Rabeprazole pharmaceutical composition as well as preparation method and application thereof

Abstract

The invention discloses a rabeprazole pharmaceutical composition as well as a preparation method and application thereof. The invention provides a rabeprazole pharmaceutical composition, the rabeprazole pharmaceutical composition comprises an active pharmaceutical ingredient and an antacid, and the active pharmaceutical ingredient is selected from one or more of rabeprazole, rabeprazole sodium, other pharmaceutically acceptable salt forms, solvates and hydrates thereof. The rabeprazole pharmaceutical composition disclosed by the invention can inhibit the rabeprazole sodium from being damaged by gastric acid, and is small in side effect, rapid in treatment, relatively good in effect and high in patient compliance; the rabeprazole pharmaceutical composition has the advantages that the rabeprazole pharmaceutical composition is simple in preparation process and good in market prospect, and is an excellent medicine for treating peptic ulcer, and a pharmaceutical preparation can be delivered into the stomach by nasal feeding for some patients who cannot be administered by themselves, so that the effect of treating stomach diseases is achieved.

Description

[0001] This application claims the benefit of priority to a prior application filed with the State Intellectual Property Office of China on February 18, 2024, with patent application number 202410180196.0, entitled “Rabeprazole Pharmaceutical Composition, Preparation Method and Use Thereof.” The entire text of the prior application is incorporated herein by reference. Technical Field

[0002] The present invention belongs to the field of pharmaceutical compositions and relates to a rabeprazole pharmaceutical composition, a preparation method and an application thereof. Background Art

[0003] Peptic ulcers are a common, chronic, and recurring disease. While their mortality rate is low, they cause significant pain to patients and increase the economic burden on the nation and its people. Peptic ulcers are well-defined mucosal diseases that can penetrate the muscularis mucosa and develop in areas of the gastrointestinal tract that come into contact with gastric fluid. These ulcers can occur in the lesser curvature of the stomach (gastric ulcers), the pyloric canal (pyloric canal ulcers), the beginning of the duodenum (so-called duodenal bulb ulcers), retroduodenal bulb ulcers, lower esophageal ulcers (gastric fluid can reflux into the lower esophagus), and Meckel's diverticulum in the distal ileum (a congenital condition that can cause ulcers).

[0004] Peptic ulcer drug research and treatment have had a significant impact on the quality of life and work potential of millions of people affected, and have helped significantly reduce the prevalence of the disease, the frequency and severity of complications, hospitalization rates, and mortality. Currently, domestic peptic ulcer drugs can be divided into proton pump inhibitors, antacids, H2 receptor antagonists, and other drugs based on their different drug types.

[0005] Rabeprazole is a novel proton pump inhibitor (PPI) used to treat acid-related diseases. It has a strong and selective inhibitory effect on Helicobacter pylori (HP). Rabeprazole has the most binding sites for the enzyme, making it the fastest-acting PPI, achieving maximum acid suppression within 5 minutes.

[0006] Because proton pump inhibitors are unstable in acid and easily degrade in the gastric acid environment, which reduces their efficacy, these drugs are usually made into enteric-coated preparations, which require special enteric-coated materials to coat their contents to prevent damage from gastric acid. Therefore, their preparation process is cumbersome and requires multiple steps.

[0007] Therefore, there is an urgent need to develop a new rabeprazole pharmaceutical preparation with good acid stability, few side effects, good efficacy and good patient compliance. Summary of the Invention

[0008] The present invention provides a rabeprazole pharmaceutical composition, which comprises a pharmaceutically active ingredient and an antacid, wherein the pharmaceutically active ingredient is selected from one or more of rabeprazole, rabeprazole sodium, and other pharmaceutically acceptable salts, solvates, and hydrates thereof.

[0009] According to an embodiment of the present invention, the antacid is a weakly alkaline compound that can neutralize gastric acid and reduce the acidity of gastric contents. It has a strong, rapid, and long-lasting antacid effect, is not easily absorbed, does not produce CO2 gas, does not cause belching and bloating, does not cause constipation or diarrhea, and has a protective and astringent effect. Preferably, the antacid is selected from one or more of sodium bicarbonate, light magnesium oxide, sodium hydroxide, calcium carbonate, and sodium carbonate.

[0010] The rabeprazole pharmaceutical composition of the present invention has a pharmaceutical active ingredient content of more than 65% under pH 2.0-6.8. The content, calculated as rabeprazole, refers to the percentage of the mass of rabeprazole to the total mass of the rabeprazole pharmaceutical composition.

[0011] According to an embodiment of the present invention, the content of the active pharmaceutical ingredient may be 0.10% to 5.00%, for example, 0.20% to 3.00%, exemplified by 0.20%, 0.30%, 0.40%, 0.48%, 0.50%, 0.56%, 0.60%, 0.70%, 0.80%, 0.833%, 0.85%, 0.90%, 0.94%, 0.95%, 1.00 %, 1.11%, 1.20%, 1.30%, 1.40%, 1.50%, 1.60%, 1.667%, 1.70%, 1.71%, 1.80%, 1.887%, 1.90%, 2.00%, 2.20%, 2.50%, 3.00%, 4.00% or 5.00%, wherein the content refers to the percentage of the mass of the active ingredient to the total mass of the rabeprazole pharmaceutical composition.

[0012] According to an embodiment of the present invention, the sodium carbonate is anhydrous sodium carbonate.

[0013] According to an embodiment of the present invention, the antacid contains at least sodium hydroxide and sodium bicarbonate.

[0014] According to an embodiment of the present invention, the total content of the antacid can be 50.00% to 95.00%, for example 80.00% to 95.00%, exemplified by 60.00%, 70.00%, 75.00%, 80.00%, 82.08%, 83.74%, 86.06%, 90.58%, 91.672%, 93.00% or 95.00%, wherein the content refers to the percentage of the total mass of all antacids to the total mass of the rabeprazole pharmaceutical composition.

[0015] According to an embodiment of the present invention, the content of sodium hydroxide is greater than 0 and not more than 0.10%, for example, 0.001% to 0.08%, exemplified by 0.002%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.06% or 0.08%, wherein the content refers to the percentage of the mass of sodium hydroxide to the total mass of the rabeprazole pharmaceutical composition.

