CN1047731C - Slow-release preparation contg. isoptin and preparing process thereof - Google Patents
Slow-release preparation contg. isoptin and preparing process thereof Download PDFInfo
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- CN1047731C CN1047731C CN95111691A CN95111691A CN1047731C CN 1047731 C CN1047731 C CN 1047731C CN 95111691 A CN95111691 A CN 95111691A CN 95111691 A CN95111691 A CN 95111691A CN 1047731 C CN1047731 C CN 1047731C
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Abstract
The present invention relates to a slow-release preparation containing medicines, such as Verapamil, etc., and a preparation method thereof. The release of medicines is controlled by a frame composed of three different types of macromolecular compounds, and the slow-release preparation comprises an alginate compound, such as sodium alginate, an enteric solubility high molecular polymer, such as a methyl propenoate copolymer, and a hydrophilic gelatin high molecular polymer, such as hydroxypropyl methyl cellulose or polyethylene oxide. After the dosages of the three macromolecular compounds are regulated, the release rate of the medicines can be conveniently and effectively regulated.
Description
The invention relates to a kind of slow releasing preparation that contains verapamil medicines such as (Verapamil) and preparation method thereof, this slow releasing preparation is made up of pharmacologically active component, three kinds of macromolecular compounds of different nature and other solid pharmaceutical preparation various additives commonly used.With these three kinds of macromolecular compounds of different nature is that substrate is formed sustained-release matrix tablets, and this in this manual sustained-release matrix tablets is also referred to as " bank " (Depot) pharmaceutical preparation.
The invention still further relates to especially a kind of can be with the speed of certain design, the slow preparation method of " bank " pharmaceutical preparation of the matrix tablet of release of pharmacologically active constituent in the intestines and stomach of human body.
Clinically, the normal requirement of ideal controlled release preparation discharges medicine with zero order release rate, to reach the stable of blood drug level.About preparing the technology that can discharge the preparation of medicine, existing a large amount of report with zero order release rate.With the carrier of matrix tablet, be a short-cut method that is commonly used to prepare the controlled release preparation of zero order release rate as medicine.
Contain the technology of " bank " medicinal tablet of verapamil medicines such as (Verapamil) about preparation, also existing multiple patent report.In patented invention in the past, usually use the substrate of one or both macromolecular compounds of different nature as sustained-release matrix tablets.For example, only use alginate (United States Patent (USP) 5132295), use the method for alginate and the mixture (United States Patent (USP) 5230901) of polyacrylate high molecular polymer and the cellulosic mixture of hydrophilic gel (United States Patent (USP) 4792452) that uses alginate and not influenced by pH value etc.It is reported simultaneously, in matrix tablet, only use alginate to be host material, in the preparation technology of medicinal tablet and storage process, usually have some problems.
The polymer that suitably adds acrylates in the prescription of alginate can overcome some difficulties to a certain extent.Yet with these two kinds of matrix tablets that macromolecular compound is made, the stripping of medicine often is subjected to the influence of pH value.Under the condition of low pH value, alginate and acrylate polymer are can not swelling and dissolved, therefore can not form the gel layer of control drug release.Medicine spreads by the capillary tube in the tablet, discharges with speed faster; On the other hand, under the condition of high pH value, the alginate swelling forms the gel layer that stops the medicine rapid release.Simultaneously, this gel layer itself is also with certain speed corrosion (i.e. dissolving), and medicine discharges by the mechanism of gel layer with the mechanism of diffusion, the corrosion by gel layer itself simultaneously.Rate of releasing drug is slower than the release under low pH value environment.
To containing alginate and not being subjected to the pharmaceutical formulation of the gelatin polymer that pH value influences, under the condition of low pH value, only manage alginate not swelling or dissolving, but be not subjected to the gelatin polymer (as hydroxypropyl emthylcellulose) that pH value influences can swelling, form the gel layer of control drug release, compare with the situation of using single-matrix and make moderate progress.Yet under the condition of high pH value, this two compounds all dissolves, but also has the corrosion phenomenon.The result of corrosion phenomenon makes the volume of matrix tablet more and more littler in the medicine process in leaching, its release surface area is reduced, thereby changed release rate of drugs.
