CN103804712A - Preparation of porous and aperture-controllable chitosan microspheres - Google Patents
Preparation of porous and aperture-controllable chitosan microspheres Download PDFInfo
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- CN103804712A CN103804712A CN201410032454.7A CN201410032454A CN103804712A CN 103804712 A CN103804712 A CN 103804712A CN 201410032454 A CN201410032454 A CN 201410032454A CN 103804712 A CN103804712 A CN 103804712A
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Abstract
Chitosan microspheres of different particle sizes and morphologies have different functions of loading medicines, sterilization, adsorption, separation and the like. The invention discloses a method for preparing the natural polymer chitosan microspheres with controllable apertures. The chitosan microspheres are prepared by using an electrostatic spraying technique, the temperature is rapidly reduced by using liquid nitrogen so as to cure the micropheres, residual solvents in the microspheres are eliminated by using a vacuum freezing drying technique so as to obtain the porous chitosan microspheres, and finally the chitosan microspheres are insoluble in water phase through glutaraldehyde cross-linking. The residual solvent amount inside the microspheres can be controlled by adjusting the ratio of solvents and the electric spraying distance so as to control the sizes of the apertures of the microspheres. The porous chitosan microspheres have large specific surface areas, and the application range of the microspheres is greatly widened, so that the chitosan microspheres have key functions in the fields of medicines, sterilization, microseparators and the like.
Description
Technical field
The invention belongs to natural macromolecular material field, relate to the preparation method of the controlled polymer microsphere in a kind of porous and aperture.
Background technology
Chitosan is as a kind of multipolymer, take β-(Isosorbide-5-Nitrae) 2-acetylaminohydroxyphenylarsonic acid glucose and β-(Isosorbide-5-Nitrae) 2 amino-glucose as unit, is the deacetylated derivative of N-of chitin.On the nitrogen-atoms of chitosan free amine group, there is 1 pair of lone-pair electron, make amino be weakly alkaline.Free amine group can be in conjunction with 1 hydrogen ion, make chitosan become positively charged linear polyelectrolyte, be adsorbed on negative charged surface, the weakly alkaline of chitosan makes its surface with weak electric charge simultaneously, therefore, chitosan is that minority has one of natural product of electric charge, has physics, chemical property and the biological function of many uniquenesses.Chitosan microball plays keying action in fields such as medicine, sterilization, tiny segregators, and the chitosan microball of different-grain diameter and pattern is being undertaken the difference in functionalitys such as carrying medicament, sterilization, fractionation by adsorption.
Electrostatic spray method is a kind of method of utilizing electrohydrodynamics fluidics polymers soln or melt to be made to micro-, nanometer ball or fibrous material.Its most outstanding advantage is the avoiding of omission, high-temperature operation of the second emulsion, can prepare microballoon without chitosan is carried out to any modification.
The present invention is mainly by regulating solvent burden ratio to make the chitosan solution that volatility is different, regulate electrostatic spray distance, chitosan solution is dispersed into fine drop under the effect of electrostatic force, fine drop is passed through the processes such as solvent evaporates, contraction in air, run into cryogenic temperature condensation at receiving trap place and become microballoon, then remove the inner residual solvent of microballoon and obtain the chitosan microball of porous by Vacuum Freezing & Drying Technology.Thereby this invention reaches the object of the pore radiuses and distribution of controlling microsphere surface by regulating the EFI distance of solvent burden ratio, electrostatic spray to control the inner residual volume of microballoon.
Summary of the invention
The object of the invention is to provide a kind of controlled chitosan microball method in aperture of preparing.This microballoon can be used as controlled release drug carrier materials, sorbent material etc.The method can operate continuously, and the microspherulite diameter of preparation and pore size are controlled and simple to operate, and mild condition is with low cost.
The concrete implementation step of the present invention is as follows:
1. the preparation of polymers soln: the preparation acetic acid of mass ratio 90/10～10/90 and the mixed solvent of deionized water or formic acid and deionized water.By chitosan (Mw=120000～200000gmol
-1) be dissolved in this mixed solvent, be configured to the chitosan solution of 1～8wt%, through fully stirring, so that dissolve completely, solution left standstill is all separated out to bubble, become homogeneous transparent solution to obtain chitosan polymer solution.
2. the preparation of Porous Chitosan Microspheres: at room temperature, the polymers soln in step 1 being placed in to 5ml syringe, is 0.1～1.0ml/h by micro-injection pump control extruded velocity; The voltage of electron spray(ES) is 15～30kV, and electron spray(ES) shower nozzle to the distance of receptor is 10～30cm; The container that liquid nitrogen is equipped with in employing is collection device, and in container, adds a certain amount of liquid nitrogen every 10～30min; Thus obtained microsphere is dry 24h in vacuum freeze drier, scanning electron microscopic observation microballoon form.
3. Porous Chitosan Microspheres is crosslinked: chitosan microball is used in airtight moisture eliminator to glutaraldehyde vapor crosslinking, reaction 24h.Advantage of the present invention:
1. what the present invention adopted is that natural macromolecular material is prepared porous nano microballoon by electron spray(ES) technology and Vacuum Freezing & Drying Technology;
2. the present invention is low for equipment requirements, and collection device, postprocessing working procedures are simple, and cost is low;
3. this method can, by regulating jet length, solvent burden ratio, realize the controllability in the aperture of chitosan microball.
4. this method, with liquid nitrogen as the refrigeration agent that reduces temperature, is conveniently easy to get, and does not pollute chitosan microball.
Accompanying drawing explanation
Fig. 1 is device schematic diagram of the present invention.H is EFI height, and G is the collection device that liquid nitrogen is housed, and in this invention, G can be salver, inwall with the vinyl disc of conducting film etc.In EFI process, chitosan solution is dispersed into countless small dropletss acting on of electrostatic high-pressure, and small droplets is at (the H that falls
1) shrink and diminish along with the volatilization of solvent in process, reach L place, due to the rapid drawdown of temperature, the solvent in small droplets is substantially non-volatile and be frozen into gradually minimicrosphere and drop in collection device.In the time reaching L place, solvent all volatilizees, and the microballoon finally obtaining is by the chitosan microball that is atresia, and in the time reaching L place, solvent does not volatilize completely, the chitosan microball that finally obtains porous, dissolvent residual is more, and the aperture of the chitosan microball obtaining is just larger, otherwise, less.
Fig. 2 is the chitosan microball configuration of surface SEM figure that the present invention obtains by embodiment 1 preparation method.
Embodiment
Embodiment 1
1. the acetic acid that preparation mass ratio is 90/10 and the mixed solvent of water.By chitosan (Mw=120000gmol
-1) be dissolved in this solvent, being mixed with mass ratio is the electron spray(ES) solution of 1wt%, then solution is fully stirred, and after dissolving completely, leaves standstill removal bubble and becomes homogeneous solution;
2. at room temperature, electron spray(ES) solution in step 1 is placed in to 5ml syringe, it is 0.1ml/h that extruded velocity is set, and EFI voltage is 20kV, and shower nozzle to the distance of receiving trap is 15cm, starts electrostatic spray, adds 20ml liquid nitrogen every 10min to receiving trap; Thus obtained microsphere is dry 24h in vacuum freeze drier;
3. the chitosan microball of preparation in step 2 is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
Embodiment 2
1. the acetic acid that preparation mass ratio is 90/10 and the mixed solvent of water.By chitosan (Mw=120000gmol
-1) be dissolved in this solvent, being mixed with mass ratio is the electron spray(ES) solution of 3wt%, then solution is fully stirred, and after dissolving completely, leaves standstill removal bubble and becomes homogeneous solution;
2. at room temperature, electron spray(ES) solution in step 1 is placed in to 5ml syringe, it is 0.1ml/h that extruded velocity is set, and EFI voltage is 20kV, and shower nozzle to the distance of receiving trap is 15cm, starts electrostatic spray, adds 20ml liquid nitrogen every 10min to receiving trap; Thus obtained microsphere is dry 24h in vacuum freeze drier;
3. the chitosan microball of preparation in step 2 is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
Embodiment 3
1. the acetic acid that preparation mass ratio is 50/50 and the mixed solvent of water.By chitosan (Mw=120000gmol
-1) be dissolved in this solvent, being mixed with mass ratio is the electron spray(ES) solution of 3wt%, then solution is fully stirred, and after dissolving completely, leaves standstill removal bubble and becomes homogeneous solution;
2. at room temperature, electron spray(ES) solution in step 1 is placed in to 5ml syringe, it is 0.1ml/h that extruded velocity is set, and EFI voltage is 20kV, and shower nozzle to the distance of receiving trap is 15cm, starts electrostatic spray, adds 20ml liquid nitrogen every 10min to receiving trap; Thus obtained microsphere is dry 24h in vacuum freeze drier;
3. the chitosan microball of preparation in step 2 is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
Embodiment 4
1. the acetic acid that preparation mass ratio is 40/60 and the mixed solvent of water.By chitosan (Mw=200000gmol
-1) be dissolved in this solvent, being mixed with mass ratio is the electron spray(ES) solution of 6wt%, then solution is fully stirred, and after dissolving completely, leaves standstill removal bubble and becomes homogeneous solution;
2. at room temperature, electron spray(ES) solution in step 1 is placed in to 5ml syringe, it is 0.1ml/h that extruded velocity is set, and EFI voltage is 20kV, and shower nozzle to the distance of receiving trap is 25cm, starts electrostatic spray, adds 20ml liquid nitrogen every 10min to receiving trap; Thus obtained microsphere is dry 24h in vacuum freeze drier;
3. the chitosan microball of preparation in step 2 is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
Embodiment 5
1. the acetic acid that preparation mass ratio is 50/50 and the mixed solvent of water.By chitosan (Mw=200000gmol
-1) be dissolved in this solvent, being mixed with mass ratio is the electron spray(ES) solution of 6wt%, then solution is fully stirred, and after dissolving completely, leaves standstill removal bubble and becomes homogeneous solution;
2. at room temperature, electron spray(ES) solution in step 1 is placed in to 5ml syringe, it is 0.1ml/h that extruded velocity is set, and EFI voltage is 20kV, and shower nozzle to the distance of receiving trap is 25cm, starts electrostatic spray, adds 20ml liquid nitrogen every 10min to receiving trap; Thus obtained microsphere is dry 24h in vacuum freeze drier;
3. the chitosan microball of preparation in step 2 is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
Embodiment 6
1. the acetic acid that preparation mass ratio is 30/70 and the mixed solvent of water.By chitosan (Mw=200000gmol
-1) be dissolved in this solvent, being mixed with mass ratio is the electron spray(ES) solution of 8wt%, then solution is fully stirred, and after dissolving completely, leaves standstill removal bubble and becomes homogeneous solution;
2. at room temperature, electron spray(ES) solution in step 1 is placed in to 5ml syringe, it is 0.1ml/h that extruded velocity is set, and EFI voltage is 20kV, and shower nozzle to the distance of receiving trap is 30cm, starts electrostatic spray, adds 20ml liquid nitrogen every 10min to receiving trap; Thus obtained microsphere is dry 24h in vacuum freeze drier;
3. the chitosan microball of preparation in step 2 is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
Claims (4)
1. a preparation method for the controlled natural polymer microballoon in porous and aperture, is characterized in that following steps:
(1) chitosan is dissolved in the mixed solvent of deionized water and acetic acid or deionized water and formic acid, preparation 1～8wt% polymers soln, is at room temperature stirred to completely and dissolves, and leaves standstill and removes bubble, becomes homogeneous transparent solution;
(2) polymers soln in step (1) is placed in to the syringe of 5ml, it is 0.1～1.0ml/h that syringe pump control extruded velocity is set, electron spray(ES) voltage 15～30kV, and shower nozzle is that 10～30cm carries out electrostatic spray to the distance between receiving trap; The container that liquid nitrogen is equipped with in employing is collection device, and in container, adds a certain amount of liquid nitrogen every 10～30min; Thus obtained microsphere is dry 24h in vacuum freeze drier, scanning electron microscopic observation microballoon form;
(3) chitosan microball in step (2) is used to glutaraldehyde vapor crosslinking in airtight moisture eliminator, reaction 24h.
2. according to the preparation method of claim 1, it is characterized in that deionized water that step (1) is used and the mass ratio of acetic acid or deionized water formic acid are 10/90～90/10.
3. according to the preparation method of claim 1, it is characterized in that the molecular weight of step (1) chitosan used is: Mw=120000～200000gmol
-1.
4. according to the preparation method of claim 1, the condition that it is characterized in that electron spray(ES) in step (2) is: under room temperature, the container that liquid nitrogen is housed is receptor, this container is indefinite, can be large iron pan, the vinyl disc of included one deck conducting film etc. of customization, in EFI process, liquid nitrogen be added 5～50ml every 10～30min, and polymers soln extruded velocity is 0.1～0.5ml/h, voltage is 15～30kV, and shower nozzle to the distance between receiving trap is 10～30cm.
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473866A (en) * | 2014-11-24 | 2015-04-01 | 张家港保税区鑫和成国际贸易有限公司 | Method for preparing hyaluronic acid gel with drug slow-release effect |
| CN104525071A (en) * | 2014-11-24 | 2015-04-22 | 张家港保税区鑫和成国际贸易有限公司 | Chitosan microsphere preparation method |
| CN105903064A (en) * | 2016-04-12 | 2016-08-31 | 中国科学院深圳先进技术研究院 | Chitosan microsphere, and preparation method and application thereof |
| CN105920658A (en) * | 2016-04-23 | 2016-09-07 | 厦门凝赋生物科技有限公司 | Porous styptic powder and preparation method thereof |
| CN106633113A (en) * | 2016-10-17 | 2017-05-10 | 武汉大学 | Preparation method of natural macromolecular hollow microspheres |
| CN106957448A (en) * | 2017-02-24 | 2017-07-18 | 黄秋丽 | A kind of xanthans modifies the preparation method of chitosan microball |
| WO2018036339A1 (en) * | 2016-08-24 | 2018-03-01 | 谭淞文 | Saccharide microparticle carrier and preparation method, using method and application of same |
| CN108042485A (en) * | 2017-11-08 | 2018-05-18 | 宁波三生生物科技有限公司 | A kind of Altrenogest preparation and preparation method thereof |
| CN108366918A (en) * | 2015-09-30 | 2018-08-03 | 爱茉莉太平洋股份有限公司 | Scoria powder particle is impregnated in poromeric composite granule, contains its cosmetic composition and preparation method thereof |
| CN111704739A (en) * | 2020-06-22 | 2020-09-25 | 苏州大学 | Porous microsphere particles for three-dimensional cell culture and preparation method thereof |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104525071A (en) * | 2014-11-24 | 2015-04-22 | 张家港保税区鑫和成国际贸易有限公司 | Chitosan microsphere preparation method |
| CN104473866A (en) * | 2014-11-24 | 2015-04-01 | 张家港保税区鑫和成国际贸易有限公司 | Method for preparing hyaluronic acid gel with drug slow-release effect |
| CN108366918A (en) * | 2015-09-30 | 2018-08-03 | 爱茉莉太平洋股份有限公司 | Scoria powder particle is impregnated in poromeric composite granule, contains its cosmetic composition and preparation method thereof |
| CN108366918B (en) * | 2015-09-30 | 2021-07-27 | 爱茉莉太平洋股份有限公司 | Composite powder obtained by impregnating volcanic cinders powder particles in porous polymer, cosmetic composition containing same, and method for producing same |
| CN105903064A (en) * | 2016-04-12 | 2016-08-31 | 中国科学院深圳先进技术研究院 | Chitosan microsphere, and preparation method and application thereof |
| CN105903064B (en) * | 2016-04-12 | 2019-06-25 | 中国科学院深圳先进技术研究院 | A kind of chitosan microball and its preparation method and application |
| CN105920658A (en) * | 2016-04-23 | 2016-09-07 | 厦门凝赋生物科技有限公司 | Porous styptic powder and preparation method thereof |
| CN105920658B (en) * | 2016-04-23 | 2020-09-25 | 厦门凝赋生物科技有限公司 | Porous hemostatic powder and preparation method thereof |
| WO2018036339A1 (en) * | 2016-08-24 | 2018-03-01 | 谭淞文 | Saccharide microparticle carrier and preparation method, using method and application of same |
| CN106633113A (en) * | 2016-10-17 | 2017-05-10 | 武汉大学 | Preparation method of natural macromolecular hollow microspheres |
| CN106957448A (en) * | 2017-02-24 | 2017-07-18 | 黄秋丽 | A kind of xanthans modifies the preparation method of chitosan microball |
| CN108042485B (en) * | 2017-11-08 | 2018-11-27 | 宁波三生生物科技有限公司 | A kind of Altrenogest preparation and preparation method thereof |
| CN108042485A (en) * | 2017-11-08 | 2018-05-18 | 宁波三生生物科技有限公司 | A kind of Altrenogest preparation and preparation method thereof |
| CN111704739A (en) * | 2020-06-22 | 2020-09-25 | 苏州大学 | Porous microsphere particles for three-dimensional cell culture and preparation method thereof |
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Application publication date: 20140521 |