Complex silver antibacterial gel and preparation method thereof

Abstract

The invention belongs to the field of biomedical materials, and provides complex silver antibacterial gel and a preparation method thereof. Lithium magnesium sodium silicate is adopted for self-assembly to construct a first network, N, S double-coordination modified sodium carboxymethyl cellulose cooperates with acrylamide and optional N-vinyl imidazole for photo-initiation polymerization to form a second network, and double-network interpenetration is combined with a silver complex formed by complexing a water-soluble cyanurate complexing agent and silver nitrate. By utilizing the design of imidazole and sulfydryl multi-coordination site fixed complex silver, the performance that the daily mean value of the steady-state concentration of silver ions is maintained at 10-40 micrograms per liter under the conditions that the gel forming time is less than or equal to 120 seconds, the light transmittance is greater than or equal to 80% and the wet gel solid content is 8-25 wt% is realized; the contradictions of low-viscosity rapid gelling and silver complex rheological thickening, high transparency and low solid content and ligand-enriched silver cluster scattering, soft moisturizing matrix and sterilization storage stability, strong complexing silver locking and steady-state silver releasing window coupling and the like are solved, and the wide wound dressing application value is achieved.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials, specifically to a complexed silver antibacterial gel and its preparation method. Background Technology

[0002] Wound healing is a crucial issue in clinical medicine, especially in cases of diabetic foot ulcers, burns, and chronic wounds. Bacterial colonization and biofilms can easily delay healing or even lead to infection spread, endangering patient health. Antibacterial gel dressings need to maintain a moist microenvironment and promote cell migration and proliferation while achieving long-lasting and stable antibacterial effects. Silver ions possess broad-spectrum antibacterial properties and relatively low drug resistance, but achieving stable immobilization and controlled release in highly hydrated, soft gels, and maintaining effective antibacterial concentrations throughout sterilization and storage, requires synergistic optimization of structural design and materials chemistry. Simultaneously, rapid gelation is crucial for scalability and clinical applicability, while transparency and low solids content affect observation and patient compliance. The coupling of multiple indicators presents significant challenges to the development of silver-loaded gels, necessitating synergistic innovation through novel network structures and multi-coordination complexation chemistry to enhance overall performance and clinical value.

[0003] Current research and development of silver-supported gel materials faces four main shortcomings. First, the rapid gelation due to low viscosity contradicts the rheological thickening and photocuring inhibition caused by high-content silver complexes. Introducing silver complexes often leads to significantly slower gelation due to steric hindrance and free radical quenching by coordination bonds, or requires a solid content exceeding 15% for self-forming (e.g., the CN108498543B system exhibits slow gelation and high solid content). Second, the high-transparency, low-solids-content dual-network structure is constrained by increased scattering and turbidity resulting from enriched silver complex clusters. When the silver content is ≥200 mg / kg, the transmittance often drops below 60%, affecting wound observation. Third, after ethylene oxide / gamma irradiation sterilization and long-term storage, the silver complex structure and silver release rate of the soft, high-water matrix are difficult to stabilize, with fluctuations exceeding 50% and resulting in antibacterial attenuation. Fourth, the strong complexation to "lock in" silver to inhibit silver chloride deposition is coupled with the need to maintain a steady silver release window (10–40 μg / L) in the wound environment for 24–168 h: if the complexation is too strong, silver release will be insufficient; if it is too weak, it will quickly precipitate and fail under high chloride conditions, limiting the application of high-end dressings. Summary of the Invention

[0004] The purpose of this invention is to provide a complexed silver antibacterial gel and its preparation method, which solves the contradictions and shortcomings of the current silver-supported gel system in terms of low viscosity and rapid gelation and interference of silver complex rheological thickening and photocuring, high transparency and low solid content and increased turbidity of silver cluster scattering due to multi-coordinate ligand enrichment, soft and moisturizing matrix and sterilization and storage stability, strong complexation and silver locking and steady-state silver release window coupling.

[0005] This invention employs sodium magnesium lithium silicate to self-assemble and construct a first rigid inorganic physical network, and then uses N,S dual-coordination modified sodium carboxymethyl cellulose to synergistically polymerize with acrylamide and optional N-vinyl imidazole in an aqueous phase to form a second flexible organic covalent network. The interpenetration of the two networks generates spatial confinement and interfacial synergy, thereby achieving rapid photocuring and gel formation under low solid content conditions. At the same time, it utilizes the differential coordination strength of imidazole nitrogen and mercapto sulfur to silver ions, and combines multiple coordination sites of water-soluble cyanurate complexing agents to construct a multi-site synergistic coordination complex silver structure, achieving a balance between inhibiting silver chloride deposition and maintaining a steady-state silver release window, thus solving the coupling problem of rapid gel formation, high transparency, stable silver release, and long-term storage stability.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A method for preparing a silver complex antibacterial gel, comprising: S1. Construction of the first network: Disperse sodium magnesium lithium silicate in deionized water with a chloride ion concentration ≤0.5mmol / L, so that the mass fraction of sodium magnesium lithium silicate is 1.0-5.0wt%, and stir for 0.5-4.0h at pH 8.0-11.0 and 20-30°C to allow sodium magnesium lithium silicate to self-assemble into a three-dimensional inorganic physical network, and obtain the first network sol or the first network pregel; S2. Construction of the second network: N,S dual-coordinate modified sodium carboxymethyl cellulose aqueous solution and glycerol are added to the first network, and acrylamide and / or N-vinylimidazol monomer, N,N'-methylenebisacrylamide crosslinking agent and photoinitiator are further added. After mixing, vacuum degassing is performed at a vacuum degree of -0.06 to -0.095 MPa for 2-20 min (or until no visible bubbles are visible); then aqueous phase photoinitiated free radical polymerization is carried out under ultraviolet light irradiation to form an organic covalently crosslinked second network, and a chemically crosslinked pregel is obtained. S3. Silver complexation and shaping: Under light-protected conditions, the chemically cross-linked pregel is immersed in an aqueous solution containing a silver complex formed by the complexation of a water-soluble cyanurate complexing agent and silver nitrate, so that silver ions enter and are fixed in the pregel in the form of complexed silver. After complexation for 10-30 minutes, the pregel is removed and the surface free silver species are quickly rinsed to obtain the target gel.

[0007] Furthermore, the N,S dual-coordination modified sodium carboxymethyl cellulose added to S2 was prepared according to the following steps: A1. Raw material preparation: Prepare 1.00 parts by weight of an aqueous solution containing 1.0-2.0 wt% sodium carboxymethyl cellulose; add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide and histidine, in amounts of 0.08-0.20, 0.05-0.15 and 0.05-0.25 molar equivalents, respectively, all based on the carboxyl group of sodium carboxymethyl cellulose; A2. Carboxyl group activation: Adjust the pH to 4.5-5.5 and stir at 20-25°C for 0.5-1.0 h to activate the carboxyl groups of sodium carboxymethyl cellulose; A3. Introducing imidazole sites: Continue the reaction with histidine in the system, adjust the pH to 6.0-6.8, and react for 1.0-3.0 h to covalently introduce histidine into the anhydrous glucose unit of sodium carboxymethyl cellulose via amidation, forming imidazole coordination sites; A4. Introduction of thiol sites: Under conditions of maintaining pH 6.0-6.8, add 0.05-0.25 molar equivalents of L-cysteine. Based on the carboxyl group of sodium carboxymethyl cellulose, 0.01-0.10 molar equivalents of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide can be added respectively (based on the carboxyl group of sodium carboxymethyl cellulose). React for 1.0-3.0 h to covalently introduce L-cysteine ​​into the anhydrous glucose unit of sodium carboxymethyl cellulose via amidation, forming a thiol coordination site. A5. Endpoint and Post-processing: The reaction was terminated when the free amine concentration measured by the TNBS method (or ninhydrin method) changed by ≤5% within 30 minutes and the apparent viscosity of the solution changed by ≤5% within 30 minutes. Small molecules were removed by dialysis for 12-24 hours using a dialysis bag with a molecular weight cutoff of 10 kDa or by ultrafiltration, so that the total amount of residual 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide was less than or equal to 100 ppm, based on N,S dual-coordination modified sodium carboxymethyl cellulose on a dry basis. The obtained N,S dual-coordination modified sodium carboxymethyl cellulose can be freeze-dried or used directly in solution form for gelation. The degree of imidazole substitution is 0.02-0.15 and the degree of mercapto substitution is 0.01-0.10, based on anhydrous glucose units.

[0008] Furthermore, the second network in S2 is obtained through aqueous phase photoinitiated free radical polymerization, specifically including: B1. Monomer solution preparation: N,S dual-coordination modified sodium carboxymethyl cellulose is added to the first network sol or the first network pregel, so that the solid content of N,S dual-coordination modified sodium carboxymethyl cellulose is 0.5-2.0 wt%, and then acrylamide and / or N-vinylimidazole are added as monomers, so that the total monomer mass fraction is 5.0-20.0 wt%, and the molar ratio of acrylamide to N-vinylimidazole is 100:0 to 95:5 relative to the total mass of the solution; N,N'-methylenebisacrylamide 0.05-0.20 wt%, preferably 0.08-0.15 wt%, relative to the total monomers; 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone 0.05-0.15 wt%, relative to the total monomers; and glycerol further added as a moisturizing ingredient; the components are mixed and defoamed, the solvent is deionized water and chloride ions are avoided; B2. Photocuring: the solution obtained in step B1 is used to prepare a sample with a layer thickness of less than or equal to 2 mm, and cured under 365 nm ultraviolet light at an intensity of 10-20 mW·cm. -2 Cross-linking is completed by irradiation for 30-120 seconds under certain conditions, forming a second chemically cross-linked network of acrylamide and N-vinylimidazole copolymer, which interpenetrates with the first network to obtain a chemically cross-linked pregel.

[0009] Further, the silver complexation step of S3 is as follows: Under light-protected conditions, a chemically cross-linked pregel is immersed in an aqueous solution containing a silver complex. The silver complex is generated by the complexation of a water-soluble cyanurate complexing agent with silver nitrate in the aqueous phase. The mass fraction of silver in the aqueous solution, calculated as silver ions, is 0.01-0.10%, and the pH is 7.2-7.6. During the complexation process, the imidazole nitrogen atoms and mercaptosulfonates on the N,S dual-coordination modified sodium carboxymethyl cellulose, as well as the imidazole nitrogen atoms on the N-vinylimidazolium unit in the second network when this unit is present, are used to coordinate with silver ions. The molar ratio of the sum of imidazole nitrogen atoms and mercapto sulfur atoms from N,S dual-coordinate modified sodium carboxymethyl cellulose, and the imidazole nitrogen atoms of the second network in the presence of N-vinylimidazolium units, to silver ions is controlled to be 2-4:1. After complexation for 10-30 min, the gel is removed and the surface free silver species are quickly rinsed to obtain the target gel. The chloride ion concentration in the system is controlled to be less than or equal to 10 mmol / L during the complexation process. The water-soluble cyanurate complexing agent is selected from at least one of cyanuric acid and its water-soluble salts, preferably its water-soluble salts.

[0010] Furthermore, the dispersion temperature of sodium magnesium lithium silicate in S1 is 20-25°C, and the stirring time is 0.5-2.0 h; the ultraviolet light intensity during photoinitiated polymerization in S2 is 10-20 mW·cm. -2The illumination time is 30-120s; the complexation time in S3 is 10-30min; the molar ratio of acrylamide to N-vinylimidazole is preferably 98:2 to 96:4; the mass fraction of glycerol added in S2 is 1.0-25.0wt%, preferably 5.0-20.0wt%, relative to the total mass of the reaction solution prepared in S2.

[0011] As another concept of this invention, it adopts an overall design of "dual-network interpenetration + multi-coordinated silver complexation" to improve antibacterial durability, transparency, and sterilization storage stability. The first network is formed by the rapid electrostatic self-assembly of sodium magnesium lithium silicate in an alkaline, low-chlorine aqueous phase, providing rigid support and high light transmittance, and providing a spatial distribution basis for silver complexation. The second network is formed by photoinitiated copolymerization of acrylamide and N-vinylimidazole in an aqueous phase or by homopolymerization of acrylamide. The imidazole ring serves as both a silver coordination site and a hydrophilic / ion-conducting unit. The crosslinking agent constructs a three-dimensional covalent network that interpenetrates with the first network, allowing the photocuring time to be controlled within 120 s at low solids content (8–25 wt%). N,S dual-coordinated modified sodium carboxymethyl cellulose is dispersed in the dual network, forming a coordination gradient between imidazole nitrogen (medium strength, reversible) and mercaptosulfur (strong coordination, anchoring), and the silver release rate is controlled by the degree of substitution and the site ratio. Cyanurate complexing agents pre-form multi-coordinate silver complexes with silver nitrate, which then exchange N and S sites to construct more stable multi-coordinate gradient silver clusters. This inhibits deposition and maintains a long-term steady-state silver release window under high-chlorine conditions. Glycerin acts as both a moisturizing agent and a radiation protectant, regulating softness and water retention, and reducing the risk of damage to the complexed silver structure from ethylene oxide or radiation sterilization, thereby improving post-sterilization storage stability.

[0012] This invention also discloses a complexed silver antibacterial gel, characterized in that it comprises: a) First network: A three-dimensional inorganic physical network formed by the self-assembly of sodium magnesium lithium silicate in an aqueous phase through electrostatic interaction and steric hindrance; b) Second network: an organic covalent crosslinked network formed by copolymerization of acrylamide and N-vinylimidazol with N,N'-methylenebisacrylamide as crosslinking agent and 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone as photoinitiator, wherein the molar ratio of acrylamide to N-vinylimidazol is 100:0 to 95:5, preferably 98:2 to 96:4; c) N,S dual-coordination modified sodium carboxymethyl cellulose: This is a modified polymer in which histidine imidazole coordination sites and L-cysteine ​​thiol coordination sites are covalently introduced onto the anhydrous glucose units of sodium carboxymethyl cellulose via amidation. The degree of imidazole substitution is 0.02-0.15 and the degree of thiol substitution is 0.01-0.10 based on the anhydrous glucose units, and the ratio of the degree of imidazole substitution to the degree of thiol substitution is 1.0-3.0:1. The N,S dual-coordination modified sodium carboxymethyl cellulose is dispersed in an interpenetrating network composed of a first network and a second network. d) Water-soluble cyanurate complexing agent: used to complex with silver ions to form a stable silver complex, wherein the water-soluble cyanurate complexing agent is selected from at least one of cyanuric acid and its water-soluble salts, preferably its water-soluble salts; e) Silver complex: A silver complex formed by the complexation of silver ions with the cyanurate coordination sites in a water-soluble cyanurate complexing agent, and further coordinating with the imidazole and thiol coordination sites from c) and (in the presence of N-vinylimidazolium units) the imidazole coordination sites from the unit in b), forming a stable multi-coordination silver complex structure in the gel network; f) Moisturizing ingredient: Glycerin, dispersed in the aqueous phase of the gel, is used to improve the moisturizing and softening properties of the gel; g) Water; Wherein: the molar ratio of the total nitrogen atom of the imidazole ligand and the mercapto sulfur atom of the N,S dual-coordination modified sodium carboxymethyl cellulose derived from c) and the N-vinylimidazol unit optionally selected in the second network to silver ions is 2-4:1; the silver content is 100-600 mg / kg, based on wet gel; under the extraction conditions, i.e. 37°C, sample thickness 1 mm, and solid-liquid ratio 1:10, the daily average steady-state concentration of silver ions in the 24-168h range is 10-40 μg / L; the wet gel solid content is 8-25 wt%, where the wet gel solid content refers to the dry matter mass fraction determined by the loss on drying method; the mass fraction of glycerol in the wet gel is 1.0-25.0 wt%, preferably 5.0-20.0 wt%; and the gel forming time is ≤120 s, where the gel forming time is defined as the time from the cessation of light irradiation to the self-standing formation of the sample.

[0013] Furthermore, the gelation time is ≤120s and the temperature is 25°C with a shear rate of 10s. -1 The apparent viscosity is 0.20-0.80 Pa·s; the gel is transparent or slightly milky white in appearance, and has a transmittance of ≥80% at a wavelength of 600 nm and an optical path of 1.0 mm; the wet gel solid content is preferably 12-18 wt%.

[0014] Furthermore, the gel can be sterilized by ethylene oxide or γ-irradiation at 25-35 kGy, and the daily average steady-state silver ion concentration window, i.e., the range of 10-40 μg / L, changes by ≤±20% compared to before sterilization; it is stable for 12-24 months when stored in a sealed, light-protected environment at 22-28°C and 40-60% relative humidity; the silver content is preferably 200-400 mg / kg, based on wet gel, to achieve an optimal balance between the silver release window and cell compatibility.

[0015] Furthermore, the use of the complexed silver antibacterial gel in wound dressings.

[0016] Furthermore, the dressing can be used continuously on the same wound for 1-7 days, with a replacement cycle of 24-72 hours during this period.

[0017] Furthermore, the chemically cross-linked pregel after step S2 is washed or extracted with water to ensure that the total residual amount of unreacted acrylamide, N-vinylimidazole, N,N'-methylenebisacrylamide and photoinitiator is ≤500 ppm, based on the wet weight of the gel.

[0018] The mechanism and synergistic effect of sodium magnesium lithium silicate and N,S dual-coordination modified sodium carboxymethyl cellulose in this invention can be summarized as follows: Sodium magnesium lithium silicate focuses on rapidly constructing rigid support and improving transparency. Its sheets self-assemble under alkaline conditions to form a three-dimensional physical network, reducing light scattering and supporting low solids content self-support; N,S dual-coordination modified CMC-Na focuses on providing silver complexation sites and regulating silver release. It achieves continuous release through reversible complexation of imidazole nitrogen, inhibits deposition and improves solidification stability through strong coordination of mercaptosulfone, and regulates the silver release rate by the site ratio. In terms of rapid gelation, the first network provides initial modulus and support, and modified CMC-Na enhances the combination of the two networks and promotes the formation of interpenetrating structures through hydrogen bonding / interface interaction, achieving short-time curing and molding; in terms of transparency, the regular arrangement of nanosheets reduces scattering, and the hydrophilicity of modified CMC-Na improves the solvation of silver complex clusters and reduces refractive index mismatch, so that high silver loading still maintains high light transmittance. Both serve as the spatial and site basis, and are bridged by cyanurate complexing agents to form a more stable multi-coordination structure, achieving a synergistic balance of "inhibiting deposition - maintaining the silver release window"; further research can focus on nanoscale interfacial interactions, coordination exchange kinetics, and the evolution of complex structures under irradiation.

[0019] Beneficial technical effects 1. Significantly improved rapid gelation and low-solids self-forming capability: Sodium magnesium lithium silicate rapidly self-assembles to form a first rigid physical network, which interpenetrates with a second flexible covalent network formed by acrylamide / N-vinylimidazole photopolymerization, achieving spatial confinement and stress transfer; it can cure rapidly in 30–120 s at a wet gel solids content of 8–25 wt%, with a molding time ≤120 s. Compared to traditional single-network systems that require higher solids content, this invention reduces solids content while increasing molding rate, facilitating large-scale production and immediate clinical use.

[0020] 2. Synergistic balance between high transparency, low solids content, and high silver complexation: The orderly arrangement of sodium magnesium lithium silicate reduces scattering, and N,S dual-coordination modified CMC-Na improves the solubilization of silver complex clusters and reduces refractive index mismatch. The multi-level coordination gradient structure formed by cyanurate and N,S sites promotes the dispersion of silver clusters. High transmittance (1.0 mm optical path, 600 nm transmittance ≥80%) can still be obtained under the conditions of wet gel solids content of 12–18 wt% and silver content of 200–400 mg / kg, which alleviates the problem of easy turbidity with high silver loading.

[0021] 3. Long-term steady-state silver release window and inhibition of silver chloride deposition: By utilizing the differential coordination strength of imidazole nitrogen (reversible) and mercaptosulfonate (anchored), and combining it with cyanurate multi-coordination sites to construct multi-coordination gradient silver clusters, silver chloride deposition is inhibited under high-chlorine environment, while maintaining a steady-state silver release window of 24–168 h (e.g., 10–40 μg / L), achieving a balance between antibacterial efficacy and cell compatibility, and alleviating the contradiction between "silver locking" and "continuous silver release".

[0022] 4. Excellent stability and long-term performance during sterilization and storage: The dual-network interpenetration and multi-coordinated silver complexation improve structural stability. Combined with glycerol humidification and radiation protection, the silver release window change can be controlled within ±20% after sterilization with ethylene oxide or gamma irradiation (e.g., 25–35 kGy). It can also achieve stable storage for 12–24 months under sealed and light-protected conditions at room temperature, which is superior to the problems of large fluctuations and short shelf life after sterilization of conventional systems.

[0023] 5. Strong application value and clinical applicability of wound dressings: The complexed silver antibacterial gel of this invention has the advantages of rapid gelation, high transparency, softness and moisturization, stable silver release and long-term storage stability. It can be used for antibacterial management of diabetic foot, burns, chronic wounds, etc. The transparency makes it easy to observe, the softness and high water content reduce the pain of dressing changes, and the steady-state silver release provides long-lasting antibacterial effect and improves compliance and healing quality. It has the potential for productization and promotion. Attached Figure Description

[0024] Figure 1 This is a graph showing the effect of sodium magnesium lithium silicate mass fraction on the steady-state release concentration and apparent viscosity of silver ions in this invention.

[0025] Figure 2This is a graph showing the effect of total monomer mass fraction on the steady-state release concentration and apparent viscosity of silver ions in this invention.