The invention provides a kind of can the minimizing, sometimes even can eliminate the slow-releasing agent of above-mentioned these problems fully.
Characteristics of the present invention are to use the host material of three kinds of dissimilar macromolecular compounds as matrix tablet, improve the problem that exists on slow-releasing agent preparation technology and the rate of release.Three kinds of dissimilar macromolecular compounds that use among the present invention are made up of the high molecular polymer and the hydrophilic gel high molecular polymer (usually not being subjected to the influence of pH value) of alginate chemical compound, enteric solubility acrylates.Change the formula proportion of these three kinds of macromolecular compounds, can regulate release rate of drugs easily.
" bank " matrix tablet by formulation of the present invention can discharge medicine with zero order release rate, under the situation of low pH value, and hydrophilic gel high molecular polymer (for example hydroxypropyl emthylcellulose) swellable, the gel layer of formation control drug release; When high pH value, the gel layer that the alginate swelling forms, also can be with certain speed corrosion, and because enteric solubility acrylates high molecular polymer can increase the erosion rate of tablet, thus can keep stable, with the irrelevant medicine dissolution speed of volume size of tablet.Compare with aforementioned existing preparation technique, the tablet that method of the present invention provided, the release mode of its medicine is more stable, better.
Below be to be described in detail to of the present invention.
Slow releasing pharmaceutical tablet provided by the present invention, by medicine components, can control the framework material that the pharmacologically active component discharges: the mixture that the high molecular polymer of alginate chemical compound, enteric solubility acrylates, hydrophilic gel high molecular polymer and the conventional various additives that are used for solid pharmaceutical preparation obtain is jointly formed.Medicine components therefrom can discharge with controllable rate.Change the consumption of these framework materials, can regulate release rate of drugs easily.By the prescription that a kind of preferred implementation of the present invention provided, can be used for " bank " (Depot) preparation of pharmaceutical dosage form especially, can control the release of contained verapamil medicine components such as (Verapamil).Certainly, prescription provided by the present invention also can be applicable to the preparation of other various pharmacologically active components; Application of the present invention should not be regarded as being confined to some specific medicine components yet, and/or their inherent characteristicses of disengaging under controlled conditions.
By the prescription that a kind of preferred implementation of the present invention provided, comprising:
1) pharmacologically active component;
2) the alginate chemical compound that exists with the water-soluble alginate form, the viscosity of the aqueous solution of its 2% (percentage by weight) in the time of 25 ℃ is about 60-10000 centipoises, preferably is about 100-6000 centipoises (measuring with Brookfield LV viscosity apparatus);
3) enteric solubility high molecular polymer component, as methacrylic acid salt copolymer acrylate polymers such as (preferably Eudragit L/S), also comprise Cellacefate (CAP), Hydroxypropyl Methylcellulose Phathalate (HPMCP), Opaseal cellulose derivatives such as (PVAP).
Enteric solubility high molecular polymer described here does not dissolve in the acid solution of pH value below 5.
4) hydrophilic gel high molecular polymer component, as cellulose derivative or poly(ethylene oxide), the viscosity of the aqueous solution of its 2% (percentage by weight) in the time of 20 ℃ is about 10-100000 centipoises, preferably is about 50-15000 centipoises (measuring with Brookfield LV viscosity apparatus);
5) routine is used for the various additives of solid pharmaceutical preparation, as in the additives such as binding agent, antiseptic, coloring agent, stabilizing agent, antitack agent, smoothing preparation, desiccant, diluent, stripping controlling agent one or more.
The total consumption of above-mentioned three kinds of dissimilar macromolecular compounds in end formulation should be 25-70% (percentage by weight) of total preparation.The mixture of macromolecular compound is made up of alginate chemical compound 40-80 weight portions, enteric solubility high molecular polymer 5-60 weight portions and hydrophilic gel high molecular polymer 6-50 weight portions.
Be applicable to that alginate chemical compound of the present invention comprises sodium alginate, potassium alginate, calcium alginate etc.;
Be applicable to that hydrophilic gel high molecular polymer of the present invention comprises cellulose derivative or poly(ethylene oxide);
Be applicable to various enteric solubility acrylate polymer of the present invention, fully described.For example: the full content that United States Patent (USP) 5230901 is disclosed, at this all by with reference to quoting.So used here " acrylate polymer " speech comprises the copolymer of the disclosed polyacrylate of this United States Patent (USP), poly-methyl acrylate, acrylic acid and methacrylic acid etc.The document of describing these materials is also just like Houben-weyl, Methoden derorgani schen Chemie, Thieme-Verlag, Stutt, 1961.It is particularly suitable that the merchant of Eudragit by name sells product.Be applicable to enteric solubility high molecular polymer of the present invention, also comprise Cellacefate (CAP), Hydroxypropyl Methylcellulose Phathalate (HPMCP), Opaseal cellulose derivatives such as (PVAP).
Enteric solubility high molecular polymer described here does not dissolve in the acid solution of pH value below 5.
All the other various additives that prescription of the present invention can add comprise:
1) one or more in the following listed binding agent:
Polyvinyl pyrrole Lip river alkane ketone, modified starch, low viscous hydroxypropyl emthylcellulose or the like.
2) one or more in the following listed filler:
Microcrystalline Cellulose, lactose, starch, calcium sulfate or the like.
3) one or more in the following listed lubricant:
Magnesium stearate or stearic acid or the like.
4) one or more in the following listed film coating agent:
Hydroxypropyl emthylcellulose, polyethylene glycols, Lac or the like.
5) one or more in the following listed coloring agent:
FD﹠amp; Food colorings such as C green dyc, lemon yellow, carmine.
Adhesive consumption can reach about 10% of tablet total weight; The consumption of lubricant can reach about 0.1%-5.0% of tablet total weight.
Below be four prescription example A of the present invention, B, C, D is made up of following component respectively: component (milligram) A B C D verapamil (Verapamil) 240 240 240 240 sodium alginates 200 180 250 200 hydroxypropyl emthylcelluloses 100 00 40 hydroxypropyl celluloses 0 80 40 0 poly(ethylene oxide) 00 60 60 methacrylic acid copolymer 0 40 80 0 Cellacefates 60 00 80 polyvinyl pyrrole Lip river alkane ketone 40 30 50 50 microcrystalline Cellulose 56 26 75 75 magnesium stearate 4455
Above-mentioned component (removing magnesium stearate) behind the mixing, is added water or water and alcoholic acid mixed liquor and carry out wet granulation in granulator in blender; Grind after the drying, add magnesium stearate (lubricant) again, repress is made sheet behind the mixing.Above-mentioned steps all is the conventional steps in the tablet formulation industry.
The prescription that the invention described above provided, particularly useful to the slow releasing tablet of preparation verapamil.Change the usage ratio of three kinds of dissimilar macromolecular compounds, can regulate release rate of drugs easily.Yet the present invention should not be regarded as being confined to the application of this medicine components.Other various medicines that need delay to discharge also belong to range of application of the present invention.For example, the present invention also will can be used for any one in the following medicine: propafcnonc, barucainidc, ncsapidil, gallopamil, bipcridcn etc.Enumerate other in the United States Patent (USP) 4792452 and be applicable to the medicine of range of application of the present invention.The full content that this United States Patent (USP) is disclosed is all quoted by reference especially at this.
" bank " matrix tablet by formulation of the present invention can discharge medicine with zero order release rate, under the situation of low pH value, and hydrophilic gel high molecular polymer (for example hydroxypropyl emthylcellulose) swellable, the gel layer of formation control drug release; When high pH value, the gel layer that the alginate swelling forms, also can be with certain speed corrosion, and because the high molecular polymer of enteric solubility acrylates can increase the erosion rate of tablet, thus can keep stable, with the irrelevant medicine dissolution speed of volume size of tablet.Compare with aforementioned existing preparation technique, the tablet that method of the present invention provided, the release mode of its medicine is more stable, better.
Following embodiment can further specify method of the present invention, but and unrestricted range of application of the present invention.
Embodiment 1,
A kind of slow releasing pharmaceutical tablet is made up of the various additives that pharmacologically active component, macromolecular compound and other solid pharmaceutical preparation are commonly used, can slowly discharge the pharmacologically active component of effective quantity with certain speed in a period of time.The mixture that this macromolecular compound is made up of alginate chemical compound, enteric solubility high molecular polymer and hydrophilic gel high molecular polymer.
Embodiment 2,
As embodiment 1 described a kind of slow releasing pharmaceutical tablet, but the alginate chemical compound is made up of in the water miscible alginate such as sodium alginate, potassium alginate, calcium alginate any one or a few, the viscosity of the aqueous solution of its 2% (percentage by weight) in the time of 25 ℃ is 60-10000 centipoises, is preferably 100-6000 centipoises (measuring with the BrookfieldLV viscosity apparatus).
Embodiment 3,
As embodiment 1,2 described a kind of slow releasing pharmaceutical tablets, but the enteric solubility high molecular polymer is by acrylate polymer, as methacrylic acid salt copolymer compositions such as (preferably Eudragit L/S); Or form by in Cellacefate (CAP), Hydroxypropyl Methylcellulose Phathalate (HPMCP), the Opaseal cellulose derivatives such as (PVAP) any one or a few.
Embodiment 4,
As embodiment 3 described a kind of slow releasing pharmaceutical tablets, the enteric solubility high molecular polymer does not here dissolve in the acid solution of pH value below 5.
Embodiment 5,
As embodiment 1,2,3,4 described a kind of slow releasing pharmaceutical tablets, but the hydrophilic gel high molecular polymer is cellulosic derivant or poly(ethylene oxide).Cellulosic derivant described here is made up of in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, methylcellulose, the sodium carboxymethyl cellulose etc. any one or a few.
Embodiment 6,
As embodiment 5 described a kind of slow releasing pharmaceutical tablets, but the viscosity of 2% (percentage by weight) aqueous solution in the time of 20 ℃ of hydrophilic gel high molecular polymer is 10-100000 centipoises, is preferably 50-15000 centipoises (measuring with the BrookfieldLV viscosity apparatus).
Embodiment 7,
As embodiment 1,2,3,4,5,6 described a kind of slow releasing pharmaceutical tablets, the consumption of the mixture of the macromolecular compound here is 25-70% (percentage by weight) of this slow releasing pharmaceutical tablet total amount.
Embodiment 8,
As embodiment 7 described a kind of slow releasing pharmaceutical tablets, but the mixture of macromolecular compound is made up of alginate chemical compound 40-80 weight portions, enteric solubility high molecular polymer 560 weight portions and hydrophilic gel high molecular polymer 6-50 weight portions.
Embodiment 9,
As embodiment 1,2,3,4,5,6,7,8 described a kind of slow releasing pharmaceutical tablets, the solid pharmaceutical preparation additive comprises one or more in the additives such as binding agent, antiseptic, coloring agent, filler, lubricant, fluidizer.
Embodiment 10,
As the preparation method of embodiment 9 described a kind of slow releasing pharmaceutical tablets, this method comprises: the additive that solid pharmaceutical preparations such as pharmacologically active component, alginate chemical compound, enteric solubility acrylates high molecular polymer, hydrophilic gel high molecular polymer and microcrystalline Cellulose is commonly used (removing magnesium stearate) mixing in blender; Add water or water and alcoholic acid mixed liquor and in granulator, carry out wet granulation; Grind after the drying; Add magnesium stearate (lubricant) again, repress is made sheet behind the mixing;
The erosion rate of tablet should be able to be dissolved and increase to the quantity of used enteric solubility acrylates high molecular polymer when high pH value, to keep the rate of dissolution of stable pharmacologically active component.
Embodiment 11,
Press embodiment 10 described methods, utilize the hydrophilic gel high molecular polymer that adds to promote the bonding of solid preparation, the formation of gel is not influenced by pH value, makes the pharmacology active constituent that stable dissolution rate be arranged when different PH.
Embodiment 12,
Press embodiment 10,11 described methods, the enteric solubility high molecular polymer that utilization adds can increase the erosion rate of solid preparation when pH value increases, and regulates the dissolution rate of pharmacologically active component.
Embodiment 13,
Press embodiment 12 described methods, but this alginate chemical compound is any one or several sharp composition in the water miscible alginate such as sodium alginate, potassium alginate, calcium alginate, the viscosity of the aqueous solution of its 2% (percentage by weight) in the time of 25 ℃ is 60-10000 centipoises, preferably is 100-6000 centipoises; The viscosity of the aqueous solution of 2% (percentage by weight) of hydrophilic gel high molecular polymer in the time of 20 ℃ is 10-100000 centipoises, preferably is 50-15000 centipoises (measuring with Brookfield LV viscosity apparatus).
Embodiment 14,
Press embodiment 7,8 described a kind of slow releasing pharmaceutical tablets, pharmacologically active component in this tablet is the verapamil (Verapamil) of 240 weight portions, the hydroxypropyl emthylcellulose that the alginate chemical compound is the sodium alginate of 200 weight portions, Cellacefate that the enteric solubility high molecular polymer is 60 weight portions, the hydrophilic gel high molecular polymer is 100 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 40 weight portions, the microcrystalline Cellulose of 56 weight portions, the magnesium stearate of 4 weight portions.
Embodiment 15,
Press embodiment 7,8 described a kind of slow releasing pharmaceutical tablets, pharmacologically active component in this tablet is the verapamil (Verapamil) of 240 weight portions, the hydroxypropyl cellulose that the alginate chemical compound is the sodium alginate of 180 weight portions, methacrylic acid copolymer that the enteric solubility high molecular polymer is 40 weight portions, the hydrophilic gel high molecular polymer is 80 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 30 weight portions, the microcrystalline Cellulose of 26 weight portions, the magnesium stearate of 4 weight portions.
Embodiment 16,
Press embodiment 7,8 described a kind of slow releasing pharmaceutical tablets, pharmacologically active component in this tablet is the verapamil (Verapamil) of 240 weight portions, the poly(ethylene oxide) that the alginate chemical compound is the sodium alginate of 250 weight portions, methacrylic acid copolymer that the enteric solubility high molecular polymer is 80 weight portions, the hydrophilic gel high molecular polymer is 60 weight portions and the hydroxypropyl cellulose of 40 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 50 weight portions, the microcrystalline Cellulose of 75 weight portions, the magnesium stearate of 5 weight portions.
Embodiment 17,
Press embodiment 7,8 described a kind of slow releasing pharmaceutical tablets, pharmacologically active component in this tablet is the verapamil (Verapamil) of 240 weight portions, the hydroxypropyl emthylcellulose that the alginate chemical compound is the sodium alginate of 200 weight portions, Cellacefate that the enteric solubility high molecular polymer is 80 weight portions, the hydrophilic gel high molecular polymer is 40 weight portions and the poly(ethylene oxide) of 60 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 50 weight portions, the microcrystalline Cellulose of 75 weight portions, the magnesium stearate of 5 weight portions.
Embodiment 18,
Press embodiment 1,2,3,4,5,6 described a kind of slow releasing pharmaceutical tablets, the consumption of the mixture of the macromolecular compound here is 25-70% (percentage by weight) of this slow releasing pharmaceutical tablet total amount; The mixture of macromolecular compound is made up of alginate chemical compound 40-80 weight portions, enteric solubility high molecular polymer 5-60 weight portions and hydrophilic gel high molecular polymer 6-50 weight portions.
Claims (16)
1, a kind of slow releasing pharmaceutical tablet, form by pharmacologically active component, macromolecular compound and other solid pharmaceutical preparation additive, it is characterized in that the mixture that macromolecular compound is made up of alginate chemical compound, enteric solubility high molecular polymer and hydrophilic gel high molecular polymer.
2, by the described a kind of slow releasing pharmaceutical tablet of claim 1, it is characterized in that described alginate chemical compound is made up of in sodium alginate, potassium alginate, the calcium alginate any one or a few, the viscosity of the aqueous solution of its 2% (percentage by weight) in the time of 25 ℃ is 60-10000 centipoises.
3,, it is characterized in that described enteric solubility high molecular polymer is made up of in methacrylic acid salt copolymer, Cellacefate, Hydroxypropyl Methylcellulose Phathalate, the Opaseal any one or a few by the described a kind of slow releasing pharmaceutical tablet of claim 2.
4, by the described a kind of slow releasing pharmaceutical tablet of claim 3, it is characterized in that described enteric solubility high molecular polymer does not dissolve in the acid solution of pH value below 5.
5, by the described a kind of slow releasing pharmaceutical tablet of claim 4, it is characterized in that described hydrophilic gel high molecular polymer is cellulosic derivant or poly(ethylene oxide); Cellulosic derivant described here is made up of in hydroxypropyl emthylcellulose, hydroxypropyl cellulose, methylcellulose, the sodium carboxymethyl cellulose any one or a few.
6, by the described a kind of slow releasing pharmaceutical tablet of claim 5, it is characterized in that the viscosity of 2% (percentage by weight) aqueous solution in the time of 20 ℃ of described hydrophilic gel high molecular polymer is 10-100000 centipoises.
7, by the described a kind of slow releasing pharmaceutical tablet of claim 6, the consumption that it is characterized in that the mixture of the macromolecular compound here is 25-70% (percentage by weight) of this slow releasing pharmaceutical tablet total amount; The mixture of macromolecular compound is made up of alginate chemical compound 40-80 weight portions, enteric solubility high molecular polymer 5-60 weight portions and hydrophilic gel high molecular polymer 6-50 weight portions.
8, by the described a kind of slow releasing pharmaceutical tablet of claim 6, the consumption that it is characterized in that the mixture of described macromolecular compound is 25-70% (percentage by weight) of this slow releasing pharmaceutical tablet total amount.
9, by the described a kind of slow releasing pharmaceutical tablet of claim 8, it is characterized in that the mixture of described macromolecular compound is made up of alginate chemical compound 40-80 weight portions, enteric solubility high molecular polymer 5-60 weight portions and hydrophilic gel high molecular polymer 6-50 weight portions.
10, by the described a kind of slow releasing pharmaceutical tablet of claim 9, it is characterized in that the pharmacologically active component in this tablet is the verapamil of 240 weight portions, the hydroxypropyl emthylcellulose that the alginate chemical compound is the sodium alginate of 200 weight portions, Cellacefate that the enteric solubility high molecular polymer is 60 weight portions, the hydrophilic gel high molecular polymer is 100 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 40 weight portions, the microcrystalline Cellulose of 56 weight portions, the magnesium stearate of 4 weight portions.
11, by the described a kind of slow releasing pharmaceutical tablet of claim 9, it is characterized in that the pharmacologically active component in this tablet is the verapamil of 240 weight portions, the hydroxypropyl cellulose that the alginate chemical compound is the sodium alginate of 180 weight portions, methacrylic acid copolymer that the enteric solubility high molecular polymer is 40 weight portions, the hydrophilic gel high molecular polymer is 80 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 30 weight portions, the microcrystalline Cellulose of 26 weight portions, the magnesium stearate of 4 weight portions.
12, by the described a kind of slow releasing pharmaceutical tablet of claim 9, it is characterized in that the pharmacologically active component in this tablet is the verapamil of 240 weight portions, the poly(ethylene oxide) that the alginate chemical compound is the sodium alginate of 250 weight portions, methacrylic acid copolymer that the enteric solubility high molecular polymer is 80 weight portions, the hydrophilic gel high molecular polymer is 60 weight portions and the hydroxypropyl cellulose of 40 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 50 weight portions, the microcrystalline Cellulose of 75 weight portions, the magnesium stearate of 5 weight portions.
13, by the described a kind of slow releasing pharmaceutical tablet of claim 9, it is characterized in that the pharmacologically active component in this tablet is the verapamil of 240 weight portions, the hydroxypropyl emthylcellulose that the alginate chemical compound is the sodium alginate of 200 weight portions, Cellacefate that the enteric solubility high molecular polymer is 80 weight portions, the hydrophilic gel high molecular polymer is 40 weight portions and the poly(ethylene oxide) of 60 weight portions and the polyvinyl pyrrole Lip river alkane ketone of 50 weight portions, the microcrystalline Cellulose of 75 weight portions, the magnesium stearate of 5 weight portions.
14, by the described a kind of slow releasing pharmaceutical tablet of claim 9, it is characterized in that described solid pharmaceutical preparation additive comprises one or more in binding agent, antiseptic, coloring agent, filler, lubricant, the fluidizer.
15, by the preparation method of the described a kind of slow releasing pharmaceutical tablet of claim 14, it is characterized in that this method comprises:
With pharmacologically active component, alginate chemical compound, enteric solubility acrylates high molecular polymer, hydrophilic gel high molecular polymer and the solid pharmaceutical preparation additive mixing in blender except that magnesium stearate; Add water or water and alcoholic acid mixed liquor and in granulator, carry out wet granulation; Grind after the drying; Add magnesium stearate again, repress is made sheet behind the mixing.
16, by the described method of claim 15, it is characterized in that this alginate chemical compound is any one or a few composition in sodium alginate, potassium alginate, the calcium alginate, the viscosity of the aqueous solution of its 2% (percentage by weight) in the time of 25 ℃ is 60-10000 centipoises; The viscosity of the aqueous solution of 2% (percentage by weight) of hydrophilic gel high molecular polymer in the time of 20 ℃ is 10-100000 centipoises.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111691A CN1047731C (en) | 1995-07-12 | 1995-07-12 | Slow-release preparation contg. isoptin and preparing process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111691A CN1047731C (en) | 1995-07-12 | 1995-07-12 | Slow-release preparation contg. isoptin and preparing process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1140055A CN1140055A (en) | 1997-01-15 |
| CN1047731C true CN1047731C (en) | 1999-12-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN95111691A Expired - Fee Related CN1047731C (en) | 1995-07-12 | 1995-07-12 | Slow-release preparation contg. isoptin and preparing process thereof |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6083532A (en) * | 1995-03-01 | 2000-07-04 | Duramed Pharmaceuticals, Inc. | Sustained release formulation containing three different types of polymers and tablet formed therefrom |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4792452A (en) * | 1987-07-28 | 1988-12-20 | E. R. Squibb & Sons, Inc. | Controlled release formulation |
| US5230901A (en) * | 1988-03-23 | 1993-07-27 | Knoll Ag | Sustained release tablet of a mixture of alginates and polyacrylates |
-
1995
- 1995-07-12 CN CN95111691A patent/CN1047731C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4792452A (en) * | 1987-07-28 | 1988-12-20 | E. R. Squibb & Sons, Inc. | Controlled release formulation |
| US5230901A (en) * | 1988-03-23 | 1993-07-27 | Knoll Ag | Sustained release tablet of a mixture of alginates and polyacrylates |
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| Publication number | Publication date |
|---|---|
| CN1140055A (en) | 1997-01-15 |
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Effective date of registration: 20110627 Address after: 201419 No. 217 Minle Road, Spark Development Zone, Fengxian District Bay Town, Shanghai Patentee after: Shanghai New Hualian Pharmaceutical Co., Ltd. Address before: 200020 No. 200, Taicang Road, Shanghai Patentee before: Shanghai Pharmaceutical (Group) Co., Ltd. |
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| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 19991229 Termination date: 20140712 |
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