[0016] According to an embodiment of the present invention, the content of sodium bicarbonate is not less than 15.00% and less than 95.00%, for example, 20.00% to 94.999%, exemplified by 25.00%, 28.57%, 30.00%, 33.33%, 40.00%, 50.00%, 60.00%, 70.00%, 76.92%, 80.00%, 84.91%, 85.00%, 90.00%, 91.667% or 93.00%, wherein the content refers to the percentage of the mass of sodium bicarbonate to the total mass of the rabeprazole pharmaceutical composition.

[0017] According to an embodiment of the present invention, the content of the light magnesium oxide may be 0 to 10.00%, for example 1.00% to 8.00%, exemplified by 2.00%, 3.00%, 4.00%, 5.00%, 5.13%, 5.66%, 6.00%, 7.00%, 8.00% or 9.00%, wherein the content refers to the percentage of the mass of the light magnesium oxide to the total mass of the rabeprazole pharmaceutical composition.

[0018] According to an embodiment of the present invention, the content of the (anhydrous) sodium carbonate may be 0 to 10.00%, for example 1.00% to 8.00%, exemplified by 2.00%, 3.00%, 4.00%, 5.00%, 5.66%, 6.00%, 7.00%, 8.00% or 9.00%, wherein the content refers to the percentage of the mass of the (anhydrous) sodium carbonate to the total mass of the rabeprazole pharmaceutical composition.

[0019] According to an embodiment of the present invention, the content of calcium carbonate can be 0 to 80.00%, for example 30.00% to 70.00%, exemplified by 35.00%, 40.00%, 44.83%, 45.00%, 50.00%, 57.48%, 60.00%, 65.00%, 70.00% or 75.00%, wherein the content refers to the percentage of the mass of calcium carbonate to the total mass of the rabeprazole pharmaceutical composition.

[0020] According to an embodiment of the present invention, the antacid can be selected from any one of the following combinations:

[0021] A combination of sodium hydroxide and sodium bicarbonate; for example, the content of sodium hydroxide is greater than 0 and does not exceed 0.10%, and the remainder is sodium bicarbonate;

[0022] A combination of sodium hydroxide, sodium bicarbonate and light magnesium oxide; for example, the content of the sodium hydroxide is greater than 0 and does not exceed 0.10%, the content of the sodium bicarbonate is 60.00% to 90.00%, and the remainder is light magnesium oxide;

[0023] A combination of sodium hydroxide, sodium bicarbonate, anhydrous sodium carbonate, and calcium carbonate; for example, the content of the sodium hydroxide is greater than 0 and not more than 0.10%, the content of the sodium bicarbonate is 15.00% to 50.00%, the content of the anhydrous sodium carbonate is greater than 0 and not more than 10.00%, and the remainder is calcium carbonate;

[0024] A combination of sodium hydroxide, sodium bicarbonate and calcium carbonate; for example, the content of the sodium hydroxide is greater than 0 and does not exceed 0.10%, the content of the sodium bicarbonate is 15.00% to 50.00%, and the rest is calcium carbonate.

[0025] According to an embodiment of the present invention, the rabeprazole pharmaceutical composition further comprises a diluent and a binder.

[0026] According to an embodiment of the present invention, the rabeprazole pharmaceutical composition further comprises one or more of a diluent, a disintegrant, a binder, a lubricant, a flavoring agent, and a fragrance. In some embodiments, the rabeprazole pharmaceutical composition further comprises a diluent, a binder, a lubricant, and a disintegrant; in some embodiments, the rabeprazole pharmaceutical composition further comprises a diluent, a binder, a flavoring agent, and a fragrance.

[0027] According to an embodiment of the present invention, the diluent refers to an inert substance added for dilution in order to increase the quality of the pharmaceutical preparation, selected from mannitol, and / or lactose, and / or microcrystalline cellulose; in an exemplary embodiment, the diluent is mannitol.

[0028] According to an embodiment of the present invention, the content of the diluent can be 0-30.00%, for example 2.00%-20.00%, exemplified by 3.00%, 4.00%, 4.428%, 5.013%, 5.262%, 5.96%, 7.41%, 7.89%, 8.65%, 9.21%, 10.00%, 11.00%, 12.00%, 13.00%, 13.31%, 14.00%, 14.16%, 15.00%, 16.00%, 17.00%, 18.00%, 19.00%, 20.00%, 21.00%, 23.00%, 25.00%, 30.00%, and the content refers to the percentage of the mass of the diluent to the total mass of the rabeprazole pharmaceutical composition.

[0029] According to an embodiment of the present invention, the disintegrant refers to a substance that causes the tablet or granules to disintegrate upon dissolution, and is selected from one or more of crospovidone, sodium carboxymethyl starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose, pregelatinized starch, and polyclirin potassium. In an exemplary embodiment, the disintegrant is crospovidone.

[0030] According to an embodiment of the present invention, the content of the disintegrant may be 0 to 30.00%, for example 0.50 to 5.00%, exemplified by 0, 0.50%, 1.00%, 1.667%, 1.89%, 2.00%, 3.00%, 4.00%, 5.00%, 10.00% or 20.00%, wherein the content refers to the percentage of the mass of the disintegrant to the total mass of the rabeprazole pharmaceutical composition.

[0031] According to an embodiment of the present invention, the binder can be a conventional additive in the art that can increase the viscosity of the dispersion medium to reduce the sedimentation velocity of the microparticles or increase the hydrophilicity of the microparticles, and is selected from one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, povidone (e.g., povidone K30), copovidone, hydroxyethyl cellulose, sodium carboxymethyl cellulose, carbomer, polyethylene oxide, and ethyl cellulose. In an exemplary embodiment, the binder is selected from hydroxypropyl cellulose and / or povidone K30.

[0032] According to an embodiment of the present invention, the content of the binder may be 0 to 10.00%, for example 0.01% to 2.00%, exemplified by 0.02%, 0.03%, 0.04%, 0.05%, 0.067%, 0.08%, 0.10%, 0.20%, 0.30%, 0.43%, 0.5%, 0.77%, 0.80%, 0.90%, 1.00%, 1.50%, 2.00%, 3.00%, 4.00% or 5.00%, wherein the content refers to the percentage of the mass of the binder to the total mass of the rabeprazole pharmaceutical composition.

[0033] According to an embodiment of the present invention, the lubricant can be a conventional lubricating substance in the art, selected from one or more of magnesium stearate, calcium stearate, sodium stearyl fumarate, stearic acid, glyceryl stearate and polyethylene glycol.

