CN102614144A - Sodium rabeprazole medicinal composite and method for preparing same - Google Patents

Abstract

The invention discloses a sodium rabeprazole medicinal composite, which contains the active substances of sodium rabeprazole and stabilizing agent, wherein the weight ratio of the stabilizing agent and the sodium rabeprazole is 0.05-10/1, and the sodium rabeprazole medicinal composite also contains other optional pharmaceutically acceptable additives. The composite uses less amount of the stabilizing agent, has good stability and a simple preparing technology.

Description

Pharmaceutical composition of a kind of RABEPRAZOLE SODIUM and preparation method thereof

Technical field

The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of pharmaceutical composition and preparation method thereof, particularly relate to a kind of rabeprazole sodium pharmaceutical composition and preparation method thereof.

Background technology

Digestive system disease is one of common frequently-occurring disease; Be main with peptic ulcer again wherein; Its mortality rate is very low, but often with severe complications, like stomach, the concurrent upper gastrointestinal hemorrhage of duodenal ulcer meeting, perforation etc.; Bring very big misery to the patient, serious threat people's health.Proton pump inhibitor is effective medicine of PUD.RABEPRAZOLE SODIUM (Rabeprazole Sodium) is the 4th proton pump inhibitor (proton pump inhibitors after omeprazole, lansoprazole and pantoprazole; PPIs); Compare with inhibitor before and to have higher pKa value; Fast activating in vivo after oral combines performance to press down the acid effect with proton pump, particularly remarkable in aspect advantages such as secretion inhibitor effect, anti-helicobacter pylori activity and drug safety and metabolism polymorphisms.

RABEPRAZOLE SODIUM, its chemical name are 2-{ [4-(3-methoxy propoxy)-3-picoline-2-yl] methanesulfinyl }-1H-benzimidazole sodium, molecular formula: C18H22N3NaO3S, molecular weight: 381.43, structural formula is:

The structures shape of RABEPRAZOLE SODIUM its to wet, light and heat are unstable, it is faster especially to meet acid degradation.Therefore, adopt common pharmacy preparation forming technique to be difficult to prepare the RABEPRAZOLE SODIUM solid preparation that meets drug standard, like tablet, capsule, granule etc.

Patent application 201110000086.4 discloses a kind of composition of compound recipe RABEPRAZOLE SODIUM Pharmaceutical composition; Wherein added the alkaline matter sodium bicarbonate with (or) magnesium hydroxide is as stabilizing agent, calculate by weight RABEPRAZOLE SODIUM: the sodium bicarbonate ratio is 1: (55～168); Perhaps RABEPRAZOLE SODIUM: sodium bicarbonate: magnesium hydroxide is 1: (30～60): (35～70); Wherein the alkaline stabiliser consumption is excessive, is unfavorable for the molding of writing out a prescription, and the dosage form gross weight of preparation same dose is excessive; Generally at (between 1170～3110mg); Be not suitable for swallowing, can only process the capsule of the form or the big specification of chewable tablet or dry suspension, therefore clinical use poor compliance.

For overcoming the deficiency of above-mentioned preparation, the inventor unexpectedly finds through concentrating on studies; In the Pharmaceutical composition of RABEPRAZOLE SODIUM, add stabilizing agent in a small amount, prepared rabeprazole sodium oral solid preparation has good stable property like tablet, capsule, granule etc.; Not only can solve the technical problem that the principal agent RABEPRAZOLE SODIUM is prone to degraded, and method for preparing is simple, the dosage form of same dose; Gross weight is littler, is more suitable for swallowing, and clinical compliance is better.

Summary of the invention

First aspect of the present invention provides a kind of Pharmaceutical composition of RABEPRAZOLE SODIUM; Contain suc as formula active component RABEPRAZOLE SODIUM, the stabilizing agent shown in (I); Wherein the weight ratio of stabilizing agent and RABEPRAZOLE SODIUM is 0.05～10: 1 and other optional pharmaceutically acceptable additive.

