CN108186555B - Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof - Google Patents

Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof Download PDF

Info

Publication number
CN108186555B
CN108186555B CN201711384740.XA CN201711384740A CN108186555B CN 108186555 B CN108186555 B CN 108186555B CN 201711384740 A CN201711384740 A CN 201711384740A CN 108186555 B CN108186555 B CN 108186555B
Authority
CN
China
Prior art keywords
hydrogel
shape memory
shape
calcium ion
parts
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201711384740.XA
Other languages
Chinese (zh)
Other versions
CN108186555A (en
Inventor
文秀芳
唐林雅
皮丕辉
徐守萍
程江
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
South China University of Technology SCUT
Original Assignee
South China University of Technology SCUT
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by South China University of Technology SCUT filed Critical South China University of Technology SCUT
Priority to CN201711384740.XA priority Critical patent/CN108186555B/en
Publication of CN108186555A publication Critical patent/CN108186555A/en
Application granted granted Critical
Publication of CN108186555B publication Critical patent/CN108186555B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • 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
    • 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
    • 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
    • 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 a shape memory hydrogel with dual responses of calcium ion complexation and oxidation reduction and a preparation method thereof. The shape memory hydrogel is prepared by dissolving 6-30 parts by mass of polysaccharide containing sulfydryl, 12-30 parts by mass of hydrophilic thermoplastic polymer, 0.12-5 parts by mass of acrylic ester and 0.01-0.08 part by mass of initiator in 50-80 parts by mass of water, initiating unsaturated bonds on the acrylic ester to carry out polymerization reaction through the initiator, and then carrying out temperature change treatment on the polymer within the range of-18-60 ℃. The hydrogel has calcium ion response shape memory performance, redox response shape memory performance and programmed dual response shape memory performance of the calcium ion response shape memory performance and the redox response shape memory performance, has good shape memory performance, mild response conditions and good biocompatibility, and has wide application prospects in the aspects of bioengineering and the like.