[0034] According to an embodiment of the present invention, the content of the lubricant can be 0-5.00%, for example 0-2.00%, exemplified by 0, 0.1%, 0.5%, 0.57%, 0.70%, 0.80%, 0.90%, 1.00%, 1.50%, where the content refers to the percentage of the mass of the lubricant to the total mass of the rabeprazole pharmaceutical composition.

[0035] According to an embodiment of the present invention, the flavoring agent plays a flavoring role in the pharmaceutical preparation (such as a film) and is selected from one or more of sucralose, aspartame, sucrose, fructose, steviol glycosides, glycyrrhizin, sodium chloride, citric acid, saccharin and saccharin sodium.

[0036] According to an embodiment of the present invention, the content of the flavoring agent can be 0 to 30.00%, for example 0.50% to 10.00%, exemplified by 0, 1.00%, 1.71%, 2.00%, 3.00%, 4.00%, 4.76%, 5.56%, 6.00%, 7.00%, 8.00%, 9.00%, and the content refers to the percentage of the mass of the flavoring agent to the total mass of the rabeprazole pharmaceutical composition.

[0037] According to an embodiment of the present invention, the aromatic agent plays a role of aroma in the pharmaceutical preparation (such as a film) and is selected from one or more of essences, spices and menthol.

[0038] According to an embodiment of the present invention, the content of the fragrance can be 0 to 30.00%, for example 0.10% to 5.00%, exemplified by 0, 0.10%, 0.20%, 0.30%, 0.38%, 0.43%, 0.44%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, 1.50%, 2.00%, 3.00%, 4.00% or 5.00%, wherein the content refers to the percentage of the mass of the fragrance to the total mass of the rabeprazole pharmaceutical composition.

[0039] According to some embodiments of the present invention, the rabeprazole pharmaceutical composition consists of a pharmaceutically active ingredient, an antacid, a diluent, a binder, a disintegrant, and a lubricant.

[0040] According to some embodiments of the present invention, the rabeprazole pharmaceutical composition is composed of a pharmaceutically active ingredient, an antacid, a diluent, a binder, a flavoring agent, and an aromatic.

[0041] According to an embodiment of the present invention, the rabeprazole pharmaceutical composition can be any of the following formulations:

[0042] Prescription 1: 1.66% rabeprazole sodium, 4.43% mannitol, 0.07% hydroxypropylcellulose, 0.01% sodium hydroxide, 91.66% sodium bicarbonate, 1.67% cross-linked polyvinylpyrrolidone, 0.50% magnesium stearate; the percentages mentioned refer to the mass percentage of each component to the total mass of the rabeprazole pharmaceutical composition;

[0043] Prescription 2: 0.83% rabeprazole sodium, 5.26% mannitol, 0.07% hydroxypropylcellulose, 0.01% sodium hydroxide, 91.67% sodium bicarbonate, 1.66% cross-linked polyvinylpyrrolidone, 0.50% magnesium stearate; the percentages mentioned refer to the mass percentage of each component to the total mass of the rabeprazole pharmaceutical composition;

[0044] Prescription 3: 1.89% rabeprazole sodium, 5.01% mannitol, 0.08% hydroxypropylcellulose, 0.01% sodium hydroxide, 84.91% sodium bicarbonate, 5.66% light magnesium oxide, 1.88% cross-linked polyvinylpyrrolidone, 0.56% magnesium stearate; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition;

[0045] Prescription 4: 0.94% rabeprazole sodium, 5.95% mannitol, 0.08% hydroxypropylcellulose, 0.01% sodium hydroxide, 84.91% sodium bicarbonate, 5.66% light magnesium oxide, 1.88% cross-linked polyvinylpyrrolidone, 0.57% magnesium stearate; the percentages mentioned refer to the percentage of the mass of each component to the total mass of the rabeprazole pharmaceutical composition;

[0046] Prescription 5: 1.71% rabeprazole sodium, 13.30% mannitol, 0.77% povidone K30, 0.03% sodium hydroxide, 76.92% sodium bicarbonate, 5.13% light magnesium oxide, 1.71% sucralose, 0.43% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition;

[0047] Prescription 6: 0.85% rabeprazole sodium, 14.16% mannitol, 0.77% povidone K30, 0.03% sodium hydroxide, 76.92% sodium bicarbonate, 5.13% light magnesium oxide, 1.71% sucralose, 0.43% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition;

[0048] Prescription 7: 1.11% rabeprazole sodium, 8.65% mannitol, 0.5% povidone K30, 0.02% sodium hydroxide, 33.33% sodium bicarbonate, 5.56% anhydrous sodium carbonate, 44.83% calcium carbonate, 5.56% sucralose, 0.44% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition;

[0049] Prescription 8: 0.56% rabeprazole sodium, 9.20% mannitol, 0.5% povidone K30, 0.02% sodium hydroxide, 33.33% sodium bicarbonate, 5.56% anhydrous sodium carbonate, 44.83% calcium carbonate, 5.56% sucralose, 0.44% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition;

[0050] Prescription 9: 0.95% rabeprazole sodium, 7.42% mannitol, 0.43% povidone K30, 0.01% sodium hydroxide, 28.57% sodium bicarbonate, 57.48% calcium carbonate, 4.76% sucralose, 0.38% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition;

[0051] Prescription 10: 0.48% rabeprazole sodium, 7.89% mannitol, 0.43% povidone K30, 0.01% sodium hydroxide, 28.57% sodium bicarbonate, 57.48% calcium carbonate, 4.76% sucralose, 0.38% (orange powder) flavor; the percentages refer to the percentage of the mass of each component to the total mass of the rabeprazole pharmaceutical composition.

[0052] The rabeprazole pharmaceutical composition of the present invention comprises 10 mg to 20 mg of the active pharmaceutical ingredient (calculated as rabeprazole), for example, 10 mg or 20 mg; and / or 800 mg to 3000 mg of an antacid, for example, 1100.06 mg of an antacid (1100 mg of sodium bicarbonate + 0.06 mg of sodium hydroxide), 960.06 mg of an antacid (900 mg of sodium bicarbonate + 0.06 mg of sodium hydroxide + 60 mg of light magnesium oxide), etc.

[0053] The present invention also provides a preparation method of the rabeprazole pharmaceutical composition, which includes but is not limited to a powder tableting method, a powder capsule filling method, a wet granulation method, a dry granulation method, a fluidized granulation method, and a pellet coating method.

