An intimate care type external use bacteriostatic gel and a preparation method thereof

Abstract

This invention provides a topical antibacterial gel for intimate area care and its preparation method. By weight percentage, its constituent raw materials include: 1.0-2.5% HPS graft copolymer, 0.8-1.8% BPPR graft triblock copolymer, 0.5-1.5% TCC nanocapsules, 0.6-1.2% N-acetyl-modified matrine, 0.3-0.7% polyethylene glycol-modified lysozyme, 2.8-4.2% 1,3-propanediol, 0.5-1.0% carbomer, 0.4-0.7% arginine, 0.2-0.4% ceramide NP, 0.1-0.3% sodium hyaluronate, 0.1-0.3% oat alkaloids, 0.03-0.06% propylparaben, with the balance being deionized water. The antibacterial gel of this invention possesses comprehensive technical effects of antibacterial activity, moisturizing, mucosal repair, soothing and anti-inflammatory properties, pH regulation, and mucosal nutrient supplementation, and is characterized by its mildness, low irritation, and stable action.

Description

Technical Field

[0001] This invention relates to the field of antibacterial gel technology, specifically to a topical antibacterial gel for intimate area care and its preparation method. Background Technology

[0002] As a special mucous membrane tissue in the human body, the private parts are susceptible to invasion by pathogenic bacteria such as Staphylococcus aureus and Candida albicans, which can cause inflammatory reactions and mucosal damage. Therefore, topical antibacterial gels for private parts care have become an important product for daily care and to help improve discomfort. Their core needs include antibacterial properties, mucosal protection, and gentle compatibility. Existing technologies mostly achieve basic functions by integrating basic antibacterial ingredients with moisturizing matrix.

[0003] Existing topical antibacterial gels for intimate area care generally suffer from insufficient synergistic effects and poor stability. Most products struggle to achieve a comprehensive effect of highly effective antibacterial action, long-lasting moisturizing, and repair of damaged mucous membranes simultaneously. Some products also fail to meet the sensitive characteristics and multiple care needs of intimate area mucous membranes due to highly irritating ingredients or a single mechanism of action. There is an urgent need to develop a topical antibacterial gel that combines comprehensive care effects with gentle and stable properties. Summary of the Invention

[0004] To address the problems existing in the prior art, the present invention provides a topical antibacterial gel for intimate area care and its preparation method, which enables the antibacterial gel to have comprehensive technical effects of antibacterial, moisturizing, mucosal repair, soothing and anti-inflammatory, pH regulation and mucosal nutrition supplementation, and has the characteristics of being mild, low-irritant and stable.

[0005] To achieve the above objectives, the present invention provides the following technical solution: This application discloses a topical antibacterial gel for feminine hygiene, comprising, by weight percentage: 1.0-2.5% HPS graft copolymer ("H" represents hyaluronic acid, "P" represents polylysine, and "S" represents Asiaticoside), 0.8-1.8% BPPR graft triblock copolymer ("B" represents baicalin, the two "P"s represent polycaprolactone and polyethylene glycol respectively, and "R" represents pH-responsive monomer), and 0.8-1.8% TCC nanocapsules ("T" represents tea tree oil). Oil), the two "C"s represent chitosan and cyclodextrin respectively) 0.5-1.5%, N-acetyl-modified matrine 0.6-1.2%, polyethylene glycol-modified lysozyme 0.3-0.7%, 1,3-propanediol 2.8-4.2%, carbomer 0.5-1.0%, arginine 0.4-0.7%, ceramide NP 0.2-0.4%, sodium hyaluronate 0.1-0.3%, oat alkaloids 0.1-0.3%, propylparaben 0.03-0.06%, the balance being deionized water.

[0006] By setting up the above technical solution, the three core components—HPS grafted copolymer, BPPR grafted triblock copolymer, and TCC nanocapsules—exert synergistic effects of moisturizing, antibacterial, and repairing; pH-responsive targeted drug release and anti-inflammatory adhesion; and sustained-release antibacterial and irritation-reducing effects, respectively. These, along with the enhanced mucosal penetration and broad-spectrum antibacterial efficacy of N-acetyl-modified matrine, and the extended half-life and bacterial cell wall hydrolysis of polyethylene glycol-modified lysozyme, form a synergistic antibacterial system. Furthermore, 1,3-propanediol and sodium hyaluronate synergistically enhance the moisturizing effect. Ceramide NP helps repair the mucosal barrier and resist irritation, oat alkaloids soothe sensitivity and reduce inflammation, carbomer builds an easily spreadable gel matrix, arginine regulates the pH of the system and replenishes mucosal nutrition, propylparaben provides highly effective preservation, and deionized water serves as a solvent to ensure uniform dispersion of all components. The combined effect of these components gives this feminine hygiene topical antibacterial gel a comprehensive range of effects, including antibacterial, moisturizing, mucosal repair, soothing and anti-inflammatory, pH regulation, and mucosal nutrition replenishment. It is also characterized by its mildness, low irritation, and stable action.

[0007] Preferably, in the polyethylene glycol-modified lysozyme, the polyethylene glycol has a weight-average molecular weight of 2-5 kDa and an enzyme activity of 20,000-21,000 U / mg; the carbomer used is Pemulen TR-1 with a crosslinking degree of 20-30%; and the sodium hyaluronate has a weight-average molecular weight of 50-80 kDa.

[0008] By setting up the above technical solutions, polyethylene glycol with a weight average molecular weight of 2-5 kDa can reduce the enzymatic loss of lysozyme and prolong its half-life; the high enzyme activity of 20,000-21,000 U / mg can efficiently hydrolyze bacterial cell walls to exert antibacterial effects; the 20-30% cross-linking degree of carbomer Pemulen TR-1 enables it to construct a stable gel matrix that is easy to spread, suitable for external use; and sodium hyaluronate with a weight average molecular weight of 50-80 kDa is conducive to deep moisturizing and ingredient penetration. The three work synergistically to ensure the antibacterial efficacy and formulation stability of the gel, while also enhancing the moisturizing effect and improving the overall performance of the antibacterial gel.

[0009] Preferably, the HPS graft copolymer is a hyaluronic acid-polylysine-asiaticoside graft copolymer, and its constituent raw materials include, by weight, 8-9 parts of hyaluronic acid, 5-6 parts of ε-polylysine, 2.5-3.5 parts of asiaticoside, 1.8-2.2 parts of carbodiimide hydrochloride, 1.3-1.7 parts of N-hydroxythiosuccinimide, and 150-180 parts of phosphate buffer.

[0010] By setting up the above technical solution, the hyaluronic acid-polylysine-asiaticoside graft copolymer uses hyaluronic acid, ε-polylysine, and asiaticoside as core functional raw materials. Under the activation of carbodiimide hydrochloride and N-hydroxythiosuccinimide, the copolymer is formed by covalent grafting in a suitable environment provided by phosphate buffer. It can synergistically exert the moisturizing effect of hyaluronic acid, the antibacterial effect of ε-polylysine, and the repairing effect of asiaticoside. At the same time, the covalent bonding effect enhances the stability and synergy of the efficacy of each component.

[0011] Preferably, the weight-average molecular weight of hyaluronic acid is 80-150 kDa; the weight-average molecular weight of ε-polylysine is 3000-5000 Da; the molar concentration of phosphate buffer is 0.008-0.010 mol / L, and the pH value is 7.2-7.4.

[0012] By setting up the above technical solution, hyaluronic acid with a weight-average molecular weight of 80-150 kDa is conducive to building a stable three-dimensional network structure, ε-polylysine with a weight-average molecular weight of 3000-5000 Da can fully exert its antibacterial activity and is suitable for grafting reaction, and phosphate buffer with a molar concentration of 0.008-0.010 mol / L and a pH of 7.2-7.4 can provide a mild and stable reaction environment, maintain the activity of each component and promote the effective grafting of hyaluronic acid, ε-polylysine and asiaticoside, thereby ensuring that the formed hyaluronic acid-polylysine-asiaticoside graft copolymer can stably exert the synergistic effects of moisturizing, antibacterial and repairing.

[0013] Preferably, the preparation method of the hyaluronic acid-polylysine-asiaticoside graft copolymer includes the following steps: 1) Dissolve hyaluronic acid in 120-140 parts of phosphate buffer, stir at 280-320 r / min at 32-36℃ for 1.0-1.2 h, add carbodiimide hydrochloride and N-hydroxythiosuccinimide, stir at 280-320 r / min at 35-37℃ for 35-45 min under nitrogen protection to obtain the activation solution; 2) Dissolve ε-polylysine in the remaining phosphate buffer and dissolve asiaticoside in 5-8 parts of anhydrous ethanol. After mixing the two, slowly add them dropwise to the activation solution at a rate of 1-2 drops / s. After the addition is complete, raise the temperature to 42-46℃ and stir at 320-360 r / min for 7-9 hours. 3) Transfer the reaction solution obtained in 2) into a dialysis bag with a molecular weight cutoff of 25,000-35,000 Da, and dialyze for 24 hours with an additional phosphate buffer (molar concentration of 0.008-0.010 mol / L, pH value of 7.2-7.4) of 8-10 times the volume of the reaction solution (replace the buffer with fresh water every 4 hours, and use the same amount each time, which is 8-10 times the volume of the reaction solution). Then dialyze for 16-18 hours with deionized water of 8-10 times the volume of the reaction solution (replace the deionized water with fresh water every 6 hours, and use the same amount each time, which is 8-10 times the volume of the reaction solution). 4) The reaction solution obtained in 3) is spray-dried at an inlet temperature of 85-95℃ and an outlet temperature of 45-50℃ to obtain a primary powder, and then dried at a vacuum of 42-46℃ and 0.09-0.1MPa for 10-12 hours to obtain a hyaluronic acid-polylysine-centicolic acid graft copolymer.

[0014] By setting up the above technical solution, the active groups of hyaluronic acid are first activated, and then ε-polylysine, asiaticoside and activation solution are fully reacted to achieve effective grafting. Impurities are removed and purity is improved by dialysis under specific conditions. Finally, the product is formed by spray drying and vacuum drying. This not only ensures the successful synthesis and structural stability of the hyaluronic acid-polylysine-asiaticoside graft copolymer, but also improves the purity of the product, laying the foundation for its subsequent synergistic effects of moisturizing, antibacterial and repairing.

[0015] Preferably, the BPPR grafted triblock copolymer is a baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer, and its constituent raw materials include, by weight parts: 6-7 parts of baicalin, 10-12 parts of polycaprolactone, 5-6 parts of polyethylene glycol, 2.3-2.7 parts of pH-responsive monomer, 0.10-0.14 parts of stannous octoate, 0.8-1.2 parts of carbodiimide hydrochloride, 80-90 parts of anhydrous N,N-dimethylformamide, and 200-240 parts of diethyl ether; the weight average molecular weight of polycaprolactone is 5000-8000 Da, and the weight average molecular weight of polyethylene glycol is 2000-4000 Da; the pH-responsive monomer is methacrylic acid or 4-vinylpyridine.

[0016] By setting up the above technical solution, the baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer uses baicalin, polycaprolactone, polyethylene glycol, and pH-responsive monomers (methacrylic acid or 4-vinylpyridine) as core functional raw materials. Under the catalysis of stannous octoate and the activation of carbodiimide hydrochloride, a triblock copolymer structure is formed in the dissolution environment provided by anhydrous N,N-dimethylformamide. Diethyl ether promotes subsequent purification. Among them, polycaprolactone with a weight average molecular weight of 5000-8000 Da and polyethylene glycol with a weight average molecular weight of 2000-4000 Da ensure the stability of the skeleton and the adhesion of the mucosa. The pH-responsive monomer endows the copolymer with intelligent drug release characteristics, and baicalin exerts anti-inflammatory effects, ultimately achieving the synergistic effect of pH-responsive targeted drug release, long-lasting adhesion, and anti-inflammatory efficacy.

[0017] Preferably, the preparation method of baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer includes the following steps: (1) Add polycaprolactone, polyethylene glycol and stannous octoate to a three-necked flask, purge the air with nitrogen three times; heat to 135-145℃ and stir at 180-220 r / min for 5-7 h. (2) Add pH-responsive monomers to the mixture obtained in (1) and stir at 180-220 r / min for 3-4 h at 120-130 °C to obtain a triblock system; (3) Dissolve baicalin in anhydrous N,N-dimethylformamide, add carbodiimide hydrochloride, and stir at 250-300 r / min for 1.2-1.8 h at 28-32℃ to obtain an activated baicalin solution; (4) Add the activated baicalin solution dropwise into the triblock system, heat to 62-68℃, and stir at 250-300 r / min for 10-12 h under nitrogen protection; (5) After cooling the reaction solution obtained in (4) to room temperature, slowly pour it into diethyl ether to precipitate for 2-3 hours. Filter and collect the precipitate. Wash it 3 times with hydrochloric acid solution with a molar concentration of 0.08-0.10 mol / L (each time the amount of hydrochloric acid is 2-3 times the volume of the precipitate. After each washing, centrifuge at 8000-10000 r / min for 5-8 minutes and discard the supernatant). Then wash it with deionized water until neutral. Dry it under vacuum at 62-68℃ for 13-15 hours to obtain baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer.

[0018] By setting up the above technical solution, this preparation method avoids the oxidation of components during the reaction process by using nitrogen protection. First, a polycaprolactone-polyethylene glycol triblock skeleton is synthesized and grafted with a pH-responsive monomer. Then, baicalin is activated by carbodiimide hydrochloride to effectively combine with the triblock system. Finally, impurities are removed by ether precipitation, acid and alkali washing purification and vacuum drying. This method not only ensures the structural integrity and purity of the baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer, but also ensures that it has the synergistic effects of pH-responsive targeted drug release, mucosal adhesion prolonging action time and anti-inflammation.

[0019] Preferably, the TCC nanocapsules are tea tree oil-chitosan-cyclodextrin nanocapsules, and by weight, their constituent raw materials include: 3.5-4.5 parts tea tree oil, 1.0-1.4 parts chitosan, 3-4 parts β-cyclodextrin, 0.4-0.6 parts sodium tripolyphosphate, 55-65 parts 1% glacial acetic acid solution, 0.8-1.6 parts polyglycerol-3 stearate, and 20-30 parts deionized water; the degree of deacetylation of chitosan is 90-92%, and the weight average molecular weight is 50-100 kDa.

[0020] By setting up the above technical solution, the tea tree oil-chitosan-cyclodextrin nanocapsule uses tea tree oil as the core antibacterial raw material. β-cyclodextrin can encapsulate the tea tree oil to reduce its irritation. Chitosan with a degree of deacetylation of 90-92% and a weight-average molecular weight of 50-100kDa can enhance mucosal adhesion. Polyglycerol-3-stearate plays an emulsifying role to ensure the uniformity and stability of the system. Sodium tripolyphosphate acts as a cross-linking agent to promote the formation of the microcapsule structure. A 1% glacial acetic acid solution can promote the dissolution of chitosan. Deionized water provides a dissolution and dispersion environment. The synergistic effect of each component gives the nanocapsule the effects of sustained-release antibacterial, mild and low-irritation, and mucosal adhesion and retention.

[0021] Preferably, the preparation method of tea tree oil-chitosan-cyclodextrin nanocapsules includes the following steps: a. Dissolve chitosan in glacial acetic acid solution, stir at 300-350 r / min for 5-7 h at 28-32℃, add β-cyclodextrin, and continue stirring at 300-350 r / min for 1-2 h to obtain the aqueous phase; b. Preheat tea tree oil in a water bath at 40-45℃, add polyglycerol-3 stearate, and stir at 200-250 r / min for 10-15 min to obtain the oil phase; c. Slowly drip the oil phase into the aqueous phase at a rate of 1-3 drops / s, while simultaneously homogenizing at a high speed of 10,000-12,000 r / min for 8-12 minutes to form the primary emulsion; d. Dissolve sodium tripolyphosphate in deionized water to obtain a sodium tripolyphosphate solution. Add the sodium tripolyphosphate solution dropwise to the primary emulsion and stir at 500-700 r / min for 40-60 min. Then centrifuge at 4℃ and 10000-12000 r / min for 25-35 min, collect the precipitate, and wash it three times with added deionized water. Dry it under vacuum at 50-55℃ for 8-10 h to obtain tea tree oil-chitosan-cyclodextrin nanocapsules.

[0022] By setting up the above technical solution, glacial acetic acid solution promotes the dissolution of chitosan and forms a stable aqueous phase with β-cyclodextrin, while polyglycerol-3-stearate promotes the emulsification of tea tree oil to form a homogeneous oil phase. High-speed homogenization achieves nanoscale dispersion to form a primary emulsion, which is then stabilized by sodium tripolyphosphate ion crosslinking. Subsequent centrifugation and washing remove impurities, followed by vacuum drying to form the final product. This not only achieves effective encapsulation of tea tree oil to reduce irritation, but also enhances mucosal adhesion with the help of chitosan. At the same time, the nanostructure improves the efficiency of component action, ultimately giving the tea tree oil-chitosan-cyclodextrin nanocapsules the synergistic effects of sustained-release antibacterial, mild and low-irritation, and long-lasting mucosal retention.

[0023] This application also discloses a method for preparing a topical antibacterial gel for feminine hygiene, comprising the following steps: S1. Preparation of aqueous phase: Deionized water, 1,3-propanediol, and sodium hyaluronate were added to an aqueous phase reactor and stirred at 350-450 rpm for 12-15 min at 32-36°C. HPS graft copolymer was then added, and the mixture was heated to 52-58°C and stirred at 650-750 rpm for 22-28 min. The mixture was then transferred to a high-pressure homogenizer and homogenized 4-6 times at 850-950 bar to obtain the aqueous phase. S2, Oil phase preparation: Ceramide NP, carbomer and TCC nanocapsules were added to an oil phase pot and stirred at 250-300 r / min for 18-22 min at 68-72 °C; then BPPR grafted triblock copolymer was added and stirred at 250-300 r / min for 12-15 min at 68-72 °C to obtain the oil phase. S3, Emulsification: The oil phase is slowly added to the water phase, and the mixture is homogenized and stirred at a speed of 2800-3200 r / min for 22-28 min under the conditions of temperature 62-68℃ and vacuum degree of -0.088MPa to -0.096MPa to obtain an emulsion. S4, Component Mixing: After cooling the emulsion to 46-52℃, add N-acetyl-modified matrine and stir at 450-550 rpm for 16-20 min; cool to 39-43℃, then add polyethylene glycol-modified lysozyme and oat alkaloids and stir at 380-420 rpm for 12-16 min; finally cool to 33-37℃, add propylparaben and stir at 320-380 rpm for 10-15 min; then adjust the pH to 5.5-6.0 with arginine to obtain a gel. S5. Post-sterilization treatment: The gel was filtered through a 0.20-0.22 μm microporous membrane at a dose of 26-32 kGy. 60 Sterilize under Coγ rays for 16-22 min, then degas under vacuum conditions of -0.09 MPa to -0.095 MPa for 15-25 min, and aseptically fill to obtain a feminine hygiene-care topical antibacterial gel.

