CN115109368B - Nano composite hydrogel and preparation method and application thereof - Google Patents
Nano composite hydrogel and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a nano composite hydrogel and a preparation method and application thereof, wherein the nano composite hydrogel comprises nano lithium alginate, sodium polyacrylate, guanylated cyclodextrin and adamantane modified PEG, a crosslinked network of the hydrogel is formed by utilizing interaction of electrostatic interaction and a host object, and the prepared hydrogel has better shear thinning, self-repairing and injectability through rheology tests and injectability tests, and gel modulus can be properly regulated and controlled through the proportion of each component. Compared with the prior art, the invention avoids the traditional gel based on nano-lithium algae soil from forming gel in a chemical crosslinking mode in the preparation aspect, realizes the formation of a gel network only through two physical interactions, is initiated in the aspect of gel formation mechanism, and has the advantages of environmental protection, no toxicity and easy operation in the gel preparation process.
Description
Technical Field
The invention relates to the field of hydrogel preparation, in particular to a nano composite hydrogel and a preparation method and application thereof.
Background
Hydrogels are widely used in various fields due to good biocompatibility and similarity to human soft tissues, are important biomedical materials, and have been widely used in drug carriers, cell carriers, auxiliary materials, facial masks, cosmetic substrates, artificial corneas and the like. In recent years, the development of nano composite hydrogel aiming at nano lithium algae soil is widely focused, and the nano lithium algae soil has better gel forming property, and the obtained gel has the properties of high transparency, high water content, high ductility, elasticity and the like and is widely applied.
Patent CN200710027522.0 discloses a nano-hydrogel material, and its preparation method and use, the nano-hydrogel material adopts a combination method of intercalation and reversible addition-fragmentation chain transfer free radical polymerization, the nano-hydrogel material is obtained by adding monomers, initiator, cross-linking agent, chain transfer agent and montmorillonite into an organic solvent system, and adopting a method of reversible addition-fragmentation chain transfer free radical polymerization in the presence of initiator.
Patent CN 201410199308.3 discloses a preparation method of a dendritic organic montmorillonite reinforced hydrogel, which uses organic montmorillonite as a physical crosslinking agent, introduces a dendritic polymer into poly (N-isopropyl acrylamide) hydrogel, and combines the two polymers together by utilizing an Atom Transfer Radical Polymer (ATRP) technology to prepare the dendritic organic montmorillonite reinforced hydrogel.
Patent CN 201610821356.0 discloses a method for preparing double-physical cross-linked self-repairing hydrogel. The invention prepares HPAAM/MMT composite hydrogel by Mixing Montmorillonite (MMT), acrylamide (AM), hydrophobic monomer octadecyl methacrylate (SMA) and sodium dodecyl benzene sulfonate (SOBS) as main raw materials, and in-situ polymerizing the precursor liquid obtained after blending by micelle.
In the prior art, the nano-lithium algae soil gel is mostly glued in a chemical crosslinking mode in the aspect of preparation, and the problem that the hydrogel converted from gel to sol can only be in an ultraviolet light wave band in a light response wavelength range by utilizing common non-substituted azobenzene photoisomerization is solved, so that the nano-lithium algae soil gel has some potential undiscovered biosafety risks.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a nano composite hydrogel and a preparation method and application thereof.
The aim of the invention can be achieved by the following technical scheme:
the first object of the invention is to provide a nano composite hydrogel which contains nano lithium alginate, sodium polyacrylate, adamantane modified PEG and guanidyl cyclodextrin, and thus has a gel network structure.
Preferably, the ratio of the components in the nanocomposite hydrogel is as follows: the mass fraction of the nano lithium algae soil is 1-10%, the mass fraction of the sodium polyacrylate is 0.02-0.1%, the mass fraction of the guanylated cyclodextrin is 0.03-0.25%, the mass fraction of the adamantane modified PEG is 0.09-0.72%, and the balance is water.
Preferably, the nano-lithiumalga soil is selected from one of commercial Laponite XLG, laponite RD, laponite RDS, laponite S482, laponite SL25, laponite EP, laponite JS, laponite XLS, laponite XL21 and Laponite D, which are all manufactured by Pick Germany.