Description

Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof
Technical Field
The invention relates to hydrogel and a preparation method thereof, in particular to hydrogel of modified carboxyl-containing polysaccharide, acrylic ester and hydrophilic thermoplastic polymer and a preparation method thereof, wherein the hydrogel has calcium ion response shape memory performance and redox response shape memory performance, and can realize the dual programmed response and shape memory functions.
Background
Hydrogels are high molecular weight polymeric materials that are hydrophilic and insoluble in water, and that have a cross-linked structure that can absorb a large amount of water (typically greater than 50% of the total mass). As a novel shape memory polymer, after the initial condition of the shape memory hydrogel is changed and fixed under a certain condition, the shape memory hydrogel can restore the initial shape thereof through the stimulation of external conditions (such as heat, electricity, light, chemical induction and the like), has good biocompatibility, and is beneficial to environmental protection and sustainable development. Therefore, the shape memory hydrogel has certain application prospect in the fields of bioengineering, medicine, textile materials and the like.
However, many shape memory hydrogels currently use primarily thermal induction to fix temporary shapes by crystallization or glass transition. However, in practical applications, the temperature is too high to cause irreversible damage to biological tissues, so that a new shape memory triggering mode needs to be developed to meet the requirements of different fields.
Disclosure of Invention
The invention aims to overcome the defects of thermal stimulation response hydrogel in biological application and provides a novel preparation method, and the shape memory hydrogel which is mild in synthetic response condition, good in biocompatibility and has double responses of calcium ion complexation and redox is synthesized.
The supermolecule effect has the characteristics of reversibility, dynamic property and strong stimulation responsiveness, and the supermolecule acting force is introduced into the shape memory hydrogel, so that the supermolecule acting force can be widely applied to the fields of drug controlled release, tissue architecture and the like by utilizing the stimulation responsiveness and sensitivity of the supermolecule acting force to the environment. Of the many applications, the most important is the use of sustained drug release. For example, water-insoluble drugs, macromolecular drugs, vaccine antigens and the like are loaded in the shape memory hydrogel, and then the drugs with required dosage are released to specific organs or target tissues of a human body or even target cells at a certain moment and at a proper speed by adjusting the structure of the hydrogel, so that the controlled release of the drugs is realized. Compared with the traditional administration systems such as tablets, injections, capsules and the like, the administration mode has the advantages that: can maintain constant blood concentration for a long time, avoid the peak valley phenomenon of the blood concentration caused by frequent administration and reduce the toxic and side effect of the medicament.
The hydrogel realizes the shape memory function through calcium ion complexation or redox; or the hydrogel realizes the shape memory function through calcium ion complexation and redox action in turn. That is, the shape-memory hydrogel can be in Ca2+Or fixed into a determined shape under the action of an oxidizing agent and can recover the shape under the action of a reducing agent or a complexing agent. The hydrogel has mild dual-response shape memory response conditions and good biocompatibility, and can be applied to the intelligent application of controlled release of the coated drug under the action of complex environments such as Glutathione (GSH) in a human body, so the hydrogel has wide application prospects in the aspects of bioengineering and the like.
The purpose of the invention is realized by the following technical scheme:
the shape memory hydrogel with calcium ion complexing and redox dual responses is characterized by being prepared by dissolving 6-30 parts by mass of polysaccharide containing sulfydryl, 12-30 parts by mass of hydrophilic thermoplastic polymer, 0.12-5 parts by mass of acrylic ester and 0.01-0.08 part by mass of initiator in 50-80 parts by mass of water, initiating unsaturated bonds on the acrylic ester to carry out polymerization reaction through the initiator, and carrying out temperature change treatment on a polymer at the temperature of-18-60 ℃;
carboxyl energy in the shape memory hydrogel and Ca in the calcium ion reagent2+Complexing action is carried out, the temporary shape of the hydrogel is fixed, calcium ions are chelated under the action of a complexing agent, and the hydrogel is restored to the original shape;
sulfydryl in the shape memory hydrogel can generate disulfide bonds to fix the temporary shape of the hydrogel under the action of an oxidizing agent, and then the disulfide bonds are reduced into sulfydryl under the action of a reducing agent, so that the hydrogel is restored to the original shape;
the shape memory hydrogel is sequentially fixed in a temporary shape under the action of a calcium ion reagent and an oxidizing agent, and then is sequentially restored to an original shape under the action of a reducing agent and a complexing agent.
To further achieve the object of the present invention, preferably, the thiol-group-containing polysaccharide is obtained by dissolving carboxyl-group-containing polysaccharide and amino-group-containing thiol-group-containing small molecule in water, and condensing carboxyl groups on the carboxyl-group-containing polysaccharide and amino groups of the amino-group-containing thiol-group-containing small molecule at room temperature to form amide reaction; the mass ratio of the carboxyl-containing polysaccharide to the amino-containing sulfydryl micromolecule to water is 10-25: 10-40: 40 to 70.
Preferably, the acrylate is one or both of ethylene glycol dimethacrylate and ethylene glycol diacrylate; the hydrophilic thermoplastic polymer is one or more of polyvinyl alcohol, agar and gelatin.
Preferably, the carboxyl-containing polysaccharide is one or more of sodium carboxymethyl cellulose, sodium alginate and xanthan gum.
Preferably, the amino-containing sulfydryl small molecule is one or more of mercaptoethylamine hydrochloride, 3-sulfydryl-1-propylamine, 2-aminothiophenol and 4-aminothiophenol.
Preferably, the initiator is one or both of ammonium persulfate and potassium persulfate.
Preferably, the calcium ion reagent is CaCl2、CaBr2And Ca (NO)3)2One or more of (a).
Preferably, the complexing agent is EDTA and Na2CO3One or two of them.
Preferably, the oxidant is H2O2One or more of sodium bromate, potassium bromate and sodium perborate; the reducing agent is one or two of DTT and cysteine.
The preparation method of the shape memory hydrogel with the dual responses of calcium ion complexation and redox is characterized by comprising the following steps: dissolving 6-30 parts of polysaccharide containing sulfydryl, 12-30 parts of hydrophilic thermoplastic polymer, 0.12-5 parts of acrylate and 0.01-0.08 part of initiator in 50-80 parts of water, and initiating unsaturated bonds on the acrylate to carry out polymerization reaction through the initiator; then the polymer is subjected to temperature change treatment at the temperature of-18-60 ℃ to obtain the shape memory hydrogel with dual responses of calcium ion complexation and oxidation reduction.
The method combines chemical crosslinking and physical crosslinking, maintains the initial shape of the hydrogel by utilizing hydrogen bonds formed between chemical crosslinking between acrylic esters and hydrophilic thermoplastic polymers, and prepares the shape memory hydrogel with double responses of calcium ion complexing and redox through the complexing action between carboxyl-containing polysaccharide and calcium ions and the reversibility of dynamic disulfide bonds.
The hydrogel prepared by the invention has good biocompatibility and double shape memory functions, and has certain application prospect in the fields of bioengineering, medicine and the like. For example, in the field of drug delivery, the drug carrier is deformed by changing conditions, so as to achieve site-specific drug delivery.
Compared with the prior art, the invention has the following advantages:
1) the hydrogel of the present invention is composed of disulfide bond compounds widely present in living bodies and other high molecular substances having good biocompatibility, and has excellent biocompatibility. Meanwhile, the hydrogel can change the shape under the GSH level of human cells, controls the release of the drug, and can be used as a drug carrier for targeted controlled release in cells;
2) the hydrogel obtained by the invention has mild response conditions, realizes the shape memory function of the hydrogel under the non-thermal condition, avoids the irreversible damage to biological tissues caused by overhigh temperature, and is beneficial to practical application;
3) the hydrogel obtained by the invention can realize double-response shape memory, and has wider application potential compared with single-response shape memory.
Concrete construction method
The present invention will be further described with reference to the following examples for better understanding of the present invention, but the embodiments of the present invention are not limited thereto.
Example 1
Adding 1g of sodium alginate and 4ml of water into a round-bottom flask, stirring and dissolving for 4h at room temperature, adding 1.13g of mercaptoethylamine hydrochloride, exhausting air in the flask by nitrogen, stirring for 24h in a dark condition, and reacting to obtain the modified sodium alginate. The corresponding position of a solvent peak of a nuclear magnetic resonance hydrogen spectrogram of the modified sodium alginate measured by a nuclear magnetic resonance apparatus (IBC Bruker Avance 400, Germany) is 4.79ppm, an absorption peak with a chemical shift of about 4ppm is an absorption peak of hydrogen on the sodium alginate, the chemical shift is 2.82ppm, two absorption peaks are arranged at 2.90ppm, the integral ratio is 1:1, and the absorption peak belongs to the absorption peak of hydrogen on methylene in mercaptoethylamine, which indicates that the mercaptoethylamine is successfully grafted on the sodium alginate.
0.5g of modified sodium alginate, 1g of polyvinyl alcohol and 0.01g of ethylene glycol dimethacrylate are dissolved in a serum bottle of 6.5ml of distilled water, 130 mu L of Sudan red coloring agent is added, the mixture is stirred uniformly until no bubbles exist, and 2mg of ammonium persulfate is added as an initiator to initiate the polymerization reaction of the ethylene glycol dimethacrylate. The mixture was stirred at 60 ℃ for 30min and cooled to room temperature. Injecting hydrogel into a silica gel tube with diameter of 1mm and length of 8cm with an injector, freezing in a refrigerator at-18 deg.C for 6h, taking out hydrogel, thawing at 20 deg.C, and standing for 1 h. The freezing-unfreezing cycle is carried out for 4 times, and the hydrogel with the diameter of 1mm, water absorption swelling property and water insolubility and certain elasticity is prepared.
The modulus of the gel is measured by adopting a model HAAKE MARS III rheometer of German ThermoFisher company, the radius of a test area is 35mm, the distance between flat plates is 0.5mm, and the scanning frequency range is 0.1-100 rad/s. The storage modulus (G ') and the dissipation modulus (G ') of the hydrogel as a function of the angular frequency (ω) can be seen to be consistently greater than the dissipation modulus G ' throughout the frequency range, indicating the nature of the elasticity exhibited by the hydrogel.
