CN105348548A - Hydrogel microspheres based on glucan and preparation method thereof - Google Patents
Hydrogel microspheres based on glucan and preparation method thereof Download PDFInfo
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- CN105348548A CN105348548A CN201510704378.4A CN201510704378A CN105348548A CN 105348548 A CN105348548 A CN 105348548A CN 201510704378 A CN201510704378 A CN 201510704378A CN 105348548 A CN105348548 A CN 105348548A
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- dextran
- aldehyde radical
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 115
- 239000004005 microsphere Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 46
- 229920001503 Glucan Polymers 0.000 title claims abstract description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 74
- 239000008367 deionised water Substances 0.000 claims abstract description 73
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 63
- 238000003756 stirring Methods 0.000 claims abstract description 47
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims abstract description 44
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims abstract description 39
- 150000001412 amines Chemical class 0.000 claims abstract description 35
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 32
- 239000007787 solid Substances 0.000 claims abstract description 26
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims abstract description 22
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 21
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000004530 micro-emulsion Substances 0.000 claims abstract description 16
- 239000002244 precipitate Substances 0.000 claims abstract description 8
- 229920002307 Dextran Polymers 0.000 claims description 168
- 239000003431 cross linking reagent Substances 0.000 claims description 34
- 239000007864 aqueous solution Substances 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000000502 dialysis Methods 0.000 claims description 20
- 238000004945 emulsification Methods 0.000 claims description 20
- 239000011259 mixed solution Substances 0.000 claims description 20
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 239000005457 ice water Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 238000010926 purge Methods 0.000 claims description 10
- 239000004627 regenerated cellulose Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- NSOXQYCFHDMMGV-UHFFFAOYSA-N Tetrakis(2-hydroxypropyl)ethylenediamine Chemical compound CC(O)CN(CC(C)O)CCN(CC(C)O)CC(C)O NSOXQYCFHDMMGV-UHFFFAOYSA-N 0.000 claims description 8
- 238000010907 mechanical stirring Methods 0.000 claims description 8
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000001593 sorbitan monooleate Substances 0.000 claims description 4
- 235000011069 sorbitan monooleate Nutrition 0.000 claims description 4
- 229940035049 sorbitan monooleate Drugs 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- -1 polyoxyethylenes Polymers 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 2
- 241000555268 Dendroides Species 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 229930182817 methionine Natural products 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 6
- 239000002245 particle Substances 0.000 abstract description 3
- 239000002861 polymer material Substances 0.000 abstract description 3
- 239000012429 reaction media Substances 0.000 abstract description 2
- 238000005119 centrifugation Methods 0.000 abstract 2
- 238000010382 chemical cross-linking Methods 0.000 abstract 2
- 238000004140 cleaning Methods 0.000 abstract 2
- 239000004971 Cross linker Substances 0.000 abstract 1
- 238000004108 freeze drying Methods 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 description 16
- 239000000499 gel Substances 0.000 description 14
- 239000011806 microball Substances 0.000 description 13
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 12
- 229920000053 polysorbate 80 Polymers 0.000 description 12
- 229920005654 Sephadex Polymers 0.000 description 7
- 239000012507 Sephadex™ Substances 0.000 description 7
- 238000009826 distribution Methods 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 5
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 1
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001459 lithography Methods 0.000 description 1
- 238000000593 microemulsion method Methods 0.000 description 1
- 238000012703 microemulsion polymerization Methods 0.000 description 1
- 239000011234 nano-particulate material Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000003058 plasma substitute Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000000207 volumetry Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/02—Dextran; Derivatives thereof
Abstract
The invention relates to hydrogel microspheres based on glucan and a preparation method thereof, which belong to the technical field of biomedical polymer materials. The method comprises the following steps: dissolving glucan in water at room temperature, adding sodium periodate to obtain a mixed liquor, stirring and dialyzing the mixed liquor, performing freeze drying on the mixed liquor to obtain a partial aldehyde glucan solid; dissolving the partial aldehyde glucan solid in deionized water, adding a cyclohexane solution with a dissolved emulsifier, adding an amine crosslinker and stirring the solution, finally collecting precipitate through centrifugation, cleaning the precipitate to obtain the chemical cross-linking type glucan hydrogel microspheres; adding sodium borohydride in the chemical cross-linking type glucan hydrogel microspheres dispersed in deionized water, stirring the material for 24 hours under room temperature, finally collecting the precipitate through centrifugation, and cleaning the precipitate by the deionized water to obtain the reduced glucan hydrogel microspheres. According to the invention, a water-in-oil anti-phase microemulsion system is taken as a reaction medium, and the glucan hydrogel microspheres with a controllable particle size and good stability can be prepared.
Description
Technical field
The present invention relates to a kind of hydrogel microsphere based on dextran and preparation method thereof, belong to biological medical polymer material technical field.
Background technology
The hydrogel three-dimensional net structure that to be a kind of polymkeric substance formed by physics or chemically crosslinked, in aqueous can be swelling and keep large quantity of moisture and can not dissolve, and hydrophilic small molecules can spread in hydrogel.Hydrogel microsphere has possessed hydrogel and the ambilateral characteristic of micro-/ nano particle simultaneously.Because it has less size, larger specific surface area etc.; also there is the dimensional stability of hydrogel and high solution-absorbency energy simultaneously; therefore; hydrogel micro-/ nano particle has huge application potential and wide application prospect (Thedevelopmentofmicrogels/nanogelsfordrugdeliveryapplica tions as bio-medical material in the field such as organizational project, useful for drug delivery; ProgressinPolymerScience, 2008.33:448-477; MicrogelsinDrugDelivery, inMicrogelSuspensions, 2011, Wiley-VCHVerlagGmbH & Co.KGaA.375-405).
Hydrogel based on natural macromolecular material has excellent biological safety, receives much concern as biomaterial.Polysaccharide is the natural polymer that a class has good biocompatibility, with the hydrogel that natural polysaccharide macromolecular material builds, there is good biocompatibility and biological degradability, be widely used in organizational project, genophore and pharmaceutical carrier as biological medical polymer material, the research at present about polysaccharide gel microballoon is mainly carried out around chitosan and Lalgine.Dextran (dextran), also known as dextran, is the bacterial polysaccharide with a large amount of free hydroxyl group on a kind of molecular structure, has good water-soluble and biological safety.From 1840s, dextran is widely used in clinical as the provisional plasma substitute of one, and the hydrogel microsphere therefore based on dextran has potential applicability in clinical practice widely as drug carrier material.
At present, be that the preparation method of hydrogel microsphere of material foundation is generally divided into four large class (NanogelsasPharmaceuticalCarriers:FiniteNetworksofInfinit eCapabilities. with polymkeric substance
angewandteChemieInternationalEdition, 2009.48:5418-5429): (1) utilizes the physical force " self-assembly " such as the hydrogen bond between polymer, close and distant waterpower, electrostatic force to form hydrogel microsphere; (2) prepare gel micro-ball by the monomer polymerization caused in microemulsion system, polymerization process can be carried out in homogeneous system, also can carry out in the out-phase environment with nano-scale; (3) by chemically crosslinked, between polymer, gel micro-ball is connected to form with covalent linkage; (4) the nano material working method such as " imprint lithography " or " microfluid " is utilized to prepare hydrogel microsphere.Wherein, polymerization single polymerization monomer normally joins in the aqueous phase (oil phase) of the no initiator containing emulsifying agent by microemulsion polymerization method, add to vigorous stirring in oil phase (aqueous phase) and form small droplets, then add initiator or form nanoparticle by high-energy radiation trigger monomer polymerization in aqueous phase (oil phase).And the reverse micro emulsion method of " water-in-oil " is preparing in hydrogel nanoparticles advantages such as having reaction conditions gentleness, gel micro-ball particle diameter easily controls, therefore be a kind of common method (TheGenerationofNanoparticlesinMiniemulsions.AdvancedMate rials, the 2001.13:765-768 that prepare micro-/ nano particulate material; MiniemulsionPolymerizationandtheStructureofPolymerandHyb ridNanoparticles.AngewandteChemieInternationalEdition, 2009.48:4488-4507), but at present less for the preparation of the bibliographical information of dextran based aquagel about the method, the reaction conditions that is suitable for and surfactant system are not yet proposed.
Summary of the invention
For above-mentioned prior art Problems existing and deficiency, the invention provides a kind of hydrogel microsphere based on dextran and preparation method thereof.The present invention proposes with " water-in-oil " Reverse Microemulsion System as reaction medium, by regulating factors such as forming the kinds of surfactants of reverse micro emulsion, content, surfactant compound ratio and emulsification method, preparation size is controlled and have the dextran based aquagel microballoon of good stability, and the present invention is achieved through the following technical solutions.
