CN106349412A - Application of N-acryloyl glycinamide-based supramolecular hydrogel used as self-repair material - Google Patents

Application of N-acryloyl glycinamide-based supramolecular hydrogel used as self-repair material Download PDF

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CN106349412A
CN106349412A CN201610702561.5A CN201610702561A CN106349412A CN 106349412 A CN106349412 A CN 106349412A CN 201610702561 A CN201610702561 A CN 201610702561A CN 106349412 A CN106349412 A CN 106349412A
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aminoacetamide
acryloyl group
self
hydrogel
monomer
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CN106349412B (en
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刘文广
戴西洋
张银宇
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Tianjin University
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Abstract

The invention discloses application of N-acryloyl glycinamide-based supramolecular hydrogel used as a self-repair material. The supramolecular hydrogelis prepared by using N-acryloyl glycinamide as monomers under induction of inducers. Due to a synergistic effect of hydrogen bonds, the hydrogel has very strong tensile and compressive strength, can resist tearing, can realize thermal plasticity and self-repair functions at higher temperature, and has very good biocompatibility.

Description

Supramolecular hydrogel based on acryloyl group Aminoacetamide is as self-repair material Application
The present patent application is female case patent application " a kind of high intensity supramolecular hydrogel and its preparation method and application " Divisional application, the applying date of parent application is on April 21st, 2015, Application No. 2015101916077.
Technical field
The present invention relates to a kind of hydrogel and preparation method, more particularly, it relates to one kind is with acryloyl group Aminoacetamide (naga) the pnaga hydrogel for monomer preparation and preparation method, have high stability, high intensity, thermoplasticity and selfreparing Function.
Background technology
Hydrogel is with water as disperse medium, hydrophilic and water-fast and can absorb large quantity of moisture and (generally contain The water yield is more than the 50% of gross mass) there is the macromolecule polymer material of cross-linked structure.Because the physical crosslinking between polymer chain Act on without being dissolved in the water with chemical crosslinking, can only be swelling and keep certain shape, meanwhile, also there is good water and ooze Permeability, biocompatibility, can reduce untoward reaction as body implant.Thus hydrogel is as excellent bio-medical material Material is used widely.But, it is outstanding as biomaterial that the mechanical performance that its high-moisture leads to hydrogel poor limits it It is the application of mechanics device, even more so for supramolecular hydrogel, typically without the effect of chemical bond, physical crosslinking super Molecular water gel mechanical strength is in general all weaker, and the supramolecular hydrogel of therefore preparation high intensity has very big showing Real and theoretical application.
In order to solve hydrogel this problem of poor mechanical property, recent scientists have developed following several high intensity Hydrogel: dual network (dn) hydrogel, intercalated inorganic Nanometer composite hydrogel (nc) and polymer microsphere composite aquogel (mmc).But these high intensity hydrogels do not have high stretch-proof and incompressible function (yoshimi tanaka, jain concurrently Ping gong, yoshihito osada.novel hydrogels with excellent mechanical performance.(mmc).But these high intensity hydrogels do not have high stretch-proof and incompressible function (yoshimi concurrently Tanaka, jain ping gong, yoshihito osada.novel hydrogels with excellent mechanical performance.prog.polym.sci.2005；30:1-9.).Pure physical crosslinking effect is only leaned on to make High intensity hydrogel.There are (sun t l, kurokawa t, kuroda s, the et al.physical such as gong recently hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity.nat.mater.2013；12:932-937.) the pure physics high intensity that scholar is made using polyelectrolyte Hydrogel, but its water content only has 50%, and polypropylene acyl group Aminoacetamide gel not only has the high intensity on mechanics, and And possess thermoplasticity and self-repair function.
Content of the invention
It is an object of the invention to overcoming the deficiencies in the prior art, provide a kind of with acryloyl group Aminoacetamide (naga) For the polymer supermolecule hydrogel of monomer, this supermolecule polymer hydrogel inherently belongs to except some showing hydrogel Property, also there is very strong stretching, Compressive Mechanical Properties, the thermoplasticity under preferable tear resistance, temperature-responsive and selfreparing Function.
The technical purpose of the present invention is achieved by following technical proposals:
A kind of high intensity supramolecular hydrogel, is made up of the polymer with acryloyl group Aminoacetamide as monomer and water, water 55 85%, in the polymer, the side chain of each repetitive is provided with two amide groups to the water content of gel, gathers Right is 1,000 5000, preferably 2,000 4000.
In above-mentioned hydrogel, water content and the degree of polymerization assume inversely prroportional relationship, and that is, water content is with the sweet ammonia of acryloyl group The increase of amide monomer consumption and decline.
The preparation method of above-mentioned hydrogel, is carried out as steps described below: by acryloyl group Aminoacetamide for monomer in aqueous phase Under the conditions of dissolve, add initiator, under anoxic condition by initiator cause acryloyl group Aminoacetamide carbon-carbon double bond carry out Radical polymerization.
In above-mentioned preparation method, described aqueous phase selects deionized water, or tap water.
In above-mentioned preparation method, the consumption of described initiator is the 3% of monomer propylene acyl group Aminoacetamide quality 5%.
In above-mentioned preparation method, the concentration of described monomer propylene acyl group Aminoacetamide is 10 60%, i.e. acrylamide The quality of base Aminoacetamide monomer/(quality of the quality+aqueous phase of acrylamido Aminoacetamide monomer).
Naga monomer is caused to react using the free radical that initiator provides.Wherein initiator can select polyphosphazene polymer Thermal initiator under the conditions of conventional aqueous phase in conjunction field, such as Ammonium persulfate. (aps), potassium peroxydisulfate (kps), or light-initiated Agent, such as 2- hydroxy-2-methyl -1- phenyl -1- acetone (irgacure 1173).If selection thermal initiator, need profit first Exclude the oxygen in reaction system, to avoid its inhibition, then basis with noble gases (as nitrogen, argon or helium) The activity of initiator and consumption, when reaction system being heated on the initiation temperature of initiator used and keep considerably long Between, such as more than 1h or longer (1-5h), to promote initiator can produce enough free radicals, initiation reaction body for a long time Persistently there is Raolical polymerizable, the final hydrogel preparing the present invention in system.If selection light trigger, wherein initiator select Select light trigger 2- hydroxy-2-methyl -1- phenyl -1- acetone (irgacure 1173).Can select transparent airtight anti- Answer container, cause radical polymerization under conditions of ultraviolet light, because light-initiated efficiency is higher than thermal initiation, because according to selected When the activity of initiator and consumption adjustment irradiation time, irradiation time can be shorter than the heat time heating time of thermal initiation, such as 20 minutes or Longer (30min-1h), with respect to thermal initiation so so that experimental period greatly reduces.
In preparation scheme, after the completion of reaction, take out copolymer from reaction vessel, remove the list not participating in reaction After body, initiator, cross-linking agent and solvent, it is immersed in water and (as soaked 7 days, changes once every 12h until reaching swelling equilibrium Water, reaches swelling equilibrium).In the inventive solutions, with acryloyl group Aminoacetamide (naga) as monomer, the water of preparation Gel, the side chain of its strand carries two amide groups, intermolecular strong intermolecular hydrogen bond action, (- ch2- ch2-)n" carbon-to-carbon " singly-bound be connected framing structure, the amide group of side chain (co-nh).Acryloyl group Aminoacetamide is causing Make initiator provide free radical under conditions of agent, then acryloyl group Aminoacetamide (naga) double bond is caused by free radical, occur poly- Close reaction, in the hydrogel material of final preparation, due to the synergism of hydrogen bond, make whole hydrogel material by polymer and water Composition.
Compared with prior art, acryloyl group Aminoacetamide (naga) in the present invention, due to the side of its polymer molecular chain Two amide groups, intermolecular strong intermolecular hydrogen bond action are carried on chain, thus the physical crosslinking effect being formed makes Acryloyl group Aminoacetamide gel has good mechanical strength and toughness, and formed by bisamide group due to this Hydrogen bond can be realized at relatively high temperatures destroying and rebuild, and gel is provided with the function of thermoplasticity and selfreparing.The present invention provides A kind of high intensity pnaga hydrogel be with acryloyl group Aminoacetamide (naga) as raw material, in the presence of initiator cause system Standby form, due to the synergism of hydrogen bond, this hydrogel have while very strong stretching, compression can anti tear, relatively It is capable of the function of thermoplasticity and selfreparing under high temperature, and good biocompatibility.
Brief description
Fig. 1 is the FTIR spectrum figure of the monomer propylene acyl group Aminoacetamide that the present embodiment uses.
