CN103483601A - Preparation method for polymeric nanometer microsphere - Google Patents
Preparation method for polymeric nanometer microsphere Download PDFInfo
- Publication number
- CN103483601A CN103483601A CN201310319385.3A CN201310319385A CN103483601A CN 103483601 A CN103483601 A CN 103483601A CN 201310319385 A CN201310319385 A CN 201310319385A CN 103483601 A CN103483601 A CN 103483601A
- Authority
- CN
- China
- Prior art keywords
- preparation
- microspheres
- monomer
- polymeric
- described step
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- PVRYOKQFLBSILA-UHFFFAOYSA-N CC(c1ccc(C)nc1)=O Chemical compound CC(c1ccc(C)nc1)=O PVRYOKQFLBSILA-UHFFFAOYSA-N 0.000 description 1
- HNTZKNJGAFJMHQ-UHFFFAOYSA-N Cc1ncccc1C(O)=O Chemical compound Cc1ncccc1C(O)=O HNTZKNJGAFJMHQ-UHFFFAOYSA-N 0.000 description 1
Images
Landscapes
- Polymerisation Methods In General (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method for a polymeric nanometer microsphere. The preparation method comprises the following steps: with trithiocarbonate represented by a formula (I) as a chain transferring agent, carrying out RAFT living polymerization to synthesize a gradient copolymer; dissolving the gradient copolymer in an organic solvent and then adding water to form a polymeric micelle solution, wherein the organic solvent and water are intermiscible; and adding the polymeric micelle solution into an aqueous solution of an inorganic salt and carrying out solvent displacement so as to obtain the polymeric nanometer microsphere, wherein a volume ratio of the polymeric micelle solution to the aqueous solution of the inorganic salt is 0.01 to 1. The polymeric nanometer microsphere prepared by using the method has good stability and uniformity, narrow particle size distribution and photoresponse characteristics and the surface of the microsphere is rich in carboxyl groups, thereby facilitating application of the polymeric nanometer microsphere as a good carrier for drugs and proteins. Moreover, the method provided by the invention has the advantages of simpleness, easy practicability, good repeatability, low energy consumption, extensive applicability and easy realization of industrialization.
Description
Technical field
The present invention relates to polymeric material field, particularly the preparation method of polymer nano-microspheres in.
Background technology
Polymer nano-microspheres refers to that size is less than 100nm, the polymer microballoon be evenly distributed.In recent years due to polymer nano-microspheres in the electron device engineering, especially nanosecond medical science is as the using value in the fields such as pharmaceutical carrier, immunodiagnosis for biomedical engineering, its preparation method receives much concern.
By monomer polymerization, be the common means that prepare polymer microballoon.Yet a lot of field of nanosecond medical science general requirement nano microsphere system is not less than 100nm containing small molecular weight impurity and the particle diameter of tensio-active agent and so on.Emulsifier-free emulsion polymerization and precipitation polymerization, because the primary particle poor stability of initial reaction stage easily is combined into macroparticle, therefore are generally used for the mono-dispersion microballoon that preparation size is greater than 100 nanometers.Prepare Nano microsphere although letex polymerization is widely used in, yet unavoidably can contain the complete monomer of unreacted and excessive emulsifying agent in system, aftertreatment is loaded down with trivial details.The Chinese patent that the patent No. is CN101703914A has been announced a kind of improved emulsion polymerisation process, but still unavoidably needs to add tensio-active agent in system.Prepare the related process complexity of the polymer microballoon of narrow dispersion by monomer polymerization in addition and technique is difficult to control.
The U.S. Patent Publication that the patent No. is US005133908A and US005118528A a kind of by synthetic polymkeric substance by dissolving--the technique of nanometer precipitation prepares the method for Nano microsphere.Prepare microballoon by the nanometer precipitator method and do not need to add tensio-active agent, and it is simple for process, energy consumption is low, suitability is wide.In the organic solvent that its preparation process is normally dissolved each other in a polymer dissolution with water, then polymers soln is added to the water and then vapors away organic solvent or polymers soln is dialysed and carried out replacement solvent in water.In the solvent exchange process due to the change of solvent property, thereby the configuration of polymkeric substance is collapsed into by random coil the preparation that a solid bead is realized Nano microsphere.Yet research shows (Soft Matter, 2011,7,1581-1588; Langmuir, 2009,25,1970-1979) owing to lacking enough stability, Nano microsphere prepared by the nanometer precipitator method generally can only exist by a very narrow regional stability in " solvent-precipitation agent-polymkeric substance " ternary phase diagrams.Therefore in preparing the detailed process of Nano microsphere, the nanometer precipitator method need Macrodilution, especially for polystyrene or the polymethylmethacrylate very hydrophobic final solid content very low (being less than 0.1%) of polymkeric substance like this, and distribution of sizes is quite inhomogeneous.
Except the size of Nano microsphere, homogeneity, the functional of Nano microsphere is also a very important aspect.In the bio-medical field, usually need the microsphere surface functionalization, thereby give Nano microsphere some special character, as just can be used for pharmaceutical carrier, biosensor and protein synthesis analysis by microsphere surface is carboxylated.And the design of initiator while to Nano microsphere is surface-functionalized, generally all needing to relate to chemical reaction that surface modification is relevant or polymerization, preparation process is difficult to control, post-processing step is loaded down with trivial details, but only by the nanometer precipitator method, is difficult to again obtain the Nano microsphere of functionalisation of surfaces.
Summary of the invention
The technical problem that the present invention solves is to provide a kind of preparation method of polymer nano-microspheres, the polymer nano-microspheres narrow diameter distribution that the method obtains, good stability and have response characteristics to light.
The invention discloses a kind of preparation method of polymer nano-microspheres, comprise the following steps:
(A) select the trithiocarbonate class shown in formula (I) as chain-transfer agent, by RAFT living polymerization composition gradient multipolymer;
(B) described gradient copolymer is dissolved in organic solvent, then adds water, form polymer micelle solution; Described organic solvent and water dissolve each other;
(C) described polymer micelle solution is joined in the aqueous solution of inorganic salt, by solvent exchange, obtain polymer nano-microspheres; The volume ratio of the aqueous solution of described polymer micelle solution and inorganic salt is 0.01～1;
Wherein, Z is the group of end with carboxyl, and R is leavings group.
Preferably, in described step (A), the monomer of described RAFT living polymerization comprises the first monomer and the second monomer, and described the first monomer is vinylbenzene or its derivative, the compound that the second monomer is esters of acrylic acid, methyl acrylic ester or vinyl pyridine class.
Preferably, in described step (B), one or more in the alcohol that described organic solvent is acetone, C1～C3, the organic acid of C1～C8, tetrahydrofuran (THF), dioxane and DMF.
Preferably, in described step (B), the mass body volume concentrations of described gradient copolymer in organic solvent is 0.01%～5%.
Preferably, in described step (B), in described polymer micelle solution, the quality percentage composition of water is 0.1%～50%.
Preferably, in described step (C), described inorganic salt are sodium bicarbonate, saleratus, sodium carbonate, salt of wormwood, sodium hydroxide, potassium hydroxide, SODIUM PHOSPHATE, MONOBASIC or potassium primary phosphate.
Preferably, in described step (C), the mass percentage concentration of described inorganic salt is 1 * 10
-3～5mmol/L.
Preferably, in described step (C), the mode of described displacement is volatilization or dialysis.
Preferably, in described step (A), described Z be carboxylic propyl group, carboxymethyl, propyloic, carboxylic butyl, phenylformic acid benzyl,
Preferably, in described step (A), described R be benzyl, the tertiary butyl ,-CH
2cN ,-C (CH
3)
2cH
2c (CH
3)
2,
Compared with prior art, the present invention is by the RAFT living polymerization, to be connected to the copolymerization end with the trithiocarbonate class of carboxyl, again in the mixed solvent of organic solvent and water by this copolymer micelle, then copolymer micelle is formed in water to the nanometer precipitation, finally organic solvent is removed, made the carboxyl of multipolymer end all by urging the surface that is connected to Nano microsphere with the trithiocarbonate class of carboxyl, form polymer nano-microspheres.Because carboxyl has electrostatic repulsion, it is distributed in the surface of polymer micelle, therefore, has improved stability and the homogeneity of polymer nano-microspheres, its narrow diameter distribution.Due to a large amount of existence of carboxyl, be conducive to the good carrier of polymer nano-microspheres as medicine and protein.Secondly, due to the surface of polymer nano-microspheres, also with the C-S key, the C-S key can fracture under UV-irradiation, and the stability of polymer nano-microspheres in aqueous dispersion reduces, form precipitation, therefore described polymer nano-microspheres has response characteristics to light to UV-light.The 3rd, the method for the invention does not need to add stablizer, obtains polymer nano-microspheres content in dispersion system higher, and the quality volumn concentration can reach 0.01%～5%, and monodispersity also is better than the conventional nanometer precipitator method.In addition, the method for the invention is simple, reproducible, and energy consumption is low, and suitability is wide, is easy to realize industrialization.
The accompanying drawing explanation
Fig. 1 is the schema that the present invention prepares polymer nano-microspheres;
The scanning electron microscope (SEM) photograph of the polymer nano-microspheres that Fig. 2 is the embodiment of the present invention 1 preparation;
The size distribution figure of the polymer nano-microspheres that Fig. 3 is the embodiment of the present invention 1 preparation;
The photoresponse figure that Fig. 4 is the polymer nano-microspheres of preparation in the embodiment of the present invention 3.
Embodiment
In order further to understand the present invention, below in conjunction with embodiment, the preferred embodiment of the invention is described, but should be appreciated that these are described is for further illustrating the features and advantages of the present invention, rather than limiting to the claimed invention.
The embodiment of the invention discloses a kind of preparation method of polymer nano-microspheres, comprise the following steps:
(A) select the trithiocarbonic acid ester compound shown in formula (I) as chain-transfer agent, by RAFT living polymerization composition gradient multipolymer;
(B) described gradient copolymer is dissolved in organic solvent, then adds water, form polymer micelle solution; Described organic solvent and water dissolve each other;
(C) described polymer micelle solution is joined in the aqueous solution of inorganic salt, by solvent exchange, obtain polymer nano-microspheres; The volume ratio of the aqueous solution of described polymer micelle solution and inorganic salt is 0.01～1;
Wherein, Z is the group of end with carboxyl, and R is leavings group.
The present invention takes full advantage of the convenience of reversible addition-fracture chain transfer polymerization (RAFT) reaction, carboxyl is introduced to the end of gradient copolymer, again in the mixed solvent of organic solvent and water by this copolymer micelle, then copolymer micelle is formed in water to the nanometer precipitation, finally organic solvent is removed, make the carboxyl of multipolymer end all by the trithiocarbonate class with carboxyl, be connected to the surface of Nano microsphere, the aqueous dispersion of the polymer nano-microspheres obtained.Described polymer nano-microspheres is the polymer nano-microspheres of a kind of photoresponse and functionalisation of surfaces.Detailed process is referring to Fig. 1, and Fig. 1 is the schema that the present invention prepares polymer nano-microspheres.
In the present invention, at first select the trithiocarbonate class shown in formula (I) as chain-transfer agent, by RAFT living polymerization composition gradient multipolymer.The monomer of described RAFT living polymerization comprises the first monomer and the second monomer, described the first monomer is preferably the vinylbenzene or derivatives thereof, vinylbenzene more preferably, the second monomer is preferably acrylate, the compound of methacrylic ester or vinyl pyridine class, vinylformic acid more preferably, methyl acrylate, ethyl propenoate, n-butyl acrylate, isobutyl acrylate, sec-butyl acrylate, the vinylformic acid n-propyl, cyclohexyl acrylate, 2-Hydroxy ethyl acrylate, 2-hydroxypropyl acrylate, methacrylic acid, methyl methacrylate, β-dimethyl-aminoethylmethacrylate, n-BMA, Propenoic acid, 2-methyl, isobutyl ester, the secondary butyl ester of methacrylic acid, n propyl methacrylate, 2-vinyl pyridine or 4-vinylpridine, most preferably be methyl acrylate, butyl methacrylate or 4-vinylpridine.Described the first monomer and the second monomer can arbitrary combination, by the RAFT living polymerization, obtain gradient copolymer.The present invention is not particularly limited the condition of described RAFT living polymerization, according to condition well known to those skilled in the art, gets final product, can thermal initiation or initiator initiation.The described trithiocarbonate class of described formula (I) is chain-transfer agent, i.e. RAFT reagent.Described in formula (I), Z is the group of end with carboxyl, be preferably carboxylic propyl group, carboxymethyl, propyloic, carboxylic butyl, phenylformic acid benzyl,
described R is leavings group, the group that with the S atom, is connected, can sloughs through the RAFT living polymerization, be preferably benzyl, the tertiary butyl ,-CH
2cN ,-C (CH
3)
2cH
2c (CH
3)
2,
Described RAFT living polymerization composition gradient multipolymer is one kettle way, and technique is simple, more economically.Through the RAFT living polymerization, the part of trithiocarbonate class except leavings group shown in formula I all is connected to the gradient copolymer end, makes the gradient copolymer end with carboxyl and C-S key.
In the present invention, after obtaining described gradient copolymer, described gradient copolymer is dissolved in organic solvent, then adds water, form polymer micelle solution.Due to the end of gradient copolymer, with carboxyl, carboxyl has wetting ability and electrostatic repulsion, and therefore, in the process that forms micella, carboxyl is distributed in the surface of polymer micelle.Described organic solvent and water dissolve each other, be preferably the alcohol of acetone, C1～C3, organic acid, tetrahydrofuran (THF), dioxane and the N of C1～C8, one or more in dinethylformamide, one or more in acetone, ethanol, acetic acid, tetrahydrofuran (THF), dioxane and DMF more preferably.The mass body volume concentrations of described gradient copolymer in organic solvent is preferably 0.01%～5%, and more preferably 0.5%～2%.In described polymer micelle solution, the quality percentage composition of water is preferably 0.1%～50%, and more preferably 5%～20%.
In the present invention, after obtaining polymer micelle, described polymer micelle solution is joined in the aqueous solution of inorganic salt, by solvent exchange, obtain polymer nano-microspheres.The volume ratio of the aqueous solution of described polymer micelle solution and inorganic salt is 0.01～1, is preferably 0.5～0.9.By solvent exchange, polymer micelle constantly shrinks the formation microballoon, forms the aqueous dispersion that contains polymer nano-microspheres in containing the aqueous solution of inorganic salt.In described aqueous dispersion, the quality volumn concentration of polymer nano-microspheres is preferably 0.01%～5%.Described inorganic salt are preferably sodium bicarbonate, saleratus, sodium carbonate, salt of wormwood, sodium hydroxide, potassium hydroxide, SODIUM PHOSPHATE, MONOBASIC or potassium primary phosphate.The mass percentage concentration of described inorganic salt is preferably 1 * 10
-3～5mmol/L.The mode of described displacement is preferably volatilization or dialysis, more preferably volatilization.
The polymer nano-microspheres obtained is detected, and its particle diameter is 20～80nm, dispersion coefficient PD.I<0.1.
Utilize UV-light to detect the response characteristics to light of described polymer nano-microspheres, in 254～365nm UV-irradiation, after 5～7 minutes, described polymer nano-microspheres gets off from good dispersion state flocculating settling.
The present invention, by the RAFT living polymerization, will be connected to the copolymerization end with the trithiocarbonate class of carboxyl, then by the nanometer precipitator method, form polymer nano-microspheres.Because carboxyl has electrostatic repulsion, it is distributed in the surface of polymer micelle, therefore, has improved stability and the homogeneity of polymer nano-microspheres, its narrow diameter distribution.Due to a large amount of existence of carboxyl, be conducive to the good carrier of polymer nano-microspheres as medicine and protein.Secondly, due to the surface of polymer nano-microspheres, also with the C-S key, the C-S key can fracture under UV-irradiation, and the stability of polymer nano-microspheres in aqueous dispersion reduces, form precipitation, therefore described polymer nano-microspheres has response characteristics to light to UV-light.The 3rd, the method for the invention does not need to add stablizer, obtains polymer nano-microspheres content in dispersion system higher, and the quality volumn concentration can reach 0.01%～5%, and monodispersity also is better than the conventional nanometer precipitator method.In addition, the method for the invention is simple, reproducible, and energy consumption is low, and suitability is wide, is easy to realize industrialization.
In order further to understand the present invention, below in conjunction with embodiment, the preparation method of polymer nano-microspheres provided by the invention is described, protection scope of the present invention is not limited by the following examples.
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent S-1-carboxylic propyl group-S '-benzyl trithiocarbonate, monomer and RAFT reagent mol ratio are 300:1, would you please clear and definite be which kind of catalyzer stirring and dissolving once after, reactor is heated to 120 ° of C, react after 12 hours, with syringe pump, the methyl methacrylate of 2.5 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 14 hours.Within first 6 hours, at the uniform velocity inject 8% of methyl methacrylate total amount, then by the instantaneous injection of 65% methyl methacrylate, within last 8 hours, at the uniform velocity inject 27% methyl methacrylate, after reaction finishes room temperature coolingly separate out, purified polymer.By nucleus magnetic hydrogen spectrum (
1h NMR) and gel permeation chromatography (GPC) gradient copolymer is characterized.The final molecular weight of polymkeric substance is 4.7 ten thousand, and molecular weight distribution is 1.38, and methyl methacrylate content is 43%.
The synthetic styrene/methacrylic acid methyl esters gradient copolymer obtained is dissolved in acetone, and concentration is 0.5%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 8%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 2mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.By scanning electron microscope (SEM) and dynamic light scattering (DLS), this microballoon is characterized.
The scanning electron microscope (SEM) photograph of the polymer nano-microspheres that Fig. 2 is the embodiment of the present invention 1 preparation, can see the Nano microsphere of regular spherical morphology in the SEM image in Fig. 2.
The size distribution figure of the polymer nano-microspheres that Fig. 3 is the embodiment of the present invention 1 preparation, this Nano microsphere size uniform of DLS digital proof in Fig. 3, polydispersity index PD.I=0.011, mean diameter is 45nm.
Embodiment 2
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent S-1-carboxylic propyl group-S '-benzyl trithiocarbonate, monomer and RAFT reagent mol ratio are 300:1, after stirring and dissolving, reactor is heated to 120 ° of C, react after 12 hours, with syringe pump, the methyl methacrylate of 2.5 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 14 hours.Within first 6 hours, at the uniform velocity inject 8% of methyl methacrylate total amount, then by the instantaneous injection of 65% methyl methacrylate, within last 8 hours, at the uniform velocity inject 27% methyl methacrylate, after reaction finishes room temperature coolingly separate out, purifying, obtain the gradient copolymer thing.
Described gradient copolymer is dissolved in tetrahydrofuran (THF), and concentration is 0.5%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 10%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 2mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until tetrahydrofuran (THF) volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Dynamic light scattering (DLS) result shows that this microballoon mean diameter is 47nm, polydispersity index PD.I=0.055, and dimensional homogeneity is good.
Embodiment 3
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent S-1-carboxylic propyl group-S '-benzyl trithiocarbonate, monomer and RAFT reagent mol ratio are 300:1, after stirring and dissolving, reactor is heated to 120 ° of C, react after 12 hours, with syringe pump, the methyl methacrylate of 2.5 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 14 hours.Within first 6 hours, at the uniform velocity inject 8% of methyl methacrylate total amount, then by the instantaneous injection of 65% methyl methacrylate, within last 8 hours, at the uniform velocity inject 27% methyl methacrylate, after reaction finishes room temperature coolingly separate out, purifying, obtain the gradient copolymer thing.
Described gradient copolymer is dissolved in acetone, and concentration is 1.5%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 6%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 20mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Dynamic light scattering (DLS) result shows that this microballoon mean diameter is 53nm, polydispersity index PD.I=0.082, and dimensional homogeneity is good.
Embodiment 4 Nano microsphere photoresponse tests
Nano microsphere solution by preparation in embodiment 3, be configured to the solution that concentration is 5mg/mL, under the 254nm ultraviolet lamp, irradiates after 7 minutes and observe.Fig. 4 is for implementing the photoresponse experiment photo of the polymer nano-microspheres of preparation in 3.As shown in Figure 4, A is pre-irradiation polymer nano-microspheres solution, is the settled solution with blue-opalescent, B is UV-irradiation post polymerization thing Nano microsphere solution, becomes muddy, and C is the polymer nano-microspheres solution after standing 2 hours, the solution layering, upper strata is clear liquid, lower floor is flocks.Verify thus the ultraviolet light response characteristic of this polymer nano-microspheres.
Embodiment 5
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent S-1-carboxylic octyl group-S '-tertiary butyl trithiocarbonate, monomer and RAFT reagent mol ratio are 300:1, after stirring and dissolving, reactor is heated to 120 ℃, react after 12 hours, with syringe pump, the methyl acrylate of 3 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 16 hours.Within first 6 hours, at the uniform velocity inject 8% of methyl acrylate total amount, then by the instantaneous injection of 65% methyl acrylate, within last 10 hours, at the uniform velocity inject 27% methyl acrylate, after reaction finishes room temperature coolingly separate out, purified polymer.By nucleus magnetic hydrogen spectrum (
1hNMR) and gel permeation chromatography (GPC) gradient copolymer is characterized.The final molecular weight of polymkeric substance is 5.3 ten thousand, and molecular weight distribution is 1.22, and methyl acrylate content is 50%.
The synthetic styrene/acrylic methyl esters gradient copolymer obtained is dissolved in acetone, and concentration is 0.5%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 12%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 2mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Characterizing the microballoon mean diameter by dynamic light scattering (DLS) is 50nm, polydispersity index PD.I=0.042, and dimensional homogeneity is good.
Embodiment 6
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent S-1-carboxylic propyl group-S '-isopropyl itrile group trithiocarbonate, monomer and RAFT reagent mol ratio are 300:1, after stirring and dissolving, reactor is heated to 120 ° of C, react after 12 hours, with syringe pump, the butyl methacrylate of 2 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 12 hours.Within first 4 hours, at the uniform velocity inject 10% of butyl methacrylate total amount, then by the instantaneous injection of 65% butyl methacrylate, within last 8 hours, at the uniform velocity inject 25% butyl methacrylate, after reaction finishes room temperature coolingly separate out, purified polymer.By nucleus magnetic hydrogen spectrum (
1h NMR) and gel permeation chromatography (GPC) gradient copolymer is characterized.The final molecular weight of polymkeric substance is 4.2 ten thousand, and molecular weight distribution is 1.28, and butyl methacrylate content is 39%.
The synthetic styrene/methacrylic acid butyl ester gradient copolymer obtained is dissolved in acetone, and concentration is 0.5%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 6%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 2mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Characterizing the microballoon mean diameter by dynamic light scattering (DLS) is 50nm, polydispersity index PD.I=0.042, and dimensional homogeneity is good.
Embodiment 7
Pass into nitrogen after 20 minutes in dry reactor, add initiator Diisopropyl azodicarboxylate (AIBN), styrene monomer and RAFT reagent S-1-carboxylic propyl group-S '-isopropyl itrile group trithiocarbonate, monomer, RAFT reagent and AIBN mol ratio are 7500:5:1, after stirring and dissolving, reactor is heated to 60 ° of C, react after 12 hours, with syringe pump, the 4-vinylpridine of 2.5 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 15 hours.Within first 6 hours, at the uniform velocity inject 10% of 4-vinylpridine total amount, then by the instantaneous injection of 65% 4-vinylpridine, within last 9 hours, at the uniform velocity inject 25% 4-vinylpridine, after reaction finishes room temperature coolingly separate out, purified polymer.By nucleus magnetic hydrogen spectrum (
1h NMR) and gel permeation chromatography (GPC) gradient copolymer is characterized.The final molecular weight of polymkeric substance is 6.1 ten thousand, and molecular weight distribution is 1.32, and 4-vinylpridine is 45%.
The synthetic vinylbenzene obtained/4-vinylpridine gradient copolymer is dissolved in tetrahydrofuran (THF), and concentration is 0.5%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 5%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 2mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Characterizing the microballoon mean diameter by dynamic light scattering (DLS) is 60nm, polydispersity index PD.I=0.059, and dimensional homogeneity is good.
Embodiment 8
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent, the Z group in described RAFT reagent is
r is
styrene monomer and catalyst molar ratio are 300:1, after stirring and dissolving, reactor is heated to 120 ° of C, after reacting 12 hours, with syringe pump, the methyl methacrylate of 2.5 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 14 hours.Within first 6 hours, at the uniform velocity inject 8% of 2-hydroxypropyl acrylate total amount, then by the instantaneous injection of 65% 2-hydroxypropyl acrylate, within last 8 hours, at the uniform velocity inject 27% 2-hydroxypropyl acrylate, after reaction finishes room temperature coolingly separate out, purifying, obtain gradient copolymer.
Described gradient copolymer is dissolved in acetone, and concentration is 1%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 6%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 2mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Dynamic light scattering (DLS) result shows that this microballoon mean diameter is 53nm, polydispersity index PD.I=0.072, and dimensional homogeneity is good.
Embodiment 9
Pass into nitrogen after 20 minutes in dry reactor, add styrene monomer and RAFT reagent, the Z group in described RAFT reagent is
r is
styrene monomer and catalyst molar ratio are 300:1, after stirring and dissolving, reactor is heated to 120 ° of C, after reacting 12 hours, with syringe pump, the methyl methacrylate of 2.5 times of equivalents of styrene monomer is joined in reactor and carries out copolyreaction, copolyreaction is carried out 14 hours.Within first 6 hours, at the uniform velocity inject 8% of vinylformic acid total amount, then by the instantaneous injection of 65% vinylformic acid, within last 8 hours, at the uniform velocity inject 27% vinylformic acid, after reaction finishes room temperature coolingly separate out, purifying, obtain gradient copolymer.
Described gradient copolymer is dissolved in tetrahydrofuran (THF), and concentration is 2%(w/v), then under agitation condition, dropwise add deionized water, stirring velocity is 300rpm, final water-content is 6%(w/w).
Above-mentioned gradient copolymer micellar solution is joined in the sodium bicarbonate aqueous solution of equivalent 20mmol/L under vigorous stirring, and stirring velocity is 600rpm.Uncovered continuation is stirred 48 hours, until acetone volatilizees fully, can obtain the polymer nano-microspheres aqueous dispersion.Dynamic light scattering (DLS) result shows that this microballoon mean diameter is 53nm, polydispersity index PD.I=0.057, and dimensional homogeneity is good.
The explanation of above embodiment is just for helping to understand method of the present invention and core concept thereof.It should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of the claims in the present invention.
To the above-mentioned explanation of the disclosed embodiments, make professional and technical personnel in the field can realize or use the present invention.Multiple modification to these embodiment will be apparent for those skilled in the art, and General Principle as defined herein can be in the situation that do not break away from the spirit or scope of the present invention, realization in other embodiments.Therefore, the present invention will can not be restricted to these embodiment shown in this article, but will meet the widest scope consistent with principle disclosed herein and features of novelty.
Claims (10)
1. the preparation method of a polymer nano-microspheres comprises the following steps:
(A) select the trithiocarbonic acid ester compound shown in formula (I) as chain-transfer agent, by RAFT living polymerization composition gradient multipolymer;
(B) described gradient copolymer is dissolved in organic solvent, then adds water, form polymer micelle solution; Described organic solvent and water dissolve each other;
(C) described polymer micelle solution is joined in the aqueous solution of inorganic salt, by solvent exchange, obtain polymer nano-microspheres; The volume ratio of the aqueous solution of described polymer micelle solution and inorganic salt is 0.01～1;
Wherein, Z is the group of end with carboxyl, and R is leavings group.
2. preparation method according to claim 1, it is characterized in that, in described step (A), the monomer of described RAFT living polymerization comprises the first monomer and the second monomer, described the first monomer is vinylbenzene or its derivative, the compound that the second monomer is esters of acrylic acid, methyl acrylic ester or vinyl pyridine class.
3. preparation method according to claim 1, is characterized in that, in described step (B), and one or more in the alcohol that described organic solvent is acetone, C1～C3, the organic acid of C1～C8, tetrahydrofuran (THF), dioxane and DMF.
4. preparation method according to claim 1, is characterized in that, in described step (B), the mass body volume concentrations of described gradient copolymer in organic solvent is 0.01%～5%.
5. preparation method according to claim 1, is characterized in that, in described step (B), in described polymer micelle solution, the quality percentage composition of water is 0.1%～50%.
6. preparation method according to claim 1, is characterized in that, in described step (C), described inorganic salt are sodium bicarbonate, saleratus, sodium carbonate, salt of wormwood, sodium hydroxide, potassium hydroxide, SODIUM PHOSPHATE, MONOBASIC or potassium primary phosphate.
7. preparation method according to claim 6, is characterized in that, in described step (C), the mass percentage concentration of described inorganic salt is 1 * 10
-3～5mmol/L.
8. preparation method according to claim 1, is characterized in that, in described step (C), the mode of described displacement is volatilization or dialysis.
9. preparation method according to claim 1, is characterized in that, in described step (A), described Z be carboxylic propyl group, carboxymethyl, propyloic, carboxylic butyl, phenylformic acid benzyl,
10. preparation method according to claim 1, is characterized in that, in described step (A), described R be benzyl, the tertiary butyl ,-CH
2cN ,-C (CH
3)
2cH
2c (CH
3)
2,
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310319385.3A CN103483601B (en) | 2013-07-26 | 2013-07-26 | Preparation method for polymeric nanometer microsphere |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310319385.3A CN103483601B (en) | 2013-07-26 | 2013-07-26 | Preparation method for polymeric nanometer microsphere |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103483601A true CN103483601A (en) | 2014-01-01 |
| CN103483601B CN103483601B (en) | 2015-05-20 |
Family
ID=49824228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310319385.3A Active CN103483601B (en) | 2013-07-26 | 2013-07-26 | Preparation method for polymeric nanometer microsphere |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103483601B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213918A (en) * | 2017-07-12 | 2017-09-29 | 中国矿业大学 | A kind of preparation method of balloon borne body of zirconium and its application in manganese base desulfurizer |
| CN109810220A (en) * | 2017-11-21 | 2019-05-28 | 万华化学（北京）有限公司 | A kind of preparation method of Hydroxylated acrylic resin |
| CN110330585A (en) * | 2019-07-23 | 2019-10-15 | 淮阴工学院 | The method that supersonic induced RAFT precipitation polymerization prepares mono-dispersion microballoon |
| CN110420351A (en) * | 2019-07-11 | 2019-11-08 | 中国科学院长春应用化学研究所 | A kind of 3D printing flexible, porous timbering material and preparation method thereof |
| CN110776384A (en) * | 2019-11-14 | 2020-02-11 | 北京理工大学 | Polymer and nano aluminum powder compounded microsphere |
| CN112500325A (en) * | 2021-02-07 | 2021-03-16 | 北京吉乃尔科技有限公司 | Alpha, omega-type chain transfer agent for reversible addition-fragmentation chain transfer RAFT polymerization, and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101974138A (en) * | 2010-10-26 | 2011-02-16 | 武汉理工大学 | Method for preparing amphiphilic gradient copolymer |
-
2013
- 2013-07-26 CN CN201310319385.3A patent/CN103483601B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101974138A (en) * | 2010-10-26 | 2011-02-16 | 武汉理工大学 | Method for preparing amphiphilic gradient copolymer |
Non-Patent Citations (1)
| Title |
|---|
| 王芳平: ""聚丙烯酸型两亲接枝共聚物的合成、表征及其水溶液中自组装行为的研究"", 《万方数据企业知识服务平台》, 26 April 2012 (2012-04-26) * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213918A (en) * | 2017-07-12 | 2017-09-29 | 中国矿业大学 | A kind of preparation method of balloon borne body of zirconium and its application in manganese base desulfurizer |
| CN107213918B (en) * | 2017-07-12 | 2020-06-09 | 中国矿业大学 | Preparation method of zirconium ball carrier and application of zirconium ball carrier in manganese-based desulfurizing agent |
| CN109810220A (en) * | 2017-11-21 | 2019-05-28 | 万华化学（北京）有限公司 | A kind of preparation method of Hydroxylated acrylic resin |
| CN109810220B (en) * | 2017-11-21 | 2021-09-07 | 万华化学（北京）有限公司 | Preparation method of hydroxyl acrylic resin |
| CN110420351A (en) * | 2019-07-11 | 2019-11-08 | 中国科学院长春应用化学研究所 | A kind of 3D printing flexible, porous timbering material and preparation method thereof |
| CN110330585A (en) * | 2019-07-23 | 2019-10-15 | 淮阴工学院 | The method that supersonic induced RAFT precipitation polymerization prepares mono-dispersion microballoon |
| CN110776384A (en) * | 2019-11-14 | 2020-02-11 | 北京理工大学 | Polymer and nano aluminum powder compounded microsphere |
| CN112500325A (en) * | 2021-02-07 | 2021-03-16 | 北京吉乃尔科技有限公司 | Alpha, omega-type chain transfer agent for reversible addition-fragmentation chain transfer RAFT polymerization, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103483601B (en) | 2015-05-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103483601B (en) | Preparation method for polymeric nanometer microsphere | |
| Zehm et al. | Synthesis of diblock copolymer nanoparticles via RAFT alcoholic dispersion polymerization: Effect of block copolymer composition, molecular weight, copolymer concentration, and solvent type on the final particle morphology | |
| Zhang et al. | Phase separation behavior and crew-cut micelle formation of polystyrene-b-poly (acrylic acid) copolymers in solutions | |
| Sun et al. | Recent advances in RAFT dispersion polymerization for preparation of block copolymer aggregates | |
| Bai et al. | Monodisperse hydrophilic polymer microspheres having carboxylic acid groups prepared by distillation precipitation polymerization | |
| Lowe et al. | Synthesis and characterization of zwitterionic block copolymers | |
| Liu et al. | Aqueous dispersion polymerization of 2-methoxyethyl acrylate for the synthesis of biocompatible nanoparticles using a hydrophilic RAFT polymer and a redox initiator | |
| Wang et al. | Micellar nucleation differential microemulsion polymerization | |
| Zeng et al. | R-RAFT or Z-RAFT? Well-defined star block copolymer nano-objects prepared by RAFT-mediated polymerization-induced self-assembly | |
| Zhu et al. | Polymerization-induced cooperative assembly of block copolymer and homopolymer via RAFT dispersion polymerization | |
| Tan et al. | Synthesis of highly monodisperse surface-functional microspheres by photoinitiated RAFT dispersion polymerization using macro-RAFT agents | |
| CN103965421B (en) | A kind of have preparation method of the Thermo-sensitive amphiphilic block copolymer of nucleocapsid structure and products thereof | |
| CN106478904A (en) | A kind of preparation method of the segmented copolymer material with temperature and pH-sensitivity | |
| CN102718894B (en) | A kind of low-temperature synthetic method of monodisperse polymer micro-sphere | |
| Xu et al. | Synthesis, characterization and self-assembly of hybrid pH-sensitive block copolymer containing polyhedral oligomeric silsesquioxane (POSS) | |
| CN107216421B (en) | A kind of monodisperse polystyrene microsphere and the preparation method and application thereof | |
| Hu et al. | Preparation and characterization of novel cationic pH-responsive poly (N, N′-dimethylamino ethyl methacrylate) microgels | |
| Rymaruk et al. | Raft dispersion polymerization of benzyl methacrylate in silicone oil using a silicone-based methacrylic stabilizer provides convenient access to spheres, worms, and vesicles | |
| CN105646891A (en) | Amphiphilic ternary molecular brush polymer and vermicular mono-molecular micelle constructed by same | |
| CN104194003A (en) | Method for preparing black monodisperse polymer microspheres | |
| Karesoja et al. | Phase Separation of Aqueous Poly (2-dimethylaminoethyl methacrylate-block-N-vinylcaprolactams) | |
| Zhang et al. | A facile, efficient and “green” route to pH-responsive crosslinked poly (methacrylic acid) nanoparticles | |
| Huang et al. | Amphiphilic fluorescent copolymers via one-pot synthesis of RAFT polymerization and multicomponent Biginelli reaction and their cells imaging applications | |
| Zeng et al. | Uncontrolled polymerization that occurred during photoinitiated RAFT dispersion polymerization of acrylic monomers promotes the formation of uniform raspberry-like polymer particles | |
| CN108641092B (en) | Preparation method of supramolecular polymer composite micelle based on hydrogen bond |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |