CN105860104A - Temperature-sensitive self-repairing hydrogel and preparation method and application thereof - Google Patents
Temperature-sensitive self-repairing hydrogel and preparation method and application thereof Download PDFInfo
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- C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2333/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
- C08J2333/06—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing only carbon, hydrogen, and oxygen, the oxygen atom being present only as part of the carboxyl radical
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Abstract
The invention provides temperature-sensitive self-repairing hydrogel and a preparation method and application thereof. The temperature-sensitive self-repairing hydrogel is formed by means of reaction of (N-isopropylacrylamide)-acrylhydrazine copolymer and a compound containing multiple carbonyl groups in an aqueous solution under the action of a catalyst, wherein the catalyst is a weak acid catalyst or an aniline catalyst, the (N-isopropylacrylamide)-acrylhydrazine copolymer comprises repetitive units A and repetitive units B, and the repetitive units A account for 20%-95% of the total mass of the copolymer. The hydrogel has temperature sensitivity and self repairability simultaneously and is good in stability, drug sustained release at different temperatures can be achieved, the hydrogel can achieve self repairing when subjected to damage, the self-repairing process is similar to that of a life body, and the hydrogel has very wide application prospects in biological medicine related fields such as artificial organs and biological indication and drug controlled release. Please see the formula in the description.
Description
Technical field
The present invention relates to a kind of hydrogel and preparation method and application, especially relate to a kind of Thermo-sensitive selfreparing hydrogel and
Preparation method and application.
Background technology
Hydrogel is the gel with water as disperse medium, is a kind of macromolecule network system, and character is soft, it is possible to keep certain
Shape, can absorb substantial amounts of water.Hydrogel be introduce in the water soluble polymer have cross-linked network a part of hydrophobic
Group and hydrophilic residue, hydrophilic residue and water molecules, be connected to netted inside by hydrone, and hydrophobic residue water-swellable
Cross linked polymer.
Temperature-sensitive hydrogel be a kind of can with the change of ambient temperature occur can the intelligent aqueous gel capable of reverse response, poly-(N-isopropyl third
Acrylamide) (PNIPAM) hydrogel is a kind of widely used temperature-sensitive hydrogel, this hydrogel occurs rapidly at about 32 DEG C
Reversible volumetric phase in version.When ambient temperature is less than 32 DEG C, hydrogel in solvent swelling state, and exceedes when ambient temperature in water
After 32 DEG C, hydrogel shrinks rapidly, presents hydrophobic property.Due to its distinctive temperature response performance, and good biofacies
Capacitive, this hydrogel is widely used in the fields such as biomedical material.
The biocompatibility temperature-sensitive hydrogel based on PNIPAM of report is based on stable chemical crosslinking mostly at present, can be used for medicine
The fields such as thing slow release, but it does not has self-healing properties, can not realize self-regeneration when sustaining damage, and limits it and is giving birth to
The application of the related fields such as artificial organ in thing field of medicaments.
Summary of the invention
It is an object of the invention to provide a kind of Thermo-sensitive selfreparing hydrogel, with solve existing temperature-sensitive hydrogel can not realize from
The problem repaired.
It is a further object of the present invention to provide a kind of method preparing Thermo-sensitive selfreparing hydrogel, so that prepare can self-regeneration
And there is the hydrogel of Thermo-sensitive.
Another object of the present invention is to provide a kind of Thermo-sensitive selfreparing hydrogel at microbial administration, artificial organ and medicine realizing controlled-release
Put the application in field.
For achieving the above object, the technical scheme is that
A kind of Thermo-sensitive selfreparing hydrogel, is existed by (NIPA)-propylene hydrazide copolymers and many carbonyl compounds
Reacting under the effect of catalyst in aqueous solution and form, wherein, described catalyst is weak acid catalyst or aniline type catalysts,
Described (NIPA)-propylene hydrazide copolymers includes repetitive A and repetitive B, described repetitive A
Accounting for the 20～95% of copolymer gross mass, described many carbonyl compounds refer to the compound at least also having two carbonyls,
In formula, R is H or C1～5Alkyl.
