An omeprazole enteric-coated capsule and its preparation method

Abstract

The present invention provides an omeprazole enteric-coated capsule and a preparation method thereof. The omeprazole enteric-coated capsule comprises omeprazole enteric-coated pellets and a capsule shell. The omeprazole enteric-coated pellets sequentially comprise, from the inside to the outside: a blank drug core layer, a first protective layer, a drug-loading layer, a second protective layer, an isolation layer and an enteric-coated layer. For the omeprazole enteric-coated capsule prepared by the present invention, through the introduction of the first protective layer, the second protective layer, an alkalizing agent, etc., the drug has good stability and release property.

Description

Technical Field

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

[0002] Omeprazole is a proton pump inhibitor, which is commonly used clinically to treat intestinal ulcers, gastric ulcers, esophagitis, etc. Omeprazole is weakly alkaline and insoluble in the gastric acid environment. Therefore, omeprazole enteric-coated capsules need to ensure that it does not dissolve in acidic conditions and completely dissolves in alkaline conditions, so as to achieve better clinical effects.

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

[0004] To solve the above problems, some other technologies purchase blank pellets and directly coat a drug-loaded layer on the blank pellets. However, the blank pellets will also have an adverse effect on the drug stability in the drug-loaded layer.

[0005] Finally, to solve problems such as excipient compatibility and product uniformity, a variety of excipients such as binders are added to the drug-loaded layer. However, improper addition and proportioning of the excipients will not only affect the product stability, but also affect the release property of the product. Summary of the Invention

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

[0007] To achieve the above purpose, the present invention provides the following technical solutions:

[0008] An omeprazole enteric-coated capsule, comprising omeprazole enteric-coated pellets and a capsule shell, and the omeprazole enteric-coated pellets sequentially include from inside to outside: a blank drug core layer, a first protective layer, a drug-loaded layer, a second protective layer, an isolation layer and an enteric layer.

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

[0010] The component of the first protective layer includes a binder and an alkaline agent;

[0011] The component of the drug-loaded layer includes omeprazole raw material medicine, hydroxymethyl chitosan, a binder, an alkaline agent, a stabilizer and a filler;

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

[0013] The components of the isolation layer are selected from oil-soluble cellulose;

[0014] The components of the enteric-coated layer include an enteric material, a lubricant, and an anti-adhesive agent.

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

[0016] In the drug-loading layer, the mass ratio of omeprazole API, hydroxymethyl chitosan, adhesive, 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-coated layer, the mass ratio of the enteric material, lubricant, and anti-adhesive agent is: 1:(0.05 - 0.1):(0.02 - 0.05).

[0019] Among them, the adhesive in the first protective layer, drug-loading layer, and second protective layer is selected from any one or more of hydroxypropyl methylcellulose, polyvinylpyrrolidone, povidone, and sodium carboxymethylcellulose;

[0020] The alkaline agent in the first protective layer, drug-loading layer, and second protective layer is 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, hydroxypropyl methylcellulose phthalate, and methacrylic resin;

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

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

[0026] Among them, the adhesive in the first protective layer and the second protective layer is different from the adhesive in the drug-loading layer.

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

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

[0029] Among them, the particle size D90 of the omeprazole raw material drug is 20-50 microns.

[0030] The present invention further provides a preparation method of an omeprazole enteric capsule, comprising the following steps:

[0031] Step S1, coating of the first protective layer: Dissolve the binder and the alkaline agent in an organic solvent, stir evenly to obtain the coating solution for the first protective layer, and spray the coating solution for the first protective layer onto the blank drug core by fluidized bed coating technology. After spraying, dry until the moisture content of the pellets is less than 5%, cool, discharge, and screen to obtain the pellets coated with the first protective layer;

[0032] Step S2, coating of the drug-loading layer: Dissolve the prescribed amount of omeprazole raw material drug, hydroxymethyl chitosan, binder, alkaline agent, stabilizer and filler in an organic solvent, stir evenly to obtain the coating solution for the drug-loading layer, and spray the coating solution for the drug-loading layer onto the pellets coated with the first protective layer by fluidized bed coating technology. After spraying, dry until the moisture content of the pellets is less than 5%, cool, discharge, and screen to obtain the pellets coated with the drug-loading layer;

