A high-adhesion gel matrix material and a method for preparing the same

Abstract

The application provides a high-adhesion gel matrix material and a preparation method thereof, and belongs to the technical field of polymer gel dressings.The gel matrix components comprise etherified modified konjac glucomannan, rosemary acid grafted hydroxypropyl chitosan, a composite natural bacteriostatic extract, white bletilla striata polysaccharide, glycerol polyacrylate, xanthan gum, povidone and the like.The etherified modified konjac glucomannan is prepared by alkalization of konjac glucomannan with a sodium hydroxide aqueous solution, and then subjected to an epoxy ring-opening etherification reaction with 2,3-epoxypropyl trimethyl ammonium chloride.The rosemary acid grafted hydroxypropyl chitosan is prepared by dissolving hydroxypropyl chitosan in a MES buffer solution containing propylene glycol, activating with EDC and NHS, and then subjected to an amide grafting reaction with rosemary acid.The composite natural bacteriostatic extract is prepared by cellulase enzymolysis of a mixture of powder of Cyperus rotundus L., corn silk and black seed, followed by papain and ficin co-enzymolysis, and then purified by an HPD500 macroporous adsorption resin column.

Description

Technical Field

[0001] This invention pertains to the field of polymeric gel dressing technology, specifically relating to a highly adhesive gel matrix material and its preparation method. Background Technology

[0002] Gels, as core carriers for clinical topical drug delivery and wound care, are widely used in skin wound repair and local drug delivery due to their excellent biocompatibility, moisturizing properties, and drug loading capacity. Currently, gel matrices are mostly prepared from a blend of natural and synthetic polymers. Carbomer, xanthan gum, carrageenan, and chitosan are the mainstream base materials in the industry. These materials can form a three-dimensional network gel structure through physical cross-linking or chemical modification, effectively loading active ingredients and providing a moist environment for wound repair, thus promoting the industrialization of topical gel formulations.

[0003] Existing conventional gel matrices have several performance defects that fail to meet the demands of efficient clinical use. Regarding adhesion, conventional gels exhibit poor adhesion to the skin surface, lacking flexibility and strong adhesion. When used on moving areas such as joints, they are prone to detachment and displacement, failing to provide sustained application to the affected area and reducing drug utilization and nursing effectiveness. In terms of antibacterial properties, single-matrix gels lack long-lasting antibacterial capabilities. While chitosan possesses some antibacterial activity, its effect is limited, inhibiting only a few bacteria and failing to comprehensively protect against common wound pathogens. Furthermore, the gel is prone to bacterial and fungal growth during use, accelerating gel deterioration and potentially triggering wound inflammation, thus worsening the damage. Strong antibacterial components often present safety concerns and irritant properties.

[0004] Furthermore, existing gel matrices generally suffer from poor compatibility in compound systems, making it difficult to simultaneously meet multiple requirements such as high adhesion, antibacterial properties, and good compatibility. Therefore, there is a need to develop novel gel matrix materials that combine high adhesion, antibacterial safety, and good compatibility with drug loading. Summary of the Invention

[0005] To address the problems of poor adhesion, poor compatibility, and unsafe antibacterial components in existing gel matrices, which can lead to bacterial infections and irritation, this invention provides a highly adhesive gel matrix material and its preparation method. The method involves preparing etherified modified konjac glucomannan, rosmarinic acid-grafted hydroxypropyl chitosan, and a composite natural antibacterial extract. With the synergistic effect of natural polymer modification and composite antibacterial components as the core, the material achieves comprehensive performance including high adhesion, broad-spectrum antibacterial activity, long-lasting moisturizing effect, and stable drug loading. The specific technical solution is as follows: A highly adhesive gel matrix material comprises the following raw materials in parts by weight: 1-1.8 parts of etherified modified konjac glucomannan, 3-4 parts of rosmarinic acid-grafted hydroxypropyl chitosan, 2-4 parts of complex natural antibacterial extract, 0.5-0.8 parts of Bletilla striata polysaccharide, 0.3-0.5 parts of glyceryl polyacrylate, 0.2-0.4 parts of xanthan gum, 0.5-0.8 parts of povidone, 0.5-0.8 parts of hydroxyethyl cellulose, 8-10 parts of glycerol, 4-5 parts of propylene glycol, 0.5-0.8 parts of sodium citrate, 0.03-0.05 parts of ethylparaben, 90-95 parts of purified water, and a 20-22 wt% triethanolamine aqueous solution to adjust the pH of the system to 6.5-7.0.

[0006] Furthermore, the etherified modified konjac glucomannan is prepared by alkalizing konjac glucomannan with sodium hydroxide aqueous solution, then performing an epoxy ring-opening etherification reaction with 2,3-epoxypropyltrimethylammonium chloride, followed by neutralization, ethanol precipitation, washing, drying, and pulverization.

[0007] Furthermore, the concentration of the sodium hydroxide aqueous solution is 4-6 wt%; the amount of 2,3-epoxypropyltrimethylammonium chloride used is 20-25% of the mass of konjac glucomannan; and the epoxy ring-opening etherification reaction is carried out at 55-60°C.

[0008] Furthermore, the preparation method of the etherified modified konjac glucomannan includes: adding konjac glucomannan to a 4-6 wt% sodium hydroxide aqueous solution, stirring and alkalizing to form an alkaline dispersion; adding 20-25% by weight of konjac glucomannan of 2,3-epoxypropyltrimethylammonium chloride to the alkaline dispersion, stirring and reacting at 55-60℃, cooling to room temperature, adjusting the pH to 7.0-7.5, adding anhydrous ethanol, stirring and settling, filtering, washing the filter cake with anhydrous ethanol, vacuum drying, and pulverizing to obtain the etherified modified konjac glucomannan.

[0009] Furthermore, the rosmarinic acid-grafted hydroxypropyl chitosan is prepared by dissolving hydroxypropyl chitosan in MES buffer containing propylene glycol, activating it with EDC and NHS, and then subjecting it to an amidation grafting reaction with rosmarinic acid, followed by dialysis purification and freeze-drying.

[0010] Furthermore, the pH value of the MES buffer is 5.5-6.0; the amount of EDC used is 30-35% of the mass of hydroxypropyl chitosan; the amount of NHS used is 20-30% of the mass of hydroxypropyl chitosan; the amount of rosmarinic acid used is 20-30% of the mass of hydroxypropyl chitosan; and the dialysis is performed using a dialysis bag with a molecular weight cutoff of 10 kDa.

[0011] Furthermore, the preparation method of rosmarinic acid-grafted hydroxypropyl chitosan includes: dissolving hydroxypropyl chitosan in MES buffer at pH 5.5–6.0, adding 1–2 wt% propylene glycol (based on the total mass of MES buffer and hydroxypropyl chitosan), and stirring to dissolve; sequentially adding 30–35% EDC and 20–30% NHS (based on the mass of hydroxypropyl chitosan), and stirring to activate; adding 20–30% rosmarinic acid (based on the mass of hydroxypropyl chitosan), and stirring to react at 25–35°C; dialyzing with a dialysis bag containing a molecular weight cutoff of 10 kDa in deionized water, and freeze-drying to obtain rosmarinic acid-grafted hydroxypropyl chitosan.

[0012] Furthermore, the compound natural antibacterial extract is prepared by enzymatic hydrolysis of a mixture of Cyperus rotundus leaf, corn silk and black cumin seed powder by cellulase, followed by co-enzymatic hydrolysis by papain and fig protease, purification by HPD500 macroporous adsorption resin column, and freeze-drying of the eluent.

[0013] Furthermore, the mass ratio of Cyperus rotundus leaves, corn silk, and black cumin seeds is (4-4.5):(3-3.2):(2-2.5); the amount of cellulase used is 0.8-1.2 wt% of the mixed powder mass, and the cellulase is enzymatically hydrolyzed at pH 4.8-5.2 and 52-55℃ for 2-3 hours; the amount of papain and fig protease used is 0.5-0.8 wt% of the mixed powder mass, and the papain and fig protease are enzymatically hydrolyzed at pH 5.5-6.0 and 53-58℃ for 1.5-2 hours; the eluent is obtained by elution with a 50-55 vol% ethanol aqueous solution.

[0014] Furthermore, the preparation method of the compound natural antibacterial extract includes: weighing the raw material dry powder according to the mass ratio of Cyperus rotundus leaf: corn silk: black cumin seed = (4-4.5):(3-3.2):(2-2.5), mixing to obtain a mixed powder, adding purified water, adjusting the pH to 4.8-5.2, adding 0.8-1.2 wt% of cellulase from the mixed powder, enzymatically hydrolyzing at 52-55℃ for 2-3 hours; inactivating the enzyme at 80-85℃, cooling to 53-58℃, adjusting the pH to 5.5-6.0, and adding 0.5-1.2 wt% of the mixed powder. 0.8 wt% papain and fig protease were hydrolyzed at 53–58 °C for 1.5–2 h; the enzymes were inactivated at 80–85 °C and cooled to room temperature; the mixture was filtered, concentrated, and the resulting sample solution was loaded onto an HPD500 macroporous adsorption resin column and rinsed with 3–4 BV of deionized water to remove impurities; 2–3 BV of the solution was eluted with 20–25 vol% ethanol aqueous solution and discarded, followed by 3–5 BV of the solution being eluted with 50–55 vol% ethanol aqueous solution and the eluent was collected, concentrated under reduced pressure, freeze-dried, pulverized, and sieved to obtain a complex natural antibacterial extract.

[0015] The preparation method of the above-mentioned highly adhesive gel matrix material includes the following steps: S1: Take 8-10% of the total mass of purified water by mass, add rosmarinic acid-grafted hydroxypropyl chitosan, stir to form a uniform slurry, and obtain pretreated chitosan. S2: According to the mass fractions, first add etherified modified konjac glucomannan, Bletilla striata polysaccharide, glyceryl polyacrylate, and xanthan gum to the remaining purified water, stir to disperse and swell; then add hydroxyethyl cellulose, stir to swell, and obtain a polymer mixture; S3: Dissolve ethylparaben in propylene glycol at 2-3 times its mass to obtain a preservative pre-solution; add glycerol, the remaining propylene glycol, sodium citrate, and the preservative pre-solution to the polymer mixture, and stir until homogeneous; S4: Add compound natural antibacterial extract and povidone, stir well; add pretreated chitosan, stir well; S5: Adjust the pH to 6.5-7.0 using a 20-22 wt% triethanolamine aqueous solution; degas under vacuum to obtain a gel.

[0016] In the preparation of the gel, the drug component is added in step S3 and / or S4: When the drug component is a water-soluble liquid or extract, it is added simultaneously with the compound natural antibacterial extract in step S4. When the drug component is a poorly soluble or fat-soluble powder, it is first pre-dispersed with propylene glycol and / or glycerol in the formula to prepare a uniform suspension, which is then added in step S3. The total amount of drug components added is 0.5 to 20 wt% of the final mass of the gel.

[0017] The present invention provides a highly adhesive gel matrix material and its preparation method, the beneficial effects of which include: I. This invention relates to a highly adhesive gel matrix material, which, with the synergistic effect of modified natural polymers and composite antibacterial components, exhibits broad-spectrum inhibitory effects against common wound pathogens. It demonstrates strong wet adhesion, good biocompatibility, long-lasting moisturizing effect, and stable drug loading. It can continuously maintain a moist repair environment, enhancing the effectiveness of nursing care and drug administration; it exhibits good drug compatibility; and it shows no significant cytotoxicity, hemolysis, or significant skin irritation in vitro.

[0018] II. Etherification-modified konjac glucomannan improves the water solubility, dispersibility and interfacial affinity of the material, allowing the gel to form a stable adsorption on the surface of moist skin; at the same time, it enhances the cross-linking ability of polymers, builds a more uniform network structure, and improves the overall cohesion, flexibility and structural stability of the gel, fundamentally solving the problems of weak adhesion, easy fall-off and poor compatibility of ordinary gels.

[0019] Third, rosmarinic acid grafted with hydroxypropyl chitosan endows the gel with a strong binding ability similar to bioadhesion, greatly improving wet adhesion; at the same time, it retains the biocompatibility of chitosan itself, and combined with the mild antibacterial effect of rosmarinic acid, so that the gel has the dual advantages of improving adhesion, assisting in antibacterial and reducing irritation, is not easy to deteriorate, and the grafted product has high purity and no free irritant groups, making it more biosafe.

[0020] IV. The compound natural antibacterial extract uses Cyperus rotundus leaf, corn silk, and black cumin seed as raw materials. It adopts cellulase pretreatment and papain and fig protease dual enzyme synergistic hydrolysis to directionally break down plant tissues, fully release antibacterial peptides and active antibacterial substances, and improve the yield of effective ingredients. Then, it is precisely enriched and purified by HPD500 macroporous adsorption resin to remove impurities and retain highly active antibacterial components, and finally obtain a broad-spectrum, mild and safe natural antibacterial system that inhibits a variety of pathogenic bacteria and fungi, without the irritation and safety hazards of chemical antibacterial agents.

[0021] V. In the overall preparation method of gel, rosmarinic acid grafted with hydroxypropyl chitosan is first made into a slurry pre-dispersion, and then other polymers are allowed to fully swell in water to ensure that each component is evenly dispersed, avoid agglomeration, particle and local uneven concentration, form a stable interpenetrating network, and improve the fineness and flexibility of the gel.

[0022] VI. The synergistic effect of etherified konjac glucomannan, rosmarinic acid-grafted chitosan, and Bletilla striata polysaccharide enhances dry and wet adhesion properties. The multi-component polymers, including etherified konjac glucomannan, hydroxypropyl chitosan, xanthan gum, and hydroxyethyl cellulose, form an interpenetrating network structure with a balance between cohesion and flexibility, making the gel less prone to breakage, water separation, and deterioration. Small-molecule humectants such as glycerin and propylene glycol form a stable moisturizing system with the polymer three-dimensional network, maintaining a long-lasting humid environment. The components have matched charges and complementary solubilities, exhibiting good loading and compatibility with most water-soluble and lipid-soluble drugs, improving drug utilization and stability. Detailed Implementation

[0023] The present invention will be further described below with reference to specific implementation examples, but the present invention is not limited to these embodiments.

[0024] Definitions: EDC is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; NHS stands for N-hydroxysuccinimide; MES is 2-(N-morpholino)ethanesulfonic acid; BV represents the bed volume.

[0025] Example 1

[0026] A highly adhesive gel matrix material comprises the following raw materials in parts by weight: 1.4 parts of etherified modified konjac glucomannan, 3.5 parts of rosmarinic acid-grafted hydroxypropyl chitosan, 0.65 parts of Bletilla striata polysaccharide, 3 parts of compound natural antibacterial extract, 0.4 parts of glycerol polyacrylate, 0.3 parts of xanthan gum, 0.65 parts of povidone, 0.7 parts of hydroxyethyl cellulose, 9 parts of glycerol, 4.5 parts of propylene glycol, 0.6 parts of sodium citrate, 0.04 parts of ethylparaben, 93 parts of purified water, and a 21wt% triethanolamine aqueous solution to adjust the pH of the system to 6.8.

[0027] The preparation method of etherified modified konjac glucomannan includes: taking konjac glucomannan pulverized through a 200-mesh sieve, adding 9 times its mass of 5wt% sodium hydroxide aqueous solution, and alkalizing it in a sealed reaction vessel at room temperature with stirring at 350 r / min for 1 h to form an alkaline dispersion; adding 23% of the mass of konjac glucomannan in 2,3-epoxypropyltrimethylammonium chloride to the alkaline dispersion, sealing and protecting from light, heating to a temperature range of 55-60℃, and stirring at 350 r / min for 4.5 h; cooling to room temperature, adjusting the pH to 7.2 with 1.1 mol / L hydrochloric acid aqueous solution to obtain a reaction solution; adding 3.5 times the volume of anhydrous ethanol to the reaction solution, stirring and settling for 45 min, filtering, and washing the filter cake repeatedly with anhydrous ethanol 3 times; vacuum drying in a vacuum-sealed oven at a temperature range of 50-55℃ for 7 h; pulverizing through a 200-mesh sieve, sealing and storing in a moisture-proof container to obtain etherified modified konjac glucomannan.

[0028] The preparation method of rosmarinic acid-grafted hydroxypropyl chitosan includes: dissolving hydroxypropyl chitosan in 90 times its weight of MES buffer at pH 5.8; adding 1.5 wt% propylene glycol (based on the total weight of MES buffer and hydroxypropyl chitosan) as a co-solvent, and stirring at 300 rpm for 20 min at room temperature until completely dissolved; sequentially adding 32% EDC and 25% NHS (based on the weight of hydroxypropyl chitosan), and stirring at 400 rpm under sealed conditions at room temperature. The mixture was stirred for 40 min; 25% rosmarinic acid (by weight of hydroxypropyl chitosan) was added, and the mixture was stirred at 250 r / min for 22 h under light-protected conditions (25-35℃) and nitrogen micro-protection. After the reaction, the mixture was placed in a dialysis bag with a molecular weight cutoff of 10 kDa and flow-dialyzed in deionized water for 76 h, with the deionized water being replaced every 10 h (dialysis was performed until there was no ninhydrin reaction and no free rosmarinic acid in the washings). The dialysate was freeze-dried to obtain rosmarinic acid-grafted hydroxypropyl chitosan.

[0029] The preparation method of the compound natural antibacterial extract includes: weighing the raw material dry powder that has passed through an 80-mesh sieve according to the mass ratio of Cyperus rotundus leaf: corn silk: black cumin seed = 4.3:3.1:2.2, and mixing them to obtain a mixed powder; adding 11 times the mass of purified water of the mixed powder, adjusting the pH to 5.0, adding 1 wt% of cellulase of the mixed powder, and enzymatically hydrolyzing at a temperature of 52-55℃ for 2.5 h in a sealed environment; inactivating the enzyme at 82℃ for 12 min in a sealed environment, and cooling to 55℃; adjusting the pH to 5.8, adding 0.65 wt% each of papain and fig protease of the mixed powder, and enzymatically hydrolyzing at a temperature of 53-58℃ for 1.5 h in a sealed environment; inactivating the enzyme at 82℃ for 12 min in a sealed environment, and cooling to room temperature; and finally filtering through a 250-mesh coarse filter. The solution is then filtered through a 0.45 μm aqueous microporous membrane. The filtrate is placed in a sealed vacuum concentration tank and concentrated to 18% of its original volume at 55–65°C. After cooling to room temperature, it is filtered again through a 0.45 μm membrane to obtain the loading solution. The solution is loaded onto an HPD500 macroporous adsorption resin column at a flow rate of 1.8 BV / h and rinsed with 3.5 BV of deionized water to remove impurities. 2.5 BV is eluted with 23 vol% ethanol aqueous solution and discarded, followed by 4 BV elution with 52 vol% ethanol aqueous solution, and the eluent is collected. The eluent is concentrated under sealed vacuum at 55–65°C to remove ethanol, freeze-dried, pulverized through a 150-mesh sieve, and sealed for storage to obtain the compound natural antibacterial extract.

[0030] The preparation method of the above-mentioned highly adhesive gel matrix material includes the following steps: S1: Take 9% of the total mass of purified water by mass, add rosmarinic acid-grafted hydroxypropyl chitosan, and stir at 280 r / min for 20 min to form a uniform slurry to obtain pretreated chitosan. S2: According to the mass fractions, first add etherified modified konjac glucomannan, Bletilla striata polysaccharide, glyceryl polyacrylate, and xanthan gum to the remaining purified water, stir to disperse and swell; then add hydroxyethyl cellulose, stir to swell until there are no visible particles, and obtain a polymer mixture; S3: Dissolve ethylparaben in 2.5 times its mass of propylene glycol (taken from the total propylene glycol in the formula) by stirring at 35-45°C to obtain a preservative pre-solution; add glycerol, the remaining propylene glycol, sodium citrate, and the preservative pre-solution to the polymer mixture, seal and heat to 35-45°C, and stir at 450 r / min for 25 min until the system is completely homogeneous; S4: Cool to 30-35℃, add compound natural antibacterial extract and povidone, stir at 450r / min for 20min until uniform; add pretreated chitosan, stir at 280r / min for 20min until uniformly dispersed; S5: Cool to room temperature, and while stirring, slowly add 21wt% triethanolamine aqueous solution to adjust the pH of the system to 6.8; then degas under vacuum for 15 min at a low stirring speed of 120 r / min to obtain a gel.

[0031] Example 2

[0032] A highly adhesive gel matrix material comprises the following raw materials in parts by weight: 1 part etherified modified konjac glucomannan, 4 parts rosmarinic acid-grafted hydroxypropyl chitosan, 0.5 parts Bletilla striata polysaccharide, 2 parts compound natural antibacterial extract, 0.5 parts glycerol polyacrylate, 0.2 parts xanthan gum, 0.8 parts povidone, 0.5 parts hydroxyethyl cellulose, 10 parts glycerol, 4 parts propylene glycol, 0.8 parts sodium citrate, 0.03 parts ethylparaben, 95 parts purified water, and a 20wt% triethanolamine aqueous solution to adjust the pH of the system to 7.0.

[0033] The preparation method of etherified modified konjac glucomannan includes: taking konjac glucomannan pulverized through a 150-mesh sieve, adding 10 times its mass of 4wt% sodium hydroxide aqueous solution, and alkalizing it in a sealed reaction vessel at room temperature with stirring at 400 r / min for 1 h to form an alkaline dispersion; adding 25% of the mass of konjac glucomannan in 2,3-epoxypropyltrimethylammonium chloride to the alkaline dispersion, sealing and protecting from light, raising the temperature to 55-60℃, and stirring at 300 r / min for 5 h; cooling to room temperature, adjusting the pH to 7.5 with 1 mol / L hydrochloric acid aqueous solution to obtain a reaction solution; adding 3 times the volume of anhydrous ethanol to the reaction solution, stirring and settling for 60 min, filtering, and washing the filter cake repeatedly with anhydrous ethanol 3 times; vacuum drying in a vacuum oven at 50-55℃ for 8 h; pulverizing through a 150-mesh sieve, sealing and storing in a moisture-proof container to obtain etherified modified konjac glucomannan.

[0034] The preparation method of rosmarinic acid-grafted hydroxypropyl chitosan includes: dissolving hydroxypropyl chitosan in 80 times its weight of MES buffer at pH 6.0; adding 1 wt% propylene glycol (based on the total weight of MES buffer and hydroxypropyl chitosan) as a co-solvent, and stirring at 350 r / min for 15 min at room temperature until completely dissolved; sequentially adding 35% EDC and 20% NHS (based on the weight of hydroxypropyl chitosan), and activating by stirring at 500 r / min under sealed conditions at room temperature. Add 30% rosmarinic acid (by weight of hydroxypropyl chitosan) to the mixture for 30 min. The mixture is stirred at 200 r / min for 24 h under light-protected conditions (25–35 °C) and nitrogen atmosphere. After the reaction, the mixture is flow-dialyzed in deionized water for 72 h using a dialysis bag with a molecular weight cutoff of 10 kDa. The deionized water is replaced every 12 h (dialysis continues until no ninhydrin reaction or free rosmarinic acid is observed in the washings). The dialysate is freeze-dried to obtain rosmarinic acid-grafted hydroxypropyl chitosan.

[0035] The preparation method of the compound natural antibacterial extract includes: weighing the raw material dry powder through a 100-mesh sieve according to the mass ratio of Cyperus rotundus leaf: corn silk: black cumin seed = 4:3.2:2, and mixing them to obtain a mixed powder; adding 10 times the mass of purified water to the mixed powder, adjusting the pH to 5.2, adding 0.8 wt% of cellulase from the mixed powder, and enzymatically hydrolyzing at 52-55℃ for 3 hours in a sealed environment; inactivating the enzyme at 80℃ for 15 minutes in a sealed environment, and cooling to 53℃; adjusting the pH to 6.0, adding 0.5 wt% each of papain and fig protease from the mixed powder, and enzymatically hydrolyzing at 53-58℃ for 2 hours in a sealed environment; inactivating the enzyme at 80℃ for 15 minutes in a sealed environment, and cooling to room temperature; and finally filtering through a 250-mesh sieve. The solution is then filtered through a 0.45 μm aqueous microporous membrane. The filtrate is placed in a sealed vacuum concentration tank and concentrated to 20% of its original volume at 55–65 °C. After cooling to room temperature, it is filtered again through a 0.45 μm membrane to obtain the loading solution. The solution is loaded onto an HPD500 macroporous adsorption resin column at a flow rate of 1.5 BV / h and rinsed with 4 BV of deionized water to remove impurities. 3 BV is eluted with 20 vol% ethanol aqueous solution and discarded, followed by 5 BV elution with 50 vol% ethanol aqueous solution, and the eluent is collected. The eluent is concentrated under sealed vacuum at 55–65 °C to remove ethanol, freeze-dried, pulverized through a 150-mesh sieve, and sealed for storage to obtain the compound natural antibacterial extract.

[0036] The preparation method of the above-mentioned highly adhesive gel matrix material includes the following steps: S1: Take 8% of the total mass of purified water by mass, add rosmarinic acid-grafted hydroxypropyl chitosan, and stir at 300 r / min for 15 min to form a uniform slurry to obtain pretreated chitosan. S2: According to the mass fractions, first add etherified modified konjac glucomannan, Bletilla striata polysaccharide, glyceryl polyacrylate, and xanthan gum to the remaining purified water, stir to disperse and swell; then add hydroxyethyl cellulose, stir to swell until there are no visible particles, and obtain a polymer mixture; S3: Dissolve ethylparaben in 3 times its mass of propylene glycol (taken from the total amount of propylene glycol in the formula) by stirring in a temperature range of 35-45℃ to obtain a preservative pre-solution; add glycerol, the remaining propylene glycol, sodium citrate, and the preservative pre-solution to the polymer mixture, seal and heat to a temperature range of 35-45℃, and stir at 400 r / min for 30 min until the system is completely homogeneous; S4: Cool to 30-35℃, add compound natural antibacterial extract and povidone, stir at 400r / min for 25min until uniform; add pretreated chitosan, stir at 250r / min for 25min until uniformly dispersed; S5: Cool to room temperature, and while stirring, slowly add 20wt% triethanolamine aqueous solution to adjust the pH of the system to 7.0; then degas under vacuum for 20 min at a low stirring speed of 80 r / min to obtain a gel.

[0037] Example 3

[0038] A highly adhesive gel matrix material comprises the following raw materials in parts by weight: 1.8 parts of etherified modified konjac glucomannan, 3 parts of rosmarinic acid-grafted hydroxypropyl chitosan, 0.8 parts of Bletilla striata polysaccharide, 4 parts of compound natural antibacterial extract, 0.3 parts of glycerol polyacrylate, 0.4 parts of xanthan gum, 0.5 parts of povidone, 0.8 parts of hydroxyethyl cellulose, 8 parts of glycerol, 5 parts of propylene glycol, 0.5 parts of sodium citrate, 0.05 parts of ethylparaben, 90 parts of purified water, and a 22wt% triethanolamine aqueous solution to adjust the pH of the system to 6.5.

