An antibacterial hydrogel dressing and its preparation method

Abstract

This invention relates to the field of biomedical materials technology, and particularly to an antibacterial hydrogel dressing and its preparation method. The effective components of the antibacterial hydrogel dressing raw material, by weight, are as follows: 5-12 parts gel matrix; 0.5-3.0 parts combined antibacterial substance; 0.1-5.0 parts emulsifier; 0.3-8.0 parts crosslinking agent; and 50-100 parts dispersant. The combined antibacterial substance comprises natural antibacterial components, synthetic antibacterial agents, and a biopolymer carrier. The antibacterial hydrogel dressing provided by this invention uses a combined antibacterial substance as the antibacterial component, with natural antibacterial components as the killing core, synthetic antibacterial agents as auxiliary synergists, and a biopolymer carrier as a delivery and protection platform. Through multi-target and multi-mechanism synergy, it achieves highly efficient, broad-spectrum, long-lasting, low-toxicity, and low-drug-resistance antibacterial effects.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to an antibacterial hydrogel dressing and its preparation method. Background Technology

[0002] Hydrogel dressings are a new type of medical material developed based on the theory of moist healing. They are composed of a hydrophilic polymer network with high water content (usually more than 50%), which can provide a moist and breathable healing environment for wounds and significantly promote tissue repair.

[0003] The matrix of hydrogel dressings is usually made of natural or synthetic polymer materials. Common natural materials include chitosan, hyaluronic acid, and silk fibroin, which have excellent biocompatibility and degradability; synthetic materials such as polyvinyl alcohol (PVA) and polyacrylic acid (PAA) form a stable three-dimensional network through chemical cross-linking, which balances mechanical properties and water absorption.

[0004] Because moist wound environments easily breed bacteria, leading to infection, delayed healing, or even worsening of the condition, endowing hydrogel dressings with efficient and long-lasting antibacterial properties has become one of the key research directions in this field.

[0005] Currently, the most common technique for introducing antibacterial properties into hydrogel dressings is physical blending, which involves introducing antibacterial agents (such as silver nanoparticles and zinc oxide nanoparticles) into the hydrogel network through mixing, soaking, or in-situ synthesis. This method is simple and allows for a wide range of antibacterial agents. However, because the antibacterial agents and the hydrogel matrix are mainly bound by physical forces, the binding force is relatively weak. When the dressing comes into contact with wound exudate, a large amount of antibacterial agent will rapidly diffuse and release within a short period of time, resulting in a burst release and a short duration of antibacterial effect.

[0006] Therefore, achieving sustained release of antibacterial agents is a technical problem that urgently needs to be solved. Summary of the Invention

[0007] To address the problem of short-lasting antibacterial effect in existing antibacterial hydrogel dressings, this invention provides an antibacterial hydrogel dressing that incorporates a biopolymer carrier to bind with antibacterial components, achieving sustained release of the antibacterial components and extending the antibacterial action time, thus solving the problem of short-lasting antibacterial effect in existing antibacterial hydrogel dressings.

[0008] The technical solution adopted by this invention to solve its technical problem is: An antibacterial hydrogel dressing, the effective components of which are as follows, by weight: 5-12 parts of gel matrix; Combined with 0.5-3.0 parts of antibacterial substance; Emulsifier 0.1-5.0 parts; Crosslinking agent 0.3-8.0 parts; Dispersant 50-100 parts; The combined antibacterial substances include natural antibacterial components, synthetic antibacterial agents, and biological polymer carriers.

[0009] Optionally, the natural antibacterial ingredient is selected from at least one of cephalosporin, antimicrobial peptide LL-37, and defensin.

[0010] Optionally, the synthetic antibacterial agent is selected from at least one of polyhexamethylene biguanide, benzalkonium chloride, and polyquaternium-47.

[0011] Optionally, the biopolymer carrier is selected from at least one of chitosan, hyaluronic acid, and sodium alginate.

[0012] Optionally, the gel matrix is ​​selected from at least one of polyethylene glycol-polyglutamic acid copolymer, polyethylene glycol-polylactic acid copolymer, polyethylene glycol-polycaprolactone copolymer, polyethylene glycol-polylysine copolymer, polyglutamic acid-polylysine copolymer, polyethylene glycol-polyaspartic acid copolymer, hyaluronic acid-polyethylene glycol copolymer, sodium alginate-polyglutamic acid copolymer, and gelatin-polyethylene glycol copolymer.

[0013] Optionally, the emulsifier is a nonionic emulsifier.

[0014] Optionally, the emulsifier is selected from at least one of polyglycerol-10-oleate, polyglycerol-6-stearate, polyglycerol-4-laurate, Tween 80, Tween 20, Span 80, poloxamer 407, and poloxamer 188.

[0015] Optionally, the crosslinking agent is selected from at least one of glycerol, hyaluronic acid, sodium alginate, xanthan gum, gelatin, silk fibroin, cyclodextrin, and polylysine.

[0016] Optionally, the dispersant is water.

[0017] Another object of the present invention is to provide a method for preparing the antibacterial hydrogel dressing as described above, comprising the following steps: S1: According to the formula, mix the biopolymer carrier and crosslinking agent, add emulsifier and dispersant, stir, and obtain polymer carrier solution; S2: Prepare gel matrix solution, natural antibacterial solution and synthetic antibacterial agent solution respectively; S3: Add the natural antibacterial solution to the polymer carrier solution, sonicate in an ice bath, add it to the gel matrix solution, then add the synthetic antibacterial agent solution to the system, adjust the pH to 6.0-7.0, and after degassing and molding, obtain the antibacterial hydrogel dressing.

[0018] The beneficial effects of this invention are: The antibacterial hydrogel dressing provided by this invention uses a combination of antibacterial substances as antibacterial components, with natural antibacterial ingredients as the killing core, synthetic antibacterial agents as auxiliary synergists, and biological polymer carriers as delivery and protection platforms. Through multi-target and multi-mechanism synergy, it achieves a highly efficient, broad-spectrum, long-lasting, low-toxicity, and low-drug-resistance antibacterial effect. Detailed Implementation

[0019] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0020] To address the short-lasting antibacterial effect of existing antibacterial hydrogel dressings, this invention provides an antibacterial hydrogel dressing. The effective components of the raw material for this antibacterial hydrogel dressing, by weight, are as follows: 5-12 parts of gel matrix; Combined with 0.5-3.0 parts of antibacterial substance; Emulsifier 0.1-5.0 parts; Crosslinking agent 0.3-8.0 parts; Dispersant 50-100 parts; Among them, combined antimicrobial substances include natural antimicrobial components, synthetic antimicrobial agents, and biological polymer carriers.

[0021] It should be noted that the raw materials of this antibacterial hydrogel dressing may also include auxiliary functional ingredients such as pH adjusters, depending on the requirements, so as to regulate the stability, biocompatibility and moisturizing effect of the system through pH adjusters. Specifically, the present invention preferably includes 1.0-20.0 parts by weight of auxiliary functional ingredients in the raw materials, and further preferably, the auxiliary functional ingredients include triethanolamine and pH 6.5 phosphate buffer, which work together to maintain the pH of the system at about 6.5, adapting to the physiological environment of the skin and preventing the inactivation of antibacterial ingredients.

[0022] The preferred dispersant in this invention is deionized water.

[0023] In existing antibacterial hydrogel dressings, the introduction of antibacterial agents through physical blending not only easily leads to burst release and short-lived antibacterial effects, but also the possibility that excessively high local concentrations of antibacterial agents may be toxic to newly formed cells, hindering tissue repair and potentially exacerbating bacterial resistance. Therefore, this invention employs a combination of antibacterial substances. The natural antibacterial components disrupt the integrity of bacterial cell membranes and inhibit key intracellular metabolic processes; synthetic antibacterial agents interfere with bacterial cell metabolism and disrupt bacterial biofilm formation; and a biopolymer carrier enables targeted delivery and controlled release of the antibacterial components, resulting in synergistic antibacterial effects and reduced toxicity.

[0024] The antibacterial hydrogel dressing provided by this invention uses a combination of antibacterial substances as antibacterial components, with natural antibacterial ingredients as the killing core, synthetic antibacterial agents as auxiliary synergists, and biological polymer carriers as delivery and protection platforms. Through multi-target and multi-mechanism synergy, it achieves a highly efficient, broad-spectrum, long-lasting, low-toxicity, and low-drug-resistance antibacterial effect.

[0025] The preferred natural antibacterial ingredient of this invention is selected from at least one of cephalosporin, antimicrobial peptide LL-37, and defensin; the above-mentioned natural antibacterial ingredients are all cationic amphiphilic polypeptides, which can bind to bacterial cell membranes through electrostatic interactions (bacterial membranes contain a large amount of anionic phospholipids, while human cell membranes are mainly composed of neutral phospholipids, thus exhibiting biological selectivity), penetrate bacterial biofilm barriers, destroy biofilm structures, and prevent bacteria from forming drug-resistant biofilms on the dressing surface.

[0026] Specifically, cephalosporin has a highly effective killing effect on both Gram-positive bacteria (such as Staphylococcus aureus) and Gram-negative bacteria (such as Escherichia coli), and can penetrate the bacterial cell membrane and inhibit respiratory chain enzyme activity; the antimicrobial peptide LL-37 is an endogenous human antimicrobial peptide that, in addition to disrupting the cell membrane, can also inhibit bacterial DNA replication and protein synthesis, and has immunomodulatory effects (promoting macrophage phagocytosis); defensins form transmembrane channels through polymerization and can also bind to peptidoglycan in the bacterial cell wall, thus hindering cell wall synthesis.

[0027] The preferred synthetic antibacterial agent of this invention is selected from at least one of polyhexamethylene biguanide, benzalkonium chloride, and polyquaternium-47.

[0028] Among them, polyhexamethylene biguanide (PHMB) is a cationic polymer that binds to bacterial cell membranes through electrostatic interactions, disrupting membrane potential balance and causing cell membrane rupture; it can penetrate bacterial cell walls, bind to intracellular DNA, inhibit DNA replication and transcription, and prevent bacterial reproduction; it also has an inhibitory effect on fungi (such as Candida albicans) and is not prone to developing drug resistance.

[0029] Benzalkonium chloride (BZK) is a quaternary ammonium salt cationic surfactant that inserts into the bacterial cell membrane through hydrophobic interactions, disrupting the lipid bilayer structure of the membrane and causing intracellular substances to leak out. It can inhibit bacterial enzyme systems (such as acetylcholinesterase) and interfere with metabolic processes. It has a rapid bactericidal effect, but long-term use may lead to mild drug resistance, so it needs to be used in combination with natural ingredients to reduce the risk.

[0030] Polyquaternium-47 (PQ-47) is a cationic water-soluble polymer that encapsulates bacteria through electrostatic adsorption, blocking bacterial adhesion to host cells; it disrupts the formation of bacterial biofilms, preventing bacterial aggregation; it has extremely low toxicity, good compatibility with biopolymer carriers, and can enhance the biosafety of the system.

[0031] The preferred biopolymer carrier of this invention is selected from at least one of chitosan, hyaluronic acid, and sodium alginate. This biopolymer carrier binds to antibacterial components through electrostatic interactions to form a stable complex, preventing the rapid loss of antibacterial components. It also encapsulates antibacterial components through hydrogen bonds and hydrophobic interactions, protecting them from degradation during storage and use (e.g., preventing antimicrobial peptides from being hydrolyzed by proteases). Furthermore, it neutralizes the cytotoxicity of synthetic antibacterial agents (e.g., the slight irritation of human cells by benzalkonium chloride) while preventing the rapid metabolism of natural antimicrobial peptides, thus prolonging the duration of action.

[0032] Chitosan itself possesses antibacterial activity, binding to bacterial cell membranes via cationic binding and simultaneously promoting wound healing (activating fibroblasts). This invention preferably uses hydrophobic chitosan, specifically, fatty acid-grafted hydrophobic chitosan, and more preferably palmitic acid-grafted hydrophobic chitosan, with a grafting degree of 10%-20%; the hydrophobic chitosan serves as a carrier to achieve sustained release.

[0033] Hyaluronic acid (HA) indirectly enhances antibacterial effects by regulating the wound microenvironment (moisturizing and anti-inflammatory), and can also bind to the antimicrobial peptide LL-37 to improve its stability and targeting.

[0034] Sodium alginate (SA) forms gel microspheres that encapsulate antibacterial components, enabling targeted release. It can also bind to calcium ions on the bacterial surface, disrupting cell membrane stability.

[0035] Furthermore, the present invention preferably combines the natural antibacterial components, synthetic antibacterial agents, and biological polymer carriers in a mass ratio of 5:6:6.

[0036] Furthermore, the present invention preferably combines the antibacterial substances as a combination of cephalosporin, polyhexamethylene biguanide (PHMB), and chitosan, or a combination of antimicrobial peptide LL-37, benzalkonium chloride (BZK), and hyaluronic acid (HA), or a combination of defensin, polyquaternium-47 (PQ-47), and sodium alginate (SA); and even more preferably, the combined antibacterial substances are composed of cephalosporin, polyhexamethylene biguanide (PHMB), and chitosan in a mass ratio of 5:6:6; wherein, cephalosporin is preferably cephalosporin B with a purity ≥95%, and chitosan is preferably fatty acid-grafted hydrophobic chitosan, and even more preferably palmitic acid-grafted hydrophobic chitosan with a grafting degree of 10%-20%. Cephalosporin B disrupts bacterial cell membranes, PHMB has a strong bactericidal effect, and hydrophobic chitosan acts as a carrier to achieve sustained release, broadly covering Gram-positive bacteria, Gram-negative bacteria, and fungi, and the three synergistically enhance the antibacterial effect.

[0037] This invention achieves broad-spectrum antibacterial activity, reduced toxicity, and long-lasting sustained release through the synergistic effect of natural antibacterial components, synthetic antibacterial agents, and biopolymer carriers.

[0038] The gel matrix in this invention is used to construct a stable gel network for the composite system, which determines the biocompatibility, solubility, and adhesion of the hydrogel dressing. This invention selects copolymers with excellent biocompatibility as the gel matrix. Specifically, the preferred gel matrix is ​​selected from at least one of polyethylene glycol-polyglutamic acid copolymer, polyethylene glycol-polylactic acid copolymer, polyethylene glycol-polycaprolactone copolymer, polyethylene glycol-polylysine copolymer, polyglutamic acid-polylysine copolymer, polyethylene glycol-polyaspartic acid copolymer, hyaluronic acid-polyethylene glycol copolymer, sodium alginate-polyglutamic acid copolymer, and gelatin-polyethylene glycol copolymer. More preferably, the gel matrix is ​​polyethylene glycol-polyglutamic acid copolymer (PEG-PGA) with a molecular weight of 10,000-50,000 Da and a PEG to PGA molar ratio of 1:(2-5), which has both good hydrophilicity and biodegradability, can closely adhere to the wound surface, and promote cell proliferation.