[0054] The present invention also provides the use of the rabeprazole pharmaceutical composition in the preparation of a pharmaceutical preparation. The pharmaceutical preparation can be an oral preparation. The dosage form of the oral pharmaceutical preparation includes but is not limited to capsules, dry suspensions, granules, tablets or powders.

[0055] The present invention also provides a pharmaceutical preparation containing the rabeprazole pharmaceutical composition.

[0056] According to an embodiment of the present invention, the pharmaceutical preparation may be an oral preparation, and the dosage form of the oral pharmaceutical preparation includes but is not limited to capsules, dry suspensions, granules, tablets or powders.

[0057] According to an embodiment of the present invention, the pharmaceutical preparation is a capsule, and the contents include the rabeprazole pharmaceutical composition, for example, the rabeprazole pharmaceutical composition is composed of a pharmaceutically active ingredient, an antacid, a diluent, a binder, a disintegrant, and a lubricant.

[0058] According to an embodiment of the present invention, the pharmaceutical preparation is a dry suspension, which is prepared from the rabeprazole pharmaceutical composition. For example, the rabeprazole pharmaceutical composition is composed of a pharmaceutical active ingredient, an antacid, a diluent, a binder, a flavoring agent, and an aromatic.

[0059] The present invention also provides use of the rabeprazole pharmaceutical composition in preparing a medicament for treating and / or preventing peptic ulcer.

[0060] According to an embodiment of the present invention, the peptic ulcer disease includes but is not limited to gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis, Zollinger-Ellison syndrome, non-erosive gastroesophageal reflux disease, and recurrence of gastric ulcer and duodenal ulcer.

[0061] The present invention also provides a method for treating and / or preventing peptic ulcer, which comprises administering a therapeutically effective amount of the rabeprazole pharmaceutical composition or pharmaceutical preparation to a patient in need.

[0062] The reagents and raw materials used in the present invention are commercially available.

[0063] The beneficial effects of the present invention are as follows: the rabeprazole pharmaceutical composition of the present invention can inhibit the destruction of rabeprazole by gastric acid, has few side effects, rapidly takes effect and has good efficacy, and has high patient compliance; for some patients who are unable to administer the drug independently, the drug preparation can be delivered to the stomach through nasogastric administration to achieve the effect of treating gastric diseases; and the rabeprazole pharmaceutical composition has a simple preparation process and good market prospects, and is an excellent drug for treating peptic ulcers.

[0064] In addition, the rabeprazole pharmaceutical composition also has good chemical stability.

[0065] In addition, the rabeprazole pharmaceutical composition has an outstanding effect in acid resistance, can slow down the degradation of rabeprazole in a gastric acid environment, further protect the stability of rabeprazole, and better exert the efficacy.

[0066] That is, the present invention provides a rabeprazole pharmaceutical composition, which is different from the prior art and has good efficacy, few side effects, good compliance and good stability, and a preparation method and application thereof.

[0067] Definitions and Explanations of Terms

[0068] The term "plurality" refers to a physical mixture of two or more species, for example, a physical mixture of two, three or more species.

[0069] The term "patient" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses or primates, and most preferably humans.

[0070] The term "therapeutically effective amount" refers to that amount of an active compound or drug that elicits the biological or medical response that is being sought in a tissue, system, animal, individual or human by a researcher, veterinarian, medical doctor or other clinician. DETAILED DESCRIPTION

[0071] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0072] Unless otherwise specified, the experimental methods in the following examples without specific conditions were performed according to conventional methods and conditions, or selected according to the product specifications.

[0073] Comparative Example 1: Rabeprazole Sodium Enteric-Coated Tablets (20 mg, trade name: Polit)

[0074] Example 1 Rabeprazole sodium bicarbonate capsules

[0075] 1) Prescription composition

[0076] Table 1

[0077] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 20 1.66 Active pharmaceutical ingredients Mannitol 53.14 4.43 diluent Hydroxypropylcellulose 0.8 0.07 Adhesives Sodium hydroxide 0.06 0.01 antacids Sodium bicarbonate 1100 91.66 antacids Cross-linked polyvinylpyrrolidone 20 1.67 disintegrants magnesium stearate 6 0.50 lubricant Gross weight 1200 100 / Gelatin empty capsules / / capsule shell

[0078] 2) Preparation method

[0079] According to the prescription in Table 1, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0080] Place half of the mannitol, rabeprazole sodium, hydroxypropyl cellulose and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0081] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0082] Sodium bicarbonate was pre-treated by passing through a 30-mesh sieve; sodium bicarbonate, cross-linked polyvinylpyrrolidone and magnesium stearate were converted and weighed according to the prescribed amount.

[0083] Place the dry granules in the mixer hopper, add sodium bicarbonate in an amount equal to the dry granules, and mix for 10 minutes; then add sodium bicarbonate twice the amount of the dry granules, and mix for 10 minutes; then add cross-linked polyvinylpyrrolidone and the remaining sodium bicarbonate, and mix for 20 minutes; then add magnesium stearate, and mix for 10 minutes to obtain the total mixed granules.

[0084] The mixed granules are filled into gelatin hollow capsules using a capsule filling machine to obtain rabeprazole sodium bicarbonate capsules.

[0085] Example 2 Rabeprazole sodium bicarbonate capsules

[0086] 1) Prescription composition

[0087] Table 2

[0088] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 10 0.83 Active pharmaceutical ingredients Mannitol 63.14 5.26 diluent Hydroxypropylcellulose 0.8 0.07 Adhesives Sodium hydroxide 0.06 0.01 antacids Sodium bicarbonate 1100 91.67 antacids Cross-linked polyvinylpyrrolidone 20 1.66 disintegrants magnesium stearate 6 0.50 lubricant Gross weight 1200 100 / Gelatin empty capsules / / capsule shell

[0089] 2) Preparation method

[0090] According to the prescription in Table 2, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0091] Place half of the mannitol, rabeprazole sodium, hydroxypropyl cellulose and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0092] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0093] Sodium bicarbonate was pre-treated by passing through a 30-mesh sieve; sodium bicarbonate, cross-linked polyvinylpyrrolidone and magnesium stearate were converted and weighed according to the prescribed amount.

