CN104119474B - A kind of surface-functionalized micro-nano polymeric hollow particle and preparation method thereof - Google Patents
A kind of surface-functionalized micro-nano polymeric hollow particle and preparation method thereof Download PDFInfo
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Abstract
Disclosure a kind of micro-nano polymeric hollow particle, particularly a kind of surface-functionalized micro-nano polymeric hollow particle and preparation method thereof. The polymerization technique first passing through a kind of simplicity prepares soluble high-molecular template particles, then the polyreaction of itaconic anhydride, NVP, cross-linking agent is caused on the surface of template particles, prepare the polymer particle of nucleocapsid structure, then dissolve the kernel in core-shell particles with the good solvent of template kernel, prepare uniform wall thickness, surface with the hollow-core construction polymer particle of reactive group. The cavity surfaces externally and internally of described polymeric hollow particle has reactive functional group, chemical bonding mode appendix can be passed through, wrap up specific active substance, medicine, biomolecule, cancer target agent, antibody etc., be conducive to micro-nano polymeric hollow particle in the application of biomedicine field.
Description
Technical field
The invention belongs to field of new, relate to a kind of micro-nano polymeric hollow particle, particularly a kind of surface-functionalized micro-nano polymeric hollow particle and preparation method thereof.
Background technology
Polymeric hollow microgranule has the characteristic of low-density, high-ratio surface, and its hollow parts can hold substantial amounts of guest molecule or large-sized object, thus producing some peculiar character based on microcosmic " parcel " effect so that hollow particle material has important application in many technical fields such as medicine, biochemistry and chemical industry. It addition, the chemical composition of the shell of polymeric hollow microgranule and thickness can be adjusted, so that the performances such as many performances of hollow granule such as optical, electrical, magnetic, heat, machinery can carry out " cutting out " within a large range.
Polymeric hollow microgranule can as the carrier of medicine because of the structure of its uniqueness, serve as delivery system, have the advantage that (one) has passive targeting, after entering blood circulation, can be absorbed by monokaryon macrophage system, arrive liver that reticuloendothelial system distribution concentrates, spleen, lung, bone marrow, the targeting moiety such as lymph, in addition can also finishing or materialization means reach the effect of active targeting through special processing such as; (2) pharmaceutical pack is wrapped in its cavity, enter internal after, by the aperture of host material or reach controlled release, slow release effect along with the degraded of substrate; (3) when being applied to the little medicine of those therapeutic index, it is possible to be substantially reduced its toxic and side effects; (4) medicine is through its parcel, is in the environment comparatively closed, and such structure can effectively prevent the destruction of internal enzyme after extraneous factor and administration, thus reaching to improve the purpose of medicine stability.
The method preparing polymeric hollow particle at present has emulsion polymerization and template etc. Seeded emulsion polymerization be so far most study, the most widely used method preparing core-shell structure copolymer/hollow-core construction polymer composite particle, summarize its basic technology and can be divided into the following steps: initially with the method synthesis seed emulsion of emulsion polymerization, then second comonomer is joined in seed emulsion and carry out repolymerization, the polymer emulsion with nucleocapsid structure can be obtained, finally remove core with suitable solvent, obtain hollow granule. The difference of the feed way according to second comonomer, seeded emulsion polymerization can be divided into again batch process, equilibrium swelling method, semi-continuous process and the techniques four kinds different such as continuity method.
Template it is critical only that template, it is generally required to prepare in advance. Chemical reaction is there is not in template in whole reaction process, polymer occurs on the surface of template to be formed and shape, therefore the shape and size of template directly determine the shape and size of gained hollow ball, reach to adjust the purpose of microsphere pattern by the pattern of adjusting template. The core one shell structure product of micro encapsulation is removed by suitable method. Caruso etc. report and utilize layer assembly method (LayerbyLayer) to prepare polymeric hollow particle, it it is representative a kind of system, there is successively absorption alternately at solid template surface by electrostatic interaction in the polyelectrolyte in this system with opposite charges, finally removes template and just obtain hollow ball. The advantage of template is in that morphology controllable is easily-controllable, and shortcoming is in that reaction condition is relatively harsh, and stability is relatively poor, and current practice is less.
Emulsion polymerization and template synthesis polymeric hollow particle have his own strong points, and traditional emulsion polymerization and seeded polymerization are prepared hollow polymer particle and had the shortcomings such as system composition complexity, particle size distribution width, product structure instability; Template has the advantages that form is controlled, but generally severe reaction conditions, complex steps, and less stable.
The present invention proposes the template particles of a kind of simple process and the preparation method of hollow granule, and obtains a kind of micro-nano polymeric hollow particle being provided simultaneously with high response anhydride group and high complexing pyrrolidone group.
Summary of the invention
It is an object of the invention to overcome the deficiency of existing micro-nano polymeric hollow particle and preparation method thereof, it is provided that the preparation method technique of a kind of surface-functionalized micro-nano polymeric hollow particle and a kind of simplicity.
Described polymeric hollow particle size is uniform, size tunable, and the wall thickness of hollow granule can be regulated and controled by kinds of processes parameter.
The cavity surfaces externally and internally of described polymeric hollow particle has reactive functional group, chemical bonding mode appendix can be passed through, wrap up specific active substance, medicine, biomolecule, cancer target agent, antibody etc., be conducive to micro-nano polymeric hollow particle in the application of biomedicine field.
The present invention provides following technical scheme:
The polymerization technique first passing through a kind of simplicity prepares soluble high-molecular template particles, then in the surface Priming Seeds polymerization of template particles, prepare the polymer particle of nucleocapsid structure, then the kernel in core-shell particles is dissolved with the good solvent of template kernel, it is possible to prepare uniform wall thickness, surface with the hollow-core construction polymer particle of reactive group.
A kind of surface-functionalized micro-nano polymeric hollow particle, described polymeric hollow particle, comprise following structure unit:
Wherein n is 10-10000, it is preferable that 100-1000.
Preferably, said structure unit is connected as cross-linked structure by cross-linking agent.
The chemical constitution of described polymeric hollow particle contains anhydride group and pyrrolidone group simultaneously.
Described anhydride group has high reaction activity, it is possible to be hydrolyzed, saponification, esterification, acidylate, the reaction such as amidatioon.
Described pyrrolidone group has complex reaction activity, it is possible to carry out ligand complex with the transition metal containing unoccupied orbital, the halogen of suction electricity, drug molecule etc.
The described micro-nano hollow granule of the copolymerized macromolecule containing anhydride group and pyrrolidone group is the polymeric hollow particle of a kind of new chemical composition, the cavity surfaces externally and internally of its particle contains anhydride group and the pyrrolidone group of high reaction activity, a series of subsequent reactions chemical, biochemical can be there is in these functional chemical group, thus providing great convenience for Post functionalization such as the chemical modification of polymeric hollow particle, bio-modification, medicine complexations, thus there is wide using value at biomedicine field.
The preparation method of a kind of surface-functionalized micro-nano polymeric hollow particle, described preparation method comprises the steps of, it is preferable that comprise the steps of simultaneously
1, soluble high-molecular template particles is prepared;
2, preparation shell monomer, polymerization initiator and solvent, be subsequently adding template particles, ultrasonic disperse, mix homogeneously;
3, letting nitrogen in and deoxidizing, is then placed in water bath with thermostatic control and heats initiated polymerization;
4, reacting complete, product high speed centrifuge separates;
5, centrifugal product is put into ultrasonic vibration in excessive propanone, centrifugal, washing, more than three times repeatedly, all kernel templates are fallen in extracting, obtain hollow polymer microsphere;
6, put into vacuum drying oven, dry at 60 DEG C of temperature to constant weight;
Wherein, described prepares soluble high-molecular template particles, and its method comprises the steps of, it is preferable that comprise the steps of simultaneously
I () template particles monomer, polymerization initiator, solvent, be dosed in the reactor equipped with nitrogen conduit, condensing tube, agitator and thermometer in setting ratio is disposable, fully dissolve mix homogeneously;
(ii) logical nitrogen deoxygenation 30min, is placed in solution system in water bath with thermostatic control and heats, temperature 45-120 DEG C, time 5-600min, stir speed (S.S.) 0-500rpm;
(iii), after completion of the reaction, after ultrasonic vibration 30min, high speed centrifuge separates, rotating speed 5000-12000rpm; With step (1) described solvent, centrifugal product being washed, recentrifuge separates, washing, repeats 3-5 time;
(iv) final centrifugal product is scattered in step (1) described solvent again by ultrasonic vibration, obtains the dispersion of chelating polymer template particle, standby.
Described template particles is selected from the polymerizate of following template particles monomer: (a) maleic anhydride and at least one in (b) acrylic acid methyl ester., ethyl acrylate, butyl acrylate, vinyl acetate, styrene, hydroxyethyl methylacrylate, vinyl pyrrolidone, cyanoacrylate, acrylic acid, methacrylic acid, acrylamide. Maleic anhydride concentration 0.1%-25%, it is preferable that 1%-10%; (b) concentration 0.1%-25%, it is preferable that 1%-10%.
Wherein, described shell monomer is selected from: itaconic anhydride, NVP, cross-linking agent. Preferably, described shell monomer is made up of itaconic anhydride, NVP and cross-linking agent.
Wherein, itaconic anhydride, NVP, amount ratio between cross-linking agent three range for: (2～4): (1～2): (1～2). Preferably, itaconic anhydride, NVP, amount ratio between cross-linking agent three range for: (2～3): (1～1.5): (1～1.5). Present inventor is it has been unexpectedly found that the ratio of three can obtain micro-nano polymer gel particle in aforementioned range, and the spherical property of described particle is good, epigranular.
Wherein, cross-linking agent is the molecule with two or more polymerizable structure, and this quasi-molecule includes but not limited to: divinylbenzene, Ethylene glycol dimethacrylate, N, N '-methylene-bisacrylamide, polyethyleneglycol diacrylate.
Described shell monomer content accounts for the 1%-50% of solution total amount, it is preferable that 5%-20%; Wherein, content of crosslinking agent accounts for the 0.1%-15% of other monomer total amounts, it is preferable that 1%-10%.
Wherein, in the preparation method of described a kind of surface-functionalized micro-nano polymeric hollow particle, described polymerization initiator is selected from the thermal polymerization that professional and technical personnel in the field are known, and this kind of initiator includes but not limited to: at least one in isopropyl benzene hydroperoxide, tert-butyl hydroperoxide, cumyl peroxide, di-tert-butyl peroxide, dilauroyl peroxide, dibenzoyl peroxide, perbenzoic acid spy's butyl ester, diisopropyl peroxydicarbonate, di-cyclohexylperoxy di-carbonate, azodiisobutyronitrile, 2,2'-Azobis(2,4-dimethylvaleronitrile).
Described initiator content accounts for the 0.01%-0.5% of solution total amount, it is preferable that 0.01%-0.1%.
Described solvent is selected from: formic acid esters, ethyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isoamyl acetate, benzyl acetate, methyl propionate, ethyl propionate, butyl propionate, methyl butyrate, ethyl n-butyrate., butyl butyrate, isoamyl butyrate, essence of Niobe, ethyl benzoate, propyl benzoate, butyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate, acetone, butanone, normal hexane, at least one in hexamethylene or more than one combination.
Preferably, described solvent is combined by organic acid alkylester did, ketone, alkanes.
Preferably, organic acid alkylester did, ketone, amount ratio between alkanes three range for: (5～8): (1～3): (1～2). Preferably, organic acid alkylester did, ketone, amount ratio between alkanes three range for: (6～7): (1～2): (1～1.5). It is highly preferred that described solvent is made up of butyl acetate, Ketohexamethylene and hexamethylene, ratio is 6: 1: 1.
It should be strongly noted that this polymerization reaction system also can normal reaction obtain micro-nano polymeric hollow particle when adding without stabilizer.
Described stir speed (S.S.) is 0-500rpm, namely when stir speed (S.S.) is 0, also can normal reaction prepare polymer latex particles, with the reacting phase ratio under stirring condition, the form of particle and size can be different. This is the another characteristic that the present invention prepares polymeric hollow particle process.
In the preparation method of a kind of surface-functionalized micro-nano polymeric hollow particle of the present invention, before reaction, monomer, polymerization initiator, optional stabilizer are dissolved in solvent, are scattered in this solvent chelating polymer template uniform particle; After polyreaction causes, system generates copolymerized macromolecule oligomer, cross-linking reaction occurs between these oligomers, after coagulative precipitation, forms bigger laminated structure; Then, these laminated structures deposit to template surface under the effect of template particle surface absorption affinity, form core-shell particles; Along with template particles continues to adsorb oligomer, laminated structure from reaction system, the particle diameter of core-shell particles constantly increases, until monomer exhausts, reaction terminates.
In course of reaction, between laminated structure inside and sheet and the sheet of crosslinking, also constantly carry out cross-linking reaction, make the housing portion of microsphere form an overall structure with high-crosslinking-degree.
Form owing to the shell of particle is overlapped mutually by the laminated structure cross-linked, so there being abundant hole between laminated structure, the strand that sheet lamellar spacing is template particles of this microcosmic is provided passage by solvent dissolution, and provide passage for drug molecule, the absorption of biomolecule, release, be conducive to hollow granule in the application of biomedicine field.
After above-mentioned core-shell particles centrifugation, put into ultrasonic vibration in excessive propanone, acetone enters inside core-shell particles by hole, the template particles at center is dissolved, centrifugal, washing, three times repeatedly, it is possible to kernel template be completely dissolved totally, finally give surface-functionalized micro-nano polymeric hollow particle.
Compared with micro-nano polymeric hollow particle prepared by other method, this hollow granule shell is the lamella superposition integrative-structure of high-crosslinking-degree, and shell is thicker, it is possible to still keeps shape invariance under dry state, and does not produce phenomenon of collapsing.
A kind of surface-functionalized micro-nano polymeric hollow particle disclosed in technique scheme and preparation method thereof, has the advantage that
1) the micro-nano hollow granule of copolymerized macromolecule prepared by the present invention is the hollow granule of a kind of new chemical composition, the cavity surfaces externally and internally of its particle contains anhydride group and the pyrrolidone group of high reaction activity, a series of subsequent reactions chemical, biochemical can be there is in these functional chemical group, thus providing great convenience for Post functionalization such as the chemical modification of polymeric hollow particle, bio-modification, medicine complexations, thus there is wide using value at biomedicine field.
2) hollow granule shell is the lamella superposition integrative-structure of high-crosslinking-degree, shell is thicker, it is possible to still keep shape invariance under dry state, and the phenomenon that do not produce to collapse, and between laminated structure, have abundant hole, provide passage for drug molecule, the absorption of biomolecule, release.
3) preparation technology of the micro-nano polymeric hollow particle of the present invention is simple, and kernel template used is easily prepared and is prone to dissolve removal, and the particle diameter of hollow granule can be regulated and controled by kinds of processes parameter, and uniform particle sizes.
A kind of surface-functionalized micro-nano polymeric hollow particle provided by the invention, it is possible to for biomedicine fields such as pharmaceutical carrier, targeting preparation, cancer diagnosis, hepatitis detection, Protein Separation, cell separation, immunosorbent.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope photo of the template particles of embodiment 1.
Fig. 2 is the transmission electron microscope photo of the template particles of embodiment 2.
Fig. 3 is the transmission electron microscope photo of the template particles of embodiment 3.
Fig. 4 is the transmission electron microscope photo of the template particles of embodiment 4.
Fig. 5 is the transmission electron microscope photo of the polymeric hollow particle of embodiment 5.
Fig. 6 is the transmission electron microscope photo of the polymeric hollow particle of embodiment 6.
Fig. 7 is the transmission electron microscope photo of the polymeric hollow particle of embodiment 7.
Fig. 8 is the transmission electron microscope photo of the polymeric hollow particle of embodiment 8.
Detailed description of the invention
Below in conjunction with drawings and Examples, technical scheme being described in further details, following example are used for illustrating the present invention, but are not used in restriction the scope of the present invention.
Fig. 1-4 is the transmission electron microscope photo of the template particles in a kind of surface-functionalized micro-nano polymeric hollow particle preparation process of the present invention, and the spherical property of described template particles is good, and epigranular, close to monodispersity.
Fig. 5-8 is the transmission electron microscope photo of a kind of surface-functionalized micro-nano polymeric hollow particle of the present invention, and described polymeric hollow particle still presents spherical, and shell mechanism is complete, and wall thickness can regulate, and epigranular, close to monodispersity.
The preparation method of micro-nano polymeric hollow particle: first prepare soluble high-molecular template particles. By template particles monomer, thermal decomposition initiating, solvent, it is dosed in the reactor equipped with nitrogen conduit, condensing tube, agitator and thermometer in setting ratio is disposable, fully dissolves mix homogeneously. Wherein, described template particles monomer is selected from: (a) maleic anhydride and at least one in (b) acrylic acid methyl ester., ethyl acrylate, butyl acrylate, vinyl acetate, styrene, hydroxyethyl methylacrylate, vinyl pyrrolidone, cyanoacrylate, acrylic acid, methacrylic acid, acrylamide, maleic anhydride concentration 0.1%-25%, preferred 1%-10%, (b) class monomer concentration 0.1%-25%, it is preferable that 1%-10%; Wherein, described thermal initiator at least one in isopropyl benzene hydroperoxide, tert-butyl hydroperoxide, cumyl peroxide, di-tert-butyl peroxide, dilauroyl peroxide, dibenzoyl peroxide, perbenzoic acid spy's butyl ester, diisopropyl peroxydicarbonate, di-cyclohexylperoxy di-carbonate, azodiisobutyronitrile, 2,2'-Azobis(2,4-dimethylvaleronitrile), initiator content accounts for the 0.1%-3% of monomer total amount, it is preferable that 0.5%-1%; Wherein, at least one in formic acid esters, ethyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isoamyl acetate, benzyl acetate, methyl propionate, ethyl propionate, butyl propionate, methyl butyrate, ethyl n-butyrate., butyl butyrate, isoamyl butyrate, essence of Niobe, ethyl benzoate, propyl benzoate, butyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate, acetone, butanone, normal hexane, the hexamethylene of described solvent or more than one combination. Logical nitrogen deoxygenation 30min, is placed in solution system in water bath with thermostatic control and heats, temperature 45-120 DEG C, time 5-600min, stir speed (S.S.) 0-500rpm; After completion of the reaction, the product high speed centrifuge obtained is separated, rotating speed 5000-12000rpm; With step (1) described solvent, centrifugal product being washed, recentrifuge separates, washing, repeats 3-5 time; Final centrifugal product is scattered in step (1) described solvent again by ultrasonic vibration, obtains the dispersion of chelating polymer template particle, standby.
Then, prepare the solution of shell monomer, polymerization initiator, solvent, mix homogeneously with the dispersion of above-mentioned template particles; Letting nitrogen in and deoxidizing 20-30min, puts into heating initiated polymerization in water bath with thermostatic control, temperature 45-120 DEG C, time 180-600min, stir speed (S.S.) 0-450rpm; Reacting complete, product high speed centrifuge separates, rotating speed 5000-12000rpm; Centrifugal product is put into ultrasonic vibration in excessive propanone centrifugal after 30 minutes, washing, three times repeatedly, all kernel templates are fallen in extracting, obtain hollow polymer microsphere; Put into vacuum drying oven, dry to constant weight at 60 DEG C of temperature.
Wherein, described shell monomer is selected from: itaconic anhydride, NVP, cross-linking agent. Preferably, described shell monomer is made up of itaconic anhydride, NVP and cross-linking agent.
Wherein, itaconic anhydride, NVP, amount ratio between cross-linking agent three range for: (2～4): (1～2): (1～2). Preferably, itaconic anhydride, NVP, amount ratio between cross-linking agent three range for: (2～3): (1～1.5): (1～1.5). Present inventor is it has been unexpectedly found that the ratio of three can obtain micro-nano polymer gel particle in aforementioned range, and the spherical property of described particle is good, epigranular.
Wherein, cross-linking agent is the molecule with two or more polymerizable structure, and this quasi-molecule includes but not limited to: divinylbenzene, Ethylene glycol dimethacrylate, N, N '-methylene-bisacrylamide, polyethyleneglycol diacrylate.
Described shell monomer content accounts for the 1%-50% of solution total amount, it is preferable that 5%-20%; Wherein, content of crosslinking agent accounts for the 0.1%-15% of other monomer total amounts, it is preferable that 1%-10%.
Wherein, in the preparation method of described-kind of surface-functionalized micro-nano polymeric hollow particle, described polymerization initiator is selected from the thermal polymerization that professional and technical personnel in the field are known, and this kind of initiator includes but not limited to: at least one in isopropyl benzene hydroperoxide, tert-butyl hydroperoxide, cumyl peroxide, di-tert-butyl peroxide, dilauroyl peroxide, dibenzoyl peroxide, perbenzoic acid spy's butyl ester, diisopropyl peroxydicarbonate, di-cyclohexylperoxy di-carbonate, azodiisobutyronitrile, 2,2'-Azobis(2,4-dimethylvaleronitrile).
Described initiator content accounts for the 0.01%-0.5% of solution total amount, it is preferable that 0.01%-0.1%.
Described solvent is selected from: formic acid esters, ethyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isoamyl acetate, benzyl acetate, methyl propionate, ethyl propionate, butyl propionate, methyl butyrate, ethyl n-butyrate., butyl butyrate, isoamyl butyrate, essence of Niobe, ethyl benzoate, propyl benzoate, butyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate, acetone, butanone, normal hexane, at least one in hexamethylene or more than one combination.
Preferably, described solvent is combined by organic acid alkylester did, ketone, alkanes.
Preferably, organic acid alkylester did, ketone, amount ratio between alkanes three range for: (5～8): (1～3): (1～2). Preferably, organic acid alkylester did, ketone, amount ratio between alkanes three range for: (6～7): (1～2): (1～1.5). It is highly preferred that described solvent is made up of butyl acetate, Ketohexamethylene and hexamethylene, ratio is 6: 1: 1.
It should be strongly noted that this polymerization reaction system also can normal reaction obtain micro-nano polymeric hollow particle when adding without stabilizer.
Described stir speed (S.S.) is 0-500rpm, namely when stir speed (S.S.) is 0, also can normal reaction prepare polymer latex particles, with the reacting phase ratio under stirring condition, the form of particle and size can be different. This is the another characteristic that the present invention prepares polymeric hollow particle process.
With the micro-nano polymer gel particle obtained under HITACHIH-800 transmission electron microscope observation difference preparation condition. By the product solvent dispersion after centrifuge washing, dilution, ultrasonic vibration 15 minutes, then draw a small amount of sample drop on Electronic Speculum copper mesh with dropper, naturally dry. Cover polyvinyl butyral resin support membrane above copper mesh, and carry out surface spray carbon process.
Particle diameter and the particle size distribution of polymer gel particle is measured with MalvemMastersize2000 laser particle size analyzer. By the product solvent dispersion after centrifuge washing, dilution (dilution factor more than 1000 times), fully shake in supersonic generator, make particle scatter, then carry out Instrumental Analysis. Data statistical analysis method is as follows:
PDI=dw/dn
D in formulai-single microspherulite diameter; dn-microsphere number average bead diameter; dw-microsphere weight average particle diameter; N-sample size; PDI-particle size distribution index.
Embodiment 1
Prepared by template particles
Maleic anhydride 2g, vinyl acetate 1.8g, benzoyl peroxide 0.03g, butyl acetate 92mL; Letting nitrogen in and deoxidizing 30min; Heating in water bath initiated polymerization, temperature 80 DEG C, time 350min; Product centrifuge separates in 5000rpm, washs 3 times with butyl acetate, is again scattered in butyl acetate by ultrasonic vibration, obtains the dispersion of chelating polymer template particle.
The transmission electron microscope photo of prepared template particles is shown in Fig. 1, template particles particle diameter 208nm, and particle size distribution coefficient 1.04, close to monodispersity.
Embodiment 2
Prepared by template particles
Maleic anhydride 2.4g, vinyl acetate 2g, azodiisobutyronitrile 0.02g, isoamyl acetate 86mL; Letting nitrogen in and deoxidizing 30min; Heating in water bath initiated polymerization, temperature 65 DEG C, time 600min; Product centrifuge separates in 5000rpm, washs 3 times with isoamyl acetate, is again scattered in isoamyl acetate by ultrasonic vibration, obtains the dispersion of chelating polymer template particle.
The transmission electron microscope photo of prepared template particles is shown in Fig. 2, template particles particle diameter 220nm, and particle size distribution coefficient 1.05, close to monodispersity.
Embodiment 3
Prepared by template particles
Maleic anhydride 3g, styrene 2.8g, azodiisobutyronitrile 0.04g, isobutyl acetate 90mL; Letting nitrogen in and deoxidizing 30min; Heating in water bath initiated polymerization, temperature 75 DEG C, time 480min; Product centrifuge separates in 5000rpm, washs 3 times with isobutyl acetate, is again scattered in isoamyl acetate by ultrasonic vibration, obtains the dispersion of chelating polymer template particle.
The transmission electron microscope photo of prepared template particles is shown in Fig. 3, template particles particle diameter 232nm, and particle size distribution coefficient 1.06, close to monodispersity.
Embodiment 4
Prepared by template particles
Maleic anhydride 2.6g, styrene 3.2g, benzoyl peroxide 0.05g, isoamyl acetate 85mL; Letting nitrogen in and deoxidizing 30min; Heating in water bath initiated polymerization, temperature 85 DEG C, time 600min; Product centrifuge separates in 5000rpm, washs 3 times with isoamyl acetate, is again scattered in isoamyl acetate by ultrasonic vibration, obtains the dispersion of chelating polymer template particle.
The transmission electron microscope photo of prepared template particles is shown in Fig. 4, template particles particle diameter 210nm, and particle size distribution coefficient 1.06, close to monodispersity.
Embodiment 5
Prepared by hollow granule
Itaconic anhydride 1.6g, NVP 0.65g, divinylbenzene 1.1g, dibenzoyl peroxide 0.03g, butyl acetate 60mL, Ketohexamethylene 10mL, normal hexane 10mL is added in the template particles dispersion of embodiment 1; Letting nitrogen in and deoxidizing 30min, puts into heating initiated polymerization in water bath with thermostatic control, temperature 85 DEG C, and reaction 8h terminates; Product centrifuge separates in 5000rpm; Centrifugal product is put into ultrasonic vibration 30 minutes in excessive propanone, centrifugal, washing, three times repeatedly, all kernel templates are fallen in extracting, obtain hollow polymer microsphere; Put into vacuum drying oven, dry to constant weight at 60 DEG C of temperature.
Fig. 5 is shown in by the transmission electron microscope photo of gained hollow granule, and the mean diameter of particle is 246nm, and particle size distribution index is 1.05, the wall thickness 15nm of hollow granule.
Embodiment 6
Prepared by hollow granule
Using the template particles of embodiment 2, other conditions are identical with embodiment 5, the difference is that only consumption respectively 3.5g, 1.5g, 2.2g of shell monomer itaconic anhydride, NVP, divinylbenzene three.
Fig. 6 is shown in by the transmission electron microscope photo of gained hollow granule, and the mean diameter of particle is 272nm, and particle size distribution index is 1.07, the wall thickness 27nm of hollow granule, it was shown that along with the increase of shell monomer concentration, the wall thickness of hollow granule increases.
Embodiment 7
Prepared by hollow granule
Using the template particles of embodiment 3, other condition is identical with embodiment 5, the difference is that only consisting of of mixed solvent used: isoamyl acetate 65mL, Ketohexamethylene 12mL, normal hexane 15mL.
Fig. 7 is shown in by the transmission electron microscope photo of gained hollow granule, and the mean diameter of particle is 283nm, and particle size distribution index is 1.06, the wall thickness 32nm of hollow granule, it was shown that by changing kind and the proportioning of reaction dissolvent, it is possible to the wall thickness of hollow regulating particle.
Embodiment 8
Prepared by hollow granule
Using the template particles of embodiment 4, other conditions are identical with embodiment 5, the difference is that only that shell monomer used and consumption thereof are: itaconic anhydride 5.6g, NVP 3.2g, polyethyleneglycol diacrylate 2.8g.
Fig. 8 is shown in by the transmission electron microscope photo of gained hollow granule, the mean diameter of particle is 306nm, particle size distribution index is 1.08, the wall thickness 45nm of hollow granule, show that the kind changing cross-linking agent still can obtain hollow granule, and along with the increase of shell monomer concentration, the wall thickness of hollow granule increases.
Comparative example 1
Other conditions are identical with embodiment 5, the difference is that only in shell monomer without cross-linker divinylbenzene. Result shows: gained product is polymer colloid substance, it is impossible to obtain hollow granule.
Comparative example 2
Other conditions are identical with embodiment 5, the difference is that only consumption respectively 3.5g, 1.5g, 0.3g of itaconic anhydride, NVP, divinylbenzene three. Result shows: containing polymer colloid substance in gained product, have a small amount of hollow granule but incomplete, it was shown that dosage of crosslinking agent is extremely important to the steadiness of shell.
Comparative example 3
Other conditions are identical with embodiment 5, the difference is that only consisting of of mixed solvent used: Ketohexamethylene 80mL, and normal hexane 15mL, without butyl acetate. Result shows: gained product is polymer colloid substance, it is impossible to obtain hollow granule. Show that solvent species and proportioning are extremely important to the formation of hollow granule.
Comparative example 4
Other conditions are identical with embodiment 5, the difference is that only consisting of of mixed solvent used: butyl acetate 65mL, and Ketohexamethylene 12mL, without normal hexane. Result shows: containing polymer colloid substance in gained product, have a small amount of hollow granule but incomplete, it was shown that solvent species and proportioning are extremely important to the formation of complete hollow granule.
Comparative example 5
Other conditions are identical with embodiment 5, the difference is that only consisting of of mixed solvent used: butyl acetate 65mL, and normal hexane 15mL, without Ketohexamethylene. Result shows: containing polymer colloid substance in gained product, have a small amount of hollow granule but incomplete, it was shown that solvent species and proportioning are extremely important to the formation of complete hollow granule.
It should be pointed out that, that the above detailed description of the invention can make those skilled in the art more fully understand the innovation invention, but restriction the innovation is invented never in any form. Therefore; although the innovation invention is had been carried out detailed description by embodiment by this specification; but; skilled artisan would appreciate that; all are without departing from the spirit of the innovation invention and the technical scheme of scope and improvement thereof, and it all should be encompassed in the middle of the protection domain of the innovation patent of invention.
Claims (5)
1. a surface-functionalized micro-nano polymeric hollow particle, the chemical constitution of described polymeric hollow particle comprises following structure unit:
Wherein, n=10-10000;
Said structure unit is connected as cross-linked structure by cross-linking agent;
The chemical constitution of described polymeric hollow particle contains anhydride group and pyrrolidone group simultaneously;
Described anhydride group has high reaction activity, it is possible to be hydrolyzed, saponification, esterification, acidylate, amidation process;
Described pyrrolidone group has complex reaction activity, it is possible to carry out ligand complex with the transition metal containing unoccupied orbital, the halogen of suction electricity, drug molecule;
Further, described polymeric hollow particle is prepared by following step:
(1) soluble high-molecular template particles is prepared;
(2) solution of preparation shell monomer, polymerization initiator and solvent, is subsequently adding template particles, ultrasonic disperse, mix homogeneously;
(3) letting nitrogen in and deoxidizing, is then placed in water bath with thermostatic control and heats initiated polymerization;
(4) reacting complete, product high speed centrifuge separates;
(5) centrifugal product is put into ultrasonic vibration in excessive propanone, centrifugal, washing, more than three times repeatedly, all kernel templates are fallen in extracting, obtain hollow polymer microsphere;
(6) put into vacuum drying oven, dry at 60 DEG C of temperature to constant weight;
Described shell monomer in above-mentioned steps comprises itaconic anhydride, NVP and cross-linking agent simultaneously, and the amount ratio between itaconic anhydride, NVP, cross-linking agent three ranges for: (2～3): (1～2): (1～2); Described solvent is ranged for (5～8) by amount ratio: (1～3): the organic acid alkylester did of (1～2), ketone, alkanes three form.
2. a kind of surface-functionalized micro-nano polymeric hollow particle as claimed in claim 1, described soluble high-molecular template particles is selected from the polymerizate of following monomer: (a) maleic anhydride and at least one in (b) acrylic acid methyl ester., ethyl acrylate, butyl acrylate, vinyl acetate, styrene, hydroxyethyl methylacrylate, vinyl pyrrolidone, cyanoacrylate, acrylic acid, methacrylic acid, acrylamide.
3. a kind of surface-functionalized micro-nano polymeric hollow particle as claimed in claim 1, in described shell monomer, the amount ratio between itaconic anhydride, NVP, cross-linking agent three ranges for: (2～3): (1～1.5): (1～1.5).
4. a kind of surface-functionalized micro-nano polymeric hollow particle as claimed in claim 1, described cross-linking agent is the molecule with two or more polymerizable structure, selected from divinylbenzene, Ethylene glycol dimethacrylate, N, N '-methylene-bisacrylamide, polyethyleneglycol diacrylate.
5. a kind of surface-functionalized micro-nano polymeric hollow particle as claimed in claim 1, described solvent is made up of butyl acetate, Ketohexamethylene and hexamethylene, and ratio is 6: 1: 1.
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| WO2007074476A1 (en) * | 2005-12-28 | 2007-07-05 | Dabur Pharma Limited | A biocompatible, non-biodegradable, non-toxic polymer useful for nanoparticle pharmaceutical compositions |
| CN101597352A (en) * | 2009-06-26 | 2009-12-09 | 北京化工大学 | Cross-linking type Sodium styrene sulfonate-maleic anhydride superpolymer and photopolymerization preparation method thereof |
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| WO2007074476A1 (en) * | 2005-12-28 | 2007-07-05 | Dabur Pharma Limited | A biocompatible, non-biodegradable, non-toxic polymer useful for nanoparticle pharmaceutical compositions |
| CN101597352A (en) * | 2009-06-26 | 2009-12-09 | 北京化工大学 | Cross-linking type Sodium styrene sulfonate-maleic anhydride superpolymer and photopolymerization preparation method thereof |
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| RU2822574C1 (en) * | 2019-10-30 | 2024-07-09 | Чайна Петролеум Энд Кемикал Корпорейшн | Fire-resistant antibacterial agent, method for production and use thereof and composition of fire-resistant antibacterial thermoplastic resin |
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