CN100469356C - Slowly released tablet of compound atenolol, and preparation method - Google Patents
Slowly released tablet of compound atenolol, and preparation method Download PDFInfo
- Publication number
- CN100469356C CN100469356C CNB2006100688587A CN200610068858A CN100469356C CN 100469356 C CN100469356 C CN 100469356C CN B2006100688587 A CNB2006100688587 A CN B2006100688587A CN 200610068858 A CN200610068858 A CN 200610068858A CN 100469356 C CN100469356 C CN 100469356C
- Authority
- CN
- China
- Prior art keywords
- atenolol
- nifedipine
- slow
- release
- granules
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
A slow-release tablet of compound atenolol is prepared through preparing fast-release particle from atenolol and less nifedipine, preparing its slow-release layer from hydrophilic gel PEG6000, rest of nifedipine and slow-release material, and die pressing.
Description
Technical field
The present invention relates to a kind of slow releasing tablet and preparation method thereof, relate in particular to a kind of slowly released tablet of compound atenolol and preparation method thereof, belong to medical technical field.
Background technology
Hypertension is a kind of common chronic disease, also is the main hazard factor of cardiovascular and cerebrovascular disease simultaneously.In recent years, along with the fast development of medical technology, depressor kind and kind also are on the increase, antihypertensive effect also obviously improves, wherein, beta-receptor blocade and calcium antagonists (CCB) are all classified the blood pressure lowering one line medicine of WHO/ISH suggestion as, and clinical efficacy is all more satisfactory.
Atenolol and nifedipine are clinical antihypertensive drug commonly used.
Atenolol is β
1Receptor blocking agent, oral administration are used for the treatment of the hypertension of various degree, and the hypotensive effect persistent period is longer, and compare safety, and main adverse reaction is to occur the bradycardia acra after the individual patient medication sometimes to feel cold feeling of fatigue etc.; Nifedipine is calcium antagonists (CCB), the oral treatment that is used for slight, moderate, serious hypertension and hypertensive crisis, be particularly useful for the hypertensive patients patients with coronary heart disease, particularly angina pectoris due to variant angina pectoris and the coronary vasospasm, promptly produce hypotensive effect behind the oral administration in the 20min, hypotensive effect is fast but acting duration is shorter, and main adverse reaction is side reactions such as the common flush of first clothes person, cardiopalmus, sinus tachycardia.At present, adopt during clinical treatment hypertension more, because two kinds of medicine blood pressure lowering mechanism are different, can produce collaborative pressure reduction effect during use in conjunction, thereby reduce dosage separately on the one hand, reduce related reactions atenolol and nifedipine drug combination; During two kinds of medication combined application, the two is cancelled out each other to the harmful effect of heart rate on the other hand, some adverse reaction rate significantly reduced than single time spent, and after the two medicine couplings to no obvious harmful effects such as patient's blood glucose, blood fat.
Yet, reach in the market in the clinical practice, how based on atenolol or nifedipine unitary agent, this makes that their use is loaded down with trivial details relatively and inconvenient.Also have producer that above-mentioned two kinds of compositions are made a compound preparation, as compound atenolol capsule and tablet that AstraZeneca company develops, commodity are called TENIF, and specification is: every capsules (or tablet) contains atenolol 50mg, nifedipine 20mg.But existing compound preparation is normal release formulation, takes twice in most one day, though single have many facilities with atenolol or nifedipine, still has to miss and the more high deficiency of cost.Application number is 03123923.4 Chinese patent, announced a kind of compound atenolol Nifedipine sustained-release preparation that existing atenolol, nifedipine folk prescription slow releasing preparation are made, in the hope of realizing its common slow release effect, reach the purpose that prolongs medication period, but, because atenolol is different with nifedipine half-life characteristics, though it has considered slow release, but be difficult to make the corrosion, diffusion, release of nifedipine and atenolol and drug effect synchronous coordination in vivo, bioavailability is not very high, and untoward reaction happens occasionally.
Summary of the invention
At the deficiencies in the prior art, the problem to be solved in the present invention provides a kind of slowly released tablet of compound atenolol and preparation method thereof, it is fast that more existing slow releasing tablet of this slow releasing tablet or capsule have the atenolol dissolution rate, and the nifedipine corrosion in hydrophilic gel, diffusion, discharge characteristics slowly, really realized making atenolol and the nifedipine purpose of drug effect synchronous coordination in vivo.
Slowly released tablet of compound atenolol of the present invention is by as the immediate-release granules A of release layer and the double-layer tablet that is pressed into as slow release layer slow-releasing granules B; It is characterized in that immediate-release granules A and slow-releasing granules B are made up of the main ingredient of following weight proportion in the described slowly released tablet of compound atenolol:
1000 of slowly released tablet of compound atenolol unit's prescriptions, specification is atenolol 50mg, nifedipine 20mg/ sheet, wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 3-24g
Pulvis Talci 0.5%～2.0%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose (K
15M) 15～140g
Pulvis Talci 0.5%～2.0%
5% PVPk
3080% alcoholic solution an amount of.
Immediate-release granules A and slow-releasing granules B preferably are made up of the main ingredient of following weight proportion in the above-mentioned slowly released tablet of compound atenolol:
1000 of slowly released tablet of compound atenolol unit's prescriptions, specification is atenolol 50mg, nifedipine 20mg/ sheet, wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 10g
Pulvis Talci 1.0%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose (K
15M) 70g
Pulvis Talci 1.0%
5% PVPk
3080% alcoholic solution an amount of.
The preparation method of above-mentioned slowly released tablet of compound atenolol, be to be mixed and made into immediate-release granules A with atenolol and a small amount of nifedipine, as release layer, be mixed and made into slow-releasing granules B with slow-release material again after with hydrophilic gel matrix material PEG6000 the surplus nifedipine being made solid dispersion, as slow release layer; Be pressed into double-layer tablet with conventional method; It is characterized in that the preparation process of described immediate-release granules A is: under the lucifuge condition, with the atenolol and the nifedipine pulverize separately of recipe quantity, cross 100 mesh sieves, with the lactose mixing of nifedipine and recipe quantity, add the abundant mixing of atenolol again, PVPk then with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 45 ℃～55 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule A; The preparation process of described slow-releasing granules B is: under the lucifuge condition, PEG6000 in 80 ℃ of fusions, is added the nifedipine of recipe quantity, vigorous stirring is to even, become solid with the frozen water quenching then, solid was placed 2 hours in 0～4 ℃ of refrigerator, promptly get solid dispersion; Described solid dispersion is pulverized, crossed 80 mesh sieves, the hypromellose of recipe quantity is pulverized, cross 100 mesh sieves, make its abundant mixing then, PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 45 ℃～55 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule B.
In the slowly released tablet of compound atenolol prescription of the present invention, principal agent is atenolol and nifedipine; PEG6000 is the pharmaceutic adjuvant of the preparation insoluble medicine solid dispersoid used always, is water-solubility carrier, and nifedipine and the PEG6000 that is insoluble in water made solid dispersion, helps increasing the release of nifedipine, improves its bioavailability; Hypromellose (HPMC) is a hydrophilic macromolecule framework material commonly used in the slow releasing tablet, physicochemical property is stable, can form gel after meeting water, the release of medicine is carried out simultaneously with diffusion and two kinds of mechanism of corrosion, can realize adjustment release speed by the usage ratio of adjusting HPMC and the specification of HPMC, be K through testing the specification of determining HPMC of the present invention
15M, consumption is seen prescription; 5% PVPk
3080% alcoholic solution be wet adhesive (80% alcoholic solution of 5% polyvinylpyrrolidone, can quicken the stripping of insoluble drug), lactose is a filler, Pulvis Talci is a conventional lubricants, good tack is arranged, can make the tablet good looking appearance of compacting.
The present invention is according to atenolol t
1/2Longer relatively, behind the oral administration hypotensive effect persistent period longer, and the characteristics of safety relatively are made into immediate-release granules; According to nifedipine t
1/2Short, eliminate fast characteristics in the body, be made into slow-releasing granules, to delay drug release rate, realize being absorbed that to enter in the body back blood drug level steady, the purpose that duration of efficacy is long reaches and makes nifedipine and atenolol drug effect synchronous coordination in vivo.