Based on a hydrogel microsphere for dextran, its structural formula can be expressed as follows:
。
A preparation method for the above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by dextran, be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 2:1 ~ 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 2 ~ 6h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 40 ~ 60 oxidized, concrete aldehyde radical degree is measured by oxammonium hydrochloride volumetry) that aldehyde radical degree is 40 ~ 60%;
(2) preparation of dextran hydrogel microballoon
Part aldehyde radical dextran solid step (1) obtained is dissolved in deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100 ~ 200mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 10 ~ 12h, finally by centrifugal collecting precipitate, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge, is scattered in deionized water and preserves;
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add sodium borohydride, at room temperature stir 24h, finally by centrifugal collecting precipitate, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water, is scattered in deionized water and preserves.
Dextran in described step (1) is any one in the dextran of molecular weight 10000g/mol ~ 100000g/mol.
In described step (2), aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:5 ~ 1:10.
Emulsifying agent in described step (2) is any one in the built agent (in this built agent, Tween80 is 5% ~ 20% of Span80 quality) of polyoxyethylenes (5) nonylplenyl ether (CO-520), sorbitan monooleate (Span80) or Span80/ sorbitan monooleate Soxylat A 25-7 (Tween80), and the add-on of emulsifying agent is 10 ~ 50% of hexanaphthene quality.
In described step (2), emulsification is mechanical stirring emulsification or ultrasonic emulsification.
Amine cross-linking agent in described step (2) be any one in quadrol, Methionin, arginine with two amino compounds, add-on is be that 1:1 ~ 2:1 adds according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent.
Amine cross-linking agent in described step (2) any one compound with two or more amino that to be molecular weight be in the dendroid polymine (PEI) of 600g/mol ~ 1800g/mol, add-on is be that 2:1 ~ 1:5 adds according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent.
In sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is 2:1 ~ 10:1 in described step (3).
The preparation process schematic process (for quadrol as linking agent) that the present invention is based on the hydrogel microsphere of dextran is as follows:
The invention has the beneficial effects as follows:
1, the dextran based aquagel microballoon that the present invention obtains is a kind of hydrogel microsphere based on natural macromolecular material, has good biological safety, stability and potential applicability in clinical practice.
2, the dextran based aquagel microballoon that the present invention relates to is obtained by reverse micro emulsion crosslinking, can regulate and control by regulating and controlling the kinds of surfactants of reverse micro emulsion, formation and emulsification method to its pattern, particle diameter.
Accompanying drawing explanation
Fig. 1 is the infrared spectrogram before and after the embodiment of the present invention 1 is reduced, and wherein a is gel micro-ball infrared spectrogram before reduction, and b is the infrared spectrogram of dextran hydrogel microballoon after reduction;
Fig. 2 is that the embodiment of the present invention 1 reduces front gel micro-ball stereoscan photograph;
Fig. 3 is that the embodiment of the present invention 2 reduces front gel micro-ball stereoscan photograph;
Fig. 4 is that the embodiment of the present invention 4 reduces front gel micro-ball stereoscan photograph;
Fig. 5 is that the embodiment of the present invention 7 reduces front gel micro-ball stereoscan photograph.
Embodiment
Below in conjunction with the drawings and specific embodiments, the invention will be further described.
Embodiment 1
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (dextran T10, molecular weight is 10000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 4h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 5kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 60 oxidized) that aldehyde radical degree is 60%;
(2) preparation of dextran hydrogel microballoon
0.15g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 150mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, vigorous stirring 15min emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (1500rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, be scattered in 2.0mL deionized water and preserve, this chemically crosslinked type dextran hydrogel microballoon obtains faint yellow solid powder by vacuum-drying, its infrared spectra is as shown in Fig. 1 (a), adopt scanning electronic microscope to observe the pattern of gel micro-ball obtained, result as shown in Figure 2: the sephadex microsphere obtained under this condition has regular globosity, microsphere features smooth surface, and size distribution is between 30 ~ 90 μm, its cyclohexane consumption is 8.0mL, and aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:8, and emulsifying agent is Span80, and add-on is the add-on of 2.0g(emulsifying agent is 32% of cyclohexane solution quality), stir as mechanical stirring, wherein amine cross-linking agent is quadrol, and add-on is be that 2:1 adds (about 18 μ L) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent,
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 50mg sodium borohydride (in sodium borohydride and dextran hydrogel microballoon, the mol ratio of C=N double bond is about 2.5:1), at room temperature stir 24h, finally by centrifugal (1500rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.Dextran hydrogel microballoon after reduction is by obtaining white solid powder after vacuum-drying, and its infrared spectra is as shown in Fig. 1 (b).
Embodiment 2
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 40, molecular weight is 40000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 4h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 60 oxidized) that aldehyde radical degree is 60%;
(2) preparation of dextran hydrogel microballoon
0.15g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 150mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, vigorous stirring 15min emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (3000rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, be scattered in 2.0ml deionized water and preserve, the pattern of scanning electronic microscope to the gel micro-ball obtained is adopted to observe, result is as shown in Figure 3: the sephadex microsphere obtained under this condition has regular globosity, microsphere features smooth surface, size distribution is between 10 ~ 50 μm, its cyclohexane consumption is 8.0mL, aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:8, and emulsifying agent is the built agent of Span80/Tween80, and add-on Span80 is 2.0g, Tween80 is the add-on of 0.2g(emulsifying agent is 35% of hexanaphthene quality), stir as mechanical stirring, wherein amine cross-linking agent is quadrol, and add-on is be that 2:1 adds (about 18 μ L) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent,
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 50mg sodium borohydride (in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is 2.5:1), at room temperature stir 24h, finally by centrifugal (3000rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.Dextran hydrogel microballoon after reduction is scattered in the Sodium phosphate dibasic-citrate buffer solution of a series of different pH, its stability is observed, result is as shown in table 1: under pH > 4.0 envrionment conditions, sephadex microsphere has satisfactory stability in aqueous, as pH value of solution < 4.0, sephadex microsphere is destructurized, less stable.
Table 1
Embodiment 3
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 70, molecular weight is 70000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 4h under room temperature, lucifuge condition, solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) after stirring is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 60 oxidized) that aldehyde radical degree is 60%;
(2) preparation of dextran hydrogel microballoon
0.1g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, vigorous stirring 15min emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (3000rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, is scattered in 2.0ml deionized water and preserves; Its cyclohexane consumption is 8.0mL, aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:8, emulsifying agent is the built agent of Span80/Tween80, add-on Span80 is 2.0g, Tween80 is the add-on of 0.4g(emulsifying agent is 38% of cyclohexane solution quality), stir as mechanical stirring; Wherein amine cross-linking agent is quadrol, and add-on is be that 2:1 adds (about 12 μ L) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent;
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 50mg sodium borohydride (in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is about 4:1), at room temperature stir 24h, finally by centrifugal (3000rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.
Embodiment 4
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 40, molecular weight is 40000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 4h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 60 oxidized) that aldehyde radical degree is 60%;
(2) preparation of dextran hydrogel microballoon
0.1g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, vigorous stirring 30min emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (4000rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, be scattered in 2.0ml deionized water and preserve, the pattern of scanning electronic microscope to the gel micro-ball obtained is adopted to observe, result is as shown in Figure 4: the sephadex microsphere obtained under this condition has regular globosity, microsphere features smooth surface, size distribution is between 2 ~ 6 μm, its cyclohexane consumption is 8.0mL, and aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:8, and emulsifying agent is CO-520, and add-on is the add-on of 3.0g(emulsifying agent is 48% of hexanaphthene quality), stir as mechanical stirring, wherein amine cross-linking agent is quadrol, and add-on is be that 2:1 adds (about 12 μ L) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent,
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 40mg sodium borohydride (in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is about 3:1), at room temperature stir 24h, finally by centrifugal (4000rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.
Embodiment 5
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 40, molecular weight is 40000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 2:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 6h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 40 oxidized) that aldehyde radical degree is 40%;
(2) preparation of dextran hydrogel microballoon
0.1g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, vigorous stirring 30min emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (3000rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, is scattered in 2.0ml deionized water and preserves; Its cyclohexane consumption is 8.0mL, the volume ratio of aldehyde radical glucan aqueous solution and hexanaphthene is 1:8, and emulsifying agent is Span80/Tween80 built agent, and add-on is Span80 is 2.0g, Tween80 is the add-on of 0.2g(emulsifying agent is 35% of hexanaphthene quality), stir as mechanical stirring; Wherein amine cross-linking agent is PEI(PEI molecular weight is 600g/mol, and its strength of solution is 0.25g/mL), add-on is be that 1:1 adds (0.2mL) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent;
(3) reduction of chemically crosslinked type dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 40mg sodium borohydride (in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is 2:1), at room temperature stir 24h, finally by centrifugal (3000rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.
Embodiment 6
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 70, molecular weight is 70000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 2:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 6h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 40 oxidized) that aldehyde radical degree is about 40%;
(2) preparation of dextran hydrogel microballoon
0.2g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 200mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, vigorous stirring 30min emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 10h, finally by centrifugal (1500rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, is scattered in 2.0ml deionized water and preserves; Its cyclohexane consumption is 10.0mL, and aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:10, and emulsifying agent is Span80, and the add-on of emulsifying agent is 10% of hexanaphthene quality, stirs as mechanical stirring; Wherein amine cross-linking agent is PEI(PEI molecular weight is 1800g/mol, and its strength of solution is 0.5g/mL), add-on is be that 2:1 adds (0.2mL) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent;
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add sodium borohydride (mol ratio of sodium borohydride and chemically crosslinked type dextran hydrogel microballoon C=N double bond is 2:1), at room temperature stir 24h, finally by centrifugal (1500rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.
Embodiment 7
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 40, molecular weight is 40000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 4h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 60 oxidized) that aldehyde radical degree is 60%;
(2) preparation of dextran hydrogel microballoon
0.1g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, ultrasonic emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (5000rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, is scattered in 2.0ml deionized water and preserves; Adopt scanning electronic microscope to observe the pattern of gel micro-ball obtained, result as shown in Figure 5: the sephadex microsphere obtained under this condition has regular globosity, and size distribution is between 200 ~ 500nm; Its cyclohexane consumption is 8.0mL, aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:8, emulsifying agent is Span80/Tween80 built agent, add-on is Span80 is 2.0g, Tween80 is the add-on of 0.2g(emulsifying agent is 35% of cyclohexane solution quality), ultrasonic emulsification condition is: power 130W, amplitude 75%; Amine cross-linking agent is quadrol, and add-on is be that 2:1 adds (about 12 μ L) according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent;
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 50mg sodium borohydride (in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is about 4:1), at room temperature stir 24h, finally by centrifugal (5000rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.
Embodiment 8
Should based on the hydrogel microsphere of dextran, its structural formula can be expressed as follows:
。
The preparation method of this above-mentioned hydrogel microsphere based on dextran, its concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by 5.0g dextran (Dextran T 40, molecular weight is 40000g/mol), be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 4h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing (molecular weight cut-off is 7kD) obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid (namely have in every 100 sugar units 60 oxidized) that aldehyde radical degree is 60%;
(2) preparation of dextran hydrogel microballoon
0.1g part aldehyde radical dextran solid step (1) obtained is dissolved in 1.0mL deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, ultrasonic emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 12h, finally by centrifugal (5000rpm, 5min) collecting precipitation thing, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge 5 ~ 6 times, is scattered in 2.0ml deionized water and preserves; Adopt scanning electronic microscope to observe the pattern of gel micro-ball obtained, result as shown in Figure 5: the sephadex microsphere obtained under this condition has regular globosity, and size distribution is between 200 ~ 500nm; Its cyclohexane consumption is 8.0mL, aldehyde radical glucan aqueous solution and hexanaphthene volume ratio are 1:8, emulsifying agent is Span80/Tween80 built agent, add-on is Span80 is 2.0g, Tween80 is the add-on of 0.2g(emulsifying agent is 35% of cyclohexane solution quality), ultrasonic emulsification condition is: power 130W, amplitude 75%; Wherein amine cross-linking agent is PEI(PEI molecular weight is 600g/mol, and its strength of solution is 0.5g/mL), add-on is be that 1:5 adds according to mol ratio amino in aldehyde radical in part aldehyde radical dextran and amine cross-linking agent;
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add 50mg sodium borohydride (in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is about 10:1), at room temperature stir 24h, finally by centrifugal (5000rpm, 5min) collecting precipitation thing, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water 5 ~ 6 times, is scattered in 2.0mL deionized water and preserves.
Below by reference to the accompanying drawings the specific embodiment of the present invention is explained in detail, but the present invention is not limited to above-mentioned embodiment, in the ken that those of ordinary skill in the art possess, various change can also be made under the prerequisite not departing from present inventive concept.
Claims (9)
1., based on a hydrogel microsphere for dextran, it is characterized in that structural formula can be expressed as follows:
。
2. a preparation method for the hydrogel microsphere based on dextran according to claim 1, is characterized in that concrete steps comprise as follows:
(1) preparation of aldehyde radical dextran
Be at room temperature that 10:100g/ml is dissolved in water according to solid-to-liquid ratio by dextran, be then placed in ice-water bath according to sugar unit/IO
4 -mol ratio is that 2:1 ~ 1:1 adds sodium periodate acquisition mixed solution, by mixed solution stirring reaction 2 ~ 6h under room temperature, lucifuge condition, the solution regenerated cellulose dialysis tubing obtained is dialysed 2 ~ 3 days in deionized water, in dialysis procedure, every 3 ~ 5h changes a deionized water, and postlyophilization of having dialysed obtains the part aldehyde radical dextran solid that aldehyde radical degree is 40 ~ 60%;
(2) preparation of dextran hydrogel microballoon
Part aldehyde radical dextran solid step (1) obtained is dissolved in deionized water and obtains the aldehyde radical glucan aqueous solution that concentration is 100 ~ 200mg/mL, at room temperature, being added by aldehyde radical glucan aqueous solution has dissolved in the cyclohexane solution of emulsifying agent, emulsification forms reverse micro emulsion, then add amine cross-linking agent and stir 10 ~ 12h, finally by centrifugal collecting precipitate, throw out obtains chemically crosslinked type dextran hydrogel microballoon after ethanol purge, is scattered in deionized water and preserves;
(3) reduction of dextran hydrogel microballoon
Obtain being scattered in the chemically crosslinked type dextran hydrogel microballoon in deionized water to step (2) and add sodium borohydride, at room temperature stir 24h, finally by centrifugal collecting precipitate, throw out obtains the dextran hydrogel microballoon after reducing after washed with de-ionized water, is scattered in deionized water and preserves.
3. the preparation method of the hydrogel microsphere based on dextran according to claim 2, is characterized in that: the dextran in described step (1) is any one in the dextran of molecular weight 10000g/mol ~ 100000g/mol.
4. the preparation method of the hydrogel microsphere based on dextran according to claim 2, is characterized in that: in described step (2), the volume ratio of aldehyde radical glucan aqueous solution and hexanaphthene is 1:5 ~ 1:10.
5. the preparation method of the hydrogel microsphere based on dextran according to claim 2, it is characterized in that: the emulsifying agent in described step (2) is any one in the built agent of polyoxyethylenes five nonylplenyl ether, sorbitan monooleate or Span80/ sorbitan monooleate Soxylat A 25-7, and the add-on of emulsifying agent is 10 ~ 50% of hexanaphthene quality.
6. the preparation method of the hydrogel microsphere based on dextran according to claim 2, is characterized in that: in described step (2), emulsification is mechanical stirring emulsification or ultrasonic emulsification.
7. the preparation method of the hydrogel microsphere based on dextran according to claim 2, it is characterized in that: the amine cross-linking agent in described step (2) be any one in quadrol, Methionin, arginine with two amino compounds, add-on is be that 1:1 ~ 2:1 adds according to mol ratio amino in aldehyde radical in part aldehyde radical dextran solid and amine cross-linking agent.
8. the preparation method of the hydrogel microsphere based on dextran according to claim 2, it is characterized in that: any one compound with two or more amino that to be molecular weight be in the dendroid polymine of 600g/mol ~ 1800g/mol of the amine cross-linking agent in described step (2), add-on is be that 2:1 ~ 1:5 adds according to mol ratio amino in aldehyde radical in part aldehyde radical dextran solid and amine cross-linking agent.
9. the preparation method of the hydrogel microsphere based on dextran according to claim 2, is characterized in that: in sodium borohydride and chemically crosslinked type dextran hydrogel microballoon, the mol ratio of C=N double bond is 2:1 ~ 10:1 in described step (3).
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