Lipid hydrocolloid silver-loaded zeolite antibacterial dressing as well as preparation method, application and preparation thereof

Abstract

According to the lipid hydrocolloid silver-loaded zeolite antibacterial dressing, the preparation method and application thereof and the preparation, zeolite confinement and ion exchange are achieved, stable release is achieved, the characteristics of rapid release in the initial stage, gradual retarding in the middle stage and tending to be stable in the later stage are shown, and sufficient silver ion concentration can be provided in the initial stage of a wound so as to play an antibacterial role; meanwhile, a certain silver ion concentration is maintained in a subsequent time period, so that the antibacterial effect is continuously exerted, the potential toxicity to tissues is reduced, and the early peak value and potential stimulation are reduced; in the formula, non-specific migration of silver to the wound edge is reduced by oleophylic / hydrophilic phases in a synergistic manner, and the silver-loaded wound dressing has broad-spectrum efficient antibacterial performance, has greater than or equal to 90% of antibacterial potential for gram positive / negative model bacteria, and is adaptive to a multi-colony loaded wound surface.

Description

Technical Field

[0001] This invention relates to the field of medical antibacterial dressing technology, specifically to a lipid hydrocolloid silver zeolite antibacterial dressing, its preparation method, application, and formulation. Background Technology

[0002] Wound infections and refractory ulcers (such as burns, diabetic foot ulcers, and postoperative exudative wounds) are often accompanied by high bacterial bioload, excessive exudate, and microenvironmental imbalance. Clinically, there is an urgent need for dressing products that combine antibacterial properties, controlled release, and support for moist healing. Silver ions are widely used in dressings due to their broad-spectrum antibacterial activity; however, traditional free silver or simple "coated" silver salts have shortcomings such as initial "burst release," short effective period, and potential stimulation of host cells. Loading silver ions onto porous carriers (such as zeolite) promises to achieve a more stable and sustained release curve through ion exchange and porous confinement, and to synergistically maintain wound moisture and mechanical stability with a hydrophilic / lipophilic composite matrix. The shortcomings of existing technologies include: uncontrollable release of antibacterial components: some existing silver dressings have high early release peaks and rapid decay in the later stages, making it difficult to meet the long-term antibacterial requirements of chronic wounds; poor carrier / matrix compatibility: insufficient compatibility between inorganic carriers and organic matrices, easily leading to formulation stratification and increased silver migration rate; gaps in system quality control: the lack of an integrated testing paradigm covering "carrier silver content—release behavior—biological evaluation" affects batch-to-batch consistency and registration compliance; incomplete biosafety assessment: some products do not adequately cover the pH of the extract, cell compatibility, and standardized antibacterial evaluation. These pain points limit the stable application of silver-based dressings in complex wounds. Summary of the Invention

[0003] To address the shortcomings and deficiencies of existing technologies, this invention provides a lipid hydrocolloid silver-loaded zeolite antibacterial dressing, its preparation method, application, and formulation, which achieves synergistic regulation of exudate absorption and controllable release of silver ions through a "primary silver loading-secondary sustained release" process.

[0004] The technical solution adopted in this invention is: a lipid hydrocolloid silver-loaded zeolite antibacterial dressing, wherein the antibacterial dressing is obtained by pressing silver ion lipid hydrocolloid and a substrate together, wherein the silver ion lipid hydrocolloid includes a silver-loaded zeolite antibacterial agent and a hydrocolloid matrix, and the silver-loaded zeolite antibacterial agent is silver ions uniformly loaded on the surface and pores of the zeolite.

[0005] Preferably, the substrate is PU film roll or polyester fiber roll.

[0006] Preferably, the hydrocolloid matrix includes styrene-isoprene-styrene triblock copolymer (SIS), light liquid paraffin, petrolatum, and sodium carboxymethyl cellulose.

[0007] Preferably, the antibacterial dressing contains 2-4% by mass of silver-loaded zeolite antibacterial agent.

[0008] A method for preparing a lipid hydrocolloid silver zeolite antibacterial dressing includes the following steps: S1. Preparation of silver-loaded zeolite antibacterial agent: Silver sulfate was added to pure water in the dark and stirred at room temperature to fully dissolve and uniformly disperse the silver sulfate in the water. Zeolite was added and stirring was continued to allow silver ions to undergo an ion exchange reaction with the zeolite, so that the silver ions were uniformly loaded on the surface and pores of the zeolite. After the reaction was completed, the reaction solution was centrifuged, the solid was collected, and washed with pure water. Finally, the water in the silver-loaded zeolite was removed by washing with anhydrous ethanol. After washing, it was dried to obtain the silver-loaded zeolite antibacterial agent. S2. Preparation of lipid hydrocolloid silver zeolite antibacterial dressing: Tween 80, silver zeolite antibacterial agent and liquid paraffin are mixed and stirred to obtain silver zeolite mixture. Styrene-isoprene-styrene triblock copolymer, light liquid paraffin and petrolatum are weighed, heated and stirred to melt. After melting, sodium carboxymethyl cellulose and silver zeolite mixture are added and stirred at 140~160℃ to obtain semi-finished silver ion lipid hydrocolloid. The semi-finished silver ion lipid hydrocolloid is laminated and shaped on PU film roll and polyester fiber roll. The laminated product is cut to the required size and sterilized.

[0009] Preferably, the heating temperature in step S2 is 140~160 ℃.

[0010] Preferably, the zeolite added in step S1 is 300-mesh zeolite.

[0011] Application of a lipid hydrocolloid silver-loaded zeolite antibacterial dressing in the preparation of complex wound repair materials.

[0012] The complex wounds mentioned include wound infections and refractory ulcers.

[0013] The beneficial effects of this invention are as follows: This invention provides a lipid hydrocolloid silver-loaded zeolite antibacterial dressing, its preparation method, application, and formulation. It achieves stable release through zeolite confinement and ion exchange, exhibiting characteristics of rapid initial release, gradual slowdown in the middle stage, and stabilization in the later stage. This helps to provide sufficient silver ion concentration in the early stage of wound healing to exert antibacterial effects, while maintaining a certain silver ion concentration in subsequent periods to continuously exert antibacterial effects and reduce potential tissue toxicity, thus lowering early peak values ​​and potential irritation. The lipophilic / hydrophilic synergistic effect in the formulation reduces non-specific migration of silver to the wound edge, exhibiting broad-spectrum and highly effective antibacterial properties, with a potential inhibition rate of ≥90% against Gram-positive / negative model bacteria, making it suitable for wounds with high colony loads.

[0014] A dual-layered porous structure silver-containing hydrocolloid dressing achieves synergistic regulation of exudate absorption and controlled silver ion release through a "primary silver loading—secondary sustained release" mechanism: First, microporous zeolite acts as a primary reservoir, restricting silver ion diffusion through its regular micropores to achieve a stable and slow basic release. Subsequently, the released silver ions further complex with the carboxyl groups of sodium carboxymethyl cellulose in the hydrocolloid matrix (the hydrocolloid itself encapsulates the silver-containing zeolite), forming a secondary sustained-release system. During the hydrocolloid's absorption and swelling process, this system further regulates the dissociation and diffusion rate of silver. This dual controlled-release mechanism effectively avoids the burst-release effect of traditional silver-containing dressings, significantly reducing the local peak concentration of silver ions while ensuring good antibacterial effects, improving cell compatibility and skin sensitization safety, and giving the dressing a combination of high absorbency, sustained antibacterial properties, and excellent biocompatibility. Attached Figure Description

[0015] Figure 1 EDS (SEM) image of silver-loaded zeolite dressing.

[0016] Figure 2 SEM images of hydrocolloid dressings (silver-loaded zeolite dressings) with different contents of Ze-Ag.

[0017] Figure 3 The silver release curve is shown in the Ze-Ag hydrocolloid dressing.

[0018] Figure 4 The diagram shows the antibacterial properties of Ze-Ag hydrocolloid dressings.

[0019] Figure 5 In vitro cytotoxicity assessment of Ze-Ag hydrocolloid dressings.

[0020] Figure 6 Blood compatibility assessment of Ze-Ag hydrocolloid dressings.

[0021] Figure 7 Skin irritation assessment of Ze-Ag hydrocolloid dressings.

[0022] Figure 8 Intradermal reaction test for Ze-Ag hydrocolloid dressing. Detailed Implementation

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative effort are all within the scope of protection of the present invention.

[0024] Example 1: Preparation of silver-loaded zeolite antibacterial agent This invention prepares a silver-loaded zeolite antibacterial agent through the following steps: First, 40 L of pure water is added to a reaction vessel, and 400 g of silver sulfate is added under light-protected conditions. The mixture is stirred at 180 rpm for 30 minutes at room temperature to ensure the silver sulfate is fully dissolved and uniformly dispersed in the water. Next, 800 g of 300-mesh zeolite is added to the reaction vessel, and stirring continues for 3 hours to promote the ion exchange reaction between silver ions and zeolite, ensuring that silver ions are uniformly loaded onto the zeolite surface and within the pores. After the reaction is complete, the reaction solution is centrifuged, the solid is collected, and washed twice with pure water. Finally, it is washed with anhydrous ethanol to remove water from the silver-loaded zeolite. The washed solid is dried in an oven at 40°C to obtain the silver-loaded zeolite antibacterial agent, which is then stored at room temperature under light-protected conditions.

[0025] Example 2: Silver-loaded zeolite dressing Prepare silver-loaded zeolite mixtures with different contents; the specific operation is as follows: weigh 30 g of Tween 80, 24 g of silver-loaded zeolite and liquid paraffin (251 g) respectively, place them in a disperser, and stir at 15000 rpm for 5 minutes to prepare silver-loaded zeolite mixtures.

[0026] Weigh 30 g of SIS (styrene-isoprene-styrene triblock copolymer), 45 g of light liquid paraffin, and 30 g of petrolatum into a reaction vessel. Heat and stir to melt the mixture under sealed conditions (electric heating, temperature 140~160℃). After melting, open the feed port and add 75 g of sodium carboxymethyl cellulose and the above-prepared silver-loaded zeolite mixture. Then cover and seal the vessel and stir thoroughly at 140~160℃ (electric heating) to form the final product.

[0027] Materials such as PU film rolls and polyester fiber rolls are mounted on a lamination and setting machine, and the semi-finished silver ion lipid hydrocolloid is laminated using the machine. The laminated product is then pressed and cut to the required size, sealed in plastic, and subjected to external irradiation sterilization. Four types of silver-loaded zeolite dressings containing 0%, 0.20%, 2.00%, and 4.00% silver were prepared using the above process.

[0028] Observation under low magnification revealed that the substrate of the silver-containing dressing was a polyester fiber structure. The polyester fibers exhibited a typical interwoven morphology, with certain pores between them. This structure contributes to the dressing's breathability and absorbency, while also providing a good carrier for the adhesion of silver particles. Under high magnification, silver-loaded zeolite particles could be clearly observed. These particles were uniformly distributed on the surface of the polyester fibers and tightly bonded to them.

[0029] Figure 1 and Figure 2 The visual characteristics of the dressing are shown. The color is due to the presence of silver-loaded zeolite in the formulation (Figure). The depth of the dressing's color is affected by the amount of silver-loaded zeolite.

[0030] Acidity and alkalinity of dressings

[0031] According to the standard YY / T 1293.4-2016 Contact Wound Dressings Part 4: Hydrocolloid Dressings, the pH value of the dressing should be controlled between 5.5 and 7.5. The pH values ​​of silver-loaded zeolite dressings with different serial numbers were measured. The experimental results showed that the pH value of the produced dressing was below 7.5. The Urgo dressing, used as a control, had a pH value of 6.7, which meets the national standard.

[0032] silver sulfate content

[0033] Experimental results showed that the silver-loaded zeolite dressing produced contained 0.27% ± 0.02% ZeAg-2.0% and 0.50% ± 0.04% ZeAg-4.0%, while the control Urgo dressing contained 2.17% ± 0.31% silver sulfate. Therefore, the silver sulfate content of the silver-loaded zeolite dressings prepared in this study was lower than that of the commercially available Urgo dressing.

[0034] Silver release curve This invention investigated the silver ion release characteristics of three silver-containing dressings: ZeAg-2%, ZeAg-4%, and Urgo. In the experiment, 0.5000 g of the dressing sample was accurately weighed and placed in 10 mL of simulated body fluid preheated to 32°C. The mixture was shaken at 32°C ± 0.5°C and 30 rpm. Samples of 1 mL were taken at time points of 0, 1, 2, 4, 8, 16, 24, 36, 48, and 72 hours, and the same volume and temperature of simulated body fluid were replenished immediately. The experimental results showed that within 0–8 hours, the three dressings exhibited rapid silver ion release rates, with release amounts of 5.95 µg (ZeAg-2%), 5.77 µg (ZeAg-4%), and 5.67 µg (Urgo), respectively, and average release rates of 0.74 µg / h, 0.72 µg / h, and 0.71 µg / h, respectively. This was attributed to the rapid release of silver ions from the dressing surface into simulated body fluids. Within 8–48 hours, the silver ion release rate gradually decreased, with release amounts of 1.74 µg, 1.80 µg, and 1.63 µg, respectively, and average release rates of 0.044 µg / h, 0.045 µg / h, and 0.041 µg / h, respectively. Within 48–72 hours, the release of silver ions further slowed and stabilized, with release amounts of 0.032 µg, 0.13 µg, and 0.30 µg, respectively, and average release rates of 0.001 µg / h, 0.005 µg / h, and 0.012 µg / h, respectively. After 72 hours, the cumulative release amounts of the three dressings were 7.7 µg, 7.7 µg, and 7.6 µg, respectively. Overall, the silver ion release process of the ZeAg-2% and ZeAg-4% dressings was similar to that of the Urgo dressing, exhibiting a rapid initial release, a gradual slowdown in the middle stage, and a tendency to stabilize in the later stage. This helps to provide sufficient silver ion concentration in the early stage of wound healing to exert antibacterial effects, while maintaining a certain silver ion concentration in the subsequent time period to continuously exert antibacterial effects and reduce potential tissue toxicity.

[0035] Antibacterial properties To evaluate the antibacterial effect of dressings with different silver-loaded zeolite contents, this study used Escherichia coli and Staphylococcus aureus as test strains. The prepared dressings were subjected to an inhibition zone test, and blank dressings and commercially available Urgo dressings were used as control groups.

[0036] For silver sulfate zeolite dressings, experimental results showed that the dressing containing 0.2% silver-loaded zeolite did not produce a clear ring, while dressings with 2.00% and 4.00% silver-loaded zeolite contents both produced obvious clear rings. The diameter of the clear ring in the 4.00% silver-loaded dressing was larger than that in the 2.00% silver-loaded dressing, indicating that higher silver-loaded zeolite content produces a stronger antibacterial effect. The antibacterial properties of the prepared 4.00% silver-loaded zeolite dressing were close to those of commercially available Urgo dressings.

[0037] Biosafety This invention evaluated the cytotoxicity of Urgo dressings (marketed products) and self-developed dressings (ZeAg-2% and ZeAg-4%). ​​The results showed that Urgo dressings exhibited strong cytotoxicity at high concentrations (100%, 50%, and 25%), with cell viability of 7.5% and 5.4%, respectively, classifying as Grade 4 (1%–24%). At low concentrations (10% and 5%), cell viability was 94.4% and 98.1%, respectively, classifying as Grade 1 (75%–99%). In contrast, the self-developed dressings showed lower cytotoxicity at high concentrations. Specifically, the ZeAg-4% and ZeAg-2% dressings showed cell viability of 13.3% and 15.9% at 100% concentration, respectively, classifying as Grade 4. At low concentrations (10% and 5%), all self-developed dressings exhibited low cytotoxicity, with cell viability close to or higher than normal levels (Grade 0 or 1). These results indicate that the independently developed dressing has better biocompatibility in terms of cytotoxicity compared to urgo dressing.

[0038] Hemolysis rate is an important indicator for assessing the impact of materials on blood components. According to international standards, materials with a hemolysis rate of less than 5% are considered to have good biocompatibility []. The silver-loaded zeolite dressings with antibacterial properties produced above were subjected to a hemolysis test to evaluate their biocompatibility. The experimental results showed that the hemolysis rate of 0909D was 5.62%, 0109C was 16.86%, and 0109D was as high as 41.14%, while the control, urgo, had a rate of 4.58%. The hemolysis rates of the prepared silver-loaded zeolite dressings were all higher than the national standard.

[0039] Skin irritation assessment experiments on New Zealand rabbits showed that, within the specified observation period (excluding 1 hour, 24 hours, 48 ​​hours, and 72 hours after patch application), no erythema or edema reactions occurred at the skin contact sites on any of the rabbits, with erythema and edema scores all being 0. Based on this, the primary irritation scores for both the test and control samples were 0, and the calculated Primary Irritation Index (PII) was also 0, indicating a very mild reaction. This demonstrates that, under the experimental conditions, the silver-loaded zeolite antibacterial dressing showed no significant irritation to the skin of New Zealand rabbits and exhibited good skin tolerance.

[0040] In an intradermal reaction test, the skin irritation of the silver-loaded zeolite antibacterial dressing was assessed. No erythema or edema appeared at the injection sites of both the test and control groups immediately after injection, at (24±2) h, (48±2) h, and at (72±2) h. According to the scoring criteria, the scores for erythema and edema at each time point were 0. Therefore, the final score for the test sample was 0. This result indicates that the extract of the silver-loaded zeolite antibacterial dressing is non-irritating to animal skin, consistent with the negative control group, and exhibits good biocompatibility.

Claims

1. A lipid-hydrocolloid silver-loaded zeolite antibacterial dressing, characterized in that, The antibacterial dressing is obtained by pressing silver ion lipid hydrocolloid and substrate together. The silver ion lipid hydrocolloid includes silver-loaded zeolite antibacterial agent and hydrocolloid matrix. The silver-loaded zeolite antibacterial agent is silver-loaded zeolite with silver ions uniformly loaded on the surface and in the pores of the zeolite.

2. The lipid-hydrocolloid silver-loaded zeolite antibacterial dressing according to claim 1, characterized in that, The substrate is PU film roll and polyester fiber roll.

3. The lipid-hydrocolloid silver-loaded zeolite antibacterial dressing according to claim 1, characterized in that, The hydrocolloid matrix includes styrene-isoprene-styrene triblock copolymer (SIS), light liquid paraffin, petrolatum, and sodium carboxymethyl cellulose.

4. The lipid hydrocolloid silver-loaded zeolite antibacterial dressing according to claim 1, characterized in that, The antibacterial dressing contains 2-4% silver-loaded zeolite antibacterial agent by mass percentage.

5. A method for preparing the lipid hydrocolloid silver-loaded zeolite antibacterial dressing according to claim 1, characterized in that, Includes the following steps: S1. Preparation of silver-loaded zeolite antibacterial agent: Silver sulfate was added to pure water in the dark and stirred at room temperature to fully dissolve and uniformly disperse the silver sulfate in the water. Zeolite was added and stirring was continued to allow silver ions to undergo an ion exchange reaction with the zeolite, so that the silver ions were uniformly loaded on the surface and pores of the zeolite. After the reaction was completed, the reaction solution was centrifuged, the solid was collected, and washed with pure water. Finally, the water in the silver-loaded zeolite was removed by washing with anhydrous ethanol. After washing, it was dried to obtain the silver-loaded zeolite antibacterial agent. S2. Preparation of lipid hydrocolloid silver zeolite antibacterial dressing: Tween 80, silver zeolite antibacterial agent and liquid paraffin are mixed and stirred to obtain silver zeolite mixture. Styrene-isoprene-styrene triblock copolymer, light liquid paraffin and petrolatum are weighed, heated and stirred to melt. After melting, sodium carboxymethyl cellulose and silver zeolite mixture are added and stirred at 140~160℃ to obtain semi-finished silver ion lipid hydrocolloid. The semi-finished silver ion lipid hydrocolloid is laminated and shaped on PU film roll and polyester fiber roll. The laminated product is cut to the required size and sterilized.

6. The preparation method according to claim 5, characterized in that, The heating temperature in step S2 is 140~160 ℃.

7. The preparation method according to claim 5, characterized in that, In step S1, the zeolite added is 300-mesh zeolite.

8. The application of the lipid hydrocolloid silver-loaded zeolite antibacterial dressing of claim 1 in the preparation of complex wound repair materials.

9. The application according to claim 8, characterized in that, The complex wounds mentioned include wound infections and refractory ulcers.

Images