[0039] The present invention preferably uses a nonionic emulsifier to adapt to the oil-in-water system, avoid interaction with antibacterial components, and improve the dispersion uniformity of hydrophobic components. Specifically, the present invention preferably uses at least one of polyglycerol-10-oleate, polyglycerol-6-stearate, polyglycerol-4-laurate, Tween 80, Tween 20, Span 80, poloxamer 407, and poloxamer 188 as the emulsifier; and further preferably uses polyglycerol-10-oleate, which has good emulsification stability, can completely encapsulate hydrophobic chitosan, and is compatible with all components.

[0040] The present invention preferably uses a physical crosslinking agent to construct a stable three-dimensional network through hydrogen bonding, hydrophobic interaction, and electrostatic interaction, without introducing chemical impurities and protecting the activity of antibacterial components. Specifically, the preferred crosslinking agent is selected from at least one of glycerol, hyaluronic acid, sodium alginate, xanthan gum, gelatin, silk fibroin, cyclodextrin, and polylysine. Glycerol is further preferred as the crosslinking agent because it has both crosslinking and moisturizing functions. It combines with gel matrices such as PEG-PGA and biopolymer carriers such as hydrophobic chitosan through hydrogen bonding to construct a stable physical crosslinking network, while reducing moisture loss from the wound surface.

[0041] Another object of the present invention is to provide a method for preparing the antibacterial hydrogel dressing as described above, the method comprising the following steps: S1: According to the formula, mix the biopolymer carrier and crosslinking agent, add emulsifier and dispersant, stir, and obtain polymer carrier solution; In this invention, the biopolymer carrier is preferably passed through a 100-mesh sieve to ensure uniform particle size. In this step, the physical crosslinking agent can first form a hydrogen bond network with the biopolymer carrier, while the nonionic emulsifier improves the compatibility of the biopolymer carrier in the aqueous phase through oil-water dispersion, thus preventing the biopolymer carrier from separating in subsequent mixing. For example, the hydrophobic chitosan solution can be prepared as follows: after drying the hydrophobic chitosan, grind it through a 100-mesh sieve, add glycerol and stir evenly, add polyglycerol-10-oleate, add deionized water, and stir at 200 r / min for 30 min. In this process, a 100-mesh sieve ensures uniform chitosan particle size. Glycerol, as a physical crosslinking agent, can first form a hydrogen bond network with chitosan. Polyglycerol-10-oleate (a nonionic emulsifier) ​​targets the hydrophobicity of chitosan and improves its compatibility in the aqueous phase through oil-water dispersion, thus preventing the hydrophobic components from separating in subsequent mixing.

[0042] S2: Prepare gel matrix solution, natural antibacterial solution and synthetic antibacterial agent solution respectively; The preferred preparation process of the gel matrix solution is as follows: First, stir a portion of deionized water at a low speed (100 r / min) for 2 min. Then, slowly and evenly sprinkle the weighed gel matrix into the deionized water. As the viscosity increases, the speed is increased to 500 r / min, and the mixture is stirred for 30 min to obtain the gel matrix mother liquor. Next, add a portion of deionized water to the gel matrix mother liquor and stir at 500 r / min for 30 min to obtain the gel matrix solution. For example, the pretreatment of PEG-PGA can be carried out according to the following process: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min, then slowly and evenly sprinkle the weighed PEG-PGA into the water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min. In this process, a combination of low-speed powder spreading and gradient speed stirring (from 100 r / min to 500 r / min) was used. First, the low speed was used to prevent the powder from clumping, and then the high speed was used to promote the swelling and dispersion of the copolymer in water, which solved the problem of the hydrophilic copolymer being difficult to dissolve uniformly. In the subsequent mixing stage, some deionized water was added to dilute the mixture and further reduce the viscosity of the matrix, providing a suitable rheological environment for the subsequent addition of antibacterial components and excipients. The natural antibacterial solution can be prepared by the following process: dissolving the natural antibacterial component in phosphate buffer and stirring until completely dissolved to obtain the natural antibacterial solution; For example, the preparation process of cephalosporin solution is as follows: dissolve cephalosporin in pH 6.5 phosphate buffer and stir until completely dissolved; As a natural antimicrobial peptide, cephalosporin has broad-spectrum antimicrobial activity and is not prone to drug resistance, but it has poor stability and is easily hydrolyzed by enzymes. In this invention, cephalosporin is dissolved in a pH 6.5 phosphate buffer solution to match the optimal pH environment for its physiological activity and avoid peptide bond hydrolysis under strong acid or strong alkaline conditions. Synthetic antibacterial agent solutions are aqueous solutions; for example, PHMB is prepared as a 10% aqueous solution, and if it is a 10% aqueous solution, it can be used directly.

[0043] S3: Add the natural antibacterial solution to the polymer carrier solution, sonicate in an ice bath, add it to the gel matrix solution, then add the synthetic antibacterial agent solution to the system, adjust the pH to 6.0-7.0, and after degassing and molding, obtain the antibacterial hydrogel dressing; The preferred temperature for ice bath ultrasound is 10±5℃, the power is 200W, the working time is 5s intervals of 10s, and the total duration is 5min. Using ice bath ultrasound, the low temperature environment can prevent the denaturation of natural antibacterial components caused by ultrasound heat generation, while pulsed ultrasound can break up aggregates through cavitation effect, while avoiding damage to peptide chain structure caused by excessive ultrasound. After adding to the gel matrix solution, stir at 300 rpm for 10 min, then increase to 400 rpm and stir for 20 min; after adding the synthetic antibacterial agent solution, keep the speed constant and stir for 15 min, then reduce to 200 rpm and stir for 5 min. This invention first mixes the natural antibacterial component-polymer carrier complex with the gel matrix, and then adds an aqueous solution of synthetic antibacterial agent to avoid electrostatic repulsion between the cationic synthetic antibacterial agent and the cationic peptide at high concentrations, thus ensuring that both antibacterial components can be uniformly dispersed in the matrix. Preferably, triethanolamine is prepared as a 10% (w / w) aqueous solution and then slowly added dropwise while maintaining a constant stirring speed until the pH reaches 6.0-7.0. The 10% triethanolamine aqueous solution is added slowly dropwise, rather than directly to the pure product. This allows for precise control of the pH rise rate, preventing excessively high local pH levels that could lead to copolymer degradation or inactivation of antibacterial components. The final pH is adjusted to 6.0-7.0 (close to the physiological pH of the skin), improving the biocompatibility of the dressing and avoiding interference with the wound microenvironment. This invention employs a physical cross-linking system throughout (cross-linking agent, biopolymer carrier, and hydrogen bonding / hydrophobic interaction of the gel matrix itself), without introducing chemical cross-linking agents. This avoids the irritation of wounds caused by residual chemical impurities, while also protecting the activity of antimicrobial peptides (chemical cross-linking agents may react with peptide bonds).

[0044] The preferred degassing molding process is as follows: vacuum degassing (-0.08~-0.09MPa) for 20-25 min, static curing for 8 h, refrigeration at 4℃ for 4 h, refrigeration at 4℃ for 2 h, and static curing at room temperature for 2 h. Vacuum degassing can effectively remove air bubbles introduced during the mixing process, preventing pores from appearing on the dressing surface that could lead to loss of antibacterial ingredients or bacterial invasion. Low-temperature refrigeration can accelerate the formation of gel networks (reduce the molecular motion rate and promote the stable binding of hydrogen bonds and hydrophobic interactions), while further protecting the activity of antibacterial components and enabling rapid molding.

[0045] This invention provides a hydrogel dressing with a broad antibacterial spectrum, strong healing-promoting ability, excellent mechanical properties, and good biocompatibility. Through the synergistic effect of multiple components, it overcomes the shortcomings of traditional hydrogel dressings and provides a simple and scalable preparation method. The hydrogel dressing with antibacterial and healing-promoting functions provided by this invention is an oil-in-water (O / W) type composite crosslinking system, mainly composed of a gel matrix, combined antibacterial substances, emulsifiers, crosslinking agents, auxiliary functional components, and dispersants.

[0046] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0047] Example 1 This embodiment provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight percentage, 0.6 parts of palmitic acid-grafted hydrophobic chitosan (grafting degree of 15%) was dried, ground and passed through a 100-mesh sieve, 3.0 parts of glycerol were added and stirred evenly, 2 parts of polyglycerol-10-oleate were added, and 5 parts of deionized water were added. The mixture was stirred at 200 r / min for 30 min to obtain a hydrophobic chitosan solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S3: Add the cephalosporin solution to the hydrophobic chitosan solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase the speed to 400r / min and stir for 20min; add the PHMB aqueous solution, stir at the same speed for 15min, then reduce the speed to 200r / min and stir for 5min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0048] Example 2 This embodiment provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight percentage, 0.6 parts of palmitic acid-grafted hydrophobic chitosan (grafting degree of 15%) was dried, ground and passed through a 100-mesh sieve, 8.0 parts of glycerol were added and stirred evenly, 5.0 parts of polyglycerol-10-oleate were added, and 5 parts of deionized water were added. The mixture was stirred at 200 r / min for 30 min to obtain a hydrophobic chitosan solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 12 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S3: Add the cephalosporin solution to the hydrophobic chitosan solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase the speed to 400r / min and stir for 20min; add the PHMB aqueous solution, stir at the same speed for 15min, then reduce the speed to 200r / min and stir for 5min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0049] Example 3 This embodiment provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight percentage, 0.6 parts of palmitic acid-grafted hydrophobic chitosan (grafting degree of 15%) was dried, ground and passed through a 100-mesh sieve, 1.0 part of glycerol was added and stirred evenly, 1.0 part of polyglycerol-10-oleate was added, and 5 parts of deionized water were added. The mixture was stirred at 200 r / min for 30 min to obtain a hydrophobic chitosan solution. S2: Stir 50 parts of deionized water at 100 rpm for 2 min. Slowly and evenly sprinkle 5 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 rpm and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 rpm for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S3: Add the cephalosporin solution to the hydrophobic chitosan solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase the speed to 400r / min and stir for 20min; add the PHMB aqueous solution, stir at the same speed for 15min, then reduce the speed to 200r / min and stir for 5min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0050] Example 4 This embodiment provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight, dry 0.6 parts of hyaluronic acid and grind it through a 100-mesh sieve. Add 4.0 parts of glycerin and stir evenly. Add 2.5 parts of polyglycerol-10-oleate and 5 parts of deionized water. Stir at 200 r / min for 30 min to obtain a hyaluronic acid solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of antimicrobial peptide LL-37 in 6 parts of pH 6.5 phosphate buffer and stir until completely dissolved to obtain an antimicrobial peptide solution. Prepare a 10% (w / w) aqueous solution of benzalkonium chloride from 0.6 parts of benzalkonium chloride. S3: Add the antimicrobial peptide solution to the hyaluronic acid solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add to the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase to 400r / min and stir for 20min; add benzalkonium chloride aqueous solution, stir at the same speed for 15min, then reduce to 200r / min and stir for 5min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0051] Example 5 This embodiment provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight, dry 0.6 parts of sodium alginate and grind it through a 100-mesh sieve. Add 4.0 parts of glycerol and stir evenly. Add 2.5 parts of polyglycerol-10-oleate and 5 parts of deionized water. Stir at 200 r / min for 30 min to obtain sodium alginate solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of defensin in 6 parts of pH 6.5 phosphate buffer and stir until completely dissolved to obtain a defensin solution; Prepare a 10% (w / w) polyquaternium salt aqueous solution by dissolving 0.6 parts of polyquaternium-47. S3: Add the defensin solution to the sodium alginate solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase to 400r / min and stir for 20min; add the polyquaternary ammonium salt aqueous solution, stir at the same speed for 15min, then reduce to 200r / min and stir for 5min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0052] Each comparative example in this invention is compared with Example 1.

[0053] Comparative Example 1 This comparative example provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight percentage, 0.6 parts of palmitic acid-grafted hydrophobic chitosan (grafting degree of 15%) was dried, ground and passed through a 100-mesh sieve, 4.0 parts of glycerol were added and stirred evenly, 2.5 parts of polyglycerol-10-oleate were added, and 5 parts of deionized water were added. The mixture was stirred at 200 r / min for 30 min to obtain a hydrophobic chitosan solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S3: Add the hydrophobic chitosan solution to the PEG-PGA matrix solution, stir at 300 r / min for 10 min, then increase to 400 r / min and stir for 20 min; add PHMB aqueous solution, stir at the same speed for 15 min, then reduce to 200 r / min and stir for 5 min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0054] Comparative Example 2 This comparative example provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight percentage, 0.6 parts of palmitic acid-grafted hydrophobic chitosan (grafting degree of 15%) was dried, ground and passed through a 100-mesh sieve, 4.0 parts of glycerol were added and stirred evenly, 2.5 parts of polyglycerol-10-oleate were added, and 5 parts of deionized water were added. The mixture was stirred at 200 r / min for 30 min to obtain a hydrophobic chitosan solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; S3: Add the cephalosporin solution to the hydrophobic chitosan solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase to 400r / min and stir for 20min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0055] Comparative Example 3 This comparative example provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: Stir 50 parts of deionized water at 100 rpm for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 rpm and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 rpm for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S2: Add the cephalosporin solution to the PEG-PGA matrix solution, stir at 300 r / min for 10 min, then increase to 400 r / min and stir for 20 min; add PHMB aqueous solution, stir at the same speed for 15 min, then reduce to 200 r / min and stir for 5 min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0056] Comparative Example 4 This comparative example provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight, dry 0.6 parts of chitosan and grind it through a 100-mesh sieve, add 4.0 parts of glycerol and stir evenly, add 2.5 parts of polyglycerol-10-oleate, add 5 parts of deionized water, stir at 200 r / min for 30 min to obtain chitosan solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S3: Add the cephalosporin solution to the chitosan solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase the speed to 400r / min and stir for 20min; add the PHMB aqueous solution, stir at the same speed for 15min, then reduce the speed to 200r / min and stir for 5min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0057] Comparative Example 5 This comparative example provides a method for preparing an antibacterial hydrogel dressing, comprising the following steps: S1: According to the weight percentage, 0.6 parts of palmitic acid-grafted hydrophobic chitosan (grafting degree of 15%) was dried, ground and passed through a 100-mesh sieve, 4.0 parts of glycerol were added and stirred evenly, 2.5 parts of polyglycerol-10-oleate were added, and 5 parts of deionized water were added. The mixture was stirred at 200 r / min for 30 min to obtain a hydrophobic chitosan solution. S2: Stir 50 parts of deionized water at a low speed of 100 r / min for 2 min. Slowly and evenly sprinkle 8 parts of PEG-PGA (molecular weight of 30000 Da, PEG to PGA molar ratio of 1:3) into the deionized water. As the viscosity increases, increase the speed to 500 r / min and stir for 30 min to obtain PEG-PGA mother liquor. Before mixing, pour 30 parts of deionized water into the PEG-PGA mother liquor and stir at 500 r / min for 30 min to obtain PEG-PGA matrix solution. Dissolve 0.5 parts of cephalosporin B (purity ≥95%) in 6 parts of pH 6.5 phosphate buffer solution and stir until completely dissolved to obtain cephalosporin solution; Prepare a PHMB aqueous solution with a mass concentration of 10% by using 0.6 parts of polyhexamethylene biguanide (PHMB); S3: Add the cephalosporin solution and PHMB aqueous solution to the hydrophobic chitosan solution, sonicate in an ice bath (10±5℃) at a power of 200W, with a working time of 5s followed by 10s intervals, for a total duration of 5min; add to the PEG-PGA matrix solution, stir at 300r / min for 10min, then increase to 400r / min and stir for 20min to obtain the reaction mixture; Prepare a 10% (w / w) triethanolamine aqueous solution by dissolving 0.3 parts of triethanolamine. Slowly add the triethanolamine aqueous solution dropwise to the reaction mixture while maintaining a constant stirring speed. Stir until the pH reaches 6.0-7.0 (around 6.5) to obtain the product. The product was subjected to vacuum degassing (-0.08~-0.09MPa) for 20-25 min, allowed to stand for 8 h, refrigerated at 4℃ for 4 h, refrigerated at 4℃ for 2 h, and allowed to stand for 2 h at room temperature to obtain an antibacterial hydrogel dressing.

[0058] The performance of the antibacterial hydrogel dressings prepared in the above embodiments and comparative examples was tested using the following methods: 1. Antibacterial performance testing: Gram-positive bacteria (Staphylococcus aureus ATCC 25923), Gram-negative bacteria (Escherichia coli ATCC 25922), fungi (Candida albicans ATCC 10231); Inhibition zone method: Prepare a concentration of 1×10 6 A bacterial suspension of CFU / mL was evenly spread on the surface of LB agar medium; dressing samples with a diameter of 10 mm were aseptically inoculated into the medium and incubated at 37℃ for 24 h; the diameter of the inhibition zone (mm) was measured, with 3 parallel samples per group, and the average value was taken; A diameter ≥15mm indicates a strong antibacterial effect.

[0059] MIC determination procedure: The dressing extract (prepared by soaking 1g of dressing in 10mL of sterile water for 24h) was serially diluted (1:2~1:128) using the micro-broth dilution method; 100μL of diluent and 100μL of bacterial suspension (1×10⁻⁶) were added to each well. 5 (CFU / mL), incubate at 37℃ for 24 h; The lowest dilution concentration at which no bacterial growth occurs is defined as the MIC value; a MIC ≤ 8 mg / mL indicates low toxicity and high efficacy.

[0060] 2. Antibacterial sustained-release effect test: Cephalosporin B (or antimicrobial peptide LL-37 / defensin), polyhexamethylene biguanide (PHMB) (or benzalkonium chloride / polyquaternium-47) High-performance liquid chromatography (HPLC): Take 0.5g of dressing sample and immerse it in 20mL of simulated wound exudate (pH 7.4 phosphate buffer, containing 0.1% serum albumin); place it in a constant temperature shaker at 37℃ and 100r / min, and take 5mL samples at 1h, 6h, 12h, 24h, 48h, 72h, and 168h (7 days) (while simultaneously adding an equal amount of fresh exudate); use HPLC to determine the concentration of antibacterial agent in the sample and calculate the cumulative release rate; Determination of sustained-release effect: 1-hour cumulative release rate ≤30% (no burst release), 72-hour cumulative release rate ≥60%, 168-hour cumulative release rate ≥85% (long-acting release).

[0061] 3. Antibacterial durability test: Continuous antibacterial test: Fix the dressing sample onto a 24-well plate and add 1 mL of bacterial suspension (1×10⁻⁶). 6 (CFU / mL) and incubate at 37℃; every 24 hours, aspirate the supernatant and add 1 mL of fresh bacterial suspension, and incubate continuously for 7 days; on the 7th day, take samples, serially dilute them, spread them on plates, and count the number of surviving colonies (CFU / mL). Persistence determination: Colony count ≤ 1 × 10⁻⁶ on day 7 3 CFU / mL, and no drug-resistant strains were produced (the MIC values ​​of the initial strains and strains after 7 days showed an increase of ≤2 times).

[0062] 4. Mechanical property testing Tensile strength and elongation at break: Cut the dressing into strips of 10mm × 50mm (2mm thick), with 5 parallel samples per group; determine the tensile strength (MPa) and elongation at break (%). Acceptable standards: tensile strength ≥ 0.3 MPa (to avoid breakage during use), elongation at break ≥ 150% (to conform to the deformation of the wound).

[0063] The test results are shown in Table 1.

[0064] Table 1 Example 1 22.47 / 21.33 / 18.68 4.28 25.63 88.32 <![CDATA[8.23×10 2 ]]> 0.454 185.32 Example 2 23.03 / 21.82 / 19.27 3.82 24.94 89.17 <![CDATA[7.55×10 2 ]]> 0.522 172.51 Example 3 21.76 / 20.55 / 17.81 4.51 27.36 86.76 <![CDATA[9.15×10 2 ]]> 0.385 193.58 Example 4 22.11 / 20.91 / 18.53 4.03 26.15 87.55 <![CDATA[8.71×10 2 ]]> 0.438 181.61 Example 5 21.90 / 20.74 / 18.28 4.32 26.87 87.16 <![CDATA[8.93×10 2 ]]> 0.411 188.54 Comparative Example 1 16.22 / 15.81 / 14.36 8.67 24.35 85.21 <![CDATA[3.55×10 2 ]]> 0.444 183.53 Comparative Example 2 17.51 / 16.94 / 15.16 7.83 28.52 84.78 <![CDATA[2.86×10 2 ]]> 0.463 180.57 Comparative Example 3 19.88 / 18.75 / 16.52 5.34 68.73 92.13 <![CDATA[1.23×10 2 ]]> 0.426 178.16 Comparative Example 4 20.37 / 19.32 / 17.24 5.12 45.23 89.54 <![CDATA[4.64×10 2 ]]> 0.434 182.48 Comparative Example 5 18.73 / 17.91 / 15.87 6.73 27.12 83.9 <![CDATA[6.33×10 2 ]]> 0.415 175.41 The difference between Comparative Example 1 and Example 1 is that no natural antibacterial components were added. Due to the lack of the cell membrane-destroying effect of cephalosporin B, the antibacterial mechanism is singular, and the antibacterial effect against drug-resistant strains is weakened.

[0065] The difference between Comparative Example 2 and Example 1 is that no synthetic antibacterial agent was added. Due to the lack of PHMB's inhibitory effect on bacterial DNA, cephalosporin was partially degraded by bacterial proteases, and the synergistic bactericidal effect disappeared.

[0066] The difference between Comparative Example 3 and Example 1 is that no biopolymer carrier was added. Due to the lack of encapsulation and sustained release effect of hydrophobic chitosan, the antibacterial agent was physically adsorbed onto the gel matrix and easily dissolved quickly.

[0067] The difference between Comparative Example 4 and Example 1 is that unmodified chitosan was used instead of hydrophobic chitosan. Because unmodified chitosan is highly hydrophilic, its hydrophobic interaction and hydrogen bonding with the antibacterial agent are weak, resulting in the inability to form a stable sustained-release system and the antibacterial agent being released too quickly.

[0068] The difference between Comparative Example 5 and Example 1 is that the cephalosporin solution and the PHMB aqueous solution were added to the hydrophobic chitosan solution at the same time. Because the cationic cephalosporin and cationic PHMB repel each other at high concentrations, the two antibacterial components are not evenly dispersed, with some areas having antibacterial agents aggregated and others lacking them.

[0069] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. An antimicrobial hydrogel dressing, characterized in that, The effective components of the raw material, by weight, are as follows: 5-12 parts of gel matrix; Combined with 0.5-3.0 parts of antibacterial substance; Emulsifier 0.1-5.0 parts; Crosslinking agent 0.3-8.0 parts; Dispersant 50-100 parts; The combined antibacterial substance comprises natural antibacterial components, synthetic antibacterial agents, and biopolymer carriers; wherein the mass ratio of natural antibacterial components, synthetic antibacterial agents, and biopolymer carriers is 5:6:6; the combined antibacterial substance is specifically a combination of cecropin, polyhexamethylene biguanide (PHMB), and palmitic acid grafted with hydrophobic chitosan with a grafting degree of 10%-20%; or a combination of antimicrobial peptide LL-37, benzalkonium chloride, and hyaluronic acid; or a combination of defensin, polyquaternium-47, and sodium alginate. The gel matrix is ​​selected from polyethylene glycol-polyglutamic acid copolymer (PEG-PGA); the emulsifier is selected from polyglycerol-10-oleate; the crosslinking agent is selected from glycerol; and the dispersant is selected from water. The method for preparing the antibacterial hydrogel dressing includes the following steps: S1: According to the formula, mix the biopolymer carrier and crosslinking agent, add emulsifier and dispersant, stir, and obtain polymer carrier solution; S2: Prepare gel matrix solution, natural antibacterial component solution and synthetic antibacterial agent solution respectively; S3: Add the natural antibacterial component solution to the polymer carrier solution, sonicate in an ice bath, add it to the gel matrix solution, then add the synthetic antibacterial agent solution to the system, adjust the pH to 6.0-7.0, and after degassing and molding, obtain the antibacterial hydrogel dressing.

2. A method of preparing an antibacterial hydrogel dressing as claimed in claim 1, characterized in that, Includes the following steps: S1: According to the formula, mix the biopolymer carrier and crosslinking agent, add emulsifier and dispersant, stir, and obtain polymer carrier solution; S2: Prepare gel matrix solution, natural antibacterial component solution and synthetic antibacterial agent solution respectively; S3: Add the natural antibacterial component solution to the polymer carrier solution, sonicate in an ice bath, add it to the gel matrix solution, then add the synthetic antibacterial agent solution to the system, adjust the pH to 6.0-7.0, and after degassing and molding, obtain the antibacterial hydrogel dressing.