Preferably, the weight ratio of stabilizing agent and RABEPRAZOLE SODIUM is 1～5: 1 in the said compositions.

Term among the present invention " stabilizing agent " is meant the additive in the preparation prescription, and the stability of drug in the preparation is had protective effect.Described stabilizing agent is to be selected from a kind of in sodium carbonate, sodium bicarbonate, calcium hydrogen phosphate, magnesium hydroxide, magnesium oxide, magnesium silicate, sodium citrate, Tris, meglumine, calcium oxide, the calcium hydroxide; Or two or more mixture wherein; Be preferably sodium carbonate, sodium bicarbonate, magnesium hydroxide, magnesium oxide, calcium oxide, calcium hydroxide; Further be preferably sodium carbonate, sodium bicarbonate, magnesium hydroxide, magnesium oxide; More preferably natrium carbonicum calcinatum, anhydrous sodium bicarbonate, magnesium hydroxide, magnesium oxide most preferably are natrium carbonicum calcinatum.

In the above-mentioned composition, if having, wherein said other pharmaceutically acceptable additive is to be selected from filler, binding agent, disintegrating agent, lubricant, the enteric film coating material one or more.

Wherein lubricant is preferably a kind of in magnesium stearate, fixed oil, the Pulvis Talci or wherein several kinds.Preferably, said lubricant quantity is 0.5% to 2.0% of whole weight of material.

The additive of preferred pharmaceutical compositions comprises microcrystalline Cellulose, lactose, hyprolose, pregelatinized Starch, polyvinylpolypyrrolidone, carboxymethyl starch sodium, mannitol, magnesium stearate, fixed oil.

In a concrete embodiment; Contain RABEPRAZOLE SODIUM, stabilizing agent, mannitol, hydroxypropyl cellulose, magnesium stearate in the pharmaceutical composition of the present invention; RABEPRAZOLE SODIUM wherein: stabilizing agent (for example natrium carbonicum calcinatum, anhydrous sodium bicarbonate, magnesium hydroxide, magnesium oxide etc.): mannitol: hydroxypropyl cellulose: the weight ratio of magnesium stearate is 5～15: 5～60: 20～100: 5～20: 0.5～1.5, and be preferably 10: 10: 80: 15: 1.15,10: 30: 60: 15: 1.15 or 10: 50: 40: 15: 1.15 preparation is also contained among the present invention.

Compositions of the present invention can be processed tablet, capsule or granule;

Preferably, the mode of taking of described compositions is for swallowing; Preferably, the ratio of active component RABEPRAZOLE SODIUM and the gross weight of preparation is 1: 9～12 in the described compositions.

Second aspect of the present invention provides the method for preparing of above-mentioned composition, and this method comprises that the weight ratio with stabilizing agent and RABEPRAZOLE SODIUM is controlled at 0.05～10: the step in 1 the scope.

In a preferred embodiment, described method is further comprising the steps of:

A. with certain amount of stabilizer, active component RABEPRAZOLE SODIUM, and dispensable pharmaceutically acceptable additive mix homogeneously except that lubricant, mixture obtained;

B. use non-water-soluble matchmaker as wetting agent,, must do granule after the drying the mixture system wet granular that obtains among the step a;

C. in dried granule, add lubricant, mixed, granulate is processed preparation as required;

D. selectively, the preparation of step c being processed adopts the enteric film coating material to carry out coating.

Preferably, the wet granular described in the step b is that the mixed material that obtains among the rapid a is mixed back system soft material with wetting agent, crosses 18 order to 20 mesh sieves then and makes;

Preferably, described non-water-soluble matchmaker is selected from ethanol, acetone, and more preferably, described non-water-soluble matchmaker is an ethanol;

Preferably, baking temperature is 40 ℃ to 60 ℃ among the step b;

Preferably, the mixing among the step c was that 14 order to 16 mesh sieves mix.

Term among the present invention " soft material " is meant: in the wet granulation technology, and the wet mix that forms behind wetting agent that the mixture adding of pulverous crude drug and additive is an amount of or the binding agent mix homogeneously.

In another preferred embodiment, described method is further comprising the steps of:

A. with certain amount of stabilizer, active component RABEPRAZOLE SODIUM, and dispensable pharmaceutically acceptable additive mix homogeneously except that lubricant, mixture obtained;

B. with the mixture that obtains among the step a, with lubricant mixed after, adopt dry granulation technology or technique of direct powder compression to process required preparation;

C. selectively, adopt the enteric film coating material to carry out coating to the preparation of processing among the step b.

In a concrete embodiment, method for preparing of the present invention be earlier will be except that lubricant other pharmaceutically acceptable additive (for example solid preparation molding excipient) and certain amount of stabilizer, mix homogeneously; Again with principal agent with the equivalent method mix homogeneously that progressively increases; (1) be that wetting agent carries out wet granulation with non-water-soluble matchmaker, the granule of preparation sieves after drying, with the mixed back of magnesium stearate tabletting; Perhaps the fill capsule perhaps prepares granule; Perhaps (2) adopt dry granulation direct compression process or direct powder compression to prepare tablet.Said method for preparing specifically comprises:

A. get excipient (like one or more of microcrystalline Cellulose, hydroxypropyl cellulose, pregelatinized Starch, mannitol, lactose etc.); Elder generation and certain amount of stabilizer (like natrium carbonicum calcinatum, sodium bicarbonate, calcium hydrogen phosphate, magnesium oxide, magnesium hydroxide, magnesium silicate, sodium citrate, Tris, meglumine, calcium oxide, calcium hydroxide etc.); Mix homogeneously, mixed adjuvant again with the principal agent RABEPRAZOLE SODIUM mix homogeneously of recipe quantity;

B. use non-water-soluble matchmaker to be wetting agent, with above-mentioned mixed material system soft material, cross 18 order to 20 mesh sieve system wet granulars, 40 ℃ to 60 ℃ on wet granular warp is dry must do granule.

C. in dried granule, add a certain amount of lubricant; It is mixed to cross 14 order to 16 mesh sieves, and granulate is the tablet of RABEPRAZOLE SODIUM according to clinical application demand compacting principal agent; Perhaps direct fill capsule prepares the capsule of required specification, and perhaps direct packaging becomes the granule of required specification.

Also can be with the supplementary material mixture of step a. preparation, with a certain amount of lubricant mixed after, adopt dry granulation technology or technique of direct powder compression, directly prepare the tablet or the capsule of required specification without wet-granulation process.

D. adopt the enteric film coating material to carry out coating to prepared label.

Compositions of the present invention can be used to prepare the medicine of treating PUD, or preparation is as the medicine of proton pump inhibitor.Therefore the third aspect of the invention provides the present composition in the purposes that is used for preparing the medicine of treating PUD, or is preparing as the purposes in the medicine of proton pump inhibitor.

The beneficial effect of the invention

Add stabilizing agent in a small amount in the Pharmaceutical composition of RABEPRAZOLE SODIUM of the present invention, help the molding of writing out a prescription, prepared rabeprazole sodium oral solid preparation (like tablet, capsule, granule etc.) has good stable property; Not only can solve the technical problem that the principal agent RABEPRAZOLE SODIUM is prone to degraded, and method for preparing is simple, cost is low; With respect to prior art, the dosage form of same dose, gross weight is littler; Be more suitable for swallowing, clinical compliance is better.

The specific embodiment

To combine embodiment that embodiment of the present invention are described in detail below, but it will be understood to those of skill in the art that the following example only is used to explain the present invention, and should not be regarded as limiting scope of the present invention.Those skilled in the art are understanding under the prerequisite of spirit of the present invention, can carry out corresponding conversion to the present invention according to the prior art and the knowledge in present technique field, and these technical schemes all fall within the scope of the present invention.Unreceipted actual conditions person in the following example and the experimental example carries out according to the condition of normal condition or manufacturer's suggestion, the unreceipted person of production firm of agents useful for same or instrument, and being can be through the conventional products of commercial acquisition.The RABEPRAZOLE SODIUM of using in the following example and the experimental example is available from Shanghai Xinyi Wanxiang Pharmaceutical Co., Ltd..

Embodiment 1

Table 1: prescription

Preparation technology:

Prescription ratio according in the table 1 takes by weighing supplementary material; At first that magnesium hydroxide, mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously; Mix with the principal agent of recipe quantity and cross 60 mesh sieves to mix homogeneously, mix with magnesium stearate at last, it is 10mg that direct powder compression prepares specification; Sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (also directly No. 3 capsules of fill prepare the rabeprazole natrium capsule that specification is 10mg).

Those skilled in the art it is further contemplated that RABEPRAZOLE SODIUM: magnesium hydroxide: mannitol: hydroxypropyl cellulose: the weight ratio of magnesium stearate is 10: 10: 80: 15: 1.15,10: 30: 60: 15: 1.15 or 10: 50: 40: 15: 1.15 preparation is also contained among the present invention.

Embodiment 2

Table 2: prescription

Preparation technology:

Prescription ratio according in the table 2 takes by weighing supplementary material; At first that natrium carbonicum calcinatum, mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously; Mix with the principal agent of recipe quantity and cross 60 mesh sieves to mix homogeneously, mix with magnesium stearate at last, it is 10mg that direct powder compression prepares specification; Sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (also directly No. 3 capsules of fill prepare the rabeprazole natrium capsule that specification is 10mg).

Those skilled in the art it is further contemplated that RABEPRAZOLE SODIUM: natrium carbonicum calcinatum: mannitol: hydroxypropyl cellulose: the weight ratio of magnesium stearate is 10: 10: 80: 15: 1.15,10: 30: 60: 15: 1.15 or 10: 50: 40: 15: 1.15 preparation is also contained among the present invention.

Embodiment 3

Table 3: prescription

Preparation technology:

Prescription ratio according in the table 3 takes by weighing supplementary material; At first that anhydrous sodium bicarbonate, mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously; Mix with the principal agent of recipe quantity and cross 60 mesh sieves to mix homogeneously, mix with magnesium stearate at last, it is 10mg that direct powder compression prepares specification; Sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (also directly No. 3 capsules of fill prepare the rabeprazole natrium capsule that specification is 10mg).

Those skilled in the art it is further contemplated that RABEPRAZOLE SODIUM: anhydrous sodium bicarbonate: mannitol: hydroxypropyl cellulose: the weight ratio of magnesium stearate is 10: 10: 80: 15: 1.15,10: 30: 60: 15: 1.15 or 10: 50: 40: 15: 1.15 preparation is also contained among the present invention.

Embodiment 4

Table 4: prescription

Preparation technology 1:

Prescription ratio according in the table 4 takes by weighing supplementary material; At first that magnesium oxide, mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously; Mix with the principal agent of recipe quantity and cross 60 mesh sieves to mix homogeneously, mix with magnesium stearate at last, it is 10mg that direct powder compression prepares specification; Sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (also directly No. 3 capsules of fill prepare the rabeprazole natrium capsule that specification is 10mg).

Perhaps the prescription in the table 4 is processed tablet or capsule according to preparation technology 2 method.

Preparation technology 2:

Prescription ratio according in the table 4 takes by weighing supplementary material, and is at first that magnesium oxide, mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously, mixes with the principal agent of recipe quantity again and excessively 60 mesh sieves to mix homogeneously; With the dehydrated alcohol is wetting agent, and the preparation soft material is crossed 20 mesh sieve system granules; After 40 ℃ of oven dry, add the magnesium stearate of recipe quantity, mix homogeneously; Tabletting; Being prepared into specification is 10mg, and sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (can be the rabeprazole sodium granules of 10mg with aluminium plastic bag sealing preparation specification directly also).

Those skilled in the art it is further contemplated that RABEPRAZOLE SODIUM: magnesium oxide: mannitol: hydroxypropyl cellulose: the weight ratio of magnesium stearate is 10: 10: 80: 15: 1.15,10: 30: 60: 15: 1.15 or 10: 50: 40: 15: 1.15 preparation is also contained among the present invention.

The comparative example 1

Table 5: contrast prescription

Preparation technology:

Prescription ratio according in the table 5 takes by weighing supplementary material; At first that sodium hydroxide, mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously; Mix with the principal agent of recipe quantity and cross 60 mesh sieves to mix homogeneously, mix with magnesium stearate at last, it is 10mg that direct powder compression prepares specification; Sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (also directly No. 3 capsules of fill prepare the rabeprazole natrium capsule that specification is 10mg).

The comparative example 2

Table 6: contrast prescription

Preparation technology:

Ratio according to the prescription of the contrast in the table 6 takes by weighing supplementary material, behind RABEPRAZOLE SODIUM, sodium bicarbonate, cross-linking sodium carboxymethyl cellulose and magnesium stearate mix homogeneously, and direct compression, the gained tablet weight is 1170mg, contains principal agent RABEPRAZOLE SODIUM 10mg.

The comparative example 3

Table 7: contrast prescription

Preparation technology:

Ratio according to the prescription of the contrast in the table 7 takes by weighing supplementary material; At first that mannitol, hydroxypropyl cellulose is mixed and cross 60 mesh sieves to mix homogeneously; Mix with the principal agent of recipe quantity and cross 60 mesh sieves to mix homogeneously, mix with magnesium stearate at last, it is 10mg that direct powder compression prepares specification; Sheet heavily is 116.15mg, and sheet directly is the rabeprazole sodium tablet of 7mm (also directly No. 3 capsules of fill prepare the rabeprazole natrium capsule that specification is 10mg).

Experimental example 1 unpackaged high-temperature sample high humidity influence factor stability relatively

Naked 60 ℃ of the high temperature that place of all prescription samples (prescription 1 is to prescription 17) with embodiment and comparative example; Under the relative humidity RH75% condition; Respectively at 0h, 4h, 8h, 12h, 24h sampling, the appearance color of observing preparation changes, and adopts following method to measure the variation of its content of degradation products.

Method for determination related substances (HPLC):

Related substance is meant in the medicine general name of other related substanceses except that the principal agent composition; Wherein mainly comprise the catabolite that the impurity introduced in the synthesis technique and storage process produce; Related substance is the important characteristic index of stability of drug products; The relative amount of related substance is big more, and medicine is more unstable.

1, chromatographic condition: immobile phase is ZORBAX SB-C18 (4.6 * 250mm, 5 μ m); With 0.05molL ^-1Potassium dihydrogen phosphate (regulating pH value to 7.0 with NaOH solution) and methanol are mobile phase, and wherein the volume ratio of potassium dihydrogen phosphate and methanol is 40: 60; The detection wavelength is 285nm.Flow velocity is 1ml/min, and sample size is 20 μ l.

2, method for determination related substances: respectively at 0h, 4h, 8h, 12h, 24h sampling, every kind of prescription is got 5 of test specimens, in the brown volumetric flask of 250ml; It is an amount of to add mobile phase; Jolting makes principal agent (RABEPRAZOLE SODIUM) dissolving, adds mobile phase to scale, with the organic membrane filtration of 0.45 μ m.Get filtrate as laboratory sample solution.Treating excess syndrome is tested sample solution 20 μ l, the injection chromatograph of liquid, and 3 times of writing down chromatogram to retention time are pressed the relative amount (%) that the peak area normalization method is measured related substance.

Preparation prescription 1 to the preparation appearance color situation of change of prescription 17 and the relative amount result of variations of related substance seen table 8 to table 15.

Table 8. embodiment 1 is the stability result of quadrat sampling article everywhere

Table 9. embodiment 2 is the stability result of quadrat sampling article everywhere

Table 10. embodiment 3 is the stability result of quadrat sampling article everywhere

Table 11. embodiment 4 is the stability result of quadrat sampling article (preparation technology 1) everywhere

Table 12. embodiment 4 is the stability result of quadrat sampling article (preparation technology 2) everywhere

Table 13. comparative example 1 is the stability result of quadrat sampling article everywhere

Table 14. comparative example 2 is the stability result of quadrat sampling article everywhere

Table 15. comparative example 3 is the stability result of quadrat sampling article everywhere

Data show in table 8 to the table 15: with respect to writing out a prescription 17 among the comparative example 3; The stability of embodiment 1 to embodiment 4 is all more excellent; The stabilizing agent that adds has positive effect to medicine stability; And in during short study on the stability (24h), embodiment 2 stability of sample all demonstrate certain advantage than embodiment 1, embodiment 3, embodiment 4 and comparative example's 1 stability, so natrium carbonicum calcinatum is preferred stabilizing agent; 16 (same ratio prescriptions in patent application 201110000086.4 claim) are compared with writing out a prescription among the comparative example 2; In equally during short study on the stability (24h); The stability of embodiment 2 and comparative example 2 are quite or excellent slightly; But among the comparative example 2 in the prescription 16 consumption of stabilizing agent all big a lot of than each prescription of embodiment 2, the increase of stabilizing agent dosage is unfavorable for that the molding of preparation, the present invention use indivisible stabilizing agent; Promptly reached Stabilization, and preparation technology is simple to medicine; And the present invention also finds through research, in the amount ranges of being screened, increases stabilizing agent dosage stability of drug is not had remarkable effect.

Simultaneously; The weight of formulation of the prescription 16 among preparation (for example specification is the tablet or the capsule of the 10mg RABEPRAZOLE SODIUM) comparative example 2 of same dosage or specification is 1170mg, and the weight of formulation of prescription 1 to prescription 12 is merely 116.15mg among the embodiment 1 to embodiment 4.Therefore, the compositions of same dose or specification, weight of formulation of the present invention is littler, and suitable patient swallows, and clinical compliance is better.

In addition, the present invention makes that preparation of compositions cost of the present invention is lower because the consumption (the particularly consumption of stabilizing agent) of adjuvant reduces.

Experimental example 2 adds the hot and humid stability test that compositing aluminium bag packs sample through the plastic-aluminum bubble-cap

1, label is carried out coating

Write out a prescription 14 among prescription 5 among the embodiment 2 and the comparative example 1, and the 17 prepared tablets of the prescription among the comparative example 3 (HPMCP HP55) carries out coating, and coating weightening finish is about 3% with the enteric solubility thin film coating material.

2, the plastic-aluminum bubble-cap adds compositing aluminium bag and packs

Tablet behind the coating in the step 1 is added after compositing aluminium bag packs with the plastic-aluminum bubble-cap; High temperature (60 ℃) high humiditys (RH75%) condition held 6 months; Respectively at 0,1,2,3,6 month sample analysis; Observe the label change color of preparation, and the determination of related substances method of employing Test Example 1 is investigated the variation of the relative amount of related substance.The result sees table 16, and the result shows that prescription 5 stability is superior to writing out a prescription 14 and write out a prescription 17, visiblely adds stabilizing agent of the present invention medicine stability is had positive effect.

Table 16. through the plastic-aluminum bubble-cap add compositing aluminium bag pack after the stability of sample result

In sum; The Pharmaceutical composition of RABEPRAZOLE SODIUM of the present invention has good stable property, and prepared is simple, and stabilizing agent dosage is few; Help the molding of writing out a prescription; Cost is low, and prepared rabeprazole sodium oral solid preparation (like tablet, capsule, granule etc.) not only can solve the technical problem that the principal agent RABEPRAZOLE SODIUM is prone to degraded, and is more suitable for swallowing.

Claims (10)

1. the pharmaceutical composition of a RABEPRAZOLE SODIUM contains suc as formula active component RABEPRAZOLE SODIUM, the stabilizing agent shown in (I), and wherein the weight ratio of stabilizing agent and RABEPRAZOLE SODIUM is 0.05～10: 1 and other optional pharmaceutically acceptable additive.

2. the compositions of claim 1, wherein the weight ratio of stabilizing agent and RABEPRAZOLE SODIUM is 1～5: 1.

3. the compositions of claim 1; Wherein, Described stabilizing agent is to be selected from a kind of in sodium carbonate, sodium bicarbonate, calcium hydrogen phosphate, magnesium hydroxide, magnesium oxide, magnesium silicate, sodium citrate, Tris, meglumine, calcium oxide, the calcium hydroxide; Or two or more mixture wherein

Be preferably sodium carbonate, sodium bicarbonate, magnesium hydroxide, magnesium oxide, calcium oxide, calcium hydroxide,

Further be preferably sodium carbonate, sodium bicarbonate, magnesium hydroxide, magnesium oxide,

More preferably natrium carbonicum calcinatum, anhydrous sodium bicarbonate, magnesium hydroxide, magnesium oxide,

Most preferably be natrium carbonicum calcinatum.

4. the compositions of claim 1, if having, wherein said other pharmaceutically acceptable additive is to be selected from filler, binding agent, disintegrating agent, lubricant, the enteric film coating material one or more,

The additive of preferred pharmaceutical compositions comprises microcrystalline Cellulose, lactose, hyprolose, pregelatinized Starch, polyvinylpolypyrrolidone, carboxymethyl starch sodium, mannitol, magnesium stearate, fixed oil.

5. the compositions of claim 4, wherein lubricant is a kind of in magnesium stearate, fixed oil, the Pulvis Talci or wherein several kinds, preferably, said lubricant quantity is 0.5% to 2.0% of whole weight of material.

6. each preparation of compositions method of claim 1 to 5, this method comprises that the weight ratio with stabilizing agent and RABEPRAZOLE SODIUM is controlled at 0.05～10: the step in 1 the scope.

7. each compositions or the method for preparing of claim 6 of claim 1 to 5, described compositions is tablet, capsule or granule;

Preferably, the mode of taking of described compositions is for swallowing;

Preferably, the ratio of active component RABEPRAZOLE SODIUM and the gross weight of preparation is 1: 9～12 in the described compositions.

8. the method for preparing of claim 6, this method also comprises:

A. with described stabilizing agent, active component RABEPRAZOLE SODIUM, and dispensable pharmaceutically acceptable additive mix homogeneously except that lubricant, mixture obtained;

B. use non-water-soluble matchmaker as wetting agent,, must do granule after the drying the mixture system wet granular that obtains among the step a;

C. in dried granule, add lubricant, mixed, granulate is processed preparation as required;

D. selectively, the preparation of step c being processed adopts the enteric film coating material to carry out coating.

Preferably, the wet granular described in the step b is that the mixed material that obtains among the rapid a is mixed back system soft material with wetting agent, crosses 18 order to 20 mesh sieves then and makes;

Preferably, described non-water-soluble matchmaker is selected from ethanol, acetone, and more preferably, described non-water-soluble matchmaker is an ethanol;

Preferably, baking temperature is 40 ℃ to 60 ℃ among the step b;

Preferably, the mixing among the step c was that 14 order to 16 mesh sieves mix.

9. the preparation of compositions method of claim 6, this method also comprises:

A. with described stabilizing agent, active component RABEPRAZOLE SODIUM, and dispensable pharmaceutically acceptable additive mix homogeneously except that lubricant, mixture obtained;

B. with the mixture that obtains among the step a, with lubricant mixed after, adopt dry granulation technology or technique of direct powder compression to process required preparation;

C. selectively, adopt the enteric film coating material to carry out coating to the preparation of processing among the step b.

10. each compositions of claim 1 to 5 is in the purposes that is used for preparing the medicine of treating PUD, or in preparation as the purposes in the medicine of proton pump inhibitor.