CN106008788B - A kind of hypotonicity Sustained release coating materials and preparation method thereof - Google Patents
A kind of hypotonicity Sustained release coating materials and preparation method thereof Download PDFInfo
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- CN106008788B CN106008788B CN201610331597.7A CN201610331597A CN106008788B CN 106008788 B CN106008788 B CN 106008788B CN 201610331597 A CN201610331597 A CN 201610331597A CN 106008788 B CN106008788 B CN 106008788B
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/14—Methyl esters, e.g. methyl (meth)acrylate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/04—Homopolymers or copolymers of esters
- C08L33/06—Homopolymers or copolymers of esters of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical
- C08L33/08—Homopolymers or copolymers of acrylic acid esters
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/04—Homopolymers or copolymers of esters
- C08L33/06—Homopolymers or copolymers of esters of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical
- C08L33/10—Homopolymers or copolymers of methacrylic acid esters
- C08L33/12—Homopolymers or copolymers of methyl methacrylate
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
- C08F220/1804—C4-(meth)acrylate, e.g. butyl (meth)acrylate, isobutyl (meth)acrylate or tert-butyl (meth)acrylate
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Abstract
The application belongs to coating material technical field, and in particular to a kind of hypotonicity Sustained release coating materials and preparation method thereof.The coating material is mainly made up of following raw material：Methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or derivatives thereof.Prepare comprising the following steps that for coating material：(1) by monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and butyl methacrylate in polymerization at 40 60 DEG C；(2) cellulose or derivatives thereof is added, continues at 65 80 DEG C and polymerize, be subsequently cooled to room temperature, get product.The coating material provided by this application has preferable filming performance and coating quality.The Sustained release coating materials provided using the present invention are coated obtained sustained release tablets and are respectively provided with preferable slow release effect in different environments, and can reduce medicine takes number of times.
Description
Technical field
The invention belongs to coating material technical field, and in particular to a kind of hypotonicity Sustained release coating materials and its preparation side
Method.
Background technology
Drug coating is to prevent the influence of medicine light, heat, tide etc. at present and go bad or cover adverse drug taste, is prevented
The main method of effective ingredient volatilization.Because macromolecule coating material can form heavily fortified point in medicinal tablet or capsule surface
Tough very thin elastic membrane, can dissolve or is disintegrated, at oral certain time or certain position especially under certain pH value again
Gradually instead of the easy moisture absorption, sugar coating material that is easily rupturable and needing thicker coating membrane.The thickness of general macromolecule coating membrane is only
For the 1-2% of traditional coating membrane, therefore can significantly it decline the time required to the clothing film of thickness needed for reaching, by decline in 8-9 hour
To 1-2 hours.
Wherein, sustained-release preparation is the principle according to insoluble drug release, by the dissolution of medicine, scattering and permeating and ion exchange
It is controlled by etc. characteristic.In most cases, mainly by selecting suitable auxiliary material, sustained release is reached using preparation technique
Medicine purpose.Film controlling type sustained release preparation is exactly the polymeric membrane that control drug release rate is enclosed with Drug Storage external application, as needed can be with
The multi-form of multi-layered type, cylinder type, ball-type or piece type is prepared into, different effects can be obtained using different film formulation and technique
The film coating slow-releasing system of fruit.
It is conventional be used to preparing slow controlled-release material have two classes：Natural polymer delays controlled-release material (such as cellulose, crust
Element, chitosan etc.), and synthesis macromolecular sustained-release material (ethylene-vinyl acetate copolymer, polyacrylic resin etc.).
Natural macromolecular material wide material sources, cost is low, small toxicity.But application is by larger limitation, such as methylcellulose
There is more incompatibility, the clothing film permeability formed when ethyl cellulose is individually coated is poor.Polyacrylic resin is most normal
One kind synthesis macromolecular sustained-release material.At present, control spacetabs type esters of acrylic acid pharmaceutical film coating material is according to medicine
Thing dissolving environment difference is divided into stomach dissolution type polyacrylic resin, enteric solubility polyacrylic resin and neutralized polyacrylic acids resin；Root
It is divided into Thief zone type acrylic resin, hyposmosis type acrylic resin and medium osmosis type acrylic resin according to osmotic strength.
It is by German Rohm Pharma (Rohm mostly the film coating material based on acrylic resin clinically used at present
Pharma) the imported product of production, but imported product is expensive；And domestic kind in terms of the performance of film, such as toughness still
There is gap, it is impossible to which satisfaction is actually needed.
The domestic patent document in terms of acrylic resin, is exemplified below：
1) patent CN102432737B《One kind sustained release intestines Acrylic Resin Emulsion liquid and its preparation method》Disclose a kind of methyl
What acrylic acid, methyl acrylate and methyl methacrylate copolymer were obtained (pH >=7) can start the positioning dissolved near colon
Release coating material.But the coating material may be only available for some drugs preparation.
2) patent CN1156500C《The preparation method of coating material as coating film of gastric disintegrable water medicine》One kind is disclosed by first
Base methyl acrylate, ethyl acrylate, methacrylic acid trimethyl ammonium chloride base three kinds of monomers of ethyl ester, using discontinuous emulsion polymerization
Method, is made stomach and collapses and ooze type soon and ooze type thin polymer film coating material slowly respectively.
3) patent CN103102445B《A kind of poly- first acrylate of pH independent forms and preparation method thereof》Then disclose one
Plant the pH as made from ethyl acrylate, methyl methacrylate, three monomers of methacrylic acid trimethyl ammonium chloride base ethyl ester non-
Poly- first acrylate of dependent form and preparation method thereof.This application provide polymethacrylate resin and solution environmental pH without
Close, be by being used in conjunction with after being mixed with some water-soluble substanceses, by controlling the dissolving of water-soluble substances to reach mixture
Dissolving, so as to realize the control release to packaging medicine.But finding suitably is used for the water-soluble substances of different pH environment, right
For Yu researcher, workload is increased.And the slow controlled release properties of the slow controlled-release material obtained after mixing are not also understood.
How to prepare a kind of cost low and meet the coating material of clinically medicine sustained and controlled release requirement, be the application potential solution
Certainly the problem of.
The content of the invention
An object of the present invention is to provide that a kind of filming performance is good, hypotonicity sustained release coating material to pH no dependences
Material.
It is a further object to provide a kind of method for preparing above-mentioned Sustained release coating materials.
In order to realize foregoing invention purpose, one of technical scheme of the application provides a kind of hypotonicity and is sustained bag
Clothing material, it is characterised in that it is mainly made up of following raw material：
Methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or its spread out
It is biological.
Preferably, methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, fiber
The weight proportion of element or derivatives thereof is 1:(0.5-1)：(0.8-1.5):(0.03-0.05).
Preferably, the cellulose is non-modified cellulose, and such as ethyl cellulose, methylcellulose, ethoxy are fine
Dimension element or HPMC；The derivative of cellulose includes cellulose acetate, HP-55 or acetic acid hydroxyl
Propyl methocel succinate etc..
Being preferably made from the raw material of the Sustained release coating materials also includes emulsifying agent, and the emulsifying agent is detergent alkylate
At least one of sodium sulfonate, NPE, glycerine stearic acid ester, polysorbas20, polysorbate40 and polysorbate60.
It is further preferred that the consumption of the emulsifying agent is methyl methacrylate, methacrylic acid chlorination dimethylamino
The 0.3-0.8% of ethyl ester, butyl methacrylate, cellulose or derivatives thereof gross weight.
Being preferably made from the raw material of the Sustained release coating materials also includes initiator, and the initiator is ammonium persulfate, mistake
At least one of potassium sulfate and sodium peroxydisulfate.
It is further preferred that the consumption of the initiator is methyl methacrylate, methacrylic acid chlorination dimethylamino
The 1-3% of ethyl ester, butyl methacrylate, cellulose or derivatives thereof gross weight.
Being preferably made from the raw material of the Sustained release coating materials also includes purified water.
It is further preferred that the consumption of the purified water is methyl methacrylate, methacrylic acid chlorination dimethylamino
3-5 times of ethyl ester, butyl methacrylate, cellulose or derivatives thereof gross weight.
Preferably, described Sustained release coating materials, it is mainly prepared from the following raw materials in parts by weight：Methyl methacrylate
Ester：Methacrylic acid chlorination dimethylamino ethyl ester：Butyl methacrylate：Ethyl cellulose=1:(0.5-0.66)：(1-
1.25)：0.03；
It is further preferred that be made the raw materials of the Sustained release coating materials also include emulsifying agent neopelex and
Polysorbas20, its consumption is methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, ethyl
The 0.3-0.4% of cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes initiator ammonium persulfate, and its consumption is methyl methacrylate
Ester, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, the 1.125-1.5% of ethyl cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes purified water, and its consumption is methyl methacrylate, methyl-prop
Olefin(e) acid chlorination dimethylamino ethyl ester, butyl methacrylate, 3.2-3.5 times of ethyl cellulose gross weight.
As a kind of preferred embodiment, a kind of hypotonicity Sustained release coating materials, it is mainly made up of following raw material：
Methyl methacrylate：Methacrylic acid chlorination dimethylamino ethyl ester：Butyl methacrylate：Ethyl cellulose=
1:0.52:1.1:0.03；
The raw material of the Sustained release coating materials, which is made, also includes emulsifying agent neopelex and polysorbas20, wherein two
The weight ratio of person is 5:1, the gross weight of the two accounts for methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, methyl
The 0.3% of butyl acrylate, ethyl cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes initiator ammonium persulfate, and its consumption is methyl methacrylate
Ester, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, the 1.35% of ethyl cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes purified water, and its consumption is methyl methacrylate, methyl-prop
Olefin(e) acid chlorination dimethylamino ethyl ester, butyl methacrylate, 3.3 times of ethyl cellulose gross weight.
Another technical scheme of the application provides a kind of method for preparing above-mentioned Sustained release coating materials, its specific steps
It is as follows：
(1) monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and the first of above-mentioned weight proportion are made
Base butyl acrylate is in polymerization at 40-60 DEG C；
(2) cellulose or derivatives thereof is added according to above-mentioned weight proportion, continues at 65-80 DEG C and polymerize, then cool down
To room temperature, get product.
Preferably, the concrete operations of polymerisation are in step (1)：
According to above-mentioned weight proportion, make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and first
Base butyl acrylate is mixed with emulsifying agent, purified water, is warming up to 40-60 DEG C, and dropwise addition purified water dissolves thereto under agitation
Initiator, continue react 2-5 hours.
It is further preferred that it is 0.8-2 hours that the time used in the initiator solution, which is added dropwise,.
It is further preferred that the emulsifying agent is neopelex, NPE, glycerine stearic acid
At least one of ester, polysorbas20, polysorbate40 and polysorbate60；
The consumption of the emulsifying agent is methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, metering system
The 0.3-0.8% of acid butyl ester, cellulose or derivatives thereof gross weight.
It is further preferred that the initiator is at least one of ammonium persulfate, potassium peroxydisulfate and sodium peroxydisulfate；It is described
The consumption of initiator is methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose
Or derivatives thereof gross weight 1-3%.
Preferably, polymerisation is carried out under gradient temperature in step (2), reaction 1-1.5 hours at 65-73 DEG C, so
After reaction 2-3 hours at 75-80 DEG C.
Preferably, a kind of method for preparing hypotonicity Sustained release coating materials, it is comprised the following steps that：
(1) according to above-mentioned weight proportion, make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester,
Butyl methacrylate is mixed with neopelex, polysorbas20, purified water, 50-60 DEG C is warming up to, under agitation to it
The ammonium sulfate that middle dropwise addition purified water dissolves, continues to react 3-4 hours, wherein it is 1-2 hours that the time used in ammonium sulfate, which is added dropwise,；
(2) according to above-mentioned weight proportion, cellulose or derivatives thereof is added, reaction 1-1.5 hours at 65-73 DEG C, then
In being reacted 2-3 hours at 75-80 DEG C, room temperature is subsequently cooled to, is got product.
In step (1), monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and methacrylic acid
Butyl ester is in the presence of initiator, at relatively low temperature (40-60 DEG C), the less oligomer of molecular weight is formed, in step (2)
In, in the presence of high temperature (65-80 DEG C), above-mentioned oligomer continues to polymerize, while wrapping cellulose of addition or derivatives thereof
Wrap up in or through wherein.Compared with prior art, the application has the advantages that：
(1) Sustained release coating materials provided herein, to the pH value no dependence of environment, level of residual monomers is low, is coated
Fluid viscosity is low, and polymer content is high.Make cellulose or derivatives thereof with acrylic resin mutually through parcel, by using difference
Cellulose of species or derivatives thereof, on the one hand enriches the species of coating material, on the other hand according to cellulose or its derivative
The dissolubility of thing and the difference of consumption, can be made the coating material of different penetrating powers.
(2) level of residual monomers is low in coating solution made from the coating material provided as the application, and viscosity is small, coating membrane film forming
Property it is good, coating membrane glossiness is high.
(3) the potassium chloride tablets sustained release tablets after the coating material coating provided by the embodiment of the present application 2 are in different environments
Preferable sustained release performance is respectively provided with (water, gastric juice, intestinal juice).
Embodiment
The present invention is further elaborated with reference to embodiment.These embodiments are only in order at purpose of explanation,
And do not limit the scope of the invention and essence.Each assay method in the embodiment of the present application, such as viscosity, residual monomer content, coating
Polymer solids content etc. in liquid, using this area conventional technical means.
Embodiment 1
A kind of hypotonicity Sustained release coating materials, it is mainly made up of following raw material：Methyl methacrylate 1kg, first
Base acrylic acid chlorination dimethylamino ethyl ester 0.5kg, butyl methacrylate 0.8kg, HPMC 0.03kg, dodecane
Base benzene sulfonic acid sodium salt 0.02kg, polysorbate60 0.05kg, ammonium persulfate 0.7kg, purified water 7.5kg.
Wherein, the method for preparing above-mentioned Sustained release coating materials is comprised the following steps that：
(1) make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and butyl methacrylate in
It polymerize at 40-60 DEG C；
(2) HPMC is added, continues at 65-80 DEG C and polymerize, be subsequently cooled to room temperature, get product.
Embodiment 2
A kind of hypotonicity Sustained release coating materials, it is mainly made up of following raw material：Methyl methacrylate 1kg, first
Base acrylic acid chlorination dimethylamino ethyl ester 0.52kg, butyl methacrylate 1.1kg, ethyl cellulose 0.03kg, dodecyl
Benzene sulfonic acid sodium salt 6.63g, polysorbas20 1.33g, ammonium persulfate 0.036kg, purified water 8.745kg.
Wherein, the method for preparing above-mentioned Sustained release coating materials is comprised the following steps that：
(1) monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate and ten are made
Dialkyl benzene sulfonic acids sodium, polysorbas20, purified water mixing, are warming up to 60 DEG C, ammonium persulfate aqueous solution are added dropwise thereto under agitation,
Continue to react 2 hours；
(2) ethyl cellulose is added, reaction 1 hour at 65 DEG C is then heated to, then in reaction 2 hours at 80 DEG C, instead
Room temperature is cooled to after should terminating, is got product.
Embodiment 3
A kind of hypotonicity Sustained release coating materials, it is mainly made up of following raw material：Methyl methacrylate 1kg, first
Base acrylic acid chlorination dimethylamino ethyl ester 1kg, butyl methacrylate 1.5kg, cellulose acetate 0.05kg, glycerine stearic acid ester
0.0284kg, potassium peroxydisulfate 0.1065kg, purified water 17.75kg.
Wherein, the method for preparing above-mentioned Sustained release coating materials is comprised the following steps that：
(1) make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and butyl methacrylate and
Glycerine stearic acid ester, purified water mixing, are warming up to 60 DEG C, persulfate aqueous solution are added dropwise thereto under agitation, continue to react 2
Hour；
(2) cellulose acetate is added, reaction 1 hour at 65 DEG C is then heated to, then in reaction 3 hours at 80 DEG C, instead
Room temperature is cooled to after should terminating, is got product.
Embodiment 4
A kind of hypotonicity Sustained release coating materials, it is mainly made up of following raw material：Methyl methacrylate 1kg, first
Base acrylic acid chlorination dimethylamino ethyl ester 1kg, butyl methacrylate 1.5kg, methylcellulose 0.03kg, detergent alkylate sulphur
Sour sodium 0.02kg, potassium peroxydisulfate 0.0258kg, purified water 11.36kg.
Wherein, the method for preparing above-mentioned Sustained release coating materials is comprised the following steps that：
(1) monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate and ten are made
Dialkyl benzene sulfonic acids sodium, purified water mixing, are warming up to 40 DEG C, persulfate aqueous solution are added dropwise thereto under agitation, continue anti-
Answer 5 hours；
(2) methylcellulose is added, then heats at 78 DEG C and reacts 4 hours, reaction is cooled to room temperature after terminating, and produces
Finished product.
Embodiment 5
A kind of hypotonicity Sustained release coating materials, it is mainly made up of following raw material：Methyl methacrylate 1kg, first
Base acrylic acid chlorination dimethylamino ethyl ester 1kg, butyl methacrylate 1.5kg, HP-55 0.03kg, nonyl
Phenol polyethenoxy ether 0.014kg, polysorbate60 0.014kg, potassium peroxydisulfate 0.1kg, purified water 11.36kg.
Wherein, the method for preparing above-mentioned Sustained release coating materials is comprised the following steps that：
(1) monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, nonyl are made
Base phenol polyethenoxy ether, polysorbate60, purified water mixing, are warming up to 50 DEG C, persulfate aqueous solution are added dropwise thereto under agitation,
Continue to react 3 hours；
(2) HP-55 is added, is warming up at 60 DEG C and reacts 2 hours, it is then small in reaction 2 at 80 DEG C
When, reaction is cooled to room temperature after terminating, and gets product.
Comparative example 1
A kind of permeability Sustained release coating materials, it is mainly by ethyl acrylate, methyl methacrylate, methacrylic acid chlorine
Change the terpolymer of trimethylamine groups ethyl ester, using azo-bis-iso-dimethyl as initiator, using ethanol as solvent, copolymerization system
；Described ethyl acrylate, methyl methacrylate, methacrylic acid trimethyl ammonium chloride base ethyl ester, the isobutyric acid two of azo two
The weight proportion of methyl esters and ethanol is 1：1.688：0.202：0.0256：1.369.
Wherein, the method for preparing above-mentioned Sustained release coating materials is comprised the following steps that：
(1) ethyl acrylate, methyl methacrylate, methacrylic acid trimethyl ammonium chloride base second are taken by the weight proportion
In ester and azo-bis-iso-dimethyl and ethanol input reactor, maintained 2 hours when being warming up to 52 DEG C, complete the first stage
Polymerization；67 DEG C are warming up to again, continues to react 2 hours, until polymerization is completed；
(2) heat up 80 DEG C concentration, steam ethanol be input amount 45% when, stop concentration, while hot discharge, be molded, then
Dry, crush, be i.e. finished product.
It is coated experiment
(totally 5 groups, every group 20) of potassium chloride piece is wrapped with made from embodiment 2-5 and comparative example 1 (referred to as contrast 1)
Clothing material is coated experiment, wherein, coating material made from embodiment 2-5 and other auxiliary material (such as antiplastering aid talcums in formula
Powder) weight proportion such as table 1 below.
The weight proportion of each composition in the coating solution of table 1
Coating process is specific as follows：(1) coating material made from embodiment 2-5 and contrast 1 is added water about 1680g, stirred evenly；
(2) talcum powder is added in remaining 1410g water；Defoamer is added, is fully homogenized with refiner 10 minutes, into mixed
Suspension；
(3) above suspension is slowly poured into permeability Sustained release coating materials aqueous dispersion, mixes slowly uniformly, will match somebody with somebody
The coating solution obtained is through 40 mesh screens.
(4) with equipment such as coating pan, peristaltic pump, spray guns, nozzle is grasped with storeroom away from 120mm, intake 7.3-
9.5m3/ min, 30 DEG C of EAT, spray air pressure 2bar, infusion rate 45g/min, do after discharging in 40 DEG C of baking ovens
Dry 24 hours.
1.1 technical indicators are determined
It is residual that the coating material that measure embodiment 2-5 and contrast 1 are provided is formulated the viscosity of obtained coating solution, monomer by table 1
Allowance, polymer content, measurement result such as table 2 below.
The technical indicator of each coating solution of table 2
1.2 coating quality
If table 3 below is the potassium chloride tablets after the coating solution that the coating material as made from embodiment 2-5 and contrast 1 is made is coated
The statistic of attribute situation of sustained release tablets.
The quality of forming film and coating quality of potassium chloride tablets sustained release tablets after table 3 is coated
| Quality of forming film and coating quality | |
| Embodiment 2 | Good film-forming property, is coated good luster |
| Embodiment 3 | Good film-forming property, is coated good luster |
| Embodiment 4 | Good film-forming property, is coated good luster |
| Embodiment 5 | Good film-forming property, is coated good luster |
| Contrast 1 | Good film-forming property, is coated gloss slightly worse |
1.3 drug release determinations are tested
Coating solution is made in coating material made from embodiment 2, through its obtained modified-release tablets of potassium chloride of coating by《Middle traditional Chinese medicines
Allusion quotation》Method is measured to release specified in 2010, measurement result such as table 4 below.
The drug release determination result of modified-release tablets of potassium chloride after the coating of table 4
As can be seen from Table 4, the modified-release tablets of potassium chloride after the coating solution coating that the coating material provided by embodiment 2 is made
Preferable release performance is respectively provided with different environment, the average cumulative burst size in water can reach 90%.
Only illustratively, the scope of the present invention is not limited thereto above-mentioned example.To those skilled in the art
For modify be it will be apparent that the present invention only limited by scope.
Claims (13)
1. a kind of hypotonicity Sustained release coating materials, it is characterised in that it is made up of following raw material：Methyl methacrylate, first
Base acrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or derivatives thereof；
Wherein, methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or its
The weight proportion of derivative is：1:（0.5-1）:（0.8-1.5）:(0.03-0.05)；
The cellulose is ethyl cellulose, methylcellulose, hydroxyethyl cellulose or HPMC；The cellulose
Derivative be cellulose acetate, HP-55 or hydroxypropyl methylcellulose acetate succinate；
The method for preparing described coating material, it is comprised the following steps that：
（1）Make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and the methyl-prop of above-mentioned weight proportion
Olefin(e) acid butyl ester is in 40-60oIt polymerize under C；
（2）Cellulose or derivatives thereof is added according to above-mentioned weight proportion, 65-80 is continued atoIt polymerize under C, is subsequently cooled to room
Temperature, gets product.
2. coating material according to claim 1, wherein, the raw material of the Sustained release coating materials, which is made, also includes emulsification
Agent, the emulsifying agent be neopelex, NPE, glycerine stearic acid ester, polysorbas20, polysorbate40 and
At least one of polysorbate60.
3. coating material according to claim 2, the consumption of the emulsifying agent is methyl methacrylate, methacrylic acid
The 0.3-0.8% of chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or derivatives thereof gross weight.
4. coating material according to claim 2, wherein, the raw material of the Sustained release coating materials, which is made, also to be included triggering
Agent, the initiator is at least one of ammonium persulfate, potassium peroxydisulfate and sodium peroxydisulfate.
5. coating material according to claim 4, the consumption of the initiator is methyl methacrylate, methacrylic acid
The 1-3% of chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or derivatives thereof gross weight.
6. coating material according to claim 4, wherein, the raw material of the Sustained release coating materials, which is made, also includes purifying
Water.
7. coating material according to claim 6, the consumption of the purified water is methyl methacrylate, methacrylic acid
3-5 times of chlorination dimethylamino ethyl ester, butyl methacrylate, cellulose or derivatives thereof gross weight.
8. coating material according to claim 1, it is mainly made up of following raw material：Methyl methacrylate：Methyl
Acrylic acid chlorination dimethylamino ethyl ester：Butyl methacrylate：Ethyl cellulose=1:（0.5-0.66）：（1-1.25）：0.03.
9. coating material according to claim 8, the raw material of the Sustained release coating materials, which is made, also includes emulsifying agent 12
Sodium alkyl benzene sulfonate and polysorbas20, its consumption are methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, methyl-prop
The 0.3-0.4% of olefin(e) acid butyl ester, ethyl cellulose gross weight；The raw material of the Sustained release coating materials, which is made, also includes initiator mistake
Ammonium sulfate, its consumption is methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, ethyl
The 1.125-1.5% of cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes purified water, and its consumption is methyl methacrylate, methacrylic acid
Chlorination dimethylamino ethyl ester, butyl methacrylate, 3.2-3.5 times of ethyl cellulose gross weight.
10. coating material according to claim 9, it is mainly made up of following raw material：
Methyl methacrylate：Methacrylic acid chlorination dimethylamino ethyl ester：Butyl methacrylate：Ethyl cellulose=1:
0.52:1.1:0.03；
The raw material of the Sustained release coating materials, which is made, also includes emulsifying agent neopelex and polysorbas20, wherein dodecane
The weight ratio of base benzene sulfonic acid sodium salt and polysorbas20 is 5:1, the gross weight of the two accounts for methyl methacrylate, methacrylic acid chlorination three
Methylamino ethyl ester, butyl methacrylate, the 0.3% of ethyl cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes initiator ammonium persulfate, and its consumption is methyl methacrylate, first
Base acrylic acid chlorination dimethylamino ethyl ester, butyl methacrylate, the 1.35% of ethyl cellulose gross weight；
The raw material of the Sustained release coating materials, which is made, also includes purified water, and its consumption is methyl methacrylate, methacrylic acid
Chlorination dimethylamino ethyl ester, butyl methacrylate, 3.3 times of ethyl cellulose gross weight.
11. a kind of prepare such as the method for the coating material according to any one of claim 1-10, it is comprised the following steps that：
（1）Make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester and the methyl-prop of above-mentioned weight proportion
Olefin(e) acid butyl ester is in 40-60oIt polymerize under C；
（2）Cellulose or derivatives thereof is added according to above-mentioned weight proportion, 65-80 is continued atoIt polymerize under C, is subsequently cooled to room
Temperature, gets product.
12. method according to claim 11, step（1）The concrete operations of middle polymerisation are：
According to above-mentioned weight proportion, make monomers methyl methacrylate, methacrylic acid chlorination dimethylamino ethyl ester, metering system
Acid butyl ester is mixed with emulsifying agent, purified water, is warming up to 40-60oC, the initiation that dropwise addition purified water dissolves thereto under agitation
Agent, continues to react 2-5 hours.
13. method according to claim 12, it is 0.8-2 hours that the time used in the initiator solution, which is added dropwise,；
The emulsifying agent is neopelex, NPE, glycerine stearic acid ester, polysorbas20, polysorbate40
At least one of with polysorbate60.
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