CN108186555A - Shape memory gel with calcium ion complexing and redox double-response and preparation method thereof - Google Patents
Shape memory gel with calcium ion complexing and redox double-response and preparation method thereof Download PDFInfo
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- CN108186555A CN108186555A CN201711384740.XA CN201711384740A CN108186555A CN 108186555 A CN108186555 A CN 108186555A CN 201711384740 A CN201711384740 A CN 201711384740A CN 108186555 A CN108186555 A CN 108186555A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F122/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides or nitriles thereof
- C08F122/10—Esters
- C08F122/1006—Esters of polyhydric alcohols or polyhydric phenols, e.g. ethylene glycol dimethacrylate
Abstract
The invention discloses shape memory gels with calcium ion complexing and redox double-response and preparation method thereof.In terms of mass fraction, shape note hydrogel is dissolved in by 6~30 parts of polysaccharide containing sulfydryl, 12~30 parts of hydrophilic thermoplastic's macromolecules, 0.12~5 part of acrylate, 0.01~0.08 part of initiator in 50~80 parts of water, polymerisation occurs for the unsaturated bond caused by initiator on acrylate, then carries out intermittent warming in the range of 18 DEG C~60 DEG C to polymer and obtains.There is subject hydrogel calcium ion to respond shape-memory properties, redox responds shape-memory properties, and the procedural double-response shape-memory properties of the two, with good shape-memory properties, response condition is mild, good biocompatibility has broad application prospects in bioengineering etc..
Description
Technical field
The present invention relates to a kind of hydrogel and preparation method thereof, more specifically, being related to a kind of modification containing carboxylated polysaccharide, third
There is calcium ion to respond shape-memory properties for olefin(e) acid ester, the high molecular hydrogel of hydrophilic thermoplastic and preparation method thereof, and oxidation is also
Original response shape-memory properties, and can realize procedural response dual above and shape memory function.
Background technology
Hydrogel is the hydrophily and not soluble in water and can absorb large quantity of moisture and (usually contain using water as decentralized medium
Water is more than the 50% of gross mass) there is the macromolecule polymer material of cross-linked structure.As a kind of novel shape memory polymers
Object, after shape memory gel changes its primary condition and fixes under certain conditions, by external condition (as heat, electricity,
Light, chemical co-ordination etc.) stimulation, and its original shape can be restored, there is good biocompatibility, be conducive to environmental protection and
Sustainable development.Therefore, shape memory gel has centainly in many fields such as bioengineering, medicine, textile material
Application prospect.
But many shape memory gels are consolidated mainly using thermal induction by crystallization or glass transition at present
Determine temporary shapes.But in practical applications, temperature is excessively high can cause biological tissue to generate irreversible damage, it is therefore desirable to develop
New shape memory triggering mode is to adapt to the demand of different field.
Invention content
Present invention aims to overcome that deficiency of the thermostimulation response water gel in biologic applications, provides a kind of new preparation
Method, synthesis response condition is mild, good biocompatibility, has the shape memory of calcium ion complexing and redox double-response
Hydrogel.
Supermolecular mechanism has the characteristics that invertibity, dynamic and stimulating responsive are strong, and supermolecular mechanism power is introduced shape
Shape remembers hydrogel, can utilize its stimulating responsive and sensibility to environment, be obtained in fields such as medicine controlled releasing, organizational structures
To being widely applied.In numerous applications, most important is exactly application in terms of medicament slow release.Such as by drug not soluble in water,
Macromolecular drug, vaccine antigen etc. are supported in shape memory gel, then by adjusting the structure of hydrogel, certain
Moment, at the appropriate speed by the drug release of required dosage to human body certain organs or target tissue or even target cell, is realized
The control release of drug.Compared with traditional drug delivery system such as tablet, injection, capsule, which is：It can
To maintain constant blood concentration for a long time, blood concentration " peak valley " phenomenon that frequent drug administration is avoided to generate reduces drug
Toxic side effect.
Subject hydrogel is complexed by calcium ion or redox realizes shape memory function；The either water
Gel passes sequentially through calcium ion complexing and redox realizes shape memory function.The namely shape memory gel energy
In Ca2+Or determining shape is fixed under oxidant effect, and shape can be restored under reducing agent or complexing agent effect.Due to this
The double-response shape memory response condition of class hydrogel is mild, and good biocompatibility can be applied in glutathione in human body
(GSH) intelligent Application of the control release of the lower coating medicine of complex environments effect such as, therefore such hydrogel is in bioengineering
Etc. have broad application prospects.
The purpose of the present invention is achieved by the following technical programs：
Shape memory gel with calcium ion complexing and redox double-response, which is characterized in that with mass parts
Number meter, by 6~30 parts of polysaccharide containing sulfydryl, 12~30 parts of hydrophilic thermoplastic's macromolecules, 0.12~5 part of acrylate, 0.01~
0.08 part of initiator is dissolved in 50~80 parts of water, and polymerisation occurs for the unsaturated bond caused by initiator on acrylate,
Then intermittent warming is carried out in the range of -18 DEG C~60 DEG C to polymer to obtain；
Carboxyl in the shape memory gel can be with the Ca in calcium ion reagent2+Complexing, fixed water-setting occurs
Glue temporary shapes, chelate out calcium ion under the action of complexing agent, and hydrogel is made to be restored to original shape；
Sulfydryl in the shape memory gel can generate cystine linkage in the effect of oxidant and fix the interim shape of hydrogel
Shape, is then reduced to sulfydryl under the action of reducing agent, and hydrogel is restored to original shape；
The shape memory gel fixes hydrogel temporary shapes under the action of calcium ion reagent and oxidant successively,
Then original shape is reverted under the action of reducing agent and complexing agent successively.
Further to realize the object of the invention, it is preferable that the polysaccharide containing sulfydryl is by containing carboxylated polysaccharide and containing amino
Sulfydryl small molecule be dissolved in water, at room temperature, the amino containing the carboxyl on carboxylated polysaccharide and amino-containing sulfydryl small molecule
Condensation forms amide and is obtained by the reaction；In terms of mass fraction, the mass ratio containing carboxylated polysaccharide, amino-containing sulfydryl small molecule and water is
10~25：10~40：40~70.
Preferably, the acrylate for one kind in ethylene glycol dimethacrylate and glycol diacrylate or
Two kinds；Hydrophilic thermoplastic's macromolecule is one or more in polyvinyl alcohol, agar and gelatin.
Preferably, described containing carboxylated polysaccharide is one or more in sodium carboxymethylcellulose, sodium alginate and xanthans.
Preferably, the amino-containing sulfydryl small molecule is mercaptoethylamine hydrochloride, 3- sulfydryl -1- propylamine, 2- aminobenzenes
It is one or more in thiophenol and 4- aminothiophenols.
Preferably, one or two of the initiator for ammonium persulfate and potassium peroxydisulfate.
Preferably, the calcium ion reagent is CaCl2、CaBr2With Ca (NO3)2In it is one or more.
Preferably, the complexing agent is EDTA and Na2CO3One or both of.
Preferably, the oxidant is H2O2, it is sodium bromate, one or more in potassium bromate and sodium perborate；The reduction
Agent is one or both of DTT and cysteine.
The preparation method of the shape memory gel that there is calcium ion complexing and redox double-response, it is special
Sign is：By 6~30 parts of polysaccharide containing sulfydryl, 12~30 parts of hydrophilic thermoplastic's macromolecules, 0.12~5 part of acrylate, 0.01
~0.08 part of initiator is dissolved in 50~80 parts of water, causes the unsaturated bond on acrylate by initiator and polymerization occurs instead
It should；Then intermittent warming is carried out in the range of -18 DEG C~60 DEG C to polymer, obtained double with calcium ion complexing and redox
The shape memory gel responded again.
The present invention will be chemically crosslinked with being physical crosslinking the mode being combined, and utilizes the chemical crosslinking between acrylate and parent
The hydrogen bond formed between hydro-thermal plastic macromolecule maintains the original shape of hydrogel, by containing network between carboxylated polysaccharide and calcium ion
The invertibity of cooperation use and dynamic cystine linkage prepares the shape memory water with calcium ion complexing and redox double-response
Gel.
Hydrogel prepared by the present invention have good biocompatibility and dual-shaped memory function, bioengineering,
The fields such as medicine have certain application prospect.For example, in field of medicine release, as pharmaceutical carrier, by changing condition
Deformation is brought it about, so as to reach drug fixed point release.
Compared with prior art, the invention has the advantages that：
1) subject hydrogel by the disulfide bond compound being widely present in life entity and other with good biological
The polymer substance of compatibility is formed, and has excellent biocompatibility.Meanwhile this hydrogel can be in human body cell GSH water
Flat lower change shape, Drug controlled release are used as the intracellular pharmaceutical carrier for targeting controlled release；
2) the hydrogel response condition that the present invention obtains is mild, and the shape memory work(of hydrogel is realized under conditions of non-thermal
Can, it avoids that temperature is excessively high to generate irreversible damage to biological tissue, is conducive to practical application；
3) hydrogel that the present invention obtains can realize double-response shape memory, and comparison substance response shape memory has
Wider application potential.
Description of the drawings
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of modified sodium alginate in the embodiment of the present invention 1.
Fig. 2 is the song that the storage modulus (G ') of the hydrogel of embodiment 1 and dissipation modulus (G ") change with angular frequency (ω)
Line chart.
Fig. 3 is that the hydrogel of embodiment 1 realizes the process schematic of shape memory under calcium ion complexing.
Fig. 4 is that the hydrogel of embodiment 1 realizes the process schematic of shape memory under redox.
Fig. 5 is the hydrogel of embodiment 1 in calcium ion complexing and the procedural double-response shape memory of redox
Process schematic.
Fig. 6 is 1 gained hydrogel photo of embodiment.
Fig. 7 is 1 gained hydrogel performance test picture of embodiment.
Specific form of construction work
To more fully understand the present invention, with reference to embodiment, the present invention is further illustrated, but the reality of the present invention
It is without being limited thereto to apply mode.
Embodiment 1
By 1g sodium alginates, 4ml water is added in round-bottomed flask, at room temperature after stirring and dissolving 4h, adds in 1.13g sulfydryl second
Amine hydrochlorate, nitrogen drain the air in flask, are stirred under the conditions of being protected from light for 24 hours, modified sodium alginate is obtained by the reaction.Fig. 1 is core
The hydrogen nuclear magnetic resonance spectrogram of modified sodium alginate that magnetic resonance device (IBC Bruker Avance 400, Germany) measures.Solvent peak
Corresponding position be the absorption peak of 4.79ppm, chemical shift 4ppm or so be the absorption peak of hydrogen on sodium alginate, chemical shift
There are two absorption peak at 2.82ppm, 2.90ppm, and integrate than being 1:1, belong to the suction of hydrogen on mercaptoethylmaine methylene
Peak is received, illustrates that mercaptoethylmaine must be successfully grafted on sodium alginate.
0.5g modified sodium alginates, 1g polyvinyl alcohol, 0.01g ethylene glycol dimethacrylates are dissolved in 6.5ml to steam
In the serum bottle of distilled water, 130 μ L tonyred coloring agents are added in, are evenly stirred until bubble-free, add in 2mg ammonium persulfates as initiation
Agent causes ethylene glycol dimethacrylate and polymerisation occurs.Mixture stirs 30min at 60 DEG C, is cooled to room temperature.With
Hydrogel is injected diameter 1mm by syringe, in the silicone tube of length 8cm, is placed in freezing 6h in -18 DEG C of refrigerators, is taken out hydrogel
It is placed at 20 DEG C and thaws, place 1h.Such freeze-thaw recycles 4 times, and a diameter of 1mm is made, water absorption and swelling and it is not soluble in water
, there is certain elastic hydrogel.
Using the modulus of German ThermoFisher companies HAAKE MARS type III rheometer measurement gels, test section half
Diameter is 35mm, and tablet spacing is 0.5mm, and range of scanned frequencies is 0.1~100rad/s.Fig. 2 is the storage modulus of hydrogel
The curve graph that (G ') and dissipation modulus (G ") change with angular frequency (ω).As can be seen that in entire frequency range, storage modulus
G ' is consistently greater than dissipation modulus G ", this shows the essence that hydrogel demonstrates flexibility.
Shape recall tests are done to sample obtained by the present embodiment：
Hydrogel is curved into ' U ' shape under the effect of 0.8N external force, keeps external force constant in 2mol/L CaCl2It is soaked in solution
5s is steeped, hydrogel shape is fixed after removing external force, then ' U ' shape hydrogel is placed in 2mol/L EDTA solution, and hydrogel returns to
Linear.Deformation process is as shown in figure 3, hydrogel is fixed as ' U ' shape by initial configuration and is finally reduced to initial configuration, explanation
There is the hydrogel good calcium ion to respond shape-memory properties.
Hydrogel is curved into square under the effect of 0.8N external force, keeps external force constant in 1mol/L H2O2It is impregnated in solution
3min, hydrogel shape is fixed after removing external force, then square hydrogel is placed in 1mol/L DTT solution, and hydrogel returns to
Linear.Deformation process is said as shown in figure 4, hydrogel is fixed as square by initial configuration and is finally reduced to initial configuration
There is the bright hydrogel preferable redox to respond shape-memory properties.
Hydrogel is curved into ' U ' shape under the effect of 0.8N external force, keeps external force constant in 2mol/L CaCl2It is soaked in solution
30s is steeped, hydrogel shape is fixed after removing external force, then another place of hydrogel is curved ' U ' shape, keeps external force constant,
1mol/L H2O23min is impregnated in solution, hydrogel is fixed as ' S ' shape after removing external force, and the hydrogel after fixation is placed in
In 1mol/L DTT solution, hydrogel returns to ' U ' shape, then the hydrogel is placed in 2mol/L EDTA solution, and hydrogel returns to
Linear.As shown in Fig. 5, hydrogel is fixed as ' S ' shape by initial configuration and is finally reduced to initial configuration deformation process, says
The bright hydrogel has calcium ion complexing, the procedural double-response shape memory function of redox.
Fig. 6 is 1 gained hydrogel photo of embodiment.Fig. 7 is 1 gained hydrogel performance test picture of embodiment.
The hydrogel of the present invention can be used as drug controlled release pharmaceutical carrier.Since GSH is horizontal (about in human body cell
10mmol/L) far above extracellular (about 2mmol/L), glutathione (GSH) can make disulfide bond by redox reaction
Fracture.Therefore, disulfide bond extracellularly can be relatively stabilized, and can be broken after cell is entered.Using this characteristic,
The hydrogel of the present invention can be used as pharmaceutical carrier, and coating medicine, is acted on by oxidant in vitro, is fixed into definite shape.People
The cystine linkage of hydrogel is reduced to mercaptan, changes pharmaceutical carrier shape, so as to fulfill drug intelligence by internal GSH as reducing agent
Energyization, can self-adjustable up to release.
Embodiment 2
By 2g sodium carboxymethylcelluloses, 12ml water is added in round-bottomed flask, at room temperature after stirring and dissolving 4h, adds in 1.25g
3- sulfydryl -1- propylamine, nitrogen drain the air in flask, stir 36h under the conditions of being protected from light, modified carboxy methyl cellulose is obtained by the reaction
Sodium.
0.5g modified carboxy methyl celluloses sodium, 0.5g agar, 0.01g glycol diacrylates are dissolved in 7ml distillations
In the serum bottle of water, 140 μ L tonyred coloring agents are added in, are evenly stirred until bubble-free, add in 0.5mg ammonium persulfates, as drawing
Agent is sent out, causes glycol diacrylate and polymerisation occurs.Mixture stirs 30min at 65 DEG C, is cooled to room temperature.With note
Hydrogel is injected diameter 1mm by emitter, and in the silicone tube of length 8cm, a diameter of 1mm is made, water absorption and swelling and it is not soluble in water,
Hydrogel with certain elasticity.The curve that the storage modulus (G ') and dissipation modulus (G ") of hydrogel change with angular frequency (ω)
It is similar with attached drawing 2.Shape recall tests are done to sample obtained by the present embodiment：
Hydrogel is curved into ' U ' shape under the effect of 1.5N external force, keeps external force constant in 1mol/L CaBr2It is soaked in solution
5s is steeped, hydrogel shape is fixed after removing external force, then ' U ' shape hydrogel is placed in 1mol/L Na2CO3In solution, hydrogel returns
To linear.Deformation process is similar with 1 attached drawing 3 of embodiment.
Hydrogel is curved into square under the effect of 1.5N external force, keeps external force constant in 2.2mol/L bromic acid sodium solutions
3min is impregnated, hydrogel shape is fixed after removing external force, then square hydrogel is placed in 1mol/L DTT solution, water-setting
Glue returns to linear.Deformation process is similar with 1 attached drawing 4 of embodiment.
Hydrogel is curved into ' U ' shape under the effect of 1.5N external force, keeps external force constant in 1mol/L CaBr2It is soaked in solution
30s is steeped, hydrogel shape is fixed after removing external force, then another place of hydrogel is curved ' U ' shape, keeps external force constant,
3min is impregnated in 1mol/L bromic acid sodium solutions, hydrogel is fixed as ' S ' shape after removing external force, and the hydrogel after fixation is placed in
In 1mol/L DTT solution, hydrogel returns to ' U ' shape, then the hydrogel is placed in 2mol/L Na2CO3In solution, hydrogel returns
To linear.Deformation process is similar with 1 attached drawing 5 of embodiment.The application prospect of this implementation is similar to Example 1.
Embodiment 3
By 4g sodium alginates, 15ml water is added in round-bottomed flask, at room temperature after stirring and dissolving 4h, adds in 1.65g 2- ammonia
Base benzenethiol, nitrogen drain the air in flask, stir 36h under the conditions of being protected from light, modified sodium alginate is obtained by the reaction.
1g modified sodium alginates, 1.5g polyvinyl alcohol, 0.02g ethylene glycol dimethacrylates are dissolved in 10ml to steam
In the serum bottle of distilled water, 200 μ L tonyred coloring agents are added in, are evenly stirred until bubble-free, add in 1.5mg ammonium persulfates, as
Initiator causes ethylene glycol dimethacrylate and polymerisation occurs.Mixture stirs 30min at 85 DEG C, is cooled to room
Temperature.Hydrogel is injected into diameter 1mm with syringe, in the silicone tube of length 8cm, freezing 6h in -18 DEG C of refrigerators is placed in, takes out water
Gel, which is placed at 30 DEG C, to thaw, and places 6h.Such freeze-thaw recycles 5 times, and a diameter of 1mm is made, water absorption and swelling and do not dissolve in
Water, there is the hydrogel of certain elasticity.The storage modulus (G ') and dissipation modulus (G ") of hydrogel change with angular frequency (ω)
Curve it is similar with attached drawing 3.Shape recall tests are done to sample obtained by the present embodiment：
Hydrogel is curved into ' U ' shape under the effect of 0.7N external force, keeps external force constant in 3mol/L CaCl2It is soaked in solution
5s is steeped, hydrogel shape is fixed after removing external force, then ' U ' shape hydrogel is placed in 1mol/L EDTA solution, and hydrogel returns to
Linear.Deformation process is similar with 1 attached drawing 3 of embodiment.
Hydrogel is curved into square under the effect of 0.7N external force, keeps external force constant in 2.2mol/L bromic acid potassium solutions
3min is impregnated, hydrogel shape is fixed after removing external force, then square hydrogel is placed in 1mol/L cysteine solutions,
Hydrogel returns to linear.Deformation process is similar with 1 attached drawing 4 of embodiment.
Hydrogel is curved into ' U ' shape under the effect of 0.7N external force, keeps external force constant in 1mol/L CaCl2It is soaked in solution
30s is steeped, hydrogel shape is fixed after removing external force, then another place of hydrogel is curved ' U ' shape, keeps external force constant,
3min is impregnated in 2mol/L bromic acid potassium solutions, hydrogel is fixed as ' S ' shape after removing external force, and the hydrogel after fixation is placed in
In 1mol/L cysteine solutions, hydrogel returns to ' U ' shape, then the hydrogel is placed in 2mol/L EDTA solution, hydrogel
Return to linear.Deformation process is similar with 1 attached drawing 5 of embodiment.The application prospect of this implementation is similar to Example 1.
Embodiment 4
By 1g sodium alginates, 7ml water is added in round-bottomed flask, at room temperature after stirring and dissolving 4h, adds in 0. 5256g 2- ammonia
Base benzenethiol, nitrogen drain the air in flask, are stirred under the conditions of being protected from light for 24 hours, modified sodium alginate is obtained by the reaction.
0.5g modified sodium alginates, 1g polyvinyl alcohol, 0.01g glycol diacrylates are dissolved in 8ml distilled water
In serum bottle, 160 μ L tonyred coloring agents are added in, are evenly stirred until bubble-free, add in 1mg ammonium persulfates, as initiator,
Cause glycol diacrylate and polymerisation occurs.Mixture stirs 30min at 60 DEG C, is cooled to room temperature.Use syringe
Hydrogel is injected into diameter 1mm, in the silicone tube of length 8cm, freezing 6h in -18 DEG C of refrigerators is placed in, takes out hydrogel and be placed in 20
It thaws at DEG C, places 1h.Such freeze-thaw recycles 4 times, and a diameter of 1mm is made, water absorption and swelling and it is not soluble in water, have
The hydrogel of certain elasticity.The storage modulus (G ') and dissipation modulus (G ") of hydrogel with the curve that angular frequency (ω) changes with it is attached
Fig. 2 is similar.Shape recall tests are done to sample obtained by the present embodiment：
Hydrogel is curved into ' U ' shape under the effect of 2.5N external force, keeps external force constant in 1mol/L Ca (NO3)2In solution
5s is impregnated, hydrogel shape is fixed after removing external force, then ' U ' shape hydrogel is placed in 2.2mol/L EDTA solution, hydrogel
Return to linear.Deformation process is similar with 1 attached drawing 3 of embodiment.
Hydrogel is curved into square under the effect of 2.5N external force, keeps external force constant in 1mol/L sodium perborate solution
3min is impregnated, hydrogel shape is fixed after removing external force, then square hydrogel is placed in 1mol/L DTT solution, hydrogel
Return to linear.Deformation process is similar with 1 attached drawing 4 of embodiment.
Hydrogel is curved into ' U ' shape under the effect of 2.5N external force, keeps external force constant in 2mol/L Ca (NO3)2In solution
30s is impregnated, hydrogel shape is fixed after removing external force, then another place of hydrogel is curved ' U ' shape, keeps external force constant,
3min is impregnated in 1mol/L sodium perborate solution, hydrogel is fixed as ' S ' shape after removing external force, and the hydrogel after fixation is placed in
In 1mol/L DTT solution, hydrogel returns to ' U ' shape, then the hydrogel is placed in 2mol/L EDTA solution, and hydrogel returns to
Linear.Deformation process is similar with 1 attached drawing 5 of embodiment.The application prospect of this implementation is similar to Example 1.
Embodiment 5
By 2g xanthans, 10ml water is added in round-bottomed flask, at room temperature after stirring and dissolving 4h, adds in 1.12g 4- aminobenzenes
Thiophenol, nitrogen drain the air in flask, stir 36h under the conditions of being protected from light, modified xantham gum is obtained by the reaction.
0.5g modified xantham gums, 0.8g agar, 0.02g ethylene glycol dimethacrylates are dissolved in 6ml distilled water
In serum bottle, 120 μ L tonyred coloring agents are added in, are evenly stirred until bubble-free, add in 1mg ammonium persulfates, as initiator,
Cause ethylene glycol dimethacrylate and polymerisation occurs.Mixture stirs 30min at 65 DEG C, is cooled to room temperature.With note
Hydrogel is injected diameter 1mm by emitter, and in the silicone tube of length 8cm, a diameter of 1mm is made, water absorption and swelling and it is not soluble in water
, there is certain elastic hydrogel.What the storage modulus (G ') and dissipation modulus (G ") of hydrogel changed with angular frequency (ω)
Curve is similar with attached drawing 2.Shape recall tests are done to sample obtained by the present embodiment：
Hydrogel is curved into ' U ' shape under the effect of 1.5N external force, keeps external force constant in 1mol/L CaCl2It is soaked in solution
5s is steeped, hydrogel shape is fixed after removing external force, then ' U ' shape hydrogel is placed in 1mol/L Na2CO3In solution, hydrogel returns
To linear.Deformation process is similar with 1 attached drawing 3 of embodiment.
Hydrogel is curved into square under the effect of 1.5N external force, keeps that external force is constant to impregnate in 2.2mol/L sodium bromates
3min, hydrogel shape is fixed after removing external force, then square hydrogel is placed in 1mol/L DTT solution, and hydrogel returns to
Linear.Deformation process is similar with 1 attached drawing 4 of embodiment.
Hydrogel is curved into ' U ' shape under the effect of 1.5N external force, keeps external force constant in 1mol/L CaCl2It is soaked in solution
30s is steeped, hydrogel shape is fixed after removing external force, then another place of hydrogel is curved ' U ' shape, keeps external force constant,
3min is impregnated in 1mol/L sodium bromates, hydrogel is fixed as ' S ' shape after removing external force, and the hydrogel after fixation is placed in 1mol/L
In DTT solution, hydrogel returns to ' U ' shape, then the hydrogel is placed in 2mol/L Na2CO3In solution, hydrogel returns to straight line
Shape.Deformation process is similar with 1 attached drawing 5 of embodiment.The application prospect of this implementation is similar to Example 1.
Embodiment 6
By 3.5g sodium alginates, 20ml water is added in round-bottomed flask, at room temperature after stirring and dissolving 4h, adds in 2.12g 2-
Aminothiophenol, nitrogen drain the air in flask, stir 36h under the conditions of being protected from light, modified sodium alginate is obtained by the reaction.
1g modified sodium alginates, 1.45g polyvinyl alcohol, 0.01g glycol diacrylates are dissolved in 10ml distilled water
Serum bottle in, add in 200 μ L tonyred coloring agents, be evenly stirred until bubble-free, 1.5 mg ammonium persulfates are added in, as initiation
Agent causes glycol diacrylate and polymerisation occurs.Mixture stirs 30min at 85 DEG C, is cooled to room temperature.With note
Hydrogel is injected diameter 1mm by emitter, in the silicone tube of length 8cm, is placed in freezing 6h in -18 DEG C of refrigerators, is taken out hydrogel and put
It thaws at 28 DEG C, places 6h.Such freeze-thaw recycles 5 times, and a diameter of 1mm is made, water absorption and swelling and it is not soluble in water,
Hydrogel with certain elasticity.The curve that the storage modulus (G ') and dissipation modulus (G ") of hydrogel change with angular frequency (ω)
It is similar with attached drawing 2.Shape recall tests are done to sample obtained by the present embodiment：
Hydrogel is curved into ' U ' shape under the effect of 1N external force, keeps external force constant in 3mol/L Ca (NO3)2It is soaked in solution
5s is steeped, hydrogel shape is fixed after removing external force, then ' U ' shape hydrogel is placed in 1mol/L EDTA solution, and hydrogel returns to
Linear.Deformation process is similar with 1 attached drawing 3 of embodiment.
Hydrogel is curved into square under the effect of 1N external force, keeps that external force is constant to soak in 1.2mol/L bromic acid potassium solutions
3min is steeped, hydrogel shape is fixed after removing external force, then square hydrogel is placed in 1mol/L cysteine solutions, water
Gel returns to linear.Deformation process is similar with 1 attached drawing 4 of embodiment.
Hydrogel is curved into ' U ' shape under the effect of 1N external force, keeps external force constant in 1mol/L Ca (NO3)2It is soaked in solution
30s is steeped, hydrogel shape is fixed after removing external force, then another place of hydrogel is curved ' U ' shape, keeps external force constant,
3min is impregnated in 1.2mol/L bromic acid potassium solutions, hydrogel is fixed as ' S ' shape after removing external force, and the hydrogel after fixation is placed in
In 1mol/L cysteine solutions, hydrogel returns to ' U ' shape, then the hydrogel is placed in 2mol/L EDTA solution, hydrogel
Return to linear.Deformation process is similar with 1 attached drawing 5 of embodiment.The application prospect of this implementation is similar to Example 1.
The above embodiment of the present invention be only to clearly illustrate example of the present invention, and not be to the present invention
Embodiment restriction.For those of ordinary skill in the art, it can also make on the basis of the above description
Other various forms of variations or variation, any modification made all within the spirits and principles of the present invention, equivalent replacement and
Improve etc., it should be included within the protection domain of the claims in the present invention.
Claims (10)
1. the shape memory gel with calcium ion complexing and redox double-response, which is characterized in that with mass fraction
Meter, by 6~30 parts of polysaccharide containing sulfydryl, 12~30 parts of hydrophilic thermoplastic's macromolecules, 0.12~5 part of acrylate, 0.01~
0.08 part of initiator is dissolved in 50~80 parts of water, and polymerisation occurs for the unsaturated bond caused by initiator on acrylate,
Then intermittent warming is carried out in the range of -18 DEG C~60 DEG C to polymer to obtain；
Carboxyl in the shape memory gel can be with the Ca in calcium ion reagent2+Complexing occurs, fixed hydrogel faces
When shape, calcium ion is chelated out under the action of complexing agent, hydrogel is made to be restored to original shape；
Sulfydryl in the shape memory gel can generate cystine linkage in the effect of oxidant and fix hydrogel temporary shapes, so
Sulfydryl is reduced under the action of reducing agent afterwards, hydrogel is restored to original shape；
The shape memory gel fixes hydrogel temporary shapes under the action of calcium ion reagent and oxidant successively, then
Successively original shape is reverted under the action of reducing agent and complexing agent.
2. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response,
It is characterized in that, the polysaccharide containing sulfydryl is dissolved in water by containing carboxylated polysaccharide and amino-containing sulfydryl small molecule, in room temperature
Under, the amino containing the carboxyl on carboxylated polysaccharide and amino-containing sulfydryl small molecule, which is condensed, to be formed amide and is obtained by the reaction；With mass parts
Number meter, the mass ratio containing carboxylated polysaccharide, amino-containing sulfydryl small molecule and water are 10~25：10~40：40~70.
3. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response,
It is characterized in that, the acrylate is one or both of ethylene glycol dimethacrylate and glycol diacrylate；
Hydrophilic thermoplastic's macromolecule is one or more in polyvinyl alcohol, agar and gelatin.
4. the shape memory gel according to claim 2 with calcium ion complexing and redox double-response,
It is characterized in that, described containing carboxylated polysaccharide is one or more in sodium carboxymethylcellulose, sodium alginate and xanthans.
5. the shape memory gel according to claim 2 with calcium ion complexing and redox double-response,
Be characterized in that, the amino-containing sulfydryl small molecule for mercaptoethylamine hydrochloride, 3- sulfydryl -1- propylamine, 2- aminothiophenols and
It is one or more in 4- aminothiophenols.
6. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response,
It is characterized in that, one or two of the initiator for ammonium persulfate and potassium peroxydisulfate.
7. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response,
It is characterized in that, the calcium ion reagent is CaCl2、CaBr2With Ca (NO3)2In it is one or more.
8. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response,
It is characterized in that, the complexing agent is EDTA and Na2CO3One or both of.
9. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response,
It is characterized in that, the oxidant is H2O2, it is sodium bromate, one or more in potassium bromate and sodium perborate；The reducing agent is
One or both of DTT and cysteine.
10. the shape memory gel according to claim 1 with calcium ion complexing and redox double-response
Preparation method, it is characterised in that：By 6~30 parts of polysaccharide containing sulfydryl, 12~30 parts of hydrophilic thermoplastic's macromolecules, 0.12~5 part
Acrylate, 0.01~0.08 part of initiator are dissolved in 50~80 parts of water, cause the unsaturation on acrylate by initiator
Polymerisation occurs for key；Then intermittent warming is carried out in the range of -18 DEG C~60 DEG C to polymer, obtained with calcium ion complexing
With the shape memory gel of redox double-response.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108992399A (en) * | 2018-09-17 | 2018-12-14 | 郑州大学 | A kind of preparation method and application of the enhanced drug combination system of EPR effect |
| CN109988343A (en) * | 2019-03-18 | 2019-07-09 | 浙江大学 | A kind of alkali soluble chitin-sodium alginate hydrogel material and preparation method thereof with shape memory function |
| CN115323528A (en) * | 2022-08-22 | 2022-11-11 | 东华大学 | Artificial muscle fiber with calcium ion response and preparation method thereof |
| TWI802291B (en) * | 2022-02-23 | 2023-05-11 | 國立清華大學 | Highly compressible shape memory double network hydrogel, use and preparation method thereof, and intervertebral disk scaffold |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102504117A (en) * | 2011-09-27 | 2012-06-20 | 浙江大学 | Aquagel with high water absorbing capacity and preparation method thereof |
| CN104672373A (en) * | 2015-01-26 | 2015-06-03 | 天津大学 | Calcium ion shape memory aquogel and application thereof in differentiation of human mesenchymal stem cell |
-
2017
- 2017-12-20 CN CN201711384740.XA patent/CN108186555B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102504117A (en) * | 2011-09-27 | 2012-06-20 | 浙江大学 | Aquagel with high water absorbing capacity and preparation method thereof |
| CN104672373A (en) * | 2015-01-26 | 2015-06-03 | 天津大学 | Calcium ion shape memory aquogel and application thereof in differentiation of human mesenchymal stem cell |
Non-Patent Citations (4)
| Title |
|---|
| BIDYADHAR MANDAL等: "Synthesis of interpenetrating network hydrogel from poly(acrylic acid-co-hydroxyethyl methacrylate) and sodium alginate: Modeling and kinetics study for removal of synthetic dyes from water", 《CARBOHYDRATE POLYMERS》 * |
| HAO MENG等: "Self-healable macro-/microscopic shape memory hydrogels based on supramolecular interactions", 《CHEM. COMMUN.》 * |
| HIMADRI SEKHAR SAMANTA等: "Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide", 《CARBOHYDRATE POLYMERS》 * |
| 李义等: "二硫键交联的巯基化壳聚糖水凝胶对蛋白质还原响应的控制释放", 《精细化工》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108992399A (en) * | 2018-09-17 | 2018-12-14 | 郑州大学 | A kind of preparation method and application of the enhanced drug combination system of EPR effect |
| CN108992399B (en) * | 2018-09-17 | 2021-04-30 | 郑州大学 | Preparation method and application of EPR effect enhanced combined drug system |
| CN109988343A (en) * | 2019-03-18 | 2019-07-09 | 浙江大学 | A kind of alkali soluble chitin-sodium alginate hydrogel material and preparation method thereof with shape memory function |
| CN109988343B (en) * | 2019-03-18 | 2020-11-13 | 浙江大学 | Alkali-soluble chitosan-sodium alginate hydrogel material with shape memory function and preparation method thereof |
| TWI802291B (en) * | 2022-02-23 | 2023-05-11 | 國立清華大學 | Highly compressible shape memory double network hydrogel, use and preparation method thereof, and intervertebral disk scaffold |
| CN115323528A (en) * | 2022-08-22 | 2022-11-11 | 东华大学 | Artificial muscle fiber with calcium ion response and preparation method thereof |
| CN115323528B (en) * | 2022-08-22 | 2024-04-12 | 东华大学 | Artificial muscle fiber with calcium ion response and preparation method thereof |
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