Because nifedipine is insoluble in water, it is very low to make the slow releasing preparation release, to cause absorption difference in the body, therefore outstanding feature of the present invention is: at first select for use hydrophilic gel matrix material PEG6000 that nifedipine is made solid dispersion, improving the dispersion and the dissolubility of nifedipine, and then be mixed and made into slow-releasing granules, realize both having improved the release of nifedipine with the hydrogel matrix slow-release material, reach the slow release purpose again, with the bioavailability of effective raising nifedipine.
And application number is the preparation of the compound atenolol Nifedipine sustained-release preparation of 03123923.4 Chinese patent, then adopts directly and slow-release material (hypromellose K100
M, hypromellose K
15M) blended method is prepared into slow-releasing granules, certainly will cause the dispersion of nifedipine and dissolubility low like this, the deficiency that bioavailability is not high.
The present invention makes immediate-release granules with atenolol, nifedipine is made slow-releasing granules, be that one deck is that immediate-release granules, one deck are slow-releasing granules, be pressed into double-layer tablet, specification is atenolol 50mg, nifedipine 20mg/ sheet, is that the specification (atenolol 100mg, nifedipine 30mg/ sheet) of compound atenolol Nifedipine sustained-release preparation of 03123923.4 Chinese patent is more reasonable than application number; Behind the oral administration, the quick stripping of atenolol, then slowly corrosion, diffusion, release from hydrophilic gel of nifedipine has realized making atenolol and the nifedipine therapeutic purposes of drug effect synchronous coordination in vivo.
Slowly released tablet of compound atenolol of the present invention only need be administered once every day, every day, dosage had reduction slightly, but can play consistently out the effect and the effect of the collaborative blood pressure lowering of atenolol and nifedipine two medicines, curative effect is significantly improved, and has significantly reduced untoward reaction.
Slowly released tablet of compound atenolol clinical application of the present invention is simple, convenient, has not only lowered drug cost, has also improved the compliance of patient's medication, has important economic value and social meaning.
Utilize slowly released tablet of compound atenolol of the present invention, in 6 domesticated dog bodies, adopt cross matching at random, liquid chromatograph mass spectrography (LC-MS) method measure single dose and multi-dose oral administration after the time process blood drug level, estimation pharmacokinetic parameter and analyze the pharmacokinetics behavior, and with the atenolol tablet that has gone on the market and Nifedipine sustained-release capsule relatively, investigate the drug release characteristic that is subjected to test preparation.
The result shows: slowly released tablet of compound atenolol of the present invention and reference preparation are the bioequivalent drug products on the degree of absorption, the Tmax of nifedipine in the slowly released tablet of compound atenolol of the present invention (slow release) and reference Nifedipine sustained release tablets does not have significant difference, shows that nifedipine has sustained releasing character in the compound sustained-released tablet of development.
The materials and methods that above-mentioned test is selected for use is as follows:
1. medicine and reagent
1.1 be subjected to test preparation: slowly released tablet of compound atenolol of the present invention (atenolol 50mg, nifedipine 20mg)
1.2 reference preparation: atenolol tablet (Wanma Pharmaceutical Co., Ltd., Zhejiang, specification: 25mg/ sheet, lot number 040604); Nifedipine sustained-release capsule (Zhejiang Tailison Pharmaceutical Co., Ltd., specification: 20mg/ grain, lot number 040202).
1.3 reagent: methanol (chromatographically pure, U.S. TEDIA company); Ammonium acetate (analytical pure, economic and technological development zone, Laiyang, Shandong Fine Chemical Works, lot number 20031209); Chloroform (chromatographically pure, U.S. TEDIA company); Sodium hydroxide (analytical pure, Inst. of Chemical Industry, Jinan City, lot number 030105).