Preferably, described weak acid catalyst is formic acid or acetic acid, and described aniline type catalysts is aniline or methylphenylamine；Institute
Stating R is H or methyl.
Preferably, described repetitive A accounts for the 50～95% of copolymer gross mass.
Preferably, described many carbonyl compounds are monomeric compound or are with two and with upper end carbonyl or the polymer of side carbonyl.
It is highly preferred that described many carbonyl compounds be terephthalaldehyde, methylglyoxal, with two end carbonyls Polyethylene Glycol or with two
The NIPA of individual end carbonyl.
The Thermo-sensitive selfreparing hydrogel good stability of the present invention, is provided simultaneously with Thermo-sensitive and self-repairability, can realize different temperatures
Under medicament slow release and the corresponding reversible state of temperature change, when sustaining damage can self-regeneration and recover its serviceability,
Increase the service life, and its self-repair procedure is close to the self-regeneration of life entity, controlled at artificial organ, microbial administration and medicine
The biological medicine association areas such as release have boundless application prospect.
A kind of method preparing Thermo-sensitive selfreparing hydrogel, comprises the following steps: by (NIPA)-acryloyl
Hydrazine copolymer is soluble in water, adds many carbonyl compounds, adds weak acid class or aniline type catalysts, mix homogeneously after fully dissolving
Rear standing, i.e. obtains Thermo-sensitive selfreparing hydrogel；Wherein, described catalyst is weak acid catalyst or aniline type catalysts,
Described (NIPA)-propylene hydrazide copolymers includes repetitive A and repetitive B, described repetitive A
Account for the 20～95% of copolymer gross mass,
In formula, R is H or C1～5Alkyl, preferably H or methyl, more preferably H.
Concretely comprising the following steps of the inventive method:
A, copolymerization, NIPA and the acrylic ester compound shown in formula I are under initiator effect, in a solvent
Carry out free-radical polymerized, obtain (NIPA)-acrylate copolymer, wherein, NIPA with
The mass ratio of acrylic ester compound is 0.25～20: 1,
In formula, R is H or C1～5Alkyl, R ＇ is C1～5Alkyl or the substituted alkyl of hydroxyl；
B, hydrazinolysis, add hydrazine hydrate in (NIPA)-acrylate copolymer and carry out hydrazinolysis, obtain (N-isopropyl
Base acrylamide)-propylene hydrazide copolymers；
C, gelation, by soluble in water for (NIPA)-propylene hydrazide copolymers, add many carbonyl compounds, fill
Divide and after dissolving, add weak acid class or aniline type catalysts, stand after mix homogeneously, i.e. obtain Thermo-sensitive selfreparing hydrogel.
The more specifically step of the inventive method is:
A, copolymerization, by 100 parts of N-isopropylacrylamides in parts by weight and 5～400 parts of (preferably 5～100 parts) acrylic acid
Ester type compound is dissolved in solvent, carries out free-radical polymerized (preferably controllable free-radical polymerisation), reaction temperature be 30～120 DEG C (excellent
Elect 60～100 DEG C as), the response time be 2～24h be preferably (12～24h), polymerization terminate after, in reactant liquor add precipitant,
Precipitation removes residual monomer, obtains (NIPA)-acrylate copolymer；
B, hydrazinolysis, be dissolved in gained (NIPA)-acrylate copolymer in solvent miscible with water, adds water
Closing hydrazine, carry out hydrazinolysis at 50～100 DEG C (preferably 60～90 DEG C), the hydrazinolysis time is 24～96h (preferably 48～72h), institute
Obtain mixture again through dialysis and lyophilization, obtain (NIPA)-propylene hydrazide copolymers；
C, gelation, by soluble in water for gained (NIPA)-propylene hydrazide copolymers, add many carbonyl compounds
And make it dissolve, add weak acid class or aniline type catalysts, stand after mix homogeneously, obtain Thermo-sensitive selfreparing hydrogel.
In the methods of the invention, the solvent in described step a is DMF, dioxane, dimethyl sulfoxide；
Described acrylic ester compound be acrylic acid methyl ester., methyl methacrylate, ethyl acrylate, ethyl methacrylate, third
One or more in olefin(e) acid butyl ester, butyl methacrylate, 2-(Acryloyloxy)ethanol or hydroxyethyl methylacrylate, preferably third
Olefin(e) acid ester.
In the methods of the invention, described step b is first to be dissolved in mutual with water by (NIPA)-acrylate copolymer
In molten solvent, adding hydrazine hydrate and carry out hydrazinolysis, solvent used is dioxane, methanol, ethanol, dimethylformamide
Or dimethyl sulfoxide.
In the methods of the invention, in described step b, the mole dosage of hydrazine hydrate is that (NIPA)-acrylate is common
5-20 times of the mole of polymers ester group.
In the methods of the invention, described many carbonyl compounds are monomeric compound or are with two and with upper end carbonyl or side carbonyl
Polymer.Preferably, described many carbonyl compounds be terephthalaldehyde, methylglyoxal, with two end carbonyls Polyethylene Glycol
Or the NIPA with two end carbonyls.
In the methods of the invention, described catalyst is formic acid, acetic acid, aniline or methylphenylamine.
In the methods of the invention, (NIPA)-propylene hydrazide copolymers described in described step c and many carbonylations
The quality sum of compound accounts for the 5～20% of hydrogel gross mass.
The inventive method first passes through NIPAM and obtains random copolymer with acrylic ester compound copolymerization；Then by gained copolymerization
Thing hydrazine hydrate hydrazinolysis；React with many carbonyl compounds the most in the presence of a catalyst, obtain with biocompatible polymer PNIPAM
For main body, biocompatibility polyvalent carbonyl compound is the hydrogel with temperature-sensing property and self-repair function of cross-linking agent.This
Bright method, by the mass ratio of two repetitives in regulation and control NIPAM-acrylic acid esters co-polymer, realizes NIPAM-acryloyl
In hydrazine copolymer, the content of two repetitives controls, so that gained hydrogel is provided simultaneously with excellent Thermo-sensitive and self-repairability.
The Thermo-sensitive selfreparing hydrogel that the present invention provides can apply to the necks such as microbial administration, artificial organ and drug controllable release
Territory.
Accompanying drawing explanation
Fig. 1 is (NIPA)-acrylate copolymer and (NIPA)-propylene hydrazide copolymers
Infrared spectrum.Wherein, P (NIPAM313-co-MA40) it is the infrared of (NIPA)-acrylate copolymer
Collection of illustrative plates, P (NIPAM313-co-AH40) it is the infared spectrum of (NIPA)-propylene hydrazide copolymers.
Fig. 2 is (NIPA)-acrylate copolymer and (NIPA)-propylene hydrazide copolymers
Nuclear magnetic spectrogram.Wherein, (NIPA)-acrylate copolymer solvent for use is CDCl3, (N-isopropyl third
Acrylamide)-propylene hydrazide copolymers solvent for use is DMSO-d6.
Fig. 3 is the selfreparing design sketch of embodiment 1 gained hydrogel.
Fig. 4 is the temperature sensitive procedure chart of embodiment 1 gained hydrogel.
Detailed description of the invention
Below in an example, the various processes not described in detail and method are conventional methods as known in the art, examination used
Agent do not show source, specification be commercially available analytical pure or chemical pure.
The embodiment of the invention discloses a kind of Thermo-sensitive selfreparing hydrogel, by the hydrazides copolymerization of (NIPA)-propylene
Thing reacts under the effect of catalyst in aqueous with many carbonyl compounds and forms, and wherein, described catalyst is weak acid based catalyst
Agent or aniline type catalysts, described (NIPA)-propylene hydrazide copolymers includes repetitive A and repetitive
B, described repetitive A account for the 20～95% of copolymer gross mass, preferably 50～95%.
