CN103910894A - Preparation method of injectable natural polysaccharide self-healing hydrogel - Google Patents
Preparation method of injectable natural polysaccharide self-healing hydrogel Download PDFInfo
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 57
- 150000004676 glycans Chemical class 0.000 title claims abstract description 20
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 20
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 47
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 43
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 43
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 43
- 239000000661 sodium alginate Substances 0.000 claims abstract description 43
- 229920001661 Chitosan Polymers 0.000 claims abstract description 41
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims abstract description 28
- 239000008363 phosphate buffer Substances 0.000 claims abstract description 16
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 claims abstract description 13
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000008367 deionised water Substances 0.000 claims description 28
- 229910021641 deionized water Inorganic materials 0.000 claims description 28
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 238000000502 dialysis Methods 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 16
- 238000004090 dissolution Methods 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 230000009514 concussion Effects 0.000 claims description 8
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 230000006196 deacetylation Effects 0.000 claims description 6
- 238000003381 deacetylation reaction Methods 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 230000000850 deacetylating effect Effects 0.000 claims description 2
- 239000000499 gel Substances 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 3
- 230000018044 dehydration Effects 0.000 abstract description 2
- 238000006297 dehydration reaction Methods 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 abstract 1
- 238000006845 Michael addition reaction Methods 0.000 abstract 1
- 238000006482 condensation reaction Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 238000007254 oxidation reaction Methods 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 28
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000002441 reversible effect Effects 0.000 description 9
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 7
- 239000000463 material Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 238000006957 Michael reaction Methods 0.000 description 1
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- 230000003044 adaptive effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000008698 shear stress Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
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Abstract
The invention relates to a preparation method of injectable natural polysaccharide self-healing hydrogel. The preparation method of the injectable natural polysaccharide self-healing hydrogel comprises the following steps: firstly synthesizing water soluble N-carboxyethyl chitosan by carrying out a Michael addition reaction on acrylic acid and chitosan, carrying out an oxidization reaction on sodium periodate and sodium alginate to obtain oxidized sodium alginate, then carrying out a dehydration condensation reaction on N-carboxyethyl chitosan and oxidized sodium alginate and on adipic dihydrazide and oxidized sodium alginate in a phosphate buffer liquid at the temperature of 37 DEG C, so as to respectively generate invertible imine bond and acylhydrazone bond, and finally preparing injectable natural polysaccharide macromolecular hydrogel with self-healing property. The preparation method of the injectable natural polysaccharide self-healing hydrogel has the advantages that a synthetic process of the injectable self-healing hydrogel is simple and green, reaction conditions are mild, the injectable self-healing hydrogel can form gel in a physiological environment and has self-healing capability, and the injectable self-healing hydrogel has a good application prospect in the fields of drug sustained release and the like.
Description
Technical field
The present invention relates to technical field of polymer materials, be particularly related to a kind of preparation method of injectable natural polysaccharide self-healing hydrogel, specifically apply N-carboxyetbyl chitosan and adipic dihydrazide and be cross-linked to form injectable gel with oxidized sodium alginate generation imine linkage and acylhydrazone key respectively, and these reversible chemical keys are given the self-healing performance that hydrogel is good.
Background technology
Macromolecule hydrogel (hydrogel) is visco-elasticity " soft, the wet " material of a class swelling large water gaging in three-dimensional macromolecule network.It is in organizational project, and the biomedical sectors such as biosensor and slow-released carrier (discharging medicine, treatment albumen or cell for embedding) have a wide range of applications.Injection aquagel is that a class can arrive precursor solution (aqueous solution being made up of the composition that forms hydrogel) injection after target position point by syringe, and a class intelligent aqueous gel capable material of original position generation solution-gel conversion.Because it has the characteristic such as form adaptive of the syringeability that can be injected in vivo with Wicresoft's intervening mode, the lesions position of filling complicated shape or reparation, conjunctive tissue, the series of problems of not only having avoided clinical operation to bring, and be applicable to the advantage operating at comparatively complicated structure, meticulous tissue site (blood vessel, nerve), obtain increasing concern and research at biomedical sector.
Be applied to biomedical injection aquagel and need to meet several key requests: (1) injection aquagel itself and precursor solution thereof should have good biocompatibility; (2) precursor solution of this injection aquagel need to have in the curing ability of target site rapid shaping; (3) precursor solution, after target site plastic is solidified, also needs it to reach rapidly certain physical strength, in order to avoid surrounding tissue extruding or deformation and hydrogel is caused to damage, but traditional injection aquagel is but difficult to meet above three requirements simultaneously.
Summary of the invention
In order to overcome the defect of above-mentioned prior art, the object of the present invention is to provide a kind of preparation method of injectable natural polysaccharide self-healing hydrogel, first the N-carboxyetbyl chitosan of the Michael reaction synthesizing water-solubility by vinylformic acid and chitosan, and obtain oxidized sodium alginate by sodium periodate and sodium alginate generation oxidizing reaction, in the phosphate buffer soln of 37 ℃, be there is to dehydration condensation with oxidized sodium alginate in N-carboxyetbyl chitosan and adipic dihydrazide more simultaneously, generate respectively reversible imine linkage and acylhydrazone key, finally prepare the injectable natural polysaccharide macromolecule hydrogel with self-healing performance, there is preparation method simple, reaction conditions gentleness, can be in plastic under physiological environment, the feature of self-healing.
In order to achieve the above object, technical scheme of the present invention is achieved in that
A preparation method for injectable natural polysaccharide self-healing hydrogel, comprises the following steps:
Step 1: add vinylformic acid in the chitosan solution of massfraction 1%～3%, the mol ratio of controlling amino and carboxyl is 1:(3～6), described deacetylating degree of chitosan 80%～100%, weight-average molecular weight 10～800kDa, at 50 ℃, stirring reaction is after 3 days, with sodium hydroxide solution regulator solution pH to 10～12 of 1mol/L, with dialysis tubing, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the N-carboxyetbyl chitosan of different degree of substitution;
Step 2: add sodium periodate in the sodium alginate soln that massfraction is 0.5%～1%, viscosity is 150～400mpa.s, the mol ratio of controlling sodium alginate and sodium periodate is 1:(0.2～1), at 25 ℃, lucifuge stirring reaction is after 5 hours, the sodium periodate reaction that adds excessive ethylene glycol to remove not run out of 1 hour, with dialysis tubing, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtain the oxidized sodium alginate of different oxidisabilities;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 5%～10%, above-mentioned three's active group mol ratio is (n-m): m:n, wherein n, m is positive integer, m ﹤ n, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 5%～10% hydrogel.
The present invention adopts N-carboxyetbyl chitosan and adipic dihydrazide to react with oxidized sodium alginate simultaneously, has the natural polysaccharide hydrogel of self-healing performance by the crosslinked preparation of reversible chemical key generating.Wherein the amino on N-carboxyetbyl chitosan and the aldehyde radical in oxidized sodium alginate generate reversible imine linkage by schiff base reaction, and oxidized sodium alginate reacts the reversible acylhydrazone key of generation simultaneously with adipic dihydrazide, these two kinds of dynamic covalent linkage all have the response feature of dynamic reversible.They are a kind of covalent linkage, kept to a certain extent covalent linkage character and can stable existence, they have again reversibility, i.e. there is running balance in the fracture of key and generation.These dynamic chemical keys are distributed in whole hydrogel network, make to exist all the time in network uncrosslinked active group, in the time that hydrogel is broken, these active groups can be cross-linked to form new reversible covalent bonds again, broken hydrogel fragment can be in this way again self-healing be combined into a complete hydrogel.In addition, the present invention adopts the natural polysaccharide material with good biocompatibility as hydrogel skeleton, building-up process is simply green, reaction conditions gentleness, it is the natural polysaccharide self-healing hydrogel that a kind of injectable is used, at medicament slow release, the biomedical sectors such as cell release have a good application prospect.
The present invention solves the problem existing in existing traditional injection water gel.Self-healing hydrogel is a kind of by the crosslinked hydrogel material that forms, has self-regeneration function of the reversible reactions such as dynamic covalent linkage or non covalent bond, and after impaired, self-healing hydrogel is repaired damaged part by the reversible reaction in network.Use for reference the concept of injectable gel, self-healing hydrogel can be put into syringe, by the shear-stress producing when the target site injection, self-healing hydrogel is injected to target site, the hydrogel fragment forming after these injections is after target site is assembled, self-regeneration becomes overall hydrogel, is filled into whole target site.Injectable self-healing hydrogel not only avoided traditional hydrogel precursor solution Cytotoxic may, and can control better its fixed position in vivo, do not need to consider the problems such as the plastic occurring in traditional injection aquagel is too fast or excessively slow.In addition, this hydrogel can be in target position self-healing, has avoided the problems such as the damage that causes because of surrounding tissue extruding or deformation.Injectable self-healing hydrogel is the type material that incorporates injectable and self-healing concept, and its appearance has practical significance to realizing the further high efficiency of injection aquagel material and intellectuality.
Embodiment
Below in conjunction with embodiment, the present invention will be described in more detail.
Embodiment mono-:
The present embodiment, comprises the following steps:
Step 1: by 1.0g deacetylation 86%, weight-average molecular weight is that 100kDa chitosan is dissolved in 50mL deionized water, be made into 2% chitosan solution, add wherein again 1.46mL vinylformic acid, stirring reaction 3 days at 50 ℃, rear sodium hydroxide solution regulator solution pH to 10～12 with 1mol/L, with the dialysis tubing of molecular weight cut-off 8000, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtaining substitution value is the N-carboxyetbyl chitosan of 46% left and right;
Step 2: the sodium alginate of 1.0g viscosity 350mpa.s is dissolved in 100mL deionized water, is made into 1% sodium alginate soln, then add wherein 0.22g sodium periodate, lucifuge stirring reaction 5 hours at 25 ℃.After having reacted, add 2mL ethylene glycol termination reaction 1 hour, then this solution is dialysed this solution with the dialysis tubing of molecular weight cut-off 3000 in deionized water, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the oxidized sodium alginate that oxidisability is 18% left and right;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 10%, above-mentioned three's active group mol ratio is that 1:1:2 mixed dissolution is in pH=7.0 phosphate buffer soln, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 10% hydrogel.
By two blocks of natural polysaccharide self-healing hydrogels that prepare being injected to small beaker with syringe, mix compacting, after 6 hours, gel pieces in small beaker heals again becomes a complete hydrogel entirety, and there is certain physical strength, confirm that this kind of hydrogel has good self-healing performance.
Embodiment bis-:
The present embodiment, comprises the following steps:
Step 1: by 1.0g deacetylation 86%, weight-average molecular weight is that 200kDa chitosan is dissolved in 50mL deionized water, is made into 2% chitosan solution, then adds wherein 1.10mL vinylformic acid, stirring reaction 3 days at 50 ℃.Use afterwards sodium hydroxide solution regulator solution pH to 10～12 of 1mol/L, with the dialysis tubing of molecular weight cut-off 8000, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtaining substitution value is the N-carboxyetbyl chitosan of 25% left and right;
Step 2: the sodium alginate of 1.0g viscosity 350mpa.s is dissolved in 100mL deionized water, is made into 1% sodium alginate soln, then add wherein 0.54g sodium periodate, lucifuge stirring reaction 5 hours at 25 ℃.After having reacted, add 2mL ethylene glycol termination reaction 1 hour, then this solution is dialysed this solution with the dialysis tubing of molecular weight cut-off 3000 in deionized water, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the oxidized sodium alginate that oxidisability is 46% left and right;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 7%, above-mentioned three's active group mol ratio is that 1:1:2 mixed dissolution is in pH=7.0 phosphate buffer soln, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 7% hydrogel.
By two blocks of natural polysaccharide self-healing hydrogels that prepare being injected to small beaker with syringe, mix compacting, after 6 hours, gel pieces in small beaker heals again becomes a complete hydrogel entirety, and there is certain physical strength, confirm that this kind of hydrogel has good self-healing performance.
