CN116102761A - Multifunctional hydrogel coating with high antibacterial agent loading efficiency and pH responsiveness, and preparation method and application thereof - Google Patents
Multifunctional hydrogel coating with high antibacterial agent loading efficiency and pH responsiveness, and preparation method and application thereof Download PDFInfo
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- CN116102761A CN116102761A CN202310009691.0A CN202310009691A CN116102761A CN 116102761 A CN116102761 A CN 116102761A CN 202310009691 A CN202310009691 A CN 202310009691A CN 116102761 A CN116102761 A CN 116102761A
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- hydrogel
- coating
- polydimethylsiloxane
- loading
- agent
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Abstract
The application discloses a multifunctional hydrogel coating with high antibacterial agent loading efficiency and pH responsiveness, and a preparation method and application thereof, and belongs to the field of biomedical materials. A composite hydrogel, the composite hydrogel comprising a substrate, a polyamphogel coating, an antimicrobial agent; the substrate is polydimethylsiloxane; the polyamphole hydrogel coating comprises polymethacrylic acid sulfobetaine; the antibacterial agent comprises povidone iodine, metallic copper ions and furacilin; the substrate is covalently bonded to the polyamphogel coating; the antimicrobial agent is non-covalently bound to the polyzwitterionic hydrogel coating. The composite hydrogel can greatly improve the loading capacity of various clinically common antibacterial agents (such as disinfectants, metal ions, antibiotics and the like) in the hydrogel coating; the antimicrobial agent may be released in a pH response.
Description
Technical Field
The application relates to a multifunctional hydrogel coating with high antibacterial agent loading efficiency and pH responsiveness, and a preparation method and application thereof, and belongs to the field of biomedical materials.
Background
Urinary tract infection associated with urinary catheters is one of the main hospital acquired infections, mainly due to the biofilm formation by bacteria such as e.coli, proteus mirabilis, etc. colonizing the urinary catheters. Among these, some pathogenic bacteria such as Proteus mirabilis release urease, decompose urea into ammonia, cause urine to alkalize, cause calcium and magnesium ions in urine to deposit in the form of calcium phosphate and magnesium phosphate, form urinary tract stones, clog urinary catheters, and even possibly cause retention or reflux of infected urine, and increase the risk of up-going infections (such as pyelonephritis or kidney infections), blood flow infections, and even death. In order to reduce bacterial attachment, inhibit biofilm formation and scale formation, it is an effective strategy to modify the surface of the device with an antimicrobial coating.
The loaded antibacterial agent is a widely used preparation mode of antibacterial coating in clinic. But the improvement of the loading of the antibacterial agent in the coating and the regulation of the release of the antibacterial agent still face great challenges. The traditional antibacterial agent release antibacterial coating strategy can quickly release and exhaust the antibacterial agent in a short time due to the limitation of the loading capacity, and bacteria can quickly multiply after surface colonization, so that the coating is invalid. How to combine the antibacterial agent and the coating carrier in a physical or chemical way to form a stable compound in the coating, and improving the loading capacity of the antibacterial agent and the combination stability of the antibacterial agent in the coating are important points of the research of the antibacterial agent release type coating.
The regulation of the rational release of the antimicrobial agent carried in the coating is another important point and difficulty in the design and construction of antimicrobial coatings. The response release of the antibacterial agent is achieved by exogenous stimuli (such as temperature, ultrasonic waves, light, electric pulses and magnetic fields) or endogenous triggers (such as pH, enzymes and redox), and bacterial infections which may occur in medical devices can be reasonably handled. Exogenous stimuli generally require subjective judgment of the infection to determine a subsequent therapeutic strategy. This means that the implant surface cannot inhibit the initial bacterial adhesion. Endogenous triggers are more time-efficient. If a bacterial infection induces a local acidity increase through anaerobic glycolysis, which can be used as an endogenous trigger for the release of a responsive drug, in a weakly acidic environment, the hydrolysis of the citric acid amide exposes the antimicrobial cationic amine groups of the AMP coating to enhance its antimicrobial properties. Similar carrier designs with pH response characteristics can avoid nonsensical drug release, thereby improving drug availability, extending antibacterial activity and reducing toxic side effects on normal tissues. One of the remarkable characteristics of urease-producing bacteria (including Proteus mirabilis, morganella, klebsiella pneumoniae, pseudomonas aeruginosa and other gram-positive bacteria such as Staphylococcus aureus and Staphylococcus saprophyticus) after infecting the urinary tract is that urea is decomposed to alkalize the urine, and deposition of calcium phosphate, magnesium phosphate and the like is caused, wherein the bacteria such as Pseudomonas aeruginosa, proteus mirabilis, klebsiella pneumoniae and the like produce high urease, and the pH value of the urine can be raised to 9-10 in a short time (within a few days), so that stones are induced to form, the urinary tract channel is blocked, and serious complications are finally caused.
Chemical bond cleavage and protonation of functional groups are common strategies to achieve pH-responsive drug delivery. For chemical bond cleavage, pH-responsive groups can be obtained by introducing linkers such as hydrazones, imines, oximes, amides, polyacetals, polyketals, ethers, orthoesters, and the like into their structures. However, low loading efficiency and cytotoxic side effects of the lysate limit its development and widespread use. The protonation/deprotonation process can achieve pH response and has higher safety. Only weakly acidic or basic functional groups such as common groups like polyacids or polybases in pH-responsive polymers, lipids, polysaccharides or polypeptides are required to achieve a responsive release. When the local pH value changes, the protonated pH response system can regulate and control the release of the antibacterial agent through the protonation or deprotonation process of the reversibly ionized carboxyl and amino, and finally the intelligent response antibacterial performance is realized.
Disclosure of Invention
According to a first aspect of the present application, there is provided a composite hydrogel, the present invention prepares a polyzwitterionic hydrogel coating and/or a polyzwitterionic hydrogel coating of composite natural polyphenols on a substrate surface by free radical polymerization, and loads clinically usual antibacterial agents such as povidone iodine, metallic copper ions, the antibiotic furacilin, etc. by various non-covalent interactions between natural polyphenols and zwitterionic groups and antibacterial agents. Povidone iodine is a complex of 1-vinyl-2-pyrrolidone homopolymer and iodine, which is combined with methacrylic acid sulfobetaine groups and tannic acid in the hydrogel coating through electrostatic action and hydrogen bonding. The copper ions form a coordination with catechol groups of tannins in the hydrogel coating, forming a stable metal-polyphenol network in the coating. Furacilin is respectively combined with tannic acid and methacrylic acid sulfobetaine groups in the hydrogel coating through hydrogen bond and electrostatic action. When the pH value changes, the hydrogen bond and coordination between the antibacterial agent and the hydrogel coating are destroyed due to the change of the structure, so that the controlled release of the antibacterial agent is realized. Meanwhile, the pH rise can change the charge condition of the hydrogel coating or the antibacterial agent, adjust the electrostatic effect of the hydrogel coating or the antibacterial agent, and trigger the response release of the antibacterial agent. In addition, under alkaline conditions, tannic acid can be hydrolyzed and shed from the hydrogel coating, and the antibacterial agent combined with the tannic acid is released into the solution, so that the antibacterial performance of the tannic acid is enhanced.