[0033] Step S3, coating of the second protective layer: Dissolve the binder and the alkaline agent in an organic solvent, stir evenly to obtain the coating solution for the second protective layer, and spray the coating solution for the second protective layer onto the pellets coated with the drug-loading layer by fluidized bed coating technology. After spraying, dry until the moisture content of the pellets is less than 5%, cool, discharge, and screen to obtain the pellets coated with the second protective layer;

[0034] Step S4, coating of the isolation layer: Dissolve the oil-soluble cellulose in an organic solvent, stir evenly to obtain the coating solution for the isolation layer, and spray the coating solution for the isolation layer onto the pellets coated with the second protective layer by fluidized bed coating technology. After spraying, dry until the moisture content of the pellets is less than 5%, cool, discharge, and screen to obtain the pellets coated with the isolation layer;

[0035] Step S5, coating of the enteric coating layer: Dissolve the enteric material, lubricant and anti-sticking agent in an organic solvent, stir evenly to obtain the coating solution for the enteric coating layer, and spray the coating solution for the enteric coating layer onto the pellets coated with the isolation layer by fluidized bed coating technology. After spraying, dry until the moisture content of the pellets is less than 5%, cool, discharge, and screen to obtain the omeprazole enteric pellets;

[0036] Step S6: Fill the enteric-coated omeprazole pellets into the hollow capsules according to the required specifications to obtain enteric-coated omeprazole capsules.

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

[0038] Step S1: The material temperature is 30 - 40 °C, the liquid spraying speed is 2 - 4 mL / min, the air volume is 30 - 40 m 3 / h, and the atomization pressure is (1 - 2)×10 5 Pa;

[0039] Step S2: The material temperature is 40 - 60 °C, the liquid spraying speed is 8 - 10 mL / min, the air volume is 50 - 60 m 3 / h, and the atomization pressure is (1 - 2)×10 5 Pa;

[0040] Step S3: The material temperature is 30 - 40 °C, the liquid spraying speed is 2 - 4 mL / min, the air volume is 30 - 40 m 3 / h, and the atomization pressure is (1 - 2)×10 5 Pa;

[0041] Step S4: The material temperature is 40 - 60 °C, the liquid spraying speed is 4 - 6 mL / min, the air volume is 40 - 50 m 3 / h, and the atomization pressure is (1 - 2)×10 5 Pa;

[0042] Step S5: The material temperature is 40 - 50 °C, the liquid spraying speed is 4 - 6 mL / min, the air volume is 40 - 50 m 3 / h, and the atomization pressure is (1 - 2)×10 5 Pa.

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

[0044] 1. In order to prevent the main drug component from contacting the components in the blank core and the isolation layer, which may lead to the degradation and damage of its components, the present invention considers setting protective layers both between the blank core and the drug-loading layer, and between the drug-loading layer and the isolation layer. The inventor selects from the common excipients of the drug-loading layer and finds that the binder and alkalizing agent that can be used to formulate the drug-loading 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 binder is different from that in the drug-loading layer, the protective effect is more obvious. Therefore, the present invention prepares the protective layer with the components of the binder and alkalizing agent that can be used to formulate the drug-loading layer, and at the same time ensures that the material selection of the binder in the protective layer is different from that of the binder in the drug-loading layer. The binder and alkalizing agent will not damage the main drug component, and at the same time can prevent the main drug component from directly contacting the components in the blank core or the isolation layer, increasing the drug stability.

[0045] 2. In order to prevent the excipients in the drug-loading layer from damaging the stability of the main drug component, considering the characteristic that the main drug is insoluble in acidic conditions, the present invention attempts to set alkalizing agents in the components of the drug-loading layer where the main drug component is located and the protective layer that may contact the main drug component. It is experimentally confirmed that the alkalizing agent can indeed reduce the rupture of the drug during the coating process and increase the drug stability.

[0046] 3. The present invention sets binders in the components of the drug-loading layer where the main component is located and the protective layer that may contact the main drug component. The binder can prevent the surface of the drug from being incomplete and ensure the shape and uniformity of the finished drug. At the same time, the present invention finds that when the component selection of the binder in the drug-loading layer is different from that of the binder in the protective layer contacting the drug-loading layer, it is more conducive to the stability of the drug. The reason may be that the functional groups of the binders with different components are different, and can ensure that adjacent coated pills are more firmly wrapped during the coating process.

[0047] 4. In the drug-loading layer of the present invention, in order to promote the compatibility, adsorption and stability of the excipients, the present invention attempts to irradiate hydroxymethyl chitosan 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. Considering the reason, it is also that the hydrogen bond breakage forms a network structure, improving the wrapping effect on the excipients and avoiding the rupture of the main drug component.

[0048] 5. By controlling the weight gain of the isolation layer and the enteric-coated layer within a reasonable range, the present invention takes into account both the stability and release properties of the drug, while ensuring the acid resistance of the product. If the weight gain is too large, it is not conducive to the release of the main drug component inside, affecting the efficacy. If the weight gain is too small, it cannot provide good coating protection for the main drug component, and the enteric-coated layer is prone to aging, affecting stability. Considering the metabolic environment of omeprazole in the intestine, the inventor sets the weight gain of the isolation layer and the enteric-coated layer at (10%-15%) and (20%-25%) respectively through optimized experiments. Within 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. By controlling the particle size of the omeprazole raw material drug within a reasonable range, the present invention takes into account both the release property and the shape uniformity. If the particle size is too small, the release property is good and it is easy to form clusters, but the product shape is poor and the uniformity is not good. If the particle size is too large, it is not easy to mix, the uniformity is poor, and the release property is poor. Specific embodiments

[0050] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. 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.

[0051] Examples 1-5

[0052] This embodiment provides a preparation method of omeprazole enteric-coated capsules, including the following steps:

[0053] Step S1: Coating of the first protective layer: Dissolve the binder and the alkaline agent in an organic solvent, stir evenly to obtain the coating solution of the first protective layer. Through the fluidized bed coating technology, spray the coating solution of the first protective layer onto the blank drug core. After the spraying is completed, dry it until the moisture content of the pellets is 1.37%, cool, discharge, and screen to obtain the pellets coated with the first protective layer.

[0054] Step S2, Coating of the drug-loading layer: Dissolve the prescribed amount of omeprazole raw material drug, irradiated hydroxymethyl chitosan (absorbed dose rate is 55 Gy / min, irradiation time is 7 hours), binder, alkaline agent, stabilizer, and filler in an organic solvent, stir evenly to obtain the coating solution of the drug-loading layer. Through the fluidized bed coating technology, spray the coating solution of the drug-loading layer onto the pellets coated with the first protective layer. After the spraying is completed, dry it until the moisture content of the pellets is 1.92%, cool, discharge, and screen to obtain the pellets coated with the drug-loading layer. Herein, the particle size D90 of the omeprazole raw material drug is 30 microns.

[0055] Step S3, Coating with the second protective layer: Dissolve the binder and the alkaline agent in an organic solvent, stir evenly to obtain the coating solution for the second protective layer, and spray the coating solution for the second protective layer onto the drug-loaded layer coated pellets through the fluidized bed coating technology. After the spraying is completed, dry until the moisture content of the pellets is 1.57%, cool, discharge, and screen to obtain the pellets coated with the second protective layer;

[0056] Step S4, Coating with the isolating layer: Dissolve the binder and the alkaline agent in an organic solvent, stir evenly to obtain the coating solution for the isolating layer, and spray the coating solution for the isolating layer onto the pellets coated with the second protective layer through the fluidized bed coating technology. After the spraying is completed, dry until the moisture content of the pellets is 1.93%, cool, discharge, and screen to obtain the pellets coated with the isolating layer;

[0057] Step S5, Coating with the enteric layer: Dissolve the enteric material, lubricant and anti-adhesive agent in an organic solvent, stir evenly to obtain the coating solution for the enteric layer, and spray the coating solution for the enteric layer onto the pellets coated with the isolating layer through the fluidized bed coating technology. After the spraying is completed, dry until the moisture content of the pellets is 1.27%, cool, discharge, and screen to obtain the enteric-coated omeprazole pellets;

[0058] Step S6, Fill the enteric-coated omeprazole pellets into the hollow capsules according to the required specifications to obtain the enteric-coated omeprazole capsules.

[0059] In the above embodiments, the selection and ratio 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 in turn.

[0060] Table 1: Selection and ratio of components in Examples 1-5

[0061]

[0062]

[0063]

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

[0065] Polyvinylpyrrolidone is purchased from the official website of Merck, product number 77627, particle size 110 microns;

[0066] Povidone is purchased from the official website of Merck, product number P2472;

[0067] Sodium carboxymethylcellulose is purchased from the official website of Merck, product number 419338, relative molecular mass 700000;

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

[0069] Microcrystalline cellulose was purchased from the official website of Merck, with product number 1.02330 and particle size of 5 - 40 microns;

[0070] Mannitol was purchased from the official website of Merck, with product number 100494 and molecular weight of 182;

[0071] Casein was purchased from the official website of Merck, with product number C7078;

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

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

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

[0075] Acrylic resin was purchased from the official website of Merck, with product number L9774;

[0076] Hydroxypropyl methylcellulose phthalate was purchased from the official website of Merck, with product number L9774 and density of 0.6 g / mL;

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

[0078] Aerosil was purchased from the official website of Merck, with product number 1.07748 and particle size of 5 - 40 microns;

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

[0080] Glyceryl monostearate is 1,2-glyceryl monostearate, purchased from the official website of Merck, with product number 43697 and molecular weight of 625.

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

[0082]

[0083] Table 3: Preparation process parameters of the 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 their ratios 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 their ratios 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 their ratios are the same as those in Example 1.

[0093] Comparative Example 4

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

[0095] Comparative Example 5

[0096] The difference from Example 1 is that the weights of the components in the isolation layer and the enteric-coated layer are 2 times those in Example 1, resulting in the weight gains of the isolation layer and the enteric-coated layer reaching 20.1% and 39.2% respectively, and other processes, materials and their ratios are the same as those in Example 1.

[0097] Comparative Example 6

[0098] The difference from Example 1 is that the weights of the components in the isolation layer and the enteric-coated layer are half of those in Example 1, resulting in the weight gains of the isolation layer and the enteric-coated layer reaching 6.3% and 12.4% respectively, and other processes, materials and their ratios are the same as those in Example 1.

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

[0100] Verification of stability effect:

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

[0102] Table 4: Results of stability effect verification

[0103]

[0104]

[0105] Among them, the total impurity content is determined by high performance liquid chromatography (General Rules 0512, Volume IV, Chinese Pharmacopoeia 2020 Edition). Calculated by the external standard method based on the peak area, the preparation methods of the reference substance and the test solution are both referred to the second method of General Rules 0931, Volume IV, Chinese Pharmacopoeia of the corresponding year edition.

[0106] Combined with the stability data of Examples 1-5, it can be seen that the omeprazole enteric-coated pellets prepared by the present invention have good stability. After 150 days of accelerated experiment, the total impurity content hardly increases, which can fully meet the product shelf life. Combined with the stability data of Comparative Example 3, it can be seen that on the premise that the hydroxymethyl chitosan is irradiated, the stability of the omeprazole enteric-coated pellets decreases slightly. It is analyzed that the hydrogen bond may not be broken, and the wrapping effect on the auxiliary material is poor, resulting in the easy rupture of the main drug component. Combined with the stability data of Comparative Examples 1-2 and Comparative Examples 4-6, it can be seen that in the case of no first protective layer, or no second protective layer, or the binder of the drug-loading layer is the same as the first and second protective layers, or the weight gain of the isolation layer and the enteric layer is insufficient, the stability of the omeprazole enteric-coated pellets decreases significantly, which also corroborates the technical concept and technical effect of the present invention.

[0107] Verification of release effect:

[0108] Referring to the release determination method in the second method of General Rules 0931, Volume IV, Chinese Pharmacopoeia 2020 Edition: Prepare a hydrochloric acid solution with a pH of 1-1.5, soak and rotate the prepared sample (omeprazole enteric-coated pellets not filled into the hollow capsule) in the acidic solution for 2 hours. Then, adjust the pH of the solution to 6.5-7.0 with sodium hydroxide and continue to rotate for 1 hour. Sampling is carried out at the time intervals shown in the following table, and the dissolution amount of each example is measured, as shown in Table 5 below.

[0109] Table 5: Verification results of release effect

[0110]

[0111]

[0112] As can be seen from the data in the above table, in the environment of simulating intestinal drug release, the omeprazole enteric-coated capsules provided by the present invention can reach a release rate of more than 90% at 15 minutes and are basically completely released at 60 minutes, with 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 will not affect the drug release. Combined with the data of Example 1 and Comparative Example 3, it can be seen that the unirradiated hydroxymethyl chitosan will reduce the drug release. Combined with the data of Example 1 and Comparative Example 5, it can be seen that the excessive weight gain of the isolation layer and the enteric layer will affect the drug release.

[0113] The above are the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. An omeprazole enteric-coated capsule, characterized in that: The omeprazole enteric-coated micro-pellets and capsule shells are included. The omeprazole enteric-coated micro-pellets include a blank drug core layer, a first protective layer, a drug-loaded layer, a second protective layer, an isolation layer and an enteric layer from the inside to the outside. The composition of the blank drug core layer is: 100 parts of sucrose; The first protective layer comprises: 1 part of hydroxypropyl methylcellulose as a binder and 1.5 parts of magnesium carbonate as an alkaline agent; The drug-carrying layer comprises: 130 parts of omeprazole API, 15 parts of hydroxymethyl chitosan, 7 parts of binder, 7 parts of alkaline agent, 8 parts of stabilizer sodium hydroxide and 40 parts of filler microcrystalline cellulose; wherein the binder is polyvinyl pyrrolidone and sodium carboxymethyl cellulose, and the alkaline agent is magnesium hydroxide and magnesium carbonate; The second protective layer comprises: 4 parts of sodium carboxymethyl cellulose as a binder and 4 parts of an alkaline agent; wherein the alkaline agent is magnesium carbonate and magnesium hydroxide; The composition of the isolation layer is: 30 parts of oil-soluble cellulose; The ingredients of the enteric layer are: 70 parts of enteric material acrylic resin, 3.5 parts of lubricant magnesium stearate and 1.4 parts of anti-adhesive talc; The hydroxymethyl chitosan was irradiated, the radiation absorption dose rate was 55 Gy / min, and the irradiation time was 7 hours; the particle size D90 of the omeprazole raw material was 20-50 μm; The above dosages are all measured based on Omeprazole Enteric-coated Capsules, and are all weight portions.

2. An omeprazole enteric-coated capsule, characterized in that: The omeprazole enteric-coated micro-pellets and capsule shells are included. The omeprazole enteric-coated micro-pellets include a blank drug core layer, a first protective layer, a drug-loaded layer, a second protective layer, an isolation layer and an enteric layer from the inside to the outside. The composition of the blank drug core layer is: 100 parts of sucrose; The first protective layer is composed of: 2 parts of polyvinyl pyrrolidone as a binder and 1.1 parts of magnesium hydroxide as an alkaline agent; The drug-carrying layer comprises: 120 parts of omeprazole raw material, 15 parts of hydroxymethyl chitosan, 7 parts of hydroxypropyl methylcellulose as a binder, 7 parts of magnesium carbonate as an alkaline agent, 8 parts of sodium dihydrogen phosphate as a stabilizer and 40 parts of mannitol as a filler; The second protective layer comprises 4 parts of a binder and 8 parts of an alkaline agent; wherein the binder is sodium carboxymethyl cellulose and povidone, and the alkaline agent is magnesium carbonate and sodium carbonate; The composition of the isolation layer is: 35 parts of oil-soluble cellulose; The ingredients of the enteric layer are: 70 parts of enteric material hydroxypropyl methylcellulose phthalate, 7 parts of lubricant micro powder silica gel and 3.5 parts of anti-adhesive agent glyceryl stearate; The hydroxymethyl chitosan was irradiated, the radiation absorption dose rate was 55 Gy / min, and the irradiation time was 7 hours; the particle size D90 of the omeprazole raw material was 20-50 μm; The above dosages are all measured based on Omeprazole Enteric-coated Capsules, and are all weight portions.

3. An omeprazole enteric-coated capsule, characterized in that: The omeprazole enteric-coated micro-pellets and capsule shells are included. The omeprazole enteric-coated micro-pellets include a blank drug core layer, a first protective layer, a drug-loaded layer, a second protective layer, an isolation layer and an enteric layer from the inside to the outside. The composition of the blank drug core layer is: 100 parts of starch; The first protective layer is composed of: 3 parts of adhesive polyvidone and 2 parts of alkaline agent sodium carbonate; The drug-carrying layer comprises: 130 parts of omeprazole raw material, 15 parts of hydroxymethyl chitosan, 7 parts of adhesive polyvinyl pyrrolidone, 7 parts of alkaline agent magnesium hydroxide, 8 parts of stabilizer sodium dihydrogen phosphate and 40 parts of filler casein; The second protective layer comprises: 8 parts of hydroxypropyl methylcellulose as a binder and 4 parts of magnesium carbonate as an alkaline agent; The composition of the isolation layer is: 40 parts of oil-soluble cellulose; The ingredients of the enteric layer are: 70 parts of enteric material methacrylic resin, 4 parts of lubricant magnesium stearate and 2 parts of anti-adhesive talc; The hydroxymethyl chitosan was irradiated, the radiation absorption dose rate was 55 Gy / min, and the irradiation time was 7 hours; the particle size D90 of the omeprazole raw material was 20-50 μm; The above dosages are all measured based on Omeprazole Enteric-coated Capsules, and are all weight portions.

4. An omeprazole enteric-coated capsule, characterized in that: The omeprazole enteric-coated micro-pellets and capsule shells are included. The omeprazole enteric-coated micro-pellets include a blank drug core layer, a first protective layer, a drug-loaded layer, a second protective layer, an isolation layer and an enteric layer from the inside to the outside. The composition of the blank drug core layer is: 100 parts of starch; The first protective layer comprises: 2 parts of sodium carboxymethyl cellulose as a binder and 2 parts of an alkaline agent; the alkaline agent is magnesium carbonate and sodium carbonate; The drug-carrying layer comprises: 140 parts of omeprazole raw material, 20 parts of hydroxymethyl chitosan, 8 parts of adhesive povidone, 8 parts of alkaline agent sodium carbonate, 9 parts of stabilizer anhydrous sodium carbonate and 45 parts of filler dextrin; The second protective layer is composed of 6 parts of polyvinyl pyrrolidone as a binder and 6 parts of magnesium hydroxide as an alkaline agent; The composition of the isolation layer is: 35 parts of oil-soluble cellulose; The ingredients of the enteric layer are: 70 parts of enteric material, 4.5 parts of lubricant and 2.5 parts of anti-adhesive talc; the enteric material is methacrylic resin and acrylic resin, the lubricant is magnesium stearate and micro-powder silica gel, and the anti-adhesive is talc and glyceryl stearate; The hydroxymethyl chitosan was irradiated, the radiation absorption dose rate was 55 Gy / min, and the irradiation time was 7 hours; the particle size D90 of the omeprazole raw material was 20-50 μm; The above dosages are all measured based on Omeprazole Enteric-coated Capsules, and are all weight portions.

5. An omeprazole enteric-coated capsule, characterized in that: The omeprazole enteric-coated micro-pellets and capsule shells are included. The omeprazole enteric-coated micro-pellets include a blank drug core layer, a first protective layer, a drug-loaded layer, a second protective layer, an isolation layer and an enteric layer from the inside to the outside. The composition of the blank drug core layer is: 100 parts of cellulose; The first protective layer comprises: 2 parts of an adhesive and 2 parts of an alkaline agent; the adhesive is povidone and polyvinyl pyrrolidone, and the alkaline agent is magnesium carbonate and magnesium hydroxide; The drug-carrying layer comprises: 140 parts of omeprazole raw material, 15 parts of hydroxymethyl chitosan, 8 parts of sodium carboxymethyl cellulose as a binder, 8 parts of an alkaline agent, 10 parts of sodium phosphate as a stabilizer and 50 parts of starch as a filler; the alkaline agent is magnesium hydroxide and sodium carbonate; The second protective layer is composed of 8 parts of adhesive polyvidone and 4 parts of alkaline agent sodium carbonate; The composition of the isolation layer is: 40 parts of oil-soluble cellulose; The ingredients of the enteric layer are: 70 parts of enteric material acrylic resin, 5 parts of lubricant and 3 parts of anti-adhesive glyceryl stearate; the lubricant is magnesium stearate and micro powder silica gel; The hydroxymethyl chitosan was irradiated, the radiation absorption dose rate was 55 Gy / min, and the irradiation time was 7 hours; the particle size D90 of the omeprazole raw material was 20-50 μm; The above dosages are all measured based on Omeprazole Enteric-coated Capsules, and are all weight portions.

6. A method for preparing the omeprazole enteric-coated capsules according to any one of claims 1 to 5, 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 with a second protective layer: dissolving a binder and an 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 a fluidized bed coating technique, drying after the spraying to a moisture content of the pellets of less than 5%, 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 liquid, spraying the isolation layer coating liquid 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 the pellets until the moisture content of the pellets is less than 5% after the spraying, 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.

7. The method for preparing omeprazole enteric-coated capsules according to claim 6, 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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