[0094] Place the dry granules in the mixer hopper, add sodium bicarbonate in an amount equal to the dry granules, and mix for 10 minutes; then add sodium bicarbonate twice the amount of the dry granules, and mix for 10 minutes; then add cross-linked polyvinylpyrrolidone and the remaining sodium bicarbonate, and mix for 20 minutes; then add magnesium stearate, and mix for 10 minutes to obtain the total mixed granules.

[0095] The mixed granules are filled into gelatin hollow capsules using a capsule filling machine to obtain rabeprazole sodium bicarbonate capsules.

[0096] Example 3 Rabeprazole sodium bicarbonate capsules

[0097] 1) Prescription composition

[0098] Table 3

[0099] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 20 1.89 Active pharmaceutical ingredients Mannitol 53.14 5.01 diluent Hydroxypropylcellulose 0.8 0.08 Adhesives Sodium hydroxide 0.06 0.01 antacids Sodium bicarbonate 900 84.91 antacids Light magnesium oxide 60 5.66 antacids Cross-linked polyvinylpyrrolidone 20 1.88 disintegrants magnesium stearate 6 0.56 lubricant Gross weight 1060 100 / Gelatin empty capsules / / capsule shell

[0100] 2) Preparation method

[0101] According to the prescription in Table 3, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0102] Place half of the mannitol, rabeprazole sodium, hydroxypropyl cellulose and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0103] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0104] Light magnesium oxide is pretreated by passing through a 30-mesh sieve; sodium bicarbonate is pretreated by passing through a 30-mesh sieve; sodium bicarbonate, light magnesium oxide, cross-linked polyvinylpyrrolidone and magnesium stearate are converted and weighed according to the prescription amount.

[0105] Place the dry granules in the mixer hopper, add sodium bicarbonate in an amount equal to the dry granules, and mix for 10 minutes; then add sodium bicarbonate twice the amount of the dry granules, and mix for 10 minutes; then add light magnesium oxide, cross-linked polyvinylpyrrolidone and the remaining sodium bicarbonate, and mix for 20 minutes; then add magnesium stearate, and mix for 10 minutes to obtain the total mixed granules.

[0106] The mixed granules are filled into gelatin hollow capsules using a capsule filling machine to obtain rabeprazole sodium bicarbonate capsules.

[0107] Example 4 Rabeprazole Sodium Bicarbonate Capsules

[0108] 1) Prescription composition

[0109] Table 4

[0110] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 10 0.94 Active pharmaceutical ingredients Mannitol 63.14 5.95 diluent Hydroxypropylcellulose 0.8 0.08 Adhesives Sodium hydroxide 0.06 0.01 antacids Sodium bicarbonate 900 84.91 antacids Light magnesium oxide 60 5.66 antacids Cross-linked polyvinylpyrrolidone 20 1.88 disintegrants magnesium stearate 6 0.57 lubricant Gross weight 1060 100 / Gelatin empty capsules / / capsule shell

[0111] 2) Preparation method

[0112] According to the prescription in Table 4, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0113] Place half of the mannitol, rabeprazole sodium, hydroxypropyl cellulose and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0114] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0115] Light magnesium oxide is pretreated by passing through a 30-mesh sieve; sodium bicarbonate is pretreated by passing through a 30-mesh sieve; sodium bicarbonate, light magnesium oxide, cross-linked polyvinylpyrrolidone and magnesium stearate are converted and weighed according to the prescription amount.

[0116] Place the dry granules in the mixer hopper, add sodium bicarbonate in an amount equal to the dry granules, and mix for 10 minutes; then add sodium bicarbonate twice the amount of the dry granules, and mix for 10 minutes; then add light magnesium oxide, cross-linked polyvinylpyrrolidone and the remaining sodium bicarbonate, and mix for 20 minutes; then add magnesium stearate, and mix for 10 minutes to obtain the total mixed granules.

[0117] The mixed granules are filled into gelatin hollow capsules using a capsule filling machine to obtain rabeprazole sodium bicarbonate capsules.

[0118] Example 5 Rabeprazole sodium bicarbonate dry suspension

[0119] 1) Prescription composition

[0120] Table 5

[0121] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 20 1.71 Active pharmaceutical ingredients Mannitol 155.7 13.30 diluent Povidone K30 9 0.77 Adhesives Sodium hydroxide 0.3 0.03 antacids Sodium bicarbonate 900 76.92 antacids Light magnesium oxide 60 5.13 antacids Sucralose 20 1.71 flavoring agents Orange powder flavor 5 0.43 fragrances Gross weight 1170 100 /

[0122] 2) Preparation method

[0123] According to the prescription in Table 5, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0124] Place half of the mannitol, rabeprazole sodium, povidone K30 and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0125] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0126] Light magnesium oxide is pretreated by passing through a 30-mesh sieve; sodium bicarbonate is pretreated by passing through a 30-mesh sieve; sodium bicarbonate, light magnesium oxide, sucralose and orange powder flavor are converted and weighed according to the prescription amount.

[0127] Place the dry granules in the mixer hopper, add an equal amount of sodium bicarbonate to the dry granules, and mix for 10 minutes. Then add twice the amount of sodium bicarbonate as the dry granules and mix for 10 minutes. Then add light magnesium oxide, sucralose, orange powder flavor, and the remaining sodium bicarbonate and mix for 20 minutes. This yields a rabeprazole sodium bicarbonate dry suspension.

[0128] Example 6 Rabeprazole sodium bicarbonate dry suspension

[0129] 1) Prescription composition

[0130] Table 6

[0131]

[0132]

[0133] 2) Preparation method

[0134] According to the prescription in Table 6, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0135] Place half of the mannitol, rabeprazole sodium, povidone K30 and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0136] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0137] Light magnesium oxide is pretreated by passing through a 30-mesh sieve; sodium bicarbonate is pretreated by passing through a 30-mesh sieve; sodium bicarbonate, light magnesium oxide, sucralose and orange powder flavor are converted and weighed according to the prescription amount.

[0138] Place the dry granules in the mixer hopper, add an equal amount of sodium bicarbonate to the dry granules, and mix for 10 minutes. Then add twice the amount of sodium bicarbonate as the dry granules and mix for 10 minutes. Then add light magnesium oxide, sucralose, orange powder flavor, and the remaining sodium bicarbonate and mix for 20 minutes. This yields a rabeprazole sodium bicarbonate dry suspension.