Fig. 2 is the FTIR spectrum figure of the acryloyl group Aminoacetamide polymer of the present embodiment synthesis.
Fig. 3 is the stretching of the polypropylene acyl group Aminoacetamide hydrogel of present invention synthesis, compresses and knotting pictorial diagram, wherein 1 is knotting, 2 stretchings, 3 compressions.
Fig. 4 is that the process of the remoldability at 50 DEG C -90 DEG C for the polypropylene acyl group Aminoacetamide hydrogel of the present invention is illustrated Figure.
Fig. 5 is to realize selfreparing at 50 90 DEG C when the polypropylene acyl group Aminoacetamide hydrogel of the present invention cuts in half Schematic diagram.
Fig. 6 is the polypropylene acyl group Aminoacetamide hydrogel pnaga-25 of the present invention and polyacrylamide hydrophilic gel in water And the stability test in carbamide, a be polyacrylamide hydrophilic gel in deionized water, b be pnaga-25 hydrogel go from In sub- water, c is pnaga-25 hydrogel in 5mol l-1Aqueous solution of urea in.
Specific embodiment
Further illustrate technical scheme with reference to specific embodiment.
In an embodiment, with glycyl amide hydrochloride and acryloyl chloride for raw material according to list of references (boustta m, colombo p e,lenglet s,et al.versatile ucst-based thermoresponsive hydrogels for loco-regional sustained drug delivery[j].journal of controlled release, 2014,174:1-6) prepared a kind of monomer propylene acyl group Aminoacetamide carrying two amide groups, chemical formula structure is such as Shown in lower chemical formula:
Demonstrate it using FTIR spectrum (platinum Elmer Co., Ltd of the U.S.) successfully to synthesize, wherein their spy Levy peak as follows: ν=3389cm-1(m,nh),3314cm-1(s,nh),3191cm-1(m,nh),1662cm-1(vs, c=o), 1626cm-1(vs, c=o), 1556cm-1(vs, nh) (refers to accompanying drawing 1).
Homopolymerization is carried out for monomer with the acryloyl group Aminoacetamide of above-mentioned synthesis, selects aqueous phase (such as ordinary tap water, to go Ionized water) for being polymerized environment, provide water environment for polymer simultaneously, initiator selects water soluble starter, synthesizes different monomers The polyacrylamide base Aminoacetamide gel of concentration, so that monomer concentration is 25% as a example, i.e. acrylamido Aminoacetamide monomer Quality/(quality of the quality+water of acrylamido Aminoacetamide monomer).
By acrylamido Aminoacetamide monomer (243mg), after the deionized water of 750 μ l is completely dissolved, add light-initiated Agent irgacure 1173 (2- hydroxy-2-methyl -1- phenyl -1- acetone) 7 μ l.Mixed liquor after inflated with nitrogen deoxygenation, by mixed liquor Inject in airtight mould, mould irradiates 40 minutes to ensure fully to cause radical polymerization in ultra-violet curing case.Subsequently beat Mold takes out gel, soaks several days in deionized water, reaches swelling equilibrium, changes above-mentioned deionized water every 12h.Using Fu In leaf infrared spectrum (platinum Elmer Co., Ltd of the U.S.) to synthesis homopolymer carry out Infrared Characterization, specifically as shown in Figure 2, base This performance and accompanying drawing 1 identical characteristic peak, in this explanation acrylamido Aminoacetamide monomer, carbon-carbon double bond is opened and is gathered Close, remaining structure there is no generation change.
Prepare the gel of different monomers concentration by same steps, carry out mechanical property, tear resistance, thermoplasticity and selfreparing Deng experimentation.This gel sample is named as pnaga-x, and what wherein x represented is the monomer concentration of gel.Change monomer propylene acyl The concentration of amido Aminoacetamide monomer, the consumption of light trigger irgacure 1173 is the 3% of monomer mass, prepares following water Gel sample pnaga-10, the supermolecule polymer of the variable concentrations of pnaga-15, pnaga-20, pnaga-25, pnaga-30 Hydrogel.
The Mechanics Performance Testing adopting the polyacrylamide base Aminoacetamide hydrogel of the test present invention with the following method is in electricity Carrying out on sub- universal testing machine (Jinan epoch company limited), the size of the sample of stretching mechanical property testing be 20mm × 10mm, thickness is 500 μm, and rate of extension is 50mm/min；The sample size of Compressive Mechanical Properties test is diameter 10mm, high 8mm Cylinder, compression speed be 10mm/min.It is 20mm × 10mm in the size of the sample carrying out stretching mechanical property testing, thickness is 500μm.The sample size of Compressive Mechanical Properties test is diameter 10mm, the cylinder of high 8mm.Tear resistance test sample size According to 1/2gbt 529-2008 a size (wide 7.5mm, long 50mm, notch length 20mm, thickness 0.5mm).This supermolecule water The tensile strength of gel, compressive strength can reach the rank of mpa.
Table 1 is the various performance parameters of hydrogel sample:
Compressive strength: during measurement, gel is compressed to machine maximum range and also cannot compress, so with answering at 90% strain Masterpiece is intensity.Pnaga-x:x represents the mass fraction of polymerized monomer, i.e. the quality of acrylamido Aminoacetamide monomer/(third The quality of the quality+water of acrylamide base Aminoacetamide monomer).The mass fraction changing polymerized monomer to 50%, 60%, polymer All show the property with above-mentioned list basic simlarity, that is, tensile strength, compression are strong in the homopolymer hydrogel of one-component Degree can reach mpa rank, and can make knotting, stretching and compression behavior with hydrogel material object, as shown in Figure 3.
Using ten thousand/ electronic scale carry out the test of hydrogel water content, weigh the weight in wet base of hydrogel first, then Hydrogel is heated under the conditions of constant temperature (50 degrees Celsius) and removes moisture removal, to constant weight, then weigh the dry weight of hydrogel, utilize (water Gel weight in wet base hydrogel dry)/hydrogel wet * 100%, you can obtain hydrogel water content.Pnaga-x:x represents polymerization The mass fraction of monomer, that is, the quality of acrylamido Aminoacetamide monomer/(quality of acrylamido Aminoacetamide monomer+ The quality of water), change x and rise to 60% by 10%, water content drops to 55% by 85%.Through gpc chromatographic determination polymer Molecular weight, the corresponding acryloyl group Aminoacetamide degree of polymerization is 1,000 5000.
Profit detects the thermoplasticity of the polyacrylamide base Aminoacetamide hydrogel of the present invention with the following method, will prepare Hydrogel fragment, put in a hermetic container of different shapes, at a temperature of 50 DEG C -90 DEG C heating 30 minutes after, allow Its self-heating is cooled to 20 25 degrees Celsius of room temperature, and the last demoulding can prepare polyacrylamide base glycyl aqueous amine of different shapes Gel (refers to Figure of description 4), and this process can repeat, and realizes recycling, is expected to mitigate environmental pressure, the i.e. present invention Polyacrylamide base Aminoacetamide hydrogel, as the application of thermoplastic polymer, processing temperature is 50 DEG C -90 DEG C.
Profit detects the self-repair function of the polyacrylamide base Aminoacetamide hydrogel of the present invention with the following method.To prepare Hydrogel cut in half, wherein half is dyeed in order to distinguish with chemical reagent rhodamine b, then will cut two halves To upper, that is, two half block hydrogels come in contact gel, put in sealing container and heat 1 hour at a temperature of 50 DEG C -90 DEG C, The gel finally cutting can be well bonded to together, and can't see interface, refers to Figure of description 5, and two blocks of water are described Gel completes self-regeneration, and that is, the polyacrylamide base Aminoacetamide hydrogel of the present invention, as the application of self-repair material, repaiies Rewarming degree is 50 DEG C -90 DEG C.
Profit detects the cytotoxicity of the polyacrylamide base Aminoacetamide hydrogel of the present invention with the following method.In order to test This high intensity supramolecular hydrogel is applied to biomaterial probability.The gel film of the present invention is cut into a diameter of 10.2mm, Soaking 2h in the ethanol (ethanol water) of percentage by volume 75% makes it sterilize, and is then washed with pbs, these gels are put into The bottom of 48 orifice plates.Chondrocyte atdca5 suspension (5 × 10 by 2ml4Cells/ml) plant in 48 orifice plates, cultivate 24 Hour.Subsequently calcein be added in 37 DEG C and 5% co2Cultivate 30 minutes under environment, fluorescence with the exciting light of 490nm and The launching light of 520nm is recorded.Cell survival rate is detected and reached more than 90%, do not find significant cytotoxicity, Test result indicate that this gel has good biocompatibility, can as the application of the biomaterials such as cytoskeleton, For example as the timbering material of cultured cartilage cell atdca5.
What prior art was commonly used is acrylamide gel hydrogel, selects the polyacrylamide base glycyl of the present invention Aqueous amine gel, is contrasted therewith.With polypropylene acyl group Aminoacetamide hydrogel pnaga-25, adopt identical work with pnaga-25 As a example skill and formula only replace the polyacrylamide hydrophilic gel of homopolymerization monomer.As shown in Figure 6, the polypropylene acyl group of the present invention The Aminoacetamide hydrogel pnaga-25 and polyacrylamide hydrophilic gel stability test in water and in carbamide, a is polypropylene In deionized water, for pnaga-25 hydrogel in deionized water, c is pnaga-25 hydrogel in 5mol to b to amide hydrogel l-1Aqueous solution of urea in.Experiment shows that this polyacrylamide base Aminoacetamide hydrogel with bisamide group has very Good stability, and this stability is to be produced due to the synergism of amide group hydrogen bond, the present invention with two The polyacrylamide base Aminoacetamide hydrogel of individual amide groups is more excellent than the only acrylamide gel with amide groups has Different performance.Prepare acrylamide gel using identical method, this gel strength too low it is impossible to referred to as high intensity water-setting Glue, in addition puts into acrylamide gel in deionized water and can disintegrate completely after a period of time；And carry the poly- of two amide groups Can very stably there is some months and not change in acrylamido Aminoacetamide hydrogel.
In the monomer amount ranges of technical solution of the present invention, adjustment initiator type/consumption, response time and reaction temperature The technological parameters such as degree, the hydrogel of final preparation is consistent substantially with the property that above-described embodiment is listed.
Above the present invention is done with exemplary description it should illustrate, in the situation of the core without departing from the present invention Under, any simple deformation, modification or other skilled in the art can not spend the equivalent of creative work equal Fall into protection scope of the present invention.

Claims (6)

1. the supramolecular hydrogel based on acryloyl group Aminoacetamide as the application of self-repair material it is characterised in that being based on The supramolecular hydrogel of acryloyl group Aminoacetamide is made up of the polymer with acryloyl group Aminoacetamide as monomer and water, water-setting 55 85%, in the polymer, the side chain of each repetitive is provided with two amide groups to the water content of glue, polymerization Spend for 1,000 5000, repair temperature and be 50 DEG C -90 DEG C, the tensile strength of hydrogel, compressive strength can reach the level of mpa Not.
2. the supramolecular hydrogel based on acryloyl group Aminoacetamide according to claim 1 answering as self-repair material With it is characterised in that the degree of polymerization preferably 2,000 4000.
3. the supramolecular hydrogel based on acryloyl group Aminoacetamide according to claim 1 answering as self-repair material With it is characterised in that being that monomer dissolves under the conditions of aqueous phase by acryloyl group Aminoacetamide, adding initiator, in anoxic condition Under by initiator cause acryloyl group Aminoacetamide carbon-carbon double bond carry out radical polymerization；Described aqueous phase selects deionized water, Or tap water；The consumption of described initiator is 3% the 5% of monomer propylene acyl group Aminoacetamide quality；Described monomer propylene The concentration of acyl group Aminoacetamide is 10 60%, i.e. the quality of acrylamido Aminoacetamide monomer/(acrylamido glycyl The quality of the quality+aqueous phase of amine monomers).
4. the supramolecular hydrogel based on acryloyl group Aminoacetamide according to claim 1 answering as self-repair material With it is characterised in that described initiator be Ammonium persulfate., persulfuric acid, or 2- hydroxy-2-methyl -1- phenyl -1- acetone.
5. the supramolecular hydrogel based on acryloyl group Aminoacetamide according to claim 1 answering as self-repair material With it is characterised in that selecting thermal initiator, then needing to exclude the oxygen in reaction system first with noble gases, to avoid it Inhibition, the then activity according to initiator and consumption, by reaction system be heated to initiator used initiation temperature it Go up and keep 1-5h.
6. the supramolecular hydrogel based on acryloyl group Aminoacetamide according to claim 1 answering as self-repair material With it is characterised in that selecting light trigger, causing radical polymerization under conditions of ultraviolet light, irradiation time is 20 points Clock or 30min-1h.
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