[0039] The preparation method of etherified modified konjac glucomannan includes: taking konjac glucomannan pulverized through a 200-mesh sieve, adding 8 times its mass of 6wt% sodium hydroxide aqueous solution, and alkalizing it in a sealed reaction vessel at room temperature with stirring at 300 r / min for 1.5 h to form an alkaline dispersion; adding 20% ​​of the mass of konjac glucomannan in 2,3-epoxypropyltrimethylammonium chloride to the alkaline dispersion, sealing and protecting from light, heating to a temperature range of 55-60℃, and stirring at 400 r / min for 4 h; cooling to room temperature, adjusting the pH to 7.0 with 1.2 mol / L hydrochloric acid aqueous solution to obtain a reaction solution; adding 4 times the volume of anhydrous ethanol to the reaction solution, stirring and settling for 30 min, filtering, and repeatedly washing the filter cake with anhydrous ethanol 4 times; vacuum drying in a vacuum-sealed oven at a temperature range of 50-55℃ for 6 h; pulverizing through a 200-mesh sieve, sealing and storing in a moisture-proof container to obtain etherified modified konjac glucomannan.

[0040] The preparation method of rosmarinic acid-grafted hydroxypropyl chitosan includes: dissolving hydroxypropyl chitosan in 100 times its weight of MES buffer at pH 5.5; adding 2wt% propylene glycol (based on the total weight of MES buffer and hydroxypropyl chitosan) as a co-solvent, and stirring at 250 rpm for 25 min at room temperature until completely dissolved; sequentially adding 30% EDC and 30% NHS (based on the weight of hydroxypropyl chitosan), and stirring at 300 rpm under sealed conditions at room temperature. The mixture was stirred for 50 min; 20% rosmarinic acid (by weight of hydroxypropyl chitosan) was added, and the mixture was stirred at 300 r / min for 20 h under light-protected conditions (25-35℃) and nitrogen atmosphere; after the reaction, the mixture was placed in a dialysis bag with a molecular weight cutoff of 10 kDa and flow-dialyzed in deionized water for 80 h, with the deionized water being replaced every 8 h (dialysis was performed until there was no ninhydrin reaction and no free rosmarinic acid in the washings); the dialysate was freeze-dried to obtain rosmarinic acid-grafted hydroxypropyl chitosan.

[0041] The preparation method of the compound natural antibacterial extract includes: weighing dry raw material powder that has passed through an 80-mesh sieve according to the mass ratio of Cyperus rotundus leaf: corn silk: black cumin seed = 4.5:3:2.5, and mixing it to obtain a mixed powder; adding 12 times the mass of purified water to adjust the pH to 4.8, adding 1.2 wt% of cellulase from the mixed powder, and enzymatically hydrolyzing at 52-55℃ for 2 hours in a sealed environment; inactivating the enzyme at 85℃ for 10 minutes in a sealed environment, and cooling to 58℃; adjusting the pH to 5.5, adding 0.8 wt% each of papain and fig protease from the mixed powder, and enzymatically hydrolyzing at 53-58℃ for 1.5 hours in a sealed environment; inactivating the enzyme at 85℃ for 10 minutes in a sealed environment, and cooling to room temperature; and passing the extract through a 325-mesh sieve. The sample was coarsely filtered, then finely filtered through a 0.45 μm aqueous microporous membrane. The filtrate was placed in a sealed vacuum concentration tank and concentrated to 15% of its original volume at 55–65 °C. After cooling to room temperature, it was filtered a second time through a 0.45 μm membrane to obtain the loading solution. The sample was loaded onto an HPD500 macroporous adsorption resin column at a flow rate of 2 BV / h and rinsed with 3 BV of deionized water to remove impurities. The 2 BV was first eluted with a 25 vol% ethanol aqueous solution and discarded, and then the 3 BV was eluted with a 55 vol% ethanol aqueous solution and the eluent was collected. The eluent was concentrated under sealed vacuum at 55–65 °C to remove ethanol, freeze-dried, pulverized through a 200-mesh sieve, and sealed for storage to obtain the compound natural antibacterial extract.

[0042] The preparation method of the above-mentioned highly adhesive gel matrix material includes the following steps: S1: Take 10% of the total mass of purified water by mass, add rosmarinic acid-grafted hydroxypropyl chitosan, and stir at 250 r / min for 25 min to form a uniform slurry to obtain pretreated chitosan. S2: According to the mass fractions, first add etherified modified konjac glucomannan, Bletilla striata polysaccharide, glyceryl polyacrylate, and xanthan gum to the remaining purified water, stir to disperse and swell; then add hydroxyethyl cellulose, stir to swell until there are no visible particles, and obtain a polymer mixture; S3: Dissolve ethylparaben in 2 times its mass of propylene glycol (taken from the total amount of propylene glycol in the formula) by stirring at a temperature of 35-45℃ to obtain a preservative pre-solution; add glycerol, the remaining propylene glycol, sodium citrate, and the preservative pre-solution to the polymer mixture, seal and heat to a temperature of 35-45℃, and stir at 500 r / min for 20 min until the system is completely homogeneous; S4: Cool to 30-35℃, add compound natural antibacterial extract and povidone, stir at 500r / min for 15min until uniform; add pretreated chitosan, stir at 300r / min for 15min until uniformly dispersed; S5: Cool to room temperature, and while stirring, slowly add 22wt% triethanolamine aqueous solution to adjust the pH of the system to 6.5; then degas under vacuum for 10 min at a low stirring speed of 150 r / min to obtain a gel.

[0043] In the above embodiments, the method of adding the drug component to the gel is optional: The drug components are added in sections during steps S3 and / or S4: 1. When the drug component is a water-soluble liquid or extract: add it simultaneously with the compound natural antibacterial extract in step S4.

[0044] 2. When the drug component is a poorly soluble or fat-soluble powder: first pre-disperse it with propylene glycol and / or glycerol in the formula to prepare a uniform suspension, and add it in step S3.

[0045] 3. The total amount of drug components added is 0.5 to 20 wt% of the final mass of the gel.

[0046] In the above embodiments, the etherified modified konjac glucomannan is a mixture of graft copolymers with uneven substitution degrees and cannot be represented by a unified chemical structural formula. The rosmarinic acid-grafted hydroxypropyl chitosan is a mixture of graft copolymers with uneven grafting rates and structures and cannot be represented by a unified chemical structural formula. The composite natural antibacterial extract is a multi-component natural mixture and cannot be represented by a unified chemical structural formula.

[0047] Comparative Example 1 The difference from Example 1 is that: etherified modified konjac glucomannan is directly replaced by konjac glucomannan, and rosmarinic acid grafted hydroxypropyl chitosan is directly replaced by hydroxypropyl chitosan.

[0048] Comparative Example 2 The difference from Example 1 is that: the etherified modified konjac glucomannan is changed to 0.65 parts, the rosmarinic acid-grafted hydroxypropyl chitosan is changed to 0.4 parts, the Bletilla striata polysaccharide is changed to 1.4 parts, and the glycerol polyacrylate is changed to 3.5 parts.

[0049] Comparative Example 3 The difference from Example 1 is that: the etherified modified konjac glucomannan is changed to 3.5 parts, the rosmarinic acid-grafted hydroxypropyl chitosan is changed to 1.4 parts, the Bletilla striata polysaccharide is changed to 0.4 parts, and the glycerol polyacrylate is changed to 0.65 parts.

[0050] Comparative Example 4 The difference from Example 1 is that in the preparation of the compound natural antibacterial extract, the ratio of Cyperus rotundus leaf: corn silk: black cumin seed = 1:5.4:3.2.

[0051] Comparative Example 5 The difference from Example 1 is that in the preparation of the compound natural antibacterial extract, the ratio of Cyperus rotundus leaf: corn silk: black cumin seed = 6.3:2.1:1.2.

[0052] Comparative Example 6 The difference from Example 1 is that fig protease is not added in the preparation of the compound natural antibacterial extract.

[0053] Comparative Example 7 The difference from Example 1 is that in the preparation of the compound natural antibacterial extract, papain and fig protease are replaced by bromelain.

[0054] Comparative Example 8 The difference from Example 1 is that in the preparation of the compound natural antibacterial extract, the HPD500 macroporous adsorption resin is replaced by S-8 macroporous adsorption resin.

[0055] The raw materials and their sources used in the above embodiments and comparative examples are as follows: Bletilla striata polysaccharide was sourced from Xi'an Muguo Biotechnology Co., Ltd., with a purity of 99%. Glyceryl polyacrylate was BASF Hispagel 200. Xanthan gum was sourced from Guangzhou Weierda Industrial Co., Ltd., with a purity of 99%. Povidone was povidone K30, sourced from Xi'an Xinfengda Pharmaceutical Excipients Co., Ltd. Hydroxyethyl cellulose was sourced from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd., with a purity of 99%. Glyceryl was sourced from Xi'an Xinfengda Pharmaceutical Excipients Co., Ltd., containing 1,2,3-propanetriol with a C3H8O3 content of not less than 98%. Propylene glycol was sourced from Xi'an Xinfengda Pharmaceutical Excipients Co., Ltd., containing 1,2-propanediol with a C3H8O2 content of not less than 98.5%. Sodium citrate was sourced from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd., with a purity of 99%. Ethylparaben was sourced from Xi'an Xinfengda Pharmaceutical Excipients Co., Ltd. Triethanolamine was sourced from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd. Konjac glucomannan was sourced from Shanxi Yishenghe Biotechnology Co., Ltd. Sodium hydroxide was sourced from Xi'an Xinfengda Pharmaceutical Excipients Co., Ltd. 2,3-Epoxypropyltrimethylammonium chloride was sourced from Hubei Qifei Pharmaceutical Chemical Co., Ltd., with a purity of 99%. Hydroxypropyl chitosan was sourced from Shandong Binzhou Zhiyuan Biotechnology Co., Ltd., in powder form. MES (2-(N-morpholino)ethanesulfonic acid), EDC (1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride), and NHS (N-hydroxysuccinimide) all had a purity of over 99%. Rosmarinic acid was sourced from Nanjing Bencao Yikang Biotechnology Co., Ltd., with a purity of over 98%. Cyperus rotundus leaves (stalks and leaves of Cyperus rotundus) were either self-made powder or purchased powder, sourced from Xi'an Siji Biotechnology Co., Ltd. Corn silk was either self-made powder or purchased powder, sourced from Anhui Sanbaimu Biotechnology Co., Ltd. Black cumin seeds were either self-made powder or purchased powder, sourced from Xi'an Weite Biotechnology Co., Ltd. Cellulase was sourced from Jiangsu Jiujia Biotechnology Co., Ltd., with an enzyme activity of 200,000 U / g. Papain was sourced from Jiangsu Yuanzhiyuan Biotechnology Co., Ltd., with an enzyme activity of 100,000 U / g. The fig protease was sourced from Shandong Yaheng Biotechnology Co., Ltd., with an enzyme activity of 800,000 U / g. The bromelain was sourced from Nanning Dongheng Huadao Biotechnology Co., Ltd., with an enzyme activity of 200,000 U / g. The HPD500 macroporous adsorption resin was sourced from Zhengzhou Aino Chemical Technology Co., Ltd., with a particle size of 0.3-1.2 mm ≥90% and a specific surface area of ​​500-550 μm. 2 / g. S-8 macroporous adsorption resin is sourced from Zhengzhou Aino Chemical Technology Co., Ltd., with a particle size of 0.315-1.25mm ≥90% and a specific surface area of ​​100-120m². 2 / g.

[0056] I. Cytotoxicity test: Sample preparation: Take each gel sample and add DMEM medium containing 10% fetal bovine serum at a ratio of 0.2 g / mL. Incubate at 37℃ and 60 r / min for 24 h to prepare a 100% concentration extract. The blank control group is pure serum-containing DMEM medium without cells, and the negative control group is high-density polyethylene reference material extract (0.2 g / mL, containing 10% fetal bovine serum DMEM, 37℃, 60 r / min, 24 h).

[0057] Detection method: L929 mouse fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin at 37℃ and 5% CO2 in an incubator, with a growth rate of 1×10⁻⁶ cells / mL. 4 Cells were seeded at a density of 1 cell / well in 96-well plates and cultured for 24 hours until adherence. The original culture medium was discarded, and 100 μL of different concentrations of sample extract was added to each well, with continued culture for 48 hours. 10 μL of CCK-8 reagent was added to each well, and the plates were incubated at 37°C in the dark for 3 hours. The absorbance (OD) was measured at 450 nm using a microplate reader. Six parallel wells were used for each sample. Cell viability (%) = (OD sample - OD blank control) / (OD negative control - OD blank control) × 100%.

[0058] II. Skin irritation test: Sample preparation: Take 0.2 g of gel sample and spread it evenly on the epidermal layer of the in vitro reconstructed human skin model, covering a contact area of ​​1 cm². 2 The negative control group was coated with an equal volume of PBS buffer.

[0059] Detection method: The treated skin model was incubated at 37℃ in a 5% CO2 incubator for 30 min; residual samples were gently rinsed with PBS buffer; MTT reagent was added and incubated for 3 h; after isopropanol lysis and extraction, the absorbance (OD) value was measured at 570 nm using a microplate reader. Three replicates were prepared for each sample. Tissue viability (%) = (OD sample - OD blank control) / (OD negative control - OD blank control) × 100%.

[0060] III. Hemolytic test: Sample preparation: The gel sample was added to physiological saline at a ratio of 0.2 g / mL and extracted at 37℃ for 24 h to obtain the sample extract; the negative control was physiological saline and the positive control was distilled water.

[0061] Detection method: Prepare a 2% rabbit erythrocyte suspension; take a test tube, add 5 mL of sample extract, physiological saline, and distilled water respectively, then add 5 mL of 2% erythrocyte suspension to each, and mix gently; incubate at 37℃ for 60 min; centrifuge at 1500 r / min for 5 min; collect the supernatant and measure the OD value at a wavelength of 540 nm. Three replicates are set for each sample. Hemolysis rate (%) = (OD value of experimental group - OD value of negative control group) / (OD value of positive control group - OD value of negative control group) × 100%.

[0062] IV. Skin Adhesion Performance Test: Sample preparation: Prepare 1cm×1cm×2mm gel sheets; remove subcutaneous fat and hair from excised pig skin, cut into 2cm×3cm suitable test pieces, and refrigerate at 4℃ for later use.

[0063] Test method: The gel sheet was tightly adhered to the surface of the detached pigskin, and a pressure of 0.5N was applied and held for 30s. The maximum peel adhesion force was measured using a texture analyzer. Five parallel samples were prepared for each sample.

[0064] V. Antibacterial performance test: Sample preparation: Gel samples were prepared into circular discs with a diameter of 6 mm and a thickness of 2 mm, sterilized by UV irradiation for 30 min, and then used aseptically.

[0065] Detected strains: Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 9027), and Candida albicans (ATCC 10231).

[0066] Detection method: Adjust the bacterial suspension concentration to 1×10⁻⁶ 8 CFU / mL was evenly spread on the surface of MHA agar medium; a portion of the gel was then coated onto the center of the medium surface in a 6 mm diameter circle. The mixture was incubated at 37°C for 24 h (bacteria) and at 28°C for 48 h (fungi), and the outer diameter of the total inhibition zone was measured. Three replicates were prepared for each sample.

[0067] VI. Moisturizing performance test: Accurately weigh 0.5 g of the gel sample and place it in a dry, clean petri dish, recording the initial mass. Place the sample in a constant temperature and humidity chamber at 25℃ and 43% relative humidity, and accurately weigh it at 1 h, 2 h, 4 h, and 8 h, recording the mass change. Three replicates are prepared for each sample. Moisture retention rate (%) = (mass after incubation / initial mass) × 100%.

[0068] VII. Compatibility testing of active ingredients: Lidocaine hydrochloride was added to the gel matrix to prepare a drug-loaded gel (final drug content 2 wt%). Lidocaine hydrochloride powder was pre-dispersed in propylene glycol according to the formulation to form a homogeneous suspension, which was then added in step S3. The drug-loaded gel was incubated at 37–40°C and 75% RH in the dark for 14 days; changes in the gel's appearance were observed (using freshly prepared drug-loaded gel as a reference). Three replicates were prepared for each sample.

[0069] Of these, Comparative Examples 1 to 3 were not tested for antibacterial properties. Comparative Examples 4 to 8 were not tested for skin adhesion, moisturizing properties, or compatibility of active ingredients.

[0070] Table 1 Test Results

[0071] Table 1 (continued) Test Results

[0072] Note: The test results are average values.

[0073] Examples 1 to 3 exhibit high adhesion, antibacterial properties, moisturizing properties, and stability. Etherified konjac glucomannan introduces cationic quaternary ammonium groups, and rosmarinic acid grafted with hydroxypropyl chitosan provides a catechol structure, achieving strong adhesion in a wet state. The multi-component polymers form an interpenetrating network, enhancing cohesion and flexibility, preventing detachment during joint bending. A complex extract of Cyperus rotundus leaf, corn silk, and black cumin seed, after targeted enzymatic hydrolysis and resin purification, is enriched with specific antimicrobial peptides and other antimicrobial components, exhibiting broad-spectrum inhibition against bacteria and fungi. The modified polysaccharide synergistically with the natural extracts eliminates the irritation of chemical antimicrobial agents, resulting in higher safety. The system pH is adjusted to 6.5-7.0, conforming to the physiological environment of the skin. The modified and purified polymers are free of free irritating groups, exhibiting excellent cell and blood compatibility. The network structure, combined with multiple moisturizers, forms a water-locking system. The components are charge-balanced, have good compatibility, and are stable for both water-soluble and lipid-soluble drug loading.

[0074] Comparative Example 1: Unmodified raw material was directly substituted; Unmodified konjac glucomannan lacks cationic groups, and rosmarinic acid-grafted hydroxypropyl chitosan was replaced with ordinary hydroxypropyl chitosan, resulting in the loss of wet adhesion active sites and a significant decrease in adhesion; Unmodified raw material has many impurities and poor solubility, leading to poor system compatibility, decreased drug loading stability, and easy deterioration.

[0075] Comparative Example 2 showed a low core substrate ratio and an imbalance of excipients; insufficient content of etherified modified konjac glucomannan and rosmarinic acid-grafted hydroxypropyl chitosan, resulting in low density of adhesive active sites and weak adhesion and cohesion; excessive auxiliary excipients disrupted the polymer compound balance, leading to a decrease in system flexibility and a slight decrease in biocompatibility.

[0076] Comparative Example 3: Excessive core substrate and insufficient auxiliary substrate; excessive core modified polymer led to excessive cross-linking density, increased gel rigidity and decreased flexibility, reduced skin adhesion and compliance, and the adhesion force was not optimal; insufficient auxiliary components such as Bletilla striata polysaccharide could not fill the interfacial micro gaps, and the moisturizing effect was weakened; excessive polymer entanglement hindered the diffusion of active ingredients.

[0077] The raw material ratios of the compound natural antibacterial extracts in Comparative Examples 4 and 5 were unbalanced; the proportions of Cyperus rotundus leaf, corn silk, and black cumin seed deviated from the optimal range, and the synergistic effect of the plant antibacterial active ingredients was destroyed, resulting in a decrease in efficacy.

[0078] Comparative Example 6 lacked figase; figase specifically cleaves proteins, releasing antimicrobial peptides and promoting the release of antimicrobial active ingredients; the absence of this enzyme leads to incomplete enzymatic hydrolysis, reduced extraction rate of effective ingredients, increased impurities, and decreased antimicrobial activity of the extract.

[0079] Comparative Example 7 was replaced with a single bromelain; the synergistic effect of papain and fig protease in deep enzymatic hydrolysis maximizes the release of antibacterial components; after being replaced with a single bromelain, the enzyme cleavage sites are different, the enzymatic hydrolysis is not targeted enough, the extraction rate of active ingredients is low and the product contains many impurities.

[0080] Comparative Example 8 was replaced with S-8; HPD500 resin showed strong selectivity and high enrichment efficiency for adsorbing moderately polar antibacterial components; S-8 resin's polarity and pore size were mismatched, making it unable to effectively retain key antibacterial substances, resulting in loss of active ingredients and insufficient removal of impurities, leading to a decline in antibacterial performance.

Claims

1. A highly adhesive gel matrix material, characterized in that, The raw materials include the following parts by weight: 1-1.8 parts of etherified modified konjac glucomannan, 3-4 parts of rosmarinic acid-grafted hydroxypropyl chitosan, 0.5-0.8 parts of Bletilla striata polysaccharide, 2-4 parts of compound natural antibacterial extract, 0.3-0.5 parts of glyceryl polyacrylate, 0.2-0.4 parts of xanthan gum, 0.5-0.8 parts of povidone, 0.5-0.8 parts of hydroxyethyl cellulose, 8-10 parts of glycerol, 4-5 parts of propylene glycol, 0.5-0.8 parts of sodium citrate, 0.03-0.05 parts of ethylparaben, 90-95 parts of purified water, and 20-22 wt% triethanolamine aqueous solution to adjust the pH of the system to 6.5-7.

0.

2. The highly adhesive gel matrix material according to claim 1, characterized in that, The etherified modified konjac glucomannan is prepared by alkalizing konjac glucomannan with sodium hydroxide aqueous solution, then performing an epoxy ring-opening etherification reaction with 2,3-epoxypropyltrimethylammonium chloride, followed by neutralization, ethanol precipitation, washing, drying and pulverization. The rosmarinic acid-grafted hydroxypropyl chitosan is prepared by dissolving hydroxypropyl chitosan in MES buffer containing propylene glycol, activating it with EDC and NHS, and then undergoing an amidation grafting reaction with rosmarinic acid, followed by dialysis purification and freeze-drying. The compound natural antibacterial extract is prepared by enzymatic hydrolysis of a mixture of Cyperus rotundus leaf, corn silk and black cumin seed powder by cellulase, followed by enzymatic hydrolysis by papain and fig protease, purification by HPD500 macroporous adsorption resin column, and freeze-drying of the eluent.

3. The highly adhesive gel matrix material according to claim 2, characterized in that, The concentration of the sodium hydroxide aqueous solution is 4-6 wt%; the amount of 2,3-epoxypropyltrimethylammonium chloride used is 20-25% of the mass of konjac glucomannan; the epoxy ring-opening etherification reaction is carried out at 55-60°C.

4. A highly adhesive gel matrix material according to claim 2 or 3, characterized in that, The preparation method of the etherified modified konjac glucomannan includes: adding konjac glucomannan to a 4-6 wt% sodium hydroxide aqueous solution, stirring and alkalizing to form an alkaline dispersion; adding 20-25% by weight of 2,3-epoxypropyltrimethylammonium chloride to the alkaline dispersion, stirring and reacting at 55-60℃, cooling to room temperature, adjusting the pH to 7.0-7.5, adding anhydrous ethanol, stirring and settling, filtering, washing the filter cake with anhydrous ethanol, vacuum drying, and pulverizing to obtain the etherified modified konjac glucomannan.

5. The highly adhesive gel matrix material according to claim 2, characterized in that, The pH of the MES buffer is 5.5–6.0; the amount of EDC used is 30–35% of the mass of hydroxypropyl chitosan; the amount of NHS used is 20–30% of the mass of hydroxypropyl chitosan; the amount of rosmarinic acid used is 20–30% of the mass of hydroxypropyl chitosan; and the dialysis is performed using a dialysis bag with a molecular weight cutoff of 10 kDa.

6. A highly adhesive gel matrix material according to claim 2 or 5, characterized in that, The preparation method of rosmarinic acid-grafted hydroxypropyl chitosan includes: dissolving hydroxypropyl chitosan in MES buffer at pH 5.5-6.0, adding 1-2 wt% propylene glycol (based on the total mass of MES buffer and hydroxypropyl chitosan), and stirring to dissolve; sequentially adding 30-35% EDC and 20-30% NHS (based on the mass of hydroxypropyl chitosan), and stirring to activate; adding 20-30% rosmarinic acid (based on the mass of hydroxypropyl chitosan), and stirring to react at 25-35°C; dialyzing with a dialysis bag containing a molecular weight cutoff of 10 kDa in deionized water, and freeze-drying to obtain rosmarinic acid-grafted hydroxypropyl chitosan.

7. The highly adhesive gel matrix material according to claim 2, characterized in that, The mass ratio of Cyperus rotundus leaves, corn silk, and black cumin seeds is (4-4.5):(3-3.2):(2-2.5); the amount of cellulase used is 0.8-1.2 wt% of the mixed powder mass, and the cellulase is enzymatically hydrolyzed at pH 4.8-5.2 and 52-55℃ for 2-3 hours; the amount of papain and fig protease used is 0.5-0.8 wt% of the mixed powder mass, and the papain and fig protease are enzymatically hydrolyzed at pH 5.5-6.0 and 53-58℃ for 1.5-2 hours; the eluent is obtained by elution with a 50-55 vol% ethanol aqueous solution.

8. A highly adhesive gel matrix material according to claim 2 or 7, characterized in that, The preparation method of the compound natural antibacterial extract includes: weighing the raw material dry powder according to the mass ratio of Cyperus rotundus leaf: corn silk: black cumin seed = (4-4.5):(3-3.2):(2-2.5), mixing to obtain a mixed powder, adding purified water, adjusting the pH to 4.8-5.2, adding 0.8-1.2 wt% of cellulase of the mixed powder, enzymatically hydrolyzing at 52-55℃ for 2-3 hours; inactivating the enzyme at 80-85℃, cooling to 53-58℃, adjusting the pH to 5.5-6.0, and adding 0.5-0.5 wt% of the mixed powder. Papain and fig protease (8 wt%) were hydrolyzed at 53–58 °C for 1.5–2 h; enzymes were inactivated at 80–85 °C and cooled to room temperature; the mixture was filtered, concentrated, and the resulting sample solution was loaded onto an HPD500 macroporous adsorption resin column and rinsed with 3–4 BV of deionized water to remove impurities; 2–3 BV of the solution was eluted with 20–25 vol% ethanol aqueous solution and discarded, followed by 3–5 BV of the solution being eluted with 50–55 vol% ethanol aqueous solution and the eluent was collected, concentrated under reduced pressure, freeze-dried, pulverized, and sieved to obtain a complex natural antibacterial extract.

9. The method for preparing a highly adhesive gel matrix material according to claim 1, characterized in that, Includes the following steps: S1: Take 8-10% of the total mass of purified water by mass, add rosmarinic acid-grafted hydroxypropyl chitosan, stir to form a uniform slurry, and obtain pretreated chitosan. S2: According to the mass fractions, first add etherified modified konjac glucomannan, Bletilla striata polysaccharide, glyceryl polyacrylate, and xanthan gum to the remaining purified water, stir to disperse and swell; then add hydroxyethyl cellulose, stir to swell, and obtain a polymer mixture; S3: Dissolve ethylparaben in propylene glycol at 2-3 times its mass to obtain a preservative pre-solution; add glycerol, the remaining propylene glycol, sodium citrate, and the preservative pre-solution to the polymer mixture, and stir until homogeneous; S4: Add compound natural antibacterial extract and povidone, stir well; add pretreated chitosan, stir well; S5: Adjust the pH to 6.5-7.0 using a 20-22 wt% triethanolamine aqueous solution; degas under vacuum to obtain a gel.

10. The method for preparing a highly adhesive gel matrix material according to claim 9, characterized in that, In the preparation of the gel, the drug component is added in step S3 and / or S4: When the drug component is a water-soluble liquid or extract, it is added simultaneously with the compound natural antibacterial extract in step S4. When the drug component is a poorly soluble or fat-soluble powder, it is first pre-dispersed with propylene glycol and / or glycerol in the formula to prepare a uniform suspension, which is then added in step S3. The total amount of drug components added is 0.5 to 20 wt% of the final mass of the gel.

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