CN107722202A - The preparation method and application of polyvinylpyrrolidone polyvinyl acetate ester block copolymer - Google Patents
The preparation method and application of polyvinylpyrrolidone polyvinyl acetate ester block copolymer Download PDFInfo
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- CN107722202A CN107722202A CN201711076879.8A CN201711076879A CN107722202A CN 107722202 A CN107722202 A CN 107722202A CN 201711076879 A CN201711076879 A CN 201711076879A CN 107722202 A CN107722202 A CN 107722202A
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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
- C08F293/00—Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule
- C08F293/005—Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent
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- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/38—Polymerisation using regulators, e.g. chain terminating agents, e.g. telomerisation
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- C08F218/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an acyloxy radical of a saturated carboxylic acid, of carbonic acid or of a haloformic acid
- C08F218/02—Esters of monocarboxylic acids
- C08F218/04—Vinyl esters
- C08F218/08—Vinyl acetate
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
- C08F226/10—N-Vinyl-pyrrolidone
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Abstract
The invention provides a kind of preparation method and application of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, it is related to block copolymer technical field, comprises the following steps：(a) azo-initiator, chain-transferring agent and NVP monomer are mixed, carries out polymerisation, obtain polyvinylpyrrolidone starting block thing；(b) vinyl acetate monomer and the azo-initiator of surplus are added in polyvinylpyrrolidone originates block thing, carry out chain propagation reaction, obtain polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, it is random to alleviate the Kollidon VA64 structure being prepared using conventional free radical polymerization methodses, and the technical problem that molecular weight distribution is very wide, polyvinylpyrrolidone-polyvinyl acetate block copolymer structure-controllable is reached, weight average molecular weight is 30,000-9 ten thousand, molecular weight distribution index is the technique effect that 1.5-2.0 disclosure satisfy that drug delivery system requirement.
Description
Technical field
The present invention relates to block copolymer technical field, more particularly, to a kind of polyvinylpyrrolidone-polyvinyl acetate
The preparation method and application of ester block copolymer.
Background technology
Amphiphilic block copolymer due to simultaneously there is hydrophilic segment and hydrophobic patch can be self-assembled into different structures, than
Such as spherical particle, cylindrical particulate, vermiform particulate or vesica shape particulate, for drug delivery system.Both sexes block is total to
Polymers is polymerized by hydrophilic polymer monomer and hydrophobic polymer monomer, and polyvinylpyrrolidone has hydrophily, nontoxicity
And biocompatibility, it is widely used as hydrophilic block thing and is used for pharmaceutical field, and polyvinyl acetate is also often as hydrophobic
Property block thing is used for drug delivery, and the synthesis of traditional polyvinylpyrrolidone-polyvinyl acetate uses radical polymerization
Conjunction mode, it is (VAc) raw material with vinyl pyrrolidone (NVP) and vinyl acetate, is made random under the initiation of initiator
Copolymer, this random copolymer medium vinyl pyrrolidones and vinyl acetate fragment are in irregular alignment, and copolymer
Very wide (the M of molecular weight distributionw/Mn), the requirement of drug delivery system can not be met.
In view of this, it is special to propose the present invention.
The content of the invention
An object of the present invention is to provide with a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer
Preparation method, to alleviate the polyvinylpyrrolidone-polyvinyl acetate being prepared using conventional free radical polymerization methodses
In copolymer, vinyl pyrrolidone and vinyl acetate fragment are in irregular alignment, and molecular weight of copolymer distribution is very wide
(Mw/Mn), the technical problem of the requirement of drug delivery system can not be met.
The preparation method of polyvinylpyrrolidone provided by the invention-polyvinyl acetate ester block copolymer, including it is as follows
Step：
(a) azo-initiator, chain-transferring agent and NVP monomer are mixed, carries out polymerisation, obtain
Block thing is originated to polyvinylpyrrolidone；
(b) vinyl alcohol monomer and the azo-initiator of surplus are added in polyvinylpyrrolidone originates block thing, entered
Row chain propagation reaction, obtains polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, and the polyvinylpyrrolidone-
The M of polyvinyl acetate ester block copolymerwFor 30,000-9 ten thousand, preferably 40,000-6 ten thousand, PDI 1.5-2.0.