Embodiment tri-
The present embodiment, comprises the following steps:
Step 1: by 1.0g deacetylation 86%, weight-average molecular weight is that 500kDa chitosan is dissolved in 50mL deionized water, be made into 2% chitosan solution, add wherein again 1.83mL vinylformic acid, stirring reaction 3 days at 50 ℃, rear sodium hydroxide solution regulator solution pH to 10～12 with 1mol/L, with the dialysis tubing of molecular weight cut-off 8000, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtaining substitution value is the N-carboxyetbyl chitosan of 38% left and right;
Step 2: the sodium alginate of 1.0g viscosity 350mpa.s is dissolved in 100mL deionized water, is made into 1% sodium alginate soln, then add wherein 1.08g sodium periodate, lucifuge stirring reaction 5 hours at 25 ℃.After having reacted, add 2mL ethylene glycol termination reaction 1 hour, then this solution is dialysed this solution with the dialysis tubing of molecular weight cut-off 3000 in deionized water, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the oxidized sodium alginate that oxidisability is 84% left and right;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 5%, above-mentioned three's active group mol ratio is that 1:1:2 mixed dissolution is in pH=7.0 phosphate buffer soln, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 5% hydrogel.
By two blocks of natural polysaccharide self-healing hydrogels that prepare being injected to small beaker with syringe, mix compacting, after 6 hours, gel pieces in small beaker heals again becomes a complete hydrogel entirety, and there is certain physical strength, confirm that this kind of hydrogel has good self-healing performance.
Claims (4)
1. a preparation method for injectable natural polysaccharide self-healing hydrogel, is characterized in that, comprises the following steps:
Step 1: add vinylformic acid in the chitosan solution of massfraction 1%～3%, the mol ratio of controlling amino and carboxyl is 1:(3～6), described deacetylating degree of chitosan 80%～100%, weight-average molecular weight 10～800kDa, at 50 ℃, stirring reaction is after 3 days, with sodium hydroxide solution regulator solution pH to 10～12 of 1mol/L, with dialysis tubing, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the N-carboxyetbyl chitosan of different degree of substitution;
Step 2: add sodium periodate in the sodium alginate soln that massfraction is 0.5%～1%, viscosity is 150～400mpa.s, the mol ratio of controlling sodium alginate and sodium periodate is 1:(0.2～1), at 25 ℃, lucifuge stirring reaction is after 5 hours, the sodium periodate reaction that adds excessive ethylene glycol to remove not run out of 1 hour, with dialysis tubing, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtain the oxidized sodium alginate of different oxidisabilities;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 5%～10%, above-mentioned three's active group mol ratio is (n-m): m:n, wherein n, m is positive integer, m ﹤ n, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 5%～10% hydrogel.
2. the preparation method of a kind of injectable natural polysaccharide self-healing hydrogel according to claim 1, is characterized in that, comprises the following steps:
Step 1: by 1.0g deacetylation 86%, weight-average molecular weight is that 100kDa chitosan is dissolved in 50mL deionized water, be made into 2% chitosan solution, add wherein again 1.46mL vinylformic acid, stirring reaction 3 days at 50 ℃, rear sodium hydroxide solution regulator solution pH to 10～12 with 1mol/L, with the dialysis tubing of molecular weight cut-off 8000, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtaining substitution value is the N-carboxyetbyl chitosan of 46% left and right;
Step 2: the sodium alginate of 1.0g viscosity 350mpa.s is dissolved in 100mL deionized water, is made into 1% sodium alginate soln, then add wherein 0.22g sodium periodate, lucifuge stirring reaction 5 hours at 25 ℃.After having reacted, add 2mL ethylene glycol termination reaction 1 hour, then this solution is dialysed this solution with the dialysis tubing of molecular weight cut-off 3000 in deionized water, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the oxidized sodium alginate that oxidisability is 18% left and right;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 10%, above-mentioned three's active group mol ratio is that 1:1:2 mixed dissolution is in pH=7.0 phosphate buffer soln, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 10% hydrogel.
3. the preparation method of a kind of injectable natural polysaccharide self-healing hydrogel according to claim 1, is characterized in that, comprises the following steps:
Step 1: by 1.0g deacetylation 86%, weight-average molecular weight is that 200kDa chitosan is dissolved in 50mL deionized water, is made into 2% chitosan solution, then adds wherein 1.10mL vinylformic acid, stirring reaction 3 days at 50 ℃.Use afterwards sodium hydroxide solution regulator solution pH to 10～12 of 1mol/L, with the dialysis tubing of molecular weight cut-off 8000, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtaining substitution value is the N-carboxyetbyl chitosan of 25% left and right;
Step 2: the sodium alginate of 1.0g viscosity 350mpa.s is dissolved in 100mL deionized water, is made into 1% sodium alginate soln, then add wherein 0.54g sodium periodate, lucifuge stirring reaction 5 hours at 25 ℃.After having reacted, add 2mL ethylene glycol termination reaction 1 hour, then this solution is dialysed this solution with the dialysis tubing of molecular weight cut-off 3000 in deionized water, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the oxidized sodium alginate that oxidisability is 46% left and right;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 7%, above-mentioned three's active group mol ratio is that 1:1:2 mixed dissolution is in pH=7.0 phosphate buffer soln, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 7% hydrogel.
4. the preparation method of a kind of injectable natural polysaccharide self-healing hydrogel according to claim 1, is characterized in that, comprises the following steps:
Step 1: by 1.0g deacetylation 86%, weight-average molecular weight is that 500kDa chitosan is dissolved in 50mL deionized water, be made into 2% chitosan solution, add wherein again 1.83mL vinylformic acid, stirring reaction 3 days at 50 ℃, rear sodium hydroxide solution regulator solution pH to 10～12 with 1mol/L, with the dialysis tubing of molecular weight cut-off 8000, this solution is dialysed in deionized water again, within one day, change water three times, the 5 days postlyophilizations of dialysing, obtaining substitution value is the N-carboxyetbyl chitosan of 38% left and right;
Step 2: the sodium alginate of 1.0g viscosity 350mpa.s is dissolved in 100mL deionized water, is made into 1% sodium alginate soln, then add wherein 1.08g sodium periodate, lucifuge stirring reaction 5 hours at 25 ℃.After having reacted, add 2mL ethylene glycol termination reaction 1 hour, then this solution is dialysed this solution with the dialysis tubing of molecular weight cut-off 3000 in deionized water, within one day, change water three times, the 5 days postlyophilizations of dialysing, can obtain the oxidized sodium alginate that oxidisability is 84% left and right;
Step 3: by the step 1 product N-carboxyetbyl chitosan with amino, with the adipic dihydrazide of diazanyl with the step 2 product oxidized sodium alginate of aldehyde radical, three's mixed dissolution is in phosphate buffer soln, total mass mark is 5%, above-mentioned three's active group mol ratio is that 1:1:2 mixed dissolution is in pH=7.0 phosphate buffer soln, at 37 ℃, by the concussion of its vortex evenly, leaving standstill and after 20 seconds, obtaining massfraction is 5% hydrogel.
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| CN105646893A (en) * | 2016-03-28 | 2016-06-08 | 东南大学 | Injectable self-healing hydrogel based on methyl vinyl ether-maleic acid copolymer/sodium alginate oxide and preparation method thereof |
| CN105749342A (en) * | 2016-04-29 | 2016-07-13 | 华南理工大学 | Bi-phase bone cartilage repairing support and preparing method thereof |
| CN105833346A (en) * | 2016-04-07 | 2016-08-10 | 福州大学 | Injected self-healing hydrogel material capable of realizing ordered release of medicine |
| CN105968390A (en) * | 2016-07-11 | 2016-09-28 | 武汉大学 | Chitosan-based self-healing gel and preparation method thereof |
| CN106009003A (en) * | 2016-07-11 | 2016-10-12 | 吉林大学 | Injectable self-repairing hydrogel based on polysaccharides, preparation method and application of hydrogel to biological tissue engineering |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101463145A (en) * | 2009-01-12 | 2009-06-24 | 武汉理工大学 | Carboxymethyl chitosan / oxidized sodium alginate self-crosslinking antibacterial hydrogel material |
-
2014
- 2014-03-28 CN CN201410123500.4A patent/CN103910894B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101463145A (en) * | 2009-01-12 | 2009-06-24 | 武汉理工大学 | Carboxymethyl chitosan / oxidized sodium alginate self-crosslinking antibacterial hydrogel material |
Non-Patent Citations (2)
| Title |
|---|
| KUEN YONG LEE ET AL.: ""Controlled degradation of hydrogels using multi-functional cross-linking molecules"", 《BIOMATERIALS》, vol. 25, no. 13, 30 June 2004 (2004-06-30), pages 2461 - 2466 * |
| 张立彦等: ""丙烯酸接枝壳聚糖水凝胶的制备及其pH敏感性"", 《化工进展》, vol. 27, no. 4, 31 December 2008 (2008-12-31) * |
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