CN101036867A - Polyethylenimine derivates nanometer hollow microspheres and the preparing method - Google Patents
Polyethylenimine derivates nanometer hollow microspheres and the preparing method Download PDFInfo
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Abstract
Provided is polyethyleneimine derivative nano hollow microspheres, wherein the microsphere shell is a crosslinked polymer formed by ester bond linkage with amino groups of branched polyethyleneimine, the grain size is 50nm to 200nm, and the hollow microspheres are stored in a closed container in dry environment at room temperature after drying. The preparation process comprises the steps of (1) preparation of nano SiO2 microspheres; (2) modification of SiO2 microspheres; (3) forming of polyethyleneimine shell; (4) crosslinking of polyethyleneimine shell; (5) etching of SiO2 core. By using the preparing process provided in the invention, the size and the thickness of polyethyleneimine derivative nano hollow microspheres cavity can be controlled easily, and the difference of the grain sizes of polyethyleneimine derivative nano hollow microspheres prepared in same process is no more than 10%.
Description
Technical field
The present invention relates to a kind of polyethylenimine derivates nanometer hollow microsphere and preparation method thereof.
Background technology
Since report polymines (PEI) such as nineteen ninety-five Boussif can be used as non-virus carrier, people had confirmed that by the transfection experiment of vivo and vitro PEI has significant gene transfection efficient, constantly carried out as the various researchs of genophore around PEI.
Application number is that 200510026746.0 Chinese patent application discloses a kind of polyethylene imine nanometer gel and application thereof, described polyethylene imine nanometer gel is by the polymine prepolymer aqueous solution, be no more than at pH under 11 the alkali condition, adopt hydrogen extracting agent to make through the ultraviolet lighting synthetic reaction, its grain diameter is 20nm～600nm.Experiment showed, that this kind polyethylene imine nanometer gel surpasses 30% to the gene transfection efficient of human tumor cells.
M.Laird Forrest discloses polyethylenimine derivates of a kind of biodegradable hypotoxicity high gene conduction efficiency and preparation method thereof and (has seen A degradable polyethylenimine derivative with low toxicityfor highly efficient gene delivery author: Forrest, M.L.Koerber, J.T.Pack, D.W. periodical: Bioconjugate Chemistry 14,934-940), cladodification PEI (800Da) is moved in the scinticounting bottle, be dissolved in distilled carrene, again equimolar diacrylate crosslinking agent is added drop-wise in the solution, seal counting vial then, shake reaction down at 45 ℃ and handed over the PEI derivative particulate of forming molecular weight 14KDa～30KDa in 6 hours, with n-hexane PEI derivative particulate deposits is come out, freeze drying is placed on-80 ℃ and preserves down.The gene transfection efficient that proves this kind PEI derivative particulate by experiment is higher than 2 times～16 times of the PEI of 25KDa, and toxicity is very low even can ignore.But weak point is that the particle diameter of PEI derivative particulate is inhomogeneous.
The polymine or the polyethylenimine derivates as genophore of above-mentioned document record are solid nanoparticle.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of polyethylenimine derivates nanometer hollow microsphere and preparation method thereof is provided, to increase the version of polyethylenimine derivates genophore.
Polyethylenimine derivates nanometer hollow microsphere of the present invention, its spherical shell are the cross-linked polymer that the amido in the cladodification polymine is connected to form by ester bond, and its particle diameter is 50nm～200nm, can at room temperature preserve after the drying.
The preparation method of above-mentioned polyethylenimine derivates nanometer hollow microsphere, processing step is as follows successively:
(1) preparation of nanometer grade silica microballoon
The ammoniacal liquor of 1 part～5 parts of tetraethoxysilanes, 5 parts～25 parts of deionized waters, 20 parts～40 parts of absolute ethyl alcohols, mass concentration 26%～28% is mixed for 18 parts～49 parts, promptly formed the nanometer grade silica microballoon in 1 hour～2 hours normal pressure, 20 ℃～70 ℃ following stirrings, adopt centrifugal separation that the nanometer grade silica microballoon is separated from suspension, standby after cleaning, the vacuum drying;
(2) modification of silicon dioxide microsphere
With 1 part～5 parts ultrasonic being dispersed in 8 parts～64 parts absolute ethyl alcohols of silicon dioxide microsphere of step (1) preparation, after ultrasonic dispersion finishes, under agitation adding and have active group NH
2Silane coupler, its addition reaches 0.05g/ml～0.1g/ml with the concentration in reaction system exceeds, even it is aminated to stir 4 hours～10 hours silicon dioxide microsphere surfaces in normal pressure, 60 ℃～80 ℃ under nitrogen protection, its reaction equation is as follows:
N=0～3; X represents hydrolyzable group
Adopt the centrifugal separation silicon dioxide microsphere that the surface is aminated from reactant liquor, to separate, standby after cleaning, the vacuum drying;
(3) formation of polymine shell
1 part～4 parts ultrasonic being dispersed in 10 parts～60 parts deionized waters of surperficial aminated silicon dioxide microsphere with step (2) preparation; after ultrasonic dispersion finishes; under agitation add 0.2 part～1.0 parts of catalyst concentrated hydrochloric acids; when the pH 8～9 of reaction system; slowly drip 4 parts～24 parts aziridine monomers; under nitrogen protection in normal pressure, stirring at room 2 days～5 days; promptly formed the polymine shell on the silicon dioxide microsphere surface in 1 day～2 days in normal pressure, 60 ℃～80 ℃ stirrings then under nitrogen protection, its reaction equation is as follows:
Adopt centrifugal separation that the microballoon of nucleocapsid structure is separated from reactant liquor, standby after cleaning, the vacuum drying;
(4) the polymine shell is crosslinked
1 part～4 parts ultrasonic being dispersed in 11 parts～88 parts methyl-sulfoxides of microballoon with the nucleocapsid structure of step (3) preparation; after ultrasonic dispersion finishes; under agitation add 1; 2.5 parts～7.5 parts of 4 butanediol diacrylates; with triethylamine reaction system pH is transferred to 8; in 50 ℃～75 ℃ stirrings 3 days～6 days, form the polymine cross-linked polymer even the amido of polymine shell is linked up by ester bond under nitrogen protection, its reaction equation is as follows:
Adopting centrifugal separation is that the nucleocapsid structure microballoon of polymine cross-linked polymer is separated from reactant liquor with shell, cleans, standby after the vacuum drying;
(5) etching of silica core
With the shell of step (4) preparation is 1 part～4 parts ultrasonic being dispersed in 10 parts～50 parts deionized waters of nucleocapsid structure microballoon of polymine cross-linked polymer, after ultrasonic dispersion finishes, under agitation add hydrofluoric acid, the addition of hydrofluoric acid is exceeded to form mass concentration 5%～20% hydrofluoric acid aqueous solution, under normal pressure, room temperature, stirred 40 minutes～8 hours, promptly finish etching to silica core, form the described polyethylenimine derivates nanometer hollow microsphere of claim 1, its reaction equation is as follows:
Solution after the etching is dialysed in deionized water to pH 6～7, be spin-dried for the final vacuum drying;
Raw materials used umber is mass parts in above-mentioned steps (1)～step (5).
In the said method, have active group NH
2Silane coupler be a kind of in gamma-aminopropyl-triethoxy-silane, N-β (aminoethyl)-γ-An Bingjisanjiayangjiguiwan, N-(β-aminoethyl)-gamma-aminopropyl-triethoxy-silane, N-β (aminoethyl)-γ-aminopropyl methyl dimethoxysilane.
In the said method, the speed that step (3) drips the aziridine monomer is 0.2ml/h～5ml/h.
The raw materials used chemical product that routinizes that is of each step of said method can be bought from market.
The present invention has following beneficial effect:
1, a kind of new structure form of hollow microsphere is provided for the polyethylenimine derivates genophore.
2, the hollow microsphere genophore can make gene enter into the inside cavity of carrier; the microballoon spherical shell plays a protective role to gene, and along with the degraded of spherical shell, gene discharges in spherical shell; with non-hollow genophore reduced in comparison time of discharging of gene, more help release to gene.
3, preserve conveniently, can at room temperature preserve after the polyethylenimine derivates nanometer hollow microsphere drying of the present invention.
4, the polyethylenimine derivates nanometer hollow microsphere shape of the method for the invention preparation is the ball-type of rule, monodispersity is better, particle diameter is evenly distributed, and adopts dynamic light scattering to measure, and the difference of the particle diameter of the polyethylenimine derivates nanometer hollow microsphere of same batch of preparation is only ± 10%.
5, adopt the method for the invention, the size of polyethylenimine derivates nanometer hollow microsphere cavity, the thickness of spherical shell are easy to control.
Description of drawings
Fig. 1, Fig. 2 are the transmission electron microscope photos of the method for the invention step (1) nanometer grade silica microballoon that obtains;
Fig. 3 is that the method for the invention step (3) obtains the nanometer grade silica microballoon for nuclear, polymine is the transmission electron microscope photo of the nucleocapsid structure microballoon of shell;
Fig. 4 is that the method for the invention step (4) obtains the nanometer grade silica microballoon for nuclear, the polymine cross-linked polymer is the transmission electron microscope photo of the nucleocapsid structure microballoon of shell;
Fig. 5 is the transmission electron microscope photo of the method for the invention step (5) polyethylenimine derivates nanometer hollow microsphere that obtains;
Fig. 6 is an infared spectrum, wherein a infared spectrum is the infared spectrum of the nanometer grade silica microballoon of the method for the invention step (1) preparation, the b infared spectrum is that the prepared nanometer grade silica microballoon of the method for the invention step (3) is the infared spectrum of the nucleocapsid structure microballoon of shell for nuclear, polymine, and the c infared spectrum is that the nanometer grade silica microballoon of the method for the invention step (4) preparation is the infared spectrum of the nucleocapsid structure microballoon of shell for nuclear, polymine cross-linked polymer; By the contrast of a, b, three infared spectrums of c, 2961 and the 2873cm that in the b infared spectrum, occur
-1The C-H vibrations peak at place should ascribe the methylene among the PEI to, and this explanation PEI successfully grows on the silicon dioxide microsphere surface; At c infared spectrum 1730cm
-1The c=o stretching vibration that the place occurs is the result of the carbonyl in 1,4 butanediol diacrylate, and this explanation 1,4 butanediol diacrylate is crosslinked in the microsphere surface success.
Fig. 7, Fig. 8 are that the nanometer grade silica microballoon of the method for the invention step (4) preparation is the dynamic light scattering figure (annotate: it is bigger than actual particle size usually that dynamic light scattering records particle diameter) of the nucleocapsid structure microballoon of shell for nuclear, polymine cross-linked polymer.
The specific embodiment
Embodiment 1
The processing step of present embodiment is as follows successively:
(1) preparation of nanometer grade silica microballoon
With tetraethoxysilane 1g, deionized water 5g, absolute ethyl alcohol 40g, the ammoniacal liquor 49g of mass concentration 26%～28% mixes in having the reaction vessel of magnetic stirring apparatus, at normal pressure, stir under 20 ℃ and promptly formed the nanometer grade silica microballoon in 2 hours, adopt centrifugal separation that the nanometer grade silica microballoon is separated from suspension, clean 3 times with absolute ethyl alcohol, use washed with de-ionized water again 3 times, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, vacuum is 0.095KPa, the form of the nanometer grade silica microballoon that obtains is seen Fig. 1, and infared spectrum is seen a collection of illustrative plates among Fig. 6;
(2) modification of silicon dioxide microsphere
