CN111378152A - Method for catalytic oxidation and functional modification of hydrogel material - Google Patents
Method for catalytic oxidation and functional modification of hydrogel material Download PDFInfo
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- CN111378152A CN111378152A CN202010345958.XA CN202010345958A CN111378152A CN 111378152 A CN111378152 A CN 111378152A CN 202010345958 A CN202010345958 A CN 202010345958A CN 111378152 A CN111378152 A CN 111378152A
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
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- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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- C08F2/46—Polymerisation initiated by wave energy or particle radiation
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- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
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Abstract
The invention discloses a method for catalytic oxidation and functional modification of a hydrogel material, which is characterized by comprising the following steps of: step one, soaking a hydrogel material in a buffer solution in which a piperidine compound is dissolved to obtain a mixed system; step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation to obtain an oxidized hydrogel material; and step three, soaking the hydrogel material subjected to the step two oxidation in a hyaluronic acid-adipic acid dihydrazide solution, and performing functional modification under the stirring condition to obtain the modified hydrogel material. The method has the advantages of controllable process, wide range of water-soluble polymers, easy acquisition of experimental reagents, no need of large experimental equipment, reaction under the conditions of normal temperature and normal pressure and the like. The modified hydrogel material prepared by the method has the advantages of high moisture retention, low protein adsorption amount, unchanged appearance, light permeability, refractive index and the like.
Description
Technical Field
The invention belongs to the technical field of high polymer materials, and particularly relates to a method for catalytic oxidation and functional modification of a hydrogel material.
Background
The macromolecular hydrogel is a gel taking water as a dispersion medium, the interior of the gel consists of a crosslinked hydrophilic macromolecular network structure, and a large amount of water is absorbed and expanded in the network structure and macroscopically shows a quasi-net-stop state without flowing. The hydrogel has adjustable strength and porosity, the surface of the hydrogel generally has strong hydrophilicity, and the special properties enable the hydrogel to have multiple application potentials and be industrially used for preparing oil-water separation membranes and the like; in the biomedical field, the hydrogel material has good biocompatibility, so that the hydrogel material is widely applied to preparation of drug delivery carriers, biosensors and biosorption-resistant surfaces, or is prepared into biomaterials such as contact lenses directly contacting human tissues.
Poly (2-hydroxymethymethacrylate), pHEMA, is a hydrophilic biomedical polymer containing hydroxyl groups and is commonly used as a cell culture substrate and a contact tissue engineering material. The contact lenses based on the pHEMA hydrogel material are mostly used in the market of the lens industry, compared with hard contact lenses, the permeation rate of oxygen and the wettability of a tear film are greatly improved, the wearing comfort of the contact lenses is greatly increased, but the phenomena of slow water loss and tear protein deposition can occur in the continuous wearing process, so that eyes are dry, astringent, itchy and painful.
As a common biological material, the polymer hydrogel is important for performing necessary chemical modification and performance optimization to improve the biological activity and biocompatibility, and because the polymer hydrogel has the characteristics of high water content, softness, translucency or transparency, porosity and the like, a modified hydrogel material with excellent performance is difficult to directly obtain by a traditional polymer material surface modification method.
One of the conventional methods for modifying the surface of a polymer material is to perform an oxidation reaction on the polymer material in a TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl, 2,2,6,6-tetramethylpiperidine oxide) oxidation system, wherein TEMPO is a stable small molecule compound containing nitroxide radicals, and is commonly used as an electron transfer agent for the oxidation reaction to oxidize polysaccharide substances, and primary alcohols in polysaccharide molecules can be selectively oxidized into corresponding aldehydes and carboxylic acids in an aqueous solution system. The TEMPO oxidation system adopts oxygen as an oxidant, laccase as a catalyst and TEMPO as an electron transfer agent, but when the oxidation system is used for an oxidation reaction process, the TEMPO as the oxidation reaction electron transfer agent can freely enter and exit the hydrogel system, so that the inside and the outside of the hydrogel material are simultaneously oxidized.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a method for catalytic oxidation and functional modification of hydrogel materials, aiming at the defects of the prior art, and the method has the advantages of controllable process, wide range of water-soluble polymers, easy obtainment of experimental reagents, no need of large experimental equipment, reaction under normal temperature and pressure and the like. The modified hydrogel material prepared by the method is beneficial to solving the problems encountered in wearing contact lenses based on pHEMA hydrogel materials in the market, and has the advantages of high moisture retention, low protein adsorption capacity, unchanged appearance, light permeability and refractive index and the like.
In order to solve the technical problems, the invention adopts the technical scheme that: a method for catalytic oxidation and functional modification of hydrogel materials is characterized by comprising the following steps:
step one, soaking a hydrogel material in a buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 4-8; the piperidine compound is 2,2,6,6-tetramethyl piperidine oxide or macromolecule grafting 2,2,6,6-tetramethyl piperidine oxide;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 8-24 hours to obtain an oxidized hydrogel material;
and step three, soaking the oxidized hydrogel material obtained in the step two in a hyaluronic acid-adipic acid dihydrazide solution, and performing functional modification for 3-5 hours under the stirring condition that the pH value is 6-8 to obtain the modified hydrogel material.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that in the buffer solution in which the piperidine compound is dissolved in the step one, the mass concentration of the piperidine compound is 100 mg/L-400 mg/L; in the step one, the volume of the buffer solution dissolved with the piperidine compound is 10-100 times of the mass of the hydrogel material, the unit of the volume of the buffer solution dissolved with the piperidine compound is mL, and the unit of the mass of the hydrogel material is g.
The method for catalytic oxidation and functionalized modification of the hydrogel material is characterized in that in the step one, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide, polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide or polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide in the step one is polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide or polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, the preparation method of the polymer grafted 2,2,6,6-tetramethylpiperidine oxide comprises the following steps:
step 101, dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 20-30 min under the condition that the pH value is 4.50-5.00 to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2-3 times of that of TEMPO-COOH;
102, dripping an aqueous solution of a high molecular compound to be grafted into the mixed solution A obtained in the step 101, magnetically stirring and reacting for 3-5 h under the condition that the pH value is 4.50-5.00, and adjusting the pH value of the solution after reaction to 7; in the aqueous solution of the macromolecular compound to be grafted, the mass percentage content of the macromolecular compound to be grafted is 0.25-1.0%; the mass of the macromolecular compound to be grafted is 2-4 times of that of TEMPO-COOH;
103, adjusting the pH value in the step 102, dialyzing the system, and freeze-drying to obtain the polymer grafted 2,2,6,6-tetramethylpiperidine oxide;
when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer compound to be grafted in step 102 is polyvinylamine, and the molecular weight of the polyvinylamine is 50-100 kDa; when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer compound to be grafted in step 102 is polyethyleneimine, and the molecular weight of the polyethyleneimine is 50 kDa-150 kDa.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that the polymer grafted 2,2,6,6-tetramethylpiperidine oxide in the step one is polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide or polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polymer grafted 2,2,6,6-tetramethylpiperidine oxide comprises the following steps:
step 201, dissolving a high molecular compound to be grafted and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 20-30 min under the condition that the pH value is 4.50-5.00 to obtain a mixed solution A;
step 202, TEMPO-NH2Dropwise adding the aqueous solution into the mixed solution A obtained in the step 201, magnetically stirring and reacting for 3-5 h under the condition that the pH value is 4.50-5.00, and adjusting the pH value of the solution after reaction to 7; the mass of the polymer compound to be grafted in step 201 is TEMPO-NH in step 20222 to 3 times of the mass;
step 203, after the pH is adjusted in the step 202, the system is dialyzed and then is freeze-dried to obtain the polymer grafted 2,2,6,6-tetramethylpiperidine oxide;
when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer compound to be grafted in step 201 is polyacrylic acid, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1.5-2 times that of the polyacrylic acid; the molecular weight of the polyacrylic acid is 50-150 kDa; when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is 2,2,6,6-tetramethylpiperidine oxide grafted by a polyethylene glycol derivative, in step 201, the polymer compound to be grafted is a four-arm polyethylene glycol carboxyl group, the terminal groups of the four-arm polyethylene glycol carboxyl group are all carboxyl groups, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1-3 times of that of the four-arm polyethylene glycol carboxyl group; the molecular weight of the four-arm polyethylene glycol carboxyl is 10kDa to 50 kDa.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that the mass percentage concentration of the acetic acid-sodium acetate buffer solution in the step one is 2.0-2.5%.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that the mass of the laccase in the second step is 0.5-2 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.025-0.05%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with the pH value of 4.5-5.5.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that the mass of the hyaluronic acid-adipic acid dihydrazide in the step three is 1-2 times of the mass of the oxidized hydrogel material.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that the preparation method of the hyaluronic acid-adipic acid dihydrazide solution in the step three comprises the following steps:
step 301, adding adipic acid dihydrazide to the aqueous solution of sodium hyaluronate to obtain a mixed solution; the mass of the adipic acid dihydrazide is 15-20 times that of the sodium hyaluronate; the mass percentage content of the sodium hyaluronate in the sodium hyaluronate water solution is 0.25-0.5%;
step 302, magnetically stirring the mixed solution obtained in the step 301 under the condition that the pH value is 4.50-5.00 for reaction for 3-5 h, and adjusting the pH value of the reacted solution to 7;
step 303, after the pH is adjusted in step 302, the reaction system is dialyzed, freeze-dried and then placed in water, and the mixture is magnetically stirred until the mixture is dissolved, so that a hyaluronic acid-adipic acid dihydrazide solution is obtained.
The method for catalytic oxidation and functional modification of the hydrogel material is characterized in that the preparation method of the hydrogel material in the first step comprises the following steps:
step 401, mixing hydroxyethyl methacrylate, ethylene glycol dimethacrylate and an initiator, and oscillating until the mixture is dissolved to obtain a mixture; the mass ratio of the hydroxyethyl methacrylate to the ethylene glycol dimethacrylate to the initiator is 3000:90:7, the initiator is Irgacure184, and the mixing oscillation time is 5-10 min;
step 402, placing the mixture obtained in the step 401 in a polymethyl methacrylate mould, and initiating for 15min under ultraviolet light to obtain an initiated system; the power of an ultraviolet lamp used by the ultraviolet light is 400 w;
step 403, under the condition of room temperature, placing the initiated system in the step 402 until the initiated system is completely cured to obtain gel;
step 404, extracting the gel obtained in the step 403 with ultrapure water to obtain a purified gel;
and 405, soaking the gel purified in the step 404 in ultrapure water until the gel is in a saturated water absorption state to obtain a hydrogel material.
Compared with the prior art, the invention has the following advantages:
1. the invention provides a method for catalytic oxidation and functional modification of a hydrogel material, which has the advantages of controllable process, wide range of water-soluble polymers, easy obtainment of experimental reagents, no need of large experimental equipment, reaction under the conditions of normal temperature and normal pressure and the like. The modified hydrogel material prepared by the method is beneficial to solving the problems encountered in wearing contact lenses based on pHEMA hydrogel materials in the market, and has the advantages of high moisture retention, low protein adsorption capacity, unchanged appearance, light permeability and refractive index and the like.
2. According to the invention, a laccase/macromolecule grafted TEMPO/oxygen oxidation system is used for oxidizing the surface of a hydrogel material to form an active group, then a click chemical reaction is used for functional modification, and a functionalized hyaluronic acid coating is grafted, so that the modification effects of hydrophilic moisture preservation and protein adsorption resistance on the surface of the hydrogel material are realized.
3. The invention uses the nitroxide free radical mediated catalytic oxidation reaction, changes the problems of violent reaction, extreme conditions and the like of the traditional oxidant, realizes the relatively mild catalytic oxidation of the surface of the hydrogel material, can controllably oxidize the hydroxyl contained in the macromolecule into aldehyde group and carboxyl, and the oxidation product is still a hydrophilic group.
4. Preferably, in the catalytic oxidation reaction of the present invention, a polymer grafted TEMPO obtained by fixing TEMPO on a side chain of a water-soluble polymer such as polyvinylamine (PVAm), polyacrylic acid (poly (acrylic acid), PAA) and the like through a chemical reaction is used as an electron transfer agent, so as to achieve the purpose of controlling the oxidation reaction to occur only on the surface of the hydrogel material and generate active groups (aldehyde group, carboxyl group), and solve the problem that the inside and outside of the hydrogel material are oxidized simultaneously due to the fact that the electron transfer agent freely enters and exits the hydrogel system in the conventional oxidation system.
5. According to the functional modification, the hyaluronic acid coating is grafted on the surface of the hydrogel material, so that the defects that the hydrogel material is easy to dehydrate and form protein deposition, pollution and the like are overcome; the hyaluronic acid-adipic dihydrazide solution is used as a functional modifier, hydrazide group functional modification is carried out on hyaluronic acid molecules, and a hydrazide group reacts with an aldehyde group generated by surface catalytic oxidation reaction, so that a hyaluronic acid molecular layer is connected to the surface of the hydrogel material, and the effects of hydrophilic moisture preservation and protein adsorption resistance of the surface of the hydrogel material are achieved.
6. Preferably, the hyaluronic acid-adipic acid dihydrazide solution is prepared by mixing sodium hyaluronate and adipic acid dihydrazide, stirring for reaction under the condition that the pH value is 4.50-5.00, dialyzing, freeze-drying and dissolving, and grafting hydrazine groups on the molecular structure of hyaluronic acid to serve as active groups, so that the next step of coating grafting is facilitated to generate a click chemistry reaction, the grafting reaction can be directly generated in a buffer solution, the reaction condition is mild, and the grafting is easy to perform.
7. Preferably, the hydrogel material is obtained by photo-initiating, curing, purifying and soaking a mixture of hydroxyethyl methacrylate, ethylene glycol dimethacrylate and an initiator for water absorption, and has the advantages of high transparency, more uniform thickness, certain toughness, no bubbles and the like.
The technical solution of the present invention is further described in detail with reference to the accompanying drawings and embodiments.
Drawings
FIG. 1 is a reaction scheme of example 2-2-1.
FIG. 2 is a reaction scheme of example 2-4-1.
FIG. 3 is a reaction scheme of example 3-1.
FIG. 4 is a reaction scheme of step one and step two in example 4-4-1.
FIG. 5 is a reaction scheme of step three in example 4-1.
FIG. 6 is a graph showing water contact angles of hydrogel materials, oxidized hydrogel materials, and modified hydrogel materials.
FIG. 7 shows the water loss of hydrogel materials, oxidized hydrogel materials and modified hydrogel materials under constant temperature and humidity conditions.
Figure 8 shows the hydrogel material, oxidized hydrogel material and modified hydrogel material protein adsorption test (p <0.05, # p <0.01 at 23 ℃ compared to the hydrogel material group).
FIG. 9 shows the refractive indices of hydrogel materials, oxidized hydrogel materials and modified hydrogel materials.
FIG. 10 is a graph of the light transmittance of hydrogel materials, oxidized hydrogel materials, and modified hydrogel materials.
FIG. 11 is a visual depiction of the appearance of hydrogel materials, oxidized hydrogel materials, and modified hydrogel materials on a substrate pattern.
Detailed Description
Examples 1 to 1
The hydrogel material of this example was a contact lens containing pHEMA (a cast contact lens from bos lun riotous year, purchased from the flagship store of tokyo, bos lun).
Examples 1-2-1
The preparation method of the hydrogel material of the embodiment comprises the following steps:
step one, mixing and oscillating 3g of hydroxyethyl methacrylate, 90mg of ethylene glycol dimethacrylate and 7mg of an initiator until the initiator is dissolved to obtain a mixture; the initiator is Irgacure184, and the mixing oscillation time is 5 min; the molecular weight of the hydroxyethyl methacrylate is 130.14g/mol, and the product number is 17348; the molecular weight of the ethylene glycol dimethacrylate is 198.22g/mol, and the product number is 335681; both the hydroxyethyl methacrylate and the ethylene glycol dimethacrylate were purchased from Sigma-Aldrich, both the hydroxyethyl methacrylate and the ethylene glycol dimethacrylate were used to remove the 4-methoxyphenol inhibitor prior to use with an inhibitor scavenger, which was purchased from Sigma-Aldrich, product No. 306312; the molecular weight of the Irgacure184 is 204.26 g/mol;
placing the mixture obtained in the step one in a polymethyl methacrylate mould, and initiating for 15min under ultraviolet light to obtain an initiated system, wherein the power of an ultraviolet lamp used by the ultraviolet light is 400w, the size of the polymethyl methacrylate mould is × 70mm, × 1mm, and the models of the ultraviolet lamps are Cure Zone 2CON-TROL-CURE, Chicago and IL;
step three, under the condition of room temperature, the system after initiation in the step two is placed for 24 hours until the system is completely solidified, and the system is discharged from a mould to obtain gel;
step four, extracting the gel obtained in the step three by using ultrapure water to obtain purified gel; ultra pure water extraction to remove unreacted monomer, crosslinker and/or initiator residues;
and step five, soaking the gel purified in the step four in ultrapure water for 24 hours until the gel is in a saturated water absorption state, so as to obtain the hydrogel material.
Examples 1-2
The preparation method of the hydrogel material of the embodiment comprises the following steps:
step one, mixing and oscillating 3g of hydroxyethyl methacrylate, 90mg of ethylene glycol dimethacrylate and 7mg of an initiator until the initiator is dissolved to obtain a mixture; the initiator is Irgacure184, and the mixing oscillation time is 8 min; the molecular weight of the hydroxyethyl methacrylate is 130.14g/mol, and the product number is 17348; the molecular weight of the ethylene glycol dimethacrylate is 198.22g/mol, and the product number is 335681; both the hydroxyethyl methacrylate and the ethylene glycol dimethacrylate were purchased from Sigma-Aldrich, both the hydroxyethyl methacrylate and the ethylene glycol dimethacrylate were used to remove the 4-methoxyphenol inhibitor prior to use with an inhibitor scavenger, which was purchased from Sigma-Aldrich, product No. 306312; the molecular weight of the Irgacure184 is 204.26 g/mol;
placing the mixture obtained in the step one in a polymethyl methacrylate mould, and initiating for 15min under ultraviolet light to obtain an initiated system, wherein the power of an ultraviolet lamp used by the ultraviolet light is 400w, the size of the polymethyl methacrylate mould is × 70mm, × 1mm, and the models of the ultraviolet lamps are Cure Zone 2CON-TROL-CURE, Chicago and IL;
step three, under the condition of room temperature, the system after initiation in the step two is placed for 12 hours until the system is completely solidified, and the system is discharged from a mould to obtain gel;
step four, extracting the gel obtained in the step three by using ultrapure water to obtain purified gel; ultra pure water extraction to remove unreacted monomer, crosslinker and/or initiator residues;
and step five, soaking the gel purified in the step four in ultrapure water for 24 hours until the gel is in a saturated water absorption state, so as to obtain the hydrogel material.
Examples 1-2 to 3
The preparation method of the hydrogel material of the embodiment comprises the following steps:
step one, mixing and oscillating 3g of hydroxyethyl methacrylate, 90mg of ethylene glycol dimethacrylate and 7mg of an initiator until the initiator is dissolved to obtain a mixture; the initiator is Irgacure184, and the mixing oscillation time is 10 min; the molecular weight of the hydroxyethyl methacrylate is 130.14g/mol, and the product number is 17348; the molecular weight of the ethylene glycol dimethacrylate is 198.22g/mol, and the product number is 335681; both the hydroxyethyl methacrylate and the ethylene glycol dimethacrylate were purchased from Sigma-Aldrich, both the hydroxyethyl methacrylate and the ethylene glycol dimethacrylate were used to remove the 4-methoxyphenol inhibitor prior to use with an inhibitor scavenger, which was purchased from Sigma-Aldrich, product No. 306312; the molecular weight of the Irgacure184 is 204.26 g/mol;
placing the mixture obtained in the step one in a polymethyl methacrylate mould, and initiating for 15min under ultraviolet light to obtain an initiated system, wherein the power of an ultraviolet lamp used by the ultraviolet light is 400w, the size of the polymethyl methacrylate mould is × 70mm, × 1mm, and the models of the ultraviolet lamps are Cure Zone 2CON-TROL-CURE, Chicago and IL;
step three, under the condition of room temperature, the system after initiation in the step two is placed for 48 hours until the system is completely solidified, and the system is discharged from a mould to obtain gel;
step four, extracting the gel obtained in the step three by using ultrapure water to obtain purified gel; ultra pure water extraction to remove unreacted monomer, crosslinker and/or initiator residues;
and step five, soaking the gel purified in the step four in ultrapure water for 24 hours until the gel is in a saturated water absorption state, so as to obtain the hydrogel material.
Example 2-1
The piperidine compound of this example was 2,2,6,6-tetramethylpiperidine oxide, purchased from Sigma-Aldrich, product number 382000, CAS No. 37149-18-1.
Example 2-2-1
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 25min under the condition that the pH value is 4.80 until the mixture is dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2.5 times that of TEMPO-COOH; the TEMPO-COOH is 4-carboxyl-2, 2,6,6-tetramethylpiperidine oxide and purchased from Sigma-Aldrich, the Co. purity in the TEMPO-COOH is 97%, the molecular weight is 200.25g/mol, the product number is 382000, and the CAS is No. 37149-18-1;
step two, dropwise adding a water solution of polyvinylamine into the mixed solution A obtained in the step one, magnetically stirring and reacting for 4 hours under the condition that the pH value is 4.80, and adjusting the pH value of the solution after reaction to 7; in the aqueous solution of the polyvinylamine, the mass percentage of the polyvinylamine is 0.5%; the mass of the polyvinylamine is 3 times of that of TEMPO-COOH; the molecular weight of the polyvinylamine is 80 kDa;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
The reaction principle of the polyvinylamine of this example is shown in FIG. 1.
Example 2-2
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 30min under the condition that the pH value is 4.50 until the mixture is dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 3 times that of TEMPO-COOH; the TEMPO-COOH is 4-carboxyl-2, 2,6,6-tetramethylpiperidine oxide and purchased from Sigma-Aldrich, the Co. purity in the TEMPO-COOH is 97%, the molecular weight is 200.25g/mol, the product number is 382000, and the CAS is No. 37149-18-1;
step two, dropwise adding a water solution of polyvinylamine into the mixed solution A obtained in the step one, magnetically stirring and reacting for 5 hours under the condition that the pH value is 4.50, and adjusting the pH value of the solution after reaction to 7; in the aqueous solution of the polyvinylamine, the mass percentage of the polyvinylamine is 0.25%; the mass of the polyvinylamine is 4 times of that of TEMPO-COOH; the molecular weight of the polyvinylamine is 50 kDa;
step three, after the pH value is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained;
examples 2-2 to 3
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 20min under the condition that the pH value is 5.00 until the mixture is dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2 times of that of TEMPO-COOH; the TEMPO-COOH is 4-carboxyl-2, 2,6,6-tetramethylpiperidine oxide and purchased from Sigma-Aldrich, the Co. purity in the TEMPO-COOH is 97%, the molecular weight is 200.25g/mol, the product number is 382000, and the CAS is No. 37149-18-1;
step two, dropwise adding a water solution of polyvinylamine into the mixed solution A obtained in the step one, magnetically stirring and reacting for 3 hours under the condition that the pH value is 5.00, and adjusting the pH value of the solution after reaction to 7; in the aqueous solution of the polyvinylamine, the mass percentage of the polyvinylamine is 1.0 percent; the mass of the polyvinylamine is 2 times of that of TEMPO-COOH; the molecular weight of the polyvinylamine is 100 kDa;
step three, after the pH value is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained;
example 2-3-1
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 25min under the condition that the pH value is 4.80 until the mixture is dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2.5 times that of TEMPO-COOH; the TEMPO-COOH is 4-carboxyl-2, 2,6,6-tetramethylpiperidine oxide and purchased from Sigma-Aldrich, the Co. purity in the TEMPO-COOH is 97%, the molecular weight is 200.25g/mol, the product number is 382000, and the CAS is No. 37149-18-1;
step two, dropwise adding a water solution of polyethyleneimine into the mixed solution A obtained in the step one, magnetically stirring and reacting for 4 hours under the condition that the pH is 4.80, and adjusting the pH of the solution after reaction to 7; in the aqueous solution of the polyethyleneimine, the mass percentage of the polyethyleneimine is 0.5%; the mass of the polyethyleneimine is 3 times of that of TEMPO-COOH; the molecular weight of the polyethyleneimine is 100 kDa;
step three, after the pH value is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained;
examples 2-3-2
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 30min under the condition that the pH value is 4.50 until the mixture is dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 3 times that of TEMPO-COOH; the TEMPO-COOH is 4-carboxyl-2, 2,6,6-tetramethylpiperidine oxide and purchased from Sigma-Aldrich, the Co. purity in the TEMPO-COOH is 97%, the molecular weight is 200.25g/mol, the product number is 382000, and the CAS is No. 37149-18-1;
step two, dropwise adding a water solution of polyethyleneimine into the mixed solution A obtained in the step one, magnetically stirring and reacting for 3 hours under the condition that the pH is 5.00, and adjusting the pH of the solution after reaction to 7; in the aqueous solution of the polyethyleneimine, the mass percentage of the polyethyleneimine is 0.25%; the mass of the polyethyleneimine is 4 times of that of TEMPO-COOH; the molecular weight of the polyethyleneimine is 50 kDa;
step three, after the pH value is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained;
examples 2 to 3
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 20min under the condition that the pH value is 5.00 until the mixture is dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2 times of that of TEMPO-COOH; the TEMPO-COOH is 4-carboxyl-2, 2,6,6-tetramethylpiperidine oxide and purchased from Sigma-Aldrich, the Co. purity in the TEMPO-COOH is 97%, the molecular weight is 200.25g/mol, the product number is 382000, and the CAS is No. 37149-18-1;
step two, dropwise adding a water solution of polyethyleneimine into the mixed solution A obtained in the step one, magnetically stirring and reacting for 5 hours under the condition that the pH is 4.50, and adjusting the pH of the solution after reaction to 7; in the aqueous solution of the polyethyleneimine, the mass percentage of the polyethyleneimine is 1.0%; the mass of the polyethyleneimine is 2 times of that of TEMPO-COOH; the molecular weight of the polyethyleneimine is 150 kDa;
step three, after the pH value is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained;
example 2-4-1
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
step one, dissolving polyacrylic acid and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water, and magnetically stirring for 25min under the condition that the pH value is 4.80 until the polyacrylic acid and the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride are dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1.8 times that of polyacrylic acid; the molecular weight of the polyacrylic acid is 80 kDa;
step two, TEMPO-NH is added2Dropwise adding the aqueous solution into the mixed solution A obtained in the first step, magnetically stirring and reacting for 4 hours under the condition that the pH value is 4.80, and adjusting the pH value of the solution after reaction to be 7; the mass of the polyacrylic acid is TEMPO-NH22.5 times of the mass; the TEMPO-NH2(4-amino-2, 2,6, 6-tetramethylpiperidinoxide) purchased from Sigma-Aldrich Co, purity 97%, molecular weight 171.26g/mol, product number 163945, CAS No. 14691-88-4;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
The reaction principle of this example is shown in FIG. 2.
Examples 2-4-2
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
step one, dissolving polyacrylic acid and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water, and magnetically stirring for 30min under the condition that the pH value is 4.50 until the polyacrylic acid and the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride are dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2 times of that of polyacrylic acid; the molecular weight of the polyacrylic acid is 50 kDa;
step two, TEMPO-NH is added2Dropwise adding the aqueous solution into the mixed solution A obtained in the first step, magnetically stirring and reacting for 5 hours under the condition that the pH value is 4.50, and adjusting the pH value of the solution after reaction to be 7; the mass of the polyacrylic acid is TEMPO-NH 22 times of the mass; the TEMPO-NH2(4-amino-2, 2,6, 6-tetramethylpiperidinoxide) purchased from Sigma-Aldrich Co, purity 97%, molecular weight 171.26g/mol, product number 163945, CAS No. 14691-88-4;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
Examples 2 to 4 to 3
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
step one, dissolving polyacrylic acid and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water, and magnetically stirring for 20min under the condition that the pH value is 5.00 until the polyacrylic acid and the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride are dissolved to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1.5 times that of polyacrylic acid; the molecular weight of the polyacrylic acid is 150 kDa;
step two,TEMPO-NH2Dropwise adding the aqueous solution into the mixed solution A obtained in the first step, magnetically stirring and reacting for 3 hours under the condition that the pH value is 5.00, and adjusting the pH value of the solution after reaction to 7; the mass of the polyacrylic acid is TEMPO-NH 23 times of the mass; the TEMPO-NH2(4-amino-2, 2,6, 6-tetramethylpiperidinoxide) purchased from Sigma-Aldrich Co, purity 97%, molecular weight 171.26g/mol, product number 163945, CAS No. 14691-88-4;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
Example 2-5-1
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving a polyethylene glycol derivative and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water, and magnetically stirring for 25min under the condition that the pH value is 4.70 until the polyethylene glycol derivative and the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride are dissolved to obtain a mixed solution A; the polyethylene glycol derivative is a four-arm polyethylene glycol carboxyl group, the terminal groups of the four-arm polyethylene glycol carboxyl group are carboxyl groups, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2 times of that of the four-arm polyethylene glycol carboxyl group; the molecular weight of the four-arm polyethylene glycol carboxyl is 30kDa
Step two, TEMPO-NH is added2Dropwise adding the aqueous solution into the mixed solution A obtained in the first step, magnetically stirring and reacting for 4 hours under the condition that the pH value is 4.70, and adjusting the pH value of the solution after reaction to be 7; the polyethylene glycol derivative has the mass of TEMPO-NH22.5 times of the mass; the TEMPO-NH2(4-amino-2, 2,6, 6-tetramethylpiperidinoxide) purchased from Sigma-Aldrich Co, purity 97%, molecular weight 171.26g/mol, product number 163945, CAS No. 14691-88-4;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
Examples 2 to 5 and 2
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving a polyethylene glycol derivative and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water, and magnetically stirring for 20min under the condition that the pH value is 4.50 until the polyethylene glycol derivative and the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride are dissolved to obtain a mixed solution A; the polyethylene glycol derivative is a four-arm polyethylene glycol carboxyl group, the terminal groups of the four-arm polyethylene glycol carboxyl group are carboxyl groups, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 3 times that of the four-arm polyethylene glycol carboxyl group; the molecular weight of the four-arm polyethylene glycol carboxyl is 10 kDa;
step two, TEMPO-NH is added2Dropwise adding the aqueous solution into the mixed solution A obtained in the first step, magnetically stirring and reacting for 3 hours under the condition that the pH value is 4.50, and adjusting the pH value of the solution after reaction to be 7; the polyethylene glycol derivative has the mass of TEMPO-NH 22 times of the mass; the TEMPO-NH2(4-amino-2, 2,6, 6-tetramethylpiperidinoxide) purchased from Sigma-Aldrich Co, purity 97%, molecular weight 171.26g/mol, product number 163945, CAS No. 14691-88-4;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
Examples 2 to 5 to 3
The piperidine compound of this embodiment is a polymer grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is a polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide, and the preparation method of the polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide includes the following steps:
dissolving a polyethylene glycol derivative and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water, and magnetically stirring for 30min under the condition that the pH value is 5.00 until the polyethylene glycol derivative and the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride are dissolved to obtain a mixed solution A; the polyethylene glycol derivative is a four-arm polyethylene glycol carboxyl group, the terminal groups of the four-arm polyethylene glycol carboxyl group are carboxyl groups, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1 time of that of the four-arm polyethylene glycol carboxyl group; the molecular weight of the four-arm polyethylene glycol carboxyl is 50 kDa;
step two, TEMPO-NH is added2Dropwise adding the aqueous solution into the mixed solution A obtained in the first step, magnetically stirring and reacting for 5 hours under the condition that the pH value is 5.00, and adjusting the pH value of the solution after reaction to be 7; the polyethylene glycol derivative has the mass of TEMPO-NH 23 times of the mass; the TEMPO-NH2(4-amino-2, 2,6, 6-tetramethylpiperidinoxide) purchased from Sigma-Aldrich Co, purity 97%, molecular weight 171.26g/mol, product number 163945, CAS No. 14691-88-4;
and step three, after the pH value of the system is adjusted to 7 in the step two, the system is dialyzed and then is freeze-dried, and the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is obtained.
Example 3-1
The preparation method of the hyaluronic acid-adipic acid dihydrazide solution of the embodiment comprises the following steps:
step one, adding adipic Acid Dihydrazide (ADH) into a sodium hyaluronate aqueous solution to obtain a mixed solution; the mass of the adipic acid dihydrazide is 20 times that of the sodium hyaluronate; the mass percentage content of the sodium hyaluronate in the sodium hyaluronate water solution is 0.25%;
step two, magnetically stirring the mixed solution obtained in the step one for reaction for 3 hours under the condition that the pH value is 4.75, and adjusting the pH value of the solution after the reaction to be 7;
and step three, dialyzing and freeze-drying the reaction system after pH adjustment in the step two, placing the reaction system into water, and magnetically stirring the reaction system until the reaction system is dissolved to obtain a hyaluronic acid-adipic acid dihydrazide (HA-Hzd) solution.
The reaction principle of this example is shown in FIG. 3.
Examples 3 to 2
The preparation method of the hyaluronic acid-adipic acid dihydrazide solution of the embodiment comprises the following steps:
step one, adding adipic acid dihydrazide into a sodium hyaluronate aqueous solution to obtain a mixed solution; the mass of the adipic acid dihydrazide is 18 times that of the sodium hyaluronate; the mass percentage content of the sodium hyaluronate in the sodium hyaluronate water solution is 0.35%;
step two, magnetically stirring the mixed solution obtained in the step one for reaction for 4 hours under the condition that the pH value is 5.0, and adjusting the pH value of the solution after the reaction to be 7;
and step three, after the pH is adjusted in the step two, the reaction system is dialyzed, freeze-dried and then placed in water, and the mixture is magnetically stirred until the mixture is dissolved, so that the hyaluronic acid-adipic acid dihydrazide solution is obtained.
Examples 3 to 3
The preparation method of the hyaluronic acid-adipic acid dihydrazide solution of the embodiment comprises the following steps:
step one, adding adipic acid dihydrazide into a sodium hyaluronate aqueous solution to obtain a mixed solution; the mass of the adipic acid dihydrazide is 15 times that of the sodium hyaluronate; the mass percentage of the sodium hyaluronate in the sodium hyaluronate water solution is 0.5%;
step two, magnetically stirring the mixed solution obtained in the step one for reaction for 5 hours under the condition that the pH value is 4.50, and adjusting the pH value of the solution after the reaction to be 7;
and step three, after the pH is adjusted in the step two, the reaction system is dialyzed, freeze-dried and then placed in water, and the mixture is magnetically stirred until the mixture is dissolved, so that the hyaluronic acid-adipic acid dihydrazide solution is obtained.
Example 4-1
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-1 with pure water for three times, and then soaking the hydrogel material in 200mL of buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 6; the piperidine compound is 2,2,6,6-tetramethylpiperidine oxide of example 2-1; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 250 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.0 percent;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 24 hours to obtain an oxidized hydrogel material; the mass of the laccase is 1 time of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.04%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5.0;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-1, and performing functional modification for 4 hours under the stirring condition that the pH value is 7 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1.5 times that of the oxidized hydrogel material; the reaction principle of step three is shown in figure 5.
Example 4-2-1
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, 1g of the hydrogel material of the embodiment 1-2-1 is washed with pure water for three times and then soaked in 100mL of buffer solution dissolved with piperidine compounds to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 4; the piperidine compound is the polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide of example 2-2-1; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 400 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.3%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 24 hours to obtain an oxidized hydrogel material; the mass of the laccase is 0.5 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.05%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with the pH value of 4.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-2, and performing functional modification for 3 hours under the stirring condition that the pH value is 8 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 2 times of that of the oxidized hydrogel material.
4-2-2
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-2 with pure water for three times, and then soaking the hydrogel material in 200mL of buffer solution in which piperidine compounds are dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with the pH value of 8; the piperidine compound is the polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide of example 2-2-2; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 200 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.0 percent;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 12 hours to obtain an oxidized hydrogel material; the mass of the laccase is 1 time of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.03%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-3, and performing functional modification for 5 hours under the stirring condition that the pH value is 6 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1 time of that of the oxidized hydrogel material.
4-2-3
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-3 with pure water for three times, and soaking the hydrogel material in 100mL of buffer solution dissolved with piperidine compounds to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 6; the piperidine compound is the polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide of example 2-2-3; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 100 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.5%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 8 hours to obtain an oxidized hydrogel material; the mass of the laccase is 2 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.025%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-1, and performing functional modification for 4 hours under the stirring condition that the pH value is 7 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1.5 times of that of the oxidized hydrogel material.
Example 4-3-1
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 1g of the hydrogel material of the embodiment 1-2-3 with pure water for three times, and soaking the hydrogel material in 100mL of buffer solution dissolved with piperidine compounds to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 4; the piperidine compound is polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide in example 2-3-1; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 400 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.3%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 24 hours to obtain an oxidized hydrogel material; the mass of the laccase is 0.5 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.05%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with the pH value of 4.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-1, and performing functional modification for 3 hours under the stirring condition that the pH value is 8 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 2 times of that of the oxidized hydrogel material.
4-3-2
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-1 with pure water for three times, and then soaking the hydrogel material in 200mL of buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with the pH value of 8; the piperidine compound is polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide of example 2-3-2; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 200 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.0 percent;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 12 hours to obtain an oxidized hydrogel material; the mass of the laccase is 1 time of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.03%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-3, and performing functional modification for 5 hours under the stirring condition that the pH value is 6 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1 time of that of the oxidized hydrogel material.
4-3-3
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-2 with pure water for three times, and then soaking the hydrogel material in 100mL of buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 6; the piperidine compound is polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide in example 2-3-3; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 100 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.5%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 8 hours to obtain an oxidized hydrogel material; the mass of the laccase is 2 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.025%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-2, and performing functional modification for 4 hours under the stirring condition that the pH value is 7 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1.5 times of that of the oxidized hydrogel material.
Example 4-4-1
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 1g of the hydrogel material of the embodiment 1-2-3 with pure water for three times, and soaking the hydrogel material in 100mL of buffer solution dissolved with piperidine compounds to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 5; the piperidine compound was polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide (Polymer-g-TEMPO) of example 2-4-1; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 400 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.3%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 24 hours to obtain an oxidized hydrogel material (Ox-pHEMA); the mass of the laccase is 0.5 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.05%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5;
the reaction principle of the first step and the second step is shown in figure 4;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide (HA-Hzd) solution obtained in the example 3-1, and performing functional modification for 3 hours under the stirring condition that the pH value is 8 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 2 times that of the oxidized hydrogel material; the reaction principle of step three is shown in figure 5.
4-4-2
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-1 with pure water for three times, and then soaking the hydrogel material in 100mL of buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with the pH value of 8; the piperidine compound is polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide of example 2-4-2; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 100 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.0 percent;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 12 hours to obtain an oxidized hydrogel material; the mass of the laccase is 1 time of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.03%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with the pH value of 4.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-3, and performing functional modification for 5 hours under the stirring condition that the pH value is 6 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1 time of that of the oxidized hydrogel material.
4-4-3
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-2 with pure water for three times, and then soaking the hydrogel material in 200mL of buffer solution in which piperidine compounds are dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 4; the piperidine compound is polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide of example 2-4-3; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 200 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.5%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 8 hours to obtain an oxidized hydrogel material; the mass of the laccase is 2 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.025%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-2, and performing functional modification for 4 hours under the stirring condition that the pH value is 7 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1.5 times of that of the oxidized hydrogel material.
Example 4-5-1
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-3 with pure water for three times, and soaking the hydrogel material in 200mL of buffer solution dissolved with piperidine compounds to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 4; the piperidine compound is 2,2,6,6-tetramethylpiperidine oxide grafted by the polyethylene glycol derivative of example 2-5-1; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 400 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.3%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 24 hours to obtain an oxidized hydrogel material; the mass of the laccase is 0.5 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.05%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with the pH value of 4.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-2, and performing functional modification for 3 hours under the stirring condition that the pH value is 8 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1 time of that of the oxidized hydrogel material.
4-5-2
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, washing 10g of the hydrogel material of the embodiment 1-2-1 with pure water for three times, and then soaking the hydrogel material in 100mL of buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 6; the piperidine compound is 2,2,6,6-tetramethylpiperidine oxide grafted by the polyethylene glycol derivative of example 2-5-2; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 100 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.0 percent;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 8 hours to obtain an oxidized hydrogel material; the mass of the laccase is 1 time of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.03%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-3, and performing functional modification for 5 hours under the stirring condition that the pH value is 6 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 1.5 times of that of the oxidized hydrogel material.
4-5-3
The method for catalytic oxidation and functional modification of the hydrogel material comprises the following steps:
step one, 1g of the hydrogel material of the embodiment 1-2-2 is washed with pure water for three times and then soaked in 100mL of buffer solution dissolved with piperidine compounds to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with the pH value of 8; the piperidine compound is 2,2,6,6-tetramethylpiperidine oxide grafted by the polyethylene glycol derivative of example 2-5-3; in the buffer solution dissolved with the piperidine compounds, the mass concentration of the piperidine compounds is 200 mg/L; the mass percentage concentration of the acetic acid-sodium acetate buffer solution is 2.5%;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 12 hours to obtain an oxidized hydrogel material; the mass of the laccase is 2 times of that of the piperidine compound, and the mass percentage content of the laccase in the laccase solution is 0.025%; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with pH of 5.5;
step three, soaking the oxidized hydrogel material obtained in the step two in the hyaluronic acid-adipic acid dihydrazide solution obtained in the embodiment 3-1, and performing functional modification for 4 hours under the stirring condition that the pH value is 7 to obtain a modified hydrogel material; the mass of the hyaluronic acid-adipic acid dihydrazide is 2 times of that of the oxidized hydrogel material.
And (3) performance testing:
and (3) carrying out performance test on the hydrogel material, the oxidized hydrogel material (step two) obtained by the method of the embodiment 4-1 to 4-5-3 and the modified hydrogel material (step three).
Contact angle measurement: the contact angle of the material was measured using a contact angle measuring instrument of the type 100-. All samples were stored in the OPTI-FREE REPLENISH contact lens solution for 14 days, the solution was changed every two days, and the contact angles were measured after 1, 4, 7 and 14 days of soaking. Before the test, after the water on the surface of the material is slightly absorbed by using KimWipe, 25 mu L of ultrapure water drop is dripped on the surface of the sample at 23 ℃, and the contact angle can be measured.
Drying and dehydration kinetics test: after soaking a dried sample of the material in ultrapure water for 24 hours to swelling equilibrium, it was removed from the water, the surface of the material was blotted using absorbent paper, then weighed to calculate the equilibrium water content, the sample was placed vertically in a constant temperature and humidity cabinet (ESL-2 CA, ESPEC North America, 50% humidity, 23 ℃ C.) rack to allow moisture to evaporate from both sides, and weighed again after a certain time interval to explore the evaporation rate versus material surface treatment for 0, 5, 10, 15, 20, 30, 60, 90 and 120 minutes.
According to fig. 6, the water contact angles of the hydrogel material, the oxidized hydrogel material and the modified hydrogel material are sequentially reduced, the contact angle is reduced from 69.7 +/-1.5 degrees to 41.5 +/-0.9 degrees by oxidation, and the contact angle of the modified hydrogel material is reduced to 35.0 +/-1.0 degrees, which shows that the hydrophilic property of the modified hydrogel material is greatly improved. The hydrogel material after modification is reduced from 35.0 +/-1.0 degrees to 31.3 +/-1.2 degrees after being stored for 7 days, and is changed to 31.6 +/-1.9 degrees on the 14 th day (p is less than 0.05 relative to the initial), and the hydrogel material after modification can still keep hydrophilic after being stored for two weeks, which indicates that the stability of the surface coating is higher. According to FIG. 7, the modified hydrogel material of the present invention has a greatly reduced water evaporation rate relative to the hydrogel material, indicating that it has a high interfacial hydrophilicity, which can prevent water from evaporating from the hydrogel material (relative humidity in air is 50%, 23 ℃). The method of the invention can improve the high moisture retention of the modified hydrogel material.
Protein adsorption test: experiments using human serum albumin as a representative protein, proteins were radiolabeled using the iodine chloride method with Na125I, then the radiolabeled samples were passed through two 3mL syringes (Bio-Rad, Hercules, CA) filled with AG 1-X4 resin to remove unbound 125I, and free iodide was measured by trichloroacetic acid precipitation of the protein, such that the free iodide content in both the radiolabeled human serum albumin and lysozyme solutions was less than 1% of the total radioactivity.
The material discs were equilibrated in PBS buffer for 24 hours, and the surface of the material was blotted with absorbent paper and then placed in a 96-well plate. Human serum albumin solution (1mg/mL, containing 10% (w/w) radiolabeled protein, 250mL) was added to wells (n ═ 4), the samples were allowed to stand at room temperature, then the samples were washed with PBS buffer (three cycles of 5 minutes each) to remove unbound protein, finally the surfaces were counted for radioactivity using a Wozard 31480 automated gamma counter (PerkinElmer) and the amount of adsorption was calculated using background-corrected surface counts.
From fig. 8, the protein adsorption of both the hydrogel material and the oxidized hydrogel material increased with time, while the modified hydrogel material showed no significant change in protein adsorption with time, maintaining low adsorption of the protein, indicating that hyaluronic acid modification can reduce the adsorption of the protein on the hydrogel material.
Material appearance, refractive index and light transmittance test: the refractive index of the sample WAs tested using a digital hand-held refractometer (Atago, Bellevue, WA), with the experiment measuring three times. The transmission between 380nm and 750nm was measured using an ultraviolet spectrophotometer (Beckman Coulter DU800) with a scan rate of 0.5 nm/s.
As shown in FIGS. 9-10, the refractive indices of the oxidized hydrogel material and the modified hydrogel material did not change significantly compared to the hydrogel material (p > 0.1 in the pair-wise comparison), and the refractive index values for all samples were between 1.332 and 1.334, very close to the refractive index of human tears. According to the data of an ultraviolet spectrophotometer, the visible light transmittance of the oxidized hydrogel material and the modified hydrogel material is more than 88% in the visible light range, is higher than that of the adult lens, and can be determined as completely transparent.
Visual material appearance:
as shown in fig. 11, the oxidized hydrogel material and the modified hydrogel material did not significantly differ from the hydrogel material in appearance. From the view point of physical and chemical properties, the modification does not significantly change the overall morphology of the material, does not cause the formation of a phase-separated structure in the gel, and hardly influences the optical properties of the hydrogel material, and the method successfully carries out catalytic oxidation and surface grafting on the material with the hyaluronic acid coating.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, changes and equivalent structural changes made to the above embodiment according to the technical spirit of the present invention still fall within the protection scope of the technical solution of the present invention.
Claims (10)
1. A method for catalytic oxidation and functional modification of hydrogel materials is characterized by comprising the following steps:
step one, soaking a hydrogel material in a buffer solution in which a piperidine compound is dissolved to obtain a mixed system; the buffer solution is acetic acid-sodium acetate buffer solution with pH of 4-8; the piperidine compound is 2,2,6,6-tetramethyl piperidine oxide or macromolecule grafting 2,2,6,6-tetramethyl piperidine oxide;
step two, adding a laccase solution into the mixed system obtained in the step one, and then introducing oxygen for catalytic oxidation for 8-24 hours to obtain an oxidized hydrogel material;
and step three, soaking the oxidized hydrogel material obtained in the step two in a hyaluronic acid-adipic acid dihydrazide solution, and performing functional modification for 3-5 hours under the stirring condition that the pH value is 6-8 to obtain the modified hydrogel material.
2. The method for catalytic oxidation and functional modification of hydrogel material as claimed in claim 1, wherein in the buffer solution dissolved with piperidine compound in step one, the mass concentration of piperidine compound is 100 mg/L-400 mg/L; in the step one, the volume of the buffer solution dissolved with the piperidine compound is 10-100 times of the mass of the hydrogel material, the unit of the volume of the buffer solution dissolved with the piperidine compound is mL, and the unit of the mass of the hydrogel material is g.
3. The method of claim 1, wherein in the step one, the polymer-grafted 2,2,6,6-tetramethylpiperidine oxide is polyvinylamine-grafted 2,2,6,6-tetramethylpiperidine oxide, polyethyleneimine-grafted 2,2,6,6-tetramethylpiperidine oxide, polyacrylic acid-grafted 2,2,6,6-tetramethylpiperidine oxide or polyethylene glycol derivative-grafted 2,2,6,6-tetramethylpiperidine oxide.
4. The method of claim 3, wherein when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide in the step one is polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide or polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, the method for preparing the polymer grafted 2,2,6,6-tetramethylpiperidine oxide comprises the following steps:
step 101, dissolving TEMPO-COOH and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 20-30 min under the condition that the pH value is 4.50-5.00 to obtain a mixed solution A; the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 2-3 times of that of TEMPO-COOH;
102, dripping an aqueous solution of a high molecular compound to be grafted into the mixed solution A obtained in the step 101, magnetically stirring and reacting for 3-5 h under the condition that the pH value is 4.50-5.00, and adjusting the pH value of the solution after reaction to 7; in the aqueous solution of the macromolecular compound to be grafted, the mass percentage content of the macromolecular compound to be grafted is 0.25-1.0%; the mass of the macromolecular compound to be grafted is 2-4 times of that of TEMPO-COOH;
103, adjusting the pH value in the step 102, dialyzing the system, and freeze-drying to obtain the polymer grafted 2,2,6,6-tetramethylpiperidine oxide;
when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyvinylamine grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer compound to be grafted in step 102 is polyvinylamine, and the molecular weight of the polyvinylamine is 50-100 kDa; when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyethyleneimine grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer compound to be grafted in step 102 is polyethyleneimine, and the molecular weight of the polyethyleneimine is 50 kDa-150 kDa.
5. The method of claim 3, wherein the polymer grafted 2,2,6,6-tetramethylpiperidine oxide in the first step is polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide or polyethylene glycol derivative grafted 2,2,6,6-tetramethylpiperidine oxide, and the method for preparing the polymer grafted 2,2,6,6-tetramethylpiperidine oxide comprises the following steps:
step 201, dissolving a high molecular compound to be grafted and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into water, and magnetically stirring for 20-30 min under the condition that the pH value is 4.50-5.00 to obtain a mixed solution A;
step 202, TEMPO-NH2Dropwise adding the aqueous solution into the mixed solution A obtained in the step 201, magnetically stirring and reacting for 3-5 h under the condition that the pH value is 4.50-5.00, and adjusting the pH value of the solution after reaction to 7; the mass of the polymer compound to be grafted in step 201 is TEMPO-NH in step 20222 to 3 times of the mass;
step 203, after the pH is adjusted in the step 202, the system is dialyzed and then is freeze-dried to obtain the polymer grafted 2,2,6,6-tetramethylpiperidine oxide;
when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is polyacrylic acid grafted 2,2,6,6-tetramethylpiperidine oxide, the polymer compound to be grafted in step 201 is polyacrylic acid, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1.5-2 times that of the polyacrylic acid; the molecular weight of the polyacrylic acid is 50-150 kDa; when the polymer grafted 2,2,6,6-tetramethylpiperidine oxide is 2,2,6,6-tetramethylpiperidine oxide grafted by a polyethylene glycol derivative, in step 201, the polymer compound to be grafted is a four-arm polyethylene glycol carboxyl group, the terminal groups of the four-arm polyethylene glycol carboxyl group are all carboxyl groups, and the mass of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 1-3 times of that of the four-arm polyethylene glycol carboxyl group; the molecular weight of the four-arm polyethylene glycol carboxyl is 10kDa to 50 kDa.
6. The method for catalytic oxidation and functional modification of a hydrogel material as claimed in claim 1, wherein the concentration of the acetic acid-sodium acetate buffer solution in the first step is 2.0-2.5% by mass.
7. The method for catalytic oxidation and functional modification of hydrogel materials according to claim 1, wherein the laccase in the second step is 0.5 to 2 times the mass of the piperidine compound, and the laccase is contained in the laccase solution in an amount of 0.025 to 0.05% by mass; the solvent of the laccase solution is acetic acid-sodium acetate buffer solution with the pH value of 4.5-5.5.
8. The method for catalytic oxidation and functional modification of hydrogel material according to claim 1, wherein the mass of the hyaluronic acid-adipic acid dihydrazide in step three is 1-2 times of the mass of the oxidized hydrogel material.
9. The method for catalytic oxidation and functional modification of hydrogel material according to claim 1, wherein the method for preparing the hyaluronic acid-adipic acid dihydrazide solution in step three comprises:
step 301, adding adipic acid dihydrazide to the aqueous solution of sodium hyaluronate to obtain a mixed solution; the mass of the adipic acid dihydrazide is 15-20 times that of the sodium hyaluronate; the mass percentage content of the sodium hyaluronate in the sodium hyaluronate water solution is 0.25-0.5%;
step 302, magnetically stirring the mixed solution obtained in the step 301 under the condition that the pH value is 4.50-5.00 for reaction for 3-5 h, and adjusting the pH value of the reacted solution to 7;
step 303, after the pH is adjusted in step 302, the reaction system is dialyzed, freeze-dried and then placed in water, and the mixture is magnetically stirred until the mixture is dissolved, so that a hyaluronic acid-adipic acid dihydrazide solution is obtained.
10. The method for catalytic oxidation and functional modification of hydrogel material according to claim 1, wherein the method for preparing hydrogel material in step one comprises the following steps:
step 401, mixing hydroxyethyl methacrylate, ethylene glycol dimethacrylate and an initiator, and oscillating until the mixture is dissolved to obtain a mixture; the mass ratio of the hydroxyethyl methacrylate to the ethylene glycol dimethacrylate to the initiator is 3000:90:7, the initiator is Irgacure184, and the mixing oscillation time is 5-10 min;
step 402, placing the mixture obtained in the step 401 in a polymethyl methacrylate mould, and initiating for 15min under ultraviolet light to obtain an initiated system; the power of an ultraviolet lamp used by the ultraviolet light is 400 w;
step 403, under the condition of room temperature, placing the initiated system in the step 402 until the initiated system is completely cured to obtain gel;
step 404, extracting the gel obtained in the step 403 with ultrapure water to obtain a purified gel;
and 405, soaking the gel purified in the step 404 in ultrapure water until the gel is in a saturated water absorption state to obtain a hydrogel material.
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