CN108948363A - A method of preparing the multiple response hydrogel of ordered structure - Google Patents
A method of preparing the multiple response hydrogel of ordered structure Download PDFInfo
- Publication number
- CN108948363A CN108948363A CN201810567510.5A CN201810567510A CN108948363A CN 108948363 A CN108948363 A CN 108948363A CN 201810567510 A CN201810567510 A CN 201810567510A CN 108948363 A CN108948363 A CN 108948363A
- Authority
- CN
- China
- Prior art keywords
- reaction
- hydrogel
- dissolved
- polyethylene glycol
- multiple response
- 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.)
- Pending
Links
Classifications
-
- 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
- C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
- C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
- C08G81/025—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyether sequences
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention belongs to technical field of polymer chemistry more particularly to a kind of methods for the multiple response hydrogel for preparing ordered structure.Firstly, having four arm polyacrylic acid (PAA) of different molecular weight using atom transfer radical polymerization preparation；Secondly, having linear polyethylene glycol (PEG) cross-linking reaction of alkynyl functionality with end respectively using copper catalysis nitrine-alkynes cycloaddition " click chemistry ", the PAA-PEG multiple response hydrogel of different crosslink densities is prepared.Hydrogel prepared by the present invention can be expected to be used widely in fields such as medicament slow release, bio-sensing, responsive materials with pH changes, calcium ion concentration changes its mechanical property, electric conductivity changes.
Description
Technical field
The present invention relates to biomedical materials field more particularly to a kind of multiple response hydrogels for preparing ordered structure
Method.
Background technique
In the technology of preparing of modern man-made organ, intellectual material controls Ions Absorption and a variety of vitamins, medicine in human body
It is had a decisive role in the absorption of object, protein and minerals.These intellectual materials can be used as biological tissue transplanting or
Person substitutes the organ of necrosis.As important intellectual material, multiple response hydrogel is formed and is had by hydrophilic polymer chains
Three-dimensional netted cross-linked structure can be swollen in water.Multiple response hydrogel also can be in vivo to the variation of external condition
Occur, such as pH, temperature, solvent polarity, the variation of salt content and electric field.The swelling ratio variation of multiple response hydrogel is pierced in nerve
Swash, plays a significant role in contraction of muscle and cell movement.
Although multiple response hydrogel may be widely used in organizational project in the future as biomaterial, mechanical
Intensity is very important.Its middle crosslink density is the most important factor for influencing multiple response hydrogel mechanical performance, because it is handed over
The control of double bond conversion rate when connection point is not only copolymerized, but also by the metal of bivalent metal ion and polymer pendant groups functional group
The influence of coordinate bond.Traditional multiple response hydrogel is to be prepared by the crosslinking points of polyfunctionality by radical copolymerization
, its internal cross-linked structure of the hydrogel prepared by this method is irregular, generates a large amount of stress defects, leads to hydrogel power
It is not high to learn intensity, is easily broken.Multiple response hydrogel with ordered structure is with regular crosslink density and uniformly
Crosslinking points distribution, to reduce the stress defect of hydrogel, therefore has higher elasticity modulus, can apply to biological group in future
Knit repair materials, such as artificial cartilage's tissue.
Summary of the invention
It is an object of the invention to overcome in the prior art multiple response hydrogel mechanical strength it is not high, be easily broken
Problem provides a kind of method of multiple response hydrogel for preparing ordered structure.
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
(1) tetra functional ATRP initiator is prepared；
(2) there are the four arm polyacrylic acid tert-butyl esters of different molecular weight using atom transfer radical polymerization preparation；
(3) the polyacrylic acid tert-butyl ester end Azide is carried out containing bromo functional groups to be modified；
(4) synthesis end has the multi-arm polyethylene glycol of alkynyl functionality；
(5) by end contain nitrine functional group the polyacrylic acid tert-butyl ester and end with alkynyl functionality using nitrine-
Alkynes cycloaddition " click chemistry " cross-linking reaction prepares polyethylene glycol tert-butyl acrylate hydrogel.
(6) by the polyacrylic acid tert-butyl ester obtained-polyethylene glycol hydrogel trifluoroacetic acid acidification, polypropylene is made
Acid-polyethylene glycol multiple response hydrogel；
Preferentially, the used reaction dissolvent described in step (1) is methylene chloride, and reaction temperature is 25 DEG C, reaction
Time 48 hours, pentaerythrite reacted molar ratio 1:4 (reaction density 50%) with bromo isobutyl acylbromide, after reaction,
The salt that mixed liquor filtering removal generates, is then washed three times with 5% NaHCO3 solution, organic phase anhydrous magnesium sulfate is dried
Night removes methylene chloride with Rotary Evaporators, finally, crude product recrystallizes three times in ethanol, normal-temperature vacuum is dried overnight.
Preferentially, used reaction dissolvent described in step (2) is toluene, tert-butyl acrylate: tetra functional ATRP
Initiator: protobromide ketone: N, N, N', N, ' N "-five methyl diethylentriamine molar ratio be 400-200:1:1:1, in nitrogen
It under protection, reacts, reacts 12-48 hours in 60 DEG C of oil bath.After reaction, reaction solution is diluted in methylene chloride, is used
200 mesh neutral aluminas remove copper catalyst.After polymer is concentrated with Rotary Evaporators, it is dissolved in tetrahydrofuran, and in methanol/water
(volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and by polymer filtration, room temperature in vacuo is dried overnight.
Preferentially, the four arm polyacrylic acid tert-butyl esters are dissolved in (reaction density in n,N-Dimethylformamide solvent in step (3)
For 0.01mol/L), it is 30 DEG C that sodium azide (reaction density 0.08mol/L) reaction temperature, which is added, the reaction time 24 hours,
Band after reaction, by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL dichloromethane
In alkane, remaining sodium azide is removed with neutral alumina.Finally, the methylene chloride in polymer solution is gone with Rotary Evaporators
It removes, is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, by polymer in alcohol/water
Filtering, it is 24 hours dry.
Preferentially, in step (4) under nitrogen protection, multi-arm polyethylene glycol is dissolved in tetrahydrofuran that (reaction density is
0.04mol/L), propargyl bromide (reaction density 0.1-0.32mol/L), sodium hydride (reaction density 0.6mol/L) are added to
In polymer solution, react 24 hours at room temperature.After reaction, polymer solution is removed with neutral alumina pillar and is hydrogenated
Sodium and by-product salt.Finally product is obtained with Rotary Evaporators removal tetrahydrofuran.
Preferentially, the molecular weight polyethylene glycol described in step (4) is 4000-15000；The multi-arm and ethylene glycol
For linear, three arms, four arm polyethylene glycol.
Preferentially, described in step (5) under nitrogen protection, multi-arm polyethylene glycol and band with alkynyl functionality
Have the four arm polyacrylic acid tert-butyl esters of nitrine functional group, cuprous bromide and N, N, N', N, ' N "-five methyl diethylentriamine with
Molar ratio (0.5-2:1:4:4) is dissolved in Isosorbide-5-Nitrae-dioxane (reaction density 20%) and is dissolved in the reaction tube being equipped with, in room temperature
It is lower to stand 24 hours, it is washed with distilled water, is finally dried at 60 DEG C to constant weight, polyethylene glycol tert-butyl acrylate is made
Hydrogel.
Preferentially, it is to be sufficiently swollen polyethylene glycol tert-butyl acrylate hydrogel two described in step (6)
In chloromethanes, trifluoroacetic acid is slowly added dropwise, reacts 24 hours at room temperature.After solvent is removed, hydrogel is immersed in deionization
In water, the trifluoroacetic acid in hydrogel is removed, deionized water washing by soaking is dried at 60 DEG C to constant weight.
