CN102311945A - Temperature-pH dual-sensitivity gel microsphere as well as preparation method and application thereof - Google Patents
Temperature-pH dual-sensitivity gel microsphere as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a gel microsphere product having temperature-pH dual-sensitivity. The average pore size of the gel microsphere is in a range of nanometers to 200 nm and the average grain size thereof is 1-100 microns. The preparation method comprises the following steps of: (1) providing an aqueous solution which is dissolved with water-soluble monomer N-isopropyl acrylamide, acrylic acid, an initiator and a cross-linking agent as an aqueous phase W; (2) providing oily substance which is dissolved with an oil soluble emulsifying agent and is insoluble with water as an oil phase O; (3) mixing the aqueous phase with the oil phase to obtain a W/O emulsion, agitating and introducing an inert gas; (4) keeping the inert gas atmosphere, adding an accelerant into the W/O emulsion, and polymerizing to obtain the gel microsphere at a temperature which is lower than the critical dissolving temperature of N-isopropyl acrylamide; and (5) washing the polymerized gel microsphere to obtain the gel microsphere product. The invention further provides application of the gel microsphere.
Description
Technical field
The present invention relates to functional high molecule material and biochemical separation, fixed enzyme vector field.More particularly, relate to a kind of gel micro-ball with temperature-pH Lazer property.
The invention still further relates to the preparation method of above-mentioned gel micro-ball.
The invention still further relates to the application of above-mentioned gel micro-ball.
Background technology
The polyphosphazene polymer collective that physical and chemical performance that intelligent aqueous gel capable is made up of hydrophilic three-dimensional cross-linked macromolecule network and medium (water) jointly and structure change with the change (like temperature, pH, optical electric field, magnetic field etc.) of external environment, application is very extensive in fields such as chemical industry, medicine, machineries.Poly N-isopropyl acrylamide (PNIPAM) is a kind of typical temperature-sensitive macromolecular, is one of the most frequently used material of temperature-sensitive hydrogel.Reversible hydrophilic and hydrophobic takes place near its hydrogel (about 32 ℃) Kraft point (LCST) changes, and when temperature is higher than LCST, shows as hydrophobicity, when temperature is lower than LCST, shows as wetting ability.Have broad application prospects in fields such as immobilized enzyme, medicine controlled releasing, cell cultures, biochemical separation, microreactors.Improve constantly along with what material function was required, research and develop the important development direction that " hybridization type " intelligent material with multiple stimulation responsiveness has become this field.N-NSC 11448 and other hydrogel monomer-grafted or copolymerization can obtain having dual susceptibility, temperature and pH are respectively physical stimulation and the chemical stimulation that very easily realizes, so the hydrogel of the dual susceptibility of preparation temperature-pH receives much concern.
Hydrogel is in application process, and its speed of response that stimulates to external world is a very important parameters.Hydrogel expands and to shrink the line style size that reaches required time of balance and hydrogel closely related, and hydrogel expands and the characteristic time τ ∝ R of contraction
2/ D, wherein R is a hydrogel linear dimension, D is the collaborative spread coefficient of hydrogel.The PNIPAM hydrogel of bibliographical information is bulk hydrogel and nanogel ball mostly at present.Bulk gels is because slow, the many shortcomings such as specific surface area is little, bad mechanical property of its stimuli responsive speed; Make its application receive a lot of restrictions, though and nanogel has solved the problems referred to above, when using, still have a lot of deficiencies; If as separating medium; Easily collecting not when using separately, use can bring very high post to press in the post, these all be nanoscale particle the problem that can't avoid.Compare with nanogel and bulk gels; The micron order gel micro-ball is because it is between nanoscale and macro-scale; The advantage of both and overcome both deficiency; Stimuli responsive speed is fast, have bigger specific surface area and be difficult for reuniting, and has many premium propertiess such as favorable mechanical performance, bringing into play more and more important effect at numerous areas.The method for preparing the small particle size microballoon has precipitation polymerization method and suspension polymerization usually.Being generally of precipitation polymerization method preparation received the microgel ball below 1 micron, this just big limitations the application of gel ball; Then have following problem when suspension polymerization prepares, promptly can not adopt conventional thermal initiation mode initiated polymerization, this is owing to the LCST of conventional thermal-initiated polymerization temperature (60-70 ℃) far above PNIPAM; Can take place after the NIPAM polymerization of water in the W/O emulsion to change mutually; Originally the emulsifying agent that was adsorbed in hydrophilic surface differs and is adsorbed in water repellent surface surely, destroys the stability of emulsion, deposition in a large number occurs; The polymkeric substance of post precipitation is agglomerated into bulk, can not obtain gel micro-ball.Therefore, whole polymerization process need keep low temperature (polymerization temperature must less than the LCST of PNIPAM).Though the ultraviolet radiation light initiation polymerization method of reporting at present is initiated polymerization at low temperatures; But there are some shortcomings inevitably in uv-light polymerization, for example receives the restriction of UV-light penetrativity, requires the polymerization system volume can not be too big; Otherwise be difficult for penetrating; Cause the polymerization system polymerization inhomogeneous, if will increase light intensity, though can strengthen penetrativity; But can bring a series of problems such as system temperature rising, biologically active substance sex change, so the uv-light polymerization preparative-scale is restricted.
In addition, the dimensional homogeneity of gel micro-ball is the conforming important assurance of stimuli responsive, and gel micro-ball prepares stirring of multi-purpose machine tool and homogenizing emulsifying method at present, and microspherulite diameter heterogeneity, the size of preparation gained are uncontrollable.Response to thermal stimulus is inconsistent, and is prone to cause embedding rate and supported quantity low, and these all can exert an influence to using effect.Therefore, need particularly size homogeneous micron order gel micro-ball preparation method of the new micron order of exploitation, intelligent aqueous gel capable is quick to satisfy, the consistent actual demand that responds.
Hydrogel microsphere is in application process; The aperture is a very important parameter; The aperture not only influences the speed of response of hydrogel microsphere to temperature; Application performance when also influencing it as carrier: as fixed enzyme vector the time, pore size directly influences the speed of enzyme supported quantity and substrate Inlet and outlet water gel, and then influences catalytic efficiency (; As pharmaceutical carrier the time, pore size all has material impact to medicine embedding rate and drug release behavior; In cell cultures and biochemical separating application, the aperture of hydrogel also is unusual important parameters.Therefore, the control to the hydrogel aperture seems very necessary.If can control the aperture of hydrogel, the just size in design aperture as required, the hydrogel in the preparation aperture of designing then.This for the application that realizes controlled as required preparation and expand hydrogel all with significant.
Chinese patent (publication number CN1328067A) discloses the preparation method that the temperature sensitive property of a kind of porous is gathered (N-NSC 11448) hydrogel, adds CaCO
3Prepare porous aquagel as pore-creating agent, can be through regulating CaCO
3The particulate size is regulated the aperture of gel, but the preparation of this method also will be with pore-creating agent CaCO after accomplishing
3Fall with dissolving with hydrochloric acid, hydrochloric acid can produce destruction to the immobilized enzyme in the gel, medicine, cell etc., and this method can not realize synchronous immobilization, complex operation, and preparation is bulk gels.Therefore, be necessary to study novel preparation method, prepare the controlled PNIPAM gel micro-ball of aperture and particle diameter, further expand its range of application.
Summary of the invention
The object of the present invention is to provide a kind of gel micro-ball with temperature-pH Lazer property.
Another purpose of the present invention is to provide the preparation method of above-mentioned gel micro-ball.
For realizing above-mentioned purpose, gel micro-ball product provided by the invention has temperature-pH Lazer property, and mean pore size is preferably 30-80nm for the number nanometer arrives 200nm; Median size be 1 μ m to 100 μ m, be preferably 20-50 μ m.
The preparation method of above-mentioned gel micro-ball provided by the invention, key step is following:
1) provide dissolved water-soluble monomer N-NSC 11448, vinylformic acid, initiator, linking agent the aqueous solution as water W;
Water-soluble monomer N-NSC 11448 and acrylic acid total concn are 0.1wt%-60wt%;
Water-soluble monomer N-NSC 11448 and acrylic acid mass ratio are 1%-100%, regulate the mean pore size of gel micro-ball through changing water-soluble monomer N-NSC 11448 and acrylic acid ratio;
The mass ratio that initiator accounts for water-soluble monomer is 0.1-10%;
The mass ratio that linking agent accounts for water-soluble monomer is 0.1-80%;
2) provide dissolved oil-soluble emulsifier and with the immiscible oily matter of water as oil phase O, oil-soluble emulsifier concentration is 1wt%-20wt%;
3) said water is mixed with oil phase obtain the w/o type emulsion, stir, logical rare gas element;
4) keep atmosphere of inert gases, in the w/o type emulsion, add accelerator, be lower than that polymerization obtains gel micro-ball under the Kraft point of N-NSC 11448, the amount that adds accelerator in every 100ml w/o type emulsion is 1-1000 μ m;
5) the gel micro-ball washing that polymerization is obtained obtains the gel micro-ball product.
The preparation method of said gel micro-ball, wherein accelerator is to quicken one type of reagent that initiator produces radical polymerization at low temperatures.
The preparation method of said gel micro-ball, wherein the w/o type emulsion adopts and its hydrophobic microporous membrane through the aperture homogeneous is obtained water.
The preparation method of said gel micro-ball, wherein attach most importance to crystalline ammonium persulphate or Potassium Persulphate of initiator; Rare gas element is nitrogen or argon gas; Emulsifying agent is sorbester p17 or poly-glycerol castor-oil plant alcohol ester.
The preparation method of said gel micro-ball, wherein oil phase O is mixture, hexanaphthene and normal heptane and the mixture of chloroform of mixture, normal heptane and chloroform of mixture, hexanaphthene and the chloroform of hexanaphthene, normal heptane, hexanaphthene and normal heptane; Wherein, the volume ratio of the volume ratio of hexanaphthene and chloroform, normal heptane and chloroform is 9: 1-5: 5.
Gel micro-ball of the present invention can be used as fixation support.
Description of drawings
Fig. 1 is principle and the schema that preparation gathers (N-NSC 11448-co-vinylformic acid) microballoon.
Fig. 2 is the microphotograph of the gel micro-ball of embodiment 1 preparation.
Fig. 3 is the electromicroscopic photograph of the gel micro-ball of embodiment 1 preparation.
Fig. 4 is the size distribution figure of the gel micro-ball of embodiment 1 preparation.
Fig. 5 is the internal structure electromicroscopic photograph of the gel micro-ball of embodiment 1 preparation.
Fig. 6 is the microphotograph of the gel micro-ball of embodiment 2 preparations.
Fig. 7 is the acrylic acid content of preparation microballoon and the graph of a relation between the microsphere average grain diameter.
Fig. 8 is the median size of preparation microballoon and the graph of a relation between the membrane pore size.
Fig. 9 is the microphotograph of the gel micro-ball of embodiment 14 preparations.
Figure 10 is the microphotograph of the gel micro-ball of embodiment 15 preparations.
Embodiment
The present invention is through adding accelerator to the W/O system; Water-soluble monomer N-NSC 11448 and vinylformic acid can be in the following polymerizations of PNIPAM Kraft point; Avoided because of the thermal initiation system temperature raises PNIPAM generation hydrophilic and hydrophobic being changed mutually in the polymerization process; Thereby can keep in the polymerization process W/O system stable, prepare gel micro-ball.When traditional thermal-initiated polymerization is reflected at the W/O polymerization system that is used for the N-NSC 11448 and prepares gel micro-ball; Change because reversible hydrophilic and hydrophobic takes place near Kraft point PNIPAM; And the polymerization temperature of thermal initiation is far above the Kraft point of PNIPAM; Can cause W/O system instability and produce a large amount of depositions, can not successfully prepare gel micro-ball.
In the gel micro-ball provided by the invention aperture, the aperture of comonomer N-NSC 11448 and acrylic acid ratio and gel micro-ball is linear, and the ratio that can regulate both is regulated the aperture of gel micro-ball.
Among the preparation method of the present invention, the W/O emulsion adopts the preparation of microporous membrane emulsion process, can regulate the particle diameter of gel micro-ball through the aperture of regulating hydrophobic microporous membrane, and the uniform particle diameter of gel micro-ball.The size distribution coefficient that is calculated as follows is not more than 20%:
C.V.＝{[∑(di-d)2/N]1/2/d}×100％
In the formula, C.V. representative diameter distribution coefficient; On behalf of each, di receive diameter of micro ball; D represents the number average median size of microballoon, d=∑ di/N; N is the microballoon quantity that is used to calculate particle diameter, and N >=200.
Method provided by the invention comprises the steps:
1) provide dissolved water-soluble monomer N-NSC 11448, vinylformic acid, initiator, linking agent the aqueous solution as water W;
2) provide dissolved oil-soluble emulsifier and with the immiscible oily matter of water as oil phase O;
3) said water is mixed with oil phase obtain the w/o type emulsion, stir, logical rare gas element;
4) keep atmosphere of inert gases, in the w/o type emulsion, add accelerator, under the Kraft point that is lower than the N-NSC 11448, carry out polymerization and obtain gel micro-ball;
5) the gel micro-ball washing that polymerization is obtained obtains the gel micro-ball product.
Among the above-mentioned preparation method, the water-soluble monomer N-NSC 11448 of the step 1 crystalline N-NSC 11448 of attaching most importance to, N-NSC 11448 and acrylic acid total concn are 0.1wt%-60wt%, are preferably 1-40%, more preferably 5wt%-20wt%; Said initiator attach most importance to crystalline ammonium persulphate or Potassium Persulphate, it is 0.1-10% that initiator accounts for monomeric mass ratio, is preferably 1-8%, more preferably 2-5%; Linking agent is tetramethyl-bisacrylamide or two vinylformic acid glycol ester, and it is 0.1-80% that linking agent accounts for monomeric mass ratio, is preferably 1-60%, more preferably 2-5%.
Among the above-mentioned preparation method; The oily matter of the oil phase of step 2 for not allowing with water can be selected from mixture, hexanaphthene and normal heptane and the mixture of chloroform of mixture, normal heptane and chloroform of mixture, hexanaphthene and the chloroform of hexanaphthene, normal heptane, hexanaphthene and normal heptane.The proportioning of normal heptane or hexanaphthene and chloroform is that 9: 1 (v/v) was to 5: 5 (v/v); More preferably 8: 2 (v/v), said oil-soluble emulsifier are Span80 or poly-glycerol castor-oil plant alcohol ester (PGPR), and concentration is 1wt%-20wt%; Be preferably 2-10%, more preferably 3wt%-8wt%
Among the above-mentioned preparation method, the w/o type emulsion of step 3 can obtain through mechanical stirring or homogenizing emulsifying method, also can obtain through supersound method, can also obtain through obtaining the microporous membrane emulsion process, is preferably through hydrophobic microporous membrane to obtain.Because when selecting the microporous membrane emulsion process for use, gel micro-ball particle diameter and membrane pore size are linear, and particle diameter is controlled amount in the 1-100 mu m range, and median size is preferably 10-80 μ m, more preferably 10-50 μ m.
Among the above-mentioned preparation method, when step 3 selected for use the microporous membrane emulsification method to prepare the W/O emulsion, crossing film pressure was 0.5-2kPa; Membrane pore size is the 0.5-50 micron; Be preferably the 2-20 micron, stirring can be adopted mechanical stirring or magnetic agitation, and magnetic agitation speed is 100～150rpm/min.
Among the above-mentioned preparation method, the rare gas element of step 3 is nitrogen or argon gas, is preferably nitrogen.The purpose of the logical rare gas element of this step is to discharge to be dissolved in the air in the W/O system, carries out smoothly to guarantee polyreaction.
Among the above-mentioned preparation method, the accelerator of step 4 is one type of reagent of initiated polymerization at low temperatures.Be preferably in present method and can quicken one type of reagent that persulfuric acid salt initiator produces radical, be preferably Tetramethyl Ethylene Diamine or sodium sulfite anhy 96 or Sodium Metabisulfite.With the Tetramethyl Ethylene Diamine is the adding method that example is explained accelerator; The amount of Tetramethyl Ethylene Diamine is 1-1000 μ l/100ml; Be preferably 10-500 μ l/100ml, at first will extract, have the oil phase of Tetramethyl Ethylene Diamine to drip extraction then as in the W/O emulsion reaction system with oil phase.Polymerization temperature must be lower than the Kraft point of N-NSC 11448, is generally 0-32 ℃, is preferably 15-30 ℃, more preferably 25-30 ℃.This is because PNIPAM is the temperature sensitive type material; Its critical invert point (LCST) if adopt the LCST of conventional thermal-initiated polymerization temperature (60-70 ℃) far above PNIPAM, can take place after the NIPAM polymerization of water in the W/O emulsion to change mutually near 32 ℃; Originally the emulsifying agent that was adsorbed in hydrophilic surface differs and is adsorbed in water repellent surface surely; Destroy the stability of emulsion, deposition in a large number occurs, can not obtain the microballoon of size homogeneous.Therefore, need add accelerator and realize being lower than polymerization under the Kraft point of PNIPAM.
Tetramethyl Ethylene Diamine joins in the W/O emulsion with after the oil phase extraction, rather than directly joins and be dissolved with monomeric water.If directly join water, very fast initiated polymerization (in the several minutes) after accelerator adds, film emulsification then needs the long time (more than the 1hr), and therefore, polymerization just takes place in water before crossing film, can not successfully prepare W/O emulsion and very easily stifled film.If accelerator directly adds without the oil phase extraction, can cause the disturbance of W/O emulsion, cause the emulsion droplet coalescence easily, be unfavorable for the preparation of homogeneous microballoon, therefore, the present invention adopts the accelerator of oil phase extraction.After adding accelerator, can guarantee the room temperature initiated polymerization.
Among the preparation method of the present invention, water-soluble monomer N-NSC 11448 and vinylformic acid mass ratio are 1%～100% (wt%); Wherein the mean pore size of gel micro-ball can be regulated through regulating water-soluble monomer N-NSC 11448 and acrylic acid ratio.Water-soluble monomer N-NSC 11448 and vinylformic acid mass ratio are preferably 3%-50% (wt%), more preferably 5%-25% (wt%).In preparing method's microspheres prepared of the present invention, the inner aperture of acrylic acid content and microballoon is linear, and the shared ratio of vinylformic acid is big more; Lazer's gel micro-ball mean pore size is more little; Otherwise the vinylformic acid proportion is more little, and the mean pore size of Lazer's gel micro-ball is big more.When accounting for the 5wt% of total monomer amount like acrylic acid content, the mean pore size of gel micro-ball is 27.04nm.
Technology of the present invention is simple, and the particle diameter of Lazer's gel micro-ball and aperture can in very large range be regulated, to meet the different needs.With compared with techniques in the past, the present invention has following advantage:
1) the invention provides a kind of preparation method of thermo-sensitive gel microballoon; Making W/O emulsion low temperature is polymerizable; Effectively avoided because of the thermal initiation system temperature raises PNIPAM generation hydrophilic and hydrophobic being changed mutually in the polymerization process, the gel micro-ball stimuli responsive speed for preparing is fast, applied range.
2) the invention provides a kind of preparation method of gel micro-ball controllable aperture, the ratio that can regulate both is regulated the aperture of gel micro-ball, can design the aperture of microballoon as required, to meet the different needs.
3) the present invention also provides the preparation method of the controlled gel micro-ball of a kind of simple uniform particle diameter, particle diameter; The W/O emulsion adopts the preparation of microporous membrane emulsion process; Can regulate the particle diameter of gel micro-ball through the aperture of regulating hydrophobic microporous membrane; And the uniform particle diameter of gel micro-ball can effectively guarantee the stimuli responsive consistence of microballoon.
Gel micro-ball product of the present invention is as the purposes of fixation support, as fixed enzyme vector, but the multiple enzyme of immobilization, like trypsinase, Quimotrase, carboxypeptidase, glycase, stomach en-, rnase etc.Can also can prepare the gel micro-ball of respective aperture according to the size adjustment microballoon aperture of cell as the carrier of immobilized cell.
Carry out more detailed description in the face of the present invention down.
If do not specialize, concentration unit used among the present invention is wt%.
Generally speaking, the invention provides a kind of preparation method of gel micro-ball.
According to an embodiment preferred; The present invention at first with the aqueous solution of water-soluble monomer N-NSC 11448, vinylformic acid, initiator, linking agent as water W; With dissolved oil-soluble emulsifier and with the immiscible oily matter of water as oil phase O; Adopt the microporous membrane of the surface hydrophobicity of process chemically modified under the nitrogen pressure effect, to press microporous membrane to prepare the W/O emulsion water, under atmosphere of inert gases, (be preferably nitrogen), will use the stripped accelerator of oil phase to add in the W/O emulsion; Under the Kraft point that is lower than the N-NSC 11448, polymerization obtains temperature-pH Lazer gel micro-ball.Through regulating water-soluble monomer N-NSC 11448 and acrylic acid ratio, can regulate the aperture of microballoon, to meet the different needs.
Among the present invention, polymerization temperature carries out under the condition that is lower than the PNIPAM Kraft point, and there is a Kraft point (LCST) in temperature sensing polymer PNIPAM, and when outside temperature was higher than this temperature, PNIPAM showed as hydrophobicity; When outside temperature was lower than this temperature, PNIPAM showed as wetting ability.If polymerization temperature is higher than the LCST of PNIPAM; In case polymerization begins; After aqueous phase water-soluble monomer NIPAM aggregated into the PNIPAM of long-chain in the W/O emulsion, PNIPAM at high temperature can be changed to hydrophobicity by wetting ability, and the emulsifying agent that is adsorbed on originally on the hydrophilic interface separates because having contacted hydrophobic interfaces; Cause the stable W/O emulsion loss of stability of script and produce deposition, can not successfully prepare gel micro-ball.If the temperature of system remains on below the LCST in the whole polymerization process always, after polymerization began, the transformation of hydrophilic and hydrophobic can not take place in PNIPAM, can not destroy the stability of W/O emulsion.Therefore, can successfully prepare required gel micro-ball.
Among the present invention, can be through regulating the aperture that water-soluble monomer N-NSC 11448 and acrylic acid ratio are regulated gel micro-ball.Gel micro-ball is widely used in fields such as immobilized enzyme, medicine controlled releasing, cell cultures, biochemical separation, microreactors, and the aperture of gel micro-ball directly influences its application.The gel micro-ball aperture not only influences the speed of response of hydrogel microsphere to temperature, also influences its application performance, and during for example as fixed enzyme vector, the aperture is too little; It is inner that enzyme is difficult to get into microballoon, and the enzyme supported quantity of microballoon will be very low, if the aperture is too big; Though enzyme is easy to get into microballoon inside, the specific surface area of microballoon is too low, also is unfavorable for the raising of supported quantity; Therefore, the aperture of microballoon and the size of enzyme will be mated appropriately, and the size in aperture also influences the discrepancy of substrate.Therefore, extremely important to the control in hydrogel aperture.The present invention can design the aperture of gel micro-ball according to application demand, through regulating the aperture that water-soluble monomer N-NSC 11448 and acrylic acid ratio are regulated gel micro-ball, to satisfy different needs.
Preparing method in the face of gel micro-ball of the present invention explains for example down.But should be appreciated that these illustrate only is for the ease of understanding the present invention better, and limitation of the scope of the invention by no means.
Embodiment 1
10g N-NSC 11448 is added in the 100ml normal hexane, be heated to 40 ℃ and make it dissolving, slowly cooling again, back to be crystallized suction filtration, the refrigerator hold over night, next day, filtration obtained filter cake, with for use behind the normal hexane recrystallization.Adopt the hydrophobic glass film as microporous membrane.N-NSC 11448,0.15g (15wt% of total monomer amount) vinylformic acid, 0.05g (15wt% of total monomer amount) methylene-bisacrylamide MBA after accurately weighing 0.85g makes with extra care are dissolved in the 8ml deionized water, stir.Add 0.05g (3wt% of total monomer amount) initiator A PS then, replenishing deionized water to TV is 10ml, and magnetic agitation makes it abundant dissolving.Get the 80ml hexanaphthene and the 20ml chloroform mixes, add 5.0g (5%g/ml of oil phase quality) emulsifying agent SPAN80, magnetic agitation makes it to mix.Under the nitrogen pressure of 2.5KPa, water is crossed 5.2 microns SPG fenestra and be pressed into oil phase, the oil phase stirring velocity is 130～140rpm, 3～4 hours time.Treat water all is pressed into the W/O emulsion that obtains the size homogeneous behind the oil phase; The above-mentioned emulsion that obtains is led to nitrogen after half a hour; 1 milliliter of the Tetramethyl Ethylene Diamine (containing Tetramethyl Ethylene Diamine 100 microlitres) that adds the hexanaphthene extraction to system; Stirring velocity remains on 170rpm during polyreaction, and 25 ℃ of following polyreactions are gathered (N-NSC 11448-co-vinylformic acid) microballoon after 4 hours.The centrifugal supernatant of abandoning under the 4000rpm rotating speed, thus obtained microsphere is washed 3 times with acetone, and de-ionized washing 3 times stores with the deionized water suspension.The microballoon aperture adopts specific surface and lacunarity analysis appearance ASAP 2020 to measure, and mean pore size is 12.18 nanometers, and the microspherulite diameter and the employing laser particle analyzer Mastersizer 2000E that distributes measure, and microsphere average grain diameter is 25.22 microns.Opticmicroscope is as shown in Figure 1, and size distribution is as shown in Figure 2.C.V. be 13.23%.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon; The difference is that keeping N-NSC 11448 and vinylformic acid total amount is 1g; The quantitative change of N-NSC 11448 is 0.95g (95wt% of total monomer amount); Acrylic acid amount is 0.05g (5wt% of total monomer amount), and being gathered (N-NSC 11448-co-vinylformic acid) microballoon mean pore size is 27.04 nanometers, and microsphere average grain diameter is 24.92 microns.C.V. be 14.47%.
Embodiment 3
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon; The difference is that keeping N-NSC 11448 and vinylformic acid total amount is 1g; The quantitative change of N-NSC 11448 is 0.90g (90wt% of total monomer amount); Acrylic acid amount is 0.10g (10wt% of total monomer amount), and being gathered (N-NSC 11448-co-vinylformic acid) microballoon mean pore size is rice in 20.45, and microsphere average grain diameter is 25.45 microns.C.V. be 15.30%.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon; The difference is that keeping N-NSC 11448 and vinylformic acid total amount is 1g; The quantitative change of N-NSC 11448 is 0.80g (80wt% of total monomer amount); Acrylic acid amount is 0.20g (20wt% of total monomer amount), and being gathered (N-NSC 11448-co-vinylformic acid) microballoon mean pore size is rice in 9.38, and microsphere average grain diameter is 24.92 microns.C.V. be 14.78%.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon; The difference is that keeping N-NSC 11448 and vinylformic acid total amount is 1g; The quantitative change of N-NSC 11448 is 0.75g (75wt% of total monomer amount); Acrylic acid amount is 0.25g (25wt% of total monomer amount), and being gathered (N-NSC 11448-co-vinylformic acid) microballoon mean pore size is rice in 4.44, and microsphere average grain diameter is 24.80 microns.C.V. be 15.01%.
The relation of gathering (N-NSC 11448-co-vinylformic acid) microballoon acrylic acid content and mean pore size that embodiment 1-5 is prepared is as shown in Figure 3.Can find out that by figure microballoon acrylic acid content and microballoon mean pore size are linear.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that polymerization temperature is 20 ℃, obtaining the microballoon mean pore size is 12.34 nanometers, and median size is 25.80 microns.C.V. be 14.42%.
Embodiment 7
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that polymerization temperature is 30 ℃, obtaining the microballoon mean pore size is 12.46 nanometers, and median size is 25.35 microns.C.V. be 16.06%.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that polymerization time is 8 hours, obtaining the microballoon mean pore size is 12.53 nanometers, and median size is 25.06 microns.C.V. be 13.80%.
Embodiment 9
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that polymerization time spends the night (more than 12 hours), obtaining the microballoon mean pore size is 12.48 nanometers, and median size is 25.57 microns.C.V. be 14.14%.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that used SPG membrane pore size is 1.4 microns, obtaining the microballoon mean pore size is 12.14 nanometers, and microsphere average grain diameter is 6.14 microns.C.V. be 15.11%.
Embodiment 11
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that used SPG membrane pore size is 2.8 microns, obtaining the microballoon mean pore size is 12.56 nanometers, and microsphere average grain diameter is 12.40 microns.C.V. be 15.32%.
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that used SPG membrane pore size is 7.2 microns, obtaining the microballoon mean pore size is 12.39 nanometers, and microsphere average grain diameter is 29.40 microns.C.V. be 15.62%.
Embodiment 13
Adopt with embodiment 1 identical apparatus and method preparation and gather (N-NSC 11448-co-vinylformic acid) microballoon, the difference is that used SPG membrane pore size is 9 microns, obtaining the microballoon mean pore size is 12.71 nanometers, and microsphere average grain diameter is 39.80 microns.C.V. be 14.79%.
Embodiment 1, prepared the gathering of embodiment 10-13 (N-NSC 11448-co-vinylformic acid) median size of microballoon and the relation of membrane pore size are as shown in Figure 5.Can find out that by figure microsphere average grain diameter and membrane pore size are linear.
Embodiment 14
Adopt and gather (N-NSC 11448-co-vinylformic acid) microballoon with embodiment 1 identical formulation, the difference is that and adopt mechanical mixing method to prepare the W/O emulsion, the microsphere average grain diameter size that obtains is heterogeneity (as shown in Figure 9) very.
Adopt and gather (N-NSC 11448-co-vinylformic acid) microballoon with embodiment 1 identical formulation, the difference is that and adopt the homogenizing emulsifying legal system to be equipped with the W/O emulsion, the microsphere average grain diameter size that obtains is heterogeneity (shown in figure 10) very.
Claims (9)
1. a gel micro-ball product has temperature-pH Lazer property, and mean pore size arrives 200nm for the number nanometer, and median size is that 1 μ m is to 100 μ m.
2. gel micro-ball product according to claim 1, wherein, mean pore size is 30-80nm, median size is 20-50 μ m.
3. the preparation method of the said gel micro-ball of claim 1, key step is following:
1) provide dissolved water-soluble monomer N-NSC 11448, vinylformic acid, initiator, linking agent the aqueous solution as water W;
Water-soluble monomer N-NSC 11448 and acrylic acid total concn are 0.1wt%-60wt%;
Water-soluble monomer N-NSC 11448 and acrylic acid mass ratio are 1%-100%, regulate the mean pore size of gel micro-ball through changing water-soluble monomer N-NSC 11448 and acrylic acid ratio;
The mass ratio that initiator accounts for water-soluble monomer is 0.1-10%;
The mass ratio that linking agent accounts for water-soluble monomer is 0.1-80%;
2) provide dissolved oil-soluble emulsifier and with the immiscible oily matter of water as oil phase O, oil-soluble emulsifier concentration is 1wt%-20wt%;
3) said water is mixed with oil phase obtain the w/o type emulsion, stir, logical rare gas element;
4) keep atmosphere of inert gases, in the w/o type emulsion, add accelerator, be lower than that polymerization obtains gel micro-ball under the Kraft point of N-NSC 11448, the amount that adds accelerator in every 100ml w/o type emulsion is 1-1000 μ m;
5) the gel micro-ball washing that polymerization is obtained obtains the gel micro-ball product.
4. according to the preparation method of the said gel micro-ball of claim 3, wherein, the accelerator foot quickens one type of reagent that initiator produces radical polymerization at low temperatures.
5. according to the preparation method of the said gel micro-ball of claim 3, wherein, the w/o type emulsion adopts and its hydrophobic microporous membrane through the aperture homogeneous is obtained water.
6. according to the preparation method of the said gel micro-ball of claim 3, wherein, initiator attach most importance to crystalline ammonium persulphate or Potassium Persulphate; Rare gas element is nitrogen or argon gas; Emulsifying agent is sorbester p17 or poly-glycerol castor-oil plant alcohol ester.
7. according to the preparation method of the said gel micro-ball of claim 3; Wherein, oil phase O is mixture, hexanaphthene and normal heptane and the mixture of chloroform of mixture, normal heptane and chloroform of mixture, hexanaphthene and the chloroform of hexanaphthene, normal heptane, hexanaphthene and normal heptane.
8. according to the preparation method of the said gel micro-ball of claim 7, wherein, the volume ratio of the volume ratio of hexanaphthene and chloroform, normal heptane and chloroform is 9: 1-5: 5.
9. the said gel micro-ball of claim 1 is as the purposes of fixation support.
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