2. instrument
Agilent 1100 Series LC/MSD high performance liquid chromatography/mass spectrographs, Agilent 1100 Series G1313A type automatic samplers; METTLER TOLEDOAX-205 electronic balance (Mettler-Toledo Instrument (Shanghai) Co., Ltd.); LDZ4-0.8 autobalance micro centrifuge (Beijing Medical Centrifugal Machine Factory); XW-80A type vortex mixer (going up Industrial Co., Ltd. of Nereid section); CX-250 ultrasonic cleaner (Beijing armarium two factories).
3. EXPERIMENTAL DESIGN
3.1 the single dose EXPERIMENTAL DESIGN adopts binary cycle two preparations trial design at random, to be tried domesticated dog and be divided into two groups (A group and B groups) at random, after the fasting 12 hours, get blank blood 3.5ml respectively, A group gives developed product compound slow-release tablet a slice, and after administration 0.5,1,1.5,2,3,4,6,8,10,12,24h extracting vein blood 3.5ml respectively; B group gives the reference preparation atenolol tablet 2 (25mg*2) and 1 of Nifedipine sustained-release capsule (20mg), and after administration 0.5,1,1.5,2,3,4,6,8,10,12,24h extracting vein blood 3.5ml.Blood sample is put in the centrifuge tube of heparinization, centrifugal 10 minutes (3500r.min
-1), separated plasma freezes preservation in-20 ℃ of refrigerator and cooled, and is to be measured.The back cross matching of one week.
3.2 the multiple dose EXPERIMENTAL DESIGN is divided into two groups (A group and B groups) at random with 6 healthy domesticated dogs, the A group gives the developed product compound slow-release tablet, each once a day a slice, 8 administrations on an empty stomach in morning every day, continuous 6 days, in the 4th, 5, before 8 administrations in 6 day morning and after the administration in morning in the 6th day 0.5,1,1.5,2,3,4,6,8,10,12,24h extracting vein blood 3.5ml respectively; The B group gives the reference preparation atenolol tablet 2 (25mg*2) and 1 of Nifedipine sustained-release capsule (20mg), once a day, 8 administrations on an empty stomach in morning every day, continuous 6 days, in the 4th, before 8 administrations in 5,6 day morning and after the administration in morning in the 6th day 0.5,1,1.5,2,3,4,6,8,10,12,24h extracting vein blood 3.5ml.Blood sample is put in the centrifuge tube of heparinization, centrifugal 10 minutes (3500r.min
-1), separated plasma freezes preservation in-20 ℃ of refrigerator and cooled, and is to be measured.The back cross matching of one week.
4. plasma sample is handled and is got the 0.5ml plasma sample, mark nimodipine (8 μ g.ml in adding
-1) 50 μ l, add 0.5mol.L
-1Sodium hydroxide solution 100 μ l add chloroform 5.0ml behind the mixing, 3min, 4000r.min are extracted in concussion
-1Centrifugal 5min draws the organic facies 4.0ml of lower floor, and 45 ℃ of water-bath nitrogen dry up, and residue adds the dissolving of 200 μ l mobile phases, and vortex 1min moves into the sample introduction bottle, gets 10 μ l sample introduction analyses.
5. experiment condition
5.1 chromatographic condition Hypersil ODS2 (5 μ m, 250 * 4.6mm) chromatographic columns; Ultraviolet detection wavelength 233nm; Mobile phase is methanol: water=70:30 (V/V), adds 0.005mol.L in the water
-1Ammonium acetate; Through 0.45 μ m filtering with microporous membrane, flow velocity is 0.8mL.min
-130 ℃ of column temperatures; Sample size 10 μ l.
5.2 mass spectrum condition API-ES ion source, positive ion mode, it is [M+H] that atenolol is measured ion
-M/Z=267.0, it is [M+H] that nifedipine is measured ion
-M/Z=347.0, it is [M+H] that interior mark nimodipine is measured ion
-M/Z=419.0, nitrogen drying temperature degree is 350 ℃, flow velocity is 13.0L.min
-1, electron spray pressure is 50psig, capillary voltage 4000V, fragment voltage are 70V.
Description of drawings
Shown in Figure 1: slowly released tablet of compound atenolol preparation technology flow chart.