Beneficial effects of the present invention: (1) present invention is a kind of using atom transfer radical polymerization and " click chemistry " phase
In conjunction with preparation multiple response hydrogel；(2) present invention, which can solve, exists in the prior art multiple response hydrogel structure
Irregular easy breakage limits application of the hydrogel in bio-medical material.
Detailed description of the invention
Fig. 1 is the multiple response hydrogel schematic diagram with ordered structure
Specific embodiment
The present invention is further illustrated combined with specific embodiments below.
Embodiment 1
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 200:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 12 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 24 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. four arm polyethylene glycol (molecular weight 4000) are dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.16mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the four arm polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' N "-five methyl diethylentriamine with molar ratio (1:1:4:4) be dissolved in 1,4- dioxane (reaction
Concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, and is finally done at 60 DEG C
It is dry to constant weight, polyethylene glycol tert-butyl acrylate hydrogel is made.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Embodiment 2
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 300:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 18 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the three arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 24 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. three arm polyethylene glycol (molecular weight 6000) are dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.1mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the three arm polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' that N "-five methyl diethylentriamine with molar ratio (1.3:1:4:4) is dissolved in 1,4- dioxane is (anti-
Answering concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, finally at 60 DEG C
Polyethylene glycol tert-butyl acrylate hydrogel is made to constant weight in drying.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Embodiment 3
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 300:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 24 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 24 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. four arm polyethylene glycol (molecular weight 10000) are dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.16mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the four arm polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' that N "-five methyl diethylentriamine with molar ratio (0.5:1:4:4) is dissolved in 1,4- dioxane is (anti-
Answering concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, finally at 60 DEG C
Polyethylene glycol tert-butyl acrylate hydrogel is made to constant weight in drying.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Embodiment 4
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 200:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 24 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 24 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. eight arm polyethylene glycol (molecular weight 15000) are dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.32mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the eight arm polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' that N "-five methyl diethylentriamine with molar ratio (0.5:1:4:4) is dissolved in 1,4- dioxane is (anti-
Answering concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, finally at 60 DEG C
Polyethylene glycol tert-butyl acrylate hydrogel is made to constant weight in drying.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Embodiment 5
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 400:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 24 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 12 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. linear polyethylene glycol (molecular weight 6000) is dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.2mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the linear polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' N "-five methyl diethylentriamine with molar ratio (2:1:4:4) be dissolved in 1,4- dioxane (reaction
Concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, and is finally done at 60 DEG C
It is dry to constant weight, polyethylene glycol tert-butyl acrylate hydrogel is made.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Embodiment 6
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 400:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 24 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 24 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. eight arm polyethylene glycol (molecular weight 10000) are dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.32mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the eight arm polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' that N "-five methyl diethylentriamine with molar ratio (0.5:1:4:4) is dissolved in 1,4- dioxane is (anti-
Answering concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, finally at 60 DEG C
Polyethylene glycol tert-butyl acrylate hydrogel is made to constant weight in drying.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Embodiment 7
A method of preparing the multiple response hydrogel of ordered structure, comprising the following steps:
1. pentaerythrite is dissolved in methylene chloride (reaction density 50%) with the molar ratio 1:4 that reacts of bromo isobutyl acylbromide,
Reaction temperature is 25 DEG C, and the reaction time 48 hours, after reaction, mixed liquor filtering removed the salt generated, then with 5%
NaHCO3 solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes methylene chloride with Rotary Evaporators, finally,
Crude product recrystallizes three times in ethanol, and normal-temperature vacuum is dried overnight；
2. tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N, N', N, ' the sub- second of N "-pentamethyl two
The molar ratio of base triamine is that 300:1:1:1 is dissolved in toluene, under nitrogen protection, reacts, reacts 12 hours in 60 DEG C of oil bath.Instead
After answering, reaction solution is diluted in methylene chloride, removes copper catalyst with 200 mesh neutral aluminas.Polymer rotation
After evaporimeter concentration, it is dissolved in tetrahydrofuran, and (volume ratio: precipitating in 1/1), removal is reaction in triplicate in methanol/water
Monomer, by polymer filtration, room temperature in vacuo is dried overnight.
3. the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L),
Be added sodium azide (reaction density 0.08mol/L) reaction temperature be 30 DEG C, the reaction time 12 hours, band after reaction,
It by n,N-Dimethylformamide solvent by vacuum distillation removal, and dissolves a polymer in 100mL methylene chloride, uses neutral oxygen
Change aluminium and removes remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydro furan
It mutters, and (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, and polymer filtration, dry 24 is small in alcohol/water
When.
4. linear polyethylene glycol (molecular weight 10000) is dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl
Bromine (reaction density 0.2mol/L), sodium hydride (reaction density 0.6mol/L) are added in polymer solution, at room temperature
Reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.Finally use
Rotary Evaporators removal tetrahydrofuran obtains product.
5. the linear polyethylene glycol with alkynyl functionality and the four arm polyacrylic acid tert-butyl esters with nitrine functional group, bromine
Change cuprous and N, N, N', N, ' N "-five methyl diethylentriamine with molar ratio (2:1:4:4) be dissolved in 1,4- dioxane (reaction
Concentration is 20%) to be dissolved in the reaction tube being equipped with, and stands 24 hours at normal temperature, is washed with distilled water, and is finally done at 60 DEG C
It is dry to constant weight, polyethylene glycol tert-butyl acrylate hydrogel is made.
6. polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride, trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoro second in hydrogel
Acid, deionized water washing by soaking are dried at 60 DEG C to constant weight.
Claims (8)
1. a kind of method for the multiple response hydrogel for preparing ordered structure, feature the following steps are included:
(1) tetra functional ATRP initiator is prepared；
(2) there are the four arm polyacrylic acid tert-butyl esters of different molecular weight using atom transfer radical polymerization preparation；
(3) the polyacrylic acid tert-butyl ester end Azide is carried out containing bromo functional groups to be modified；
(4) synthesis end has the multi-arm polyethylene glycol of alkynyl functionality；
(5) by end contain nitrine functional group the polyacrylic acid tert-butyl ester and end with alkynyl functionality using nitrine-alkynes ring
Addition " click chemistry " cross-linking reaction prepares polyethylene glycol tert-butyl acrylate hydrogel.
(6) by the polyacrylic acid tert-butyl ester obtained-polyethylene glycol hydrogel trifluoroacetic acid acidification, polyacrylic acid-is made
Polyethylene glycol multiple response hydrogel.
2. according to claim 1, a method of preparing the multiple response hydrogel of ordered structure, it is characterised in that step
Suddenly reaction dissolvent used in (1) is methylene chloride, and reaction temperature is 25 DEG C, the reaction time 48 hours, pentaerythrite and bromine
For the reaction molar ratio 1/4 (reaction density 50%) of isobutyl acylbromide, after reaction, the salt that mixed liquor filtering removal generates,
Then with 5% NaHCO3Solution washs three times, and organic phase is dried overnight with anhydrous magnesium sulfate, removes dichloro with Rotary Evaporators
Methane, finally, crude product recrystallizes three times in ethanol, normal-temperature vacuum is dry.
3. according to claim 1, a method of preparing the multiple response hydrogel of ordered structure, it is characterised in that:
Reaction dissolvent used in step (2) be toluene, tert-butyl acrylate: tetra functional ATRP initiator: protobromide ketone: N, N,
N', N, ' the molar ratio of N "-five methyl diethylentriamine is 400-200:1:1:1, under nitrogen protection, in 60 DEG C of oil bath
Reaction is reacted 12-48 hours.After reaction, reaction solution is diluted in methylene chloride, is removed with 200 mesh neutral aluminas
Copper catalyst.After polymer is concentrated with Rotary Evaporators, be dissolved in tetrahydrofuran, and methanol/water (volume ratio: precipitating in 1/1),
Removal is the monomer of reaction in triplicate, and by polymer filtration, room temperature in vacuo is dry.
4. according to claim 1, a method of preparing the multiple response hydrogel of ordered structure, it is characterised in that step
Suddenly the four arm polyacrylic acid tert-butyl esters are dissolved in n,N-Dimethylformamide solvent (reaction density 0.01mol/L) by (3), are added
Sodium azide (reaction density 0.08mol/L) reaction temperature is 30 DEG C, the reaction time 24 hours, band after reaction, by N,
Dinethylformamide solvent is dissolved a polymer in 100mL methylene chloride by vacuum distillation removal, uses neutral alumina
Remove remaining sodium azide.Finally, the methylene chloride in polymer solution is removed with Rotary Evaporators, it is dissolved in tetrahydrofuran,
And (volume ratio: precipitating in 1/1), removal is the monomer of reaction in triplicate, dry by polymer filtration in alcohol/water.
5. according to claim 1, a method of preparing the multiple response hydrogel of ordered structure, it is characterised in that step
Suddenly (4), under nitrogen protection, multi-arm polyethylene glycol is dissolved in tetrahydrofuran (reaction density 0.04mol/L), propargyl bromide
(reaction density 0.1-0.32mol/L), sodium hydride (reaction density 0.6mol/L) is added in polymer solution, in room temperature
Lower reaction 24 hours.After reaction, polymer solution removes sodium hydride and by-product salt with neutral alumina pillar.
6. according to claim 5, a method of preparing the multiple response hydrogel of ordered structure, described in poly- second
Glycol molecular weight is 4000-15000；The multi-arm and ethylene glycol is linear, three arms, four arm polyethylene glycol.
7. according to claim 1, a method of preparing the multiple response hydrogel of ordered structure, it is characterised in that step
Suddenly in (5) under nitrogen protection, the multi-arm polyethylene glycol with alkynyl functionality and the four arm polypropylene with nitrine functional group
Tert-butyl acrylate, cuprous bromide and N, N, N', N, ' N "-five methyl diethylentriamine with molar ratio (0.5-2:1:4:4) is dissolved in 1,
4- dioxane (reaction density 20%) is dissolved in the reaction tube being equipped with, and is stood 24 hours at normal temperature, is washed with distilled water,
It is dry, polyethylene glycol tert-butyl acrylate hydrogel is made.
8. according to claim 1, a method of preparing the multiple response hydrogel of ordered structure, it is characterised in that step
Suddenly polyethylene glycol tert-butyl acrylate hydrogel is sufficiently swollen in methylene chloride by (6), and trifluoroacetic acid is slowly added dropwise,
It reacts 24 hours at room temperature.After solvent is removed, hydrogel impregnates in deionized water, removes the trifluoroacetic acid in hydrogel,
Deionized water washing by soaking, it is dry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810567510.5A CN108948363A (en) | 2018-06-05 | 2018-06-05 | A method of preparing the multiple response hydrogel of ordered structure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810567510.5A CN108948363A (en) | 2018-06-05 | 2018-06-05 | A method of preparing the multiple response hydrogel of ordered structure |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108948363A true CN108948363A (en) | 2018-12-07 |
Family
ID=64493624
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810567510.5A Pending CN108948363A (en) | 2018-06-05 | 2018-06-05 | A method of preparing the multiple response hydrogel of ordered structure |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108948363A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103289099A (en) * | 2013-06-07 | 2013-09-11 | 中科院广州化学有限公司 | Amphiphilic acid-sensitive ternary molecular brush polymer constructed acid-sensitive nanocapsule |
| CN103665387A (en) * | 2013-12-09 | 2014-03-26 | 东南大学 | Method for preparing accurate polymer network |
| CN105646891A (en) * | 2016-03-14 | 2016-06-08 | 中科院广州化学有限公司南雄材料生产基地 | Amphiphilic ternary molecular brush polymer and vermicular mono-molecular micelle constructed by same |