Further, the chain tra nsfer initiator is selected from S- (2- cyanoisopropyls)-O- ethoxy-dithioformic acids ester, S-
Benzyl-O- ethoxy-dithioformic acids ester, S- (α-methylbenzyl)-O- ethoxy-dithioformic acids ester, the S- tert-butyl group-O- ethyls are yellow
At least one of ortho esters, S- isopropyl-O- ethoxy-dithioformic acid esters.
Further, the azo-initiator is azodiisobutyronitrile, ABVN or azo diisobutyl amidine.
Further, the mass ratio of PVP starting block thing and vinyl acetate monomer is (1-5)：
(5-1).
Further, the mol ratio of NVP monomer and chain-transferring agent is 1000：(4-8).
Further, in step (a), the mol ratio of NVP monomer and azo-initiator is
1000：(0.8-1.2).
Further, in step (a), azo-initiator, chain-transferring agent and NVP monomer are lazy
Property gas shield under carry out polymerisation, and polymeric reaction temperature is 55-65 DEG C, and polymerization reaction time is 4-6 hours, preferably
For 5 hours.
Further, in step (b), polyvinylpyrrolidone starting block thing is protected with vinyl alcohol monomer in inert gas
Shield is lower to carry out chain propagation reaction, and reaction temperature is 55-65 DEG C, and polymerization reaction time is 3.5-4.5 hours, preferably 4 hours.
Further, the one kind of inert gas in nitrogen, helium or argon gas.
The second object of the present invention is to provide above-mentioned polyvinylpyrrolidone-polyvinyl acetate ester block copolymer
The application of polyvinylpyrrolidone made from preparation method-polyvinyl acetate ester block copolymer, to alleviate using tradition freely
In the Kollidon VA64 that base polymerization methodses are prepared, vinyl pyrrolidone and acetic acid
Vinyl acetate fragment is in irregular alignment, and molecular weight of copolymer is distributed very wide (Mw/Mn), drug delivery system can not be met
It is required that technical problem.
The polyvinyl pyrrole that the preparation method of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer is prepared
Application of the alkanone-polyvinyl acetate ester block copolymer in drug delivery system.
The preparation method of polyvinylpyrrolidone provided by the invention-polyvinyl acetate ester block copolymer, passes through first
Step obtains having chain-transferring agent end group functional first by N- vinylpyrrolidones in the presence of initiator and chain-transferring agent
Block (PVP blocks) is originated, second step adds vinyl acetate monomer and the azo of surplus in starting block (PVP blocks)
Class initiator, chain propagation reaction is carried out, polyvinyl acetate (PVAc) block is introduced, obtains polyvinylpyrrolidone-poly- second
Vinyl acetate block copolymer so that the structure of copolymer can in polyvinylpyrrolidone-polyvinyl acetate ester block copolymer
Control, narrow molecular weight distribution, PDI 1.5-2.0, disclosure satisfy that the requirement of drug delivery system.
Embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the present invention.It is unreceipted specific in embodiment
Condition person, the condition suggested according to normal condition or manufacturer are carried out.Agents useful for same or the unreceipted production firm person of instrument, it is
The conventional products that can be obtained by commercially available purchase.
According to an aspect of the present invention, the invention provides a kind of polyvinylpyrrolidone-polyvinyl acetate block
The preparation method of copolymer, comprises the following steps：
(a) azo-initiator, chain-transferring agent and NVP monomer are mixed, carries out polymerisation, obtain
Block thing is originated to polyvinylpyrrolidone；
(b) azo that vinyl acetate monomer and surplus are added in polyvinylpyrrolidone originates block thing triggers
Agent, chain propagation reaction is carried out, obtains polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, the polyvinylpyrrolidine
The M of ketone-polyvinyl acetate ester block copolymerwFor 30,000-9 ten thousand, preferably 40,000-6 ten thousand, PDI 1.5-2.0.
The preparation method of polyvinylpyrrolidone provided by the invention-polyvinyl acetate ester block copolymer, passes through first
Step obtains making end group functional with chain-transferring agent first by N- vinylpyrrolidones in the presence of initiator and chain-transferring agent
Starting block (PVP blocks), second step adds vinyl acetate monomer and surplus in starting block (PVP blocks)
Azo-initiator, carry out chain propagation reaction, by polyvinyl acetate (PVAc) block introduce, obtain polyvinylpyrrolidone-
Polyvinyl acetate ester block copolymer so that the knot of copolymer in polyvinylpyrrolidone-polyvinyl acetate ester block copolymer
Structure is controllable, narrow molecular weight distribution, PDI 1.5-2.0, disclosure satisfy that the requirement of drug delivery system.
Gather made from the preparation method of polyvinylpyrrolidone provided by the invention-polyvinyl acetate ester block copolymer
The typical but non-limiting mass fraction of the molecular weight of vinylpyrrolidone-polyvinyl acetate is as being 30,000,3.2 ten thousand, 3.4
Ten thousandth, 3.6 ten thousand, 3.8 ten thousand, 40,000,4.2 ten thousand, 4.4 ten thousand, 4.6 ten thousand, 4.8 ten thousand, 50,000,5.2 ten thousand, 5.4 ten thousand, 5.6 ten thousand, 5.8 ten thousand, 60,000,
6.2 ten thousand, 6.4 ten thousand, 6.6 ten thousand, 6.8 ten thousand, 70,000,7.2 ten thousand, 7.4 ten thousand, 7.6 ten thousand, 7.8 ten thousand, 80,000,8.2 ten thousand, 8.4 ten thousand, 8.6 ten thousand, 8.8
Ten thousandth, 90,000.
Chain tra nsfer radical reaction is one kind in controllable free-radical polymerisation technology, and it controls polymerization by chain-transferring agent
The degree and molecular weight distribution of reaction, and modifiable functional group can be obtained in the end of the chain, and then continue with another kind of monomer
Polymerization, obtains the block polymer of specific block structure, accomplishes accurately to control copolymer structure so that block copolymer can answer
For in the field higher to structural requirement.
The present invention relates to prepare polyvinylpyrrolidone-polyvinyl acetate ester block copolymer by chain transfer polymerization method
Method, its reaction expression is：
As can be seen that in a preferred embodiment of the invention, chain-transferring agent is selected from S- (2- cyanoisopropyls)-O-
Ethoxy-dithioformic acid ester, S- benzyl-O- ethoxy-dithioformic acids ester, S- (α-methylbenzyl)-O- ethoxy-dithioformic acids ester, uncle S-
At least one of butyl-O- ethoxy-dithioformic acids ester, S- isopropyl-O- ethoxy-dithioformic acid esters.
By being used as chain-transferring agent from xanthic acid esters so that NVP monomer triggers in azo
Under the initiation of agent, the starting block (PVP blocks) with end group functional is first obtained, then vinyl acetate is added in block is originated
Ester monomer carries out chain growth, to introduce polyvinyl acetate (PVAc) block, is accurately controlled so as to obtain structure, molecular weight exists
30000-9 ten thousand, PDI are 1.5-2.0 polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, meet drug delivery system
The requirement of system.
In a preferred embodiment of the invention, azo-initiator is azodiisobutyronitrile, ABVN or idol
Nitrogen diisobutyl amidine.
In a preferred embodiment of the invention, the quality of PVP starting block thing and vinyl alcohol monomer
Than for (1-5)：(5-1).
By the way that the mass ratio of NVP monomer and vinyl alcohol monomer is arranged to (1-5)：(5-1),
So that the molecular weight of obtained Kollidon VA64 is 30,000-9 ten thousand, and polyvinylpyrrolidine
Ratio between the polymerization degree n of ketone and the degree of polymerization m of polyvinyl acetate is (1-7)：(1-4), accurately to control polyethylene
The structure of pyrrolidones-VA, reach the requirement of newtype drug transmission system.
In a preferred embodiment of the invention, the mol ratio of NVP monomer and chain-transferring agent is
1000：(4-8).
When the mol ratio of NVP monomer and chain-transferring agent is 1000：When (4-8), it is generated poly-
The structure control of vinylpyrrolidone starting block thing is more accurate, the subsequently block copolymerization with being generated after vinyl acetate polyisocyanate polyaddition
The molecular weight distribution of thing is narrower.
In a preferred embodiment of the invention, in step (a), NVP monomer draws with azo
The mol ratio for sending out agent is 1000：(0.8-1.2).
When the mol ratio of NVP monomer and azo-initiator is 1000：When (0.8-1.2), its
The rate of polymerization of NVP monomer is fast, and yield is high, obtains polyvinylpyrrolidone-polyvinyl acetate copolymerization
The structure of thing is accurate, narrow molecular weight distribution.
In a preferred embodiment of the invention, in step (a), azo-initiator, chain-transferring agent and N- vinyl
Pyrrolidone monomeric carries out polymerisation under inert gas shielding, and polymeric reaction temperature is 55-65 DEG C, during polymerisation
Between be 4-6 hours, preferably 5 hours.
By using inert gas shielding, to avoid NVP monomer from being oxidized in the course of the polymerization process, lead
Obtained starting block thing (PVP) degree of polymerization heterogeneity is caused, obtained polyvinylpyrrolidone-polyvinyl acetate block is total to
The molecular weight distribution of polymers is wide, or causes polymerisation to fail, and can not meet the requirement of drug delivery system.
In a preferred embodiment of the invention, in step (b), polyvinylpyrrolidone starting block thing and vinyl alcohol list
Body carries out chain propagation reaction under inert gas shielding, and reaction temperature is 55-65 DEG C, and polymerization reaction time is that 3.5-4.5 is small
When, preferably 4 hours
By using inert gas shielding, to avoid polyvinylpyrrolidone starting block thing from existing with vinyl acetate monomer
Be oxidized during chain propagation reaction, the polyvinylpyrrolidone-polyvinyl acetate ester block copolymer for causing to obtain
Molecular weight distribution is wide, can not meet the requirement of drug delivery system.
In a preferred embodiment of the invention, the one kind of inert gas in nitrogen, helium or argon gas.
The preparation method of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer of the present invention is prepared poly-
Vinylpyrrolidone-polyvinyl acetate ester block copolymer disclosure satisfy that drug delivery system accurately needs to structure control,
It can be used in drug delivery system.
Technical scheme provided by the invention is further described with reference to embodiment and comparative example.
Embodiment 1
Present embodiments provide a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method bag
Include following steps：
(a) it is even by NVP monomer 160mol and S- benzyl-O- ethoxy-dithioformic acid ester 0.64mol
The different heptonitrile 0.16mol of nitrogen two is added in three-necked flask, adds absolute ethyl alcohol 40mL, and replaces argon gas three times, and flask is put into water
60 DEG C of stirring reactions are heated in bath, concentrated solvent after reacting 5 hours, then concentrate is added in absolute ether and precipitated
Precipitation obtains polyvinylpyrrolidone starting block thing；
(b) take polyvinylpyrrolidone starting block thing 10g to be dissolved in absolute ethyl alcohol, be made into the poly- second that concentration is 30%
Alkene pyrrolidone solution, vinyl acetate monomer 2g, ABVN 10mg are then added, reaction replaces argon gas three times, instead
Under conditions of 60 DEG C stirring reaction 4 hours, reaction solution Precipitation in absolute ether should be added after concentrating, is filtrated to get poly- second
Alkene pyrrolidone-polyvinyl acetate ester block copolymer.
Embodiment 2
Present embodiments provide a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method bag
Include following steps：
(a) by NVP monomer 160mol and S- (α-methylbenzyl)-O- ethoxy-dithioformic acid esters
1.28mol, azodiisobutyronitrile 0.16mol are added in three-necked flask, add absolute ethyl alcohol 40mL, and replacement of helium is three times, will
Flask, which is put into water-bath, is heated to 60 DEG C of stirring reactions, concentrated solvent after reacting 5 hours, is then added to concentrate anhydrous
Precipitation obtains polyvinylpyrrolidone starting block thing in ether；
(b) take polyvinylpyrrolidone starting block thing 10g to be dissolved in absolute ethyl alcohol, be made into the poly- second that concentration is 30%
Alkene pyrrolidone solution, vinyl acetate monomer 50g, azodiisobutyronitrile 10mg are then added, react replacement of helium three times, instead
Under conditions of 60 DEG C stirring reaction 4 hours, reaction solution Precipitation in absolute ether should be added after concentrating, is filtrated to get poly- second
Alkene pyrrolidone-polyvinyl acetate ester block copolymer.
Embodiment 3
Present embodiments provide a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method bag
Include following steps：
(a) by NVP monomer 160mol and S- (2- cyanoisopropyls)-O- ethoxy-dithioformic acid esters
0.8mol, azodiisobutyronitrile 0.16mol are added in three-necked flask, add absolute ethyl alcohol 40mL, and replace nitrogen three times, will be burnt
Bottle, which is put into water-bath, is heated to 60 DEG C of stirring reactions, concentrated solvent after reacting 5 hours, concentrate then is added into anhydrous second
Precipitation obtains polyvinylpyrrolidone starting block thing in ether；
(b) take polyvinylpyrrolidone starting block thing 10g to be dissolved in absolute ethyl alcohol, be made into the poly- second that concentration is 30%
Alkene pyrrolidone solution, vinyl acetate monomer 6g, azodiisobutyronitrile 10mg are then added, reaction replaces nitrogen three times, instead
Under conditions of 60 DEG C stirring reaction 4 hours, reaction solution Precipitation in absolute ether should be added after concentrating, is filtrated to get poly- second
Alkene pyrrolidone-polyvinyl acetate ester block copolymer.
Embodiment 4
Present embodiments provide a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 3 is, in step (b), the vinyl acetate of addition is 20g.
Embodiment 5
Present embodiments provide a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 3 is, in step (b), the vinyl acetate of addition is 10g.
Comparative example 1
This comparative example provides a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 5 is, in step (b), the vinyl acetate of addition is 80g.
Comparative example 2
This comparative example provides a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 5 is, in step (b), the vinyl acetate of addition is 1g.
Comparative example 3
This comparative example provides a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 5 is, in step (a), NVP monomer and S- (2- cyanoisopropyls)-
The mol ratio of O- ethoxy-dithioformic acid esters is 1000：1.
Comparative example 4
This comparative example provides a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 5 is, in step (a), NVP monomer and S- (2- cyanoisopropyls)-
The mol ratio of O- ethoxy-dithioformic acid esters is 1000：15.
Comparative example 5
This comparative example provides a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 5 is, in step (a), NVP monomer and NVP list
The mol ratio of body and azodiisobutyronitrile is 1000：0.4.
Comparative example 6
This comparative example provides a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, its preparation method with
The difference of embodiment 5 is, in step (a), NVP monomer and NVP list
The mol ratio of body and azodiisobutyronitrile is 1000：2.
The polyvinylpyrrolidone that embodiment 1-5 is provided-polyvinyl acetate ester block copolymer and comparative example 1-6
The polyvinylpyrrolidone of offer-polyvinyl acetate ester block copolymer carries out Mw、Mn, PDI and K values measure, it is as a result as follows
Shown in table：
1 polyvinylpyrrolidone of table-polyvinyl acetate ester block copolymer performance data table
As can be seen from the above table, polyvinylpyrrolidone-polyvinyl acetate ester block copolymer that embodiment 1-5 is provided
Weight average molecular weight be 30,000-9 ten thousand, PDI is that 1.5-2K values are 25-45, its structure-controllable, narrow molecular weight distribution, Neng Gouman
The requirement of sufficient drug delivery system.
It can be seen that only when NVP monomer by embodiment 1-5 and comparative example 1-2 contrast
Mass ratio with vinyl alcohol monomer is (1-5)：When (5-1), obtained polyvinylpyrrolidone-polyvinyl acetate block
The structure-controllable of copolymer, narrow molecular weight distribution, it disclosure satisfy that the requirement of drug delivery system.
It can be seen that only when NVP monomer by embodiment 1-5 and comparative example 3-4 contrast
Mol ratio with chain-transferring agent is 1000：When (4-8), obtained polyvinylpyrrolidone-polyvinyl acetate block copolymerization
Thing structure-controllable degree height and narrow molecular weight distribution, could meet the requirement of drug delivery system.
It can be seen that only when NVP monomer by embodiment 1-5 and comparative example 5-6 contrast
Mol ratio with azo-initiator is 1000：When (0.8-1.2), obtained polyvinylpyrrolidone-polyvinyl acetate
Block copolymer structure degree of controllability height and narrow molecular weight distribution, could meet the requirement of drug delivery system.
Finally it should be noted that：Various embodiments above is merely illustrative of the technical solution of the present invention, rather than its limitations；To the greatest extent
The present invention is described in detail with reference to foregoing embodiments for pipe, it will be understood by those within the art that：Its according to
The technical scheme described in foregoing embodiments can so be modified, either which part or all technical characteristic are entered
Row equivalent substitution；And these modifications or replacement, the essence of appropriate technical solution is departed from various embodiments of the present invention technology
The scope of scheme.
Claims (10)
1. the preparation method of a kind of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, it is characterised in that including as follows
Step：
(a) azo-initiator, chain-transferring agent and NVP monomer are mixed, carries out polymerisation, gathered
Vinylpyrrolidone originates block thing；
(b) vinyl acetate monomer and the azo-initiator of surplus are added in polyvinylpyrrolidone originates block thing, entered
Row chain propagation reaction, obtain polyvinylpyrrolidone-polyvinyl acetate ester block copolymer, the polyvinylpyrrolidone-poly-
The M of vinyl acetate ester block copolymerwFor 30,000-9 ten thousand, preferably 40,000-6 ten thousand, PDI 1.5-2.0.
2. the preparation method of polyvinylpyrrolidone according to claim 1-polyvinyl acetate ester block copolymer, it is special
Sign is that the chain tra nsfer initiator is selected from S- (2- cyanoisopropyls)-O- ethoxy-dithioformic acids ester, S- benzyl-O- ethyl xanthan
Acid esters, S- (α-methylbenzyl)-O- ethoxy-dithioformic acids ester, the S- tert-butyl group-O- ethoxy-dithioformic acids ester, S- isopropyl-O- ethyls are yellow
At least one of ortho esters.
3. the preparation method of polyvinylpyrrolidone according to claim 1-polyvinyl acetate ester block copolymer, it is special
Sign is that the azo-initiator is azodiisobutyronitrile, ABVN or azo diisobutyl amidine.
4. the preparation of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer according to claim any one of 1-3
Method, it is characterised in that it is (1-5) that PVP, which originates block thing and the mass ratio of vinyl acetate monomer,：(5-
1)。
5. the preparation of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer according to claim any one of 1-3
Method, it is characterised in that the mol ratio of NVP monomer and chain-transferring agent is 1000：(4-8).
6. the preparation of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer according to claim any one of 1-3
Method, it is characterised in that in step (a), the mol ratio of NVP monomer and azo-initiator is 1000：
(0.8-1.2)。
7. the preparation of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer according to claim any one of 1-3
Method, it is characterised in that in step (a), azo-initiator, chain-transferring agent and NVP monomer are in inertia
Carrying out polymerisation under gas shield, and polymeric reaction temperature is 55-65 DEG C, polymerization reaction time is 4-6 hours, preferably 5
Hour.
8. the system of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer according to any one of claim 1-3
Preparation Method, it is characterised in that in step (b), polyvinylpyrrolidone starting block thing is with vinyl acetate monomer in indifferent gas
Body protection is lower to carry out chain propagation reaction, and reaction temperature is 55-65 DEG C, and polymerization reaction time is 3.5-4.5 hours, and preferably 4 is small
When.
9. the preparation method of polyvinylpyrrolidone according to claim 7-polyvinyl acetate ester block copolymer, it is special
Sign is, the one kind of inert gas in nitrogen, helium or argon gas.
10. the preparation of polyvinylpyrrolidone-polyvinyl acetate ester block copolymer according to claim any one of 1-8
Application of the polyvinylpyrrolidone that the method is prepared-polyvinyl acetate ester block copolymer in drug delivery system.
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| CN201711076879.8A Pending CN107722202A (en) | 2017-11-06 | 2017-11-06 | The preparation method and application of polyvinylpyrrolidone polyvinyl acetate ester block copolymer |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109384883A (en) * | 2018-10-31 | 2019-02-26 | 焦作中维特品药业股份有限公司 | A kind of preparation method of copolyvidone VA64 |
| CN109679009A (en) * | 2019-01-02 | 2019-04-26 | 黄山邦森新材料有限公司 | A kind of preparation method of 30 POVIDONE K 30 BP/USP 60 |
| CN110787647A (en) * | 2019-11-11 | 2020-02-14 | 上海输血技术有限公司 | Platelet leukocyte-removing filter membrane and preparation method thereof |
| CN113881001A (en) * | 2020-07-02 | 2022-01-04 | 彭之皓 | Block copolymer and process for producing the same |
| CN114306377A (en) * | 2022-01-05 | 2022-04-12 | 成都科宏达科技有限公司 | Copolymer solution and preparation method and application thereof |
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2017
- 2017-11-06 CN CN201711076879.8A patent/CN107722202A/en active Pending
Non-Patent Citations (2)
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| NATHALIE BAILLY ET AL: "Synthesis, Characterization, and Self-Assembly of Poly(N-vinylpyrrolidone)-block-poly(vinyl acetate)", 《AUSTRALIAN JOURNAL OF CHEMISTRY》 * |
| NICK FANDRICH ET AL: "Characterization of New Amphiphilic Block Copolymers of N-Vinyl Pyrrolidone and Vinyl Acetate, 1- Analysis of Copolymer Composition, End Groups, Molar Masses and Molar Mass Distributions", 《MACROMOLECULAR CHEMISTRY AND PHYSICS》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109384883A (en) * | 2018-10-31 | 2019-02-26 | 焦作中维特品药业股份有限公司 | A kind of preparation method of copolyvidone VA64 |
| CN109679009A (en) * | 2019-01-02 | 2019-04-26 | 黄山邦森新材料有限公司 | A kind of preparation method of 30 POVIDONE K 30 BP/USP 60 |
| CN110787647A (en) * | 2019-11-11 | 2020-02-14 | 上海输血技术有限公司 | Platelet leukocyte-removing filter membrane and preparation method thereof |
| CN110787647B (en) * | 2019-11-11 | 2024-01-19 | 上海输血技术有限公司 | Platelet leukocyte-removing filter membrane and preparation method thereof |
| CN113881001A (en) * | 2020-07-02 | 2022-01-04 | 彭之皓 | Block copolymer and process for producing the same |
| CN113881001B (en) * | 2020-07-02 | 2023-11-24 | 彭之皓 | Block copolymer and process for producing the same |
| CN114306377A (en) * | 2022-01-05 | 2022-04-12 | 成都科宏达科技有限公司 | Copolymer solution and preparation method and application thereof |
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