The specific embodiment
Embodiment 1
Slowly released tablet of compound atenolol unit's prescription (1000, specification is atenolol 50mg, nifedipine 20mg/ sheet), wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 10g
Pulvis Talci 1.0%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose (K
15M) 70g
Pulvis Talci 1.0%
5% PVPk
3080% alcoholic solution an amount of.
The preparation method of above-mentioned slowly released tablet of compound atenolol, be to be mixed and made into immediate-release granules A with atenolol and a small amount of nifedipine, as release layer, be mixed and made into slow-releasing granules B with slow-release material again after with hydrophilic gel matrix material PEG6000 the surplus nifedipine being made solid dispersion, as slow release layer; Be pressed into double-layer tablet with conventional method;
Wherein: the preparation process of described immediate-release granules A is: under the lucifuge condition, with the atenolol and the nifedipine pulverize separately of recipe quantity, cross 100 mesh sieves, then with the lactose mixing of nifedipine and recipe quantity, add the abundant mixing of atenolol again, the PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 50 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule A; The preparation process of described slow-releasing granules B is: under the lucifuge condition, PEG6000 in 80 ℃ of fusions, is added the nifedipine of recipe quantity, vigorous stirring is to even, become solid with the frozen water quenching then, solid was placed 2 hours in 0～2 ℃ of refrigerator, promptly get solid dispersion; Described solid dispersion is pulverized, crossed 80 mesh sieves, the hypromellose of recipe quantity is pulverized, cross 100 mesh sieves, make its abundant mixing then, PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 50 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule B.
Embodiment 2
Slowly released tablet of compound atenolol unit's prescription (1000, specification is atenolol 50mg, nifedipine 20mg/ sheet), wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 3g
Pulvis Talci 0.5%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose (K
15M) 15g
Pulvis Talci 0.5%
5% PVPk
3080% alcoholic solution an amount of.
The preparation method of above-mentioned slowly released tablet of compound atenolol, be to be mixed and made into immediate-release granules A with atenolol and a small amount of nifedipine, as release layer, be mixed and made into slow-releasing granules B with slow-release material again after with hydrophilic gel matrix material PEG6000 the surplus nifedipine being made solid dispersion, as slow release layer; Be pressed into double-layer tablet with conventional method;
Wherein: the preparation process of described immediate-release granules A is: under the lucifuge condition, with the atenolol and the nifedipine pulverize separately of recipe quantity, cross 100 mesh sieves, then with the lactose mixing of nifedipine and recipe quantity, add the abundant mixing of atenolol again, the PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 45 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule A; The preparation process of described slow-releasing granules B is: under the lucifuge condition, PEG6000 in 80 ℃ of fusions, is added the nifedipine of recipe quantity, vigorous stirring is to even, become solid with the frozen water quenching then, solid was placed 2 hours in 0～4 ℃ of refrigerator, promptly get solid dispersion; Described solid dispersion is pulverized, crossed 80 mesh sieves, the hypromellose of recipe quantity is pulverized, cross 100 mesh sieves, make its abundant mixing then, PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 45 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule B.
Embodiment 3
Slowly released tablet of compound atenolol unit's prescription (1000, specification is atenolol 50mg, nifedipine 20mg/ sheet), wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 24g
Pulvis Talci 2.0%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose (K
15M) 140g
Pulvis Talci 2.0%
5% PVPk
3080% alcoholic solution an amount of.
The preparation method of above-mentioned slowly released tablet of compound atenolol, be to be mixed and made into immediate-release granules A with atenolol and a small amount of nifedipine, as release layer, be mixed and made into slow-releasing granules B with slow-release material again after with hydrophilic gel matrix material PEG6000 the surplus nifedipine being made solid dispersion, as slow release layer; Be pressed into double-layer tablet with conventional method;
Wherein: the preparation process of described immediate-release granules A is: under the lucifuge condition, with the atenolol and the nifedipine pulverize separately of recipe quantity, cross 100 mesh sieves, then with the lactose mixing of nifedipine and recipe quantity, add the abundant mixing of atenolol again, the PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 55 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule A; The preparation process of described slow-releasing granules B is: under the lucifuge condition, PEG6000 in 80 ℃ of fusions, is added the nifedipine of recipe quantity, vigorous stirring is to even, become solid with the frozen water quenching then, solid was placed 2 hours in 0～4 ℃ of refrigerator, promptly get solid dispersion; Described solid dispersion is pulverized, crossed 80 mesh sieves, the hypromellose of recipe quantity is pulverized, cross 100 mesh sieves, make its abundant mixing then, PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 55 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule B.
Claims (3)
1. slowly released tablet of compound atenolol is by as the immediate-release granules A of release layer and the double-layer tablet that is pressed into as slow release layer slow-releasing granules B; It is characterized in that immediate-release granules A and slow-releasing granules B are made up of the main ingredient of following weight proportion in the described slowly released tablet of compound atenolol:
1000 of slowly released tablet of compound atenolol unit's prescriptions, specification is atenolol 50mg, nifedipine 20mg/ sheet, wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 3-24g
Pulvis Talci 0.5%～2.0%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose K
15M15～140g
Pulvis Talci 0.5%～2.0%
5% PVPk
3080% alcoholic solution an amount of.
2. slowly released tablet of compound atenolol as claimed in claim 1 is characterized in that, immediate-release granules A and slow-releasing granules B are made up of the main ingredient of following weight proportion in the described slowly released tablet of compound atenolol:
1000 of slowly released tablet of compound atenolol unit's prescriptions, specification is atenolol 50mg, nifedipine 20mg/ sheet, wherein:
Immediate-release granules A contains:
Atenolol 50g
Nifedipine 5g
Lactose 10g
Pulvis Talci 1.0%
5% PVPk
3080% alcoholic solution an amount of
Slow-releasing granules B contains:
Nifedipine 15g
PEG6000 60g
Hypromellose K
15M70g
Pulvis Talci 1.0%
5% PVPk
3080% alcoholic solution an amount of.
3. the preparation method of claim 1 or 2 described slowly released tablet of compound atenolol, be to be mixed and made into immediate-release granules A with atenolol and a small amount of nifedipine, as release layer, be mixed and made into slow-releasing granules B with slow-release material again after with hydrophilic gel matrix material PEG6000 the surplus nifedipine being made solid dispersion, as slow release layer; Be pressed into double-layer tablet with conventional method; It is characterized in that the preparation process of described immediate-release granules A is: under the lucifuge condition, with the atenolol and the nifedipine pulverize separately of recipe quantity, cross 100 mesh sieves, with the lactose mixing of nifedipine and recipe quantity, add the abundant mixing of atenolol again, PVPk then with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 45 ℃～55 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule A; The preparation process of described slow-releasing granules B is: under the lucifuge condition, PEG6000 in 80 ℃ of fusions, is added the nifedipine of recipe quantity, vigorous stirring is to even, become solid with the frozen water quenching then, solid was placed 2 hours in 0～4 ℃ of refrigerator, promptly get solid dispersion; Described solid dispersion is pulverized, crossed 80 mesh sieves, the hypromellose of recipe quantity is pulverized, cross 100 mesh sieves, make its abundant mixing then, PVPk with 5%
3080% alcoholic solution be wet adhesive, add in batches and mix, make and be fit to the soft material of granulating, cross 20 mesh sieve system wet granulars, 45 ℃～55 ℃ dry must do granule, crosses 18 mesh sieve granulate, the adding mass percent is 1% Pulvis Talci, makes granule B.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100688587A CN100469356C (en) | 2006-09-08 | 2006-09-08 | Slowly released tablet of compound atenolol, and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100688587A CN100469356C (en) | 2006-09-08 | 2006-09-08 | Slowly released tablet of compound atenolol, and preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1915224A CN1915224A (en) | 2007-02-21 |
| CN100469356C true CN100469356C (en) | 2009-03-18 |
Family
ID=37736384
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100688587A Expired - Fee Related CN100469356C (en) | 2006-09-08 | 2006-09-08 | Slowly released tablet of compound atenolol, and preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100469356C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103845299B (en) * | 2012-12-07 | 2016-06-29 | 亚宝药业集团股份有限公司 | A kind of slow releasing tablet treating cardiovascular disease and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1262627A (en) * | 1997-07-11 | 2000-08-09 | 史密丝克莱恩比彻姆有限公司 | Composition |
| CN1452966A (en) * | 2003-05-20 | 2003-11-05 | 广州贝氏药业有限公司 | Compound Atenolol-Nifedipine slow releasing prepn |
-
2006
- 2006-09-08 CN CNB2006100688587A patent/CN100469356C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1262627A (en) * | 1997-07-11 | 2000-08-09 | 史密丝克莱恩比彻姆有限公司 | Composition |
| CN1452966A (en) * | 2003-05-20 | 2003-11-05 | 广州贝氏药业有限公司 | Compound Atenolol-Nifedipine slow releasing prepn |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1915224A (en) | 2007-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2018241128B2 (en) | Compositions and Methods for Transmucosal Absorption | |
| KR101213345B1 (en) | Composition containing anti-dementia drug | |
| FI114285B (en) | Process for preparing sustained release pharmaceutical dosage unit form | |
| CN103083318A (en) | Bilayer tablet comprising telmisartan and amlodipine | |
| EA014652B1 (en) | Crush-resistant tablets intended to prevent accidental misuse and unlawful diversion | |
| KR101667081B1 (en) | Solid pharmaceutical fixed dose compositions comprising irbesartan and amlodipine, their preparation and their therapeutic application | |
| CN105935358B (en) | One seed sand library is than bent Valsartan sustained release agent and preparation method thereof | |
| CN101229148A (en) | Glonoin Orally disintegrating tablets preparation of and preparing method thereof | |
| CN104173312A (en) | Sustained-release tablet containing felodipine and metoprolol salt and preparation method of sustained-release tablet containing felodipine and metoprolol salt | |
| CN102276516B (en) | Levamlodipine besylate crystals, preparation method thereof and brand-new medicinal composition containing crystals | |
| JP2004531548A (en) | Compression method for the production of sodium phenytoin dosage form | |
| CN103908443A (en) | Propafenone hydrochloride sustained-release capsule and preparation method thereof | |
| CN101721384A (en) | Levamlodipine beaylate tablets and preparation method thereof | |
| CN100469356C (en) | Slowly released tablet of compound atenolol, and preparation method | |
| CN106018618B (en) | Escitalopram oxalate tablet composition and quality control method | |
| TW201138767A (en) | Solid pharmaceutical fixed dose compositions comprising ramipril and amlodipine, and their preparation | |
| CN102552200A (en) | Felodipine sustained-release tablets | |
| CN101288670A (en) | Composition of atorvastatin and L-amlodipine and preparation method thereof | |
| CN102846625A (en) | Stable valsartan, amlodipine and hydrochlorothiazide pharmaceutical composition and preparation method thereof | |
| Qiu et al. | Design of sustained-release matrix systems for a highly water-soluble compound, ABT-089 | |
| CN102824644B (en) | High-stability sustained-release tablet prepared by using hydroxy propyl cellulose | |
| CN101023951A (en) | Slow-released preparation containing hydrochlorothiazide and clonidine hydrochloride and its preparing method | |
| JP2000119190A (en) | Tablet containing chinese orthodox medicine and capsule filled with chinese orthodox medicine and tablet containing crude drug and capsule filled with crude drug, production of tablet containing chinese orthodox medicine, production of capsule filled with chinese orthodox medicine, production of tablet containing crude drug and production of capsule filled with crude drug mature | |
| CN101849940B (en) | Medicinal composition for treating hypertension | |
| CN111603449A (en) | Levamlodipine besylate tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 277513 No. 3288 Yikang Road, Shandong, Tengzhou Patentee after: SHANDONG YIKANG PHARMACEUTICAL CO., LTD. Address before: 277513 No. 3288 Yikang Road, Shandong, Tengzhou Patentee before: Shandong Yikang Pharmaceutical Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090318 Termination date: 20160908 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |