CN106349480B - A kind of heat-light sensitive hydrogel and preparation method thereof - Google Patents
A kind of heat-light sensitive hydrogel and preparation method thereof Download PDFInfo
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- CN106349480B CN106349480B CN201610705208.2A CN201610705208A CN106349480B CN 106349480 B CN106349480 B CN 106349480B CN 201610705208 A CN201610705208 A CN 201610705208A CN 106349480 B CN106349480 B CN 106349480B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
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- 230000004048 modification Effects 0.000 claims abstract description 18
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- 238000006482 condensation reaction Methods 0.000 claims abstract description 9
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 50
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- 229920001983 poloxamer Polymers 0.000 claims description 22
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 21
- 229960000502 poloxamer Drugs 0.000 claims description 21
- 239000002202 Polyethylene glycol Substances 0.000 claims description 17
- 229920001223 polyethylene glycol Polymers 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
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- 239000012153 distilled water Substances 0.000 claims description 10
- 230000001376 precipitating effect Effects 0.000 claims description 9
- 239000002994 raw material Substances 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- -1 alkene acyl chlorides Chemical class 0.000 claims description 7
- 239000012265 solid product Substances 0.000 claims description 7
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 claims description 6
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 5
- HNXGGWNCFXZSAI-UHFFFAOYSA-N 2-morpholin-2-ylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1CNCCO1 HNXGGWNCFXZSAI-UHFFFAOYSA-N 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 5
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- 238000001035 drying Methods 0.000 claims description 5
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- 229940014800 succinic anhydride Drugs 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 4
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 claims description 4
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
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- 238000006467 substitution reaction Methods 0.000 claims description 3
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- 230000006196 deacetylation Effects 0.000 claims description 2
- 238000003381 deacetylation reaction Methods 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims 1
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- 238000009833 condensation Methods 0.000 abstract description 5
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- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 abstract description 3
- 150000001263 acyl chlorides Chemical class 0.000 abstract description 2
- 238000004401 flow injection analysis Methods 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 description 12
- 206010034960 Photophobia Diseases 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 208000013469 light sensitivity Diseases 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 230000008542 thermal sensitivity Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 2
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- XDQGMXYCBZNEAG-UHFFFAOYSA-N C(C)[C]CCCN(C)C Chemical compound C(C)[C]CCCN(C)C XDQGMXYCBZNEAG-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
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- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
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- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
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- 230000000052 comparative effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
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- 210000003205 muscle Anatomy 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
-
- 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
- C08J2387/00—Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
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- Chemical Kinetics & Catalysis (AREA)
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- Polymers & Plastics (AREA)
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- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
Abstract
The invention discloses a kind of heat-light sensitive hydrogels and preparation method thereof, and the high molecular polymer which is grafted by chitosan and thereon collectively forms；Photosensitive part is made of the olefinic double bonds being grafted on chitosan and high molecular polymer.In the hydrogel preparation process, olefinic double bonds modification is realized in the acyl chlorides condensation for first passing through high molecular polymer one end, its other end is then carried out carboxylated modification；Then under condensing agent existence condition, the high molecular polymer of modification is grafted on chitosan, and is further advanced by the grafted olefin double bond on chitosan of the condensation reaction between chitosan and acrylic acid, so that heat-light sensitive hydrogel be prepared.Heat of the invention-light Lazer hydrogel is solution state, it can be achieved that flow injection, when temperature is increased to 30-40 DEG C, 1-5min can form gel at 4-25 DEG C；, in the case where dominant wavelength is the ultraviolet irradiation of 365nm, its gel strength, which can be obtained, after 3-8min is remarkably reinforced for it.
Description
Technical field
The invention belongs to field of biomedical materials, and in particular to one kind has heat-light sensitive hydrogel and its preparation
Method.
Background technique
The multicomponent system that hydrogel is made of high molecular three-dimensional network and water, is one kind generally existing in nature
The mass part (such as the muscle of human body, blood vessel, eyeball organ) of physical form, living organism is all being made of hydrogel.
Hydrogel can be generally divided into conventional hydrogels and environmental sensitive hydrogels, and environmental sensitive hydrogels have intelligence.
Environmental sensitive hydrogels fix in medicine controlled release carrier, organizational project, organized enzyme, in terms of all have
Applications well prospect, research also become current hot spot.Many thermo-responsive hydro gels have the gelling temp for being comparable to 37 DEG C, can be by it
As pharmaceutical carrier or for injecting, thus temperature-sensitive hydrogel also becomes the research direction of hydrogel emphasis.However, due to
The response speed of temperature-sensitive hydrogel is extended influence by temperature, most of not have syringeability, after needing to shape in vitro, then
In human body by operation transplantation, the pain on more bodies and burden economically so are brought to patient；In addition, existing
Temperature-sensitive hydrogel intensity it is inadequate, its degradation is accelerated into the dilution of body fluid after internal, above-mentioned reason makes temperature sensitive
Property hydrogel is very limited in use.
Summary of the invention
The technical problem to be solved by the invention is to provide a kind of heat-light sensitive hydrogel and preparation method thereof, water-settings
There is glue Lazer's property also to have ultraviolet light sensitive characteristic while retaining temperature-sensitive hydrogel flow injection characteristic and make hydrogel
It in vivo can rapid curing.
In order to solve the above-mentioned technical problem, the technical solution adopted by the present invention is that: a kind of system of heat-light sensitive hydrogel
Preparation Method, based on chitosan, high molecular polymer one end is grafted on chitosan hydrogel by condensation reaction, constitutes heat
Quick part；The olefinic double bonds and chitosan that the high molecular polymer other end is grafted and the condensation reaction with acryloyl chloride are logical
The condensation reaction crossed between acrylic acid and the olefinic double bonds being grafted collectively form photosensitive part, heat-light sensitive water is prepared
Gel；The high molecular polymer be one of polyethylene glycol, poloxamer, wherein the molecular weight of polyethylene glycol be 1000~
2000；Poloxamer molecules amount is 7000~13000.
Specifically, comprising the following steps:
(1) the olefinic double bonds modification of high molecular polymer
20~50g of high molecular polymer is taken to be dissolved in toluene of the 50~100mL by drying process, and addition 0.11~
0.100~0.398g acryloyl chloride is added dropwise, at 30~50 DEG C in 0.44g triethylamine under 500~700 revs/min of stirring condition
3~5h of isothermal reaction；It is cooling, removal triethylamine hydrochloride crystal is filtered, filtrate is handled using n-hexane, and precipitating, warp is precipitated
Filter olefinic double bonds modification high molecular polymer；
(2) carboxylated of high molecular polymer
In a kettle, sequentially add 0.05~0.20g of succinic anhydride, 0.061~0.244g of 4-dimethylaminopyridine and
After dissolution, 3.16~12.64g step is all added dropwise into reaction kettle for Isosorbide-5-Nitrae -15~50mL of dioxane, magnetic agitation to raw material
Suddenly the high molecular polymer that gained olefinic double bonds are modified in (1), reacts at room temperature 12~36h after being added dropwise；Pass through rotary evaporation
Instrument removes reaction dissolvent, and n-hexane is added into reaction residual and carries out precipitating to obtain mixed liquor, mixed liquor is filtered and used just
Hexane washs 3-4 times to get carboxylated high molecular polymer；
(3) heat-light sensitive hydrogel preparation
The carboxylated high molecular polymer being prepared in 1~6g step (2), 10~40mL are sequentially added to reaction kettle
The 2-morpholine ethane sulfonic acid solution of 0.1~0.5mol/L, stirring dissolve solid, and 1g chitosan is added, and matter is added dropwise to dissolving in stirring
The hydrochloric acid that specific concentration is 20% is measured, adjusts pH value of reaction system to 3-4；1- ethyl-(the 3- dimethylamino of 0.2~0.8g is added
Base propyl) carbodiimide hydrochloride and 0.1~0.4g n-hydroxysuccinimide, and after reaction 12~for 24 hours is stirred at room temperature, to
0.11~0.22g acrylic acid, the reaction was continued 12h are added in reaction system；By reaction solution move to molecular cut off be 5000~
In 14000 bag filter, is carried out dialysis treatment 5~6 days using distilled water, and changed water every 6~8 hours, it is cold to be put into refrigerator
It is lyophilized dry, obtains white fluffy solid product；Take the white fluffy solid 0.1~0.4g of product, be dissolved in 5~20g 4~
It can get Re-light sensitive hydrogel in 25 DEG C of distilled water.
The molecular weight of chitosan is 1.5 × 104~3 × 104, deacetylation degree of substitution >=85%.
Heat made from above-mentioned preparation method-light sensitive hydrogel.
The beneficial effects of the present invention are: heat of the invention-light sensitive hydrogel is solution state, it can be achieved that stream at 4-25 DEG C
Dynamic injection, when temperature is increased to 30-40 DEG C, 1-5min can form gel.In the ultraviolet light irradiation that dominant wavelength is 365nm
Under, its gel strength, which can be obtained, after 3-8min is remarkably reinforced.
Detailed description of the invention
Fig. 1 be using poloxamer as the heating of the series of heat of high molecular polymer-light sensitive hydrogel before, it is after heating and purple
(wherein, a is to heat up by the series of heat of high molecular polymer-light sensitive hydrogel of poloxamer to photo after outer light irradiation
Preceding photo；B is photo after being heated up using poloxamer as the series of heat of high molecular polymer-light sensitive hydrogel；C is to moor Lip river
Husky nurse be high molecular polymer series of heat-light sensitive hydrogel heating after and the photo after ultraviolet light).
Specific embodiment
Invention is further described in detail with reference to the accompanying drawings and detailed description:
Heat of the invention-light sensitive hydrogel preparation method design philosophy is that the temperature-sensitive part of the hydrogel is by shell
Glycan and the high molecular polymer being grafted thereon collectively form；Photosensitive part is by the alkene that is grafted on chitosan and high molecular polymer
Hydrocarbon double bond is constituted.In hydrogel preparation process, the acyl chlorides condensation reaction for first passing through high molecular polymer one end realizes that alkene is double
Key modification, then carries out carboxylated modification for its other end；Then in condensation reagent 1- ethyl-(3- dimethylaminopropyl) carbon
Diimmonium salt hydrochlorate and have activated carbonyl n-hydroxysuccinimide under conditions of, the high molecular polymer of modification is grafted to
On chitosan, it is further advanced by the grafted olefin double bond on chitosan of the condensation reaction between chitosan and acrylic acid, to make
Standby to obtain heat-light sensitive hydrogel, specific preparation method is main including the following steps:
(1) the olefinic double bonds modification of high molecular polymer
20~50g of high molecular polymer is taken to be dissolved in toluene of the 50~100mL by drying process, and addition 0.11~
0.44g triethylamine, then under 500~700 revs/min of stirring condition be added dropwise 0.100~0.398g acryloyl chloride, 30~50
3~5h of isothermal reaction at DEG C；It is cooling, removal triethylamine hydrochloride crystal is filtered, filtrate is handled using n-hexane, and it is heavy to be precipitated
Form sediment, filtered olefinic double bonds modification high molecular polymer；
(2) carboxylated of high molecular polymer
In three-necked flask, 0.05~0.20g of succinic anhydride, 0.061~0.244g of 4-dimethylaminopyridine are sequentially added
With Isosorbide-5-Nitrae -15~50mL of dioxane, after dissolution, 3.16~12.64g is all added dropwise into reaction flask for magnetic agitation to raw material
The high molecular polymer of gained olefinic double bonds modification, reacts at room temperature 12~36h in step (1) after being added dropwise；Then pass through rotation
Turn evaporimeter and remove reaction dissolvent, and n-hexane is added in backward reaction residual and carries out precipitating to obtain mixed liquor, mixed liquor carries out
It filters and washs 3-4 times with n-hexane to get carboxylated high molecular polymer；
(3) heat-light sensitive hydrogel preparation
Sequentially add the carboxylated high molecular polymer being prepared in 1~6g step (2) into reaction flask, 10~
The 2-morpholine ethane sulfonic acid solution of 40mL0.1~0.5mol/L, stirring dissolve solid, and 1g chitosan is then added, and stir to molten
The hydrochloric acid that concentration is 20% is added dropwise in solution, adjusts pH value of reaction system to 3-4；1- ethyl-(the 3- dimethyl of 0.2~0.8g is added
Aminopropyl) carbodiimide hydrochloride and 0.1~0.4gN- HOSu NHS, and after reaction 12~for 24 hours is stirred at room temperature, to
0.11~0.22g acrylic acid, the reaction was continued 12h are added in reaction system；It is 5000 that reaction solution, which is then moved to molecular cut off,
In~14000 bag filter, is carried out dialysis treatment 5~6 days, and changed water every 6~8 hours, be then put into cold using distilled water
The freeze-drying of jelly machine, obtains white fluffy solid product；The white fluffy solid 0.1~0.4g of product is taken, it is dissolved in 5~
It can get Re-light sensitive hydrogel in 4~25 DEG C of distilled water of 20g.
The high molecular polymer be one of polyethylene glycol, poloxamer, wherein the molecular weight of polyethylene glycol be
1000~2000；Poloxamer molecules amount is 7000~13000；The molecular weight of chitosan is 1.5 × 104~3 × 104, take off
Acetyl degree degree of substitution >=85%.
Heat of the invention-light sensitive water-setting, consists of: the polyphosphazene polymer that temperature-sensitive part is grafted by chitosan and thereon
Object is closed to collectively form；Photosensitive part is made of the olefinic double bonds being grafted on chitosan and high molecular polymer.
The present invention is directed to the temperature-sensitive hydrogel low problem of gel strength in application process, by being grafted on chitosan
High molecular polymer makes it have Thermo-sensitive, by chitosan and high molecular polymer grafted olefin double bond make it have light
Quick property, so that the hydrogel of preparation has heat-light Lazer property, which has certain fluidity, it can be achieved that injection；Together
When, hydrogel intensity can be enhanced using ultraviolet light after it is injected in vivo using its light sensitivity.
Embodiment 1
It is 12584 poloxamers for being as high molecular polymer using molecular weight, with carboxylated poloxamer and chitosan matter
For amount is than 2:1
It takes poloxamer 25g to be dissolved in toluene of the 60mL by drying process, and 0.22g triethylamine is added, then 600
Rev/min stirring condition under 0.199g acryloyl chloride is added dropwise, isothermal reaction 3h at 45 DEG C；Cooling, suction filtration goes three second of demineralizing acid
Amine crystal, filtrate are handled using n-hexane, and precipitating is precipitated, filtered olefinic double bonds modification poloxamer；At three mouthfuls
In flask, succinic anhydride 0.1g, 4-dimethylaminopyridine 0.122g and Isosorbide-5-Nitrae-dioxane 25mL are sequentially added, magnetic agitation is extremely
Raw material all after dissolution, the poloxamer of 3.16g olefinic double bonds modification is added dropwise into reaction flask, is reacted at room temperature after being added dropwise
12h；Reaction dissolvent then is removed by Rotary Evaporators, and backward reaction residual kind is added n-hexane and carries out precipitating to obtain mixing
Liquid, mixed liquor filter and wash 3-4 times with n-hexane to get carboxylated poloxamer；2g is sequentially added into reaction flask
Obtained carboxylated poloxamer, the 2-morpholine ethane sulfonic acid solution of 20mL0.1mol/L, stirring dissolve solid, 1g are then added
The hydrochloric acid that concentration is 20% is added dropwise to dissolving in chitosan, stirring, adjusts pH value of reaction system to 3-4；The 1- second of 0.4g is added
Base-(3- dimethylaminopropyl) carbodiimide hydrochloride and 0.2gN- HOSu NHS, and reaction 12h is stirred at room temperature
Afterwards, 0.11g acrylic acid, the reaction was continued 12h are added into reaction system；It is 12000 that reaction solution, which is then moved to molecular cut off,
Bag filter in, carried out dialysis treatment 5 days using distilled water, and changed water every 6 hours, be then put into refrigerator freeze-drying,
Obtain white fluffy solid product；White fluffy solid product 0.1g is taken, is dissolved in obtain in 4 DEG C of distilled water of 5g
Heat-light sensitive hydrogel, is denoted as hydrogel A.
Embodiment 2
The poloxamer for being 12584 using molecular weight is high molecular polymer, the quality of carboxylated poloxamer and chitosan
For 3:1.
Carboxylated poloxamer dosage in embodiment 1 is adjusted to 3g, the dosage of condensation reagent increases original half,
His raw material dosage is constant, and reaction condition is constant, can get Re-light sensitive hydrogel, be denoted as hydrogel B.
Embodiment 3
The poloxamer for being 12584 using molecular weight is high molecular polymer, the quality of carboxylated poloxamer and chitosan
For 4:1.
Carboxylated poloxamer dosage in embodiment 1 is adjusted to 4g, the dosage of condensation reagent increases original 1 times,
His raw material dosage is constant, and reaction condition is constant, can get Re-light sensitive hydrogel, be denoted as hydrogel C.
By three kinds described in embodiment 1,2 and 3, hydrogel A, B and C difference are heat-treated and ultraviolet light is handled,
Heat-light sensitive hydrogel thermal sensitivity and light sensitivity are had studied by hydrogel intensity, as a result as shown in Figure 1.From Fig. 1 a
As can be seen that hydrogel is solution state before heating up, mobility is preferable；As shown in Figure 1 b, by different series prepared by difference
In the water-bath that 37 DEG C of hydrogel solution, after 2min, hydrogel A, B and C start to be changed into gel state, but intensity is little, still has
There is certain mobility；By through heating heating after serial hydrogel A, B and C photoinitiator I2959 effect and dominant wavelength
Photo after irradiating 3min under the ultraviolet lamp of 365nm is as illustrated in figure 1 c, it can be clearly seen that, hydrogel is strong after ultraviolet light
Degree is remarkably reinforced, and can be hung for a long time in the reagent bottle of handstand without falling from bottom of bottle.Above-mentioned picture comparative illustration, this
Prepared heat-light sensitive the hydrogel of application has good thermal sensitivity and light sensitivity.
Embodiment 4
The polyethylene glycol for being 2000 using molecular weight as high molecular polymer, the quality of carboxyl polyethylene glycol and chitosan
For 4:1.
Taking polyethylene glycol 25g is dissolved in toluene of the 60mL by drying process, and 0.22g triethylamine is added, then fast
0.199g acryloyl chloride, isothermal reaction 3h at 45 DEG C are added dropwise under fast stirring condition；It is cooling, removal triethylamine hydrochloride crystal is filtered,
Filtrate is handled using n-hexane, and precipitating is precipitated, filtered olefinic double bonds modification polyethylene glycol；In three-necked flask,
Succinic anhydride 0.1g, 4-dimethylaminopyridine 0.122g and Isosorbide-5-Nitrae-dioxane 25mL are sequentially added, magnetic agitation is complete to raw material
After portion's dissolution, it is added dropwise to the polyethylene glycol of 3.16g olefinic double bonds modification into reaction flask, reacts at room temperature 12h after being added dropwise；And
Reaction dissolvent is removed by Rotary Evaporators afterwards, and backward reaction residual kind is added n-hexane and carries out precipitating to obtain mixed liquor, mixes
Liquid is closed filter and wash 3-4 times with n-hexane to get carboxyl polyethylene glycol；Sequentially add what 4g was obtained into reaction flask
Carboxyl polyethylene glycol, the 2-morpholine ethane sulfonic acid solution of 40g 0.1mol/L, stirring dissolve solid, and it is poly- that 1g shell is then added
The hydrochloric acid that concentration is 20% is added dropwise to dissolving in sugar, stirring, adjusts pH value of reaction system to 3-4；1- ethyl-(3- of 0.8g is added
Dimethylaminopropyl) carbodiimide hydrochloride and 0.4g n-hydroxysuccinimide, and after reaction 12h is stirred at room temperature, to anti-
Addition 0.11g acrylic acid is answered in system, the reaction was continued 12h；Reaction solution is then moved into the bag filter that molecular cut off is 5000
In, it is carried out dialysis treatment 5~6 days using distilled water, and changed water every 6~8 hours, is then put into refrigerator freeze-drying, obtains
White fluffy solid product；White fluffy solid product 0.1g is taken, being dissolved in can get Re-in 4 DEG C of distilled water of 5g
Light sensitive hydrogel.
Above-mentioned hydrogel is distinguished into the processing of heat-treated and ultraviolet light, heat-light is had studied by hydrogel intensity
The thermal sensitivity and light sensitivity of sensitive hydrogel, hydrogel is solution state before heating up, and mobility is preferable；By prepared water-setting
In the water-bath that 35 DEG C of sol solution, after 2min, hydrogel starts to be changed into gel state, but intensity is little, still has certain stream
Dynamic property；Hydrogel serial after heating heating is irradiated under the effect of photoinitiator I2959 and the ultraviolet lamp of dominant wavelength 365nm
After 3min, the intensity of hydrogel is remarkably reinforced after ultraviolet light, can be hung for a long time in the reagent bottle of handstand without
It is fallen from bottom of bottle.Heat prepared by the application-light sensitive hydrogel has good thermal sensitivity and light sensitivity.
Embodiment 5
The polyethylene glycol for being 2000 using molecular weight is high molecular polymer, the mass ratio of carboxyl polyethylene glycol and chitosan
For 6:1.
Carboxyl polyethylene glycol dosage in embodiment 4 is adjusted to 6g, the dosage of condensation reagent increases original half,
His raw material dosage is constant, and reaction condition is constant, and the heat-light that can obtain the mass ratio 6:1 of carboxyl polyethylene glycol and chitosan is double
Sensitive aquagel.
Above-mentioned hydrogel is distinguished into the processing of heat-treated and ultraviolet light, heat-light is had studied by hydrogel intensity
The thermal sensitivity and light sensitivity of sensitive hydrogel, hydrogel is solution state before heating up, and mobility is preferable；By prepared water-setting
In the water-bath that 37 DEG C of sol solution, after 3min, hydrogel starts to be changed into gel state, but intensity is little, still has certain stream
Dynamic property；Hydrogel serial after heating heating is irradiated under the effect of photoinitiator I2959 and the ultraviolet lamp of dominant wavelength 365nm
After 5min, the intensity of hydrogel is remarkably reinforced after ultraviolet light, can be hung for a long time in the reagent bottle of handstand without
It is fallen from bottom of bottle.Heat prepared by the application-light sensitive hydrogel has good thermal sensitivity and light sensitivity.
In conclusion the contents of the present invention are not limited in the above embodiments, the knowledgeable people in same area can
Can propose other embodiments easily within technological guidance's thought of the invention, but this embodiment is included in this hair
Within the scope of bright.
Claims (4)
1. a kind of heat-light sensitive hydrogel preparation method, which is characterized in that hydrogel is based on chitosan, macromolecule
Polymer one end is grafted on chitosan by condensation reaction, constitutes temperature-sensitive part；The high molecular polymer other end is by with third
The condensation reaction of alkene acyl chlorides and alkene that the olefinic double bonds and chitosan being grafted are grafted by the condensation reaction between acrylic acid
Hydrocarbon double bond collectively forms photosensitive part, and heat-light sensitive hydrogel is prepared；The high molecular polymer be polyethylene glycol,
One of poloxamer, wherein the molecular weight of polyethylene glycol is 1000~2000；Poloxamer molecules amount be 7000~
13000。
2. heat according to claim 1-light sensitive hydrogel preparation method, which comprises the following steps:
(1) the olefinic double bonds modification of high molecular polymer
It takes 20~50g of high molecular polymer to be dissolved in toluene of the 50~100mL by drying process, and 0.11~0.44g is added
0.100~0.398g acryloyl chloride, constant temperature at 30~50 DEG C is added dropwise in triethylamine under 500~700 revs/min of stirring condition
React 3~5h；It is cooling, removal triethylamine hydrochloride crystal is filtered, filtrate is handled using n-hexane, precipitating is precipitated, through filtering
Obtain the high molecular polymer of olefinic double bonds modification；
(2) carboxylated of high molecular polymer
In a kettle, 0.05~0.20g of succinic anhydride, 0.061~0.244g of 4-dimethylaminopyridine and Isosorbide-5-Nitrae-are sequentially added
After dissolution, 3.16~12.64g step (1) is all added dropwise into reaction kettle for 15~50mL of dioxane, magnetic agitation to raw material
The high molecular polymer of middle gained olefinic double bonds modification, reacts at room temperature 12~36h after being added dropwise；It is removed by Rotary Evaporators
N-hexane is added into reaction residual and carries out precipitating to obtain mixed liquor for reaction dissolvent, and mixed liquor filter and washed with n-hexane
3-4 times is washed to get carboxylated high molecular polymer；
(3) heat-light sensitive hydrogel preparation
Sequentially add the carboxylated high molecular polymer being prepared in 1~6g step (2) to reaction kettle, 10~40mL 0.1~
The 2-morpholine ethane sulfonic acid solution of 0.5mol/L, stirring dissolve solid, and 1g chitosan is added, and mass ratio is added dropwise to dissolving in stirring
The hydrochloric acid that concentration is 20% adjusts pH value of reaction system to 3-4；1- ethyl-(the 3- dimethylamino third of 0.2~0.8g is added
Base) carbodiimide hydrochloride and 0.1~0.4g n-hydroxysuccinimide, and after reaction 12~for 24 hours is stirred at room temperature, Xiang Fanying
0.11~0.22g acrylic acid, the reaction was continued 12h are added in system；It is 5000~14000 that reaction solution, which is moved to molecular cut off,
It in bag filter, is carried out dialysis treatment 5~6 days using distilled water, and changed water every 6~8 hours, is put into refrigerator freeze-drying,
Obtain white fluffy solid product；The white fluffy solid 0.1~0.4g of product is taken, 4~25 DEG C of steamings of 5~20g are dissolved in
It can get Re-light sensitive hydrogel in distilled water.
3. heat according to claim 1 or 2-light sensitive hydrogel preparation method, which is characterized in that the chitosan
Molecular weight is 1.5 × 104~3 × 104, deacetylation degree of substitution >=85%.
4. heat made from preparation method as described in any one of claims 1-3-light sensitive hydrogel.
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| CN101664563A (en) * | 2009-09-21 | 2010-03-10 | 杭州国纳科技有限公司 | Preparation method of anti-bacterial hydrogel dressing |
| CN102718991A (en) * | 2012-04-05 | 2012-10-10 | 天津大学 | High strength injectable hydrogel and preparation method thereof |
| CN103301788A (en) * | 2012-03-09 | 2013-09-18 | 中国科学院大连化学物理研究所 | Alginate-chitosan microcapsule modified via PEG grafting and preparation and application thereof |
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| CN101664563A (en) * | 2009-09-21 | 2010-03-10 | 杭州国纳科技有限公司 | Preparation method of anti-bacterial hydrogel dressing |
| CN103301788A (en) * | 2012-03-09 | 2013-09-18 | 中国科学院大连化学物理研究所 | Alginate-chitosan microcapsule modified via PEG grafting and preparation and application thereof |
| CN102718991A (en) * | 2012-04-05 | 2012-10-10 | 天津大学 | High strength injectable hydrogel and preparation method thereof |
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