CN101293943A - Galactosyl temperature-responsive polymer hydrogel and preparation method thereof - Google Patents
Galactosyl temperature-responsive polymer hydrogel and preparation method thereof Download PDFInfo
- Publication number
- CN101293943A CN101293943A CNA2008100536051A CN200810053605A CN101293943A CN 101293943 A CN101293943 A CN 101293943A CN A2008100536051 A CNA2008100536051 A CN A2008100536051A CN 200810053605 A CN200810053605 A CN 200810053605A CN 101293943 A CN101293943 A CN 101293943A
- Authority
- CN
- China
- Prior art keywords
- galactosyl
- hydrogel
- temperature
- gac
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Materials For Medical Uses (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention discloses a galactosyl-based temperature-sensitive polymer hydrogel and a preparation method thereof. The hydrogel is a Poly (NIPAAm-co-GAC) copolymerized hydrogel. The preparation method comprises three steps of: (1) synthesizing an intermediate L-NH2 with an aminogalactose group; (2) synthesizing an intermediate monomer GAC with galactosyl group and double bonds; and (3) preparing the Poly (NIPAAm-co-GAC) copolymerized hydrogel by using the NIPAAm (N-isopropylacrylamide) and the intermediate monomer GAC. The hydrogel has good temperature response and biocompatibility, and has good identification effect on hepatocytes; and can be used as a matrix material in tissue engineering for promoting cell adhension and growth in cell culture, and the cells can be automatically detached due to the temperature sensitivity of the hydrogel.
Description
Technical field
The present invention relates to a kind of intelligent polymer material technology, be specially a kind of responsive to temperature type N-N-isopropylacrylamide (N-isopropylacrylamide that has, NIPAAm) with galactosyl monomer (GAC) copolymer hydrogel and preparation method thereof technology, belong to functional high polymer material field.
Background technology
Field of tissue engineering technology combines with biomaterial and somatomedin with the whole bag of tricks application viable cell and develops substituent to repair, to keep or keep the function of tissue and organ.Engineering tissue often is planted in seed cell (culturing cell or stem cell) on the biological activity degraded support that mechanics and chemical signal can be provided the cell guiding differentiation and is assembled into three-dimensional tissue.
Organizational project often adopts hydrogel (polymer network that promptly contains hydrophilic radical) as the cell release vehicle.The similar of hydrogel is in intravital macromole constituent, and biocompatibility is good.Their water-wetted surface has low surface free energy, has caused protein seldom to attach to the surface.And the character of gels-soft and rubbery has minimized the repulsion with surrounding tissue.Hydrophobic chain can promote the attaching of cell.
The used in tissue engineering hydrogel at first will be considered its biocompatibility, particularly inflammatory reaction, and therefore, great majority research mainly concentrates on the natural polyalcohol hydrogel.
Life is relevant with polymkeric substance in essence at it, and the most important constituent of viable cell (protein, sugar and nucleic acid) all is biomacromolecules, and they all can nonlinear response external stimulus.This type of responsiveness comes from the interaction of high Collaboration.Up to now people to the function of protein and nucleic acid know more, less to the function understanding of polysaccharide.Polysaccharide such as glycosaminoglycan constituent (heparin, hyaluronic acid) etc. are all as tissue engineering bracket, immune barrier film material, cell culture vector and medicine and gene release vehicle.There are some researches show that the synthetic macromolecule that contains glycosyl has cellular affinity preferably, help cell absorption.
[Lopina ST, Wu G et al. biomaterial, 1996 such as Rowly; 17:559-69 (Lopina ST, Wu G et al.Biomaterials, 1996; 17:559-69.)] the report cell that contains RGD (cell adhesion albumen) alginate that attach the ligand modification have improved the expression that sarcoplast and difference are shown one's color.Reported also that simultaneously galactose moiety discerned by the hepatitis B acceptor (ASGP-R) of surface of hepatocytes and improve hepatocellular attaching.
[Jun Yang such as Yang Jun, Mitsuaki G et al. biomaterial, 23 (2002) 471-479. (JunYang, Mitsuaki G et al.Biomaterials 23 (2002) 471-479.)] promoted to act between hepatocellular attaching and liver cell and alginate with the alginate of semi-lactosi modification part, in three-dimensional cultivation, improved encapsulated hepatocellular liver function then as ASGP-R.
Taek Wong Chung etc. [Zhang Can, fourth Ya. China Medicine University's journal, 2003,34 (5): 387-390.] utilize that the lactobionic acid have galactosyl is covalently bound to be used for detecting hepatocellular feature to chitosan.Prepared the three-dimensional foam sponge body support frame of forming by Protanal TXF 200 (ALG) and galactosyl chitosan (GC) so that the mechanical property of hepatocellular recognition signal and raising ALG cavernous body to be provided.
Utilize galactosyl to be coupled in the macromole, and then be prepared into various cavernous bodies, porous support etc. has realization more, but does not see the synthetic report that the galactosyl hydrogel is arranged.
Natural polyalcohol hydrogel has its limitation, and intelligent etc. as not having, this just impels people that the natural polymer hydrogel is carried out modification.PNIPAM (PNIPAAm) gel is typical temperature sensitive intelligent material, and the lower critical solution temperature (LCST) of PNIPAM (PNIPAAm) in water can produce transformation mutually near 32 ℃ under this temperature.The research of PNIPAAm thermo-sensitive gel much concentrates on aspects such as the immobilization of drug release, enzyme and bioseparation.[Zhang Xianzheng, Zhuo Renxi such as Zhang Xianzheng.SCI, 2000,21:1309-1311] use acrylamide (AAm) and NIPAAm copolymerization to synthesize hydrogel with fast temperature sensitivity, and its application at aspects such as switch-valve and artificial-muscles is looked forward to.[Teruo Okano such as Okano, NorikoYamada, MinakoOkuhara et al. biomaterial, 16 (1995) 297-303 (Teruo Okano, NorikoYamada, MinakoOkuhara et al.Biomaterials 16 (1995) 297-303)] utilize PNIPAM (PNIPAAm) to carry out cell culture studies, still, when using PNIPAAm separately, its biocompatibility is not high.
As seen from the above analysis, though PNIPAAm has temperature sensitivity, aspect wetting ability and biocompatibility, show not enough.PNIPAAm gel based on glycosyl galactose not only has temperature-responsive, and the saccharification polymkeric substance has affinity for cell, can improve the characteristics that cell attaches, and in addition, galactose component has good targeting for liver cell.
Summary of the invention
The technical problem that quasi-solution of the present invention is determined is, designs a kind of novel intelligent macromolecule hydrogel, and this intelligent aqueous gel capable had both had temperature sensitivity preferably, also has excellent biological compatibility, higher wetting ability and cellular affinity simultaneously.The variation of hydrophilic and hydrophobic can take place by attemperation in this gel, is used for organizational project, cell cultures, can realize the natural desorption of cell, the function damage of avoiding tryptic digestion method pair cell to cause.
The invention provides a kind of galactosyl temperature-responsive polymer hydrogel, this hydrogel is N-N-isopropylacrylamide and the monomeric multipolymer of modification galactosyl, and its mass percent is as follows: the ratio of N-N-isopropylacrylamide and galactosyl monomer (GAC) is 1: 0.2～1.The N-N-isopropylacrylamide provides the temperature sensitivity of material, and the adding of modification semi-lactosi makes material have better biocompatibility, higher wetting ability and cellular affinity.
The preparation method of galactosyl temperature-responsive polymer hydrogel of the present invention comprises the steps:
(1) the intermediate L-NH of synthetic semi-lactosi end amino
2: with lactobionic acid (LA) and quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the dimethyl sulfoxide (DMSO) (DMSO), making its mass ratio is 4-6: 1, and mixing solutions concentration is 0.5-1g/ml, reaction 2-4h when temperature is 70-80 ℃ is with precipitating in the mixture solution impouring chloroform, then with product L-NH
2Vacuum-drying.
(2) the synthetic middle monomer GAC of galactosyl that has two keys: the intermediate L-NH and the vinylformic acid (AAc) of semi-lactosi end amino are dissolved in respectively in the dimethyl sulfoxide (DMSO) (DMSO), making its mass ratio is 4-6: 1, the solution melting concn is 0.2-0.5g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.05-0.15wt%, at room temperature whirlpool stirs 20-30h, use the chloroform precipitating, unreacted reactant is removed in vacuum-drying.
(3) preparation poly (NIPAAm-co-GAC) copolymer hydrogel: take by weighing GAC and monomer NIPAAm respectively by mass ratio GAC: NIPAAm=0.2～1: 1; Both are dissolved in and make mixing solutions in the deionized water, and mixed liquid concentration is controlled at 0.05～0.2g/ml; The MBAA that adds concentration and be 1-2wt% in mixing solutions is as linking agent, fully the dissolving back is logical nitrogen 10-30 minute, the TEMED that adds APS that weight is 0.02-0.04wt% and 0.05-0.15wt% again is as initiator system, continue to feed nitrogen more than 10 minutes, mixture is injected glass mold, polymerized at room temperature 24～48h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is dipped to a few week with deionized water, makes it in water, reach balance, promptly get the target macromolecule hydrogel.
Beneficial effect: compared with prior art, the galactosyl temperature-responsive polymer hydrogel that the present invention proposes has comprehensive performance: owing to have two functional group's galactosyls that its performance had crucial influence in its molecular structure, with PNIPAM macromolecular chain with temperature-responsive, therefore, this hydrogel has good temperature-responsive and excellent biological compatibility, have swelling behavior and higher mechanical property preferably simultaneously, document reported once that monomer concentration was that swelling ratio in the time of 25 ℃ of the homopolymerization N-N-isopropylacrylamide hydrogel of 15wt% (swelling ratio is meant that a certain temperature is issued to when stablizing solvent swelling state hydrogel and its vacuum-drying to the mass ratio of the gel of constant weight) is about 7[referring to document: " research of N-N-isopropylacrylamide/N-vinyl pyrrolidone hydrogel ", Liu Yuyang, Fan Xiaodong, Shao Yinghui, the functional polymer journal, 2000,13:380-385].And hydrogel of the present invention is under same ambient conditions, and swelling ratio can reach 20-25, and this product also has good integrity simultaneously, is difficult for brokenly, shows comparatively ideal mechanical property.In addition, the introducing of galactosyl makes it have good recognition reaction to liver cell.Because its good overall characteristic, galactosyl temperature-responsive type hydrogel of the present invention can be used widely at aspects such as the tissue engineering bracket material that needs high strength and/or biocompatibility, cell culture medium materials.
Galactosyl temperature-responsive polymer hydrogel of the present invention, because an end coupling has functional group's semi-lactosi cyclic group in its molecular structure, this group can be to the asialoglycoprotein receptor specific recognition in the liver cell, simultaneously in the grafting N-isopropylacrylamide monomer, caused this gel to have the self-regulating function of certain hydrophilic/hydrophobic, therefore, given this hydrogel good temperature-responsive, in addition, the introducing of galactosyl, make it have good targeting to liver cell, has good biocompatibility, can be used in the cell cultures, can realize the natural desorption of cell, the cell function damage of having avoided the tryptic digestion method to cause.The present invention is applicable to the preparation of various substrate materials in the organizational project like this, can be designed to the material to the specific cells reaction.
The present invention is from synthetic L-NH
2Intermediate sets out, selecting lactobionic acid is because the lactobionic acid cost is reasonable as introducing the galactosyl part, toxicity is low, biocompatibility is good, be because vinylformic acid is with low cost, stable in properties with vinylformic acid as the monomer of introducing the two keys of reactive behavior in addition, belong to conventional medicine, reaction residue is removed easily.
Preparation method's technology of the present invention is simple, and all has good controllability, just can carry out under atmospheric pressure state; Used reagent is conventional reagent, does not need specific installation, and is with low cost, is suitable for applying.
The hydrogel of the present invention preparation is the space multistory network structure on the microstructure of space, the mutual crosslinked composition mesh architecture of macromolecular chain, and fluid water is wherein involved can not unrestricted flow, thereby show certain elasticity, and can keep certain shape.
Embodiment
The present invention further is described below:
The preparation method of a kind of galactosyl temperature-responsive polymer hydrogel of the present invention's design mainly comprises three steps:
Below provide specific embodiments of the invention, but the present invention is not subjected to the restriction of embodiment:
Embodiment 1:
(1) with 12g lactobionic acid (LA) and 3g quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the 30ml dimethyl sulfoxide (DMSO) (DMSO), the about 2h of reaction when temperature is 70 ℃ is with precipitating in the mixture solution impouring chloroform, the product vacuum-drying of separating out.
(2) with the intermediate L-NH of semi-lactosi end amino
2And vinylformic acid (AAc) is dissolved in the 20ml dimethyl sulfoxide (DMSO) (DMSO) L-NH respectively
2With vinylformic acid (AAc) mass ratio be 4: 1, the solution melting concn is 0.2g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.1wt%; At room temperature whirlpool stirs 20h, uses the chloroform precipitating, and vacuum-drying gets product GAC.
(3) by mass ratio GAC: NIPAAm=0.2: 1 takes by weighing GAC and monomer NIPAAm respectively, both are dissolved in and make the 0.05g/ml mixing solutions in the deionized water, add 1wt%MBAA and make linking agent, fully the logical nitrogen in dissolving back is 10 minutes, add weight again and be 0.02wt%APS and 0.05wt%TEMED as initiator system, continue to feed nitrogen 10 minutes, mixture is injected glass mold, polymerized at room temperature 24h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is soaked a week with deionized water, make it in water, reach balance, promptly get the target macromolecule hydrogel.
Embodiment 2:
(1) with 12g lactobionic acid (LA) and 2g quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the 20ml dimethyl sulfoxide (DMSO) (DMSO), the about 2h of reaction when temperature is 70 ℃ is with precipitating in the mixture solution impouring chloroform, the product vacuum-drying of separating out.
(2) with the intermediate L-NH of semi-lactosi end amino
2And vinylformic acid (AAc) is dissolved in the 20ml dimethyl sulfoxide (DMSO) (DMSO) L-NH respectively
2With vinylformic acid (AAc) mass ratio be 6: 1, the solution melting concn is 0.5g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.05wt%; At room temperature whirlpool stirs 30h, uses the chloroform precipitating, and vacuum-drying gets product GAC.
(3) by mass ratio GAC: NIPAAm=0.5: 1 takes by weighing GAC and monomer NIPAAm respectively, both are dissolved in and make the 0.1g/ml mixing solutions in the deionized water, add 2wt%MBAA and make linking agent, fully the logical nitrogen in dissolving back is 20 minutes, add weight again and be 0.04wt%APS and 0.1wt%TEMED as initiator system, continue to feed nitrogen 12 minutes, mixture is injected glass mold, polymerized at room temperature 30h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is soaked a week with deionized water, make it in water, reach balance, promptly get the target macromolecule hydrogel.
Embodiment 3:
(1) with 12g lactobionic acid (LA) and 3g quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the 15ml dimethyl sulfoxide (DMSO) (DMSO), the about 4h of reaction when temperature is 80 ℃ is with precipitating in the mixture solution impouring chloroform, the product vacuum-drying of separating out.
(2) with the intermediate L-NH of semi-lactosi end amino
2And vinylformic acid (AAc) is dissolved in the 20ml dimethyl sulfoxide (DMSO) (DMSO) L-NH respectively
2With vinylformic acid (AAc) mass ratio be 6: 1, the solution melting concn is 0.3g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.15wt%; At room temperature whirlpool stirs 25h, uses the chloroform precipitating, and vacuum-drying gets product GAC.
(3) by mass ratio GAC: NIPAAm=0.8: 1 takes by weighing GAC and monomer NIPAAm respectively, both are dissolved in and make the 0.2g/ml mixing solutions in the deionized water, add 2wt%MBAA and make linking agent, fully the logical nitrogen in dissolving back is 30 minutes, add weight again and be 0.04wt%APS and 0.15wt%TEMED as initiator system, continue to feed nitrogen 12 minutes, mixture is injected glass mold, polymerized at room temperature 48h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is soaked a week with deionized water, make it in water, reach balance, promptly get the target macromolecule hydrogel.
Embodiment 4:
(1) with 12g lactobionic acid (LA) and 3g quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the 25ml dimethyl sulfoxide (DMSO) (DMSO), the about 4h of reaction when temperature is 75 ℃ is with precipitating in the mixture solution impouring chloroform, the product vacuum-drying of separating out.
(2) with the intermediate L-NH of semi-lactosi end amino
2And vinylformic acid (AAc) is dissolved in the 20ml dimethyl sulfoxide (DMSO) (DMSO) L-NH respectively
2With vinylformic acid (AAc) mass ratio be 5: 1, the solution melting concn is 0.4g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.15wt%; At room temperature whirlpool stirs 25h, uses the chloroform precipitating, and vacuum-drying gets product GAC.
(3) by mass ratio GAC: NIPAAm=0.9: 1 takes by weighing GAC and monomer NIPAAm respectively, both are dissolved in and make the 0.2g/ml mixing solutions in the deionized water, add 2wt%MBAA and make linking agent, fully the logical nitrogen in dissolving back is 30 minutes, add weight again and be 0.04wt%APS and 0.15wt%TEMED as initiator system, continue to feed nitrogen 12 minutes, mixture is injected glass mold, polymerized at room temperature 48h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is soaked a week with deionized water, make it in water, reach balance, promptly get the target macromolecule hydrogel.
Embodiment 5:
(1) with 12g lactobionic acid (LA) and 3g quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the 25ml dimethyl sulfoxide (DMSO) (DMSO), the about 4h of reaction when temperature is 75 ℃ is with precipitating in the mixture solution impouring chloroform, the product vacuum-drying of separating out.
(2) with the intermediate L-NH of semi-lactosi end amino
2And vinylformic acid (AAc) is dissolved in the 20ml dimethyl sulfoxide (DMSO) (DMSO) L-NH respectively
2With vinylformic acid (AAc) mass ratio be 5: 1, the solution melting concn is 0.4g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.15wt%; At room temperature whirlpool stirs 25h, uses the chloroform precipitating, and vacuum-drying gets product GAC.
(3) by mass ratio GAC: NIPAAm=1: 1 takes by weighing GAC and monomer NIPAAm respectively, both are dissolved in and make the 0.2g/ml mixing solutions in the deionized water, add 2wt%MBAA and make linking agent, fully the logical nitrogen in dissolving back is 30 minutes, add weight again and be 0.04wt%APS and 0.15wt%TEMED as initiator system, continue to feed nitrogen 12 minutes, mixture is injected glass mold, polymerized at room temperature 48h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is soaked a week with deionized water, make it in water, reach balance, promptly get the target macromolecule hydrogel.
Embodiment 6:
(1) with 12g lactobionic acid (LA) and 3g quadrol (NH
2CH
2CH
2NH
2) be dissolved in respectively in the 25ml dimethyl sulfoxide (DMSO) (DMSO), the about 4h of reaction when temperature is 75 ℃ is with precipitating in the mixture solution impouring chloroform, the product vacuum-drying of separating out.
(2) with the intermediate L-NH of semi-lactosi end amino
2And vinylformic acid (AAc) is dissolved in the 20ml dimethyl sulfoxide (DMSO) (DMSO) L-NH respectively
2With vinylformic acid (AAc) mass ratio be 5: 1, the solution melting concn is 0.4g/ml, adding total concn is 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDC.HCL) and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.15wt%; At room temperature whirlpool stirs 25h, uses the chloroform precipitating, and vacuum-drying gets product GAC.
(3) by mass ratio GAC: NIPAAm=0.6: 1 takes by weighing GAC and monomer NIPAAm respectively, both are dissolved in and make the 0.2g/ml mixing solutions in the deionized water, add 2wt%MBAA and make linking agent, fully the logical nitrogen in dissolving back is 30 minutes, add weight again and be 0.04wt%APS and 0.15wt%TEMED as initiator system, continue to feed nitrogen 12 minutes, mixture is injected glass mold, polymerized at room temperature 48h gets poly (NIPAAm-co-GAC) copolymer hydrogel.The gained copolymer hydrogel is soaked a week with deionized water, make it in water, reach balance, promptly get the target macromolecule hydrogel.
Claims (6)
1. galactosyl temperature-responsive polymer hydrogel, comprise the N-N-isopropylacrylamide, it is characterized in that this hydrogel is N-N-isopropylacrylamide and the monomeric multipolymer of modification galactosyl, the monomeric mass percent of N-N-isopropylacrylamide and galactosyl is 1: 0.2～1; Its preparation method comprises: the intermediate L-NH of (1) synthetic semi-lactosi end amino
2(2) the synthetic galactosyl monomer that has two keys; (3) preparation poly (NIPAAm-co-GAC) copolymer hydrogel.
2. galactosyl temperature-responsive polymer hydrogel according to claim 1 is characterized in that the mass percent 1: 0.2,1: 0.5,1: 0.6,1: 0.8,1: 0.9 or 1: 1 of N-N-isopropylacrylamide and galactosyl monomer (GAC).
3. galactosyl temperature-responsive polymer hydrogel preparation method as claimed in claim 1 comprises the steps: the intermediate L-NH of (1) synthetic semi-lactosi end amino
2: lactobionic acid and quadrol are dissolved in the dimethyl sulfoxide (DMSO), and mixing solutions concentration is 0.5-1g/ml, reaction 2-4h in the time of 70-80 ℃, and mixture solution impouring chloroform precipitating, vacuum-drying gets intermediate L-NH
2(2) synthetic galactosyl monomer: the intermediate and the vinylformic acid of semi-lactosi end amino are dissolved in dimethyl sulfoxide (DMSO), the solution melting concn is 0.2-0.5g/ml, adding total concn is 1-3-dimethylamino-propyl-3-ethyl-carbodiimide hydrochloride and the N-hydroxy thiosuccinimide (Sulfo-NHS) of 0.05-0.15wt%, stir 20-30h, the chloroform precipitating, unreacted reactant is removed in vacuum-drying; (3) preparation copolymer hydrogel: mass ratio 0.2～1: the water-soluble mixing solutions of making of 1 GAC and N-N-isopropylacrylamide, mixed liquid concentration 0.05～0.2g/ml; Adding concentration is the MBAA of 1-2wt%, logical nitrogen 10-30 minute, add the APS of 0.02-0.04wt% and the TEMED of 0.05-0.15wt%, logical nitrogen, mixture is injected glass mold, and polymerization 24～48h gets copolymer hydrogel, the copolymer hydrogel deionized water soaks at least one week, gets galactosyl temperature-responsive polymer hydrogel.
4. according to the described galactosyl temperature-responsive polymer hydrogel preparation method of claim 3, it is characterized in that the monomeric mass percent of N-N-isopropylacrylamide and galactosyl is 1: 0.2,1: 0.5,1: 0.6,1: 0.8,1: 0.9 or 1: 1.
5. galactosyl temperature-responsive polymer hydrogel preparation method according to claim 3 is characterized in that middle lactobionic acid of described step (1) and quadrol mass ratio are 4-6: 1.
6. galactosyl temperature-responsive polymer hydrogel preparation method according to claim 3 is characterized in that the intermediate and the vinylformic acid mass ratio of semi-lactosi end amino in the described step (2) is 4-6: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100536051A CN101293943B (en) | 2008-06-23 | 2008-06-23 | Galactosyl temperature-responsive polymer hydrogel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100536051A CN101293943B (en) | 2008-06-23 | 2008-06-23 | Galactosyl temperature-responsive polymer hydrogel and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101293943A true CN101293943A (en) | 2008-10-29 |
| CN101293943B CN101293943B (en) | 2011-05-11 |
Family
ID=40064503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100536051A Expired - Fee Related CN101293943B (en) | 2008-06-23 | 2008-06-23 | Galactosyl temperature-responsive polymer hydrogel and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101293943B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010118950A3 (en) * | 2009-04-15 | 2010-12-09 | Basf Se | Method for producing unsaturated acylamidoalkyl polyhydroxy acid amides |
| CN102432746A (en) * | 2011-09-26 | 2012-05-02 | 天津工业大学 | Temperature-responsive L-amino-acid-modified chiral high-molecular hydrogel |
| CN103080295A (en) * | 2010-08-31 | 2013-05-01 | 学校法人东京女子医科大学 | Temperature-responsive substrate for cell culture and method for producing same |
| CN110099996A (en) * | 2016-12-22 | 2019-08-06 | Dic株式会社 | Cell culture substrate |
| CN111690090A (en) * | 2020-06-30 | 2020-09-22 | 闽江学院 | Glycosylated photonic crystal hydrogel and application thereof in influenza virus detection |
-
2008
- 2008-06-23 CN CN2008100536051A patent/CN101293943B/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010118950A3 (en) * | 2009-04-15 | 2010-12-09 | Basf Se | Method for producing unsaturated acylamidoalkyl polyhydroxy acid amides |
| CN102421787A (en) * | 2009-04-15 | 2012-04-18 | 巴斯夫欧洲公司 | Method for producing unsaturated acylamidoalkyl polyhydroxy acid amides |
| JP2012524041A (en) * | 2009-04-15 | 2012-10-11 | ビーエーエスエフ ソシエタス・ヨーロピア | Method for producing unsaturated acrylamide alkyl polyhydroxy acid amide |
| CN102421787B (en) * | 2009-04-15 | 2015-11-25 | 巴斯夫欧洲公司 | Prepare the method for unsaturated acyl aminoalkyl group polyhydroxy amides |
| CN103080295A (en) * | 2010-08-31 | 2013-05-01 | 学校法人东京女子医科大学 | Temperature-responsive substrate for cell culture and method for producing same |
| CN103080295B (en) * | 2010-08-31 | 2014-08-27 | 学校法人东京女子医科大学 | Temperature-responsive substrate for cell culture and method for producing same |
| CN102432746A (en) * | 2011-09-26 | 2012-05-02 | 天津工业大学 | Temperature-responsive L-amino-acid-modified chiral high-molecular hydrogel |
| CN110099996A (en) * | 2016-12-22 | 2019-08-06 | Dic株式会社 | Cell culture substrate |
| US11427803B2 (en) | 2016-12-22 | 2022-08-30 | Fujifilm Corporation | Cell culture substrate |
| CN111690090A (en) * | 2020-06-30 | 2020-09-22 | 闽江学院 | Glycosylated photonic crystal hydrogel and application thereof in influenza virus detection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101293943B (en) | 2011-05-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101293943B (en) | Galactosyl temperature-responsive polymer hydrogel and preparation method thereof | |
| Konno et al. | Temporal and spatially controllable cell encapsulation using a water-soluble phospholipid polymer with phenylboronic acid moiety | |
| CN1754893B (en) | Ionic hydrophilic high molecular weight redox ploymers for use in enzymatic electrochemical-based sensors | |
| Miyata et al. | Biomolecule-sensitive hydrogels | |
| CN100575939C (en) | Be used for redox polymer based on electrochemical sensor | |
| CN103948962B (en) | Method for preparing growth-factor bound thermo-sensitive hydrogel biocarrier | |
| Bartkowiak et al. | Alginate− Oligochitosan microcapsules. II. control of mechanical resistance and permeability of the membrane | |
| Sakai et al. | Synthesis and characterization of both ionically and enzymatically cross-linkable alginate | |
| CN101824123B (en) | High-strength temperature-sensitive hydrogel as well as preparation method and application thereof | |
| CN109734851B (en) | Temperature-sensitive polymer, synthesis method thereof and temperature-sensitive injectable hydrogel | |
| Singh et al. | Proliferation of chondrocytes on a 3-D modelled macroporous poly (hydroxyethyl methacrylate)–gelatin cryogel | |
| CN100519629C (en) | Poly L-glutamic acid-poly N-isopropylacrylamide graft copolymer and preparation method thereof | |
| US11441120B2 (en) | Cell culture substrate | |
| Zhao et al. | Inhibition of protein adsorption and cell adhesion on PNIPAAm-grafted polyurethane surface: Effect of graft molecular weight | |
| Tang et al. | Robust MeO2MA/vinyl-4, 6-diamino-1, 3, 5-triazine copolymer hydrogels-mediated reverse gene transfection and thermo-induced cell detachment | |
| JP2001037472A (en) | Three dimensional cell-culturing base medium and cell culture using the same | |
| US8883503B2 (en) | Hydrogel scaffolds for tissue engineering | |
| Kobayashi et al. | Oligosaccharide-carrying styrene-type macromers. Polymerization and specific interactions between the polymers and liver cells | |
| CN102140171B (en) | Glutathione-modified chitosan copolymer serving as non-viral gene carrier material and preparation and application thereof | |
| CN101979419A (en) | High-strength hydrogel with anti-adsorption function and preparation method thereof | |
| CN105295077A (en) | Temperature sensitive type polyion liquid gel and preparation method thereof | |
| CN102161728A (en) | Semi-interpenetrating-network nano composite hydrogel with biocompatibility and temperature sensitivity, and preparation method and application thereof | |
| Reddy et al. | Monosaccharide-responsive phenylboronate-polyol cell scaffolds for cell sheet and tissue engineering applications | |
| CN101857683A (en) | Different types of chitosan methacrylate and preparation method thereof | |
| JPH08319300A (en) | Immobilization of lectin and base for cell using the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110511 Termination date: 20180623 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |