celsius, spray speed 4-6mL / min, air volume 40-50m 3 / h, atomization pressure (1-2) × 10 5 Pa.

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