Preferably, the weight average molecular weight of the sodium polyacrylate is one or more of 1000-5000000.
Preferably, the adamantane modified PEG is one or more of linear PEG, three-arm PEG, four-arm PEG and eight-arm PEG, the molecular weight of the adamantane modified PEG is one or more of 5000, 10000, 20000 and 40000, and the modification rate of adamantane to the end group of PEG is one or more of 60%,70%,80%,90% and 100%.
Preferably, the guanylated cyclodextrin is one or more of alpha-guanidyl cyclodextrin, beta-guanidyl cyclodextrin and gamma-guanidyl cyclodextrin, and the degree of substitution of the guanidyl functional group is mono-to full-substitution.
The second object of the present invention is to provide a method for preparing the nanocomposite hydrogel, which specifically comprises the following steps:
(1) Firstly, slowly adding nano lithium algae soil into high-speed mechanically stirred pure water in batches, wherein the rotating speed is 1000-1500r/min, and the duration is about 10-20 minutes until colorless transparent nano dispersion liquid is formed;
(2) Slowly adding the sodium polyacrylate aqueous solution into the nano dispersion liquid in the step (1), and continuously stirring for 10-20 minutes at the rotating speed of 900-1500r/min until a stable colorless transparent nano dispersion liquid is formed;
(3) Under the condition that the rotating speed is unchanged, dropwise adding the guanylate cyclodextrin water solution into the solution in the step (2) while stirring, and continuously stirring for 5-10 minutes after adding;
(4) Under the condition of unchanged rotating speed, dropwise adding the adamantane modified PEG aqueous solution into the solution in the step (3) while stirring, and continuously stirring for 5-10 minutes after adding;
(5) After all the above steps are completed, the obtained pre-gel solution is kept stand on a table surface for about 1 to 24 hours, and then stable nano composite hydrogel can be obtained.
Preferably, the preparation method of the adamantane modified PEG specifically comprises the following steps:
(1) Preparation of carboxyl-terminated PEG: dissolving PEG in toluene solution, performing azeotropic distillation to remove water at 140 ℃ under normal pressure, pumping and air-exchanging the reaction device for three times after the completion of the reaction, enabling the reaction device to be in an inert gas state, adding anhydrous dichloromethane and succinic anhydride serving as reaction solvents, placing the reaction device in an ice bath, stirring, dissolving 4-dimethylaminopyridine serving as a reaction catalyst in the anhydrous dichloromethane, slowly adding the reaction catalyst into the previous mixed solution through a microinjection pump, controlling the dropwise adding time to be about 2 hours, enabling the reaction to react for 4 hours under the ice bath condition, removing the ice bath, enabling the reaction solution to continue to react for 24 hours under normal temperature condition, transferring all the reaction solution to a rotary evaporation flask after the reaction is completed, concentrating the reaction solution through a rotary evaporator, adding deionized water, stirring, adjusting pH to an acid range of 2-4 and the like through hydrochloric acid, adding dichloromethane for extraction, saturated salt water for washing, finally collecting an organic phase, drying through anhydrous sodium sulfate for 12 hours, filtering, concentrating the filtrate through a rotary evaporator, settling through anhydrous diethyl ether, and suction filtering, and drying to obtain carboxyl-terminated PEG compound;
(2) Preparation of adamantane modified PEG: adding carboxyl-terminated PEG into a reaction bottle, heating to 120 ℃, simultaneously starting an oil pump to perform vacuum pumping and water removal for 2 hours, then cooling the system to room temperature, dissolving carboxyl-terminated PEG by using anhydrous DMF and anhydrous DCM added into the reaction bottle, adding N-hydroxybutyryl imine and EDC, stirring the reaction solution at room temperature overnight, then adding triethylamine and 1-amantadine into the reaction solution, continuing stirring and reacting for two days at room temperature, washing with dilute hydrochloric acid solution for three times, washing with saturated saline solution for three times, merging the water phases, extracting once, combining the organic phases, drying overnight with anhydrous sodium sulfate, filtering to remove inorganic salts, concentrating the solution by using a rotary evaporator, settling by using anhydrous diethyl ether, performing suction filtration, and drying to obtain the adamantane modified PEG compound.
Preferably, the preparation method of the guanidyl cyclodextrin specifically comprises the following steps:
1) Preparation of bromocyclodextrin: the purchased beta-cyclodextrin was dried with an oven, followed by the following experimental procedure: dissolving triphenylphosphine in anhydrous DMF, cooling to 0deg.C under stirring, dissolving N-bromobutyrylimine in anhydrous DMF, dropwise adding NBS solution into the stirring triphenylphosphine solution under nitrogen protection, controlling dropwise speed for 30min, dissolving dried beta-cyclodextrin in anhydrous DMF, and collecting Ph 3 The P/NBS mixed solution is added into the beta-cyclodextrin solution drop by drop at room temperature, after the drop is finished, the temperature of the reaction system is raised to 80 ℃ to ensure that the brown solution presented by the reaction system is N at 80 DEG C 2 Continuously reacting for 5 hours in the atmosphere, after the reaction is finished, adding a methanol solution into the reaction solution at room temperature, continuously stirring for 30 minutes, cooling the reacted solution to-15 ℃ by utilizing an ice salt bath, adjusting the pH value of the system to 9 by utilizing sodium methoxide at the temperature, continuously stirring for 1 hour, finally pouring the reacted mixed solution into 1L of ice water which is being stirred to form a large amount of precipitate, filtering the precipitate, washing by utilizing methanol, and drying to finally obtain the brominated cyclodextrin;
2) Preparation of cyclodextrin azide: dissolving bromocyclodextrin in anhydrous DMF, adding sodium azide, stirring the suspension of the bromocyclodextrin and the sodium azide in nitrogen atmosphere of 60-80 ℃ for reaction for 24 hours, concentrating the reacted solution by using a rotary evaporator, settling by a large amount of ice water, carrying out suction filtration on the settled solid, washing and drying to finally obtain the cyclodextrin azide;
3) Preparation of an aminated cyclodextrin: dissolving cyclodextrin azide in anhydrous DMF, adding triphenylphosphine, observing nitrogen bubbles gradually generated in a reaction bottle after adding for about one hour, gradually disappearing the generated nitrogen bubbles, adding 35wt% of concentrated ammonia water into the system dropwise, changing the reaction system to be beige after adding, continuously stirring at room temperature for 18 hours, concentrating the reaction solution by a rotary evaporator, settling by ethanol, washing the sediment by ethanol, and then carrying out vacuum drying on the obtained product to obtain the aminated cyclodextrin;
4) Preparation of guanylated cyclodextrin: dissolving aminated cyclodextrin as free base in anhydrous DMF, adding into a mixed solution composed of 1H-pyrazole-formamidine hydrochloride and diisopropylethylamine, reacting the whole system in nitrogen atmosphere at 60-80 ℃ for 8H, adding repeated equivalent of 1H-pyrazole-formamidine hydrochloride and diisopropylethylamine again, continuing to react in nitrogen atmosphere for 14H, adding diethyl ether dropwise into the solution after the reaction is finished, forming suspension, continuing stirring for 2H, standing for a period of time, pouring out supernatant, collecting viscous solid in a bottle, dissolving the viscous solid in a small amount of deionized water, adding ethanol into a reaction bottle, immediately forming a large amount of white precipitate, concentrating the precipitate at the bottom of a centrifuge tube by centrifugation, pouring out supernatant, dissolving the bottom solid in a proper amount of deionized water, dialyzing for 24H by a dialysis bag with a cut-off molecular weight of 100-500, and freeze-drying the solution after the dialysis is finished to obtain the guanylated cyclodextrin.
Compared with the prior art, the invention has the following beneficial effects:
firstly, the invention avoids the traditional gel based on nano lithium algae clay, which is formed into gel in the aspect of preparation by mostly utilizing chemical crosslinking, the invention realizes the formation of gel network by only two physical interactions, the gel forming mechanism aspect is the initiative, the gel preparation process is environment-friendly and nontoxic, the operation is easy, and the problems of small molecular monomer residue, catalyst residue and the like caused by insufficient crosslinking reaction are not brought, thus realizing the separate proceeding of raw material preparation and gel preparation.
Second, the nano-lithium alginate physical cross-linked hydrogel prepared by the method has good biocompatibility, wherein each component in the gel has been proved to have good biosafety, and the content of each component is also at a low level on the basis, so that even if some potential undiscovered biosafety risks exist, the content can be reduced or avoided as much as possible.
Thirdly, the nano lithium alginate physical cross-linked hydrogel prepared by the method has good shear thinning characteristic and self-repairing characteristic, the organic combination of the two points can lead the gel to have good injectability and the characteristic of quickly recovering into gel after injection, and the storage modulus and the energy consumption modulus of the gel can be well regulated and controlled by adjusting the proportion of each component of the gel.
Fourth, the prepared nano-lithium alginate physical crosslinked hydrogel prepared by the invention has good properties, and is expected to have good development prospects in the biomedical fields such as drug carriers, tissue engineering scaffolds and other cell carriers, masks, cosmetic substrates, biological 3D printing substrates and the like.
Drawings
Fig. 1 is a mechanism diagram of nano-lithium alginate physical cross-linked hydrogel formation provided by the invention.
FIG. 2 is a graph showing the results of the rheological test of the gel in example 1.
FIG. 3 is a graph showing the results of the gel injectability test in example 1.
Detailed Description
In the conception process of the technical scheme, the nano-lithium algae soil (Laponite) has high charge loading, namely, a great amount of negative charges carried on the surface of the nano-lithium algae soil (Laponite) are utilized to carry out electrostatic interaction with the guanidine cyclodextrin with positive charges, which is synthesized through a series of chemical reactions, and meanwhile, two physical interactions are utilized to carry out main object interactions between adamantane and the cyclodextrin, so that the nano-composite hydrogel with high water content is prepared, and meanwhile, the self-aggregation of the nano-lithium algae soil (Laponite) is easy to occur because the self-structure edge of the nano-lithium algae soil (Laponite) also has positive charges, and in order to ensure the dispersion process and the stability after dispersion, the positive charges on the neutralization edge of sodium polyacrylate are adopted, so that the nano-lithium algae soil can be always in a nano-dispersion state, and the integrity of a gel percolation network and the structural consistency are ensured. In addition, compared with other patents, the invention does not involve direct chemical crosslinking reaction in the gel preparation process, the hydrogel is directly obtained only by two physical interactions, the content of each component is at a lower level, and the whole gel takes water as the main component, thus the invention has the technical characteristics of green and environmental protection.
The invention will now be described in detail with reference to the drawings and specific examples. In the technical scheme, the characteristics of preparation means, materials, structures or composition ratios and the like which are not explicitly described are regarded as common technical characteristics disclosed in the prior art.
Example 1
The preparation method of the adamantane modified PEG in the scheme specifically comprises the following steps:
(1) Preparation of carboxyl-terminated PEG: dissolving PEG in toluene solution, performing azeotropic distillation to remove water at 140 ℃ under normal pressure, pumping and air-exchanging the reaction device for three times after the completion of the reaction, enabling the reaction device to be in an inert gas state, adding anhydrous dichloromethane and succinic anhydride serving as reaction solvents, placing the reaction device in an ice bath, stirring, dissolving 4-dimethylaminopyridine serving as a reaction catalyst in the anhydrous dichloromethane, slowly adding the reaction catalyst into the previous mixed solution through a microinjection pump, controlling the dropwise adding time to be about 2 hours, enabling the reaction to react for 4 hours under the ice bath condition, removing the ice bath, enabling the reaction solution to continue to react for 24 hours under normal temperature condition, transferring all the reaction solution to a rotary evaporation flask after the reaction is completed, concentrating the reaction solution through a rotary evaporator, adding deionized water, stirring, adjusting pH to an acid range of 2-4 and the like through hydrochloric acid, adding dichloromethane for extraction, saturated salt water for washing, finally collecting an organic phase, drying through anhydrous sodium sulfate for 12 hours, filtering, concentrating the filtrate through a rotary evaporator, settling through anhydrous diethyl ether, and suction filtering, and drying to obtain carboxyl-terminated PEG compound;
(2) Preparation of adamantane modified PEG: adding carboxyl-terminated PEG into a reaction bottle, heating to 120 ℃, simultaneously starting an oil pump to perform vacuum pumping and water removal for 2 hours, then cooling the system to room temperature, dissolving carboxyl-terminated PEG by using anhydrous DMF and anhydrous DCM added into the reaction bottle, adding N-hydroxybutyryl imine and EDC, stirring the reaction solution at room temperature overnight, then adding triethylamine and 1-amantadine into the reaction solution, continuing stirring and reacting for two days at room temperature, washing with dilute hydrochloric acid solution for three times, washing with saturated saline solution for three times, merging the water phases, extracting once, combining the organic phases, drying overnight with anhydrous sodium sulfate, filtering to remove inorganic salts, concentrating the solution by using a rotary evaporator, settling by using anhydrous diethyl ether, performing suction filtration, and drying to obtain the adamantane modified PEG compound.
The preparation method of the guanidyl cyclodextrin in the scheme specifically comprises the following steps:
1) Preparation of bromocyclodextrin: the purchased beta-cyclodextrin was dried with an oven, followed by the following experimental procedure: dissolving triphenylphosphine in anhydrous DMF, cooling to 0deg.C under stirring, dissolving N-bromobutyrylimine in anhydrous DMF, dropwise adding NBS solution into the stirring triphenylphosphine solution under nitrogen protection, controlling dropwise speed for 30min, dissolving dried beta-cyclodextrin in anhydrous DMF, and collecting Ph 3 The P/NBS mixed solution is added into the beta-cyclodextrin solution drop by drop at room temperature, after the drop is finished, the temperature of the reaction system is raised to 80 ℃ to ensure that the brown solution presented by the reaction system is N at 80 DEG C 2 Continuously reacting for 5 hours in the atmosphere, after the reaction is finished, adding a methanol solution into the reaction solution at room temperature, continuously stirring for 30 minutes, cooling the reacted solution to-15 ℃ by utilizing an ice salt bath, adjusting the pH value of the system to 9 by utilizing sodium methoxide at the temperature, continuously stirring for 1 hour, finally pouring the reacted mixed solution into 1L of ice water which is being stirred to form a large amount of precipitate, filtering the precipitate, washing by utilizing methanol, and drying to finally obtain the brominated cyclodextrin;
2) Preparation of cyclodextrin azide: dissolving bromocyclodextrin in anhydrous DMF, adding sodium azide, stirring the suspension of the bromocyclodextrin and the sodium azide in nitrogen atmosphere of 60-80 ℃ for reaction for 24 hours, concentrating the reacted solution by using a rotary evaporator, settling by a large amount of ice water, carrying out suction filtration on the settled solid, washing and drying to finally obtain the cyclodextrin azide;
3) Preparation of an aminated cyclodextrin: dissolving cyclodextrin azide in anhydrous DMF, adding triphenylphosphine, observing nitrogen bubbles gradually generated in a reaction bottle after adding for about one hour, gradually disappearing the generated nitrogen bubbles, adding 35wt% of concentrated ammonia water into the system dropwise, changing the reaction system to be beige after adding, continuously stirring at room temperature for 18 hours, concentrating the reaction solution by a rotary evaporator, settling by ethanol, washing the sediment by ethanol, and then carrying out vacuum drying on the obtained product to obtain the aminated cyclodextrin;
4) Preparation of guanylated cyclodextrin: dissolving aminated cyclodextrin as free base in anhydrous DMF, adding into a mixed solution composed of 1H-pyrazole-formamidine hydrochloride and diisopropylethylamine, reacting the whole system in nitrogen atmosphere at 60-80 ℃ for 8H, adding repeated equivalent of 1H-pyrazole-formamidine hydrochloride and diisopropylethylamine again, continuing to react in nitrogen atmosphere for 14H, adding diethyl ether dropwise into the solution after the reaction is finished, forming suspension, continuing stirring for 2H, standing for a period of time, pouring out supernatant, collecting viscous solid in a bottle, dissolving the viscous solid in a small amount of deionized water, adding ethanol into a reaction bottle, immediately forming a large amount of white precipitate, concentrating the precipitate at the bottom of a centrifuge tube by centrifugation, pouring out supernatant, dissolving the bottom solid in a proper amount of deionized water, dialyzing for 24H by a dialysis bag with a cut-off molecular weight of 100-500, and freeze-drying the solution after the dialysis is finished to obtain the guanylated cyclodextrin.
The preparation steps of the nanocomposite hydrogel in this example were as follows:
1) Firstly, 100mg of nano-lithium algae soil (Laponite XLG) is slowly added into 3mL of high-speed mechanically stirred pure water in batches, the rotating speed is 1500r/min, the duration is about 20 minutes, and colorless transparent nano-dispersion liquid is formed;
2) Adding 1mL of sodium polyacrylate (molecular weight MW 2100 or so) aqueous solution (3 mg/mL) into the nano dispersion liquid, and continuously stirring at the rotating speed of 900r/min for 10 minutes until a stable colorless transparent nano dispersion liquid is formed;
3) Under the condition that the rotating speed is unchanged, 0.5mL of beta-guanylate cyclodextrin water solution (3 mg/mL) is added dropwise into the solution while stirring, and stirring is continued for 5 minutes after the addition;
4) Under the condition that the rotation speed is unchanged, 0.5mL of adamantane modified PEG (linear, MW=10000 or so) aqueous solution (10 mg/mL) is added dropwise into the solution while stirring, and stirring is continued for 5 minutes after the addition;
5) After all the operations are completed, the obtained pre-formed glue solution is kept stand on a table top for 24 hours, and then the stable adamantane modified PEG, guanylated cyclodextrin and nano composite hydrogel can be obtained.
The gel was subjected to rheological tests on the basis of example 1, in particular as follows: the rheometer selects a flat plate with the diameter of 25mm, and the gel is sucked out by a suction pipe to be dropped on the flat rheometer by about 0.5mL, then the distance between the flat plates is controlled to be 1mm, the edge is sealed by dimethyl silicone oil to prevent volatilization in the gel testing process, and specific testing parameters of the rheometer are as follows: strain time sweep (f=1 Hz, strain=0.5%), strain frequency sweep (f=0.01-10 Hz, strain=0.5%) temperatures were all 25 ℃. Continuous step-strain sweep (1% and 100% strain respectively), shear-thinning test (shear rate range 10) -3 -10 3 s -1 ) The test results are shown in fig. 2.
The gel was subjected to injectability experiments based on example 1, and the gel was introduced into a syringe barrel of a medical syringe, and extrusion injection was performed using a needle having a diameter of 0.2mm, as shown in fig. 3.
Example 2
The preparation steps of the nanocomposite hydrogel in this example were as follows:
1) Firstly, 50mg of nano-lithium algae soil (Laponite XLS) is slowly added into 3mL of high-speed mechanically stirred pure water in batches, the rotating speed is 1500r/min, the duration is about 20 minutes, and colorless transparent nano-dispersion liquid is formed;
2) Adding 1mL of sodium polyacrylate (MW=5000 or so) aqueous solution (1 mg/mL) into the nano dispersion liquid, and continuously stirring for 10 minutes at the rotating speed of 900r/min until a stable colorless transparent nano dispersion liquid is formed;
3) Dropwise adding 0.5mL of alpha-guanylated cyclodextrin aqueous solution (5 mg/mL) into the solution while stirring under the condition of constant rotating speed, and continuously stirring for 5 minutes after adding;
4) Under the condition that the rotation speed is unchanged, 0.5mL of adamantane modified PEG (three arms, MW=15000 or so) aqueous solution (36 mg/mL) is added dropwise into the solution while stirring, and stirring is continued for 5 minutes after the addition;
5) After all the operations are completed, the obtained preformed gum solution is kept stand on a table top for 4 hours, and then the stable adamantane modified PEG, guanylated cyclodextrin and nano composite hydrogel can be obtained.
Example 3
The preparation steps of the nanocomposite hydrogel in this example were as follows:
1) Firstly, 500mg of nano-lithium algae soil (Laponite RD) is slowly added into 3mL of high-speed mechanically stirred pure water in batches, the rotating speed is 1500r/min, and the duration is about 20 minutes until colorless and transparent nano-dispersion liquid is formed;
2) Adding 1mL of sodium polyacrylate (MW=100000) aqueous solution (5 mg/mL) into the nano dispersion liquid, and continuously stirring at the rotating speed of 900r/min for 10 minutes until a stable colorless transparent nano dispersion liquid is formed;
3) Under the condition that the rotating speed is unchanged, 0.5mL of gamma-guanylate cyclodextrin water solution (10 mg/mL) is added dropwise into the solution while stirring, and stirring is continued for 5 minutes after the addition;
4) Under the condition that the rotating speed is unchanged, 0.5mL of adamantane modified PEG (four arms, MW20000 or so) aqueous solution (50 mg/mL) is added dropwise into the solution while stirring, and stirring is continued for 5 minutes after the addition;
5) After all the operations are completed, the obtained pre-formed glue solution is kept stand on a table top for 8 hours, and then the stable adamantane modified PEG, guanylated cyclodextrin and nano composite hydrogel can be obtained.
Example 4
The preparation steps of the nanocomposite hydrogel in this example were as follows:
1) Firstly, 250mg of nano-lithium algae soil (Laponite XLS) is slowly added into 3mL of high-speed mechanically stirred pure water in batches, the rotating speed is 1500r/min, the duration is about 20 minutes, and until colorless transparent nano-dispersion liquid is formed;
2) Adding 1mL of sodium polyacrylate (MW=5000000) aqueous solution (10 mg/mL) into the nano dispersion liquid, and continuously stirring at the rotating speed of 900r/min for 10 minutes until a stable colorless transparent nano dispersion liquid is formed;
3) Dropwise adding 0.5mL of alpha-guanylated cyclodextrin aqueous solution (25 mg/mL) into the solution while stirring under the condition of constant rotation speed, and continuously stirring for 5 minutes after adding;
4) Under the condition that the rotating speed is unchanged, 0.5mL of adamantane modified PEG (three arms, MW=15000 or so) aqueous solution (72 mg/mL) is added dropwise into the solution while stirring, and stirring is continued for 5 minutes after the addition;
5) After all the operations are completed, the obtained pre-formed glue solution is kept stand on a table top for 24 hours, and then the stable adamantane modified PEG, guanylated cyclodextrin and nano composite hydrogel can be obtained.
The previous description of the embodiments is provided to facilitate a person of ordinary skill in the art in order to make and use the present invention. It will be apparent to those skilled in the art that various modifications can be readily made to these embodiments and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above-described embodiments, and those skilled in the art, based on the present disclosure, should make improvements and modifications without departing from the scope of the present invention.
Claims (9)
1. The nano composite hydrogel is characterized by comprising nano lithium alginate, sodium polyacrylate, adamantane modified PEG and guanidyl cyclodextrin;
the ratio of each component in the nano composite hydrogel is as follows:
the mass fraction of the nano lithium algae soil is 1% -10%, the mass fraction of the sodium polyacrylate is 0.02% -0.1%, the mass fraction of the guanylated cyclodextrin is 0.03% -0.25%, the mass fraction of the adamantane modified PEG is 0.09% -0.72%, and the balance is water.
2. The nanocomposite hydrogel of claim 1, wherein the adamantane-modified PEG is a combination of one or more of linear PEG, three-arm PEG, four-arm PEG, and eight-arm PEG.
3. The nanocomposite hydrogel of claim 1, wherein the guanidinated cyclodextrin is selected from the group consisting of α -guanidinated cyclodextrin, β -guanidinated cyclodextrin, and a combination of one or more of γ -guanidinated cyclodextrins, wherein the degree of substitution of the guanidinated functional group is mono-to fully substituted.
4. A method of preparing a nanocomposite hydrogel according to claim 1, comprising the steps of:
s1: adding nano lithium algae soil into water and stirring to obtain a solution A;
s2: adding the sodium polyacrylate aqueous solution into the solution A, and continuously stirring to obtain a mixed solution B;
s3: adding the guanylated cyclodextrin aqueous solution into the mixed solution B, continuously stirring to obtain a solution C,
s4: adding an aqueous solution of adamantane modified PEG into the solution C, and continuously stirring to obtain a preformed gum solution;
s5: and standing the preformed adhesive solution to obtain the nano composite hydrogel.
5. The method of preparing a nanocomposite hydrogel according to claim 4, wherein the process of preparing the guanylated cyclodextrin comprises the steps of:
preparation of bromocyclodextrin: will Ph 3 Dissolving P in DMF, cooling, adding NBS, dissolving beta-cyclodextrin, adding Ph 3 P/NBS mixed solution, N 2 Reacting in atmosphere, adding methanol after the reaction is finished, stirring, cooling, adjusting pH to be alkaline with sodium methoxide, stirring, precipitating, filtering, washing with methanol, and drying to obtain brominated cyclodextrin;
preparation of cyclodextrin azide: dissolving bromocyclodextrin in DMF, adding sodium azide and nitrogen for reaction, concentrating, settling, suction filtering, washing and drying to obtain the cyclodextrin azide;
preparation of an aminated cyclodextrin: dissolving the cyclodextrin azide in DMF, adding triphenylphosphine, adding concentrated ammonia water, continuously stirring, concentrating, settling, washing with ethanol, and drying to obtain the aminated cyclodextrin;
preparation of guanylated cyclodextrin: dissolving the aminated cyclodextrin with anhydrous DMF, adding the mixture into a mixed solution of 1H-pyrazole-formamidine hydrochloride and diisopropylethylamine for reaction at the temperature of 60-90 ℃, adding the 1H-pyrazole-formamidine hydrochloride and diisopropylethylamine again for continuous reaction, adding diethyl ether after the reaction, stirring, standing, pouring supernatant, collecting viscous solid, dissolving with water, adding ethanol for precipitation, centrifuging, pouring supernatant, dissolving bottom solid, dialyzing, and freeze-drying to obtain the guanylated cyclodextrin.
6. The method for preparing the nanocomposite hydrogel according to claim 4, wherein the method for synthesizing adamantane-modified PEG comprises the following steps:
preparation of carboxyl-terminated PEG: removing water from PEG, adding solvent and succinic anhydride, stirring in ice bath, adding catalyst, removing ice bath, continuing to react at normal temperature, concentrating, adjusting pH to acidity, extracting, washing with water, drying, settling, suction filtering, and drying to obtain carboxyl-terminated PEG compound;
preparation of adamantane modified PEG: and (3) removing water from carboxyl-terminated PEG, adding a solvent, adding N-hydroxybutyrylimine and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, stirring overnight at room temperature, adding triethylamine and 1-amantadine, stirring at room temperature for reaction, after the reaction is finished, washing with acid, washing with salt, merging water phases, extracting, drying, concentrating, and finally settling by utilizing diethyl ether, filtering and drying to obtain the adamantane modified PEG compound.
7. The method for preparing a nanocomposite hydrogel according to claim 6, wherein the carboxyl-terminated PEG is prepared by concentrating and then adjusting the pH to 2-4.
8. The method for preparing a nanocomposite hydrogel according to claim 5, wherein the temperature of the cyclodextrin azide is 60-80 ℃.
9. The use of a nanocomposite hydrogel according to claim 1, as a self-repairing and injectable supramolecular hydrogel for the preparation of pharmaceutical carriers, cell carriers, masks, cosmetic substrates, 3D printing substrates.
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| CN105111341A (en) * | 2015-09-06 | 2015-12-02 | 华南理工大学 | Sticky high-mechanical-strength nano hybrid hydrogel and preparation method thereof |
| CN106311171A (en) * | 2016-08-31 | 2017-01-11 | 武汉理工大学 | Gel converted from sol on basis of host-guest interaction and preparation method of gel |
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| CN105111341A (en) * | 2015-09-06 | 2015-12-02 | 华南理工大学 | Sticky high-mechanical-strength nano hybrid hydrogel and preparation method thereof |
| CN106311171A (en) * | 2016-08-31 | 2017-01-11 | 武汉理工大学 | Gel converted from sol on basis of host-guest interaction and preparation method of gel |
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| Mingyu Guo et al. ; .Supramolecular Hydrogels Made of End-Functionalized Low-Molecular-Weight PEG and R-Cyclodextrin and Their Hybridization with SiO2 Nanoparticles through Host-Guest Interaction .《Macromolecules》.2008,第41卷9744-9749 . * |
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