CN102886232A - Device for preparing polymer microsphere with controllable grain size and method thereof - Google Patents
Device for preparing polymer microsphere with controllable grain size and method thereof Download PDFInfo
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- CN102886232A CN102886232A CN2012103978591A CN201210397859A CN102886232A CN 102886232 A CN102886232 A CN 102886232A CN 2012103978591 A CN2012103978591 A CN 2012103978591A CN 201210397859 A CN201210397859 A CN 201210397859A CN 102886232 A CN102886232 A CN 102886232A
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Abstract
The invention relates to a device for preparing polymer microspheres with controllable grain size and a method thereof. The device comprises a disposable dropper, a cover plate with a hole, a reactor, a temperature control system and a magnetic force stirring system, wherein the cover plate is covered above the reactor, four fixing legs are arranged below the cover plate, so as to fix the cover plate above the reactor, the disposable dropper is inserted and matched with the hole of the cover plate, the reactor is placed in a constant-temperature bath of the temperature control system, one temperature probe is inserted into water of a constant-temperature water bath, and a magnetic force stirrer of the magnetic force stirring system is placed on inner bottom of the constant-temperature water bath. With adoption of the device and method disclosed by the invention, the polymer microspheres with regular and controllable grain size can be prepared; and the polymer microspheres can be taken as a drug carrier, a fluorescent mark carrier, a cell growth carrier and the like. Grain size distribution of the prepared microspheres is smaller, and the phenomenon that volatilation of organic solvent is prevented as massive microspheres gather together and a polymer membrane is formed on water surface can be effectively avoided. With adoption of the device provided by the invention, all the parameters are accurate, operation is more standard, and repeatability is strong, so that the device provided by the invention is more beneficial to market promotion.
Description
Technical field
The present invention relates to a kind of controlled polymer microsphere devices and methods therefor of particle diameter for preparing.
Background technology
Polymer microsphere refers to that material is made of macromolecular material, the sphere of particle size range between the 1-1000 micron or hollow body or the entity of class sphere.Its Main Function be enrichment medicine, fluorescence or magnetisable material at microsphere surface, or it is wrapped in the microsphere, serve as slow releasing carrier of medication, drug targeting carrier, fluorescent mark carrier and magnetic function carrier.
The method for preparing at present microballoon mainly contains (1) spray drying process, (2) supercritical fluid method, (3) monomer polymerization method and (4) solvent evaporation method.With first three methods contrast, the operating process of solvent evaporation method is simpler, so most of microballoon all adopts the method preparation (such as application number: 201010126667.8; 200310113439.7; 201110114305.1).The method also exists simultaneously particle size to be difficult to control, and particle size distribution range is excessive, and the problems such as microballoon out-of-shape need be carried out the subsequent operations such as separation of particle diameter (such as application number: 200810083448.9).The further utilization that this has restricted solvent evaporation method has increased production cost simultaneously.
So a kind of new method or the process units that can effectively control polymer microsphere particle size and distribution seems particularly important.
Summary of the invention
One of the object of the invention provides a kind of device for preparing the controlled polymer microsphere of particle diameter.
Two of purpose of the present invention is to provide the method that adopts this this molecule microballoon of device preparation.
For achieving the above object, the present invention adopts following technical scheme:
A kind of device for preparing the controlled polymer microsphere of particle diameter, comprise disposable dropper, cover plate, reactor, temperature-controlling system and magnetic agitation system with holes, it is characterized in that cover plate covers on reactor, there are four fixing feet that it is fixed on above the reactor below the cover plate, the hole inserting of disposable dropper and cover plate, reactor is placed in the thermostat of temperature-controlling system, and the magnetic stir bar that temperature probe is inserted in a magnetic agitation system in the water of Water Tank with Temp.-controlled is placed at the interior end of Water Tank with Temp.-controlled.
The material of above-mentioned disposable dropper is glass or etch-proof plastics.
Above-mentioned disposable dropper is the tubulose vertebral body structure, and the upper end is larger, and the lower end is less, and the pore size scope of lower ending opening is 0.5-3 mm, and body can be inserted on the dividing plate with holes fixing.
The planar profile of the cover plate of above-mentioned (2) with holes is square, and it is porose to distribute on the diagonal, being arranged as centered by the interstitial hole of its hole, and a straight path is arranged to both sides symmetrically.
The preparation method of the polymer microsphere that a kind of particle diameter is controlled adopts above-mentioned device, it is characterized in that the concrete steps of the method are:
A. select suitable disposable dropper, insert in the jack of reactor cover plate;
B. dispose stabiliser solution as water, pour in the reactor, put one piece of magnetic stir bar in the reactor;
C. the cover plate among the step a is held in the reactor top, is fixed by four fixing feet of cover plate lower end;
D. the reactor among the step c is placed in the Water Tank with Temp.-controlled of temperature-controlling system, temperature probe is put into the water of Water Tank with Temp.-controlled, open temperature-controlling system, regulate temperature to 4-40 ℃;
E. open the magnetic agitation system, regulate mixing speed at 50-300 rpm;
F. the microballoon component is dissolved in have and prepares organic phase in the solvent, organic phase is injected disposable dropper, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper on the cover plate; The mass ratio of described microballoon component and stabilizing agent is: 5:0.05-5:50.
G. after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove destabilizing agent by centrifugal or filter method, can obtain the polymer microsphere of required particle diameter.
The particle diameter of the microballoon that said method is prepared is 1 μ m-800 μ m; , microspherulite diameter is spherical or the ellipsoid shape.
The component of above-mentioned microballoon is that biology can fall. at least a in the macromolecular material of solution, biological nondegradable macromolecular material and the on-macromolecular material.
Above-mentioned biodegradable macromolecular material is PLA, polycaprolactone or poly-olefin(e) acid; The nondegradable macromolecular material of described biology is polystyrene; Described on-macromolecular material is DNA, medicine, protein, micromolecular compound, fluorescent material, nano-silicon or Nano Silver
Above-mentioned aqueous phase stabilizing agent is polyvinyl alcohol, polyethylene glycol or enuatrol, and its concentration range is 0.05-3g/100ml.
The concentration of material is 1-50g/100ml in the above-mentioned organic phase.
The present invention's imagination is dissolved macromolecular material in the organic solvent, drips aqueous phase by special device, obtains the polymer microsphere of rule by stirring the volatilization organic solvent.Prepared microspherulite diameter is between the 1 μ m-800 μ m, and is convenient to be controlled to be particle diameter and the distribution of microballoon, and outward appearance is spherical or the ellipsoid shape, mainly applies to pharmaceutical carrier, fluorescence labeling, and cell carriers etc. also can be used for other field.
Described preparation facilities is mainly by magnetic agitation speed, the pore size of disposable dropper lower ending opening and in particle size and the distribution of the determining positions polymer microsphere of cover plate; Kind and the concentration of component of macromolecular material in the while organic phase, the kind of aqueous phase stabilizing agent and concentration, the factors such as reaction temperature also can exert an influence to particle size and the distribution of polymer microsphere.
The material of described disposable dropper can be glass, also can be etch-proof plastics, should preferentially select glass, and the pore size scope of its lower ending opening is 0.5-3 mm.During use, disposable dropper lower end should be immersed in water liquid level below, prevents that the water surface from forming polymeric membrane and causing the organic solvent volatilization.
Described aqueous phase stabilizing agent can be in polyvinyl alcohol, polyethylene glycol, the enuatrol one or more, should preferentially be chosen as polyvinyl alcohol, and its concentration range is 0.05-3g/100ml.
The concentration unit of material is 1-50g/100ml in the described organic phase.
The reaction temperature that described temperature-controlling system provides is 4-40 ℃.
The mixing speed that described magnetic agitation system provides is 50-300 rpm.
The preparation method of the polymer microsphere that a kind of particle diameter disclosed by the invention is controlled and the device of preparation.Use method and apparatus of the present invention, can prepare particle diameter rule and controlled polymer microsphere; The particle diameter of prepared microballoon is 1 μ m-800 μ m, and outward appearance is spherical or the ellipsoid shape, can be used as the carrier of pharmaceutical carrier, fluorescent mark carrier, Growth of Cells etc.Use device provided by the invention can pass through to regulate magnetic agitation speed, the pore size of disposable dropper lower ending opening and in the particle size of the Position Control polymer microsphere of dividing plate, shorten distribution, prepared polymer microsphere regular shape, repeatability is better.Its device allows the small-scale production of the microballoon of repetition, also can enlarge the production scale that material quantity enlarge microballoon by control.
Under the identical condition, use device provided by the invention under Action of Gravity Field, with organic phase slowly at the uniform velocity splash into aqueous phase, reducing microballoon reunites in a large number, avoid water surface formation polymeric membrane and hinder the phenomenon that organic solvent volatilizees, prepared microballoon distributes less with the particle diameter of the microballoon that uses conventional methods preparation; Can accurately unite owing to use this to install all parameters, operate more standard, repeatability is stronger, more is conducive to marketing.
Description of drawings
Fig. 1 is the schematic diagram of polymer microsphere preparation facilities of the present invention and use thereof.Wherein 1-6 is the core of device, and 1 is dividing plate, and 2 is the hole on the dividing plate, 3 is reaction chamber, 4 is disposable dropper, and 5 is the fixator of dividing plate lower end, and 6 is the Water Tank with Temp.-controlled in the temperature-controlling system, 7 is the magnetic agitation system, 8 is temperature controller, and 9 is the temperature probe in the temperature-controlling system, and 10 is prepared polymer microsphere, 11 is organic phase, and 12 is stirrer.
Fig. 2 is the profile of the core of apparatus of the present invention.
Fig. 3 is the top view of the core of apparatus of the present invention.
Fig. 4 is the upward view of the core of apparatus of the present invention.
Fig. 5 is the side view of the core of apparatus of the present invention.
Fig. 6 is the prepared polylactic acid microsphere of polymer microsphere preparation facilities of the present invention.
Fig. 7 be the particle diameter of the prepared polylactic acid microsphere of polymer microsphere preparation facilities of the present invention distribute and the same terms under the conventional method preparation the particle diameter distribution of polylactic acid microsphere.Wherein 1 for conventional method preparation the particle diameter of polylactic acid microsphere distribute, 2 be the particle diameter distribution of the prepared polylactic acid microsphere of device provided by the invention.
The specific embodiment
Embodiment 1:The device of the polymer microsphere that preparation particle diameter of the present invention is controlled, comprise disposable dropper 4, with holes 2 cover plate 1, reactor 3, temperature-controlling system 8 and magnetic agitation system 7, it is characterized in that cover plate 1 covers on reactor 3, there are four fixing feet 5 that it is fixed on above the reactor 3 below the cover plate 1, hole 2 insertings of disposable dropper 4 and cover plate 1, reactor 3 is placed in the thermostat 6 of temperature-controlling system 8, and the magnetic stir bar 12 that temperature probe 9 is inserted in a magnetic agitation system in the water of Water Tank with Temp.-controlled 6 is placed at the interior end of Water Tank with Temp.-controlled 6.
Embodiment 2: the concrete steps of method of the present invention are:
A. select suitable disposable dropper 4, insert in the jack 2 of reactor 3 cover plates 1;
B. dispose stabiliser solution as water, pour in the reactor 3, put one piece of magnetic stir bar 12 in the reactor 3;
C. the cover plate 1 among the step a is held in reactor 3 tops, fixing by four fixing feet 5 of cover plate 3 lower ends;
D. the reactor 3 among the step c is placed in the Water Tank with Temp.-controlled 6 of temperature-controlling system 8, temperature probe 9 is put into the water of Water Tank with Temp.-controlled 6, open temperature-controlling system, regulate temperature to 4-40 ℃;
E. open the magnetic agitation system, regulate mixing speed at 50-300 rpm;
F. the microballoon component is dissolved in have and prepares organic phase in the solvent, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1; The mass ratio of described microballoon component and stabilizing agent is: 5:0.05-5:50.
G. after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove destabilizing agent by centrifugal or filter method, can obtain the polymer microsphere of required particle diameter.
Embodiment 3:Selecting the lower ending opening aperture is the disposable dropper 4 of 0.5mm, inserts in the hole 2 of corresponding cover plate 1.The 3g/100ml PVA solution of configuration 200ml is water, pours in the reactor 3, puts one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, close temperature-controlling system, reaction temperature is room temperature, opens the magnetic agitation system, and regulating mixing speed is 300 rpm.The 1g PLA is dissolved in the 20ml chloroform, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the dividing plate, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polylactic acid microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polylactic acid microsphere most, and minority is the ellipsoid shape, and average grain diameter is 1.05 ± 0.85 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polylactic acid microsphere that obtains has a small amount of agglomeration, and its average grain diameter is 1.21 ± 1.32 μ m.
Conclusion: adopt the polylactic acid microsphere particle size and distribution of device preparation provided by the invention all less than the prepared polylactic acid microsphere of traditional operation method.
Embodiment 4:Selecting the lower ending opening aperture is the disposable dropper 4 of 3mm, inserts in the hole 2 of corresponding cover plate 1.The 1g/100ml PVA solution of configuration 200ml is water, pours in the reactor 3, puts one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 4 ℃, opens the magnetic agitation system, and regulating mixing speed is 100 rpm.The 1g PLA is dissolved in the carrene, form organic phase, organic phase is injected disposable dropper, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polylactic acid microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polylactic acid microsphere most, and minority is the ellipsoid shape, and average grain diameter is 488 ± 57.0 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polylactic acid microsphere that obtains has a small amount of agglomeration, and its average grain diameter is 490 ± 102.2 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: the prepared polylactic acid microsphere of the polylactic acid microsphere average grain diameter that adopts device provided by the invention preparation and traditional operation method approaches, but the particle diameter distribution that particle diameter distributes and is significantly less than the prepared microballoon of traditional operation method.
Embodiment 5:Selecting the lower ending opening aperture is the disposable dropper 4 of 1mm, inserts in the hole 2 of corresponding cover plate 1.The 0.05g/100ml PVA solution of configuration 200ml is water, pour in the reactor 3, put one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 10 ℃, open the magnetic agitation system, regulating mixing speed is 100 rpm.The 1g PLA is dissolved in the carrene, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polylactic acid microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polylactic acid microsphere most, and minority is the ellipsoid shape, and average grain diameter is 704 ± 33.8 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polylactic acid microsphere that obtains has a large amount of agglomerations, and its average grain diameter is 730 ± 118.5 μ m.Conclusion: the prepared polylactic acid microsphere of the polylactic acid microsphere average grain diameter that adopts device provided by the invention preparation and traditional operation method approaches, but the particle diameter distribution that particle diameter distributes and is significantly less than the prepared microballoon of traditional operation method.
Embodiment 6:Selecting the lower ending opening aperture is the disposable dropper 4 of 1mm, inserts in the hole 2 of corresponding cover plate 1.The 0.1g/100ml PVA solution of configuration 200ml is water, pour in the reactor 1, put one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 10 ℃, open the magnetic agitation system, regulating mixing speed is 100 rpm.With the 0.5g PLA just and the 0.5g polycaprolactone be dissolved in the 20ml chloroform, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polylactic acid and caprolactone microballoon of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polylactic acid and caprolactone microballoon most, and minority is the ellipsoid shape, and average grain diameter is 637 ± 22.7 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polylactic acid and caprolactone microballoon that obtains has a large amount of agglomerations, and its average grain diameter is 634 ± 161.1 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: the prepared microballoon of the polylactic acid and caprolactone microsphere average grain diameter that adopts device provided by the invention preparation and traditional operation method approaches, but the particle diameter distribution that particle diameter distributes and is significantly less than the prepared microballoon of traditional operation method.
Embodiment 7:Selecting the lower ending opening aperture is the disposable dropper 4 of 1mm, inserts in the hole 2 of corresponding cover plate 1.The 1g/100ml PVA solution of configuration 200ml is water, pours in the reactor 3, puts one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 20 ℃, opens the magnetic agitation system, and regulating mixing speed is 200 rpm.The 1g PLA is dissolved in the carrene, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the dividing plate, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polylactic acid microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, observing prepared polylactic acid microsphere most is the ellipsoid shape, and minority is spherical, and average grain diameter is 481 ± 61.4 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polylactic acid microsphere that obtains has a large amount of agglomerations, and its average grain diameter is 502 ± 158.0 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: adopt the polylactic acid microsphere average grain diameter of device preparation provided by the invention and average grain diameter and the distribution that distribution is significantly less than the prepared microballoon of traditional operation method.
Embodiment 8:Selecting the lower ending opening aperture is the disposable dropper 4 of 1mm, inserts in the hole of corresponding dividing plate.The 0.05g/100ml PVA solution of configuration 200ml is water, pour in the reactor, put one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 10 ℃, open the magnetic agitation system, regulating mixing speed is 100 rpm.The 1g polystyrene is dissolved in the 20ml chloroform, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polystyrene microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polystyrene microsphere most, and only a few is the ellipsoid shape, and average grain diameter is 405 ± 37.7 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polystyrene microsphere that obtains has a large amount of agglomerations, and its average grain diameter is 502 ± 89.2 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: adopt the polystyrene microsphere average grain diameter of device preparation provided by the invention and average grain diameter and the distribution that distribution is significantly less than the prepared microballoon of traditional operation method.
Embodiment 9:Selecting the lower ending opening aperture is the disposable dropper 4 of 2mm, inserts in the hole 2 of corresponding cover plate 1.The 0.5g/100ml PVA solution of configuration 200ml is water, pour in the reactor 3, put one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 10 ℃, open the magnetic agitation system, regulating mixing speed is 50 rpm.The 1g polystyrene is dissolved in the carrene, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polystyrene microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polystyrene microsphere most, and minority is the ellipsoid shape, and average grain diameter is 771 ± 13.5 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polystyrene microsphere that obtains has a large amount of agglomerations, and its average grain diameter is 702 ± 55.4 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: adopt the polystyrene microsphere average grain diameter of device preparation provided by the invention and average grain diameter and the distribution that distribution is significantly less than the prepared microballoon of traditional operation method.
Embodiment 10:Selecting the lower ending opening aperture is the disposable dropper 4 of 2mm, inserts in the hole 2 of corresponding cover plate 1.The 0.5g/100ml PVA solution of configuration 200ml is water, pour in the reactor 3, put one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 10 ℃, open the magnetic agitation system, regulating mixing speed is 150 rpm.The 1g polystyrene is dissolved in the carrene, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polystyrene microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, it is spherical observing prepared polystyrene microsphere most, and minority is the ellipsoid shape, and average grain diameter is 771 ± 13.5 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polystyrene microsphere that obtains has a large amount of agglomerations, and its average grain diameter is 800 ± 72.1 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: adopt the polystyrene microsphere average grain diameter of device preparation provided by the invention and average grain diameter and the distribution that distribution is significantly less than the prepared microballoon of traditional operation method.
Embodiment 11:Selecting the lower ending opening aperture is the disposable dropper 4 of 2mm, inserts in the hole 2 of corresponding cover plate 1.The 2g/100ml PVA solution of configuration 200ml is water, pours in the reactor 3, puts one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 40 ℃, opens the magnetic agitation system, and regulating mixing speed is 250 rpm.The 1g polystyrene is dissolved in the carrene, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polystyrene microsphere of required particle diameter.
By particle size determination instrument and scanning electron microscope analysis, observing prepared polystyrene microsphere most is the ellipsoid shape, and minority is spherical, and average grain diameter is 237 ± 47.8 μ m.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polystyrene microsphere that obtains has a large amount of agglomerations, and its average grain diameter is 202 ± 115.7 μ m.Simultaneously, in the preparation process, the water surface occurs and form the phenomenon that polymeric membrane hinders the organic solvent volatilization.
Conclusion: adopt the polystyrene microsphere average grain diameter of device preparation provided by the invention and average grain diameter and the distribution that distribution is significantly less than the prepared microballoon of traditional operation method.
Embodiment 12:Selecting the lower ending opening aperture is the disposable dropper 4 of 2mm, inserts in the hole 2 of corresponding cover plate 1.The 2g/100ml PVA solution of configuration 200ml is water, pours in the reactor, puts one piece of magnetic stir bar 12, cover plate 1 is held in reactor 3 tops, fixing by fixing feet 5, open temperature-controlling system 8, setting reaction temperature is 10 ℃, opens the magnetic agitation system, and regulating mixing speed is 150 rpm.In being dissolved in the rhodamine B of 1g polystyrene and 5mg in the 20ml chloroform, form organic phase, organic phase is injected disposable dropper 4, treat that organic phase splashes into aqueous phase fully, extract the disposable dropper 4 on the cover plate 1, magnetic agitation 24 hours, after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove PVA by centrifugal or filter method, can obtain the polystyrene microsphere of the load red fluorescent material rhodamine B of required particle diameter.
By particle size determination instrument, scanning electron microscope analysis and fluorescence microscope, observing prepared polystyrene microsphere most is the ellipsoid shape, and minority is spherical, and average grain diameter is 512 ± 34.2 μ m, and microballoon is aobvious red under fluorescence microscope.
Adopt above-mentioned identical organic phase and water component, do not use this device, directly organic phase is poured or directly is added drop-wise to into aqueous phase, mixing speed magnetic agitation same as described above 24 hours, after removing PVA by centrifugal or filter method, the polylactic acid microsphere that obtains has a small amount of agglomeration, and its average grain diameter is 584 ± 93.11 μ m.
Conclusion: adopt the polystyrene microsphere particle size and distribution of load red fluorescent material rhodamine B of device provided by the invention preparation all less than the polystyrene microsphere of the prepared load red fluorescent material rhodamine B of traditional operation method.
Claims (10)
1. device for preparing the controlled polymer microsphere of particle diameter, comprise disposable dropper (4), the cover plate of (2) with holes (1), reactor (3), temperature-controlling system (8) and magnetic agitation system (7), it is characterized in that cover plate (1) covers on reactor (3), there are four fixing feet (5) that it is fixed on above the reactor (3) below the cover plate (1), hole (2) inserting of disposable dropper (4) and cover plate (1), reactor (3) is placed in the thermostat (6) of temperature-controlling system (8), and the magnetic stir bar (12) that a temperature probe (9) is inserted in a magnetic agitation system in the water of Water Tank with Temp.-controlled (6) is placed at the interior end of Water Tank with Temp.-controlled (6).
2. the device of the controlled polymer microsphere of preparation particle diameter according to claim 1, the material that it is characterized in that described disposable dropper (4) is glass or etch-proof plastics.
3. the device of the controlled polymer microsphere of preparation particle diameter according to claim 1, it is characterized in that described disposable dropper (4) is the tubulose vertebral body structure, the upper end is larger, and the lower end is less, the pore size scope of lower ending opening is 0.5-3 mm, and body can be inserted on the dividing plate with holes fixing.
4. the device of the controlled polymer microsphere of preparation particle diameter according to claim 1, the planar profile that it is characterized in that the cover plate (1) of described (2) with holes is square, it is porose to distribute on the diagonal, being arranged as centered by the interstitial hole of its hole (2), a straight path is arranged to both sides symmetrically.
5. the preparation method of the controlled polymer microsphere of a particle diameter, adopt according to power: profit requires each described device in 1-5, it is characterized in that the concrete steps of the method are:
A. select suitable disposable dropper (4), insert in the jack (2) of reactor (3) cover plate (1);
B. dispose stabiliser solution as water, pour in the reactor (3), put one piece of magnetic stir bar (12) in the reactor (3);
C. the cover plate among the step a (1) is held in reactor (3) top, fixing by four fixing feet (5) of cover plate (3) lower end;
D. the reactor among the step c (3) is placed in the Water Tank with Temp.-controlled (6) of temperature-controlling system (8), temperature probe (9) is put into the water of Water Tank with Temp.-controlled (6), open temperature-controlling system, regulate temperature to 4-40 ℃;
E. open the magnetic agitation system, regulate mixing speed at 50-300 rpm;
F. the microballoon component is dissolved in have and prepares organic phase in the solvent, organic phase is injected disposable dropper (4), treat that organic phase splashes into aqueous phase fully, extract the disposable dropper (4) on the cover plate (1); The mass ratio of described microballoon component and stabilizing agent is: 5:0.05～5:50;
G. after organic solvent volatilizees fully, close temperature-controlling system and magnetic agitation system, remove destabilizing agent by centrifugal or filter method, can obtain the polymer microsphere of required particle diameter.
6. the method for the above according to claim 5, the particle diameter that it is characterized in that the microballoon that the method is prepared is 1 μ m-800 μ m; , microspherulite diameter is spherical or the ellipsoid shape.
7. method according to claim 5, the component that it is characterized in that described microballoon are at least a in biodegradable macromolecular material, biological nondegradable macromolecular material and the on-macromolecular material.
8. method according to claim 7 is characterized in that described biodegradable macromolecular material is PLA, polycaprolactone or poly-olefin(e) acid; The nondegradable macromolecular material of described biology is polystyrene; Described on-macromolecular material is DNA, medicine, protein, micromolecular compound, fluorescent material, nano-silicon or Nano Silver.
9. method according to claim 5 is characterized in that described aqueous phase stabilizing agent is polyvinyl alcohol, polyethylene glycol or enuatrol, and its concentration range is 0.05～3g/100ml.
10. method according to claim 5, the concentration that it is characterized in that material in the described organic phase is 1～50g/100ml.
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| CN104227011A (en) * | 2014-08-29 | 2014-12-24 | 南京邮电大学 | Device for preparing nano-metallic material in macroscopic amount and preparation method for nano-metallic material |
| CN105061652A (en) * | 2015-08-21 | 2015-11-18 | 哈尔滨工业大学 | Preparation method of DNA-polymer hollow microspheres |
| CN108704578A (en) * | 2018-04-20 | 2018-10-26 | 中国药科大学 | A kind of equipment of continuous production microballoon and its application |
| CN110681323A (en) * | 2019-08-26 | 2020-01-14 | 上海摩漾生物科技有限公司 | Golf ball type degradable microsphere with micro-topological structure and preparation method thereof |
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