[0139] Example 7 Rabeprazole sodium bicarbonate dry suspension

[0140] 1) Prescription composition

[0141] Table 7

[0142]

[0143]

[0144] 2) Preparation method

[0145] According to the prescription in Table 7, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0146] Place half of the mannitol, rabeprazole sodium, povidone K30 and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0147] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0148] Pre-treat sodium bicarbonate by passing through a 30-mesh sieve; pre-treat anhydrous sodium carbonate by passing through a 30-mesh sieve; pre-treat calcium carbonate by passing through a 30-mesh sieve; convert and weigh sodium bicarbonate, anhydrous sodium carbonate, calcium carbonate, sucralose and orange powder flavor according to the prescription amount.

[0149] Place the dry granules in the mixer hopper, add an equal amount of sodium bicarbonate to the dry granules, and mix for 10 minutes. Then add twice the amount of sodium bicarbonate as the dry granules and mix for 10 minutes. Then add anhydrous sodium carbonate, calcium carbonate, sucralose, orange powder flavor, and the remaining sodium bicarbonate and mix for 20 minutes. This yields a rabeprazole sodium bicarbonate dry suspension.

[0150] Example 8 Rabeprazole sodium bicarbonate dry suspension

[0151] 1) Prescription composition

[0152] Table 8

[0153] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 10 0.56 Active pharmaceutical ingredients Mannitol 165.7 9.20 diluent Povidone K30 9 0.5 Adhesives Sodium hydroxide 0.3 0.02 antacids Sodium bicarbonate 600 33.33 antacids anhydrous sodium carbonate 100 5.56 antacids calcium carbonate 807 44.83 antacids Sucralose 100 5.56 flavoring agents Orange powder flavor 8 0.44 fragrances Gross weight 1800 100 /

[0154] 2) Preparation method

[0155] According to the prescription in Table 8, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0156] Place half of the mannitol, rabeprazole sodium, povidone K30 and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0157] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0158] Pre-treat sodium bicarbonate by passing through a 30-mesh sieve; pre-treat anhydrous sodium carbonate by passing through a 30-mesh sieve; pre-treat calcium carbonate by passing through a 30-mesh sieve; convert and weigh sodium bicarbonate, anhydrous sodium carbonate, calcium carbonate, sucralose and orange powder flavor according to the prescription amount.

[0159] Place the dry granules in the mixer hopper, add an equal amount of sodium bicarbonate to the dry granules, and mix for 10 minutes. Then add twice the amount of sodium bicarbonate as the dry granules and mix for 10 minutes. Then add anhydrous sodium carbonate, calcium carbonate, sucralose, orange powder flavor, and the remaining sodium bicarbonate and mix for 20 minutes. This yields a rabeprazole sodium bicarbonate dry suspension.

[0160] Example 9 Rabeprazole sodium bicarbonate dry suspension

[0161] 1) Prescription composition

[0162] Table 9

[0163] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 20 0.95 Active pharmaceutical ingredients Mannitol 155.7 7.42 diluent Povidone K30 9 0.43 Adhesives Sodium hydroxide 0.3 0.01 antacids Sodium bicarbonate 600 28.57 antacids calcium carbonate 1207 57.48 antacids Sucralose 100 4.76 flavoring agents Orange powder flavor 8 0.38 fragrances Gross weight 2100 100 /

[0164] 2) Preparation method

[0165] According to the prescription in Table 9, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0166] Place half of the mannitol, rabeprazole sodium, povidone K30 and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0167] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0168] Sodium bicarbonate was pretreated by passing through a 30-mesh sieve; calcium carbonate was pretreated by passing through a 30-mesh sieve; sodium bicarbonate, calcium carbonate, sucralose and orange powder flavor were converted and weighed according to the prescription amount.

[0169] Place the dry granules in the mixer hopper, add an equal amount of sodium bicarbonate to the dry granules, and mix for 10 minutes. Then add twice the amount of sodium bicarbonate as the dry granules and mix for 10 minutes. Then add calcium carbonate, sucralose, orange powder flavor, and the remaining sodium bicarbonate and mix for 20 minutes. This yields a rabeprazole sodium bicarbonate dry suspension.

[0170] Example 10 Rabeprazole sodium bicarbonate dry suspension

[0171] 1) Prescription composition

[0172] Table 10

[0173] name Unit amount (mg) percentage(%) effect Rabeprazole sodium 10 0.48 Active pharmaceutical ingredients Mannitol 165.7 7.89 diluent Povidone K30 9 0.43 Adhesives Sodium hydroxide 0.3 0.01 antacids Sodium bicarbonate 600 28.57 antacids calcium carbonate 1207 57.48 antacids Sucralose 100 4.76 flavoring agents Orange powder flavor 8 0.38 fragrances Gross weight 2100 100 /

[0174] 2) Preparation method

[0175] According to the prescription in Table 10, take sodium hydroxide and add an appropriate amount of purified water to prepare a sodium hydroxide solution.

[0176] Place half of the mannitol, rabeprazole sodium, povidone K30 and the remaining mannitol in a wet granulator, turn on the stirring blade and cutting blade, and pre-mix for 5 minutes.

[0177] Turn on the stirring blade and the cutting blade, and add the sodium hydroxide solution at the same time. After the addition of liquid is completed, continue granulation for 1 minute; after the granulation is completed, wet granulation and fluidized drying are carried out to remove moisture from the wet granules; after the drying is completed, dry granulation is carried out and the weight of the dry granules is weighed.

[0178] Sodium bicarbonate was pretreated by passing through a 30-mesh sieve; calcium carbonate was pretreated by passing through a 30-mesh sieve; sodium bicarbonate, calcium carbonate, sucralose and orange powder flavor were converted and weighed according to the prescription amount.

[0179] Place the dry granules in the mixer hopper, add an equal amount of sodium bicarbonate to the dry granules, and mix for 10 minutes. Then add twice the amount of sodium bicarbonate as the dry granules and mix for 10 minutes. Then add calcium carbonate, sucralose, orange powder flavor, and the remaining sodium bicarbonate and mix for 20 minutes. This yields a rabeprazole sodium bicarbonate dry suspension.

[0180] Example 11

[0181] The samples of Example 1 and Example 2 were packaged using oral high-density polyethylene bottles and high-density polyethylene / polypropylene child-safe combination bottle caps, each bottle containing one solid medicinal polyethylene bottled silica gel desiccant.

[0182] The above samples were placed under long-term conditions (25°C, 60% RH) for 6 months, intermediate conditions (30°C, 65% RH) for 6 months, and accelerated conditions (40°C, 75% RH) for 3 months. The results of the relevant substances were good, as shown in Table 11.

[0183] Table 11

[0184] Sample name Sample retention conditions / time Maximum single impurity (%) Total impurities (%) Example 1 Sample 0 days 0.11 0.11 Example 1 Sample Long-term conditions 6 months 0.11 0.11 Example 1 Sample Intermediate conditions 6 months 0.15 0.15 Example 1 Sample Acceleration conditions March 0.20 0.40 Example 2 Sample 0 days 0.15 0.15 Example 2 Sample Long-term conditions 6 months 0.16 0.16 Example 2 Sample Intermediate conditions 6 months 0.19 0.27 Example 2 Sample Acceleration conditions March 0.41 0.90

[0185] Note: Reporting limit 0.05%.

[0186] Example 12

[0187] The active ingredient degradation of embodiment 1, embodiment 2, embodiment 4 is assessed in a simulated gastric acid environment. Test conditions are hydrochloric acid solution (adding 3.8ml hydrochloric acid in 1 liter of purified water, stirring), simulated gastric acid solution (72ml hydrochloric acid solution and 240ml purified water mix). Embodiment 1, embodiment 2, embodiment 4 are added to the simulated gastric acid solution respectively, are placed in a constant temperature oscillation box, and vibrated 30 minutes at 37 ℃, and the active ingredient content is detected by sampling. As shown in table 12, embodiment 1, embodiment 2, embodiment 4 prescriptions can effectively protect the active ingredient.

[0188] Table 12

[0189] Sample name Active ingredient content (%) Example 1 73.5 Example 2 71.1 Example 4 87.8

[0190] Example 13

[0191] Samples of Control Example 1 (Drug R) and Example 1 (Drug T) were taken for in vivo PK study in healthy subjects. The rabeprazole sodium enteric-coated tablets in Control Example 1 were selected as the control substance, and the rabeprazole sodium bicarbonate capsules in Example 1 were used as the test substance. The dose of rabeprazole sodium was 20 mg. Each subject was administered one capsule of the control substance and one capsule of the test substance. Blood was collected periodically for the control substance group and the test substance group to detect blood drug concentrations. The results of the bioequivalence analysis of pharmacokinetic parameters are shown in Table 13.

[0192] Table 13

[0193] parameter Geometric mean ratio (T / R, %) Intra-individual variation (%) <![CDATA[C max ]]> 122.68 34.28 <![CDATA[AUC las t]]> 91.99 20.64 <![CDATA[AUC INF _obs]]> 91.74 20.20

[0194] From the above results, it can be seen that the drug peak concentration of the sample in Example 1 is relatively higher, and the area under the drug-time curve is similar to that of Control Example 1. The results are good and in line with expectations.

[0195] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A rabeprazole pharmaceutical composition, characterized in that: The rabeprazole pharmaceutical composition comprises: a pharmaceutically active ingredient and an antacid, wherein the pharmaceutically active ingredient is selected from one or more of rabeprazole, rabeprazole sodium, and other pharmaceutically acceptable salts, solvates, and hydrates thereof.

2. The rabeprazole pharmaceutical composition according to claim 1, wherein: Under the condition of pH 2.0-6.8, the content of the active ingredient of the pharmaceutical composition can reach more than 65%, and the content is calculated based on rabeprazole, which refers to the percentage of the mass of rabeprazole to the total mass of the rabeprazole pharmaceutical composition; and / or, the antacid is selected from one or more of sodium bicarbonate, magnesium oxide, sodium hydroxide, calcium carbonate and sodium carbonate; and / or, the content of the pharmaceutically active ingredient is 0.10% to 5.00%, where the content refers to the percentage of the mass of the pharmaceutically active ingredient to the total mass of the rabeprazole pharmaceutical composition; and / or, The total content of the antacid is 50.00% to 95.00%, where the content refers to the percentage of the total mass of all antacids to the total mass of the rabeprazole pharmaceutical composition; and / or, the antacid contains at least one or more of sodium hydroxide, sodium bicarbonate, calcium carbonate, and sodium carbonate; And / or, the sodium carbonate is anhydrous sodium carbonate.

3. The rabeprazole pharmaceutical composition according to claim 2, wherein: The content of sodium hydroxide is greater than 0 and does not exceed 0.10%, and the content refers to the percentage of the mass of sodium hydroxide to the total mass of the rabeprazole pharmaceutical composition; and / or, the content of sodium bicarbonate is not less than 15.00% and less than 95.00%, wherein the content refers to the percentage of the mass of sodium bicarbonate to the total mass of the rabeprazole pharmaceutical composition; And / or, the content of the light magnesium oxide is 0-10.00%, where the content refers to the percentage of the mass of the light magnesium oxide to the total mass of the rabeprazole pharmaceutical composition; and / or, the content of sodium carbonate is 0-10.00%, wherein the content refers to the percentage of the mass of sodium carbonate to the total mass of the rabeprazole pharmaceutical composition; And / or, the content of calcium carbonate is 0-80.00%, wherein the content refers to the percentage of the mass of calcium carbonate to the total mass of the rabeprazole pharmaceutical composition; And / or, the antacid is selected from any one of the following combinations: a combination of sodium hydroxide and sodium bicarbonate; a combination of sodium hydroxide, sodium bicarbonate, and light magnesium oxide; a combination of sodium hydroxide, sodium bicarbonate, anhydrous sodium carbonate, and calcium carbonate; a combination of sodium hydroxide, sodium bicarbonate, and calcium carbonate; And / or, the rabeprazole pharmaceutical composition further comprises one or more of a diluent, a disintegrant, a binder, a lubricant, a flavoring agent and an aromatic agent.

4. The rabeprazole pharmaceutical composition according to claim 3, wherein: The diluent is selected from mannitol and / or lactose and / or microcrystalline cellulose; and / or, The disintegrant is selected from one or more of crospovidone, sodium carboxymethyl starch, crospovidone sodium, low-substituted hydroxypropyl cellulose, pregelatinized starch and polyclinic potassium; and / or, The binder is selected from one or more of hydroxypropyl cellulose, hypromellose, povidone, copovidone, hydroxyethyl cellulose, sodium carboxymethyl cellulose, carbomer, polyethylene oxide and ethyl cellulose; and / or, The lubricant is selected from one or more of magnesium stearate, calcium stearate, sodium stearyl fumarate, stearic acid, glyceryl stearate and polyethylene glycol; and / or, The flavoring agent is selected from one or more of sucralose, aspartame, sucrose, fructose, steviol glycosides, glycyrrhizin, sodium chloride, citric acid, saccharin and saccharin sodium; and / or, The aromatic agent is selected from one or more of essence, spices and menthol.

5. The rabeprazole pharmaceutical composition according to claim 3 or 4, wherein: The content of the diluent is 0-30.00%, and the content refers to the percentage of the mass of the diluent to the total mass of the rabeprazole pharmaceutical composition; and / or, The content of the disintegrant is 0-30.00%, and the content refers to the percentage of the mass of the disintegrant to the total mass of the rabeprazole pharmaceutical composition; and / or, The content of the binder is 0-10.00%, and the content refers to the percentage of the mass of the binder to the total mass of the rabeprazole pharmaceutical composition; and / or, The content of the lubricant is 0-5.00%, and the content refers to the percentage of the mass of the lubricant to the total mass of the rabeprazole pharmaceutical composition; and / or, The content of the flavoring agent is 0-30.00%, and the content refers to the percentage of the mass of the flavoring agent to the total mass of the rabeprazole pharmaceutical composition; and / or, The content of the aromatic agent is 0-30.00%, and the content refers to the percentage of the mass of the aromatic agent to the total mass of the rabeprazole pharmaceutical composition; And / or, the rabeprazole pharmaceutical composition contains 10 mg to 20 mg of the active pharmaceutical ingredient; and / or, contains 800 mg to 3000 mg of an antacid.

6. The rabeprazole pharmaceutical composition according to claim 1, wherein: The rabeprazole pharmaceutical composition is selected from any one of the following prescriptions: Prescription 1: 1.66% rabeprazole sodium, 4.43% mannitol, 0.07% hydroxypropylcellulose, 0.01% sodium hydroxide, 91.66% sodium bicarbonate, 1.67% cross-linked polyvinylpyrrolidone, 0.50% magnesium stearate; the percentages mentioned refer to the mass percentage of each component to the total mass of the rabeprazole pharmaceutical composition; Prescription 2: 0.83% rabeprazole sodium, 5.26% mannitol, 0.07% hydroxypropylcellulose, 0.01% sodium hydroxide, 91.67% sodium bicarbonate, 1.66% cross-linked polyvinylpyrrolidone, 0.50% magnesium stearate; the percentages mentioned refer to the mass percentage of each component to the total mass of the rabeprazole pharmaceutical composition; Prescription 3: 1.89% rabeprazole sodium, 5.01% mannitol, 0.08% hydroxypropylcellulose, 0.01% sodium hydroxide, 84.91% sodium bicarbonate, 5.66% light magnesium oxide, 1.88% cross-linked polyvinylpyrrolidone, 0.56% magnesium stearate; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition; Prescription 4: 0.94% rabeprazole sodium, 5.95% mannitol, 0.08% hydroxypropylcellulose, 0.01% sodium hydroxide, 84.91% sodium bicarbonate, 5.66% light magnesium oxide, 1.88% cross-linked polyvinylpyrrolidone, 0.57% magnesium stearate; the percentages mentioned refer to the percentage of the mass of each component to the total mass of the rabeprazole pharmaceutical composition; Prescription 5: 1.71% rabeprazole sodium, 13.30% mannitol, 0.77% povidone K30, 0.03% sodium hydroxide, 76.92% sodium bicarbonate, 5.13% light magnesium oxide, 1.71% sucralose, 0.43% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition; Prescription 6: 0.85% rabeprazole sodium, 14.16% mannitol, 0.77% povidone K30, 0.03% sodium hydroxide, 76.92% sodium bicarbonate, 5.13% light magnesium oxide, 1.71% sucralose, 0.43% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition; Prescription 7: 1.11% rabeprazole sodium, 8.65% mannitol, 0.5% povidone K30, 0.02% sodium hydroxide, 33.33% sodium bicarbonate, 5.56% anhydrous sodium carbonate, 44.83% calcium carbonate, 5.56% sucralose, 0.44% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition; Prescription 8: 0.56% rabeprazole sodium, 9.20% mannitol, 0.5% povidone K30, 0.02% sodium hydroxide, 33.33% sodium bicarbonate, 5.56% anhydrous sodium carbonate, 44.83% calcium carbonate, 5.56% sucralose, 0.44% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition; Prescription 9: 0.95% rabeprazole sodium, 7.42% mannitol, 0.43% povidone K30, 0.01% sodium hydroxide, 28.57% sodium bicarbonate, 57.48% calcium carbonate, 4.76% sucralose, 0.38% (orange powder) flavor; the percentages mentioned refer to the mass of each component as a percentage of the total mass of the rabeprazole pharmaceutical composition; Prescription 10: 0.48% rabeprazole sodium, 7.89% mannitol, 0.43% povidone K30, 0.01% sodium hydroxide, 28.57% sodium bicarbonate, 57.48% calcium carbonate, 4.76% sucralose, 0.38% (orange powder) flavor; the percentages refer to the percentage of the mass of each component to the total mass of the rabeprazole pharmaceutical composition.

7. A method for preparing the rabeprazole pharmaceutical composition according to any one of claims 1 to 6, comprising but not limited to powder tableting, powder encapsulation, wet granulation, dry granulation, fluidized granulation and pellet coating.

8. Use of the rabeprazole pharmaceutical composition according to any one of claims 1 to 6 in the preparation of a pharmaceutical preparation; Preferably, the pharmaceutical preparation is an oral pharmaceutical preparation; For example, the dosage form of the oral pharmaceutical preparation includes but is not limited to capsules, dry suspensions, granules, tablets or powders.

9. A pharmaceutical preparation, characterized in that The pharmaceutical preparation comprises the rabeprazole pharmaceutical composition according to any one of claims 1 to 6; Preferably, the pharmaceutical preparation is an oral pharmaceutical preparation, including but not limited to capsules, dry suspensions, granules, tablets or powders.

10. Use of the rabeprazole pharmaceutical composition according to any one of claims 1 to 6 in the preparation of a medicament for treating and / or preventing peptic ulcer; Preferably, the peptic ulcer disease includes but is not limited to gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis, Zollinger-Ellison syndrome, non-erosive gastroesophageal reflux disease, and recurrence of gastric ulcer and duodenal ulcer.

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