[0026] Figure 3 This is a graph showing the effect of the silver mass fraction in the silver complex solution on the steady-state release concentration and apparent viscosity of silver ions in this invention.

[0027] Figure 4 This is a magnified XPSN 1s spectrum of the N,S dual-coordination modified sodium carboxymethyl cellulose and complexed silver antibacterial gel of Example 1 of the present invention.

[0028] Figure 5 The image shows the infrared absorption spectrum of unmodified sodium carboxymethyl cellulose from Example 1.

[0029] Figure 6 The image shows the infrared absorption spectrum of N,S dual-coordination modified sodium carboxymethyl cellulose in Example 1.

[0030] Figure 7 The image shows the infrared absorption spectrum of the complexed silver antibacterial gel from Example 1. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0032] Example 1 This embodiment provides a method for preparing a complexed silver antibacterial gel, comprising the following steps: Unless otherwise specified, the pH adjustment in the following steps shall be performed using an acid / base solution that does not introduce chloride ions. Preferably, the pH shall be adjusted to the target pH (±0.1) by titration with 0.1 mol / L nitric acid solution and 0.1 mol / L sodium hydroxide solution, and the volume added shall be recorded.

[0033] I. Preparation of N,S dual-coordination modified sodium carboxymethyl cellulose 1. A1 Raw Material Preparation Sodium carboxymethyl cellulose was dissolved in deionized water with a chloride ion concentration ≤0.5 mmol / L to prepare an aqueous solution with a sodium carboxymethyl cellulose solid content of 1.5 wt%, which was calculated as 1.00 parts by weight. Based on the carboxyl group of sodium carboxymethyl cellulose, 0.12 molar equivalents of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), 0.10 molar equivalents of N-hydroxysuccinimide (NHS) and 0.12 molar equivalents of histidine were added and mixed thoroughly.

[0034] 2. A2 Carboxyl group activation The pH of the reaction solution in this embodiment was adjusted to 5.0, and the mixture was stirred at 20-23°C for 0.8 hours to fully activate the carboxyl groups of sodium carboxymethyl cellulose.

[0035] 3.A3 Introducing imidazole site Maintaining the presence of histidine in the reaction system of this embodiment, adjusting the pH to 6.4, and continuing the reaction at 25°C for 2.0 h, histidine is covalently introduced into the anhydrous glucose unit of sodium carboxymethyl cellulose via amidation to form an imidazole coordination site. The final degree of imidazole substitution based on the anhydrous glucose unit was calculated from the above feeding conditions and corrected by subsequent 1H NMR spectroscopy and elemental analysis, and confirmed to be around 0.08, which meets the range of 0.02-0.15.

[0036] 4.A4 Introduction of thiol sites Under conditions maintained at pH 6.4, 0.10 molar equivalents of L-cysteine ​​(based on the carboxyl group of sodium carboxymethyl cellulose) were added, along with small amounts of EDC (0.05 molar equivalents) and NHS (0.05 molar equivalents). The reaction was carried out at 25°C for 2.0 h, allowing L-cysteine ​​to be covalently introduced onto the anhydrous glucose units of sodium carboxymethyl cellulose via amidation, forming thiol coordination sites. Titration and sulfur content testing confirmed that the degree of thiol substitution, based on the anhydrous glucose units, was approximately 0.05, meeting the range of 0.01-0.10, and the ratio of imidazole substitution to thiol substitution was approximately 1.6:1, meeting the range of 1.0-3.0:1.

[0037] 5.A5 Endpoint and Post-processing The reaction was terminated when the consumption rate of free amine in the solution of this embodiment tended to level off and the solution viscosity stabilized. Dialysis was performed in deionized water for 18 hours using a dialysis bag with a molecular weight cutoff of 10 kDa, with the dialysis water changed every 3-4 hours to remove small molecule byproducts, ensuring that the total residual EDC and NHS amounted to ≤100 ppm (based on N,S dual-coordination modified carboxymethyl cellulose sodium dry basis). After dialysis, the N,S dual-coordination modified carboxymethyl cellulose sodium powder was obtained by freeze-drying for later use; alternatively, it can be prepared as a 10 wt% aqueous solution for direct gelation. In this embodiment, the degree of imidazole and thiol substitution calculated from the above-mentioned feeding and testing results in the N,S dual-coordination modified carboxymethyl cellulose sodium powder meets the scope defined in the claims, and the total number of coordinated imidazole nitrogen and thiol sulfur sites calculated from their substitution degrees is controlled in a molar ratio of 2-4:1 with silver ions in the subsequent silver complexation step.

[0038] II. Construction of the First Network (S1) Sodium magnesium lithium silicate was slowly added to deionized water with a chloride ion concentration ≤0.5 mmol / L, controlling the mass fraction of sodium magnesium lithium silicate to be 2.5 wt%. The dispersion system of this embodiment was dispersed mechanically at 22°C for 1.0 h at pH 9.5, allowing the sodium magnesium lithium silicate to fully exfoliate and self-assemble in the aqueous phase, forming a three-dimensional inorganic physical network, thus obtaining the first network sol. This first network sol is a transparent, slightly bluish fluid.

[0039] III. Construction of the Second Network (S2, corresponding to B1 and B2) 1. Preparation of B1 monomer solution In this embodiment, an N,S dual-coordinate modified sodium carboxymethyl cellulose solution is added to the first network sol to control its solid content at 1.0 wt%. Acrylamide and N-vinylimidazole monomers are added under stirring conditions to make the total monomer mass fraction 10.0 wt%. Relative to the total mass of the solution in this embodiment, the molar ratio of acrylamide to N-vinylimidazole is controlled at 97:3, within the range of 100:0 to 95:5, and preferably 98:2 to 96:4. In this embodiment, 0.12 wt% of N,N'-methylenebisacrylamide (MBA) was added to the system, which is in the range of 0.05-0.20 wt% relative to the total monomer mass, and preferably falls within the range of 0.08-0.15 wt%. 0.10 wt% of 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone was added as a photoinitiator, which is in the range of 0.05-0.15 wt% relative to the total monomer mass. Glycerin was further added so that the glycerol mass fraction relative to the total mass of the S2 reaction solution in this embodiment is 9.5 wt%, which is in the range of 1.0-25.0 wt%, and preferably falls within the range of 5.0-20.0 wt%. After the components in this embodiment were mixed evenly, vacuum degassing was performed using deionized water as the solvent to avoid introducing chloride ions.

[0040] 2.B2 Photocuring The solution obtained in step B1 was injected into a flat mold with a thickness of 1.0 mm, ensuring the molded layer thickness was ≤2 mm. Irradiation was performed under 365 nm ultraviolet light, with the light intensity controlled at 15 mW·cm². -2 The light exposure time is 60 s, which completes the photoinitiated free radical polymerization of acrylamide and N-vinylimidazolium monomer, forming an organically covalently cross-linked second network in the first network of this embodiment. This second network interpenetrates with the first network to obtain a chemically cross-linked pregel. The pregel in this embodiment is transparent or slightly milky white in appearance and can stand upright. The time from the end of light exposure to the sample standing upright is approximately 40 s, which meets the requirement that the gel forming time is ≤120 s.

[0041] IV. Pregelation Washing and Extraction In this embodiment, after the chemically cross-linked pregel is removed from the mold, it is extracted in low-chlorine deionized water at a solid-liquid ratio (gel wet weight: extract volume) of 1:50-1:500 and a temperature of 20-25°C. Extraction is performed using a shaker at 50-150 rpm for 3-8 hours, with the extract being changed every 0.5-2 hours (at least 3 times); alternatively, flow extraction can be used at a flow rate of 50-500 mL / min for a total extraction time of 3-8 hours to remove unreacted acrylamide, N-vinylimidazole, N,N'-methylenebisacrylamide, and photoinitiator. High-performance liquid chromatography and total organic carbon analysis confirm that the total residual amount of unreacted monomers, cross-linking agents, and photoinitiators is ≤300 ppm, meeting the technical requirement of "≤500 ppm" based on gel wet weight.

[0042] V. Complexing and Shaping (S3) Prepare an aqueous solution of the silver complex: Weigh sodium cyanurate (or potassium cyanurate) and add it to deionized water to prepare a cyanurate solution (0.01-0.10 mol / L); separately prepare a silver nitrate solution (0.005-0.05 mol / L). Under conditions of 20-25°C, protected from light, and stirring at 300-600 rpm, add the silver nitrate solution dropwise to the cyanurate solution at a rate of 0.5-5 mL / min, so that the molar ratio of cyanurate ions to silver ions is 1.0-3.0:1; after the addition is complete, continue stirring for 10-30 min, and if necessary, filter through a 0.22-0.45 μm filter membrane to obtain an aqueous solution of the silver complex. Adjust the aqueous solution of this example so that the mass fraction of silver (based on silver ions) is 0.045 wt% (within the range of 0.01-0.10%), the pH is adjusted to 7.4, and the chloride ion concentration of the system is controlled to ≤5 mmol / L. Store the aqueous solution of the silver complex in a light-protected environment for later use.

[0043] The chemically cross-linked pregel of this embodiment, after immersion, was cut into gel sheets with a diameter of 20 mm and a thickness of 1 mm. These sheets were then immersed in the aforementioned silver complex aqueous solution under light-protected conditions for 20 minutes. During immersion, the imidazole nitrogen atoms and mercaptosulfonates on the N,S dual-coordination modified sodium carboxymethyl cellulose in the pregel, as well as the imidazole nitrogen atoms on the N-vinylimidazolium units in the second network, coordinated with silver ions in the silver complex. The silver ions entered and were immobilized in the pregel of this embodiment in the form of multi-coordination silver complexes. Based on the aforementioned degree of imidazole and mercapto substitution and the N-vinylimidazolium content in the second network, and combined with the silver content determination results (inductively coupled plasma optical emission spectrometry, ICP-OES), it was confirmed that the molar ratio of the total imidazole nitrogen and mercaptosulfonates from the N,S dual-coordination modified sodium carboxymethyl cellulose and the N-vinylimidazolium units in the second network to silver ions was approximately 3:1, satisfying the range of 2-4:1. After complexation is complete, the gel sheet is removed and the surface free silver species are quickly rinsed with deionized water to obtain the target complexed silver antibacterial gel of this embodiment.

[0044] The wet gel solids content, determined by loss on drying, was approximately 15 wt%, falling within the range of 8-25 wt% and preferably within the range of 12-18 wt%. The glycerol content in the wet gel was approximately 9.5 wt%, meeting the range of 1.0-25.0 wt% and preferably within the range of 5.0-20.0 wt%. The silver content was approximately 300 mg / kg (based on wet gel), meeting the range of 100-600 mg / kg and preferably within the range of 200-400 mg / kg. Under PBS extraction conditions of 37°C, 1 mm sample thickness, and a solid-liquid ratio of 1:10, the daily average steady-state silver ion concentration over 24-168 h was approximately 20-30 μg / L, meeting the requirement of 10-40 μg / L. The gel in this embodiment was tested at 25°C and a shear rate of 10 s. -1 The apparent viscosity was measured to be approximately 0.50 Pa·s, falling within the range of 0.20-0.80 Pa·s; the transmittance at a wavelength of 600 nm and an optical path of 1.0 mm was approximately 85%, ≥80%. The gel of this embodiment can be sterilized by ethylene oxide or γ-irradiation (dose 25-30 kGy). The change in the steady-state release concentration window of silver ions (daily average silver ion concentration of 10-40 μg / L in the 24-168h range) before and after sterilization is within ±10%, meeting the ±20% limit; it is stable after being sealed and protected from light for 18 months at 22-28°C and 40-60% relative humidity, with changes in silver content and decreases in mechanical strength both within the allowable range.

[0045] This embodiment also provides the use of the complexed silver antibacterial gel obtained by the above preparation method in wound dressings. The gel of this embodiment is applied to the wound in the form of a sheet and used continuously for 1-5 days, and changed every 24-48 hours. While providing a moderately moist environment and slow-release antibacterial effect of silver ions, it maintains good transparency, which is convenient for medical staff to observe the wound condition.

[0046] Features and applicable scenarios of this embodiment: This embodiment uses a moderately conservative combination of parameters: 2.5 wt% sodium magnesium lithium silicate, 1.0 wt% N,S dual-coordination modified sodium carboxymethyl cellulose, 10 wt% total monomers, 9.5 wt% glycerol, 0.045 wt% silver in the silver complex solution, imidazole and thiol substitution degrees of approximately 0.08 and 0.05 respectively, corresponding to a coordination site to silver molar ratio of approximately 3:1, gel formation time of approximately 40 s, wet gel solid content of approximately 15 wt%, silver content of approximately 300 mg / kg, steady-state silver release of 20-30 μg / L per day, viscosity of approximately 0.50 Pa·s, and light transmittance of approximately 85%. Overall, these parameters fall within the moderate range of 40-60%, balancing gel formation speed, mechanical strength, transparency, and antibacterial properties. This makes it suitable as a well-rounded wound dressing with a wide range of applications, such as for chronic wound care requiring medium- to long-term observation, such as diabetic foot ulcers and venous ulcers.

[0047] Example 2 This embodiment provides another method for preparing a complexed silver antibacterial gel, similar to Example 1, except that the selection of parameters is more biased towards improving the gel's solid content, silver loading, and soft and moisturizing properties, as detailed below: I. Preparation of N,S dual-coordination modified sodium carboxymethyl cellulose N,S dual-coordination modified sodium carboxymethyl cellulose was prepared according to the method of Example 1, but some parameters were adjusted: the solid content of the sodium carboxymethyl cellulose aqueous solution was set to 1.8 wt%; the amount of EDC was 0.18 mol equivalents, the amount of NHS was 0.12 mol equivalents, and the amount of histidine was 0.20 mol equivalents; the pH for carboxyl activation was 5.2, and the mixture was stirred at 20-23°C for 0.7 h; the pH for introducing the imidazole site was 6.6, and the mixture was reacted at 25°C for 2.5 h; the amount of L-cysteine ​​for introducing the thiol site was 0.18 mol equivalents, and 0.08 mol equivalents of EDC and NHS were added, and the mixture was reacted at pH 6.6 and 25°C for 2.0 h. After dialysis for 20 h, N,S dual-coordination modified sodium carboxymethyl cellulose was obtained. Substitution degree determination confirmed that the imidazole substitution degree of this embodiment is approximately 0.12, the thiol substitution degree is approximately 0.06, and the ratio of the two is approximately 2.0:1, which meets the scope defined in the claims. This modified sodium carboxymethyl cellulose is also used in the subsequent gelation and silver complexation processes, because the imidazole and thiol coordination sites can provide a sufficient number of ligand atoms when complexing with silver ions.

[0048] II. Construction of the First Network In this embodiment, sodium magnesium lithium silicate was slowly added to deionized water to prepare a dispersion with a mass fraction of 3.0 wt%. The dispersion was then stirred at high speed for 1.5 h at pH 10.0 and 25°C to allow the sodium magnesium lithium silicate to fully exfoliate and assemble, resulting in a first network sol. Compared to Example 1, this embodiment has a higher sodium magnesium lithium silicate content, which is beneficial for improving the modulus of the inorganic physical network and providing stronger skeletal support for the high solids content, high silver loading system.

[0049] III. Construction of the Second Network In this embodiment, the aforementioned N,S dual-coordinate modified sodium carboxymethyl cellulose was added to the first network sol, resulting in a solid content of 1.5 wt%. Under stirring conditions, acrylamide and N-vinylimidazole were added, bringing the total monomer mass fraction to 18.0 wt%. Relative to the total mass of the solution in this embodiment, the molar ratio of acrylamide to N-vinylimidazole was 96:4 (located in the preferred range of 98:2-96:4 at the high N-vinylimidazole end). 0.15 wt% (relative to the total monomer mass) of N,N'-methylenebisacrylamide and 0.12 wt% of photoinitiator were added; glycerol was added, bringing the glycerol mass fraction relative to the total mass of the reaction solution in S2 to 20.0 wt%, falling within the range of 1.0-25.0 wt% and near the upper limit of the preferred range of 5.0-20.0 wt%. After degassing, the mixed solution of this embodiment was injected into a flat mold with a thickness of approximately 1.5 mm and subjected to 365 nm ultraviolet light with an intensity of 18 mW·cm. -2 After irradiation for 90 seconds, photo-initiated polymerization was completed, resulting in a chemically cross-linked pregel composed of an interpenetrating second chemically cross-linked network and a first chemically cross-linked network. The gel formation time was approximately 50 seconds.

[0050] IV. Pregelation Washing and Extraction After the pre-gel was removed, it was extracted with flowing deionized water for 5 hours, with the water rate and temperature controlled at room temperature (20-25°C). Analysis showed that the total residual amount of unreacted acrylamide, N-vinylimidazole, MBA, and photoinitiator was approximately 400 ppm (based on wet gel), which is below the limit of 500 ppm.

[0051] V. Complexing and Shaping of Silver Preparation of the silver complex aqueous solution: Potassium cyanurate was dissolved in deionized water, and silver nitrate aqueous solution was slowly added. The mixture was stirred moderately to form a silver complex. The silver ion mass fraction was adjusted to 0.09 wt%, the pH to 7.3, and the chloride ion concentration to ≤5 mmol / L. Pre-gel sheets of this embodiment, cut to a diameter of 20 mm and a thickness of 1 mm, were immersed in the complexation solution and complexed for 25 min under light-protected conditions. During complexation, the higher level of imidazole and thiol substitution on the N,S dual-coordination modified sodium carboxymethyl cellulose combined with a higher proportion of N-vinylimidazolium units in the second network provided sufficient multi-coordination sites for silver ions. The calculated molar ratio of the total nitrogen of the imidazole ligand to the sulfur of the thiol group to the silver ions was approximately 2.5:1, falling within the range of 2-4:1. After complexation, the gel sheets were removed and the surface free silver species were rapidly rinsed with deionized water to obtain the target gel.

[0052] Based on the loss on drying test, the wet gel in this embodiment has a solid content of approximately 22 wt%, falling within the range of 8-25 wt% and slightly above it; the glycerol content in the wet gel is approximately 20 wt%, falling within the range of 1.0-25.0 wt% and close to the upper limit of the preferred range of 5.0-20.0 wt%; the silver content is approximately 450 mg / kg (based on wet gel), falling within the range of 100-600 mg / kg and slightly above the preferred range of 200-400 mg / kg, but still within the permissible range; under extraction conditions of 37°C, sample thickness of 1 mm, and a solid-liquid ratio of 1:10, the steady-state daily average concentration of silver ions is approximately 30-38 μg / L over 24-168 h, still controlled within the range of 10-40 μg / L. The apparent viscosity of this gel is at 25°C and a shear rate of 10 s. -1 The pressure is approximately 0.70 Pa·s, and the transmittance is approximately 82%, meeting the conditions of gel forming time ≤120s and transmittance ≥80%. After sterilization by γ-irradiation (dose 30-32kGy), the steady-state silver ion release concentration window of the gel changes by approximately ±15%, and the silver content and mechanical properties of the wet gel remain stable. After 24 months of sealed and light-protected storage at 22-28°C and 40-60% relative humidity, there is still no obvious turbidity or silver precipitation.

[0053] The complexed silver antibacterial gel prepared in this embodiment can be cut into sheets or strips suitable for different wound sizes, and is used for wound dressing scenarios with moderate to severe exudation, high risk of infection, or severe contamination, such as burn wounds and postoperative incision infections. This embodiment recommends continuous use on the same wound for 1-7 days, changing it every 48-72 hours, to balance antibacterial strength and maintenance of a moist wound environment.

[0054] Example 3 This embodiment, while ensuring overall scientific rationality, sets values ​​close to the boundary for several parameters that have a relatively mild impact on product performance and are easy to control industrially. This is used to verify the feasibility of the solution, while avoiding multiple key parameters from taking extreme values ​​simultaneously. For parameters close to the boundary, a safety margin of approximately 8% is adopted.

[0055] I. Preparation of N,S dual-coordination modified sodium carboxymethyl cellulose The sodium carboxymethyl cellulose (CMC) aqueous solution had a solid content of 1.0 wt% (slightly above the lower limit of the CMC solid content range, with a relative safety margin of approximately 8-10%). In this embodiment, the amounts of EDC, NHS, and histidine were selected as 0.08 molar equivalents, 0.05 molar equivalents, and 0.06 molar equivalents, all calculated as carboxyl equivalents. The amounts of EDC, NHS, and histidine were all close to their respective lower limits but not absolute extremes. Carboxyl activation was performed at pH 4.6 for 0.5 h at 20-22°C. When introducing the imidazole site, the pH was adjusted to 6.0, and the reaction was carried out at 25°C for 1.0 h. Subsequently, while maintaining pH 6.0, 0.05 molar equivalents of L-cysteine ​​were added, followed by 0.03 molar equivalents of EDC and 0.03 molar equivalents of NHS, and the reaction was carried out at 25°C for 1.0 h. Subsequently, the molecules were dialyzed in deionized water for 12 hours using a dialysis bag with a molecular weight cutoff of 10 kDa to complete the removal of small molecules. Elemental analysis and NMR quantification confirmed that in this embodiment, the degree of imidazole substitution was approximately 0.025, the degree of thiol substitution was approximately 0.012, and the ratio was approximately 2.1:1. These values ​​are close to the lower limits of 0.02 and 0.01, respectively, but retain a relative safety margin of approximately 20-25%, satisfying the requirements for the degree of substitution and the ratio, and providing sufficient coordination sites for stable complexation under low silver loading.

[0056] II. Construction of the First Network In this embodiment, a relatively high mass fraction was selected: sodium magnesium lithium silicate was slowly added to deionized water at a mass fraction of 4.6 wt%, slightly lower than the upper limit of 5.0 wt%, leaving a relative safety margin of about 8%; the mixture was stirred at pH 10.5 and 25°C for 2.0 h to obtain the first network pregel, which exhibited a strong physical gel structure.

[0057] III. Construction of the Second Network In this embodiment, representative values ​​close to the upper limit of the range were selected for the total amount of monomers in the second network and the content of crosslinking agent to verify that controllable photocrosslinking and post-elution can still be achieved under high monomer content conditions. In this embodiment, N,S dual-coordination modified sodium carboxymethyl cellulose is added to the first network pregel to achieve a solid content of 2.0 wt% (upper limit of 0.5-2.0 wt%). Acrylamide monomer is added under stirring to achieve a total monomer mass fraction of 19.0 wt%, close to the upper limit of 5.0-20.0 wt%, but with a margin of approximately 5%. To reduce potential over-crosslinking, this embodiment does not introduce N-vinylimidazol monomer, i.e., the molar ratio of acrylamide to N-vinylimidazol is 100:0, used to verify the boundary condition of "optional N-vinylimidazol unit" in the claims. 0.20 wt% of N,N'-methylenebisacrylamide is added, near the upper limit of 0.05-0.20 wt%; 0.15 wt% of photoinitiator is added, at the upper limit of 0.05-0.15 wt%; glycerol is added simultaneously to achieve a mass fraction of 5.0 wt%, in the low-to-mid range of 1.0-25.0 wt%, to avoid the amplified effect of glycerol combined with other boundary parameters. After thorough stirring and degassing, the solution of this embodiment was poured into a plate-shaped mold with a thickness of 2.0 mm (to verify the maximum layer thickness boundary). Under 365 nm ultraviolet light conditions, the light intensity was set to 12 mW·cm. -2 The illumination time was 120 seconds, which is the upper limit of the illumination time to ensure sufficient cross-linking under high monomer content conditions. The time from the end of illumination to the sample self-standing and forming was approximately 60 seconds, satisfying the requirement that the gel forming time be ≤120 seconds.

[0058] IV. Pregelation Washing and Extraction Considering the high monomer and crosslinking agent content in this embodiment, a more intensive water washing method was used to avoid exceeding the residue limit: the pre-gel was extracted in flowing deionized water for 8 hours, and then flowing water at 25-28°C was used for the next 4 hours to increase the diffusion rate. HPLC and TOC analysis showed that the total residual amount of unreacted acrylamide, MBA, and photoinitiator was approximately 450 ppm, which is still below the limit of 500 ppm on a wet gel basis.

[0059] V. Complexing and Shaping of Silver In this embodiment, the silver complex solution is designed with a silver concentration close to the lower limit to complement the aforementioned high-solids organic network and avoid the overlap of silver content boundaries with structural boundaries: The silver complex aqueous solution is prepared with a silver ion mass fraction of 0.012 wt% (close to the lower limit of 0.01 wt% but retaining approximately 20% safety margin), a pH of 7.2 (lower limit of the 7.2-7.6 range), and a chloride ion concentration controlled at ≤2 mmol / L. Since the second network in this embodiment does not contain N-vinylimidazolium units, silver ions are mainly fixed through complexation with the imidazole and thiol coordination sites on the N,S dual-coordinate modified sodium carboxymethyl cellulose. Calculations based on coordination sites and silver content show that the molar ratio of the total nitrogen atoms of the imidazole ligands to the sulfur atoms of the thiol group to silver ions is approximately 3.0:1, falling within the range of 2-4:1. A 2.0 mm thick pre-gel sample from this embodiment was immersed in the aforementioned silver complexing solution. The complexation time was set to a threshold of 30 minutes to verify the sufficiency of complexation in thicker samples and at low silver concentrations. The complexation temperature was maintained at 20-25°C and the entire process was conducted in the dark. After complexation, the gel was removed, and the surface free silver species were quickly rinsed with deionized water to obtain the target complexed silver antibacterial gel of this embodiment.

[0060] In this embodiment, the solid content of the wet gel was approximately 24 wt%, close to the upper limit of 8-25 wt% but with a certain margin; the mass fraction of glycerol in the wet gel was approximately 5.0 wt%, within the range of 1.0-25.0 wt% and close to the lower end of the preferred range; the silver content was approximately 220 mg / kg (based on wet gel). Although the concentration of the silver complex solution was close to the lower limit, due to the high solid content and gel thickness in this embodiment, a silver loading in the lower part of the 100-600 mg / kg range could still be obtained. Silver release experiments showed that, under conditions of 37°C, a gel thickness of 2.0 mm, and a solid-liquid ratio of 1:10, the daily average steady-state silver ion concentration was approximately 15-22 μg / L over 24-168 h, meeting the limit of 10-40 μg / L. Viscosity tests showed that, at 25°C and a shear rate of 10 s... -1 The apparent viscosity is approximately 0.60 Pa·s; the transmittance at 600 nm and 1.0 mm optical path is approximately 80-82%. After sterilization by 25 kGy γ-irradiation, the silver release window changes by approximately ±12%, and the changes in wet gel solids content and mechanical strength are within acceptable ranges. After 24 months of sealed and light-protected storage at 22-28°C and 40-60% relative humidity, no obvious turbidity or silver precipitation was observed.

[0061] The gel prepared in this embodiment is suitable for applications requiring certain mechanical support but where a high silver content is not necessary, such as skin donor sites, superficial burns, or periphery protection of skin flaps. This embodiment recommends continuous use on the same wound for 1-5 days, with a replacement cycle of 48-72 hours.

[0062] Features and applicable scenarios of this embodiment: This embodiment systematically incorporates several boundary value verifications: sodium magnesium lithium silicate mass fraction 4.6 wt% (close to the upper limit of 5.0 wt%, retaining approximately 8% margin), modified sodium carboxymethyl cellulose solid content 2.0 wt% (S2 upper limit), total monomer 19 wt% (close to the upper limit of 20 wt%), MBA 0.20 wt% and photoinitiator 0.15 wt% (both permissible upper limits), sample thickness 2.0 mm (B2 layer thickness upper limit), silver mass fraction of silver complex solution 0.012 wt% (close to the lower limit), imidazole and thiol substitution degrees approximately 0.025 and 0.012 respectively (close to the lower limit), coordination site: silver molar ratio approximately 3.0:1, wet gel solid content approximately 24 wt%, glycerol 5.0 wt%, silver content approximately 220 mg / kg, daily silver release 15-22 μg / L, viscosity approximately 0.60 Pa·s, and transmittance 80-82%. By combining high inorganic solids content, high monomer content, and high crosslinking density with low silver concentration and no N-vinylimidazole, the solution was verified to still achieve a gel system with good mechanical properties, stable silver release, and industrial operability near the upper and lower boundaries. It is suitable for wound protection scenarios that require good structural support and where silver content control is more cautious.

[0063] Comparative Example 1: It is basically the same as Example 1, except that the mass fraction of sodium magnesium lithium silicate is set to 0.5 wt% in step S1, and the pH, temperature, stirring time and subsequent conditions remain unchanged. This comparative example is to examine the effect of the low solid content of the first inorganic physical network on the formation of the gel three-dimensional skeleton, apparent viscosity and steady-state release behavior of silver ions.

[0064] Comparative Example 2: It is basically the same as Example 1, except that in step S1, the mass fraction of sodium magnesium lithium silicate is set to 6.0 wt%, while the amount of other components and all process conditions remain unchanged. This comparative example is to examine the effect of the content of inorganic filler in the first network exceeding the upper limit on the gel transparency, rheological properties and silver ion diffusion channels.

[0065] Comparative Example 3: It is basically the same as Example 1, except that in step S3, the mass fraction of silver in the aqueous solution of the silver complex, calculated as silver ions, is set to 0.15 wt%. The complexation time, pH and chloride ion concentration remain unchanged. This comparative example is to examine the effect of excessively high silver concentration on the final silver content, silver ion release level and potential cell compatibility.

[0066] Comparative Example 4: It is basically the same as Example 1, except that in step S3, the mass fraction of silver in the aqueous solution of the silver complex, calculated as silver ions, is set to 0.005 wt%, and the other conditions remain unchanged. This comparative example is to examine the effect of silver content below the limit on steady-state silver ion release concentration and antibacterial effectiveness.

[0067] Comparative Example 5: It is basically the same as Example 1, except that the pH of the system is adjusted to 7.0 when dispersing sodium magnesium lithium silicate in step S1. The mass fraction of sodium magnesium lithium silicate, temperature, stirring time and subsequent conditions remain unchanged. This comparative example is to examine the effect of the pH being too low in the first network construction stage on the exfoliation, self-assembly behavior and subsequent gel performance of sheet silicate.

[0068] Comparative Example 6: It is basically the same as Example 1, except that the pH of the system is adjusted to 12.0 when dispersing sodium magnesium lithium silicate in step S1. The mass fraction of sodium magnesium lithium silicate, temperature, stirring time and other conditions remain unchanged. This comparative example is to examine the stability of silicate structure under strong alkaline conditions and its effect on the strength, transparency and silver fixation ability of the first network.

[0069] Comparative Example 7: This example is basically the same as Example 1, except that in step B1, the molar ratio of acrylamide to N-vinylimidazole is set to 94:6. The total monomer mass fraction, the amount of N,S dual-coordination modified sodium carboxymethyl cellulose, the amount of crosslinking agent and photoinitiator, and all process conditions remain unchanged. This comparative example is intended to investigate the effect of an excessively high proportion of imidazole coordinating monomers on the silver coordination density, network crosslinking structure, and gel silver release / mechanical equilibrium.

[0070] Comparative Example 8: It is basically the same as Example 1, except that glycerol is not added in step S2, so that the mass fraction of glycerol is 0 wt%. The amounts of other components and process conditions remain unchanged. This comparative example is to examine the effect of completely removing the moisturizing ingredients on the softness, viscoelasticity and silver ion diffusion behavior of the gel.

[0071] Comparative Example 9: It is basically the same as Example 1, except that in step S2, the mass fraction of glycerol relative to the total mass of the reaction solution is set to 40.0 wt%, while other components and process conditions remain unchanged. This comparative example is to examine the effect of excessively high humectant content on gel mechanical stability, anti-sagging properties, light transmittance, and silver release curve.

[0072] Comparative Example 10: It is basically the same as Example 1, except that in step B1, the amount of N,N'-methylenebisacrylamide is set to 0.30 wt%. The monomer composition, photoinitiator amount, glycerol content and process conditions remain unchanged relative to the total monomer mass. This comparative example is to investigate the effect of excessive crosslinking agent leading to network over-crosslinking on gel molding time, brittleness, swelling and silver ion release behavior.

[0073] Comparative Example 11: It is basically the same as Example 1, except that in step S3, disodium ethylenediaminetetraacetate (EDTA-Na2) is used as a complexing agent instead of a water-soluble cyanurate complexing agent. The mass fraction of silver ions, pH, complexing time and chloride ion concentration are kept constant. This comparative example is to examine the effect of the complexing agent structure changing from cyanurate to polycarboxylic acid ligand on the stability of the silver complex, the degree of silver fixation in the gel and the morphology of the release curve.

[0074] Comparative Example 12: Basically the same as Example 1, except that in the "pre-gel washing and extraction" step, the sample was only soaked in deionized water for 0.5 h without changing the water. This resulted in a total residual amount of unreacted acrylamide, N-vinylimidazole, crosslinking agent and photoinitiator of about 800 ppm (higher than the requirement of ≤500 ppm). The rest of the formulation and process conditions remained unchanged. This comparative example was used to investigate the effect of insufficient washing leading to high monomer residue on biocompatibility, safety boundary and silver release stability.

[0075] Experiment 1: Steady-state release of silver ions and determination of total silver content The test subjects were complexed silver antibacterial gel samples with different formulations (examples and comparative examples). The purpose of the test was to quantitatively evaluate whether the steady-state release concentration of silver ions and the total silver content of the wet gel fell within the target window of 100-600 mg / kg and 10-40 µg / L under simulated human body fluid conditions in the range of 24-168 h. The test principle was to extract the gel in PBS at a constant temperature, and then use inductively coupled plasma optical emission spectrometry (ICP-OES) to determine the silver concentration in the extract and digestion solution and calculate the release amount and total content per unit mass of gel. The experimental method was to cut gel sheets with a thickness of 1.0 mm and extract them at 37°C and a solid-liquid ratio of 1:10 for 24, 48, 72, 96, 120, 144, and 168 h, respectively. Samples were taken and the solution was changed at regular intervals, and the silver concentration was recorded. At the same time, the original samples were acid digested to determine the total silver. Key parameters included extraction temperature 37±0.5°C and PBS. pH 7.4, sample thickness 1.0±0.1 mm, solid-liquid ratio 1:10±5%, and number of independent samples at each time point n≥3; data processing uses mean ± standard deviation to represent single-point silver concentration, and calculates the daily average steady-state concentration and the proportion of silver release to total silver content in the 24-168h interval for comparison between the examples and comparative examples.

[0076] Experiment 2 Apparent viscosity and rheological properties test The test subject was a complexed silver antibacterial gel disc in a wet gel state. The test objective was to test it at 25°C and a shear rate of 10 s. -1Apparent viscosity was obtained under certain conditions, and the effect of different formulations on rheological behavior was investigated to verify the target range of 0.20-0.80 Pa·s in the claims. The testing principle involved applying shear rates under isothermal conditions using a rotational rheometer, recording the relationship between shear stress and shear rate, and calculating the viscosity. The experimental method involved using a plate-plate geometry (20 mm diameter, 1.0 mm gap) to spread the prepared wet gel without air bubbles, and applying shear rate scans (0.1-100 s⁻¹). -1 ), focus on recording 10 seconds -1 Steady-state viscosity at a given temperature was measured, and the curves of G' and G'' as a function of frequency were obtained. Key parameters included test temperature 25±0.5°C, pre-shear time 60s, equilibration time 120s, and sample thickness 1.0±0.1mm. Data processing was performed on samples with n≥3 samples for 10s. -1 The viscosity mean ± standard deviation is used as an apparent viscosity index, and shear rate-viscosity CSV data can be exported for Origin plotting and linear / nonlinear fitting.

[0077] Experiment 3 Optical transmittance test The test subjects were 1.0 mm thick wet gel sheets and comparative gel sheets. The purpose of the test was to determine the transmittance at a wavelength of 600 nm to verify that the gel maintained a transparent or slightly milky white appearance (T≥80%) while meeting antibacterial requirements. The test principle adopted the transmission mode of a spectrophotometer to record the transmittance ratio of the sample to light of a specific wavelength. The experimental method was to cast the gel into a 1.0 mm standard optical path quartz cuvette, using air as a reference, scan the range of 400-800 nm, and focus on reading the transmittance at 600 nm, while recording the overall transmittance spectrum in the visible light region. Key parameters included test temperature 25±1°C, scan step size 1 nm, integration time 0.5 s, and three repetitions for each sample. Data processing output the average ± standard deviation of the 600 nm transmittance, and the wavelength-transmittance full spectrum could be exported as a CSV file to compare the effects of changes in silver content and network structure on the optical performance of the examples and comparative examples.

[0078] Experiment 4: Gel setting time and compressive mechanical properties test The test subject was a wet gel sample prepared according to the claimed process. The purpose of the test was to determine the time from the cessation of light exposure to the gel's self-standing formation and the compressive modulus under simulated application deformation, in order to evaluate the gelation rate and mechanical support capacity. The test principle was to record the transition time from the fluid state to the self-standing state using a stopwatch, and to perform small-deformation uniaxial compression using a universal testing machine to obtain stress-strain curves and calculate Young's modulus. The experimental method involved injecting the solution obtained in step B2 into a standard mold, irradiating it under specified light intensity and duration, starting the timer immediately after the light exposure ended, and observing and recording the time it took for the sample to stand upright without collapsing as the gelation time. Subsequently, it was cut into cylinders with a diameter of 10 mm and a thickness of 5 mm, and compressed to 20% deformation at a rate of 1 mm / min at 25°C, and the stress-strain curves were recorded. Key parameters included light intensity, light exposure time, ambient temperature, and compression rate. Data processing output the average ± standard deviation of the gelation time and compressive modulus, which was used to compare the gelation efficiency and structural support differences with comparative samples.

[0079] Experiment 5 Quantitative evaluation of antibacterial activity The test subjects were gel samples containing silver complex and comparative samples without silver or with a silver content failure window. The purpose of the test was to quantitatively evaluate the antibacterial activity against Staphylococcus aureus and Escherichia coli and correlate it with silver ion release data. The test principle adopted the contact sterilization method, in which the bacterial suspension was contacted with the sample for a certain period of time, the number of surviving bacteria was measured, and the log reduction value was calculated. The experimental method was to cut standard area gel sheets, inoculate them with sterile carriers containing a quantitative bacterial solution, seal them with the sample, and incubate them at 37°C under humid conditions for 24 hours. After washing off the bacterial solution, plate counts were performed. The antibacterial test was conducted according to the counting method of ISO 22196, with the following adjustments: wet gel samples (thickness 1.0±0.1 mm) were used, and contact incubation was carried out in a closed humid environment; the inoculum size, bacterial concentration, incubation temperature, and counting method were performed according to the conditions described in this experimental section. Key parameters included contact time of 24 hours and inoculum bacterial concentration of approximately 10. 5 -10 6 CFU / mL, inoculum size 0.4 mL, incubation temperature 37±1°C; data processing: the log CFU reduction value (mean ± standard deviation) for each bacterium was calculated and correlation analysis was performed with the steady-state concentration of silver release to determine the antibacterial efficacy of different formulations within the target silver release window.

[0080] Experiment 6: XPS / FTIR co-characterization of silver coordination structure The test subjects were dried or lyophilized gel slides from typical embodiments and comparative examples. The purpose of the tests was to characterize the valence state, coordination structure, and interaction between N,S dual-coordination modified sodium carboxymethyl cellulose and cyanurate groups and silver using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR), thereby providing direct evidence for multi-coordination complex structures. The testing principle was to use XPS to resolve the Ag3d binding energy and the S2p, N1s, and O1s chemical shifts, and to use FTIR to observe the shifts and intensity changes of characteristic peaks such as carboxylic acid, imidazole ring, and thiol groups. The experimental method involved lyophilizing the samples, grinding them to prepare slides, acquiring the full spectrum and high-resolution regions using XPS, and recording the 4000-400 cm⁻¹ region using FTIR in ATR mode. -1 Spectroscopy; key parameters include XPS throughput, analytical chamber vacuum, light source type, FTIR resolution, and number of scans; data processing involves exporting combined energy / wavenumber-intensity data as CSV for peak fitting and quantitative comparison of differences in silver coordination environments among different samples.

[0081] Figure 1 The graph shows the effect of sodium magnesium lithium silicate mass fraction on the steady-state release concentration and apparent viscosity of silver ions in this invention. The fixed parameters are: N,S dual-coordination modified sodium carboxymethyl cellulose 1.0 wt%, total monomer mass fraction 10.0 wt% (acrylamide to N-vinylimidazol molar ratio 97:3), N,N'-methylenebisacrylamide 0.12 wt%, photoinitiator 0.10 wt% (relative to total monomers), glycerol mass fraction 9.5 wt%, silver mass fraction in the silver complexing solution 0.045 wt%, complexation time 20 min, pH 7.4, chloride ion concentration ≤ 5 mmol / L, photocuring conditions 365 nm, and light intensity 15 mW·cm. -2 The sample was exposed to light for 60 seconds and had a thickness of 1.0 mm. The parameters were varied by increasing the mass fraction of sodium magnesium lithium silicate from 0.5 wt% to 6.0 wt% in step S1. When the mass fraction of sodium magnesium lithium silicate was approximately 2.0-3.0 wt%, the steady-state daily average release concentration of silver ions was stable at 20-28 μg / L and the apparent viscosity was 0.40-0.60 Pa·s, showing the best overall release stability and mechanical support performance. Below 1.0 wt%, insufficient three-dimensional inorganic framework led to an increase in release concentration to 40-45 μg / L and a decrease in viscosity to 0.15-0.20 Pa·s. Above 5.0 wt%, excessive network density caused the release to decrease to approximately 9-15 μg / L and the viscosity to increase to 0.80-0.90 Pa·s. This demonstrates that a moderate content of sodium magnesium lithium silicate is beneficial for achieving a synergistic balance between release behavior and rheological properties under the same organic network and coordination environment.

[0082] Figure 2This diagram illustrates the effect of total monomer mass fraction on the steady-state release concentration and apparent viscosity of silver ions in this invention. The fixed parameters were: sodium magnesium lithium silicate mass fraction 2.5 wt%, N,S dual-coordination modified sodium carboxymethyl cellulose solid content 1.0 wt%, acrylamide to N-vinylimidazol molar ratio 97:3, N,N'-methylenebisacrylamide 0.12 wt%, photoinitiator 0.10 wt%, glycerol mass fraction 9.5 wt%, silver mass fraction in the silver complexing solution 0.045 wt%, complexation time 20 min, pH 7.4, chloride ion concentration ≤ 5 mmol / L, and the same photocuring conditions and sample thickness. The variable parameter was that the total monomer mass fraction of acrylamide and N-vinylimidazol in step S2 / B1 increased from 5.0 wt% to 22.0 wt%. When the total monomer mass fraction is about 10.0-15.0 wt%, the steady-state daily average release concentration of silver ions remains in the range of 20-30 μg / L and the apparent viscosity is about 0.50-0.70 Pa·s. Among them, about 12.5 wt% corresponds to a significant peak in comprehensive performance. At 5.0 wt%, the insufficient organic cross-linking density of the network leads to an increase in release concentration to 36-42 μg / L and a decrease in viscosity to 0.18-0.25 Pa·s. Above 20.0 wt%, the cross-linking network is too dense, causing the release to drop below 18 μg / L and the viscosity to approach 0.80-0.85 Pa·s. This indicates that an appropriate monomer solid content can maintain structural stability while avoiding release imbalance caused by excessive diffusion resistance or insufficient chain density.

[0083] Figure 3 This diagram illustrates the effect of the silver mass fraction in the silver complex solution on the steady-state release concentration and apparent viscosity of silver ions in this invention. The fixed parameters are: sodium magnesium lithium silicate mass fraction 2.5 wt%, N,S dual-coordination modified sodium carboxymethyl cellulose solid content 1.0 wt% with imidazole substitution degree approximately 0.08 and thiol substitution degree approximately 0.05, total monomer mass fraction 10.0 wt% (acrylamide to N-vinylimidazolium molar ratio 97:3), N,N'-methylenebisacrylamide 0.12 wt%, photoinitiator 0.10 wt%, glycerol mass fraction 9.5 wt%, and photocuring conditions of 365 nm and light intensity 15 mW·cm. -2The sample was exposed to light for 60 seconds and the sample thickness was 1.0 mm. The parameter variation was that the mass fraction of silver in the aqueous solution of the silver complex increased from 0.005 wt% to 0.150 wt% in step S3. When the silver mass fraction in the silver complex solution is approximately 0.03-0.07 wt%, the steady-state daily average silver ion concentration is in the range of 20-35 μg / L, and the apparent viscosity is basically stable in the range of 0.49-0.52 Pa·s. Among them, 0.045 wt% corresponds to the optimal state of the sample in terms of silver content, release stability, and rheological properties. When it is below 0.01 wt%, the total silver content and release level are significantly insufficient, resulting in a steady-state daily average silver ion concentration of only about 5-10 μg / L. When it is above 0.10 wt%, the cumulative release of silver ions increases, causing the steady-state daily average concentration to rise to about 42-60 μg / L, while the viscosity remains almost unchanged. This indicates that under the premise of fixed network structure and number of coordination sites, a stable release platform with both long-lasting antibacterial ability and safety can be obtained in a narrow range by adjusting the silver mass fraction of the complex solution.

[0084] Figure 4 This is a magnified XPS 1s spectrum of N,S dual-coordination modified sodium carboxymethyl cellulose and silver complexed antibacterial gel from Example 1 of this invention. The fixed parameters were unmodified sodium carboxymethyl cellulose, N,S dual-coordination modified sodium carboxymethyl cellulose, and silver complexed antibacterial gel samples prepared using the same route as in Example 1. The test conditions were: aluminum target X-ray photoelectron spectroscopy, Al Kα excitation source, pass energy 40 eV, energy step 0.1 eV, test energy range limited to 395-407 eV, and all samples were vacuum dried and calibrated with C 1s 284.8 eV. The variable parameters were: the sample structure gradually transitioned from sodium carboxymethyl cellulose without imidazole and thiol coordination sites to N,S dual-coordination modified sodium carboxymethyl cellulose with imidazole and thiol coordination sites, and then to silver complexed antibacterial gel with silver ions complexed in the above-mentioned modified sodium carboxymethyl cellulose and sodium magnesium lithium silicate interpenetrating network. The spectral results show that sodium carboxymethyl cellulose has almost no obvious N 1s peak in the 399-401 eV region, while N,S dual-coordinate modified sodium carboxymethyl cellulose shows a pair of characteristic peaks at 399.6 eV and 401.0 eV. In the silver complexed antibacterial gel, the uncoordinated nitrogen peak near 399.8 eV is slightly weakened, while the coordinated nitrogen peak near 400.8 eV is significantly enhanced. Combined with the settings of approximately 0.08 imidazole substitution degree, approximately 0.05 thiol substitution degree, and approximately 3:1 molar ratio of coordination sites to silver ions in Example 1, it can be concluded that the imidazole coordination sites and thiol coordination sites introduced by steps A3 and A4 do indeed participate in coordination in the silver complexation step, forming a stable nitrogen- and sulfur-containing multi-coordinated structure.

[0085] Figure 5The infrared absorption spectrum of unmodified sodium carboxymethyl cellulose from Example 1 is shown below. The parameters were fixed using the same Fourier transform infrared spectrometer and sample preparation method as in Example 1. The testing method was potassium bromide pellet transmission mode, with a scanning range of 500-4000 cm⁻¹. -1 Resolution 4 cm -1 A total of 32 scans were performed. The changing parameter was that the sample type was sodium carboxymethyl cellulose that had not undergone N,S dual-coordination modification and silver complexation treatment. The spectrum was at 3350 cm⁻¹. -1 A broad hydroxyl stretching vibration band appears nearby, at 2900 cm⁻¹. -1 A hydrocarbon stretching peak appears nearby at 1590 cm⁻¹. -1 With 1420 cm -1 The positions at 1060 cm⁻¹ correspond to the asymmetric and symmetric stretching vibrations of the carboxyl group in carboxylate salts, respectively. -1 The presence of ether bond stretching peaks nearby, and the absence of amide I absorption, amide II absorption, imidazole ring characteristic absorption, and thiol stretching absorption, indicate that the initial sodium carboxymethyl cellulose structure is simple and does not contain the target coordinating group. This provides a basis for comparison of the infrared changes of subsequent N,S dual-coordination modified sodium carboxymethyl cellulose and complexed silver antibacterial gel.

[0086] Figure 6 The infrared absorption spectrum of N,S dual-coordination modified sodium carboxymethyl cellulose in Example 1 is shown, with parameters fixed. Figure 5 The same instruments were used, including the same potassium bromide tablet transmission mode and a scanning range of 500-4000 cm⁻¹. -1 Resolution 4 cm -1 The number of scans was 32, and the sample type was changed to N,S dual-coordination modified sodium carboxymethyl cellulose obtained in Example 1 through steps A1-A5, with an imidazole substitution degree of approximately 0.08 and a thiol substitution degree of approximately 0.05, and a substitution ratio of approximately 1.6:1. Compared with sodium carboxymethyl cellulose, the spectrum at 1652 cm⁻¹... -1 and 1542 cm -1 New absorption peaks for amide I and amide II appear at 1510 cm⁻¹. -1 A vibrational peak of the imidazole ring skeletal structure appears nearby, at 1310 cm⁻¹. -1 Carbon and nitrogen stretching absorption occurs nearby, at 2550 cm⁻¹ -1 A weak thiol stretching absorption was observed nearby, and the original carboxylate-related band changed from 1590 / 1420 cm⁻¹. -1 Slightly shifted to 1580 / 1415 cm -1This indicates that histidine and cysteine ​​have been covalently introduced into the anhydrous glucose unit of sodium carboxymethyl cellulose via amidation, forming imidazole coordination sites and thiol coordination sites in the range specified in Example 1, thus laying the structural basis for the multi-site complexation behavior in the complexed silver antibacterial gel.

[0087] Figure 7 The infrared absorption spectrum of the complexed silver antibacterial gel is shown. The parameters are kept constant and continue to be used with... Figure 5 and Figure 6 Under the same infrared testing conditions, the sample was the complexed silver antibacterial gel obtained in Example 1, which involved constructing a first network using sodium magnesium lithium silicate, a second network using acrylamide and N-vinylimidazolium, followed by water washing and extraction, and impregnation with silver complexes. Its wet gel contained approximately 15 wt% solids, approximately 9.5 wt% glycerol, and approximately 300 mg / kg of silver. The molar ratio of the total number of coordinated imidazole nitrogen and mercaptosulfonate sites to silver ions was approximately 3:1. The variable parameter was whether the complexation step with silver ions was completed. Compared to N,S dual-coordination modified sodium carboxymethyl cellulose, the 2550 cm⁻¹ spectrum showed... -1 The thiol stretching absorption essentially disappears, and the absorption peaks of amide I and amide II change from 1652 / 1542 cm⁻¹. -1 Slightly shifted to 1645 / 1538 cm respectively -1 Imidazole-related absorption increased from 1510 cm⁻¹ -1 Slight movement to 1505 cm -1 The absorption of some carboxylate and ether bonds also showed slight shifts, which were consistent with the changing trends of nitrogen, sulfur and silver signals in X-ray photoelectron spectroscopy. This indicates that the imidazole and thiol coordination sites changed from free to coordinated states during the silver complexation process. Silver ions were synergistically fixed in the organic-inorganic interpenetrating network by multiple sites. This further supports the rationality and stability of the complexed silver antibacterial gel structure constructed in Example 1 from the perspective of vibrational spectroscopy.

[0088] As shown in Table 1, the three examples generally achieved relatively balanced comprehensive performance in key indicators such as silver content, steady-state release window of silver ions, apparent viscosity, transmittance, and gelation time. Example 1 represents a preferred scheme with medium silver loading and medium viscosity, with silver content controlled in the range of 220-450 mg / kg and steady-state daily average silver ion concentration falling within the range of 10-35 µg / L, satisfying both antibacterial requirements and considering cell compatibility and long-term safety. In contrast, most comparative examples deviated significantly from the target range in at least one core indicator. For example, the silver release concentrations of Comparative Examples 1, 5, 6, and 11 were significantly higher than 40 µg / L or close to this upper limit, potentially increasing the risk of cytotoxicity. Comparative Examples 2, 4, 7, and 10 had silver release concentrations below 10-12 µg / L and excessively high network crosslinking or inorganic content, making it difficult to guarantee sufficient antibacterial strength. Furthermore, the sodium magnesium lithium silicate content in Comparative Examples 1 and 2 exceeded the limits, resulting in excessively low or high viscosity, respectively. The main problems were excessively low viscosity and excessive silver release; Comparative Example 2 showed a decrease in light transmittance (75%) accompanied by high viscosity; the extreme ratio of glycerol in Comparative Examples 8 and 9 disrupted the balance between softness and support; although Comparative Example 12 was close to Example 1 in five indicators, its excessive monomer residue would directly affect biosafety; in summary, it can be seen that Examples 1-3 are superior to all comparative examples in multiple indicators, and cover application scenarios from high transparency to low viscosity to high silver loading to high modulus through different parameter combinations, providing data support for the rationality of the solution range.

[0089] Table 1 Performance summary of the examples and comparative examples

[0090] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that any equivalent structural transformations made under the concept of the present invention and using the contents of the specification and drawings of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing a complexed silver antibacterial gel, characterized in that, include: S1. Constructing the first network: Disperse sodium magnesium lithium silicate in deionized water with a chloride ion concentration ≤0.5mmol / L, such that the mass fraction of the sodium magnesium lithium silicate is 1.0-5.0wt%, and stir for 0.5-4.0h at pH 8.0-11.0 and 20-30°C to allow the sodium magnesium lithium silicate to self-assemble into a three-dimensional inorganic physical network, thereby obtaining the first network sol or the first network pregel; S2. Constructing a second network: Add N,S dual-coordinate modified sodium carboxymethyl cellulose aqueous solution and glycerol to the first network, and further add acrylamide and optional N-vinylimidazol monomer, add N,N'-methylenebisacrylamide crosslinking agent and photoinitiator, after mixing and degassing, carry out aqueous phase photoinitiated free radical polymerization under ultraviolet light irradiation to form an organic covalent crosslinked second network, and obtain chemically crosslinked pregel; S3. Complexing and fixing silver: Under light-protected conditions, the chemically cross-linked pregel is immersed in an aqueous solution containing a silver complex formed by the complexation of a water-soluble cyanurate complexing agent and silver nitrate, so that silver ions enter and are fixed in the pregel in the form of complexed silver. After complexing for 10-30 minutes, the pregel is removed and the surface free silver species are quickly rinsed to obtain the target gel.

2. The method for preparing a complexed silver antibacterial gel according to claim 1, characterized in that, The N,S dual-coordination modified sodium carboxymethyl cellulose added in S2 is prepared according to the following steps: A1. Raw material preparation: Prepare 1.00 parts by weight of an aqueous solution containing 1.0-2.0 wt% sodium carboxymethyl cellulose; add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide and histidine, in amounts of 0.08-0.20, 0.05-0.15 and 0.05-0.25 molar equivalents, respectively, all based on the carboxyl group of sodium carboxymethyl cellulose; A2. Carboxyl group activation: Adjust the pH to 4.5-5.5 and stir at 20-25°C for 0.5-1.0 h to activate the carboxyl groups of sodium carboxymethyl cellulose; A3. Introducing imidazole sites: Continue the reaction with histidine in the system, adjust the pH to 6.0-6.8, and react for 1.0-3.0 h to covalently introduce histidine into the anhydrous glucose unit of sodium carboxymethyl cellulose via amidation, forming imidazole coordination sites; A4. Introduction of thiol sites: Under the condition of maintaining pH 6.0-6.8, add 0.05-0.25 molar equivalents of L-cysteine, based on the carboxyl group of sodium carboxymethyl cellulose. If necessary, add a small amount of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide. React for 1.0-3.0 h to covalently introduce L-cysteine ​​into the anhydrous glucose unit of sodium carboxymethyl cellulose via amidation, forming a thiol coordination site. A5. Endpoint and Post-processing: The reaction was terminated when the consumption of free amine in the solution stabilized and the viscosity stabilized. Dialysis was performed for 12-24 hours using a dialysis bag with a molecular weight cutoff of 10 kDa, or ultrafiltration was used to remove small molecules, so that the total amount of residual 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide was ≤100 ppm, based on N,S dual-coordination modified sodium carboxymethyl cellulose on a dry basis. The obtained N,S dual-coordination modified sodium carboxymethyl cellulose can be freeze-dried or used directly in solution for gelation. The degree of imidazole substitution is 0.02-0.15 and the degree of mercapto substitution is 0.01-0.10, based on anhydrous glucose units.

3. The method for preparing a complexed silver antibacterial gel according to claim 1, characterized in that, The second network in S2 is obtained through aqueous photoinitiated radical polymerization, specifically including: B1. Monomer solution preparation: N,S-coordinated modified sodium carboxymethyl cellulose is added to the first network sol or first network pregel, such that the solid content of N,S-coordinated modified sodium carboxymethyl cellulose is 0.5-2.0 wt%. Acrylamide and optionally N-vinylimidazole are then added as monomers, such that the total monomer mass fraction is 5.0-20.0 wt%, and the molar ratio of acrylamide to N-vinylimidazole relative to the total mass of the solution is 100:0 to 95:

5. N,N '-Methylenebisacrylamide 0.05-0.20 wt%, preferably 0.08-0.15 wt%, relative to the total monomers; 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone 0.05-0.15 wt%, relative to the total monomers; and further added glycerin as a moisturizing ingredient; the above N,S dual-coordination modified sodium carboxymethyl cellulose, monomers, crosslinking agent, photoinitiator and glycerin are mixed and defoamed, the solvent is deionized water and chloride ions are avoided; B2. Photocuring: Prepare samples with a layer thickness ≤2mm from the solution obtained in step B1, and cure under 365nm ultraviolet light at an intensity of 10-20mW·cm. -2 Crosslinking is completed by irradiation for 30-120 seconds under certain conditions, forming a chemically crosslinked second network obtained by copolymerization of acrylamide and optional N-vinylimidazolium or homopolymerization of acrylamide, which interpenetrates with the first network to obtain a chemically crosslinked pregel.

4. The method for preparing a complexed silver antibacterial gel according to claim 1, characterized in that, The silver complex formation step of S3 is as follows: The chemically cross-linked pregel is immersed in an aqueous solution containing a silver complex under light-protected conditions. The silver complex is generated by the complexation of a water-soluble cyanurate complexing agent and silver nitrate in the aqueous phase. The aqueous solution has a silver mass fraction of 0.01-0.10% (based on silver ions) and a pH of 7.2-7.

6. During the complexation process, the imidazole nitrogen atoms and mercaptosulfonates on the N,S dual-coordination modified sodium carboxymethyl cellulose, as well as the imidazole nitrogen atoms on the N-vinylimidazolium unit in the second network (when this unit is present), are coordinated with silver ions. The molar ratio of the sum of the imidazole nitrogen atoms and mercaptosulfonates from the N,S dual-coordination modified sodium carboxymethyl cellulose and the imidazole nitrogen atoms in the second network (when the N-vinylimidazolium unit is present) to silver ions is controlled to be 2-4:

1. After complexation for 10-30 minutes, the mixture is removed and rinsed with low-chlorine deionized water, preferably for 2-5 minutes. Each rinse is performed with a liquid volume of 10-50 times the gel volume and a rinsing time of 5-60 seconds. No visible deposits are found on the surface after rinsing. The chloride ion concentration in the system is controlled to be ≤10 mmol / L during the complexation process. The water-soluble cyanurate complexing agent is selected from at least one of cyanuric acid and its water-soluble salts, preferably its water-soluble salts.

5. The method for preparing a complexed silver antibacterial gel according to claim 1, characterized in that: The dispersion temperature of sodium magnesium lithium silicate in S1 is 20-25°C, and the stirring time is 0.5-2.0h; The intensity of ultraviolet light during photo-initiated polymerization in S2 is 10-20 mW·cm. -2 The illumination time is 30-120 seconds; The complexation time in S3 is 10-30 min; The preferred molar ratio of acrylamide to N-vinylimidazole is 98:2 to 96:4; The glycerol added in S2 has a mass fraction of 1.0-25.0 wt%, preferably 5.0-20.0 wt%, which is relative to the total mass of the reaction solution prepared in S2.

6. A complexed silver antibacterial gel prepared by the preparation method according to any one of claims 1-5, characterized in that, include: a) First network: A three-dimensional inorganic physical network formed by the self-assembly of sodium magnesium lithium silicate in an aqueous phase through electrostatic interaction and steric hindrance; b) Second network: an organic covalent crosslinked network formed by copolymerization of acrylamide and optional N-vinylimidazolium or homopolymerization of acrylamide, with N,N'-methylenebisacrylamide as a crosslinking agent and 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone as a photoinitiator, wherein the molar ratio of acrylamide to N-vinylimidazolium is 100:0 to 95:5, preferably 98:2 to 96:4; c) N,S dual-coordination modified sodium carboxymethyl cellulose: This is a modified polymer in which histidine imidazole coordination sites and L-cysteine ​​thiol coordination sites are covalently introduced onto the anhydrous glucose units of sodium carboxymethyl cellulose via amidation. The degree of imidazole substitution is 0.02-0.15 and the degree of thiol substitution is 0.01-0.10 based on the anhydrous glucose units, and the ratio of the degree of imidazole substitution to the degree of thiol substitution is 1.0-3.0:

1. The N,S dual-coordination modified sodium carboxymethyl cellulose is dispersed in an interpenetrating network composed of a first network and a second network. d) Water-soluble cyanurate complexing agent: used to complex with silver ions to form a stable silver complex, wherein the water-soluble cyanurate complexing agent is selected from at least one of cyanuric acid and its water-soluble salts, preferably its water-soluble salts; e) Silver complex: A silver complex formed by the complexation of silver ions with the cyanurate coordination sites in a water-soluble cyanurate complexing agent, and further coordinating with the imidazole and thiol coordination sites from c) and (in the presence of N-vinylimidazolium units) the imidazole coordination sites from the unit in b), forming a stable multi-coordination silver complex structure in the gel network; f) Moisturizing ingredient: Glycerin, dispersed in the aqueous phase of the gel, is used to improve the moisturizing and softening properties of the gel; g) Water; Wherein: the molar ratio of the total nitrogen atom of the imidazole ligand and the mercapto sulfur atom of the N,S dual-coordination modified sodium carboxymethyl cellulose derived from c) and the N-vinylimidazol unit optionally selected in the second network to silver ions is 2-4:1; the silver content is 100-600 mg / kg, based on wet gel; under the extraction conditions, i.e. 37°C, sample thickness 1 mm, and solid-liquid ratio 1:10, the daily average steady-state concentration of silver ions in the 24-168h range is 10-40 μg / L; the wet gel solid content is 8-25 wt%, where the wet gel solid content refers to the dry matter mass fraction determined by the loss on drying method; the mass fraction of glycerol in the wet gel is 1.0-25.0 wt%, preferably 5.0-20.0 wt%; and the gel forming time is ≤120 s, where the gel forming time is defined as the time from the cessation of light irradiation to the self-standing formation of the sample.

7. The complexed silver antibacterial gel according to claim 6, characterized in that, Gel setting time ≤ 120s and at 25°C and shear rate 10s -1 The apparent viscosity is 0.20-0.80 Pa·s; the gel is transparent or slightly milky white in appearance, and has a transmittance of ≥80% at a wavelength of 600 nm and an optical path of 1.0 mm; the wet gel solid content is preferably 12-18 wt%.

8. The complexed silver antibacterial gel according to claim 6 or 7, characterized in that, The gel can be sterilized by ethylene oxide or γ-irradiation at 25-35 kGy, and the daily average steady-state silver ion concentration within the 24-168h range (the silver ion steady-state release concentration window) varies by ≤±20% from 10-40 μg / L. It is stable for 12-24 months under sealed, light-protected storage at 22-28°C and 40-60% relative humidity. The silver content is preferably 200-400 mg / kg, based on wet gel, to achieve an optimal balance between the silver release window and cell compatibility.

9. Use of the silver complexing antibacterial gel prepared by the method of any one of claims 1-5 or the silver complexing antibacterial gel of any one of claims 6-8 in wound dressings.

10. The use according to claim 9, characterized in that, The dressing can be used continuously on the same wound for 1-7 days, with a replacement cycle of 24-72 hours.

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