In formula, R is H or C1～5Alkyl, preferably H or methyl.
Described weak acid catalyst is formic acid or acetic acid, and described aniline type catalysts is aniline or methylphenylamine.
The embodiment of the invention also discloses the preparation method of Thermo-sensitive selfreparing hydrogel, comprise the following steps:
A, copolymerization, by 100 parts of N-isopropylacrylamides in parts by weight and 5～400 parts of (preferably 5～100 parts) acrylic acid
Ester type compound is dissolved in solvent, carries out free-radical polymerized (preferably active free radical polymerization), reaction temperature be 30～120 DEG C (excellent
Elect 60～100 DEG C as), the response time be 2～24h be preferably (12～24h), polymerization terminate after, in reactant liquor add precipitant,
Precipitation removes residual monomer, obtains (NIPA)-acrylate copolymer.Wherein, acrylic ester compound is
Acrylic acid methyl ester., methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, methacrylic acid fourth
One or more in ester, 2-(Acryloyloxy)ethanol or hydroxyethyl methylacrylate, preferably acrylate；The solvent used is
DMF, dioxane or dimethyl sulfoxide, the consumption of solvent is 120～1000 parts.
B, hydrazinolysis, be dissolved in gained (NIPA)-acrylate copolymer in solvent miscible with water, adds water
Closing hydrazine, carry out hydrazinolysis at 50～100 DEG C (preferably 60～90 DEG C), the hydrazinolysis time is 24～96h (preferably 48～72h), institute
Obtain mixture again through dialysis and lyophilization, obtain (NIPA)-propylene hydrazide copolymers.Solvent used is two
Oxygen six ring, methanol, ethanol, dimethylformamide or dimethyl sulfoxide.
C, gelation, by soluble in water, according to total solids content for gained (NIPA)-propylene hydrazide copolymers
5-20% adds deionized water, adds many carbonyl compounds and makes it fully dissolve, adding weak acid catalyst or aniline type catalysts,
After mix homogeneously, stand, obtain self-catalysis repair hydrogel；Many carbonyl compounds used are monomeric compound or with two
And with upper end carbonyl or the polymer of side carbonyl, preferably terephthalaldehyde, methylglyoxal, Polyethylene Glycol with two end carbonyls
Or the NIPA with two end carbonyls；Used catalyst is formic acid, acetic acid, aniline or methylphenylamine.
Embodiment 1
Copolymerization: by 10g NIPAM, 1g acrylic acid methyl ester., 5mg azodiisobutyronitrile (AIBN) and 50mg DDMAT
Chain-transferring agent (i.e. dodecyl trithiocarbonate) is dissolved in 15mL dioxane, and adds it to the reaction bulb of 50mL
In, it is warming up to 60 DEG C in removing system after oxygen under magnetic stirring and carries out reversible addition-fragmentation chain transfer free radical polymerization, reaction
Time is 24h, after reaction terminates, reaction system is cooled down, with petroleum ether precipitation twice, removes unreacted monomer, and vacuum is done
Dry white powder, is NIPAM methyl acrylate copolymer, weigh calculating monomer conversion and mean molecule quantity, copolymerization
In thing, repetitive NIPAM is about 10: 1 with the mass ratio of repetitive acrylic acid methyl ester..
Hydrazinolysis: above-mentioned for 5g copolymer is dissolved in the mixed solvent of 5mL ethanol and 10mL hydrazine hydrate, is warming up to 80 DEG C, hydrazine
Solve 48h, then reactant mixture is loaded in bag filter, deionized water dialysis 48h, remove unnecessary hydrazine hydrate and ethanol, cold
Lyophilizing is dry, obtains the hydrazinolysis thing of copolymer, for white powder.
Gelation: be dissolved in 18g water by above-mentioned for 1g hydrazinolysis thing, adds 0.95g (following with the Polyethylene Glycol of two terminal aldehyde groups
Referred to as the molecular weight of CHO-PEG-CHO, PEG is 2300), after fully dissolving, addition 1g glacial acetic acid, mix homogeneously,
Stand 1min, i.e. can get Thermo-sensitive selfreparing hydrogel.
Gained NIPA-polymethyl acrylate copolymer and hydrazinolysis thing thereof are carried out infrared detection and nuclear-magnetism table
Levying, result is as depicted in figs. 1 and 2.
Infrared spectrum as shown in Figure 1 is it can be seen that at 3298cm-1There is-NH functional group, 2972cm-1There is-CH official's energy
Group；Additionally containing 1730cm in copolymer-1And 1646cm-1It is respectively the absworption peak of the acrylate C=O corresponding with amide,
Demonstrate the structure of its copolymerization.1730cm after hydrazinolysis-1The absworption peak at place disappears, it was demonstrated that ester bond is hydrazides by hydrazinolysis.
Nuclear magnetic spectrogram shown in Fig. 2, it can be seen that 3.65ppm, distinguishes corresponding polymethyl acrylate and PNIPAM at 4.00ppm
Construction unit, it is possible to obtain mol ratio and the weight ratio of two kinds of repetitives from peak area ratio, result show its weight ratio with
Rate of charge is close；After hydrazinolysis, the peak at 3.65ppm disappears, and the peak type of the PNIPAM of correspondence is constant, it was demonstrated that ester bond is by hydrazine
Solve, and amido link stands intact, at 9.7ppm, occur in that the proton peak that hydrazides is corresponding simultaneously, illustrate that hydrazinolysis has obtained target product
Thing.
As it is shown on figure 3, gained hydrogel is cut (such as Fig. 3 b), it can realize selfreparing (such as Fig. 3 c) in 24h, and is
Make under the effect of additional pull strength, also will not rupture (such as Fig. 3 d) along incision.
Shown in Fig. 4 is the temperature sensitive procedure chart of selfreparing hydrogel, and hydrogel has the preferably transparency (such as Fig. 4 a) when room temperature,
Be heated to when 40 DEG C become opaque gel (such as Fig. 4 b), when temperature is gradually lowered transparency gradually step up (such as Fig. 4 c) and
Gradually become fully transparent (such as Fig. 4 d), show the temperature-sensing property of completely reversibility.
Embodiment 2
Copolymerization: 10g NIPAM, 40g acrylic acid methyl ester., 5mg azodiisobutyronitrile (AIBN) and 50mg CPDB chain are turned
Move agent (i.e. dithiobenzoic acid cyano group isopropyl ester) to be dissolved in 50mL dioxane, and add it to the reaction bulb of 100mL
In, it is warming up to 60 DEG C in removing system after oxygen under magnetic stirring and carries out reversible addition-fragmentation chain transfer free radical polymerization, reaction
Time is 24h, after reaction terminates, reaction system is cooled down, with petroleum ether precipitation twice, removes unreacted monomer, and vacuum is done
Dry micro-yellow powder, is NIPAM methyl acrylate copolymer, weigh calculating monomer conversion and mean molecule quantity, poly-
In compound, the mass ratio of two repetitives is about 1: 4.
Hydrazinolysis: above-mentioned for 5g copolymer is dissolved in 10mL methanol, is subsequently adding 10mL hydrazine hydrate, be warming up to 80 DEG C, hydrazine
Solve 72h, then reactant mixture is loaded in bag filter, deionized water dialysis 48h, remove unnecessary hydrazine hydrate and methanol,
Lyophilization, obtains the hydrazinolysis thing of copolymer, for white powder.
Gelation: be dissolved in 58g water by above-mentioned for 1g hydrazinolysis thing, adds 5.3g CHO-PEG-CHO (PEG molecular weight is 2300),
After fully dissolving, add 3g glacial acetic acid, mix homogeneously, stand 1min, i.e. can get Thermo-sensitive selfreparing hydrogel.
Embodiment 3
Copolymerization: 10gNIPAM, 2g methyl methacrylate and 0.1g PMDETA (PMDETA) are dissolved in
In 15mL dioxane, and add it in the reaction bulb of 50mL, after the oxygen in removing system, add 0.1gCuBr
And under magnetic agitation and nitrogen are protected, be warming up to 60 DEG C carry out atom transfer and move radical polymerization, the response time is 16h, reaction
After end, by reaction system cooling dilution, peroxidating aluminum post is to remove CuBr, and with petroleum ether precipitation twice, removing unreacted
Monomer, be vacuum dried to obtain white powder, i.e. NIPAM methylmethacrylate copolymer, two repetitives in copolymer
Mass ratio is about 5: 1.
Hydrazinolysis: above-mentioned for 5g copolymer is dissolved in 10mL ethanol, is subsequently adding 5mL hydrazine hydrate, be warming up to 90 DEG C, hydrazinolysis
48h, then loads in bag filter by reactant mixture, deionized water dialysis 48h, removes unnecessary hydrazine hydrate and ethanol, freezing
It is dried, obtains the hydrazinolysis thing of copolymer, for white powder.
Gelation: be dissolved in 21g water by above-mentioned for 1g hydrazinolysis thing, adds 4.25g CHO-PEG-CHO (PEG molecular weight is 2300),
After fully dissolving, add 0.5g aniline, mix homogeneously, stand 1min, i.e. can get Thermo-sensitive selfreparing hydrogel.
Embodiment 4
Copolymerization: 10gNIPAM, 10g butyl acrylate and 0.2g azodiisobutyronitrile are dissolved in 20mL dioxane, and will
It joins in the reaction bulb of 100mL, is warming up to 60 DEG C and carries out general radical polymerization, instead under magnetic agitation and nitrogen are protected
It is 8h between Ying Shi, after reaction terminates, reaction system is cooled down, with petroleum ether precipitation twice, remove unreacted monomer, vacuum
Be dried to obtain white powder, i.e. NIPAM butyl acrylate copolymer, the mass ratio of two of which construction unit is 1: 1.
Hydrazinolysis: above-mentioned for 5g copolymer is dissolved in the mixed solvent of 5mL methanol and 10mL hydrazine hydrate, is warming up to 80 DEG C, hydrazine
Solve 48h, then reactant mixture is loaded in bag filter, deionized water dialysis 48h, remove unnecessary hydrazine hydrate and methanol, cold
Lyophilizing is dry, obtains the hydrazinolysis thing of copolymer, for white powder.
Gelation: be dissolved in 60g water by above-mentioned for 1g hydrazinolysis thing, adds 5g CHO-PEG-CHO (PEG molecular weight is 2300),
After fully dissolving, add 3g monomethylaniline., mix homogeneously, stand 1min, i.e. can get Thermo-sensitive selfreparing hydrogel.
Embodiment 5
Copolymerization, hydrazinolysis are with embodiment 1.
Gelation: be dissolved in the saturated solution of 10g terephthalaldehyde by 1g gained hydrazinolysis thing, after fully dissolving, adds 0.2g benzene
Amine, mix homogeneously, stand 1min, i.e. can get Thermo-sensitive selfreparing hydrogel.
Embodiment 6
Copolymerization: by 10g NIPAM, 1g 2-(Acryloyloxy)ethanol and 50mgCPDB chain-transferring agent (i.e. dithiobenzoic acid cyano group
Isopropyl ester) it is dissolved in 15mL dioxane, and add it in the reaction bulb of 50mL, at magnetic after oxygen in removing system
Being warming up to 60 DEG C under power stirring and carry out reversible addition-fragmentation chain transfer free radical polymerization, the response time is 24h, after reaction terminates,
Reaction system is cooled down, with petroleum ether precipitation twice, removes unreacted monomer, be vacuum dried to obtain white powder, be NIPAM
Hydroxyethylacrylate copolymer, weigh calculating monomer conversion and mean molecule quantity, the mass ratio obtaining two repetitives is 10: 1.
Hydrazinolysis: above-mentioned for 5g copolymer is dissolved in the mixed solvent of 5mL ethanol and 10mL hydrazine hydrate, is warming up to 80 DEG C, hydrazine
Solve 48h, then reactant mixture is loaded in bag filter, deionized water dialysis 48h, remove unnecessary hydrazine hydrate and ethanol, cold
Lyophilizing is dry, obtains the hydrazinolysis thing of copolymer, for white powder.
Gelation: be dissolved in 17.6g water by above-mentioned for 1g hydrazinolysis thing, (PEG molecular weight is to add 1.04g CHO-PEG-CHO
2300), after fully dissolving, add 1g acetic acid, stand 1min, i.e. can get self-catalysis repair hydrogel.
Embodiment 7
Copolymerization: by 10g NIPAM, 0.5g acrylic acid methyl ester., 5mg azodiisobutyronitrile (AIBN) and 50mg DDMAT
Chain-transferring agent (i.e. dodecyl trithiocarbonate) is dissolved in 15mL dioxane, and adds it to the reaction of 50mL
In Ping, it is warming up to 60 DEG C in removing system after oxygen under magnetic stirring and carries out reversible addition-fragmentation chain transfer free radical polymerization, instead
It is 24h between Ying Shi, after reaction terminates, reaction system is cooled down, with petroleum ether precipitation twice, remove unreacted monomer, vacuum
It is dried to obtain white powder, is NIPAM methyl acrylate copolymer, weigh calculating monomer conversion and mean molecule quantity, altogether
In polymers, repetitive NIPAM is about 20: 1 with the mass ratio of repetitive acrylic acid methyl ester..
Hydrazinolysis: above-mentioned for 5g copolymer is dissolved in the mixed solvent of 5mL ethanol and 10mL hydrazine hydrate, is warming up to 80 DEG C, hydrazine
Solve 72h, then reactant mixture is loaded in bag filter, deionized water dialysis 48h, remove unnecessary hydrazine hydrate and ethanol, cold
Lyophilizing is dry, obtains the hydrazinolysis thing of copolymer, for white powder.
Gelation: be dissolved in 18g water by above-mentioned for 1g hydrazinolysis thing, adds the 0.90g Polyethylene Glycol (PEG with two terminal aldehyde groups
Molecular weight is 4300), after fully dissolving, add 1g glacial acetic acid, mix homogeneously, stand 1min, i.e. can get Thermo-sensitive and review one's lessons by oneself
Rehydration gel.
Embodiment 8: selfreparing is tested.
Embodiment 1～7 products therefrom is carried out selfreparing experiment, specifically comprises the following steps that and the hydrogel obtained is cut into two along centre
Half, then joint-cutting alignment is put together, after 24h, observe reparation situation, and solidifying along the stretching checking of joint-cutting vertical direction with tweezers
Whether glue is repaired.Result shows: prepared hydrogel can realize selfreparing in 24h, even and if at the work of additional pull strength
Under with, also will not rupture along incision.
Embodiment 9: Thermo-sensitive is tested.
Hydrogel embodiment 1～7 prepared immerses in 40 DEG C of hot water, and gel is gradually become the opaquest from transparent；By water-setting
Glue takes out from hot water, is put under the room temperature condition of 25 DEG C standing, and hydrogel transparency is gradually increased and eventually becomes and initial shape
The identical gel of state, it was demonstrated that the reversibility of hydrogel Thermo-sensitive, the hydrogel that the present invention prepares can be used for microbial administration.
It is still identical with original state that this experiment is repeated 8 times rear outward appearance.
Claims (10)
1. a Thermo-sensitive selfreparing hydrogel, is characterized in that, by (NIPA)-propylene hydrazide copolymers with
Many carbonyl compounds and react under the effect of catalyst form in aqueous, and wherein, described catalyst is weak acid catalyst
Or aniline type catalysts, described (NIPA)-propylene hydrazide copolymers includes repetitive A and repetitive
B, described repetitive A account for the 20～95% of copolymer gross mass,
In formula, R is H or C1～5Alkyl.
Thermo-sensitive selfreparing hydrogel the most according to claim 1, is characterized in that, described weak acid catalyst is formic acid
Or acetic acid, described aniline type catalysts is aniline or methylphenylamine；Described R is H or methyl.
Thermo-sensitive selfreparing hydrogel the most according to claim 1, is characterized in that, described repetitive A accounts for copolymer
The 50～95% of gross mass.
Thermo-sensitive selfreparing hydrogel the most according to claim 1, is characterized in that, described many carbonyl compounds are monomer
Compound or be with two and with upper end carbonyl or the polymer of side carbonyl.
5. the method preparing Thermo-sensitive selfreparing hydrogel, is characterized in that, comprises the following steps: (N-isopropyl propylene
Amide)-propylene hydrazide copolymers is soluble in water, adds many carbonyl compounds, and add weak acid class after fully dissolving or phenyl amines is urged
Agent, stands after mix homogeneously, i.e. obtains Thermo-sensitive selfreparing hydrogel；Wherein, described catalyst be weak acid catalyst or
Aniline type catalysts, described (NIPA)-propylene hydrazide copolymers includes repetitive A and repetitive B,
Described repetitive A accounts for the 20～95% of copolymer gross mass,
In formula, R is H or C1～5Alkyl.
Method the most according to claim 5, is characterized in that, described (NIPA)-propylene hydrazides copolymerization
Thing is prepared according to the following steps:
A, copolymerization, NIPA and the acrylic ester compound shown in formula I are under initiator effect, at solvent
In carry out free-radical polymerized, obtain (NIPA)-acrylate copolymer,
In formula, R is H or C1～5Alkyl, R ＇ is C1～5Alkyl or the substituted alkyl of hydroxyl；
B, hydrazinolysis, add hydrazine hydrate in (NIPA)-acrylate copolymer and carry out hydrazinolysis, obtain (N-
N-isopropylacrylamide)-propylene hydrazide copolymers.
Method the most according to claim 5, is characterized in that, described step b is first by (NIPA)
-acrylate copolymer is dissolved in solvent miscible with water, adds hydrazine hydrate and carries out hydrazinolysis.
8. according to the method described in claim 5 or 6, it is characterized in that, described many carbonyl compounds are monomeric compound or are
With two and with upper end carbonyl or the polymer of side carbonyl.
Method the most according to claim 8, is characterized in that, described many carbonyl compounds be terephthalaldehyde, methylglyoxal,
Polyethylene Glycol with two end carbonyls or the NIPA with two end carbonyls.
10. the Thermo-sensitive selfreparing hydrogel described in claim 1 is in microbial administration, artificial organ and drug controllable release
Application.
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| CN106832310A (en) * | 2017-01-22 | 2017-06-13 | 河北大学 | A kind of degradable selfreparing hydrogel and preparation method and application |
| CN106905472A (en) * | 2017-04-18 | 2017-06-30 | 北京蛋白质组研究中心 | A kind of functionalization responsive to temperature type polymer and preparation method and application |
| CN107892732A (en) * | 2017-12-13 | 2018-04-10 | 广东工业大学 | A kind of temperature-sensitive hydrogel and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106832310A (en) * | 2017-01-22 | 2017-06-13 | 河北大学 | A kind of degradable selfreparing hydrogel and preparation method and application |
| CN106832310B (en) * | 2017-01-22 | 2019-09-24 | 河北大学 | A kind of degradable selfreparing hydrogel and the preparation method and application thereof |
| CN106905472A (en) * | 2017-04-18 | 2017-06-30 | 北京蛋白质组研究中心 | A kind of functionalization responsive to temperature type polymer and preparation method and application |
| CN107892732A (en) * | 2017-12-13 | 2018-04-10 | 广东工业大学 | A kind of temperature-sensitive hydrogel and preparation method thereof |
| CN107892732B (en) * | 2017-12-13 | 2020-10-23 | 广东工业大学 | Temperature-sensitive hydrogel and preparation method thereof |
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