The sample obtained in this example was subjected to shape memory testing:
bending hydrogel into 'U' shape under 0.8N external force, and keeping the external force unchanged at 2mol/L CaCl2Soaking in the solution for 5s, removing external force to fix the shape of the hydrogel, and placing the 'U' -shaped hydrogel in 2mol/L EDTA solution to make the hydrogel return to linear shape. During the deformation process, the hydrogel is fixed into a 'U' shape from the initial shape and is finally reduced to the initial shape, which indicates that the hydrogel is solidifiedThe glue has good calcium ion response shape memory performance.
Bending hydrogel into right angle shape under 0.8N external force action, and keeping external force unchanged at 1mol/L H2O2Soaking in the solution for 3min, removing external force, fixing the shape of the hydrogel, and placing the right-angle hydrogel in 1mol/L DTT solution to make the hydrogel return to linear shape. In the deformation process, the hydrogel is fixed into a right-angle shape from the initial shape and is finally reduced into the initial shape, which shows that the hydrogel has better redox response shape memory performance.
Bending hydrogel into 'U' shape under 0.8N external force, and keeping the external force unchanged at 2mol/L CaCl2Soaking in the solution for 30s, removing external force to fix the shape of hydrogel, bending another part of hydrogel into 'U' shape, and keeping external force unchanged at 1mol/L H2O2Soaking in the solution for 3min, removing external force, fixing the hydrogel into 'S' -shape, placing the fixed hydrogel in 1mol/L DTT solution, returning the hydrogel to 'U' -shape, and placing the hydrogel in 2mol/L EDTA solution, and returning the hydrogel to linear shape. In the deformation process, the hydrogel is fixed into an S shape from the initial shape and is finally reduced into the initial shape, which shows that the hydrogel has the double response shape memory functions of calcium ion complexation and redox programming.
The hydrogel of the present invention can be used as a drug controlled release drug carrier. Since the intracellular GSH level (about 10mmol/L) is much higher than the extracellular (about 2mmol/L) in human cells, Glutathione (GSH) can break the disulfide bonds by redox reactions. Thus, disulfide bonds can be relatively stable outside the cell, yet can be broken once inside the cell. By utilizing the characteristics, the hydrogel can be used as a drug carrier, coats drugs in vitro and is fixed into a certain shape under the action of an oxidant. GSH in human body is used as a reducing agent to reduce disulfide bonds of the hydrogel into mercaptan and change the shape of a drug carrier, thereby realizing intelligent and self-regulated release of the drug.
Example 2
Adding 2g of sodium carboxymethylcellulose and 12ml of water into a round-bottom flask, stirring and dissolving for 4 hours at room temperature, adding 1.25g of 3-mercapto-1-propylamine, exhausting air in the flask by using nitrogen, stirring for 36 hours under a dark condition, and reacting to obtain the modified sodium carboxymethylcellulose.
0.5g of modified sodium carboxymethylcellulose, 0.5g of agar and 0.01g of ethylene glycol diacrylate are dissolved in a 7ml distilled water serum bottle, 140 mu L of Sudan red coloring agent is added, the mixture is stirred uniformly until no bubbles exist, 0.5mg of ammonium persulfate is added to serve as an initiator, and the ethylene glycol diacrylate is initiated to carry out polymerization reaction. The mixture was stirred at 65 ℃ for 30min and cooled to room temperature. The hydrogel is injected into a silica gel tube with the diameter of 1mm and the length of 8cm by an injector to prepare the hydrogel with the diameter of 1mm, water-absorbing swelling but water-insoluble property and certain elasticity. The curves of storage modulus (G ') and dissipation modulus (G') of the hydrogel as a function of angular frequency (ω) were similar to those of example 1. The sample obtained in this example was subjected to shape memory testing:
bending hydrogel into U shape under the action of 1.5N external force, and keeping the external force unchanged at 1mol/L CaBr2Soaking in the solution for 5s, removing external force to fix the shape of hydrogel, and placing the 'U' -shaped hydrogel in 1mol/L Na2CO3In solution, the hydrogel returns to a straight line shape. The deformation process was similar to example 1.
Bending the hydrogel into a right-angle shape under the action of 1.5N external force, soaking in 2.2mol/L sodium bromate solution for 3min while keeping the external force unchanged, removing the external force to fix the shape of the hydrogel, and then placing the right-angle hydrogel in 1mol/L DTT solution to enable the hydrogel to return to a straight shape. The deformation process was similar to example 1.
Bending hydrogel into U shape under the action of 1.5N external force, and keeping the external force unchanged at 1mol/L CaBr2Soaking in the solution for 30S, removing external force to fix the shape of hydrogel, bending another part of hydrogel into 'U' -shape, maintaining the external force unchanged, soaking in 1mol/L sodium bromate solution for 3min, removing external force to fix the hydrogel into 'S' -shape, placing the fixed hydrogel in 1mol/L DTT solution, returning the hydrogel to 'U' -shape, and placing the hydrogel in 2mol/L Na2CO3In solution, the hydrogel returns to a straight line shape. The deformation process was similar to example 1. The application prospect of the implementation is similar to that of the embodiment 1.
Example 3
Adding 4g of sodium alginate and 15ml of water into a round-bottom flask, stirring and dissolving for 4h at room temperature, adding 1.65g of 2-aminothiophenol, exhausting air in the flask by using nitrogen, stirring for 36h under a dark condition, and reacting to obtain the modified sodium alginate.
1g of modified sodium alginate, 1.5g of polyvinyl alcohol and 0.02g of ethylene glycol dimethacrylate are dissolved in a serum bottle of 10ml of distilled water, 200 mu L of Sudan red coloring agent is added, the mixture is stirred uniformly until no bubbles exist, 1.5mg of ammonium persulfate is added as an initiator, and the ethylene glycol dimethacrylate is initiated to carry out polymerization reaction. The mixture was stirred at 85 ℃ for 30min and cooled to room temperature. Injecting hydrogel into a silica gel tube with diameter of 1mm and length of 8cm with an injector, freezing in a refrigerator at-18 deg.C for 6h, taking out hydrogel, thawing at 30 deg.C, and standing for 6 h. The freezing-unfreezing cycle is carried out for 5 times, and the hydrogel with the diameter of 1mm, water absorption swelling property and water insolubility and certain elasticity is prepared. The curves of storage modulus (G ') and dissipation modulus (G') of the hydrogel as a function of angular frequency (ω) were similar to those of example 1. The sample obtained in this example was subjected to shape memory testing:
bending hydrogel into 'U' shape under the action of 0.7N external force, and keeping the external force unchanged at 3mol/L CaCl2Soaking in the solution for 5s, removing external force to fix the shape of the hydrogel, and placing the 'U' -shaped hydrogel in 1mol/L EDTA solution to make the hydrogel return to linear shape. The deformation process was similar to example 1.
Bending the hydrogel into a right-angle shape under the action of 0.7N external force, soaking in 2.2mol/L potassium bromate solution for 3min while keeping the external force unchanged, removing the external force to fix the shape of the hydrogel, and then placing the right-angle hydrogel in 1mol/L cysteine solution to enable the hydrogel to return to a straight shape. The deformation process was similar to example 1.
Bending hydrogel into 'U' shape under 0.7N external force, and keeping the external force unchanged at 1mol/L CaCl2Soaking in the solution for 30S, removing external force to fix the shape of the hydrogel, bending the other part of the hydrogel into 'U' -shape, maintaining the external force unchanged, soaking in 2mol/L potassium bromate solution for 3min, removing external force to fix the hydrogel into 'S' -shape, placing the fixed hydrogel in 1mol/L cysteine solutionIn the above step, the hydrogel was returned to the ` U ` shape, and then the hydrogel was placed in a 2mol/L EDTA solution, and the hydrogel was returned to the linear shape. The deformation process was similar to example 1. The application prospect of the implementation is similar to that of the embodiment 1.
Example 4
Adding 1g of sodium alginate and 7ml of water into a round-bottom flask, stirring and dissolving for 4h at room temperature, adding 0.5256g of 2-aminothiophenol, exhausting air in the flask by using nitrogen, stirring for 24h in a dark condition, and reacting to obtain the modified sodium alginate.
0.5g of modified sodium alginate, 1g of polyvinyl alcohol and 0.01g of ethylene glycol diacrylate are dissolved in a serum bottle of 8ml of distilled water, 160 mu L of Sudan red coloring agent is added, the mixture is stirred uniformly until no bubbles exist, 1mg of ammonium persulfate is added to serve as an initiator, and the ethylene glycol diacrylate is initiated to carry out polymerization reaction. The mixture was stirred at 60 ℃ for 30min and cooled to room temperature. Injecting hydrogel into a silica gel tube with diameter of 1mm and length of 8cm with an injector, freezing in a refrigerator at-18 deg.C for 6h, taking out hydrogel, thawing at 20 deg.C, and standing for 1 h. The freezing-unfreezing cycle is carried out for 4 times, and the hydrogel with the diameter of 1mm, water absorption swelling property and water insolubility and certain elasticity is prepared. The curves of storage modulus (G ') and dissipation modulus (G') of the hydrogel as a function of angular frequency (ω) were similar to those of example 1. The sample obtained in this example was subjected to shape memory testing:
bending hydrogel into 'U' shape under the action of 2.5N external force, and keeping the external force constant at 1mol/L Ca (NO)3)2Soaking in the solution for 5s, removing external force to fix the shape of the hydrogel, and placing the 'U' -shaped hydrogel in 2.2mol/L EDTA solution to make the hydrogel return to linear shape. The deformation process was similar to example 1.
Bending the hydrogel into a right-angle shape under the action of 2.5N external force, keeping the external force unchanged, soaking in 1mol/L sodium perborate solution for 3min, removing the external force, fixing the shape of the hydrogel, and then placing the right-angle hydrogel in 1mol/L DTT solution to enable the hydrogel to return to a straight shape. The deformation process was similar to example 1.
Bending hydrogel into 'U' shape under the action of 2.5N external force, and keeping the external force unchanged at 2mol/L Ca (NO)3)2Soaking in the solution for 30s, removingRemoving external force, fixing the shape of the hydrogel, bending the other part of the hydrogel into a 'U' -shape, keeping the external force unchanged, soaking in 1mol/L sodium perborate solution for 3min, removing the external force, fixing the hydrogel into an 'S' -shape, placing the fixed hydrogel in 1mol/L DTT solution, enabling the hydrogel to return to the 'U' -shape, placing the hydrogel in 2mol/L EDTA solution, and enabling the hydrogel to return to the linear shape. The deformation process was similar to example 1. The application prospect of the implementation is similar to that of the embodiment 1.
Example 5
Adding 2g of xanthan gum and 10ml of water into a round-bottom flask, stirring and dissolving for 4 hours at room temperature, adding 1.12g of 4-aminothiophenol, exhausting the air in the flask by nitrogen, stirring for 36 hours in a dark condition, and reacting to obtain the modified xanthan gum.
0.5g of modified xanthan gum, 0.8g of agar and 0.02g of ethylene glycol dimethacrylate are dissolved in a serum bottle of 6ml of distilled water, 120 mu L of Sudan red coloring agent is added, the mixture is stirred uniformly until no bubbles exist, 1mg of ammonium persulfate is added as an initiator, and the ethylene glycol dimethacrylate is initiated to carry out polymerization reaction. The mixture was stirred at 65 ℃ for 30min and cooled to room temperature. The hydrogel is injected into a silica gel tube with the diameter of 1mm and the length of 8cm by an injector to prepare the hydrogel with the diameter of 1mm, water-absorbing swelling but water-insoluble property and certain elasticity. The curves of storage modulus (G ') and dissipation modulus (G') of the hydrogel as a function of angular frequency (ω) were similar to those of example 1. The sample obtained in this example was subjected to shape memory testing:
bending hydrogel into 'U' shape under the action of 1.5N external force, and keeping the external force unchanged at 1mol/L CaCl2Soaking in the solution for 5s, removing external force to fix the shape of hydrogel, and placing the 'U' -shaped hydrogel in 1mol/L Na2CO3In solution, the hydrogel returns to a straight line shape. The deformation process was similar to example 1.
Bending the hydrogel into a right-angle shape under the action of 1.5N external force, soaking in 2.2mol/L sodium bromate for 3min while keeping the external force unchanged, removing the external force to fix the shape of the hydrogel, and then placing the right-angle hydrogel in 1mol/L DTT solution to enable the hydrogel to return to a straight shape. The deformation process was similar to example 1.
Mixing the hydrogelBending into 'U' shape under the action of 1.5N external force, and keeping the external force unchanged at 1mol/L CaCl2Soaking in the solution for 30S, removing external force to fix the shape of hydrogel, bending another part of hydrogel into 'U' -shape, maintaining the external force unchanged, soaking in 1mol/L sodium bromate for 3min, removing external force to fix the hydrogel into 'S' -shape, placing the fixed hydrogel in 1mol/L DTT solution, returning the hydrogel to 'U' -shape, and placing the hydrogel in 2mol/L Na2CO3In solution, the hydrogel returns to a straight line shape. The deformation process was similar to example 1. The application prospect of the implementation is similar to that of the embodiment 1.
Example 6
Adding 3.5g of sodium alginate and 20ml of water into a round-bottom flask, stirring and dissolving for 4 hours at room temperature, adding 2.12g of 2-aminothiophenol, exhausting air in the flask by nitrogen, stirring for 36 hours in a dark condition, and reacting to obtain the modified sodium alginate.
1g of modified sodium alginate, 1.45g of polyvinyl alcohol and 0.01g of ethylene glycol diacrylate are dissolved in a serum bottle of 10ml of distilled water, 200 mu L of Sudan red coloring agent is added, the mixture is stirred uniformly until no bubbles exist, 1.5mg of ammonium persulfate is added to be used as an initiator, and the ethylene glycol diacrylate is initiated to carry out polymerization reaction. The mixture was stirred at 85 ℃ for 30min and cooled to room temperature. Injecting hydrogel into a silica gel tube with diameter of 1mm and length of 8cm with an injector, freezing in a refrigerator at-18 deg.C for 6h, taking out hydrogel, thawing at 28 deg.C, and standing for 6 h. The freezing-unfreezing cycle is carried out for 5 times, and the hydrogel with the diameter of 1mm, water absorption swelling property and water insolubility and certain elasticity is prepared. The curves of storage modulus (G ') and dissipation modulus (G') of the hydrogel as a function of angular frequency (ω) were similar to those of example 1. The sample obtained in this example was subjected to shape memory testing:
bending hydrogel into 'U' shape under the action of 1N external force, and keeping the external force unchanged at 3mol/L Ca (NO)3)2Soaking in the solution for 5s, removing external force to fix the shape of the hydrogel, and placing the 'U' -shaped hydrogel in 1mol/L EDTA solution to make the hydrogel return to linear shape. The deformation process was similar to example 1.
The hydrogel is bent into a right-angle shape under the action of 1N external force, the external force is kept unchanged, the hydrogel is soaked in 1.2mol/L potassium bromate solution for 3min, the shape of the hydrogel is fixed after the external force is removed, then the right-angle hydrogel is placed in 1mol/L cysteine solution, and the hydrogel returns to a straight shape. The deformation process was similar to example 1.
Bending hydrogel into 'U' shape under the action of 1N external force, and keeping the external force unchanged at 1mol/L Ca (NO)3)2Soaking the hydrogel in the solution for 30S, removing the external force, fixing the shape of the hydrogel, bending the other part of the hydrogel into a 'U' -shape, keeping the external force unchanged, soaking the hydrogel in 1.2mol/L potassium bromate solution for 3min, removing the external force, fixing the hydrogel into an 'S' -shape, placing the fixed hydrogel in 1mol/L cysteine solution, returning the hydrogel to the 'U' -shape, placing the hydrogel in 2mol/L EDTA solution, and returning the hydrogel to the straight shape. The deformation process was similar to example 1. The application prospect of the implementation is similar to that of the embodiment 1.
The above examples of the present invention are merely examples for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. Other variations and modifications of the present invention, based on the above teachings, may occur to those of ordinary skill in the art, and it is intended that all such modifications, equivalents and improvements that fall within the spirit and scope of the present invention be included within the scope of the appended claims.

Claims (7)

1. The shape memory hydrogel with calcium ion complexing and redox dual responses is characterized by being prepared by dissolving 6-30 parts by mass of polysaccharide containing sulfydryl, 12-30 parts by mass of hydrophilic thermoplastic polymer, 0.12-5 parts by mass of acrylic ester and 0.01-0.08 part by mass of initiator in 50-80 parts by mass of water, initiating unsaturated bonds on the acrylic ester to carry out polymerization reaction through the initiator, and carrying out temperature change treatment on a polymer at the temperature of-18-60 ℃; the sulfhydryl-containing polysaccharide is obtained by dissolving carboxyl-containing polysaccharide and amino-containing sulfhydryl micromolecules in water, and condensing carboxyl on the carboxyl-containing polysaccharide and amino of the amino-containing sulfhydryl micromolecules at room temperature to form an amide reaction; the mass ratio of the carboxyl-containing polysaccharide to the amino-containing sulfydryl micromolecule to water is 10-25: 10-40: 40-70; the carboxyl-containing polysaccharide is one or more of sodium carboxymethylcellulose, sodium alginate and xanthan gum; the amino-containing sulfydryl micromolecules are one or more of sulfydryl ethylamine hydrochloride, 3-sulfydryl-1-propylamine, 2-amino thiophenol and 4-amino thiophenol; the hydrophilic thermoplastic polymer is polyvinyl alcohol or agar;
carboxyl energy in the shape memory hydrogel and Ca in the calcium ion reagent2+Complexing action is carried out, the temporary shape of the hydrogel is fixed, calcium ions are chelated under the action of a complexing agent, and the hydrogel is restored to the original shape;
sulfydryl in the shape memory hydrogel can generate disulfide bonds to fix the temporary shape of the hydrogel under the action of an oxidizing agent, and then the disulfide bonds are reduced into sulfydryl under the action of a reducing agent, so that the hydrogel is restored to the original shape;
the shape memory hydrogel fixes the temporary shape of the hydrogel under the action of a calcium ion reagent and an oxidizing agent in sequence, then recovers to the original shape under the action of a reducing agent and a complexing agent in sequence,
the polymer is subjected to temperature change treatment at the temperature of between 18 ℃ below zero and 60 ℃ below zero, namely, hydrogel is injected into a silica gel tube with the diameter of 1mm and the length of 8cm by using an injector, the silica gel tube is placed in a refrigerator at the temperature of 18 ℃ below zero for freezing for 6 hours, the hydrogel is taken out and unfrozen at the temperature of 20 ℃ or 28 ℃ or 30 ℃, and the hydrogel is placed for 1 hour or 6 hours; such freeze-thaw cycles are 4 or 5 times.
2. The shape memory hydrogel with calcium ion complexation and redox dual response of claim 1, wherein the acrylate is one or both of ethylene glycol dimethacrylate and ethylene glycol diacrylate.
3. The shape memory hydrogel according to claim 1, wherein the initiator is one or both of ammonium persulfate and potassium persulfate.
4. The composition of claim 1 having a calcium ion complexing and redox coupleThe shape memory hydrogel with re-response is characterized in that the calcium ion reagent is CaCl2、CaBr2And Ca (NO)3)2One or more of (a).
5. The shape memory hydrogel according to claim 1, wherein the complexing agent is EDTA and Na2CO3One or two of them.
6. The shape memory hydrogel according to claim 1, wherein the oxidizing agent is H2O2One or more of sodium bromate, potassium bromate and sodium perborate; the reducing agent is one or two of DTT and cysteine.
7. The method for preparing a shape memory hydrogel having a dual response of calcium ion complexation and redox according to claim 1, wherein: dissolving 6-30 parts of polysaccharide containing sulfydryl, 12-30 parts of hydrophilic thermoplastic polymer, 0.12-5 parts of acrylate and 0.01-0.08 part of initiator in 50-80 parts of water, and initiating unsaturated bonds on the acrylate to carry out polymerization reaction through the initiator; then the polymer is subjected to temperature change treatment at the temperature of-18-60 ℃ to obtain the shape memory hydrogel with dual responses of calcium ion complexation and oxidation reduction.
CN201711384740.XA 2017-12-20 2017-12-20 Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof Active CN108186555B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201711384740.XA CN108186555B (en) 2017-12-20 2017-12-20 Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201711384740.XA CN108186555B (en) 2017-12-20 2017-12-20 Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof

Publications (2)

Publication Number Publication Date
CN108186555A CN108186555A (en) 2018-06-22
CN108186555B true CN108186555B (en) 2020-11-24

Family

ID=62576962

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201711384740.XA Active CN108186555B (en) 2017-12-20 2017-12-20 Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof

Country Status (1)

Country Link
CN (1) CN108186555B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108992399B (en) * 2018-09-17 2021-04-30 郑州大学 Preparation method and application of EPR effect enhanced combined drug system
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
CN115323528B (en) * 2022-08-22 2024-04-12 东华大学 Artificial muscle fiber with calcium ion response and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
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 (2)

* Cited by examiner, † Cited by third party
Title
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;Bidyadhar Mandal等;《Carbohydrate Polymers》;20130610;第257-269页 *
Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide;Himadri Sekhar Samanta等;《Carbohydrate Polymers》;20130907;第666-678页 *

Also Published As

Publication number Publication date
CN108186555A (en) 2018-06-22

Similar Documents

Publication Publication Date Title
CN108186555B (en) Shape memory hydrogel with calcium ion complexing and redox dual responses and preparation method thereof
Lu et al. The formation mechanism of hydrogels
CN110128682B (en) Sulfhydryl-aldehyde crosslinking hydrogel material and preparation method and application thereof
Mahinroosta et al. Hydrogels as intelligent materials: A brief review of synthesis, properties and applications
Brannon-Peppas Preparation and characterization of crosslinked hydrophilic networks
CN110698697B (en) Preparation method of polyethyleneimine-polyvinyl alcohol hydrogel with self-healing performance
CN108676178B (en) Preparation method of modified polysaccharide hydrogel and prepared modified polysaccharide hydrogel
Gajra⃰⃰⃰⃰ et al. Poly vinyl alcohol hydrogel and its pharmaceutical and biomedical applications: A review
KARADAĞ et al. Swelling of superabsorbent acrylamide/sodium acrylate hydrogels prepared using multifunctional crosslinkers
Liu et al. Homogeneous and real super tough multi-bond network hydrogels created through a controllable metal ion permeation strategy
JP6085887B2 (en) Gels and hydrogels
Nagam et al. A comprehensive review on hydrogels
CN108192020B (en) Preparation method of intelligent zwitterionic polymer material
Işıklan et al. Synthesis and characterization of pH-and temperature-sensitive materials based on alginate and poly (N-isopropylacrylamide/acrylic acid) for drug delivery
Awasthi et al. Nanoparticle-reinforced polyacrylamide hydrogel composites for clinical applications: a review
CN106084278A (en) A kind of semi-intercrossing network nanometer heterozygosis hydrogel and its preparation method and application
Kumar et al. Synthetic polymer hydrogels
CN113667141A (en) Alginate hydrogel for resisting protein adhesion and preparation method and application thereof
CN106188584B (en) A kind of derivatives of hyaluronic acids hydrogel and preparation method thereof
CN112089685B (en) Preparation method of temperature response type bacterial cellulose antibacterial nanogel
Chatterjee et al. A detailed discussion on interpenetrating polymer network (IPN) based drug delivery system for the advancement of health care system
CN102127234A (en) Method for preparing intumescent hydrogel
CA2878051A1 (en) Strain-promoted crosslinking of peg-based hydrogels via copper-free cycloaddition
CN108003266B (en) A kind of quadruple stimuli responsive polyaminoacid nanogel and its preparation method and application
Fellin et al. Direct-Ink Write 3D Printing Multistimuli-Responsive Hydrogels and Post-Functionalization Via Disulfide Exchange

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant