CN104146947A - Anti-hypertensive medicinal preparation and preparation method thereof - Google Patents
Anti-hypertensive medicinal preparation and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 52
- 230000003276 anti-hypertensive effect Effects 0.000 title abstract 5
- 239000000463 material Substances 0.000 claims abstract description 19
- 239000003085 diluting agent Substances 0.000 claims abstract description 18
- 239000000314 lubricant Substances 0.000 claims abstract description 18
- 239000011230 binding agent Substances 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 40
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 40
- 239000008187 granular material Substances 0.000 claims description 26
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- 235000019359 magnesium stearate Nutrition 0.000 claims description 20
- 239000002220 antihypertensive agent Substances 0.000 claims description 18
- 229940127088 antihypertensive drug Drugs 0.000 claims description 18
- 108010061435 Enalapril Proteins 0.000 claims description 15
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 claims description 15
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- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
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- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
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- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an anti-hypertensive medicinal preparation and a preparation method thereof. The anti-hypertensive medicinal preparation comprises a quick-release part and a slow-release part in a mass ratio of 1 to 1-1 to 4, wherein the quick-release part comprises an active ingredient A, a water-soluble diluent, a disintegrating agent, a dry binder and a lubricant which are used as raw materials; and the slow-release part comprises an active ingredient B, a slow-release framework material, a diluent, a binder and a lubricant which are used as raw materials. Formulas of the quick-release part and the slow-release part are improved, so that the medicinal active ingredients of the preparation disclosed by the invention can take effect quickly and maintain a long-time anti-hypertensive effect. The preparation method disclosed by the invention is simple and convenient, the anti-hypertensive medicinal preparation is used once a day and does not need to be given frequently, the compliance of patients can be improved, meanwhile, the effective plasma-medicament concentration can be kept within a treatment range with the minimum fluctuation in the whole administration period, and the stable plasma-medicament concentration can furthest reduce adverse effect and improve the treatment effect.
Description
Technical field
This area relates to field of medicine preparations, is specifically related to a kind of antihypertensive drug preparation and preparation method thereof.
Background technology
< < China hypertension prevention and control guide (third edition) the > > of Ministry of Public Health revision in 2010 points out, the existing Hypertension number of China is about 200,000,000 people, in every 10 adults, just has 2 hyperpietics; And hypertension awareness, treatment rate and control rate are obviously lower, respectively lower than 50%, 40% and 10%.In addition, guide points out, China approximately has 1.3 hundred million hyperpietics not know oneself to suffer from hypertension at present, known, oneself suffers from hypertensive crowd, approximately has 3,000 ten thousand not treatments; In accepting the patient of Treatment of Hypertension, there is 75% blood pressure not reach level of control.Therefore the control for hypertension has become the another task of top priority of uplifting the people's living standard.A large amount of evidences show, effectively treat sickness rate, complication rate and case fatality rate that hypertension can significantly reduce cardiovascular event.Therefore, hypertension therapeutic object is to be the prevention infringement of target organ and the generation of cardiovascular disease, the death of avoiding apoplexy, coronary heart disease etc. to cause.Hypertension therapeutic main target is reach mark blood pressure, to reducing to greatest extent cardiovascular and cerebrovascular disease morbidity and death risk.The height of blood pressure depends on circulation volume, peripheral vascular resistance and heart output, mainly by sympathetic nerve and renin angiotensin aldosterone system, mediates.Antihypertensive drug is categorized as by its mechanism of action: sympatholytic thing, vasodilation medicine, the medicine (benazepril, enalapril, Losartan Potassium) that acts on renin-angiotensin system, calcium-ion channel antagonists, diuretic (hydrochlorothiazide) etc.
At present, the antihypertensive drug of selling on domestic market be take rapid release product as main, more common product has Benazepril hydrochloride contents in tablets, enalapril maleate sheet, cilnidipine sheet, losastan potassium/hydrochlorothiazide tablets etc., in addition, also have some slow release product listings, as felodipine sustained-release tablets, isosorbide mononitrate sustained release tablets, Captopril Sustained-rdease Tablets etc.
Because hypertension drug has certain feature of taking medicine, as generally needed long-term taking, need to maintain a constant blood drug level, but the initial stage of taking medicine needs again to discharge to reach the fastest therapeutic effect fast, common quick release product on domestic market can quick acting, but because general drug half-life is shorter, cannot maintain in the long period blood drug level of effective therapeutic effect, and although common slow releasing preparation can maintain effective blood drug level, comparatively slow in the onset of administration initial activity composition.
Occurred in the market utilizing that prepared by bi-layer tablet press has different curative effects or have quick-acting and double-deck combination drug long-acting concurrently, as CN 200910012373 discloses a kind of oral sustained release hypotensive composition, but the method providing according to this invention, the immediate release section of the double-layer tablet preparing is the highest stripping only 27.6% in 10 minutes, and immediate release section accounts for 25% left and right of whole compound preparation, illustrate that the stripping in 10 minutes of whole compound preparation, less than 10%, cannot play the effect of quick acting; And slow-released part stripping after 12 hours increases, illustrate that this compound preparation acted on after 12 hours on a declining curve.
Summary of the invention
It is slower that technical problem to be solved by this invention is to have overcome in prior art resisting hypertension compound medicine onset speed, and the shortcoming that drug release timeliness is shorter, provides a kind of antihypertensive drug preparation and preparation method thereof.By the composition and engineering of immediate release section and slow-released part is improved, a kind of antihypertensive drug preparation is provided, can take into account onset speed, maintain longer resisting hypertension effect simultaneously.Preparation method simple process of the present invention, the dosage of prepared antihypertensive drug preparation is for once a day, without frequent drug administration, can improve patient's compliance, simultaneously during whole medication, the blood drug level that can remain valid is in the minimum therapeutic domain that fluctuates, and stable blood drug level can reduce untoward reaction to greatest extent, improves curative effect.
The present invention solves the problems of the technologies described above by the following technical programs.
The invention provides a kind of antihypertensive drug preparation, it comprises an immediate release section and a slow-released part; Wherein, the mass ratio of described immediate release section and described slow-released part is 1:1～1:4; The raw material of described immediate release section comprises active components A, water-soluble diluent, disintegrating agent, dry adhesives and lubricant; The raw material of described slow-released part comprises active component B, sustained-release matrix material, diluent, binding agent and lubricant; Described active components A and described active component B are same ingredient, and described ingredient is benazepril hydrochloride, enalapril maleate, cilnidipine or isosorbide mononitrate; The mass ratio of described active components A and described active component B is 1:1～1:6; The mass content that described active components A accounts for described immediate release section is 2.5%～6.25%; The mass content that described active component B accounts for described slow-released part is 4%～6.25%.
The mass ratio of described immediate release section and described slow-released part is preferably 1:2～1:3.
The mass ratio of described active components A and described active component B is preferably 1:2～1:4.
In described immediate release section, described water-soluble diluent is the conventional water-soluble diluent using in this area, is preferably one or more in lactose, mannitol and erythrose; The mass content of described water-soluble diluent is preferably and accounts for 50%～62.5% of described immediate release section.
In described immediate release section, described disintegrating agent is the conventional disintegrating agent using in this area, is preferably polyvinylpolypyrrolidone and/or cross-linking sodium carboxymethyl cellulose; The mass content of described disintegrating agent is preferably and accounts for 10%～18.75% of described immediate release section.
In described immediate release section, described dry adhesives is the conventional dry adhesives using in this area, is preferably microcrystalline Cellulose; The mass content of described dry adhesives is preferably and accounts for 18%～25% of described immediate release section.
In described immediate release section, described lubricant is the conventional lubricant using in this area, is preferably magnesium stearate; The mass content of described lubricant is preferably and accounts for 1.15%～5% of described immediate release section.
In described slow-released part, described sustained-release matrix material is the conventional sustained-release matrix material using in this area, is preferably one or more in hypromellose, sodium alginate and carbomer; Described hypromellose is preferably hypromellose K15 and/or hypromellose K100; The mass content of described sustained-release matrix material is preferably and accounts for 46%～55% of described slow-released part.
In described slow-released part, described diluent is the conventional diluent using in this area, is preferably a kind of in microcrystalline Cellulose and pregelatinized Starch; The mass content of described diluent is preferably and accounts for 20%～42% of described slow-released part.
In described slow-released part, described binding agent is the conventional binding agent using in this area, is preferably polyvidone and/or hypromellose, more preferably polyvidone or hypromellose; The mass content of described binding agent is preferably and accounts for 1%～4% of described slow-released part.
In described slow-released part, described lubricant is the conventional lubricant using in this area, is preferably one or more in silicon dioxide, magnesium stearate and Pulvis Talci; The mass content of described lubricant is preferably and accounts for 2.5%～17.5% of described slow-released part.
The present invention also provides a kind of preparation method of described antihypertensive drug preparation, and it comprises the following steps:
(1) prepare respectively rapid release material and slow release material, wherein, described rapid release material is prepared as follows: after the raw material of described immediate release section is mixed, granulate, obtain; Described slow release material is prepared as follows: by described active component B, described sustained-release matrix material and described mixing diluents, carry out wet granulation, then wet granular and described binding agent are sheared, after drying, add described lubricant, obtain;
(2) prepared rapid release material and slow release material are carried out to tabletting, form a pair of synusia being formed by an immediate release section and a slow-released part.
In the preparation of described rapid release material, described mixing preferably for to carry out in V-Mixer, and the frequency of described mixing is preferably 10Hz～20Hz, and incorporation time is preferably 20min～40min.The method of described granulation and condition are method and the condition of this area routine, are generally wet granulation or dry granulation.
In the preparation of described slow release material, described mixing preferably for to carry out in wet mixing pelletizer, and described speed of agitator is preferably 1350rpm～1650rpm, and described incorporation time is preferably 1～2 minute.The rotating speed of described shearing is preferably 2700rpm～3300rpm; The time of described shearing is preferably 1～2min; The described dry dry 4～6h at 50～60 ℃ that is preferably.The method of described wet granulation and condition are method and the condition of this area routine.
In step (2), described tabletting preferably adopts bi-layer tablet press to carry out.By this area general knowledge, described immediate release section is formed by described rapid release material, and described slow-released part is formed by described slow release material.
Meeting on the basis of this area general knowledge, above-mentioned each optimum condition, can combination in any, obtains the preferred embodiments of the invention.
Agents useful for same of the present invention and raw material be commercially available obtaining all.
Positive progressive effect of the present invention is:
Adopt method of the present invention to prepare the simple process of hypertension drug preparation, the dosage of the active component of prepared antihypertensive drug preparation is for once a day, without frequent drug administration, also can improve patient's compliance, in administration 10 minutes, the releasing ratio of active component is 30～50%, the sustainable release of remaining active component is more than 16 hours, and the blood drug level that can at least remain valid in 16 hours, therefore during whole medication, the blood drug level that can remain valid is in the minimum therapeutic domain that fluctuates, stable blood drug level can reduce untoward reaction to greatest extent, improve curative effect.
The specific embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, according to conventional method and condition, or selects according to catalogue.
Embodiment 1 enalapril maleate sheet
Immediate release section:
| Enalapril maleate | 5mg |
| Lactose | 60mg |
| Polyvinylpolypyrrolidone | 12mg |
| Microcrystalline Cellulose | 18mg |
| Magnesium stearate | 5mg |
Slow-released part:
| Enalapril maleate | 10mg |
| Hypromellose K100 | 75mg |
| Hypromellose K15 | 35mg |
| Microcrystalline Cellulose | 40mg |
| 10% polyvidone ethanol | 70mg |
| Silicon dioxide | 30mg |
| Magnesium stearate | 5mg |
Preparation process is as follows:
Immediate release section: in V-Mixer, setting hybrid frequency is 10Hz by enalapril maleate, lactose, polyvinylpolypyrrolidone, microcrystalline Cellulose and magnesium stearate, mixes 20 minutes, obtains granule 1;
Slow-released part: it is 1350rpm that enalapril maleate, hypromellose K100, hypromellose K15, microcrystalline Cellulose are set to mixing rotating speed in wet mixing pelletizer, be dry mixed 2 minutes, add 10% polyvidone ethanol, setting and shearing rotating speed is 3000rpm, open and shear 1 minute, wet granular in 50 ℃ dry 6 hours, dry granule adds silicon dioxide and magnesium stearate mix homogeneously after 16 order granulate, obtains granule 2;
Granule 1 and granule 2 are used to bi-layer tablet press tabletting, obtain.
Embodiment 2 cilnidipine sheets
Immediate release section:
| Cilnidipine | 2mg |
| Mannitol | 50mg |
| Cross-linking sodium carboxymethyl cellulose | 8mg |
| Microcrystalline Cellulose | 19mg |
| Magnesium stearate | 1mg |
Slow-released part:
| Cilnidipine | 8mg |
| Hypromellose K100 | 42mg |
| Carbomer | 50mg |
| Pregelatinized Starch | 75mg |
| 2% hypromellose liquid | 100mg |
| Magnesium stearate | 5mg |
Preparation process is as follows:
Immediate release section: in V-Mixer, setting hybrid frequency is 15Hz by cilnidipine, mannitol, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose and magnesium stearate, mixes 30 minutes, obtains granule 1;
Slow-released part: it is 1350rpm that cilnidipine, hypromellose K100, carbomer, pregelatinized Starch are set to mixing rotating speed in wet mixing pelletizer, be dry mixed, 1 minute, add 2% hypromellose liquid, setting and shearing rotating speed is 2700rpm, opens and shears 1 minute, and wet granular is dried 4 hours in 55 ℃, dry granule adds magnesium stearate mix homogeneously after 16 order granulate, obtains granule 2;
Granule 1 and granule 2 are used to bi-layer tablet press tabletting, obtain.
Embodiment 3 isosorbide mononitrate sheets
Immediate release section:
| Isosorbide mononitrate | 5mg |
| Red tinea sugar alcohol | 40mg |
| Cross-linking sodium carboxymethyl cellulose | 13mg |
| Microcrystalline Cellulose | 20mg |
| Magnesium stearate | 2mg |
Slow-released part:
| Isosorbide mononitrate | 15mg |
| Sodium alginate | 128mg |
| Pregelatinized Starch | 80mg |
| 10% polyvidone 95% ethanol | 100mg |
| Magnesium stearate | 5mg |
| Pulvis Talci | 2mg |
Preparation process is as follows:
Immediate release section: in V-Mixer, setting hybrid frequency is 10Hz by isosorbide mononitrate, red tinea sugar alcohol, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose and magnesium stearate, mixes 20 minutes, obtains granule 1;
Slow-released part: isosorbide mononitrate, sodium alginate, pregelatinized Starch being set in wet mixing pelletizer to mixing rotating speed is 1500rpm, be dry mixed 2 minutes, add 10% polyvidone 95% ethanol, setting and shearing rotating speed is 3000rpm, open and shear 2 minutes, wet granular in 50 ℃ dry 5 hours, dry granule adds magnesium stearate and Pulvis Talci mix homogeneously after 16 order granulate, obtains granule 2;
Granule 1 and granule 2 are used to bi-layer tablet press tabletting, obtain.
Embodiment 4 Benazepril hydrochloride contents in tablets
Immediate release section:
| Benazepril hydrochloride | 5mg |
| Mannitol | 40mg |
| Cross-linking sodium carboxymethyl cellulose | 15mg |
| Microcrystalline Cellulose | 18mg |
| Magnesium stearate | 2mg |
Slow-released part:
| Benazepril hydrochloride | 15mg |
| Hypromellose K15 | 130mg |
| Pregelatinized Starch | 82mg |
| 10% povidone solution | 100mg |
| Magnesium stearate | 2mg |
| Pulvis Talci | 5mg |
Preparation process is as follows:
Immediate release section: in V-Mixer, setting hybrid frequency is 20Hz by benazepril hydrochloride, mannitol, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose and magnesium stearate, mixes 40 minutes, obtains granule 1;
Slow-released part: by benazepril hydrochloride, hypromellose K15, pregelatinized Starch in wet mixing pelletizer, setting mixing rotating speed is 1650rpm, be dry mixed 1.5 minutes, add 10% povidone solution, setting and shearing rotating speed is 3300rpm, opens and shears 1.5 minutes, and wet granular is dried 5 hours in 60 ℃, dry granule adds magnesium stearate and Pulvis Talci mix homogeneously after 16 order granulate, obtains granule 2;
Granule 1 and granule 2 are used to bi-layer tablet press tabletting, obtain.
Comparative example's 1 enalapril maleate sheet
In 200910234299.6 1 kinds of enalapril maleate sheets of Chinese patent and preparation method thereof, the embodiment 1 of Instructions Page 3 prepares enalapril maleate sheet.
Comparative example's 2 Sinetipin capsules
According in Chinese patent 200910117272.9 Sinetipin capsules and preparation method thereof and quality determining method, the embodiment 1 of Instructions Page 3 prepares Sinetipin capsule.
Comparative example's 3 isosorbide mononitrate sustained release tabletses
In 201210169963.5 1 kinds of isosorbide mononitrate sustained release tabletses of Chinese patent and preparation method thereof, the embodiment 1 of description page 5 prepares isosorbide mononitrate sustained release tablets.
Comparative example 4
This test example 4 relates to by the prepared oral sustained release hypotensive medicine preparation of the disclosed embodiment 1 of CN 200910012373 release conditions in vitro.
Investigation project and the method for inspection are as follows:
Dissolution: with reference to 2010 editions two of Chinese Pharmacopoeias, take 0.1N hydrochloric acid as release medium, rotating speed is per minute 100 to turn, after 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, get solution appropriate, filter, get subsequent filtrate as need testing solution.Adopt the test release of enalapril maleate and all labetalols of HPLC method, calculate the meansigma methods of 6.Concrete data are as shown in the table:
As can be seen from the above table, the oral sustained release hypotensive medicine of preparing with reference to the CN 200910012373 disclosed embodiments 1 in vivo dissolution after 12 hours no longer increases substantially, and dissolution absolute value is only in 90% left and right.
Effect embodiment 1
This test example 1 relates to by embodiments of the invention 1 and the prepared enalapril maleate sheet of comparative example 1 release conditions in vitro.
Sample source
Sample is the product that embodiment 1 and comparative example 1 obtain.
Assay
Investigation project and the method for inspection are as follows:
Dissolution: with reference to 2010 editions two of Chinese Pharmacopoeias, take water 500ml as dissolution medium, rotating speed is per minute 100 to turn, after 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, get solution appropriate, filter, get subsequent filtrate as need testing solution.Adopt HPLC method to test, calculate the meansigma methods of 6.The stripping curve of comparing embodiment sample and comparative example's sample, concrete data are as shown in the table:
As can be seen from the above table, with reference to the prepared enalapril maleate sheet of the embodiment of the present invention state in a kind of slow stripping all the time in vitro, the enalapril maleate sheet that explanation prepares according to the present invention is more lasting action time with respect to common enalapril maleate sheet, can reduce patient's medicining times.
Effect embodiment 2
This test example 2 relates to by embodiments of the invention 2 and the prepared cilnidipine preparation of comparative example 2 release conditions in vitro.
One, sample source
Sample is the product that embodiment 2 and comparative example 2 obtain.
Two, assay
Investigation project and the method for inspection are as follows:
Dissolution: with reference to 2010 editions two of Chinese Pharmacopoeias, the 0.4% sodium dodecyl sulfate solution 900ml of take is dissolution medium, rotating speed is per minute 75 to turn, after 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, get solution appropriate, filter, get subsequent filtrate as need testing solution.Adopt ultraviolet spectrophotometer method to test, calculate the meansigma methods of 6.The stripping curve of comparing embodiment sample and comparative example's sample, concrete data are as shown in the table:
As can be seen from the above table, with reference to the prepared cilnidipine sheet of the embodiment of the present invention state in a kind of slow stripping all the time in vitro, and final absolute dissolution value will be higher than comparative example 2 dissolution, the cilnidipine sheet that explanation prepares according to the present invention is more lasting action time with respect to common cilnidipine sheet, patient's medicining times can be reduced, and better curative effect can be reached.
Effect embodiment 3
This test example 3 relates to by embodiments of the invention 3 and the prepared isosorbide mononitrate preparation of comparative example 3 release conditions in vitro.
One, sample source
Sample is the product that embodiment 3 and comparative example 3 obtain.
Two, assay
Investigation project and the method for inspection are as follows:
Dissolution: with reference to 2010 editions two of Chinese Pharmacopoeias, take water 500ml as release medium, rotating speed is per minute 50 to turn, after 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, get solution appropriate, filter, get subsequent filtrate as need testing solution.Adopt HPLC method to test, calculate the meansigma methods of 6.The stripping curve of comparing embodiment sample and comparative example's sample, concrete data are as shown in the table:
As can be seen from the above table, with reference to the prepared isosorbide mononitrate sheet of the embodiment of the present invention in vivo the dissolution in 1 hour to obviously be better than contrast and implement 3 dissolution, and final absolute dissolution value will be higher than comparative example 3 dissolution, the isosorbide mononitrate sheet that explanation prepares according to the present invention is faster with respect to common isosorbide mononitrate sustained release tablets onset time, and the curative effect finally reaching is better.
Claims (10)
1. an antihypertensive drug preparation, is characterized in that, comprises an immediate release section and a slow-released part; Wherein, the mass ratio of described immediate release section and described slow-released part is 1:1～1:4; The raw material of described immediate release section comprises active components A, water-soluble diluent, disintegrating agent, dry adhesives and lubricant; The raw material of described slow-released part comprises active component B, sustained-release matrix material, diluent, binding agent and lubricant; Described active components A and described active component B are same ingredient, and described ingredient is benazepril hydrochloride, enalapril maleate, cilnidipine or isosorbide mononitrate; The mass ratio of described active components A and described active component B is 1:1～1:6; The mass content that described active components A accounts for described immediate release section is 2.5%～6.25%; The mass content that described active component B accounts for described slow-released part is 4%～6.25%.
2. antihypertensive drug preparation according to claim 1, is characterized in that, the mass ratio of described immediate release section and described slow-released part is 1:2～1:3; And/or the mass ratio of described active components A and described active component B is 1:2～1:4.
3. antihypertensive drug preparation according to claim 1, is characterized in that, in described immediate release section, described water-soluble diluent is one or more in lactose, mannitol and erythrose; The mass content of described water-soluble diluent is to account for 50%～62.5% of described immediate release section;
And/or described disintegrating agent is polyvinylpolypyrrolidone and/or cross-linking sodium carboxymethyl cellulose; The mass content of described disintegrating agent is to account for 10%～18.75% of described immediate release section.
4. antihypertensive drug preparation according to claim 1, is characterized in that, in described immediate release section, described dry adhesives is microcrystalline Cellulose; The mass content of described dry adhesives is to account for 18%～25% of described immediate release section;
And/or described lubricant is magnesium stearate; The mass content of described lubricant is to account for 1.15%～5% of described immediate release section.
5. antihypertensive drug preparation according to claim 1, is characterized in that, in described slow-released part, described sustained-release matrix material is one or more in hypromellose, sodium alginate and carbomer; The mass content of described sustained-release matrix material is to account for 46%～55% of described slow-released part;
And/or in described slow-released part, described diluent is a kind of in microcrystalline Cellulose and pregelatinized Starch; The mass content of described diluent is to account for 20%～42% of described slow-released part;
And/or in described slow-released part, described binding agent is polyvidone and/or hypromellose; The mass content of described binding agent is to account for 1%～4% of described slow-released part.
6. antihypertensive drug preparation according to claim 5, is characterized in that, described hypromellose is hypromellose K15 and/or hypromellose K100;
And/or described binding agent is polyvidone or hypromellose.
7. antihypertensive drug preparation according to claim 1, is characterized in that, in described slow-released part, described lubricant is one or more in silicon dioxide, magnesium stearate and Pulvis Talci; The mass content of described lubricant is to account for 2.5%～17.5% of described slow-released part.
8. a preparation method for the antihypertensive drug preparation as described in claim 1～7 any one, is characterized in that, it comprises the following steps:
(1) prepare respectively rapid release material and slow release material, wherein, described rapid release material is prepared as follows: after the raw material of described immediate release section is mixed, granulate, obtain; Described slow release material is prepared as follows: by described active component B, described sustained-release matrix material and described mixing diluents, carry out wet granulation, then wet granular and described binding agent are sheared, after drying, add described lubricant, obtain;
(2) prepared rapid release material and slow release material are carried out to tabletting, form a pair of synusia being formed by an immediate release section and a slow-released part.
9. preparation method according to claim 8, is characterized in that, in the preparation of described rapid release material, described in be blended in V-Mixer and carry out, the frequency of described mixing is 10Hz～20Hz, incorporation time is 20min～40min; Described granulation is wet granulation or dry granulation.
10. preparation method according to claim 8, is characterized in that, in the preparation of described slow release material, described in be blended in wet mixing pelletizer and carry out, described speed of agitator is 1350rpm～1650rpm, described incorporation time is 1～2 minute; The rotating speed of described shearing is 2700rpm～3300rpm; The time of described shearing is 1～2min; Described being dried as dry 4～6h at 50～60 ℃; Described tabletting adopts bi-layer tablet press to carry out.
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