A composite hydrogel, the composite hydrogel comprising a substrate, a polyamphogel coating, an antimicrobial agent;
the substrate is polydimethylsiloxane;
the polyamphole hydrogel coating comprises polymethacrylic acid sulfobetaine;
the antibacterial agent comprises povidone iodine, metallic copper ions and furacilin;
the substrate is covalently bonded to the polyamphogel coating;
the antimicrobial agent is linked to the polyamphogel coating by a non-covalent effect.
Optionally, the non-covalent interactions include hydrogen bonding, coordination bonding, electrostatic interactions.
Alternatively, the antimicrobial agent is loaded at 0.10 μg/cm 2 ～7000μg/cm 2 。
Alternatively, the loading of the antimicrobial agent is independently selected from 0.10 μg/cm 2 、0.50μg/cm 2 、1μg/cm 2 、1.5μg/cm 2 、2μg/cm 2 、2.5μg/cm 2 、3μg/cm 2 、3.5μg/cm 2 、4μg/cm 2 、4.5μg/cm 2 、5μg/cm 2 、5.5μg/cm 2 、6μg/cm 2 、6.5μg/cm 2 、7μg/cm 2 、7.5μg/cm 2 、8μg/cm 2 、8.5μg/cm 2 、9μg/cm 2 、9.5μg/cm 2 、10μg/cm 2 、10.5μg/cm 2 、11μg/cm 2 、11.5μg/cm 2 、12μg/cm 2 、12.5μg/cm 2 、13μg/cm 2 、13.5μg/cm 2 、14μg/cm 2 、14.5μg/cm 2 、15μg/cm 2 、15.5μg/cm 2 、16μg/cm 2 、16.5μg/cm 2 、17μg/cm 2 、17.5μg/cm 2 、18μg/cm 2 、18.5μg/cm 2 、19μg/cm 2 、19.5μg/cm 2 、20μg/cm 2 、20.5μg/cm 2 、21μg/cm 2 、21.5μg/cm 2 、22μg/cm 2 、22.5μg/cm 2 、23μg/cm 2 、23.5μg/cm 2 、24μg/cm 2 、24.5μg/cm 2 、25μg/cm 2 、25.5μg/cm 2 、26μg/cm 2 、26.5μg/cm 2 、27μg/cm 2 、27.5μg/cm 2 、28μg/cm 2 、28.5μg/cm 2 、29μg/cm 2 、29.5μg/cm 2 、30μg/cm 2 、50μg/cm 2 、100μg/cm 2 、500μg/cm 2 、1000μg/cm 2 、2000μg/cm 2 、3000μg/cm 2 、4000μg/cm 2 、5000μg/cm 2 、6000μg/cm 2 、7000μg/cm 2 Any value therein or any range therebetween.
Alternatively, the povidone-iodine loading is 2.00mg/cm 2 ～7.00mg/cm 2 。
Alternatively, the povidone-iodine loading is independently selected from 2.00mg/cm 2 、2.20mg/cm 2 、2.50mg/cm 2 、3.00mg/cm 2 、3.50mg/cm 2 、4.00mg/cm 2 、4.50mg/cm 2 、5.00mg/cm 2 、5.22mg/cm 2 、5.50mg/cm 2 、6.00mg/cm 2 、6.50mg/cm 2 、7.00mg/cm 2 Any value therein or any range therebetween.
Alternatively, the metallic copper ion is supported at a level of 0.10 μg/cm 2 ～5.5μg/cm 2 。
Alternatively, the loading of metallic copper ions is independently selected from 0.10 μg/cm 2 、0.12μg/cm 2 、0.50μg/cm 2 、1.00μg/cm 2 、1.50μg/cm 2 、2.00μg/cm 2 、2.50μg/cm 2 、3.00μg/cm 2 、3.50μg/cm 2 、4.00μg/cm 2 、4.44μg/cm 2 、4.50μg/cm 2 、5.00μg/cm 2 、5.50μg/cm 2 Any value therein or any range therebetween.
Optionally, the loading amount of the furacilin is 3.00 mug/cm 2 ～30μg/cm 2 。
Alternatively, the loading of the furacilin is independently selected from 3 μg/cm 2 、3.3μg/cm 2 、3.5μg/cm 2 、4μg/cm 2 、4.5μg/cm 2 、5μg/cm 2 、5.5μg/cm 2 、6μg/cm 2 、6.5μg/cm 2 、7μg/cm 2 、7.5μg/cm 2 、8μg/cm 2 、8.5μg/cm 2 、9μg/cm 2 、9.5μg/cm 2 、10μg/cm 2 、10.5μg/cm 2 、11μg/cm 2 、11.5μg/cm 2 、12μg/cm 2 、12.5μg/cm 2 、13μg/cm 2 、13.5μg/cm 2 、14μg/cm 2 、14.5μg/cm 2 、15μg/cm 2 、15.5μg/cm 2 、16μg/cm 2 、16.5μg/cm 2 、17μg/cm 2 、17.5μg/cm 2 、18μg/cm 2 、18.5μg/cm 2 、19μg/cm 2 、19.5μg/cm 2 、20μg/cm 2 、20.5μg/cm 2 、21μg/cm 2 、21.5μg/cm 2 、22μg/cm 2 、22.5μg/cm 2 、23μg/cm 2 、23.5μg/cm 2 、24μg/cm 2 、24.5μg/cm 2 、25μg/cm 2 、25.5μg/cm 2 、26μg/cm 2 、26.3μg/cm 2 、26.5μg/cm 2 、27μg/cm 2 、27.5μg/cm 2 、28μg/cm 2 、28.5μg/cm 2 、29μg/cm 2 、29.5μg/cm 2 、30μg/cm 2 Any value therein or any range therebetween.
Optionally, the polyzwitterionic hydrogel coating includes a natural polyphenol therein.
Optionally, the natural polyphenol is selected from at least one of tannic acid, tannic acid derivative, gallic acid derivative, procyanidine derivative.
Optionally, the natural polyphenol is linked to the antimicrobial agent by the non-covalent effect.
Optionally, the mass ratio of the natural polyphenol in the polyamphogel coating is 0-20wt%.
According to a second aspect of the present application, a method of preparing a composite hydrogel is provided.
The preparation method of the composite hydrogel comprises the following steps:
s1, immersing polydimethylsiloxane subjected to glow discharge plasma treatment into a solution containing an initiator I to obtain surface activated polydimethylsiloxane;
s2, mixing materials containing zwitterionic monomers, a cross-linking agent and an initiator II, and deoxidizing to obtain hydrogel prepolymer;
s3, immersing the surface-activated polydimethylsiloxane into the hydrogel prepolymer liquid, and reacting to obtain the polydimethylsiloxane with the hydrogel coating;
s4, immersing the polydimethylsiloxane of the hydrogel coating into a solution containing an antibacterial agent, and loading to obtain the composite hydrogel.
Optionally, in step S1, the solvent in the solution containing the initiator i is selected from at least one of acetone, ethanol, isopropanol.
The initiator I is at least one selected from benzoyl peroxide, diphenyl ketone, 4-methyl diphenyl ketone and azodiisobutyronitrile.
Optionally, in step S1, the concentration of benzoyl peroxide is 0.5wt% to 16wt%.
Optionally, in step S1, the glow discharge plasma treatment time is 0.5min to 5min.
Optionally, in step S1, the immersion time is 2min to 10min.
Optionally, in step S1, after immersion, rinsing to obtain a surface-activated polydimethylsiloxane.
Optionally, in step S2, the zwitterionic monomer is selected from at least one of betaine methacrylate sulfonate and 2-methacryloyloxyethyl phosphorylcholine.
Optionally, in step S2, the crosslinking agent comprises a physical crosslinking agent and/or a chemical crosslinking agent.
Optionally, in step S2, the chemical crosslinking agent is at least one selected from polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, and N, N' -methylenebisacrylamide.
Optionally, in step S2, the physical crosslinking agent is the natural polyphenol.
Optionally, in step S2, the initiator ii is at least one selected from ammonium persulfate, 2-hydroxy-2-methyl-1-phenyl-1-propanone, α -ketoglutaric acid, and potassium persulfate.
Optionally, in step S2, the mass content of the zwitterionic monomer in the hydrogel prepolymer is 20wt% to 60wt%.
Optionally, in the step S2, the mass content of the chemical cross-linking agent in the hydrogel prepolymer solution is 0.10-0.40 wt%.
Optionally, in the step S2, the mass content of the initiator II in the hydrogel prepolymer solution is 0.01-0.20 wt%.
Alternatively, in step S3, the reaction conditions are as follows:
the temperature is 50-90 ℃;
the time is 70 min-720 min.
Optionally, in step S3, the reaction is performed in a water bath shaker.
Optionally, in step S4, the solvent in the solution containing the antibacterial agent is selected from at least one of water and physiological saline.
Optionally, in step S4, the concentration of the antibacterial agent in the solution containing the antibacterial agent is 0.01wt% to 17wt%.
Optionally, in step S4, the concentration of povidone-iodine in the solution containing the antibacterial agent is 0wt% to 10wt%.
Optionally, in step S4, the concentration of the metallic copper ions is 0wt% to 7wt%.
Optionally, in the step S4, the concentration of the furacilin is 0wt% to 0.1wt%.
The concentration of povidone iodine, the concentration of metallic copper ions and the concentration of furacilin are not 0 at the same time.
Optionally, in step S4, the conditions of the load are as follows:
the temperature is 30-40 ℃;
the time is 1 h-72 h.
Optionally, in step S4, the loading is performed in a thermostatic oscillator.
According to a third aspect of the present application there is provided the use of a composite hydrogel.
The composite hydrogel and/or the application of the composite hydrogel obtained by the preparation method in the urinary tract infection material.
The beneficial effects that this application can produce include:
1) According to the composite hydrogel, the antibacterial agent is loaded by utilizing the non-covalent effects of the zwitterionic groups and/or the plant polyphenol in the hydrogel coating through the electrostatic effect, the hydrogen bond, the coordination bond and the like, so that the loading amount of various clinically common antibacterial agents (such as metal ions, disinfectants, antibiotics and the like) in the hydrogel coating can be greatly improved; the antimicrobial agent may be released in a pH response.
2) The preparation method of the composite hydrogel is simple and efficient.
Drawings
Fig. 1 shows a schematic representation of the hydrogel coating/hydrogel-on-carrier coating preparation of the present application.
FIG. 2 shows the antimicrobial loading capacity of example 1 and polydimethylsiloxanes of the present application, wherein a is the iodine loading; b is copper ion loading; and c is furacilin loading.
FIG. 3 shows the pH responsive release results of example 2 of the present application, wherein a is the cumulative release of PT 8-I; b is the accumulated release amount of PT 8-Cu; c is the cumulative release of PT 8-NFZ.
Fig. 4 shows the antibacterial and bacteriostatic results of example 1 and example 2 of the present application.
Fig. 5 shows the results of inhibition of bacteriostasis in example 1 and example 2 of the present application.
Fig. 6 shows the antibacterial properties and inhibition of stone formation of example 1 and example 2 of the present application.
Fig. 7 shows the results of calcium and magnesium contents in the stones on the surfaces of the materials of example 1 and example 2.
FIG. 8 shows a scanning electron microscope image of the cross-section of the urinary catheter, the bladder of an experimental rabbit and the urinary catheter collected 7 days after implantation of example 2-I (i.e., PT 8-I) and polydimethylsiloxane (i.e., control) of the present application in animals.
FIG. 9 shows the bacterial content of urine 7 days after the polydimethylsiloxane and example 2-I of the present application were implanted in animals. The background shaded area represents the normal reference value range.
FIG. 10 shows the bacterial content of the catheter surface and the calcium and magnesium content of the surface stones 7 days after the polydimethylsiloxane of example 2-I of the present application was implanted in an animal. The background shaded area represents the normal reference value range.
FIG. 11 shows the results of blood routine tests of example 2-I and polydimethylsiloxane of the present application after 7 days of implantation in animals and of rabbits without a urinary catheter (i.e., blank), where a is the white blood cell count, b is the neutrophil count, and c is the neutrophil fraction. The background shaded area represents the normal reference value range.
FIG. 12 shows histological analysis of the bladder and urethra of an animal 7 days after implantation of example 2-I and polydimethylsiloxane of the present application and of the bladder and urethra of a rabbit without a urinary catheter. Arrows represent inflammatory cells.
Detailed Description
The present application is described in detail below with reference to examples, but the present application is not limited to these examples.
Unless otherwise indicated, all starting materials in the examples of the present application were purchased commercially.
The analytical method in the examples of the present application is as follows:
the elemental content analysis was performed using an inductively coupled plasma emission spectrometer (model: ARCOS, spectrum, germany).
The analysis of the stone component was performed by means of energy dispersive X-ray spectroscopy (model: provided 8230, hitachi, japan).
Furacilin content analysis was performed using an ultraviolet-visible spectrophotometer (model: cary 300, agilent, usa).
The loading of the antimicrobial in the examples of the present application was calculated as follows:
wherein X is 0 To the concentration of copper ions before loading, X 1 Copper release after loadingThe concentration of the subunits, V is the volume of the supporting solution and S is the surface area of the coating.
Wherein X is 0 For loading concentration of furacilin, X 1 For the concentration of furacilin after loading, V is the volume of the loading solution and S is the surface area of the coating.
Wherein X is 0 For the concentration of povidone iodine before loading, X 1 For the concentration of povidone-iodine after loading, V is the volume of the loading solution and S is the surface area of the coating.
Example 1
(1-I) preparation of hydrogel coating
2g of benzoyl peroxide was dissolved in 18g of acetone solvent and stirred until the solution was clear and transparent, giving an acetone solution of 10wt% benzoyl peroxide.
22.3g of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (betaine methacrylate) is dissolved in 20mL of deionized water, stirred until the mixture is fully dissolved, 90mg of polyethylene glycol dimethacrylate is added, stirred until the mixture is fully dissolved, 23mg of ammonium persulfate is added, stirred until the mixture is clear and transparent, and nitrogen is introduced into the mixture for 30min to remove oxygen, thereby obtaining hydrogel prepolymer ([ 2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide with a mass content of 52.58wt%, polyethylene glycol dimethacrylate with a mass content of 0.21wt% and ammonium persulfate with a mass content of 0.05 wt%).
After the surface of 1cm×3 cm-sized polydimethylsiloxane was treated with glow discharge plasma for 3min, the surface was immersed in an acetone solution of 10wt% benzoyl peroxide for 5min, and after the immersion, the polydimethylsiloxane was rinsed with an appropriate amount of isopropyl alcohol. Adding the hydrogel prepolymer into the mixture, and reacting the mixture for 90 minutes in a water bath oscillator at the temperature of 80 ℃ to obtain the polydimethylsiloxane of the water-containing gel coating, which is named as PT0, wherein the schematic diagram of the preparation process is shown in figure 1.
(1-II) preparation of hydrogel coating
2g of benzoyl peroxide was dissolved in 18g of acetone solvent and stirred until the solution was clear and transparent, giving an acetone solution of 10wt% benzoyl peroxide.
3.7g of tannic acid is dissolved in 20mL of deionized water, stirred until the tannic acid is fully dissolved, 22.3g of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is added, stirred until the tannic acid is fully dissolved, 90mg of polyethylene glycol dimethacrylate is added, stirred until the tannic acid is fully dissolved, 23mg of ammonium persulfate is added, stirred until the solution is clear and transparent, nitrogen is introduced into the solution for 30min to remove oxygen, and hydrogel prepolymer (the mass content of tannic acid is 8.02wt%, the mass content of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is 48.36wt%, the mass content of polyethylene glycol dimethacrylate is 0.19wt%, and the mass content of ammonium persulfate is 0.05 wt%) is obtained.
After the surface of 1cm×3 cm-sized polydimethylsiloxane was treated with glow discharge plasma for 3min, the surface was immersed in an acetone solution of 10wt% benzoyl peroxide for 5min, and after the immersion, the polydimethylsiloxane was rinsed with an appropriate amount of isopropyl alcohol. Adding the hydrogel prepolymer into the mixture, and reacting the mixture for 90 minutes in a water bath oscillator at the temperature of 80 ℃ to obtain the polydimethylsiloxane of the water-containing gel coating, which is named as PT8, wherein the schematic diagram of the preparation process is shown in figure 1.
Example 2
(2-I) preparation of povidone iodine-loaded hydrogel coating
2g of benzoyl peroxide was dissolved in 18g of acetone solvent and stirred until the solution was clear and transparent, giving an acetone solution of 10wt% benzoyl peroxide.
3.7g of tannic acid is dissolved in 20mL of deionized water, stirred until the tannic acid is fully dissolved, 22.3g of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is added, stirred until the tannic acid is fully dissolved, 90mg of polyethylene glycol dimethacrylate is added, stirred until the tannic acid is fully dissolved, 23mg of ammonium persulfate is added, stirred until the solution is clear and transparent, nitrogen is introduced into the solution for 30min to remove oxygen, and hydrogel prepolymer (the mass content of tannic acid is 8.02wt%, the mass content of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is 48.36wt%, the mass content of polyethylene glycol dimethacrylate is 0.19wt%, and the mass content of ammonium persulfate is 0.05 wt%) is obtained.
After the surface of 1cm×3 cm-sized polydimethylsiloxane was treated with glow discharge plasma for 3min, the surface was immersed in an acetone solution of 10wt% benzoyl peroxide for 5min, and after the immersion, the polydimethylsiloxane was rinsed with an appropriate amount of isopropyl alcohol. Adding the hydrogel prepolymer solution into a water bath oscillator at 80 ℃ for reaction for 90min to obtain polydimethylsiloxane of the aqueous gel coating, immersing 10mL of 1wt% povidone iodine solution (the solvent is deionized water) into the water bath oscillator at 37 ℃ for loading for 24 hours to obtain polydimethylsiloxane of the aqueous gel coating loaded with povidone iodine, which is named PT8-I, and the preparation process is schematically shown in figure 1.
(2-II) preparation of copper-loaded hydrogel coating
2g of benzoyl peroxide was dissolved in 18g of acetone solvent and stirred until the solution was clear and transparent, giving an acetone solution of 10wt% benzoyl peroxide.
3.7g of tannic acid is dissolved in 20mL of deionized water, stirred until the tannic acid is fully dissolved, 22.3g of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is added, stirred until the tannic acid is fully dissolved, 90mg of polyethylene glycol dimethacrylate is added, stirred until the tannic acid is fully dissolved, 23mg of ammonium persulfate is added, stirred until the solution is clear and transparent, nitrogen is introduced into the solution for 30min to remove oxygen, and hydrogel prepolymer (the mass content of tannic acid is 8.02wt%, the mass content of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is 48.36wt%, the mass content of polyethylene glycol dimethacrylate is 0.19wt%, and the mass content of ammonium persulfate is 0.05 wt%) is obtained.
After the surface of 1cm×3 cm-sized polydimethylsiloxane was treated with glow discharge plasma for 3min, the surface was immersed in an acetone solution of 10wt% benzoyl peroxide for 5min, and after the immersion, the polydimethylsiloxane was rinsed with an appropriate amount of isopropyl alcohol. Adding the hydrogel prepolymer solution into a water bath oscillator at 80 ℃ for reaction for 90min to obtain polydimethylsiloxane of the aqueous gel coating, immersing 10mL of 11.25mg/mL copper sulfate solution (the solvent is deionized water) into the water bath oscillator at 37 ℃ for loading for 24 hours to obtain polydimethylsiloxane of the aqueous gel coating loaded with copper ions, which is named PT8-Cu, and the preparation process is schematically shown in figure 1.
Preparation of (2-III) furacilin-loaded hydrogel coating
2g of benzoyl peroxide was dissolved in 18g of acetone solvent and stirred until the solution was clear and transparent, giving an acetone solution of 10wt% benzoyl peroxide.
3.7g of tannic acid is dissolved in 20mL of deionized water, stirred until the tannic acid is fully dissolved, 22.3g of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is added, stirred until the tannic acid is fully dissolved, 90mg of polyethylene glycol dimethacrylate is added, stirred until the tannic acid is fully dissolved, 23mg of ammonium persulfate is added, stirred until the solution is clear and transparent, nitrogen is introduced into the solution for 30min to remove oxygen, and hydrogel prepolymer (the mass content of tannic acid is 8.02wt%, the mass content of [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide is 48.36wt%, the mass content of polyethylene glycol dimethacrylate is 0.19wt%, and the mass content of ammonium persulfate is 0.05 wt%) is obtained.
After the surface of 1cm×3 cm-sized polydimethylsiloxane was treated with glow discharge plasma for 3min, the surface was immersed in an acetone solution of 10wt% benzoyl peroxide for 5min, and after the immersion, the polydimethylsiloxane was rinsed with an appropriate amount of isopropyl alcohol. Adding the hydrogel prepolymer solution into a water bath oscillator at 80 ℃ for reaction for 90min to obtain polydimethylsiloxane of the hydrogel coating, immersing 10mL of 0.2mg/mL of nitrofural solution (the solvent is normal saline) into the water bath oscillator at 37 ℃ for loading for 24 hours to obtain polydimethylsiloxane of the hydrogel coating loaded with nitrofural, which is named PT8-NFZ, and the preparation process is schematically shown in figure 1.
EXAMPLE 3 hydrogel coating loading Condition
1 cm. Times.3 cm of unmodified polydimethylsiloxane (i.e., PDMS) and 1 cm. Times.3 cm of the sample of example 1 (i.e., PT0, PT 8) were immersed in 10mL of a 1wt% povidone-iodine solution (the solvent was deionized water) and placed in a constant temperature shaker at 37℃for loading for 24 hours. Before and after soakingThe iodine content of the solution is measured by an inductively coupled plasma emission spectrometer after dilution by a certain multiple, the loading condition is shown in figure 2, and the iodine content (the loading amount is 5.22 mg/cm) of the sample of the embodiment 1-II (namely PT 8) 2 ) Greater than the sample of example 1-I (i.e., PT 0) (loading of 2.2mg/cm 2 ) And is an unmodified polydimethylsiloxane (loading of 0.84mg/cm 2 ) Is a factor of 6.2, indicating that the example 1-II sample is capable of increasing the povidone-iodine loading of the antimicrobial.
1 cm. Times.3 cm of unmodified polydimethylsiloxane (i.e., PDMS) and 1 cm. Times.3 cm of the sample of example 1 (i.e., PT0, PT 8) were immersed in 10mL of 11.25mg/mL copper sulfate solution (the solvent was deionized water) and placed in a constant temperature shaker at 37℃for loading for 24 hours. The copper element content was measured by inductively coupled plasma emission spectrometer after dilution by a factor of the solution before and after soaking, the loading is shown in FIG. 2, and the sample of example 1-II (i.e., PT 8) was loaded with copper ion content (load amount was 4.438. Mu.g/cm) in 24 hours 2 ) Greater than the sample of example 1-I (i.e., PT 0) (loading of 0.124. Mu.g/cm) 2 ) And was unmodified polydimethylsiloxane (loading 0.008. Mu.g/cm) 2 ) Is 554.75 times greater than the sample of example 1-II to provide enhanced copper ion loading of the antimicrobial.
1 cm. Times.3 cm of unmodified polydimethylsiloxane (i.e., PDMS) and 1 cm. Times.3 cm of the sample of example 1 (i.e., PT0, PT 8) were immersed in 10mL of 0.2mg/mL nitrofural solution (the solvent was physiological saline) and placed in a constant temperature shaker at 37℃for loading for 24 hours. Taking solutions before and after soaking, diluting by a certain multiple, and measuring nitrofurazone content by ultraviolet-visible spectrophotometer, wherein the loading condition is shown in figure 2, and the sample of example 1-II (PT 8) is loaded with nitrofurazone content (loading amount is 26.29 μg/cm) within 24 hours 2 ) Greater than unmodified polydimethylsiloxane (loading of 4.59. Mu.g/cm) 2 ) And example 1-I sample (i.e., PT 0) (load amount of 3.31. Mu.g/cm) 2 ) The samples of example 1-II are shown to be capable of increasing the loading of the antimicrobial agent furacilin.
The invention selects the typical antibacterial agent disinfectant povidone iodine, metal ion copper ion and antibiotic furacilin commonly used in clinic for coating load. Povidone iodine is a complex of 1-vinyl-2-pyrrolidone homopolymer and iodine, and is respectively combined with methacrylic acid sulfobetaine groups and tannic acid in the hydrogel coating through electrostatic action and hydrogen bonds. The copper ions form a coordination with catechol groups of tannins in the hydrogel coating, forming a stable metal-polyphenol network in the coating. Furacilin is respectively combined with tannic acid and methacrylic acid sulfobetaine groups in the hydrogel coating through hydrogen bond and electrostatic action. From this, it is reasonably speculated that the hydrogel coating of example 1-II (i.e., PT 8) has a universally high loading function for various antimicrobial agents based on the various non-covalent interactions provided by tannic acid and zwitterionic groups.
Example 4 pH responsive Release of hydrogel coatings
Immersing the sample of example 2-I in acidic (pH=4), neutral (pH=7) and alkaline (pH=10) PBS solutions respectively, placing in a constant-temperature oscillator at 37deg.C, taking the release solution every 24 hours, diluting by a certain multiple, and measuring iodine content by inductively coupled plasma emission spectrometer, wherein the release curve is shown in FIG. 3, and the iodine release amount of example 2-I in alkaline environment for 24 hours is 0.08mg/cm 2 Is higher than the acid (0.03 mg/cm) 2 ) And neutral (0.06 mg/cm) 2 ) Release amount in the Environment until day 7 example 2-I released iodine in alkaline environment at 0.19mg/cm 2 Is significantly higher than the acidity (0.05 mg/cm) 2 ) And neutral (0.08 mg/cm) 2 ) The amount released in the environment indicates that example 2-I has pH responsive release properties and releases more iodine under alkaline conditions, and is effective in responding and responding to bacterial infections during alkalization of urine.
Immersing the sample of example 2-II in acidic (pH=4), neutral (pH=7) and alkaline (pH=10) PBS solutions respectively, placing in a constant-temperature oscillator at 37deg.C, taking release solution every 24 hours, diluting by a certain multiple, and measuring copper element content by inductively coupled plasma emission spectrometer, wherein the release curve is shown in FIG. 3, and the copper ion release amount of example 2-I in alkaline environment for 24 hours is 1.36 μg/cm 2 Is significantly higher than the acidity (0.015. Mu.g/cm) 2 ) And neutral (0.047. Mu.g/cm) 2 ) Amount of copper ion released from the environment until day 7 example2-II the amount of released copper ions in alkaline environment was 2.69. Mu.g/cm 2 Is released in an acidic environment (0.05. Mu.g/cm) 2 ) Is 53.8 times the release in a neutral environment (0.047. Mu.g/cm) 2 ) Is 57 times that of the sample, it is demonstrated that example 2-I has pH responsive release properties and releases more copper ions under alkaline conditions, and is able to effectively respond and cope with bacterial infections in urine alkalization.
Immersing the samples of examples 2-III in acidic (pH=4), neutral (pH=7) and alkaline (pH=10) PBS solutions respectively, placing in a constant-temperature oscillator at 37 ℃, taking release solution every 24 hours, diluting for a certain multiple, and measuring nitrofurazone content by an ultraviolet-visible spectrophotometer, wherein the release curve is shown in FIG. 3, and the nitrofurazone release amount of example 2-I in alkaline environment for 24 hours is 2.87 mu g/cm 2 Is significantly higher than the acidity (0.37. Mu.g/cm) 2 ) And neutral (0.35. Mu.g/cm) 2 ) Release amount of furacilin in the environment until day 7, example 2-III released furacilin in alkaline environment in an amount of 12.36. Mu.g/cm 2 Is released in an acidic environment (1.96. Mu.g/cm) 2 ) Is 6.3 times that of the release amount in a neutral environment (1.06. Mu.g/cm) 2 ) Is 11.7 times as large as that of the example 2-I, which shows that the example 2-I has pH response release performance, releases more furacilin under alkaline conditions, can effectively respond and can respond to bacterial infection during urine alkalization.
Example 5 antibacterial adhesion Properties of hydrogel coatings
Centrifuging the cultured Escherichia coli strain solution at 2700rpm twice, removing supernatant, adding PBS buffer solution, and suspending to maintain the strain solution at about 10 8 cell/mL concentration range. Samples of 1 cm. Times.1 cm polydimethylsiloxane, example 1 and example 2 were placed in 24-well plates, each covered with 1mL of bacterial liquid for 4 hours, and incubated in a 37℃incubator. After 4 hours, the bacterial suspension in each well plate was aspirated, and washed three times with 1mL of PBS buffer, and the non-adherent escherichia coli was removed, the sample was transferred to a 15mL centrifuge tube, 10mL of PBS buffer was added, and sonicated in an ultrasonic cleaner for 10 minutes. Diluting with PBS buffer solution to a certain multiple, uniformly coating 100 μl of bacterial liquid on LB solid medium, and inverting to 37 deg.C incubatorIs cultured for 18 hours. After 18 hours, the number of colonies on each solid medium was counted and the number of E.coli adhering to the surface of the material was counted, and the result is shown in FIG. 4, the number of E.coli adhering to the surface of the hydrogel coating of example 1-II (2.3X10) 5 CFU/cm 2 ) Less than polydimethylsiloxane (2X 10) 6 CFU/cm 2 ) The hydrogel coating was demonstrated to have a certain antibacterial adhesion property, and E.coli (the number of bacteria adhered to the PT8-Cu surface was 866 CFU/cm) adhered to the surface of the hydrogel coating of example 2 2 The number of bacteria adhering to the PT8-NFZ surface was 1166CFU/cm 2 And, (ii) significantly less than example 1, wherein no E.coli was detected on the surface of the hydrogel coating of example 2-I, indicating that the hydrogel coating has more excellent antibacterial and bacteriostatic properties.
Example 6 urinary tract infection simulation experiment
1cm by 1cm of polydimethylsiloxane, the samples of examples 1 and 2mL of the mixture containing 10 8 Mixing artificial urine of CFU/mL Proteus mirabilis with a 15mL centrifuge tube, placing in a 37 ℃ constant temperature incubator for shaking culture at 100rpm, measuring the pH value of the solution every 24 hours, and replacing fresh 10-containing urine 8 The artificial urine of CFU/mL Proteus mirabilis is continuously placed in a constant temperature incubator at 37 ℃ for shaking culture at 100rpm, the pH value change of the artificial urine is shown as shown in figure 5, the polydimethylsiloxane and the sample of the example 1-I have no sterilization performance, the Proteus mirabilis in bacterial liquid releases urease, urea is decomposed into ammonia, the artificial urine of the polydimethylsiloxane (pH=9.10) and the sample of the example 1-I (pH=9.07) are alkaline at 24 hours, the alkalization trend of the artificial urine of the sample of the example 1-II and the sample of the example 2 is slowed down, the sample of the example 1-II and the sample of the example 2 have sterilization performance, the influence of the Proteus mirabilis on the artificial urine can be alleviated, and the alkalization of the urine can be inhibited, wherein the artificial urine of the sample of the example 2-I is still at a normal level at the pH=5.37 at the 7 th day, and the sample of the example 2-I has excellent and continuous antibacterial performance.
1cm by 1cm of polydimethylsiloxane (i.e., PDMS), examples 1 and 2 were placed in 24 well plates, each 1mL containing 10 8 CFU/mL Proteus mirabilisIs replaced with fresh 10 at intervals of 24 hours 8 CFU/mL Proteus mirabilis artificial urine. On days 1 and 7, 1mL of 3% glutaraldehyde is used for fixing bacteria on the surface of the material, 1mL of 25%, 1mL of 50%, 1mL of 75% and 1mL of 100% gradient ethanol are used for gradient elution respectively, the conditions of bacteria and stones on the surface of the material are observed through a scanning electron microscope, as shown in figure 6, a large amount of Proteus mirabilis and stones are accumulated on the surface of PDMS on day 1, the surface of the hydrogel coating of the embodiment 1-II is less than that of the Proteus mirabilis and stones adhered to the PDMS, the accumulated stones and the adhesion growth of Proteus mirabilis on the surface of the hydrogel coating of the embodiment 2 are obviously reduced, thicker bacterial biofilms and accumulated stones are grown on the surface of the sample of the PDMS and the sample of the embodiment 1-I on day 7, and fewer Proteus mirabilis and stones are present on the surface of the hydrogel coating of the embodiment 2, and the hydrogel coating of the embodiment 2 has excellent antibacterial performance and can inhibit stone formation.
1cm by 1cm of polydimethylsiloxane (i.e., PDMS), examples 1 and 2 were placed in 24 well plates, each 1mL containing 10 8 CFU/mL artificial urine of Proteus mirabilis, fresh 10-containing urine was replaced every 24h 8 CFU/mL Proteus mirabilis artificial urine. Taking out the material every 24h, 72h and 168h, digesting with concentrated nitric acid, diluting to a certain multiple, and determining the condition of the calculus component on the surface of the material by using an inductively coupled plasma emission spectrometer, wherein the content of the calculus component on the surface of the material is shown in figure 7, the content of calcium and magnesium in the calculus on the surface of the material is gradually increased along with the time increase, the calcium and magnesium contents of PDMS, the hydrogel coating of example 1 and the hydrogel coating of example 2 can reduce the formation and adhesion of the calculus, the calcium and magnesium contents on the surface of the hydrogel coating of example 2 are less than those of the hydrogel coating of example 1-II, and the calcium content on the surface of the sample of example 1-II is 39.45 mu g/cm at the 7 th day 2 Magnesium content of 4.61. Mu.g/cm 2 Example 2-II sample surface calcium content was 17.70. Mu.g/cm 2 Magnesium content of 2.95. Mu.g/cm 2 Example 2-III sample surface calcium content was 27.99. Mu.g/cm 2 Magnesium content of 3.47. Mu.g/cm 2 Wherein the calcium and magnesium content (m) of the sample surface of example 2-I Ca ＝3.31μg/cm 2 ，m Mg ＝0.32μg/cm 2 ) At a minimum, the aqueous gel-loaded coating has excellent antibacterial performance, can inhibit the alkalization of artificial urine and the formation of stones, wherein the sample in the embodiment 2-I has better effects of inhibiting the formation of stones and relieving urinary tract infection.
Example 7 animal experiments
Animal experiments were approved by the institutional animal ethics committee of the university of Ningbo (ethics: NBU 20220133) according to the national guidelines. The in vivo performance of the coating was assessed by implantation of a urinary catheter in male New Zealand rabbits (2-3 kg). An ethylene oxide sterilized silicone catheter (8 Fr, original or PT8-I coating) was inserted transurethrally into the rabbit bladder. The balloon was inflated by injecting 3ml of sterile physiological saline, and the catheter was sutured to the abdomen of the rabbit to fix the catheter. The health status of the experimental rabbits was monitored daily. Blood and urine samples of rabbits were collected over time for routine blood and bacterial testing. Animals were sacrificed 7 days later and bladder, urethra, kidneys, catheters were collected. The bacterial content in urine was determined by plate counting. Tissues were fixed with 10% formalin, stained with H & E, and observed using an optical microscope (DFC 450C, licar, germany). Scanning Electron Microscopy (SEM) and energy spectroscopy (EDS) were used to analyze the formation of scale on the catheter surface. The calcium and magnesium contents are measured by an ICP-OES method by adopting a nitric acid digestion method to dissolve the scale on the surface of the catheter.
After 7 days of implantation, the catheter was removed from the rabbit and as shown in FIG. 8, a large number of metabolites and crystals deposited at the tip of the polydimethylsiloxane catheter (i.e., control group) and the catheter lumen was completely blocked and a large number of crystals and bacteria deposited in the bladder. In contrast, the example 2-I (i.e., PT 8-I) coated catheters were relatively clean, no blockage was observed, and no significant scabbing of the bladder was observed. SEM images showed that the lumen of the catheter of the control group was filled with scaling crystals. In contrast, the lumen of PT8-I coated catheters was clean and free of scale, indicating that PT8-I coatings were effective in inhibiting bacterial infection and scale formation in vivo.
In animal experiments, no urine bag was used and the catheter remained open throughout the experiment. Thus, microorganisms from the external environment can spontaneously migrate through the catheter lumen into the body, causing infection in the animal. As shown in the figure 9 of the drawings,the bacterial count in the original urine is negligible. After 3 days the bacteria count of the control group exceeded 10 5 CFU/mL, indicated that mycouria was present in the animals. The bacterial count in the urine of group PT8-I remained at 10 for 7 days 2 Below CFU/mL, it is shown that the coating can prevent bacterial growth in urine. As shown in fig. 10a, the harvested catheter sections were subjected to bacterial counting and quantification of calcium and magnesium in the scale. As shown in FIG. 10b, the surface bacteria count of the catheter tip (1.5 cm length) of the control group was 1.3X10 9 CFU, the surface bacteria of the catheter is seriously planted. In contrast, the PT8-I coated catheter tip had a bacterial count of 2.3X10 4 CFU indicated that PT8-I coated catheters could significantly reduce bacterial colonization. The calcium and magnesium deposition contents of different parts of the catheter are quantified through ICP-OES. As shown in FIGS. 10c, d, the scaling formation along the catheter surface was significantly inhibited in the PT8-I group compared to the control group. The PT8-I coating has excellent anti-scaling capability due to stronger antibacterial performance and release of antibacterial drugs. As shown in FIG. 11, typical immune related indicators such as white blood cell count (WBC), neutrophil count (NEUT), neutrophil ratio (NEUT%) were within normal range, while the control group was significantly higher than the reference value, indicating that bacterial infection occurred in animals.
The rabbit bladder and urethra were harvested 7 days after implantation for histological analysis. As shown in fig. 12a, neutrophils significantly infiltrated in the control bladder tissue, suggesting bladder tissue inflammation, while PT8-I group was significantly reduced. As shown in fig. 12b, a large number of neutrophil infiltrates and a large number of vacuoles were visible in the urethra in the control group. In contrast, the PT8-I group had fewer vacuoles and more normal epithelial cells, indicating that the PT8-I coating on the catheter reduced bacterial invasion of bladder tissue, thereby inhibiting bacterial colonization and scaling formation and maintaining cleanliness of the urinary system.
The foregoing description is only a few examples of the present application and is not intended to limit the present application in any way, and although the present application is disclosed in the preferred examples, it is not intended to limit the present application, and any person skilled in the art may make some changes or modifications to the disclosed technology without departing from the scope of the technical solution of the present application, and the technical solution is equivalent to the equivalent embodiments.
Claims (10)
1. A composite hydrogel, which is characterized by comprising a substrate, a polyamphogen hydrogel coating and an antibacterial agent;
the substrate is polydimethylsiloxane;
the polyamphole hydrogel coating comprises polymethacrylic acid sulfobetaine;
the antibacterial agent comprises povidone iodine, metallic copper ions and furacilin;
the substrate is covalently bonded to the polyamphogel coating;
the antimicrobial agent is linked to the polyamphogel coating by a non-covalent effect.
2. The composite hydrogel of claim 1, wherein the non-covalent interactions include hydrogen bonding, coordination bonding, electrostatic interactions;
preferably, the antimicrobial agent is loaded at 0.10 μg/cm 2 ～7000μg/cm 2 ；
Preferably, the povidone-iodine loading is 2.00mg/cm 2 ～7.00mg/cm 2 ；
Preferably, the loading of the metallic copper ions is 0.10 mug/cm 2 ～5.5μg/cm 2 ；
Preferably, the loading amount of the furacilin is 3.00 mug/cm 2 ～30μg/cm 2 。
3. The composite hydrogel of claim 1, wherein the polyzwitterionic hydrogel coating comprises a natural polyphenol therein;
preferably, the natural polyphenol is selected from at least one of tannic acid, tannic acid derivative, gallic acid derivative, procyanidine derivative.
4. The composite hydrogel of claim 1, wherein the natural polyphenol is linked to the antimicrobial agent by the non-covalent effect;
preferably, the mass ratio of the natural polyphenol in the polyamphogel coating is 0-20wt%.
5. The method for producing a composite hydrogel according to any one of claims 1 to 4, comprising the steps of:
s1, immersing polydimethylsiloxane subjected to glow discharge plasma treatment into a solution containing an initiator I to obtain surface activated polydimethylsiloxane;
s2, mixing materials containing zwitterionic monomers, a cross-linking agent and an initiator II, and deoxidizing to obtain hydrogel prepolymer;
s3, immersing the surface-activated polydimethylsiloxane into the hydrogel prepolymer liquid, and reacting to obtain the polydimethylsiloxane with the hydrogel coating;
s4, immersing the polydimethylsiloxane of the hydrogel coating into a solution containing an antibacterial agent, and loading to obtain the composite hydrogel.
6. The process according to claim 5, wherein in step S1, the solvent in the solution containing the initiator I is at least one selected from the group consisting of acetone, ethanol and isopropanol;
preferably, the initiator I is at least one selected from benzoyl peroxide, benzophenone, 4-methyl benzophenone and azodiisobutyronitrile;
preferably, in the step S1, the concentration of the benzoyl peroxide is 0.5-16 wt%;
preferably, in the step S1, the time of glow discharge plasma treatment is 0.5 min-5 min;
preferably, in the step S1, the immersion time is 2-10 min;
preferably, in step S1, after immersion, the surface-activated polydimethylsiloxane is obtained by rinsing.
7. The preparation method according to claim 1, wherein in the step S2, the zwitterionic monomer is at least one selected from the group consisting of sulfobetain methacrylate and 2-methacryloyloxyethyl phosphorylcholine;
preferably, in step S2, the crosslinking agent comprises a physical crosslinking agent and/or a chemical crosslinking agent;
preferably, in step S2, the chemical crosslinking agent is at least one selected from polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, N' -methylenebisacrylamide;
preferably, in step S2, the physical crosslinking agent is the natural polyphenol;
preferably, in the step S2, the initiator ii is at least one selected from ammonium persulfate, 2-hydroxy-2-methyl-1-phenyl-1-propanone, α -ketoglutaric acid, and potassium persulfate;
preferably, in the step S2, the mass content of the zwitterionic monomer in the hydrogel prepolymer is 20wt% -60 wt%;
preferably, in the step S2, the mass content of the chemical cross-linking agent in the hydrogel prepolymer solution is 0.10wt% to 0.40wt%;
preferably, in the step S2, the mass content of the initiator II in the hydrogel prepolymer liquid is 0.01-0.20 wt%.
8. The method according to claim 1, wherein in step S3, the reaction conditions are as follows:
the temperature is 50-90 ℃;
the time is 70 min-720 min;
preferably, in step S3, the reaction is carried out in a water bath shaker.
9. The method according to claim 1, wherein in step S4, the solvent in the solution containing the antibacterial agent is at least one selected from the group consisting of water and physiological saline;
preferably, in step S4, the conditions of the load are as follows:
the temperature is 30-40 ℃;
the time is 1 h-72 h;
preferably, in step S4, the loading is performed in a thermostatic oscillator.
10. Use of a composite hydrogel according to any one of claims 1 to 4 and/or a composite hydrogel obtained by a method of preparation according to any one of claims 5 to 9 in a urinary tract infection material.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120244097A1 (en) * | 2011-03-21 | 2012-09-27 | Broda Technologies Co., Ltd. | Reversely thermo-reversible hydrogel compositions |
| CN109529128A (en) * | 2018-11-30 | 2019-03-29 | 中国科学院长春应用化学研究所 | A kind of anti-infective coating and preparation method thereof |
| CN114191620A (en) * | 2021-11-17 | 2022-03-18 | 中国科学院宁波材料技术与工程研究所 | Hydrogel coating, supported antibacterial coating, and preparation method and application thereof |
| US20220332902A1 (en) * | 2021-04-09 | 2022-10-20 | Colorado School Of Mines | Radical crosslinked zwitterionic gels and uses thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120244097A1 (en) * | 2011-03-21 | 2012-09-27 | Broda Technologies Co., Ltd. | Reversely thermo-reversible hydrogel compositions |
| CN109529128A (en) * | 2018-11-30 | 2019-03-29 | 中国科学院长春应用化学研究所 | A kind of anti-infective coating and preparation method thereof |
| US20220332902A1 (en) * | 2021-04-09 | 2022-10-20 | Colorado School Of Mines | Radical crosslinked zwitterionic gels and uses thereof |
| CN114191620A (en) * | 2021-11-17 | 2022-03-18 | 中国科学院宁波材料技术与工程研究所 | Hydrogel coating, supported antibacterial coating, and preparation method and application thereof |
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