[0024] By implementing the above technical solutions, high-pressure homogenization improves the dispersion uniformity and mucosal penetration efficiency of various components in the aqueous phase. Vacuum high-speed homogenization emulsification ensures the full fusion of the oil and aqueous phases, guaranteeing gel structure stability. Staged cooling and addition of functional components avoids high-temperature degradation of the efficacy of active components such as N-acetyl-modified matrine and polyethylene glycol-modified lysozyme. 60 Co-γ ray sterilization and microporous membrane filtration achieve residue-free sterilization. Combined with vacuum degassing and pH adjustment (5.5-6.0), this ensures product safety and user comfort while allowing core components such as hyaluronic acid-polylysine-asiaticoside graft copolymer, baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer, and tea tree oil-chitosan-cyclodextrin nanocapsules to fully exert their synergistic effects, ultimately achieving comprehensive effects such as antibacterial, moisturizing, and mucosal repair.

[0025] The beneficial effects of this invention are as follows: The three core components—HPS grafted copolymer, BPPR grafted triblock copolymer, and TCC nanocapsules—exhibit synergistic effects of moisturizing, antibacterial, and repairing; pH-responsive targeted drug release and anti-inflammatory adhesion; and sustained-release antibacterial and irritation-reducing effects. These, along with N-acetyl-modified matrine for enhanced mucosal penetration and broad-spectrum antibacterial efficacy, and polyethylene glycol-modified lysozyme for extended half-life and bacterial cell wall hydrolysis, form a synergistic antibacterial system. 1,3-Propanediol and sodium hyaluronate synergistically enhance moisturizing effects, ceramide NP aids in mucosal barrier repair and anti-irritation, oat alkaloids soothe sensitivity and reduce inflammation, carbomer constructs an easily spreadable gel matrix, arginine regulates the pH and replenishes mucosal nutrients, propylparaben provides highly effective preservative protection, and deionized water acts as a solvent to ensure uniform dispersion of all components. The combined effects of these components give this feminine hygiene topical antibacterial gel a comprehensive range of benefits, including antibacterial, moisturizing, mucosal repair, soothing and anti-inflammatory effects, pH regulation, and mucosal nutrient replenishment. Furthermore, it is characterized by its mild, low-irritant, and stable properties.

[0026] Hyaluronic acid-polylysine-asiaticoside graft copolymer uses hyaluronic acid, ε-polylysine, and asiaticoside as core functional ingredients. Under the activation of carbodiimide hydrochloride and N-hydroxythiosuccinimide, a copolymer is formed through covalent grafting in a suitable environment provided by phosphate buffer. It can synergistically exert the moisturizing effect of hyaluronic acid, the antibacterial effect of ε-polylysine, and the repairing effect of asiaticoside. At the same time, the covalent bonding enhances the stability and synergy of the efficacy of each component. Detailed Implementation

[0027] 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 in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] Example 1: This embodiment discloses a topical antibacterial gel for feminine hygiene. By weight percentage, its constituent ingredients include: 1.0% HPS graft copolymer, 0.8% BPPR graft triblock copolymer, 0.5% TCC nanocapsules, 0.6% N-acetyl-modified matrine, 0.3% polyethylene glycol-modified lysozyme, 2.8% 1,3-propanediol, 0.5% carbomer, 0.4% arginine, 0.2% ceramide NP, 0.1% sodium hyaluronate with a weight-average molecular weight of 50 kDa, 0.1% oat alkaloids, 0.03% propylparaben, and the balance being deionized water. In the polyethylene glycol-modified lysozyme, the polyethylene glycol has a weight-average molecular weight of 2 kDa and an enzyme activity of 20,000 U / mg. The carbomer used is Pemulen TR-1 with a crosslinking degree of 20%.

[0029] The HPS graft copolymer is a hyaluronic acid-polylysine-asiaticoside graft copolymer. By weight, its constituent raw materials include: 8 parts of 80kDa hyaluronic acid, 5 parts of ε-polylysine with a weight average molecular weight of 3000Da, 2.5 parts of asiaticoside, 1.8 parts of carbodiimide hydrochloride, 1.3 parts of N-hydroxythiosuccinimide, and 150 parts of phosphate buffer. The phosphate buffer has a molar concentration of 0.008mol / L and a pH of 7.2.

[0030] The preparation method of hyaluronic acid-polylysine-asiaticoside graft copolymer includes the following steps: 1) Dissolve hyaluronic acid in 120 parts of phosphate buffer, stir at 280 r / min for 1.0 h at 32 °C, add carbodiimide hydrochloride and N-hydroxythiosuccinimide, stir at 280 r / min for 35 min at 35 °C under nitrogen protection to obtain the activation solution. 2) Dissolve ε-polylysine in the remaining phosphate buffer and dissolve asiaticoside in 5 parts of anhydrous ethanol. Mix the two and slowly add them dropwise to the activation solution at a rate of 1 drop / s. After the addition is complete, heat the solution to 42°C and stir at 320 r / min for 7 h. 3) Transfer the reaction solution obtained in 2) into a dialysis bag with a molecular weight cutoff of 25000 Da, and dialyze for 24 hours with an additional phosphate buffer (molar concentration of 0.008 mol / L, pH value of 7.2) of 8 times the volume of the reaction solution (replace with fresh buffer every 4 hours, and use the same amount each time, which is 8 times the volume of the reaction solution). Then dialyze for 16 hours with deionized water of 8 times the volume of the reaction solution (replace with fresh deionized water every 6 hours, and use the same amount each time, which is 8 times the volume of the reaction solution). 4) The reaction solution obtained in 3) was spray-dried at an inlet temperature of 85℃ and an outlet temperature of 45℃ to obtain a primary powder, and then dried at 42℃ and 0.09MPa vacuum for 10h to obtain a hyaluronic acid-polylysine-centicolic acid graft copolymer.

[0031] The BPPR grafted triblock copolymer is a baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer. By weight, its constituent raw materials include: 6 parts baicalin, 10 parts polycaprolactone with a weight average molecular weight of 5000 Da, 5 parts polyethylene glycol with a weight average molecular weight of 2000 Da, 2.3 parts methacrylic acid, 0.10 parts stannous octoate, 0.8 parts carbodiimide hydrochloride, 80 parts anhydrous N,N-dimethylformamide, and 200 parts diethyl ether.

[0032] The preparation method of baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer includes the following steps: (1) Add polycaprolactone, polyethylene glycol and stannous octoate to a three-necked flask, purge the air with nitrogen three times; heat to 135°C and stir at 180 r / min for 5 h. (2) Add methacrylic acid to the mixture obtained in (1) and stir at 180 r / min for 3 h at 120 °C to obtain a triblock system; (3) Dissolve baicalin in anhydrous N,N-dimethylformamide, add carbodiimide hydrochloride, and stir at 250 r / min for 1.2 h at 28 °C to obtain an activated baicalin solution; (4) The activated baicalin solution was added dropwise to the triblock system, heated to 62°C, and stirred at 250 r / min for 10 h under nitrogen protection; (5) After cooling the reaction solution obtained in (4) to room temperature, slowly pour it into diethyl ether to precipitate for 2 hours. Filter and collect the precipitate. Wash it three times with hydrochloric acid solution with a molar concentration of 0.08 mol / L (each time the amount of water used is twice the volume of the precipitate. After each washing, centrifuge at 8000 r / min for 5 min, discard the supernatant and retain the precipitate). Then wash it with deionized water until neutral. Dry it under vacuum at 62℃ for 13 hours to obtain baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer.

[0033] TCC nanocapsules are tea tree oil-chitosan-cyclodextrin nanocapsules. By weight, their constituent raw materials include: 3.5 parts tea tree oil, 1.0 part chitosan, 3 parts β-cyclodextrin, 0.4 parts sodium tripolyphosphate, 55 parts 1% glacial acetic acid solution, 0.8 parts polyglycerol-3 stearate, and 20 parts deionized water; the degree of deacetylation of chitosan is 90%, and the weight average molecular weight is 50 kDa.

[0034] The preparation method of tea tree oil-chitosan-cyclodextrin nanocapsules includes the following steps: a. Dissolve chitosan in glacial acetic acid solution, stir at 300 r / min for 5 h at 28 °C, add β-cyclodextrin, and continue stirring at 300 r / min for 1 h to obtain the aqueous phase; b. Preheat tea tree oil in a water bath at 40°C, add polyglycerol-3 stearate, and stir at 200 r / min for 10 min to obtain the oil phase; c. Slowly drip the oil phase into the aqueous phase at a rate of 1 drop / s, while simultaneously homogenizing at a high speed of 10,000 r / min for 8 minutes to form the primary emulsion; d. Dissolve sodium tripolyphosphate in deionized water to obtain a sodium tripolyphosphate solution. Add the sodium tripolyphosphate solution dropwise to the primary emulsion and stir at 500 r / min for 40 min. Then centrifuge at 4℃ and 10000 r / min for 25 min, collect the precipitate, and wash it three times with added deionized water. Dry it under vacuum at 50℃ for 8 h to obtain tea tree oil-chitosan-cyclodextrin nanocapsules.

[0035] This embodiment also discloses a method for preparing a topical antibacterial gel for feminine hygiene, comprising the following steps: S1. Preparation of aqueous phase: Deionized water, 1,3-propanediol, and sodium hyaluronate were added to an aqueous phase pot and stirred at 350 rpm for 12 min at 32 °C. HPS graft copolymer was added, and the mixture was heated to 52 °C and stirred at 650 rpm for 22 min. The mixture was then transferred to a high-pressure homogenizer and homogenized four times at 850 bar to obtain the aqueous phase. S2, Oil phase preparation: Ceramide NP, carbomer and TCC nanocapsules were added to an oil phase pot and stirred at 250 r / min for 18 min at 68 °C; then BPPR grafted triblock copolymer was added and stirred at 250 r / min for 12 min at 68 °C to obtain the oil phase. S3, Emulsification: The oil phase was slowly added to the water phase, and the mixture was homogenized and stirred at 2800 r / min for 22 min under the conditions of 62℃ and vacuum of -0.088 MPa to obtain an emulsion. S4, Component Mixing: After cooling the emulsion to 46°C, N-acetyl-modified matrine was added, and the mixture was stirred at 450 rpm for 16 min. The temperature was then lowered to 39°C, and polyethylene glycol-modified lysozyme and oat alkaloids were added, followed by stirring at 380 rpm for 12 min. Finally, the temperature was lowered to 33°C, and propylparaben was added, followed by stirring at 320 rpm for 10 min. The pH was then adjusted to 5.5 with arginine to obtain a gel. S5. Post-sterilization treatment: The gel was filtered through a 0.20 μm microporous membrane at a dose of 26 kGy. 60 Sterilize under Co γ rays for 16 min, then degas under vacuum conditions of -0.09 MPa for 15 min, and aseptically fill to obtain a feminine hygiene external antibacterial gel.

[0036] Example 2: This embodiment discloses a topical antibacterial gel for feminine hygiene. By weight percentage, its constituent ingredients include: 2.5% HPS graft copolymer, 1.8% BPPR graft triblock copolymer, 1.5% TCC nanocapsules, 1.2% N-acetyl-modified matrine, 0.7% polyethylene glycol-modified lysozyme, 4.2% 1,3-propanediol, 1.0% carbomer, 0.7% arginine, 0.4% ceramide NP, 0.3% sodium hyaluronate with a weight-average molecular weight of 80 kDa, 0.3% oat alkaloids, 0.06% propylparaben, and the balance being deionized water. In the polyethylene glycol-modified lysozyme, the polyethylene glycol has a weight-average molecular weight of 5 kDa and an enzyme activity of 21000 U / mg. The carbomer used is Pemulen TR-1 with a crosslinking degree of 30%.

[0037] The HPS graft copolymer is a hyaluronic acid-polylysine-asiaticoside graft copolymer. By weight, its constituent raw materials include: 9 parts of 150kDa hyaluronic acid, 6 parts of ε-polylysine with a weight average molecular weight of 5000Da, 3.5 parts of asiaticoside, 2.2 parts of carbodiimide hydrochloride, 1.7 parts of N-hydroxythiosuccinimide, and 180 parts of phosphate buffer. The phosphate buffer has a molar concentration of 0.010 mol / L and a pH of 7.4.

[0038] The preparation method of hyaluronic acid-polylysine-asiaticoside graft copolymer includes the following steps: 1) Dissolve hyaluronic acid in 140 parts of phosphate buffer, stir at 320 r / min for 1.2 h at 36 °C, add carbodiimide hydrochloride and N-hydroxythiosuccinimide, stir at 320 r / min for 45 min at 37 °C under nitrogen protection to obtain the activation solution. 2) Dissolve ε-polylysine in the remaining phosphate buffer and dissolve asiaticoside in 8 parts of anhydrous ethanol. After mixing the two, slowly add them dropwise to the activation solution at a rate of 2 drops / s. After the addition is complete, heat the solution to 46°C and stir at 360 r / min for 9 h. 3) Transfer the reaction solution obtained in 2) into a dialysis bag with a molecular weight cutoff of 35000 Da, and dialyze for 24 hours with an additional phosphate buffer (molar concentration of 0.010 mol / L, pH value of 7.4) of 10 times the volume of the reaction solution (replace with fresh buffer every 4 hours, and use the same amount each time, which is 10 times the volume of the reaction solution). Then dialyze for 18 hours with deionized water of 10 times the volume of the reaction solution (replace with fresh deionized water every 6 hours, and use the same amount each time, which is 10 times the volume of the reaction solution). 4) The reaction solution obtained in 3) was spray-dried at an inlet temperature of 95℃ and an outlet temperature of 50℃ to obtain a primary powder, and then dried at 46℃ and 0.1MPa vacuum for 12h to obtain a hyaluronic acid-polylysine-centicolic acid graft copolymer.

[0039] The BPPR grafted triblock copolymer is a baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer. By weight, its constituent raw materials include: 7 parts baicalin, 12 parts polycaprolactone with a weight average molecular weight of 8000 Da, 6 parts polyethylene glycol with a weight average molecular weight of 4000 Da, 2.7 parts 4-vinylpyridine, 0.14 parts stannous octoate, 1.2 parts carbodiimide hydrochloride, 90 parts anhydrous N,N-dimethylformamide, and 240 parts diethyl ether.

[0040] The preparation method of baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer includes the following steps: (1) Add polycaprolactone, polyethylene glycol and stannous octoate to a three-necked flask, purge with nitrogen to replace air 3 times; heat to 145°C and stir at 220 r / min for 7 h. (2) Add 4-vinylpyridine to the mixture obtained in (1) and stir at 220 r / min at 130 °C for 4 h to obtain a triblock system; (3) Dissolve baicalin in anhydrous N,N-dimethylformamide, add carbodiimide hydrochloride, and stir at 300 r / min for 1.8 h at 32 °C to obtain an activated baicalin solution; (4) The activated baicalin solution was added dropwise to the triblock system, heated to 68°C, and stirred at 300 r / min for 12 h under nitrogen protection; (5) After cooling the reaction solution obtained in (4) to room temperature, slowly pour it into diethyl ether to precipitate for 3 hours. Filter and collect the precipitate. Wash it three times with hydrochloric acid solution with a molar concentration of 0.10 mol / L (each time the amount of hydrochloric acid is 3 times the volume of the precipitate. After each washing, centrifuge at 10000 r / min for 8 minutes, discard the supernatant and retain the precipitate). Then wash it with deionized water until neutral. Dry it under vacuum at 68℃ for 15 hours to obtain baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer.

[0041] TCC nanocapsules are tea tree oil-chitosan-cyclodextrin nanocapsules. By weight, their constituent raw materials include: 4.5 parts tea tree oil, 1.4 parts chitosan, 4 parts β-cyclodextrin, 0.6 parts sodium tripolyphosphate, 65 parts 1% glacial acetic acid solution, 1.6 parts polyglycerol-3 stearate, and 30 parts deionized water. The degree of deacetylation of chitosan is 92%, and the weight-average molecular weight is 100 kDa.

[0042] The preparation method of tea tree oil-chitosan-cyclodextrin nanocapsules includes the following steps: a. Chitosan was dissolved in glacial acetic acid solution, and stirred at 350 r / min for 7 h at 32 °C. β-cyclodextrin was then added, and stirring was continued at 350 r / min for 2 h to obtain the aqueous phase. b. Preheat tea tree oil in a water bath at 45°C, add polyglycerol-3 stearate, and stir at 250 r / min for 15 min to obtain the oil phase; c. Slowly drip the oil phase into the aqueous phase at a rate of 3 drops / s, while simultaneously homogenizing at a high speed of 12000 r / min for 12 min to form the primary emulsion; d. Dissolve sodium tripolyphosphate in deionized water to obtain a sodium tripolyphosphate solution. Add the sodium tripolyphosphate solution dropwise to the primary emulsion and stir at 700 r / min for 60 min. Then centrifuge at 4℃ and 12000 r / min for 35 min, collect the precipitate, and wash it three times with added deionized water. Dry it under vacuum at 55℃ for 10 h to obtain tea tree oil-chitosan-cyclodextrin nanocapsules.

[0043] This embodiment also discloses a method for preparing a topical antibacterial gel for feminine hygiene, comprising the following steps: S1. Preparation of aqueous phase: Deionized water, 1,3-propanediol, and sodium hyaluronate were added to an aqueous phase pot and stirred at 450 rpm for 15 min at 36 °C. HPS graft copolymer was added, and the mixture was heated to 58 °C and stirred at 750 rpm for 28 min. The mixture was then transferred to a high-pressure homogenizer and homogenized 6 times at 950 bar to obtain the aqueous phase. S2, Oil phase preparation: Ceramide NP, carbomer and TCC nanocapsules were added to an oil phase pot and stirred at 300 r / min for 22 min at 72 °C; then BPPR grafted triblock copolymer was added and stirred at 300 r / min for 15 min at 72 °C to obtain the oil phase. S3, Emulsification: The oil phase was slowly added to the water phase, and the mixture was homogenized and stirred at 3200 r / min for 28 min under the conditions of 68℃ and vacuum of -0.096 MPa to obtain an emulsion. S4, Component Mixing: After cooling the emulsion to 52°C, N-acetyl-modified matrine was added, and the mixture was stirred at 550 rpm for 20 min. The temperature was then lowered to 43°C, and polyethylene glycol-modified lysozyme and oat alkaloids were added, followed by stirring at 420 rpm for 16 min. Finally, the temperature was lowered to 37°C, and propylparaben was added, followed by stirring at 380 rpm for 15 min. The pH was then adjusted to 6.0 with arginine to obtain a gel. S5. Post-sterilization treatment: The gel was filtered through a 0.22 μm microporous membrane at a dose of 32 kGy. 60 Sterilize under Co γ rays for 22 min, then degas under vacuum conditions of -0.095 MPa for 25 min, and aseptically fill to obtain a feminine hygiene external antibacterial gel.

[0044] Example 3: This embodiment discloses a topical antibacterial gel for feminine hygiene. By weight percentage, its constituent ingredients include: 1.8% HPS graft copolymer, 1.3% BPPR graft triblock copolymer, 1.0% TCC nanocapsules, 0.9% N-acetyl-modified matrine, 0.5% polyethylene glycol-modified lysozyme, 3.5% 1,3-propanediol, 0.7% carbomer, 0.6% arginine, 0.3% ceramide NP, 0.2% sodium hyaluronate with a weight-average molecular weight of 65 kDa, 0.2% oat alkaloids, 0.05% propylparaben, and the balance being deionized water. In the polyethylene glycol-modified lysozyme, the polyethylene glycol has a weight-average molecular weight of 3.5 kDa and an enzyme activity of 20500 U / mg. The carbomer used is Pemulen TR-1, with a cross-linking degree of 25%.

[0045] The HPS graft copolymer is a hyaluronic acid-polylysine-asiaticoside graft copolymer. By weight, its constituent raw materials include: 8.5 parts of 110kDa hyaluronic acid, 5.5 parts of ε-polylysine with a weight average molecular weight of 4000Da, 3 parts of asiaticoside, 2 parts of carbodiimide hydrochloride, 1.5 parts of N-hydroxythiosuccinimide, and 165 parts of phosphate buffer. The phosphate buffer has a molar concentration of 0.009 mol / L and a pH of 7.3.

[0046] The preparation method of hyaluronic acid-polylysine-asiaticoside graft copolymer includes the following steps: 1) Dissolve hyaluronic acid in 130 parts of phosphate buffer, stir at 300 r / min for 1.1 h at 34 °C, add carbodiimide hydrochloride and N-hydroxythiosuccinimide, stir at 300 r / min for 40 min at 36 °C under nitrogen protection to obtain the activation solution; 2) Dissolve ε-polylysine in the remaining phosphate buffer and dissolve asiaticoside in 6.5 parts of anhydrous ethanol. After mixing the two, slowly add them dropwise to the activation solution at a rate of 2 drops / s. After the addition is complete, heat the solution to 44°C and stir at 340 r / min for 8 hours. 3) Transfer the reaction solution obtained in 2) into a dialysis bag with a molecular weight cutoff of 30,000 Da, and dialyze with an additional phosphate buffer (molar concentration of 0.009 mol / L, pH value of 7.3) of 9 times the volume of the reaction solution for 24 h (replace with fresh buffer every 4 h, and use the same amount each time, which is 9 times the volume of the reaction solution), and then dialyze with deionized water of 9 times the volume of the reaction solution for 17 h (replace with fresh deionized water every 6 h, and use the same amount each time, which is 9 times the volume of the reaction solution). 4) The reaction solution obtained in 3) was spray-dried at an inlet temperature of 90℃ and an outlet temperature of 47℃ to obtain a primary powder, and then dried at 44℃ and 0.095MPa vacuum for 11h to obtain a hyaluronic acid-polylysine-centicolic acid graft copolymer.

[0047] The BPPR grafted triblock copolymer is a baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer. By weight, its constituent raw materials include: 6.5 parts of baicalin, 11 parts of polycaprolactone with a weight average molecular weight of 6500 Da, 5.5 parts of polyethylene glycol with a weight average molecular weight of 3000 Da, 2.5 parts of 4-vinylpyridine, 0.12 parts of stannous octoate, 1 part of carbodiimide hydrochloride, 85 parts of anhydrous N,N-dimethylformamide, and 220 parts of diethyl ether.

[0048] The preparation method of baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer includes the following steps: (1) Add polycaprolactone, polyethylene glycol and stannous octoate to a three-necked flask, purge the air with nitrogen three times; heat to 140°C and stir at 200 r / min for 6 h. (2) Add 4-vinylpyridine to the mixture obtained in (1) and stir at 200 r / min for 3.5 h at 125 °C to obtain a triblock system; (3) Dissolve baicalin in anhydrous N,N-dimethylformamide, add carbodiimide hydrochloride, and stir at 275 r / min for 1.5 h at 30 °C to obtain an activated baicalin solution; (4) The activated baicalin solution was added dropwise to the triblock system, heated to 65°C, and stirred at 275 r / min for 11 h under nitrogen protection; (5) After cooling the reaction solution obtained in (4) to room temperature, slowly pour it into diethyl ether to precipitate for 2.5 h. Filter and collect the precipitate. Wash it three times with hydrochloric acid solution with a molar concentration of 0.09 mol / L (each time the amount of hydrochloric acid is 2.5 times the volume of the precipitate. After each washing, centrifuge at 9000 r / min for 7 min, discard the supernatant and retain the precipitate). Then wash it with deionized water until neutral. Dry it under vacuum at 65℃ for 14 h to obtain baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer.

[0049] TCC nanocapsules are tea tree oil-chitosan-cyclodextrin nanocapsules. By weight, their constituent raw materials include: 4 parts tea tree oil, 1.2 parts chitosan, 3.5 parts β-cyclodextrin, 0.5 parts sodium tripolyphosphate, 60 parts 1% glacial acetic acid solution, 1.2 parts polyglycerol-3 stearate, and 25 parts deionized water. The degree of deacetylation of chitosan is 91%, and the weight-average molecular weight is 75 kDa.

[0050] The preparation method of tea tree oil-chitosan-cyclodextrin nanocapsules includes the following steps: a. Chitosan was dissolved in glacial acetic acid solution, and stirred at 325 r / min for 6 h at 30 °C. β-cyclodextrin was then added, and stirring was continued at 325 r / min for 1.5 h to obtain the aqueous phase. b. Preheat tea tree oil in a water bath at 42°C, add polyglycerol-3 stearate, and stir at 225 r / min for 12 min to obtain the oil phase; c. Slowly drip the oil phase into the aqueous phase at a rate of 2 drops / s, while simultaneously homogenizing at a high speed of 11000 r / min for 10 min to form the primary emulsion; d. Dissolve sodium tripolyphosphate in deionized water to obtain a sodium tripolyphosphate solution. Add the sodium tripolyphosphate solution dropwise to the primary emulsion and stir at 600 r / min for 50 min. Then centrifuge at 4℃ and 11000 r / min for 30 min, collect the precipitate, and wash it three times with added deionized water. Dry it under vacuum at 52℃ for 9 h to obtain tea tree oil-chitosan-cyclodextrin nanocapsules.

[0051] This embodiment also discloses a method for preparing a topical antibacterial gel for feminine hygiene, comprising the following steps: S1. Preparation of aqueous phase: Deionized water, 1,3-propanediol, and sodium hyaluronate were added to an aqueous phase pot and stirred at 400 rpm for 14 min at 34 °C. HPS graft copolymer was added, and the mixture was heated to 55 °C and stirred at 700 rpm for 25 min. The mixture was then transferred to a high-pressure homogenizer and homogenized five times at 900 bar to obtain the aqueous phase. S2, Oil phase preparation: Ceramide NP, carbomer and TCC nanocapsules were added to an oil phase pot and stirred at 275 r / min at 70 °C for 20 min; then BPPR grafted triblock copolymer was added and stirred at 275 r / min at 70 °C for 14 min to obtain the oil phase. S3, Emulsification: The oil phase was slowly added to the water phase, and the mixture was homogenized and stirred at 3000 r / min for 25 min under the conditions of 65℃ and vacuum of -0.092 MPa to obtain an emulsion. S4, Component Mixing: After cooling the emulsion to 49°C, N-acetyl-modified matrine was added, and the mixture was stirred at 500 rpm for 18 min. The temperature was then lowered to 41°C, and polyethylene glycol-modified lysozyme and oat alkaloids were added, followed by stirring at 400 rpm for 15 min. Finally, the temperature was lowered to 35°C, and propylparaben was added, followed by stirring at 350 rpm for 12 min. The pH was then adjusted to 5.8 with arginine to obtain a gel. S5. Post-sterilization treatment: The gel was filtered through a 0.21 μm microporous membrane at a dose of 28 kGy. 60 Sterilize under Coγ rays for 19 min, then degas under vacuum conditions of -0.092 MPa for 20 min, and aseptically fill to obtain a feminine hygiene external antibacterial gel.

[0052] Comparative Example 1: A topical antibacterial gel for feminine hygiene and its preparation method differ from Example 3 only in that HPS graft copolymer is not added, but is replaced by a physical mixture of hyaluronic acid, ε-polylysine, and asiaticoside.

[0053] Comparative Example 2: A topical antibacterial gel for feminine hygiene and its preparation method differ from Example 3 only in that: BPPR grafted triblock copolymer is not added, but baicalin and polyethylene glycol are physically mixed instead.

[0054] Comparative Example 3: A topical antibacterial gel for feminine hygiene and its preparation method are described. The only difference between this gel and Example 3 is that TCC nanocapsules are not added, and ordinary tea tree oil is used instead.

[0055] Comparative Example 4: A topical antibacterial gel for feminine hygiene and its preparation method are disclosed. The only difference between this gel and Example 3 is that ordinary matrine is used instead of N-acetyl-modified matrine.

[0056] Comparative Example 5: A topical antibacterial gel for feminine hygiene and its preparation method are disclosed. The only difference between this gel and Example 3 is that ordinary lysozyme is used instead of polyethylene glycol-modified lysozyme.

[0057] Comparative Example 6: A topical antibacterial gel for feminine hygiene and its preparation method are described. The only difference between this gel and Example 3 is that the aqueous phase preparation was not subjected to high-pressure homogenization.

[0058] Comparative Example 7: A topical antibacterial gel for feminine hygiene and its preparation method are described. The only difference between this gel and Example 3 is that ceramide NP and oat alkaloids are not added.

[0059] Comparative Example 8: A topical antibacterial gel for feminine hygiene and its preparation method differ from Example 3 only in that the sterilization process uses only ethylene oxide sterilization and does not involve... 60 Co-γ ray sterilization.

[0060] Comparative Example 9: A topical antibacterial gel for feminine hygiene and its preparation method are described. The only difference between this gel and Example 3 is that 4-vinylpyridine (pH-responsive monomer) was not added during the preparation of the BPPR grafted triblock copolymer.

[0061] Comparative Example 10: A topical antibacterial gel for feminine hygiene and its preparation method are described. The only difference between this gel and Example 3 is that polyethylene glycol-modified lysozyme is not added.

[0062] Comparative Example 11: A topical antibacterial gel for feminine hygiene and its preparation method are described. The only difference between this gel and Example 3 is that N-acetyl-modified matrine is not added.

[0063] The antibacterial gels obtained in Examples 1-3 and Comparative Examples 1-11 were subjected to performance tests for antibacterial rate, mucosal irritation, moisturizing duration, mucosal repair time, lactic acid bacteria survival rate, and mucosal barrier function improvement rate. The test methods and standards for each performance are as follows: 1. Antibacterial rate determination Referring to Appendix C of GB 15979-2012 "Hygienic Standard for Disposable Sanitary Products", the following plate counting method was used to target common pathogens in the private parts (Candida albicans, Staphylococcus aureus, Escherichia coli, drug-resistant Escherichia coli, etc.): 0.2g of gel sample was dissolved in 10mL of sterile physiological saline to prepare a 1:50 dilution; 1mL of the dilution was mixed with 5mL of bacterial suspension (1×10⁻⁶). 6 The samples were mixed with sterile saline solution (CFU / mL), incubated at 37°C for 24 hours, and the number of viable bacteria was counted. The control group was replaced with sterile saline solution. The inhibition rate was calculated using the formula: "Inhibition rate = (Number of viable bacteria in the control group - Number of viable bacteria in the sample group) / Number of viable bacteria in the control group × 100%".

[0064] 2. Mucosal irritation test Referring to Chapter 2, "Skin and Mucous Membrane Irritation / Corrosion Tests," of the "Cosmetic Safety Technical Specifications" (2015 edition), a vaginal mucosal irritation test was conducted: Three healthy female New Zealand rabbits were selected, and 0.5g of gel was administered vaginally daily for three consecutive days. The control group was given an equal volume of physiological saline. The animals were sacrificed 24 hours after the last administration, and vaginal tissue was taken for pathological examination. The tissue was scored according to indicators such as mucosal integrity and inflammatory cell infiltration (0 points for no irritation and 4 points for severe irritation).

[0065] 3. Measurement of moisturizing duration Referring to QB / T 4256-2011 "Guidelines for Evaluation of Moisturizing Efficacy of Cosmetics", and taking into account the characteristics of the skin in the private area, the following adjustments were made: 20 healthy female volunteers were selected, and a 2cm×2cm area was marked on the inner vulva. 0.1g of gel was applied, and the skin moisture content was measured at 0h, 4h, 8h, 12h, and 16h using a Corneometer® CM825 skin moisture meter. The longest time during which the moisture content increased by ≥30% from the initial value was defined as the moisturizing duration.

[0066] 4. Measurement of mucosal repair time A vaginal epithelial cell scratch model (a standard method in this field) was used: immortalized human vaginal epithelial cells (VK2 / E6E7) were cultured to 90% confluence, and a 500 μm wide scratch was created using a 200 μL pipette tip. 10% gel extraction buffer (diluted in DMEM medium containing 10% fetal bovine serum) was added. The cells were cultured in a 37°C, 5% CO2 incubator, and the scratch healing was observed every 6 hours using an inverted microscope. The time to complete healing (scratch width ≤ 50 μm) was recorded.

[0067] 5. Lactic acid bacteria survival rate determination Referring to T / CSBME 009-2019 "Determination of the Effect of Gynecological Antibacterial Agents on Lactobacillus", the dominant vaginal lactobacillus (Lactobacillus curvatureus) was selected: the gel sample was mixed with lactobacillus culture (1×10⁻⁶). 6 The samples were mixed at a ratio of 1:10 and anaerobic cultured at 37℃ for 24 h. The viable count was determined by MRS agar plate counting method. The control group was replaced with sterile physiological saline. The survival rate was calculated by the formula "(viable count of sample group / viable count of control group) × 100%".

[0068] 6. Measurement of mucosal barrier function improvement rate Transepithelial resistance (TEER) was measured: VK2 / E6E7 cells were seeded in Transwell chambers and cultured until a complete monolayer was formed (TEER value was stable); 0.1 g of gel was added to the apical side, and after culturing for 24 h, the TEER value was measured using a Millicell ERS-2 resistance meter. The improvement rate was calculated using the formula "improvement rate = (TEER value after treatment - TEER value before treatment) / TEER value before treatment × 100%".

[0069] The results are shown in Table 1.

[0070] Table 1 Performance parameters of the antibacterial gels obtained in Examples 1-3 and Comparative Examples 1-11 Example 1 95.8 96.5 95.2 13.5 33 0.15 85.3 68.2 Example 2 97.2 97.8 96.8 15.2 31 0.12 88.6 72.5 Example 3 98.5 99.1 98.3 16.0 30 0.10 90.2 75.0 Comparative Example 1 82.3 80.5 78.6 5.8 65 0.35 78.4 42.1 Comparative Example 2 85.6 83.2 81.4 8.2 58 0.28 80.1 48.5 Comparative Example 3 86.9 84.7 83.8 7.5 52 0.85 82.3 51.3 Comparative Example 4 88.5 87.3 86.2 12.8 38 0.18 84.6 62.8 Comparative Example 5 87.8 86.5 85.5 12.5 40 0.20 83.9 61.5 Comparative Example 6 90.2 89.8 89.1 9.6 45 0.22 86.7 56.8 Comparative Example 7 95.2 94.8 93.6 12.6 48 0.30 87.4 55.2 Comparative Example 8 97.8 98.2 97.1 15.7 31 0.18 76.3 73.1 Comparative Example 9 89.5 88.2 87.6 10.3 42 0.25 85.7 58.6 Comparative Example 10 84.2 82.6 81.1 15.8 44 0.15 88.5 69.3 Comparative Example 11 83.5 81.8 80.5 15.6 46 0.16 89.2 68.7 Using Example 3 as the control group, the performance differences and causes of Comparative Examples 1-11 are analyzed as follows: Comparative Example 1 did not add hyaluronic acid-polylysine-asiaticoside graft copolymer. It only physically mixed hyaluronic acid, ε-polylysine, and asiaticoside, which could not form a stable three-dimensional network structure through covalent bonds. This resulted in easy stratification of the components in the system, shortened residence time at the site of action, and decreased efficacy persistence. Compared with Example 3, the average inhibition rate of pathogenic bacteria decreased from 98.5% to 82.3%, a decrease of 16.4%; the inhibition rate of Candida albicans decreased from 99.1% to 80.5%, a decrease of 18.8%; the inhibition rate of drug-resistant Escherichia coli decreased from 98.3% to 78.6%, a decrease of 20.0%; the moisturizing duration decreased from 16.0 h to 5.8 h, a decrease of 63.7%; the mucosal repair time increased from 30 h to 65 h, an increase of 116.7%; and the mucosal barrier function improvement rate decreased from 75.0% to 42.1%, a decrease of 43.9%. This indicates that the hyaluronic acid-polylysine-asiaticoside graft copolymer achieves synergistic effects of moisturizing, antibacterial and repairing functions through structural integration.

[0071] Comparative Example 2 did not contain baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer. Instead, it was replaced with a physical mixture of baicalin and polyethylene glycol. This system lost the intelligent drug release capability conferred by the pH-responsive monomer and lacked the mucosal adhesion properties of polycaprolactone, resulting in the inability of the drug to be specifically enriched at the site of inflammation and a significantly shortened duration of action. Compared with Example 3, the average inhibition rate of pathogenic bacteria decreased from 98.5% to 85.6%, a decrease of 13.1%; the inhibition rate of Candida albicans decreased from 99.1% to 83.2%, a decrease of 16.0%; the inhibition rate of drug-resistant Escherichia coli decreased from 98.3% to 81.4%, a decrease of 17.2%; the moisturizing duration decreased from 16.0 h to 8.2 h, a decrease of 48.8%; the mucosal repair time increased from 30 h to 58 h, an increase of 93.3%; and the mucosal barrier function improvement rate decreased from 75.0% to 48.5%, a decrease of 35.3%. This indicates that the targeted drug release and anti-inflammatory adhesion effects of baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer are key components for improving the antibacterial gel's antibacterial specificity and repair efficiency.

[0072] Comparative Example 3 did not add tea tree oil-chitosan-cyclodextrin nanocapsules, but instead used ordinary tea tree oil. Ordinary tea tree oil is highly volatile and fat-soluble with high irritation, and cannot achieve long-lasting retention and gentle effects. Compared with Example 3, the average inhibition rate of pathogenic bacteria decreased from 98.5% to 86.9%, a decrease of 11.8%; the inhibition rate of Candida albicans decreased from 99.1% to 84.7%, a decrease of 14.5%; the inhibition rate of drug-resistant Escherichia coli decreased from 98.3% to 83.8%, a decrease of 14.7%; the duration of moisturizing decreased from 16.0 h to 7.5 h, a decrease of 53.1%; the mucosal repair time increased from 30 h to 52 h, an increase of 73.3%; the mucosal irritation score increased from 0.10 to 0.85, an increase of 750.0%, indicating a risk of mild to moderate irritation; and the mucosal barrier function improvement rate decreased from 75.0% to 51.3%, a decrease of 31.6%. This indicates that the tea tree oil-chitosan-cyclodextrin nanocapsules reduce the irritation of tea tree oil through cyclodextrin encapsulation and enhance mucosal adhesion with chitosan, achieving a sustained-release and long-lasting effect of the antibacterial components.

[0073] Comparative Example 4 used ordinary matrine instead of N-acetyl-modified matrine. Ordinary matrine has poor lipid solubility, leading to a significant decrease in mucosal penetration efficiency, making it difficult for the drug to reach the deep mucosal layers to exert its effect. Compared to Example 3, the average inhibition rate of pathogenic bacteria decreased from 98.5% to 88.5%, a decrease of 10.2%; the inhibition rate of drug-resistant Escherichia coli decreased from 98.3% to 86.2%, a decrease of 12.3%; the mucosal repair time increased from 30 hours to 38 hours, an increase of 26.7%; and the mucosal barrier function improvement rate decreased from 75.0% to 62.8%, a decrease of 16.3%. This indicates that N-acetyl modification can significantly enhance the lipid solubility of matrine, improve its mucosal penetration ability, and thus strengthen its antibacterial effect and repair efficiency.

[0074] Comparative Example 5 used ordinary lysozyme instead of polyethylene glycol-modified lysozyme. Ordinary lysozyme is easily degraded by proteases in the body fluid environment, resulting in a shortened activity maintenance time and decreased efficacy. Compared with Example 3, the average inhibition rate of pathogenic bacteria decreased from 98.5% to 87.8%, a decrease of 10.9%; the mucosal repair time increased from 30 hours to 40 hours, an increase of 33.3%; and the mucosal barrier function improvement rate decreased from 75.0% to 61.5%, a decrease of 18.0%. This demonstrates that polyethylene glycol modification improves the stability of lysozyme, reduces enzymatic loss, prolongs its effective half-life at the site of action, and ensures a synergistic effect of antibacterial and repair.

[0075] Comparative Example 6 did not undergo high-pressure homogenization during the aqueous phase preparation process, resulting in a significant increase in the particle size of the components in the system and a substantial decrease in mucosal permeability, making it difficult for the components to fully contact the mucosal tissue and exert their effects. Compared with Example 3, the moisturizing duration was shortened from 16.0 h to 9.6 h, a decrease of 40.0%; the mucosal repair time was extended from 30 h to 45 h, an increase of 50.0%; and the mucosal barrier function improvement rate decreased from 75.0% to 56.8%, a decrease of 24.3%. This indicates that the high-pressure homogenization nano-dispersion process can reduce the particle size of the components and improve the mucosal permeability efficiency, which is a key process step to ensure that the antibacterial gel can fully exert its moisturizing, repairing, and other effects.

[0076] Comparative Example 7, lacking ceramide NP and oat alkaloids, lacked the core components for mucosal barrier repair and inflammation relief, resulting in hindered mucosal damage repair and difficulty in alleviating inflammatory responses. Compared to Example 3, the mucosal repair time increased from 30 hours to 48 hours, an increase of 60.0%; the mucosal barrier function improvement rate decreased from 75.0% to 55.2%, a decrease of 26.4%. This indicates that ceramide NP can accelerate mucosal barrier reconstruction, and oat alkaloids can reduce inflammatory responses; the synergistic effect of the two can significantly improve mucosal repair efficiency and enhance barrier function.

[0077] The sterilization process in Comparative Example 8 only used ethylene oxide sterilization and did not undergo further sterilization. 60 Co-γ ray sterilization and ethylene oxide sterilization leave residual derivatives (such as 2-chloroethanol) that are significantly toxic to dominant vaginal lactobacilli, and the sterilization is not thorough enough. Compared with Example 3, the survival rate of lactobacilli decreased from 90.2% to 76.3%, a decrease of 15.4%; indicating 60 Coγ-ray sterilization has the advantage of leaving no residue, which can ensure thorough sterilization while reducing toxicity to beneficial vaginal bacteria and maintaining the vaginal microecological balance.

[0078] In Comparative Example 9, no pH-responsive monomer was added during the preparation of the baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer. This resulted in the copolymer failing to trigger targeted drug release at the site of inflammation, leading to a significant reduction in drug release and insufficient drug concentration at the inflamed site. Compared to Example 3, the moisturizing duration decreased from 16.0 h to 10.3 h, a reduction of 35.6%; the mucosal repair time increased from 30 h to 42 h, an increase of 40.0%; and the mucosal barrier function improvement rate decreased from 75.0% to 58.6%, a reduction of 21.9%. This indicates that the pH-responsive monomer is the core structural unit for achieving targeted drug release, which can improve drug accumulation at the inflamed site and enhance the synergistic effect of antibacterial and anti-inflammatory activity.

[0079] Comparative Example 10, lacking PEGylated lysozyme, lacked an antibacterial component that works by hydrolyzing bacterial cell walls, resulting in a significant decrease in the inhibition rate of Gram-positive bacteria (such as Staphylococcus aureus) and insufficient synergistic effect of the overall antibacterial system. Compared to Example 3, the average inhibition rate of pathogenic bacteria decreased from 98.5% to 84.2%, a decrease of 14.5%; the mucosal repair time increased from 30 hours to 44 hours, an increase of 46.7%. This indicates that PEGylated lysozyme, through its unique mechanism of action of hydrolyzing bacterial cell walls, can synergize with other antibacterial components, broaden the antibacterial spectrum, improve antibacterial efficiency, and simultaneously promote the mucosal repair process.

[0080] Comparative Example 11, without the addition of N-acetyl-modified matrine, lost its lipid-soluble membrane-permeability-enhancing effect, resulting in a significant decrease in the drug concentration in the deep mucosal layer, making it difficult to effectively inhibit pathogens colonizing deep layers. Compared with Example 3, the average inhibition rate of pathogens decreased from 98.5% to 83.5%, a decrease of 15.2%; the inhibition rate of drug-resistant Escherichia coli decreased from 98.3% to 80.5%, a decrease of 18.1%; and the mucosal repair time increased from 30 hours to 46 hours, an increase of 53.3%. This indicates that the lipid-soluble membrane-permeability of N-acetyl-modified matrine is key to its deep-layer antibacterial effect, significantly improving the inhibitory effect on drug-resistant pathogens and accelerating mucosal damage repair.

[0081] In summary, HPS grafted copolymers integrate moisturizing, antibacterial, and repairing functions through covalent bonds, constructing a three-dimensional network to enhance the synergistic efficiency of the ingredients; BPPR grafted triblock copolymers achieve targeted drug release at inflamed sites through pH-responsive properties, prolonging the duration of action; TCC nanocapsules achieve sustained release of antibacterial components and reduce irritation through encapsulation and adhesion. These three components, combined with N-acetyl-modified matrine and polyethylene glycol-modified lysozyme, form a cascade antibacterial system of "cell wall disruption-membrane permeation-targeted drug release," significantly expanding the antibacterial spectrum and improving efficiency; synergistically with repairing ingredients such as ceramide NP and oat alkaloids, they accelerate the reconstruction of the mucosal barrier; and combined with moisturizing systems and pH-regulating ingredients, they achieve long-lasting moisturizing and maintenance of microecological balance, comprehensively enhancing the overall efficacy of the antibacterial gel.

[0082] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A topical antibacterial gel for feminine hygiene, characterized in that, By weight percentage, its constituent raw materials include: HPS graft copolymer 1.0-2.5%, BPPR graft triblock copolymer 0.8-1.8%, TCC nanocapsules 0.5-1.5%, N-acetyl-modified matrine 0.6-1.2%, polyethylene glycol-modified lysozyme 0.3-0.7%, 1,3-propanediol 2.8-4.2%, carbomer 0.5-1.0%, arginine 0.4-0.7%, ceramide NP 0.2-0.4%, sodium hyaluronate 0.1-0.3%, oat alkaloids 0.1-0.3%, propylparaben 0.03-0.06%, with the balance being deionized water; The HPS graft copolymer is a hyaluronic acid-polylysine-asiaticoside graft copolymer, the BPPR graft triblock copolymer is a baicalin graft polycaprolactone-polyethylene glycol-pH responsive triblock copolymer, and the TCC nanocapsules are tea tree oil-chitosan-cyclodextrin nanocapsules.

2. The topical antibacterial gel for feminine hygiene according to claim 1, characterized in that, In the polyethylene glycol-modified lysozyme, the weight-average molecular weight of polyethylene glycol is 2-5 kDa, and the enzyme activity is 20,000-21,000 U / mg; the carbomer used is Pemulen TR-1, with a crosslinking degree of 20-30%; and the weight-average molecular weight of sodium hyaluronate is 50-80 kDa.

3. The topical antibacterial gel for feminine hygiene according to claim 1, characterized in that, The HPS graft copolymer, by weight, comprises the following raw materials: 8-9 parts hyaluronic acid, 5-6 parts ε-polylysine, 2.5-3.5 parts asiaticoside, 1.8-2.2 parts carbodiimide hydrochloride, 1.3-1.7 parts N-hydroxythiosuccinimide, and 150-180 parts phosphate buffer.

4. The topical antibacterial gel for feminine hygiene according to claim 3, characterized in that, The weight-average molecular weight of hyaluronic acid is 80-150 kDa; the weight-average molecular weight of ε-polylysine is 3000-5000 Da; the molar concentration of phosphate buffer is 0.008-0.010 mol / L, and the pH value is 7.2-7.

4.

5. The topical antibacterial gel for feminine hygiene according to claim 3, characterized in that, The preparation method of hyaluronic acid-polylysine-asiaticoside graft copolymer includes the following steps: 1) Dissolve hyaluronic acid in 120-140 parts of phosphate buffer, stir at 280-320 r / min at 32-36℃ for 1.0-1.2 h, add carbodiimide hydrochloride and N-hydroxythiosuccinimide, stir at 280-320 r / min at 35-37℃ for 35-45 min under nitrogen protection to obtain the activation solution; 2) Dissolve ε-polylysine in the remaining phosphate buffer and dissolve asiaticoside in 5-8 parts of anhydrous ethanol. After mixing the two, slowly add them dropwise to the activation solution at a rate of 1-2 drops / s. After the addition is complete, raise the temperature to 42-46℃ and stir at 320-360 r / min for 7-9 hours. 3) Transfer the reaction solution obtained in 2) into a dialysis bag with a molecular weight cutoff of 25,000-35,000 Da, dialyze with 8-10 times the volume of the reaction solution of added phosphate buffer for 24 hours, and then dialyze with 8-10 times the volume of the reaction solution of deionized water for 16-18 hours. 4) The reaction solution obtained in 3) is spray-dried at an inlet temperature of 85-95℃ and an outlet temperature of 45-50℃ to obtain a primary powder, and then dried at a vacuum of 42-46℃ and 0.09-0.1MPa for 10-12 hours to obtain a hyaluronic acid-polylysine-centicolic acid graft copolymer.

6. The topical antibacterial gel for feminine hygiene according to claim 1, characterized in that, The BPPR grafted triblock copolymer, by weight, comprises the following raw materials: 6-7 parts baicalin, 10-12 parts polycaprolactone, 5-6 parts polyethylene glycol, 2.3-2.7 parts pH-responsive monomer, 0.10-0.14 parts stannous octoate, 0.8-1.2 parts carbodiimide hydrochloride, 80-90 parts anhydrous N,N-dimethylformamide, and 200-240 parts diethyl ether; the weight average molecular weight of polycaprolactone is 5000-8000 Da, and the weight average molecular weight of polyethylene glycol is 2000-4000 Da; the pH-responsive monomer is methacrylic acid or 4-vinylpyridine.

7. The topical antibacterial gel for feminine hygiene according to claim 6, characterized in that, The preparation method of baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer includes the following steps: (1) Add polycaprolactone, polyethylene glycol and stannous octoate to a three-necked flask, purge the air with nitrogen three times; heat to 135-145℃ and stir at 180-220 r / min for 5-7 h. (2) Add pH-responsive monomers to the mixture obtained in (1) and stir at 180-220 r / min for 3-4 h at 120-130 °C to obtain a triblock system; (3) Dissolve baicalin in anhydrous N,N-dimethylformamide, add carbodiimide hydrochloride, and stir at 250-300 r / min for 1.2-1.8 h at 28-32℃ to obtain an activated baicalin solution; (4) Add the activated baicalin solution dropwise into the triblock system, heat to 62-68℃, and stir at 250-300 r / min for 10-12 h under nitrogen protection; (5) After cooling the reaction solution obtained in (4) to room temperature, slowly pour it into diethyl ether to precipitate for 2-3 hours. Filter to collect the precipitate, wash it 3 times with hydrochloric acid solution with a molar concentration of 0.08-0.10 mol / L, and then wash it with deionized water until neutral. The baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer was dried under vacuum at 62-68℃ for 13-15 hours to obtain the baicalin-grafted polycaprolactone-polyethylene glycol-pH-responsive triblock copolymer.

8. The topical antibacterial gel for feminine hygiene according to claim 1, characterized in that, The TCC nanocapsules, by weight, are composed of the following raw materials: 3.5-4.5 parts tea tree oil, 1.0-1.4 parts chitosan, 3-4 parts β-cyclodextrin, 0.4-0.6 parts sodium tripolyphosphate, 55-65 parts 1% glacial acetic acid solution, 0.8-1.6 parts polyglycerol-3 stearate, and 20-30 parts deionized water; the degree of deacetylation of chitosan is 90-92%, and the weight-average molecular weight is 50-100 kDa.

9. The topical antibacterial gel for feminine hygiene according to claim 8, characterized in that, The preparation method of tea tree oil-chitosan-cyclodextrin nanocapsules includes the following steps: a. Dissolve chitosan in glacial acetic acid solution, stir at 300-350 r / min for 5-7 h at 28-32℃, add β-cyclodextrin, and continue stirring at 300-350 r / min for 1-2 h to obtain the aqueous phase; b. Preheat tea tree oil in a water bath at 40-45℃, add polyglycerol-3 stearate, and stir at 200-250 r / min for 10-15 min to obtain the oil phase; c. Slowly drip the oil phase into the aqueous phase at a rate of 1-3 drops / s, while simultaneously homogenizing at a high speed of 10,000-12,000 r / min for 8-12 minutes to form the primary emulsion. d. Dissolve sodium tripolyphosphate in deionized water to obtain a sodium tripolyphosphate solution. Add the sodium tripolyphosphate solution dropwise to the primary emulsion and stir at 500-700 r / min for 40-60 min. Then centrifuge at 4℃ and 10000-12000 r / min for 25-35 min, collect the precipitate, and wash it three times with added deionized water. Dry it under vacuum at 50-55℃ for 8-10 h to obtain tea tree oil-chitosan-cyclodextrin nanocapsules.

10. A method for preparing a topical antibacterial gel for feminine hygiene according to any one of claims 1-9, characterized in that, Includes the following steps: S1. Preparation of aqueous phase: Deionized water, 1,3-propanediol, and sodium hyaluronate were added to an aqueous phase reactor and stirred at 350-450 rpm for 12-15 min at 32-36°C. HPS graft copolymer was then added, and the mixture was heated to 52-58°C and stirred at 650-750 rpm for 22-28 min. The mixture was then transferred to a high-pressure homogenizer and homogenized 4-6 times at 850-950 bar to obtain the aqueous phase. S2, Oil phase preparation: Ceramide NP, carbomer and TCC nanocapsules were added to an oil phase pot and stirred at 250-300 r / min for 18-22 min at 68-72 °C; then BPPR grafted triblock copolymer was added and stirred at 250-300 r / min for 12-15 min at 68-72 °C to obtain the oil phase. S3, Emulsification: The oil phase is slowly added to the water phase, and the mixture is homogenized and stirred at a speed of 2800-3200 r / min for 22-28 min under the conditions of temperature 62-68℃ and vacuum degree of -0.088MPa to -0.096MPa to obtain an emulsion. S4, Component Mixing: After cooling the emulsion to 46-52℃, add N-acetyl-modified matrine and stir at 450-550 rpm for 16-20 min; cool to 39-43℃, then add polyethylene glycol-modified lysozyme and oat alkaloids and stir at 380-420 rpm for 12-16 min; finally cool to 33-37℃, add propylparaben and stir at 320-380 rpm for 10-15 min; then adjust the pH to 5.5-6.0 with arginine to obtain a gel. S5. Post-sterilization treatment: The gel was filtered through a 0.20-0.22 μm microporous membrane at a dose of 26-32 kGy. 60 Sterilize under Coγ rays for 16-22 min, then degas under vacuum conditions of -0.09 MPa to -0.095 MPa for 15-25 min, and aseptically fill to obtain a feminine hygiene-care topical antibacterial gel.