CN112961375A - Chitosan-based self-repairing hydrogel and preparation method thereof - Google Patents
Chitosan-based self-repairing hydrogel and preparation method thereof Download PDFInfo
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- CN112961375A CN112961375A CN202110162810.7A CN202110162810A CN112961375A CN 112961375 A CN112961375 A CN 112961375A CN 202110162810 A CN202110162810 A CN 202110162810A CN 112961375 A CN112961375 A CN 112961375A
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
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- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
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- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
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- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
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Abstract
The application belongs to the technical field of hydrogel, and particularly relates to chitosan-based self-repairing hydrogel and a preparation method thereof. The application provides chitosan-based self-repairing hydrogel which comprises a structure shown in a formula I and a structure shown in a formula II; forming chitosan-based self-repairing hydrogel by self-assembling and connecting the site 1 of the formula I and the site 1 of the formula II based on adamantane-cyclodextrin host-guest; wherein the ratio of m to n is (200) 400) 1; x is an integer of 23-30, y is an integer of 217-272, and z is an integer of 3-8; r is a repeating unit of the temperature-sensitive polymer. The preparation method comprises the following steps: reacting the formula V and the formula VI, the temperature-sensitive monomer, the accelerant, the initiator and the solvent to prepare the chitosan-based self-repairing hydrogel. The application provides a chitosan-based self-repairing hydrogel and a preparation method thereof, which can effectively solve the technical defects of single function, non-injectability and low service life caused by the fact that the conventional hydrogel cannot be self-repaired.
Description
Technical Field
The application belongs to the technical field of hydrogel, and particularly relates to chitosan-based self-repairing hydrogel and a preparation method thereof.
Background
Skin plays a vital role in maintaining homeostasis and preventing invasion of microorganisms and chemicals. However, skin with limited healing capacity is also highly vulnerable to trauma such as burns and bruises. Generally, the preferred choice for skin rejuvenation is autologous skin grafting, but the short supply and demand of donor skin and the inevitable appearance of new wounds at the donor site limit its widespread use. Therefore, wound dressings have become the predominant therapy for repairing skin lesions. Among various types of wound dressings, hydrogels are widely regarded by researchers because of their unique advantages (e.g., maintenance of a moist wound environment can accelerate recovery). In particular injectable hydrogel dressings, which have unique properties such as coating the drug in situ, filling wounds (even irregular spaces), adhering wounds and the like.
With the increasingly strengthened concepts of low carbon, environmental protection and sustainable development, the new materials are bound to develop towards the direction of multifunction and high intelligence. Injectable hydrogel dressings can fill, adhere to and protect wounds, but most hydrogels do not have strong elasticity, which results in hydrogels that are easily deformed and damaged by external forces, and that fail to repair themselves after damage, which shortens the life span of the hydrogel and causes infection.
Therefore, the development of an injectable hydrogel with temperature-sensitive and self-repairing properties is a technical problem to be solved by those skilled in the art.
Disclosure of Invention
In view of the above, the application provides a chitosan-based self-repairing hydrogel and a preparation method thereof, which can effectively solve the technical defects of low service life caused by single function, non-injectability and non-self-repairing of the conventional gel.
The first aspect of the application provides a chitosan-based self-repairing hydrogel which comprises a structure shown as a formula I and a structure shown as a formula II;
the 1 site of the formula I and the 1 site of the formula II are connected based on adamantane-cyclodextrin host-guest self-assembly to form chitosan-based self-repairing hydrogel;
wherein the ratio of m to n is (200-400) 1; x is an integer of 23-30, y is an integer of 217-272, and z is an integer of 3-8;
and R is a repeating unit of a temperature-sensitive polymer, and the temperature-sensitive polymer is formed by polymerizing a temperature-sensitive monomer.
In another embodiment, the temperature sensitive monomer is selected from one or more of N-isopropylacrylamide, N-N-propylacrylamide, N-cyclopropylacrylamide, N-diethylacrylamide, N-vinylisopropylamide, N-vinyl-N-propionamide, N-vinylcaprolactam, N-vinylpyrrolidone, N-acryloylpyrrolidine, N-acryloyl-N' -N-propylpiperazine, N- (2, 2-dimethyl-1, 3-dioxan-5 ol) -acrylamide and N- (2-ethoxy-1, 3-dioxan-5 ol) -acrylamide.
Specifically, when the temperature-sensitive monomer is N-isopropylacrylamide, the structural formula of the formula II is as follows:
specifically, the chitosan-based self-repairing hydrogel formed by self-assembling and connecting the site 1 of the formula I and the site 1 of the formula II based on adamantane-cyclodextrin host-guest has a structure shown in a formula III;
in particular, of the formula IThe specific chemical structural formula of the compound is shown as a formula IV,
in particular, of the formula IDerived from cyclodextrinsThe formula IAnd said formula IVIs the same site.
In particular, the structure shown in formula IIIThe site of the (2) is a copolymerization connecting site of the temperature-sensitive monomer and the formula VI.
The second aspect of the present application provides a method for preparing a chitosan-based self-repairing hydrogel, comprising:
the formula V, the formula VI, the temperature sensitive monomer, the accelerant, the evocating agent and the solvent are reacted to prepare the formula IIIThe chitosan-based self-repairing hydrogel;said x1Is an integer of 31 to 38, y1Is an integer from 217 to 272;
the temperature-sensitive monomer is selected from one or more of N-isopropylacrylamide, N-N-propylacrylamide, N-cyclopropylacrylamide, N-diethylacrylamide, N-vinyl-isopropylacrylamide, N-vinyl-N-propionamide, N-vinylcaprolactam, N-vinylpyrrolidone, N-acryloylpyrrolidine, N-acryloyl-N' -N-propylpiperazine, N- (2, 2-dimethyl-1, 3-dioxan-5 ol) -acrylamide and N- (2-ethoxy-1, 3-dioxan-5 ol) -acrylamide.
Specifically, when the temperature-sensitive monomer is N-isopropylacrylamide NIPAM, the structural formula of the formula III is as follows:and 2 of the formula III is a copolymerization connecting site of the temperature-sensitive monomer and the formula VI.
Specifically, the preparation method of the chitosan-based self-repairing hydrogel comprises the following steps: after 0.1-1 part by mass of formula V is fully dissolved in 10 parts by mass of solvent, 0.01-0.1 part by mass of formula VI is added respectively. And standing in a refrigerator for 1h after vortex oscillation is carried out for 10-15 min. And then adding 0.2-2 parts by mass of temperature-sensitive monomer, and stirring at room temperature until the temperature-sensitive monomer is fully dissolved. Adding 0.01-0.1 part by mass of an initiator, carrying out vortex oscillation mixing for 3-5 min, and then adding 0.01-0.1 part by mass of an accelerator. And continuing to oscillate at a high speed for 3-8 min, and then carrying out sealing reaction at 20-25 ℃ for 18-28 h to obtain the chitosan-based self-repairing hydrogel shown in the formula III.
In another embodiment, the temperature sensitive monomer is selected from the group consisting of N-isopropylacrylamide; in the formula IIThe ". times.2" site is the site of co-polymerization of N-isopropylacrylamide to formula VI.
In another embodiment, the method of preparing formula v comprises:
reacting the formula VII with a formula VIII to obtain a formula V;
specifically, the preparation method of the formula V comprises the following steps: dissolving 2-5 parts by mass of the formula VII in 40-50 parts by mass of deionized water, and fully stirring to obtain a clear solution. Adding 2-3 parts by mass of formula VIII, stirring strongly at room temperature for 1-2h, and then heating to 70-80 ℃ for reflux for 24-36 h. After cooling, dialysis, concentration and freeze-drying to obtain a yellow or yellowish product of formula V. The synthetic route of formula V is as follows:
in another embodiment, the process for preparing formula vii comprises:
reacting formula IX with propylene oxide to produce formula VII;
In another embodiment, the process for preparing formula IX comprises: will be provided withReacting with NaOH to obtain a compound of formula IX; said x2Is an integer of 248 and 310.
Specifically, the preparation method of the formula VII comprises the following steps: mixing CS 1-3 parts by mass of chitosanAnd adding 10-15 parts by mass of isopropanol liquid into the reactor, stirring for 15-45 min, adding 3-5 parts by mass of NaOH solution, continuously stirring at room temperature for 30-80 min, and refrigerating overnight. After thawing, adding 3-5 parts by mass of tetramethylammonium chloride, and slowly adding 10-18 parts by mass of propylene oxide. And continuing stirring for 30-80 min after the dripping is finished. Heating to 30-50 ℃ and refluxing overnight. Cooling, filtering, washing the filter residue with anhydrous ethanol for 2-3 times, and dissolving in water again. Adjusting the pH value of the solution to 7 by using 1M HCl, and then dialyzing for 50-60 h. Concentrating, and freeze drying to obtain product of formula IX, x2Is an integer of 248 and 310. The synthetic route of formula VII is as follows:
in another embodiment, the process for preparing formula viii comprises: will be provided withAndthe specific chemical structural formula of the prepared VIII is shown in the specification
Specifically, the preparation method of the formula VIII comprises the following steps: adding 5-15 parts by mass of beta-cyclodextrin and 1.5-3 parts by mass of 1-p-toluenesulfonylimidazole into deionized water, and strongly stirring at room temperature for 2-4 hours. Adding NaOH solution and then continuing stirring for 15-60 min. After removing the unreacted insoluble matter by filtration, an HCl solution is added to adjust the pH of the filtrate to 7 to 8. The resulting mixture was precipitated at low temperature for 18-36h, then filtered to collect the filter residue, washed with ice water and acetone respectively multiple times to obtain the crude product. And recrystallizing the crude product in hot water for 2-3 times to obtain a product of the formula VIII. The synthetic route for formula VIII is:
in another embodiment, the process for preparing formula viii comprises:
reacting beta-cyclodextrin with 1-p-toluenesulfonylimidazole to prepare the formula VIII.
In another embodiment, the process for preparing formula vi comprises:
reacting formula X with formula XI to obtain formula VI;
specifically, the preparation method of the formula VI comprises the following steps: adding 1 part by mass of 1-adamantanol and 20-40 parts by mass of anhydrous dichloromethane into a reactor, stirring until the mixture is fully dissolved, and adding 1-3 parts by mass of triethylamine. And stirring the mixed solution at low temperature for 15-40 min. Diluting 1-3 parts by mass of acryloyl chloride with 5-10 parts by mass of anhydrous dichloromethane, and dropwise adding the acryloyl chloride into the mixed solution at low temperature through a constant-pressure dropping funnel. After the dripping is finished, slowly raising the temperature to the room temperature and continuously stirring for 18-36 h. Filtering out insoluble substances after the reaction is finished, and collecting filtrate; respectively using 0.1-0.3M HCl aqueous solution and NaHCO for filtrate3After the solution was washed with distilled water 3 times in this order, the organic phase was collected and concentrated under reduced pressure at low temperature. Purifying by using a column chromatography method, wherein an eluent is V ethyl acetate and V n-hexane ═ 1 (15-20). The product of formula VI is stored at low temperature for further use. The synthetic route for formula VI is as follows:
in another embodiment, the accelerator is selected from one or more of tetramethylethylenediamine, sodium sulfite, and sodium thiosulfate; the initiator is selected from ammonium persulfate or/and potassium persulfate; the solvent is selected from water or an aqueous solution of an inorganic salt.
In another embodiment, the aqueous solution of inorganic salts is selected from PBS buffer.
In another embodiment, the amount of the organic acid compound is, in parts by mass,
in another embodiment, the reaction temperature is 20-25 ℃, and the reaction time is 18-28 h.
In another embodiment, the preparation method further comprises impurity removal of the chitosan-based self-repairing hydrogel, wherein the impurity removal comprises: and repeatedly soaking the chitosan-based self-repairing hydrogel in warm water and ice water for shrinkage-swelling treatment.
Specifically, the impurity removal method of the chitosan-based self-repairing hydrogel comprises the following steps: and sequentially soaking the chitosan-based self-repairing hydrogel in ice water at 60 ℃ to perform a shrinkage-swelling process, and circulating for 3-4 times to remove unreacted monomers and impurities in the chitosan-based self-repairing hydrogel, thereby obtaining the high-purity chitosan-based self-repairing hydrogel.
The third aspect of the application discloses application of the chitosan-based self-repairing hydrogel in wound dressing.
The method comprises the steps of reacting a temperature-sensitive monomer, an accelerant, an initiator and a solvent in a formula V, reacting adamantane acrylate (AMDA) in the formula VI with Chitosan (CS) step by step, grafting beta-cyclodextrin to form cyclodextrin modified chitosan (HPCS-CD) in the formula V, inducing the cyclodextrin modified chitosan to be spontaneously assembled in an aqueous solution through the interaction of a host and an object to form a stable supermolecular structure, and copolymerizing the temperature-sensitive monomer and ADMA to form a temperature-sensitive polymer chain and cross-linking the HPCS-CD mutually to form single-network hydrogel. According to the chitosan-based self-repairing hydrogel, a supermolecular structure formed by interaction of HPCS-CD and ADMA is used as a core for constructing a gel network, the gel network is endowed with high modifiability, the temperature-sensitive polymer is endowed with temperature sensitivity of the chitosan-based self-repairing hydrogel, the adsorption-release of the hydrogel can be regulated and controlled through temperature, and the hydrogel can realize gel-sol conversion after low-temperature swelling, so that the chitosan-based self-repairing hydrogel has high injectability. According to test data, the chitosan-based self-repairing hydrogel has a self-repairing function of rapid temperature responsiveness and injectability, and can be applied to the fields of biomedicine, intelligent textiles, intelligent sensing and new energy.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
FIG. 1 is a schematic diagram of a structural formula of a chitosan-based self-repairing hydrogel of the present application;
FIG. 2 is a graph showing the result of an injectability test of a chitosan-based self-repairing hydrogel provided in an embodiment of the present application;
FIG. 3 is a graph showing a self-repair performance test result of the chitosan-based self-repair hydrogel provided in the embodiment of the present application;
fig. 4 is a temperature response performance test result of the chitosan-based self-repairing hydrogel provided in the embodiment of the present application.
Detailed Description
The application provides a chitosan-based self-repairing hydrogel and a preparation method thereof, which are used for solving the technical defects of low service life caused by single function, non-injectability and incapability of self-repairing of the conventional gel. The technical solutions in the embodiments of the present application will be described clearly and completely below, and it should be understood that the described embodiments are only a part of the embodiments of the present application, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
The raw materials used in the following examples are all commercially available or self-made.
The preparation of formula VI is as follows: adding 1 part by mass of 1-adamantanol and 20-40 parts by mass of anhydrous dichloromethane into a reactor, stirring until the mixture is fully dissolved, and adding 1-3 parts by mass of triethylamine. Keeping the mixed solution constantly stirred at 0 ℃ for 15-40 min. Diluting 1-3 parts by mass of acryloyl chloride with 5-10 parts by mass of anhydrous dichloromethane, and dropwise adding the diluted acryloyl chloride into the mixed solution at 0 ℃ through a constant-pressure dropping funnel. After the dripping is finished, slowly raising the temperature to the room temperature and continuously stirring for 18-36 h. Filtration after completionRemoving insoluble substances, and collecting filtrate; the filtrate is respectively treated with 0.1-0.3M HCl aqueous solution and 0.5 wt% NaHCO3After the solution was washed with distilled water 3 times in this order, the organic phase was collected and concentrated under reduced pressure at low temperature. Purifying by column chromatography, wherein the volume ratio of ethyl acetate to n-hexane is 1 (15-20). The product of formula VI is stored at low temperature for further use.
The preparation of formula VIII is as follows: adding 5-15 parts by mass of beta-cyclodextrin and 1.5-3 parts by mass of 1-p-toluenesulfonylimidazole into 250mL of deionized water, and strongly stirring at room temperature for 2-4 hours. Adding 10 wt% NaOH solution (50mL) and then continuing stirring for 15-60 min. After removing unreacted insoluble materials by filtration, a 1M HCl solution is added to adjust the pH of the filtrate to 7 to 8. The resulting mixture was precipitated at low temperature for 18-36h, then filtered to collect the filter residue, washed with ice water and acetone respectively for 3 times to obtain the crude product. And recrystallizing the crude product in hot water for 2-3 times to obtain a product of the formula VIII.
The preparation method of the formula VII is as follows: adding 1-3 parts by mass of chitosan CS and 10-15 parts by mass of isopropanol liquid into a reactor, stirring for 15-45 min, adding 3-5 parts by mass of 33 wt% NaOH solution, continuously stirring at room temperature for 30-80 min, and refrigerating overnight. And after thawing, adding 3-5 parts by mass of 10 wt% tetramethylammonium chloride, and slowly adding 10-18 parts by mass of propylene oxide. And continuing stirring for 30-80 min after the dripping is finished. Heating to 30-50 ℃ and refluxing overnight. And cooling and filtering, washing filter residues with absolute ethyl alcohol for 2-3 times, and dissolving the filter residues in water again. Adjusting the pH of the solution to 7 by using 1M HCl, and dialyzing for 50-60 h by using an MWC 3500 dialysis bag. After concentration, the product of formula VII is obtained by freeze drying.
The preparation method of the formula V is as follows: dissolving 2-5 parts by mass of formula VII in 40-50 parts by mass of deionized water, and fully stirring to obtain a clear solution. Adding 2-3 parts by mass of formula VIII, stirring strongly at room temperature for 1-2h, heating to 70-80 ℃, and refluxing for 24-36 h. After cooling, the mixture was transferred to dialysis bags of MWC 3500 for dialysis for 3 days, concentrated and lyophilized to obtain a yellow or pale yellow product of formula V.
The preparation method of the chitosan-based self-repairing hydrogel comprises the following steps: after 0.1 to 1 part by mass of formula V is sufficiently dissolved in 10 parts by mass of PBS buffer, 0.01 to 0.1 part by mass of formula VI is added. And standing in a refrigerator for 1h after vortex oscillation is carried out for 10-15 min. And then adding 0.2-2 parts by mass of a temperature-sensitive monomer, and stirring at room temperature until the temperature-sensitive monomer is fully dissolved. 0.01 to 0.1 mass part of APS is added, and 0.01 to 0.1 mass part of TEMED is added after vortex oscillation and mixing for 3 to 5 min. And continuing to oscillate at a high speed for 3-8 min, and then carrying out sealing reaction at 20-25 ℃ for 18-28 h to obtain the chitosan-based self-repairing hydrogel. Forming chitosan-based self-repairing hydrogel by self-assembly connection of a site 1 and a site 1 based on adamantane-cyclodextrin host-guest as shown in figure 1; the ". 2" in FIG. 1 is the site of attachment of the temperature sensitive monomer to formula VI.
The impurity removal method of the chitosan-based self-repairing hydrogel comprises the following steps: and sequentially soaking the prepared hydrogel in ice water at 60 ℃ to perform a shrinkage-swelling process, and circulating for 3-4 times to remove unreacted monomers and impurities in the hydrogel, thereby obtaining the high-purity chitosan-based self-repairing hydrogel.
Example 1
The embodiment of the application provides a preparation method of chitosan-based self-repairing hydrogel, which specifically comprises the following steps:
the preparation of adamantane acrylate (AMDA) of formula VI is as follows: 1-adamantanol (3.04g,20mmol) and anhydrous dichloromethane (60mL) were added to the reactor, stirred until fully dissolved, and triethylamine (3g,29.7mmol) was added. The mixed solution was kept stirring at 0 ℃ for 40 min. 25mL of acryloyl chloride (3.62g,40mmol) diluted with anhydrous dichloromethane was added dropwise to the above mixed solution at 0 ℃ through a constant pressure dropping funnel. After the addition was complete, the temperature was slowly raised to room temperature and stirring was continued for 18 h. Filtering out insoluble substances after the reaction is finished, and collecting filtrate; the filtrate was washed with 0.1M HCl aqueous solution and 0.5 wt% NaHCO, respectively3After the solution was washed with distilled water 3 times in this order, the organic phase was collected and concentrated under reduced pressure at low temperature. Purifying by column chromatography, wherein the eluent is ethyl acetate and n-hexane 1:15 to obtain formula VI, and storing at low temperature for later use.
The preparation of formula VIII-CDOTs is as follows: beta-cyclodextrin (36.3g,32mmol) and 1-p-toluenesulfonylimidazole (6.67g,30mmol) were added to deionized water (250mL) and stirred vigorously at room temperature for 3 h. Stirring was continued for 30min after the addition of 10 wt% NaOH solution (50 mL). After removing unreacted insoluble materials by filtration, 1M HCl solution was added to adjust the pH of the filtrate to 7.5. The resulting mixture was precipitated at low temperature for 18h, then filtered to collect the filter residue, washed with ice water and acetone respectively for 3 times to obtain the crude product. Recrystallizing the crude product in hot water for 2-3 times to obtain the product of the formula VIII.
The preparation of formula VII-HPCS is as follows: chitosan CS (3g) and isopropanol solution (50mL) were added to the reactor and stirred for 30min, then 33 wt% NaOH solution (10g) was added and stirring continued at room temperature for 60min, after which it was refrigerated overnight. After thawing, 10 wt% tetramethylammonium chloride (10mL) was added and 50mL propylene oxide was added slowly. Stirring is continued for 60min after the dripping is finished. The mixture was heated to 45 ℃ and refluxed overnight. Cooling, filtering, washing the filter residue with anhydrous ethanol for 2-3 times, and dissolving in water again. The pH of the solution was adjusted to 7 with 1M HCl and dialyzed against a dialysis bag of MWC 3500 for 60 h. After concentration, the product of formula VII is obtained by freeze drying.
The preparation of formula V-HPCS-CD is as follows: formula VII (6.5g) was dissolved in 150mL deionized water and stirred well to give a clear solution. Adding formula VIII (6.5g), stirring strongly at room temperature for 1-2h, and heating to 80 ℃ for refluxing for 24 h. After cooling, the mixture was transferred to dialysis bags of MWC 3500 for dialysis for 3 days, concentrated and lyophilized to obtain a yellow or pale yellow product of formula V.
The preparation method of the chitosan-based self-repairing hydrogel comprises the following steps: after dissolving formula V (0.5g) well in 10mL PBS to form a HPCS-CD solution, 10mg of formula VI (formula VI was added as 0.1g/mL methanol solution of formula VI, i.e., 0.1mL methanol solution of formula VI was added at a concentration of 0.1 g/mL). Standing in refrigerator for 1h after vortex oscillation for 15 min. Then, a temperature-sensitive monomer NIPAM (1.35g,12mmol) was added thereto, and the mixture was stirred at room temperature until it was sufficiently dissolved. APS (0.01g) was added and mixed by vortexing for 3min before adding 100. mu.L TEMED. And continuing to oscillate at a high speed for 5min, and then carrying out sealing reaction at 20 ℃ for 19h to obtain the chitosan-based self-repairing hydrogel. And sequentially soaking the prepared hydrogel in ice water at 60 ℃ to perform a contraction-swelling process, and circulating for 3 times to remove unreacted monomers and impurities in the hydrogel to prepare the high-purity chitosan-based self-repairing hydrogel.
Comparative example 1
The comparative example of the application provides a control product, and the specific method comprises the following steps:
10mL of HPCS-CD solution (formula V (0.5g) was dissolved well in 10mL of PBS to prepare HPCS-CD solution) and 0.1mL of HPCS-CD solution (formula V (0.5g) was dissolved well in 10mL of PBS to prepare HPCS-CD solution) were mixed, vortexed for 15min and then allowed to stand in a refrigerator for 1 h. Then the monomer NIPAM (1.35g,12mmol) was added and stirred at room temperature until fully dissolved. APS (0.01g) was added and mixed by vortexing for 3min before adding 100. mu. LTEMED. And continuing to oscillate at a high speed for 5min, and then sealing and reacting at 20 ℃ for 19h to obtain a control product 1.
The comparative product 1 of this comparative example failed to form a hydrogel.
Comparative example 2
The comparative example of the application provides a control product, and the specific method comprises the following steps:
10mL of 0.1g/mL methanol solution of the formula VI and 0.1mL of 0.1g/mL methanol solution of the formula VI are mixed, vortex oscillation is carried out for 15min, and then the mixture is placed in a refrigerator for 1 h. Then the monomer NIPAM (1.35g,12mmol) was added and stirred at room temperature until fully dissolved. APS (0.01g) was added and mixed by vortexing for 3min before adding 100. mu. LTEMED. And continuing to oscillate at a high speed for 5min, and then sealing and reacting at 20 ℃ for 19h to obtain a control product 2.
The control product 2 of this comparative example failed to form a hydrogel.
Example 2
The embodiment of the application provides a preparation method of chitosan-based self-repairing hydrogel, which specifically comprises the following steps:
with reference to the method of example 1, except that 15mg was substituted for the amount of formula VI (10mg), i.e., 0.15mL of 0.1g/mL methanol solution of formula VI was added, and the remaining steps were identical to example 1, chitosan-based self-repairing hydrogel was successfully prepared.
Example 3
The embodiment of the application provides a preparation method of chitosan-based self-repairing hydrogel, which specifically comprises the following steps:
referring to the method of example 1, except for replacing the monomer N-isopropylacrylamide (NIPAM) with N-N-propylacrylamide (NNPA), i.e., the same amount of NNPA, the remaining steps are identical to those of example 1, the chitosan-based self-repairing hydrogel is successfully prepared.
Example 4
The embodiment of the application provides an injectability test of chitosan-based self-repairing hydrogel, which comprises the following specific steps:
the chitosan-based self-repairing hydrogel in example 1 is placed at 4 ℃ and swelled in a dyeing solution at a low temperature, so that the hydrogel undergoes a gel-sol state change, the sol-sol hydrogel is sucked into a needle tube, and then the gel-sol hydrogel is injected onto a glass dish, as shown in fig. 2, a in fig. 2 is a real object diagram of the injection process of the chitosan-based self-repairing hydrogel, b is a real object diagram of the chitosan-based self-repairing hydrogel after injection (the pattern of injection can be clearly seen to be "123 ABC"), and fig. 2 illustrates that the chitosan-based self-repairing hydrogel of the present application has injectability and dyeability.
Example 5
The embodiment of the application provides a self-repairing performance test of chitosan-based self-repairing hydrogel, which comprises the following specific steps:
the chitosan-based self-repairing hydrogel of example 1 is diced, dyed, deionized water is added at the interface, and the bonded interface is placed for 24 hours, and as a result, as shown in fig. 3, a in fig. 3 is a real object diagram of the hydrogel of example 1 after being diced and dyed, b is a real object diagram of the hydrogel of example 1 after being added with deionized water at the interface, c is a real object diagram of the hydrogel of example 1 after being bonded with each other and placed for 24 hours to clamp the gel, d is a real object diagram of the hydrogel of example 1 after being repaired and stretched, and the hydrogel interface can be found to disappear and the crack can be basically repaired in fig. 3 d, and fig. 3 shows that the chitosan-based self-repairing hydrogel of the present application has better self-repairing performance after being placed for 24 hours at room temperature.
Example 6
The embodiment of the application provides a temperature response performance test of chitosan-based self-repairing hydrogel, which comprises the following specific steps:
the chitosan-based self-repairing hydrogel in the example 1 is placed in a warm water bath at 37 ℃ for 10 minutes, and then the volume and the color of the chitosan-based self-repairing hydrogel are observed, so that the result is shown in fig. 4, the left graph in fig. 1 is a real graph before heating, the right graph in fig. 1 is a real graph after heating, and fig. 4 illustrates that the volume and the color of the chitosan-based self-repairing hydrogel in the example 1 are changed, and the temperature sensitivity is reflected.
The chitosan-based self-repairing hydrogels prepared in examples 2 and 3 were tested according to the procedures of examples 4 to 6, and the injectability, self-repairing performance and temperature response performance of the chitosan-based self-repairing hydrogels prepared in examples 2 and 3 were all similar to those of the chitosan-based self-repairing hydrogel of example 1.
The foregoing is only a preferred embodiment of the present application and it should be noted that those skilled in the art can make several improvements and modifications without departing from the principle of the present application, and these improvements and modifications should also be considered as the protection scope of the present application.
Claims (10)
1. A chitosan-based self-repairing hydrogel is characterized by comprising a structure shown in a formula I and a structure shown in a formula II;
the 1 site of the formula I and the 1 site of the formula II are connected based on adamantane-cyclodextrin host-guest self-assembly to form chitosan-based self-repairing hydrogel;
wherein the ratio of m to n is (200-400) 1; x is an integer of 23-30, y is an integer of 217-272, and z is an integer of 3-8;
and R is a repeating unit of a temperature-sensitive polymer, and the temperature-sensitive polymer is formed by polymerizing a temperature-sensitive monomer.
2. The chitosan-based self-healing hydrogel of claim 1, wherein the temperature sensitive monomer is selected from one or more of N-isopropylacrylamide, N-propylacrylamide, N-cyclopropylacrylamide, N-diethylacrylamide, N-vinyl isopropylamide, N-vinyl-N-propionamide, N-vinylcaprolactam, N-vinylpyrrolidone, N-acryloylpyrrolidine, N-acryloyl-N' -N-propylpiperazine, N- (2, 2-dimethyl-1, 3-dioxan-5 ol) -acrylamide, and N- (2-ethoxy-1, 3-dioxan-5 ol) -acrylamide.
3. A preparation method of the chitosan-based self-repairing hydrogel of claim 1 or 2, which is characterized by comprising the following steps:
reacting a temperature-sensitive monomer, an accelerant, an initiator and a solvent in a formula V and a formula VI to prepare the chitosan-based self-repairing hydrogel in claim 1 or 2;said x1Is an integer of 31 to 38, y1Is an integer from 217 to 272;
the temperature-sensitive monomer is selected from one or more of N-isopropylacrylamide, N-N-propylacrylamide, N-cyclopropylacrylamide, N-diethylacrylamide, N-vinyl-isopropylacrylamide, N-vinyl-N-propionamide, N-vinylcaprolactam, N-vinylpyrrolidone, N-acryloylpyrrolidine, N-acryloyl-N' -N-propylpiperazine, N- (2, 2-dimethyl-1, 3-dioxan-5 ol) -acrylamide and N- (2-ethoxy-1, 3-dioxan-5 ol) -acrylamide.
6. The process of claim 4, wherein the process of preparing formula VIII comprises:
reacting beta-cyclodextrin with 1-p-toluenesulfonylimidazole to prepare the formula VIII.
8. the method according to claim 3, wherein the accelerator is one or more selected from the group consisting of tetramethylethylenediamine, sodium sulfite, and sodium thiosulfate; the initiator is selected from ammonium persulfate or/and potassium persulfate; the solvent is selected from water or an aqueous solution of an inorganic salt.
10. the preparation method according to claim 3, wherein the reaction temperature is 20-25 ℃ and the reaction time is 18-28 h.
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