-
2018
- 2018-06-05 CN CN201810567510.5A patent/CN108948363A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103289099A (en) * | 2013-06-07 | 2013-09-11 | 中科院广州化学有限公司 | Amphiphilic acid-sensitive ternary molecular brush polymer constructed acid-sensitive nanocapsule |
| CN103665387A (en) * | 2013-12-09 | 2014-03-26 | 东南大学 | Method for preparing accurate polymer network |
| CN105646891A (en) * | 2016-03-14 | 2016-06-08 | 中科院广州化学有限公司南雄材料生产基地 | Amphiphilic ternary molecular brush polymer and vermicular mono-molecular micelle constructed by same |
Non-Patent Citations (2)
| Title |
|---|
| ZHOU C. ET AL.: "Synthesis and characterization of well-defined PAA-PEG multi-responsive hydrogels by ATRP and click chemistry", 《RSC ADVANCES》 * |
| 周超: "基于大分子精确合成设计制备具有规整结构的功能聚合物网络的研究", 《中国博士学位论文全文数据库工程科技I辑》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106633111B (en) | A kind of preparation method of high strength poly vinyl alcohol base double-network hydrogel | |
| CN106432759B (en) | Preparation method of high-strength polyvinyl alcohol hydrogel | |
| CN105175755B (en) | High stretching dual network physical cross-linking hydrogel of a kind of high intensity and preparation method thereof | |
| CN109485877B (en) | High-temperature and low-temperature resistant high-toughness organic hydrogel and preparation method thereof | |
| CN107903406A (en) | A kind of preparation method of three network aqueous gel of high intensity selfreparing | |
| CN105199281B (en) | It is a kind of to possess superelevation mechanical strength and the hydrogel of chemical stability | |
| CN110551296B (en) | Pectin-based double-physical crosslinked hydrogel and preparation method and application thereof | |
| CN104877087B (en) | A kind of temperature-sensitive hydrogel with bioactivity and preparation method thereof | |
| CN102504229B (en) | Synthesis method of in-situ-enhanced thermosensitive polymer and degradable in-situ-enhanced injectable thermosensitive hydrogel | |
| CN106397646A (en) | High-strength super-molecular hydrogel, preparation method therefor and application of high-strength super-molecular hydrogel | |
| CN109535449A (en) | A kind of preparation method of the high tough chitosan-based hydrogel of high-low temperature resistant | |
| CN112876613B (en) | Preparation method of high-strength light cellulose-based bionic protection material | |
| CN109971042A (en) | A kind of high intensity dual network amphoteric ion hydrogel and preparation method thereof | |
| CN110563968B (en) | Preparation method of high-strength high-tensile ionic conductive hydrogel | |
| CN101748511A (en) | Preparation method of temperature response macromolecular gelatinous fibre material and products thereof | |
| CN109503768A (en) | A kind of preparation method of high tough sticky weather-resistance polyethylene alcohol radical double-network hydrogel | |
| CN110627976B (en) | Tussah silk fibroin hydrogel and preparation method and application thereof | |
| CN108864443A (en) | A kind of electroactive hydrogel of bio-medical and preparation method thereof | |
| CN111253535A (en) | Preparation method of novel photoinduced self-repairing nano composite hydrogel | |
| CN108948363A (en) | A method of preparing the multiple response hydrogel of ordered structure | |
| US20060235114A1 (en) | Temperature-responsive hydrogel | |
| CN111760073B (en) | Tectorial membrane implantation medical instrument and preparation method thereof | |
| CN107936267A (en) | A kind of preparation method and expansion of stem cells and collection method of two ionic starch base expansion of stem cells hydrogel | |
| CN115252885B (en) | Hydrogel dressing crosslinked by multiple hydrogen bonds and preparation and application thereof | |
| CN112111162A (en) | Rapidly-curable double-network hydrogel and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181207 |