CN1191831C - Compound Atenolol-Nifedipine slow releasing prepn - Google Patents
Compound Atenolol-Nifedipine slow releasing prepn Download PDFInfo
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- CN1191831C CN1191831C CNB031239234A CN03123923A CN1191831C CN 1191831 C CN1191831 C CN 1191831C CN B031239234 A CNB031239234 A CN B031239234A CN 03123923 A CN03123923 A CN 03123923A CN 1191831 C CN1191831 C CN 1191831C
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- atenolol
- nifedipine
- preparation
- slow
- hpmc
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Abstract
The present invention relates to a compound Atenolol-Nifedipine slow releasing preparation and application of the compound slow releasing preparation in medical treatment. The compound slow releasing preparation adopts Atenolol and Nifedipine as medicine active ingredients. Ingredients which have the slow releasing function are slow releasing material. The preparation can also contain medicine acceptable carriers.
Description
Technical field:
The present invention relates to the compound slow release preparation that a kind of compound medicine slow releasing preparation, particularly atenolol and nifedipine are formed, and the application of this compound slow release preparation in medical treatment.
Background technology:
Atenolol is the beta receptor antagonist, works by suppressing beta receptor, and it is to the β of heart
1Receptor has tangible retardation, but to bronchus and vascular smooth muscle β
2The retardation of receptor is very little.At cardiovascular field, be mainly used in treatment hypertension and coronary heart disease at present, also be used for the arrhythmia that sympathetic activation or catecholamine increase cause.
Nifedipine, be a kind of flow of calcium ions blocker or slow channel blocking agent, the retardance calcium ion passes through the passage of cardiac muscle or smooth muscle cell face and enters in the cell, cause whole body blood vessel thus, comprise that antiotasis coronarius lowers and expands, thereby can bring high blood pressure down, increase the coronary blood confession, and can suppress spontaneous or the caused coronary vasospasm of ergometrine.Can suppress myocardial contraction on the other hand, myocardium work done is lowered, oxygen consumption reduces, allevating angina pectoris.
At present clinical how single with atenolol or nifedipine, on the market based on atenolol or nifedipine unitary agent.Consider that two kinds of medicines are having certain synergism aspect the treatment cardiovascular, a compound preparation is made with above-mentioned two kinds of compositions by external at present existing many producers, as far back as 1993, ICI-PHARMA company has just developed the atenolol-nifedipine tablet of compound recipe, and, some dosage forms appearance such as capsule are arranged successively again later in Italy's listing.This compound preparation has been described among the U.S. Pat P4808413.This compound preparation of external listing is normal release formulation at present, takes twice on 1st, though single have many facilities with atenolol or nifedipine, still has to miss and the more high inconvenience of cost.
In view of existing atenolol, each folk prescription slow releasing preparation of nifedipine in the market, the normal release formulation of its clinical effectiveness has better therapeutic, therefore, the present invention is on the basis of existing preparation, proposition makes two kinds of mutual synergism of composition, form the slow releasing preparation of compound recipe, realize slow release effect jointly.
Summary of the invention:
The invention provides a kind of pharmaceutical preparation of slow release, said preparation, adds slow-release material and medicine acceptable carrier and makes as active constituents of medicine with atenolol and nifedipine.
Slow releasing preparation of the present invention can pass through oral administration.
Slow releasing preparation of the present invention can be made the oral dosage form of various confessions by the formulation preparation technology of the best, and these peroral dosage forms can comprise: tablet, capsule, granule, liposome, pill etc.
Slow releasing preparation of the present invention is tablet and capsule preferably.
The slow-release material that slow releasing preparation of the present invention is selected can be any material that can play slow releasing function.These slow-release materials can be, cellulose family, and pyrrolidinone compounds, polyalcohols, Sargassum acids, stearic acid can be selected their one or more mixing in use.
Slow releasing preparation of the present invention with atenolol and nifedipine as active constituents of medicine, their content can be the 1-99% of total formulation weight amount, other compositions are slow-release material and medicine acceptable auxiliary, and the content of these slow-release materials and medicine acceptable auxiliary can be the 1-99% of total formulation weight amount.
For each agent medicament, as each sheet or each capsules, the effective dose of its active constituents of medicine can be 10-1000mg, wherein, atenolol can be 5-700mg, nifedipine can be 5-300mg, preferably atenolol can be 20-400mg, nifedipine can be 10-100mg, and more preferably atenolol can be 50-200mg, and nifedipine can be 15-60mg, the dosage that particularly preferably is atenolol is 12.5-150mg, the dosage of nifedipine is 5-50mg, and most preferably the dosage of atenolol is 100mg, and the dosage of nifedipine is 30mg.
The present invention also comprises the preparation method of compound slow release preparation, comprises nifedipine, atenolol are mixed with slow-release material.
The preparation method of compound slow release preparation of the present invention also comprises nifedipine, atenolol is mixed with slow-release material and medicine acceptable carrier.
Slow releasing tablet of the present invention can prepare by the following method:
Atenolol, nifedipine are mixed with the pharmaceutical purpose composition respectively, thereby obtain preferred the processing and processing characteristics, operable medicinal ingredient comprises binding agent, filler, lubricant, disintegrating agent and other pharmaceutically acceptable auxiliaries.
Preferably with atenolol, nifedipine respectively with mix homogeneously such as one or more slow-release materials, filler, disintegrating agent, add a certain amount of binder solution respectively, wet granulation, with the granule oven dry of gained separately to a certain degree, add lubricant, wherein a kind of granule (nifedipine or atenolol) is pressed into the tablet of certain specification and size, more another kind of granule is mixed with above-mentioned slow releasing tablet of pressing, and is pressed into double-layer sustained release tablets.
Slow-release material can use one or more following polymers, but is not limited to following substances: hydroxypropyl methylcellulose (K
4M, K
10M), sodium alginate, chitosan, polyvinyl alcohol, stearic acid, glyceryl monostearate, Brazil wax, ethyl cellulose, polymethyl methacrylate etc.
The compound sustained-released double-layer tablet of above-mentioned gained, wherein one deck is a Nifedipine sustained release tablets, and another layer is the atenolol sustained-release sheet, and two compositions are 24 hours slow release in vivo and discharge.
In preparation process, also can atenolol, nifedipine is evenly mixed with above-mentioned various compositions together, through suitably handling, be pressed into single that is fit to specification and size.
Slow releasing capsule of the present invention can prepare by the following method:
With atenolol, nifedipine respectively with suitable component, comprise mix homogeneously such as binding agent, filler, through suitably handling, make the core piller respectively.Gained core piller is used for further processing.
Preferably atenolol, nifedipine are dissolved in respectively or are suspended in the appropriate solvent, add suitable adhesive, filler etc. and be made into coating solution.By the fluid bed suspension coating method, the coating solution of above-mentioned preparation is wrapped in respectively on the celphere, obtain containing the pastille piller of atenolol or nifedipine respectively.
Desire is endorsed to be water-insoluble kind nuclear or water miscible kind nuclear with the kind that active substance adds layer.The former contains single or blended different oxide, cellulose, organic polymer and other materials, and the latter is contained single or blended different organic salt, sugar and other materials.
In addition, available inert species is examined laminating method, powder lamination method, is extruded/technologies such as spheronization, and preparation contains the core material of active substance, and the gained core pellet is used for further processing.
Use suitable packaging technique, on above-mentioned core piller, slow-release material can be dispersed or dissolved in the water or in the appropriate organic solvent with one or more slow-release material separate application.Can use one or more following polymers as the sustained release coating layer, but be not limited to following substances: cellulose acetate, ethyl cellulose, hypromellose, Eudragit NE 30D, Eudragit RL 100, Eudragig RS 100 etc.
The sustained release coating layer can contain pharmaceutically useful plasticizer so that obtain the consistency and elasticity of necessary mechanical strength such as slow release layer.Described plasticizer can include, but are not limited to phthalic acid ester, Polyethylene Glycol, spermol or other plasticizers.In this slow release layer, also can comprise additive such as dispersant, coloring agent, antiplastering aid etc.
With the slow-release micro-pill of difference gained, mix homogeneously is loaded capsule by a certain percentage, promptly gets compound sustained release capsules.
In the preparation process of above-mentioned slow-release micro-pill, also can be with atenolol, nifedipine is included in the same micropill, make compound recipe pastille piller, with the compound recipe pastille piller bundled slow-releasing layer of gained, at last the compound sustained-released piller of gained is loaded capsule again, promptly get compound sustained release capsules of the present invention.
Slow releasing preparation provided by the present invention, compare with existing preparation, patient's medicining times is kept to once a day, overcomes and miss, take more convenient, curative effect will add outstanding, reduce the cost of taking medicine, made two medicines together can stable existence simultaneously, prolonged the storage life, lowered side effect, effect is even more ideal.
The specific embodiment:
Further specify the present invention by the following examples.
Embodiment 1: the preparation of tablet
Prescription: (1000 consumptions)
Atenolol 100g
Nifedipine 30g
HPMC?
K100M) 50.5g
HPMC?
K15M 42.5g
Microcrystalline Cellulose 45g
Lactose 30g
Magnesium stearate 2.2g
10%PVP solution is an amount of
Technology:
Take by weighing atenolol 100g, HPMC
K100M20.5g, HPMC
K15M20g, microcrystalline Cellulose 20g, lactose 15g, evenly mixed, add an amount of 10%PVP solution, wet granulation, the oven dry of gained granule adds a certain amount of lubricant to a certain degree, is pressed into the tablet that is fit to specification and size.
Take by weighing nifedipine 30g, HPMC
K100M30g, HPMC
K15M22.5g, microcrystalline Cellulose 10g, lactose 15g, mixed evenly, add an amount of 10%PVP solution, wet granulation, the oven dry of gained granule adds a certain amount of lubricant to a certain degree, evenly mixed with the above-mentioned atenolol sustained-release sheet of pressing, be pressed into 1000 double-layer tablet.Promptly get compound slow-release tablet of the present invention.
Embodiment 2: the preparation of tablet
Prescription: (1000 consumptions)
Atenolol 120g
Nifedipine 40g
HPMC?
K100M) 55g
HPMC?
K15M 45g
Microcrystalline Cellulose 55g
Lactose 20g
Magnesium stearate 3.2g
10%PVP solution is an amount of
Technology:
Take by weighing atenolol, nifedipine, the HPMC of recipe quantity
K100M, HPMC
K15M, microcrystalline Cellulose, lactose, evenly mixed, add an amount of 10%PVP solution, wet granulation, the oven dry of gained granule adds lubricant to a certain degree, is pressed into the tablet that is fit to specification and size.
Embodiment 3: capsular preparation
The ball core:
Atenolol 100g
Nifedipine 30g
Microcrystalline Cellulose 80g
Lactose 50g
10%PVP is an amount of
Slow release layer:
Eudragit?NE?30D 20g
Pulvis Talci 2.5g
Pure water 190ml
Technology:
Take by weighing atenolol 100g, microcrystalline Cellulose 30g, lactose 20g, mix homogeneously adds a certain amount of 10%PVP solution, by extrude/spheronization prepares the pastille piller of the about 2mm of diameter.Other takes by weighing EudragitNE30D8.5g, Pulvis Talci 1.0g, pure water 80ml, is mixed with sustained release coating solution, the gained coating solution is wrapped on the pastille piller of above-mentioned preparation, promptly gets the atenolol sustained-release piller.
Take by weighing nifedipine 30g, microcrystalline Cellulose 50g, lactose fruit 30g, mix homogeneously adds a certain amount of 10%PVP solution, by extrude/spheronization prepares the pastille piller of the about 2mm of diameter.Other takes by weighing EudragitNE 30D 11.5g, Pulvis Talci, and 1.5g, pure water 110ml are mixed with sustained release coating solution, the gained coating solution is wrapped on the nifedipine pastille piller of above-mentioned preparation, promptly gets the Nifedipine sustained-release piller.
Nifedipine sustained-release piller, atenolol sustained-release piller mix homogeneously with gained are filled into 1000 capsules, make to contain atenolol 100mg, nifedipine 30mg in every capsules.Promptly get compound sustained release capsules of the present invention.
Embodiment 4: capsular preparation
The ball core:
Atenolol 120g
Nifedipine 40g
Microcrystalline Cellulose 60g
Lactose 40g
10%PVP is an amount of
Slow release layer:
Eudragit NE?30D 30g
Pulvis Talci 3.5g
Pure water 290ml
Technology:
Take by weighing atenolol, nifedipine, microcrystalline Cellulose, the lactose of recipe quantity, mix homogeneously adds a certain amount of 10%PVP solution, by extrude/spheronization prepares the pastille piller of the about 2mm of diameter.Other takes by weighing Eudragit NE30D, Pulvis Talci, pure water, is mixed with sustained release coating solution, the gained coating solution is wrapped on the pastille piller of above-mentioned preparation, promptly gets compound sustained-released piller, and is encapsulated subsequently.
Claims (1)
1, a kind of compound slow release preparation, the slow preparation of this compound recipe is a slow releasing tablet, active constituents of medicine is atenolol and nifedipine, it is characterized in that, per 1000 by
Atenolol 100g
Nifedipine 30g
HPMC
K100M) 50.5g
HPMC?
K15M 42.5g
Microcrystalline Cellulose 45g
Lactose 30g
Magnesium stearate 2.2g
10%PVP solution is made in right amount, and its preparation method is as follows, takes by weighing atenolol 100g, HPMC
K100M20.5g, HPMC
K15M20g, microcrystalline Cellulose 20g, lactose 15g, evenly mixed, add an amount of 10%PVP solution, wet granulation, the oven dry of gained granule adds lubricant, compressed tablets, other takes by weighing nifedipine 30g, HPMC
K100M30g, HPMC
K15M22.5g, microcrystalline Cellulose 10g, lactose 15g, mixed evenly add an amount of 10%PVP solution, wet granulation, the oven dry of gained granule adds lubricant, with above-mentioned to press the atenolol sustained-release sheet to mix even, is pressed into 1000 double-layer tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031239234A CN1191831C (en) | 2003-05-20 | 2003-05-20 | Compound Atenolol-Nifedipine slow releasing prepn |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031239234A CN1191831C (en) | 2003-05-20 | 2003-05-20 | Compound Atenolol-Nifedipine slow releasing prepn |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1452966A CN1452966A (en) | 2003-11-05 |
| CN1191831C true CN1191831C (en) | 2005-03-09 |
Family
ID=29260300
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031239234A Expired - Fee Related CN1191831C (en) | 2003-05-20 | 2003-05-20 | Compound Atenolol-Nifedipine slow releasing prepn |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1191831C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100401058C (en) * | 2006-04-14 | 2008-07-09 | 张宏业 | Joint measurement method of nitrendipine and atenolol |
| CN100469356C (en) * | 2006-09-08 | 2009-03-18 | 山东益康药业有限公司 | Slowly released tablet of compound atenolol, and preparation method |
| CN102512394B (en) * | 2011-12-15 | 2013-10-23 | 浙江泰利森药业有限公司 | Nifedipine sustained release tablets and preparation process thereof |
| CN103349651B (en) * | 2013-07-29 | 2014-08-27 | 德州博诚制药有限公司 | Nifedipine sustained release tablet and preparation method thereof |
-
2003
- 2003-05-20 CN CNB031239234A patent/CN1191831C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1452966A (en) | 2003-11-05 |
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