The adding of 8g absolute ethyl alcohol is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 8g absolute ethyl alcohol of silicon dioxide microsphere 1g with step (1) preparation, after ultrasonic dispersion finishes, under agitation add the gamma-aminopropyl-triethoxy-silane coupling agent, the concentration of its addition in reaction system is 0.05g/ml, under nitrogen protection in normal pressure, even 4 hours silicon dioxide microsphere surfaces of 80 ℃ of stirrings are aminated, adopt the centrifugal separation silicon dioxide microsphere that the surface is aminated from reactant liquor, to separate, with the ultrasonic dispersion-centrifugation of absolute ethyl alcohol 3 times, use the ultrasonic dispersion-centrifugation of deionized water 3 times again, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095KPa;
(3) formation of polymine shell
The adding of 10g deionized water is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 10g deionized water of surperficial aminated silicon dioxide microsphere 1g with step (2) preparation, after ultrasonic dispersion finishes, the concentrated hydrochloric acid 0.24g that under agitation adds mass concentration 37% is as catalyst, after adding concentrated hydrochloric acid, when the pH of reaction system reaches 8, speed with 0.2ml/h drips 4g aziridine monomer, under nitrogen protection in normal pressure, room temperature (26 ℃～35 ℃) stirred 5 days, again under nitrogen protection in normal pressure, 60 ℃ are stirred 1 day promptly at silicon dioxide microsphere surface formation polymine shell, adopt centrifugal separation that the microballoon of nucleocapsid structure is separated from reactant liquor, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, baking temperature is 40 ℃, vacuum is 0.095Kpa, and institute's nanometer grade silica microballoon that obtains is nuclear, polymine is that the form of the nucleocapsid structure microballoon of shell is seen Fig. 3, and infared spectrum is seen the b collection of illustrative plates among Fig. 6;
(4) the polymine shell is crosslinked
The adding of 11g methyl-sulfoxide is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 11g methyl-sulfoxide of microballoon 1g with the nucleocapsid structure of step (3) preparation, after ultrasonic dispersion finishes, under agitation add 1,4 butanediol diacrylate 2.5g, with triethylamine reaction system pH is transferred to 8, under nitrogen protection, in normal pressure, 56 ℃ were stirred 5 days, make the amido of polymine shell be linked up formation polymine cross-linked polymer by ester bond, adopting centrifugal separation is that the nucleocapsid structure microballoon of polymine cross-linked polymer is separated from reactant liquor with shell, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, baking temperature is 40 ℃, vacuum is 0.095Kpa, institute's nanometer grade silica microballoon that obtains is nuclear, the polymine cross-linked polymer is that the form of the nucleocapsid structure microballoon of shell is seen Fig. 4, infared spectrum is seen the c collection of illustrative plates among Fig. 6, dynamic light scattering figure sees Fig. 7, as can be seen from Figure 7,85% particle diameter is distributed in the 190nm-260nm scope, its particle size is more even, and distribution is narrower;
(5) etching of silica core
The adding of 20g deionized water is had in the plastics reaction vessel of magnetic stirring apparatus, with the shell of step (4) preparation is ultrasonic being dispersed in the 20g deionized water of nucleocapsid structure microballoon 1g of polymine cross-linked polymer, after ultrasonic dispersion finishes, the hydrofluoric acid aqueous solution that under agitation adds hydrofluoric acid formation mass concentration 5%, at normal pressure, room temperature (32 ℃) stirred 40 minutes down, promptly finish etching to silica core, form polyethylenimine derivates nanometer hollow microsphere shown in Figure 5, solution after the etching is dialysed in deionized water to pH 7, use Rotary Evaporators that solution is spin-dried for then, institute's polyethylenimine derivates nanometer hollow microsphere that obtains dry 24h in vacuum drying chamber, baking temperature is 40 ℃, and vacuum is 0.095Kpa.
Put into closed container after the polyethylenimine derivates nanometer hollow microsphere vacuum drying of present embodiment preparation, under room temperature, dry environment, preserve and get final product.
Embodiment 2
The processing step of present embodiment is as follows successively:
(1) preparation of nanometer grade silica microballoon
With tetraethoxysilane 5g, deionized water 25g, absolute ethyl alcohol 20g, the ammoniacal liquor 49g of mass concentration 26%～28% mixes in having the reaction vessel of magnetic stirring apparatus, at normal pressure, stir under 40 ℃ and promptly formed the nanometer grade silica microballoon in 2 hours, adopt centrifugal separation that the nanometer grade silica microballoon is separated from suspension then, clean 3 times with absolute ethyl alcohol, use washed with de-ionized water again 3 times, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, vacuum is 0.095KPa, and the form of the nanometer grade silica microballoon that obtains is seen Fig. 2;
(2) modification of silicon dioxide microsphere
The adding of 64g absolute ethyl alcohol is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 64g absolute ethyl alcohol of silicon dioxide microsphere 5g with step (1) preparation, after ultrasonic dispersion finishes, under agitation add N-β (aminoethyl)-γ-An Bingjisanjiayangjiguiwan coupling agent, the concentration of its addition in reaction system is 0.1g/ml, under nitrogen protection in normal pressure, even 10 hours silicon dioxide microsphere surfaces of 80 ℃ of stirrings are aminated, adopt the centrifugal separation silicon dioxide microsphere that the surface is aminated from reactant liquor, to separate then, with the ultrasonic dispersion-centrifugation of absolute ethyl alcohol 3 times, use the ultrasonic dispersion-centrifugation of deionized water 3 times again, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095KPa;
(3) formation of polymine shell
The adding of 30g deionized water is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 30g deionized water of surperficial aminated silicon dioxide microsphere 2g with step (2) preparation, after ultrasonic dispersion finishes, the concentrated hydrochloric acid 0.45g that under agitation adds mass concentration 37% is as catalyst, after adding concentrated hydrochloric acid, when the pH of reaction system reaches 9, speed with 1ml/h drips 24g aziridine monomer, under nitrogen protection in normal pressure, room temperature (26-34 ℃) stirred 2 days, again under nitrogen protection in normal pressure, 80 ℃ are stirred 2 days promptly at silicon dioxide microsphere surface formation polymine shell, adopt centrifugal separation that the microballoon of nucleocapsid structure is separated from reactant liquor, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, baking temperature is 40 ℃, vacuum is 0.095Kpa, and institute's nanometer grade silica microballoon that obtains is nuclear, polymine is the form of the nucleocapsid structure microballoon of shell;
(4) the polymine shell is crosslinked
The adding of 30g methyl-sulfoxide is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 30g methyl-sulfoxide of microballoon 2g with the nucleocapsid structure of step (3) preparation, after ultrasonic dispersion finishes, under agitation add 1,4 butanediol diacrylate 5.0g, with triethylamine reaction system pH is transferred to 8, under nitrogen protection in normal pressure, 50 ℃ were stirred 6 days, even the amido of polymine shell is linked up by ester bond and forms the polymine cross-linked polymer, adopting centrifugal separation is that the nucleocapsid structure microballoon of polymine cross-linked polymer is separated from reactant liquor with shell, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, baking temperature is 40 ℃, vacuum is 0.095Kpa, institute's nanometer grade silica microballoon that obtains is nuclear, the polymine cross-linked polymer is that the dynamic light scattering figure of the nucleocapsid structure microballoon of shell sees Fig. 8, as can be seen from Figure 8,90% particle diameter is distributed in 50nm～70nm scope, its particle size is more even, and distribution is narrower;
(5) etching of silica core
The adding of 30g deionized water is had in the plastics reaction vessel of magnetic stirring apparatus, with the shell of step (4) preparation is ultrasonic being dispersed in the 30g deionized water of nucleocapsid structure microballoon 2g of polymine cross-linked polymer, after ultrasonic dispersion finishes, the hydrofluoric acid aqueous solution that under agitation adds hydrofluoric acid formation mass concentration 10%, at normal pressure, room temperature (28 ℃) stirred 40 minutes down, promptly finish etching to silica core, the polyethylenimine derivates nanometer hollow microsphere, solution after the etching is dialysed in deionized water to pH 6, use Rotary Evaporators that solution is spin-dried for then, institute's polyethylenimine derivates nanometer hollow microsphere that obtains dry 24h in vacuum drying chamber, baking temperature is 40 ℃, and vacuum is 0.095Kpa.
Put into closed container after the polyethylenimine derivates nanometer hollow microsphere vacuum drying of present embodiment preparation, under room temperature, dry environment, preserve and get final product.
Embodiment 3
The processing step of present embodiment is as follows successively:
(1) preparation of nanometer grade silica microballoon
The ammoniacal liquor 18g of tetraethoxysilane 2g, deionized water 10g, absolute ethyl alcohol 30g, mass concentration 26%～28% is mixed in having the reaction vessel of magnetic stirring apparatus, promptly formed the nanometer grade silica microballoon in 1 hour normal pressure, 70 ℃ of following stirrings, adopt centrifugal separation that the nanometer grade silica microballoon is separated from suspension then, clean 3 times with absolute ethyl alcohol, use washed with de-ionized water again 3 times, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095KPa;
(2) modification of silicon dioxide microsphere
The adding of 16g absolute ethyl alcohol is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 16g absolute ethyl alcohol of silicon dioxide microsphere 1g with step (1) preparation, after ultrasonic dispersion finishes, under agitation add N-(β-aminoethyl)-gamma-aminopropyl-triethoxy-silane coupling agent, the concentration of its addition in reaction system is 0.07g/ml, under nitrogen protection in normal pressure, even 6 hours silicon dioxide microsphere surfaces of 70 ℃ of stirrings are aminated, adopt the centrifugal separation silicon dioxide microsphere that the surface is aminated from reactant liquor, to separate then, with the ultrasonic dispersion-centrifugation of absolute ethyl alcohol 3 times, use the ultrasonic dispersion-centrifugation of deionized water 3 times again, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095KPa;
(3) formation of polymine shell
The adding of 15g deionized water is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 15g deionized water of surperficial aminated silicon dioxide microsphere 1g with step (2) preparation, after ultrasonic dispersion finishes, the concentrated hydrochloric acid 0.2g that under agitation adds mass concentration 37% is as catalyst, after adding concentrated hydrochloric acid, when the pH of reaction system reaches 8, speed with 3ml/h drips 10g aziridine monomer, under nitrogen protection in normal pressure, room temperature (24 ℃～34 ℃) stirred 4 days, again under nitrogen protection in normal pressure, 65 ℃ are stirred 1 day promptly at silicon dioxide microsphere surface formation polymine shell, adopt centrifugal separation that the microballoon of nucleocapsid structure is separated from reactant liquor, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, and baking temperature is 40 ℃, and vacuum is 0.095Kpa;
(4) the polymine shell is crosslinked
The adding of 20g methyl-sulfoxide is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 20g methyl-sulfoxide of microballoon 1g with the nucleocapsid structure of step (3) preparation, after ultrasonic dispersion finishes, under agitation add 1,4 butanediol diacrylate 3.2g, with triethylamine reaction system pH is transferred to 8, under nitrogen protection in normal pressure, 60 ℃ were stirred 3 days, even the amido of polymine shell is linked up by ester bond and forms the polymine cross-linked polymer, adopting centrifugal separation is that the nucleocapsid structure microballoon of polymine cross-linked polymer is separated from reactant liquor with shell, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095Kpa;
(5) etching of silica core
The adding of 10g deionized water is had in the plastics reaction vessel of magnetic stirring apparatus, with the shell of step (4) preparation is ultrasonic being dispersed in the 10g deionized water of nucleocapsid structure microballoon 1g of polymine cross-linked polymer, after ultrasonic dispersion finishes, the hydrofluoric acid aqueous solution that under agitation adds hydrofluoric acid formation mass concentration 10%, at normal pressure, room temperature (30 ℃) stirred 3 hours down, promptly finish etching to silica core, the polyethylenimine derivates nanometer hollow microsphere, solution after the etching is dialysed in deionized water to pH 7, use Rotary Evaporators that solution is spin-dried for then, institute's polyethylenimine derivates nanometer hollow microsphere that obtains dry 24h in vacuum drying chamber, baking temperature is 40 ℃, and vacuum is 0.095Kpa.
The polyethylenimine derivates nanometer hollow microsphere of present embodiment preparation, its 90% particle diameter is distributed in 96nm～104nm scope, puts into closed container after the vacuum drying, preserves to get final product under room temperature, dry environment.
Embodiment 4
The processing step of present embodiment is as follows successively:
(1) preparation of nanometer grade silica microballoon
The ammoniacal liquor 30g of tetraethoxysilane 4g, deionized water 20g, absolute ethyl alcohol 40g, mass concentration 26%～28% is mixed in having the reaction vessel of magnetic stirring apparatus, promptly formed the nanometer grade silica microballoon in 2 hours normal pressure, 60 ℃ of following stirrings, adopt centrifugal separation that the nanometer grade silica microballoon is separated from suspension then, clean 3 times with absolute ethyl alcohol, use washed with de-ionized water again 3 times, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095KPa;
(2) modification of silicon dioxide microsphere
The adding of 32g absolute ethyl alcohol is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 32g absolute ethyl alcohol of silicon dioxide microsphere 4g with step (1) preparation, after ultrasonic dispersion finishes, under agitation add N-β (aminoethyl)-γ-aminopropyl methyl dimethoxysilane coupling agent, the concentration of its addition in reaction system is 0.05g/ml, under nitrogen protection in normal pressure, even 8 hours silicon dioxide microsphere surfaces of 60 ℃ of stirrings are aminated, adopt the centrifugal separation silicon dioxide microsphere that the surface is aminated from reactant liquor, to separate then, with the ultrasonic dispersion-centrifugation of absolute ethyl alcohol 3 times, use the ultrasonic dispersion-centrifugation of deionized water 3 times again, dry 8h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095KPa;
(3) formation of polymine shell
The adding of 60g deionized water is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 60g deionized water of surperficial aminated silicon dioxide microsphere 4g with step (2) preparation, after ultrasonic dispersion finishes, the concentrated hydrochloric acid 1.0g that under agitation adds mass concentration 37% is as catalyst, after adding concentrated hydrochloric acid, when the pH of reaction system reaches 8, speed with 5ml/h drips 10g aziridine monomer, under nitrogen protection in normal pressure, room temperature (24 ℃～36 ℃) stirred 5 days, again under nitrogen protection in normal pressure, 75 ℃ are stirred 2 days promptly at silicon dioxide microsphere surface formation polymine shell, adopt centrifugal separation that the microballoon of nucleocapsid structure is separated from reactant liquor, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, and baking temperature is 40 ℃, and vacuum is 0.095Kpa;
(4) the polymine shell is crosslinked
The adding of 88g methyl-sulfoxide is had in the reaction vessel of magnetic stirring apparatus, ultrasonic being dispersed in the 88g methyl-sulfoxide of microballoon 4g with the nucleocapsid structure of step (3) preparation, after ultrasonic dispersion finishes, under agitation add 1,4 butanediol diacrylate 7.5g, with triethylamine reaction system pH is transferred to 8, under nitrogen protection in normal pressure, 75 ℃ were stirred 3 days, even the amido of polymine shell is linked up by ester bond and forms the polymine cross-linked polymer, adopting centrifugal separation is that the nucleocapsid structure microballoon of polymine cross-linked polymer is separated from reactant liquor with shell, with the ultrasonic dispersion-centrifugation of deionized water 3 times, dry 24h is standby in vacuum drying chamber then, baking temperature is 40 ℃, and vacuum is 0.095Kpa;
(5) etching of silica core
The adding of 50g deionized water is had in the plastics reaction vessel of magnetic stirring apparatus, with the shell of step (4) preparation is ultrasonic being dispersed in the 50g deionized water of nucleocapsid structure microballoon 4g of polymine cross-linked polymer, after ultrasonic dispersion finishes, the hydrofluoric acid aqueous solution that under agitation adds hydrofluoric acid formation mass concentration 20%, at normal pressure, room temperature (34 ℃) stirred 8 hours down, promptly finish etching to silica core, the polyethylenimine derivates nanometer hollow microsphere, solution after the etching is dialysed in deionized water to pH 6～7, use Rotary Evaporators that solution is spin-dried for then, institute's polyethylenimine derivates nanometer hollow microsphere that obtains dry 24h in vacuum drying chamber, baking temperature is 40 ℃, and vacuum is 0.095Kpa.
The polyethylenimine derivates nanometer hollow microsphere of present embodiment preparation, its 80% particle diameter is distributed in 173nm～185nm scope, puts into closed container after the vacuum drying, preserves to get final product under room temperature, dry environment.
Claims (4)
1, a kind of polyethylenimine derivates nanometer hollow microsphere, the spherical shell that it is characterized in that described hollow microsphere are the cross-linked polymer that the amido in the cladodification polymine is connected to form by ester bond, and the particle diameter of described hollow microsphere is 50nm～200nm.
2, the preparation method of the described polyethylenimine derivates nanometer hollow microsphere of a kind of claim 1 is characterized in that processing step is as follows successively:
(1) preparation of nanometer grade silica microballoon
The ammoniacal liquor of 1 part～5 parts of tetraethoxysilanes, 5 parts～25 parts of deionized waters, 20 parts～40 parts of absolute ethyl alcohols, mass concentration 26%～28% is mixed for 18 parts～49 parts, promptly formed the nanometer grade silica microballoon in 1 hour～2 hours normal pressure, 20 ℃～70 ℃ following stirrings, adopt centrifugal separation that the nanometer grade silica microballoon is separated from suspension, standby after cleaning, the vacuum drying;
(2) modification of silicon dioxide microsphere
With 1 part～5 parts ultrasonic being dispersed in 8 parts～64 parts absolute ethyl alcohols of silicon dioxide microsphere of step (1) preparation, after ultrasonic dispersion finishes, under agitation adding and have active group NH
2Silane coupler, its addition reaches 0.05g/ml～0.1g/ml with the concentration in reaction system and exceeds, even it is aminated to stir 4 hours～10 hours silicon dioxide microsphere surfaces in normal pressure, 60 ℃～80 ℃ under nitrogen protection, adopt the centrifugal separation silicon dioxide microsphere that the surface is aminated from reactant liquor, to separate, standby after cleaning, the vacuum drying;
(3) formation of polymine shell
1 part～4 parts ultrasonic being dispersed in 10 parts～60 parts deionized waters of surperficial aminated silicon dioxide microsphere with step (2) preparation, after ultrasonic dispersion finishes, under agitation add 0.2 part～1.0 parts of catalyst concentrated hydrochloric acids, when the pH 8～9 of reaction system, slowly drip 4 parts～24 parts aziridine monomers, under nitrogen protection in normal pressure, stirring at room 2 days～5 days, then under nitrogen protection in normal pressure, 60 ℃～80 ℃ are stirred 1 day～2 days promptly at silicon dioxide microsphere surface formation polymine shell, adopt centrifugal separation that the microballoon of nucleocapsid structure is separated from reactant liquor, clean, standby after the vacuum drying;
(4) the polymine shell is crosslinked
1 part～4 parts ultrasonic being dispersed in 11 parts～88 parts methyl-sulfoxides of microballoon with the nucleocapsid structure of step (3) preparation, after ultrasonic dispersion finishes, under agitation add 1,2.5 parts～7.5 parts of 4 butanediol diacrylates, with triethylamine reaction system pH is transferred to 8, under nitrogen protection, stirred 3 days～6 days in 50 ℃～75 ℃, even the amido of polymine shell is linked up by ester bond and forms the polymine cross-linked polymer, adopting centrifugal separation is that the nucleocapsid structure microballoon of polymine cross-linked polymer is separated from reactant liquor with shell, cleans, standby after the vacuum drying;
(5) etching of silica core
With the shell of step (4) preparation is 1 part～4 parts ultrasonic being dispersed in 10 parts～50 parts deionized waters of nucleocapsid structure microballoon of polymine cross-linked polymer, after ultrasonic dispersion finishes, under agitation add hydrofluoric acid, the addition of hydrofluoric acid is exceeded to form mass concentration 5%～20% hydrofluoric acid aqueous solution, at normal pressure, stirred 40 minutes～8 hours under the room temperature, promptly finish etching to silica core, form the described polyethylenimine derivates nanometer hollow microsphere of claim 1, solution after the etching is dialysed in deionized water to pH 6～7, be spin-dried for the final vacuum drying;
Raw materials used umber is mass parts in above-mentioned steps (1)～step (5).
3,, it is characterized in that having active group NH according to the preparation method of the described polyethylenimine derivates nanometer hollow microsphere of claim 2
2Silane coupler be a kind of in gamma-aminopropyl-triethoxy-silane, N-β (aminoethyl)-γ-An Bingjisanjiayangjiguiwan, N-(β-aminoethyl)-gamma-aminopropyl-triethoxy-silane, N-β (aminoethyl)-γ-aminopropyl methyl dimethoxysilane.
4,, it is characterized in that the speed of dropping aziridine monomer in the step (3) is 0.2ml/h～5ml/h according to the preparation method of claim 2 or 3 described polyethylenimine derivates nanometer hollow microspheres.
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| CN102036773A (en) * | 2008-03-19 | 2011-04-27 | 巴斯夫欧洲公司 | Metallic nanoparticles stabilised with derivatisied polyethylenimines or polyvinylamines |
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| CN104399427A (en) * | 2014-12-16 | 2015-03-11 | 莆田学院 | Preparation method and application of porous silicon dioxide microsphere adsorbent |
| CN108202140A (en) * | 2016-12-16 | 2018-06-26 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | The seed mediated growth method of polyethyleneimine prepares silicon core silver core-shell nanoparticles |
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