Antibacterial wound flushing fluid and preparation method thereof

Abstract

The invention relates to the technical field of wound disinfection, in particular to antibacterial wound flushing fluid and a preparation method thereof.The preparation method comprises the following steps that according to the formula amount, vitamin E and glycerin are mixed at 40-50 DEG C, and a mixture A is formed; adding poloxamer into water according to the formula ratio, stirring until the poloxamer is dissolved, and adding the poloxamer into the mixture A to form a mixture B; adding sodium citrate, sodium chloride and L-menthol into water according to the formula ratio to form a mixture C; adding copper gluconate into the mixture C according to the formula ratio to form a mixture D; dropwise adding the mixture B into the mixture D to form a mixture E; adjusting the pH value of the mixture E to 4.5-6.5, filtering, filling and sterilizing to obtain the antibacterial wound flushing fluid. The preparation process is optimized, so that the prepared antibacterial wound flushing fluid has excellent stability; through the coordination effect of all the components, the prepared flushing fluid has a remarkable antibacterial effect.

Description

Technical Field

[0001] The present invention relates to the technical field of wound disinfection, and in particular to an antibacterial wound flushing liquid and a preparation method thereof. Background Art

[0002] Currently, a wide variety of wound irrigants are used clinically, but all have limitations. Conventional saline primarily cleans wounds but has weak antibacterial properties, making it ineffective in preventing and controlling wound infections. While irrigants containing chemical disinfectants have strong antibacterial properties, they are often highly irritating to wound tissue, affecting wound healing and potentially leading to delayed wound healing and scarring.

[0003] In recent years, copper-based compounds have attracted attention due to their broad-spectrum antibacterial properties and angiogenesis-promoting effects. However, their poor stability makes them prone to metal ion deposition when used in irrigating fluids, which limits the application of copper-based compounds in irrigating fluids. Summary of the Invention

[0004] In order to solve the problem of poor stability of copper-based compounds when used in irrigation solutions in the prior art, the present invention provides a method for preparing an antibacterial wound irrigation solution. During the preparation process, citrate ions are introduced to form a stable complex with copper ions, thereby reducing the concentration of free copper ions and the risk of metal ion deposition, thereby solving the problem of poor stability of copper-based compounds when used in irrigation solutions in the prior art.

[0005] The technical solution adopted by the present invention to solve its technical problem is: A method for preparing an antibacterial wound irrigating solution comprises the following steps: S1: Mix vitamin E and glycerin according to the formula at 40-50°C to form mixture A; S2: Add poloxamer to water at 40-50°C according to the formula amount, stir until dissolved, and then add it to the mixture A to form a mixture B; S3: Add sodium citrate, sodium chloride, and L-menthol to water at 40-50°C according to the formula to form a mixture C; S4: adding copper gluconate to the mixture C according to the formula amount to form a mixture D; S5: adding the mixture B dropwise into the mixture D to form a mixture E; S6: adjusting the pH of the mixture E to 4.5-6.5 to obtain an antibacterial wound rinsing solution.

[0006] Optionally, the vitamin E is d-α-tocopherol.

[0007] Optionally, the poloxamer is selected from at least one of poloxamer 188, poloxamer 407, poloxamer 237, poloxamer 338, and poloxamer 124.

[0008] Optionally, in parts by weight, the amount of vitamin E added in step S1 is 0.05-1 parts; the amount of glycerol added is 3-15 parts.

[0009] Optionally, the amount of poloxamer added in step S2 is 1-3 parts by weight.

[0010] Optionally, the amount of sodium citrate added in step S3 is 0.2-1.5 parts by weight.

[0011] Optionally, the amount of sodium chloride added in step S3 is 0.5-1.5 parts by weight.

[0012] Optionally, the amount of L-menthol added in step S3 is 0.01-0.5 parts by weight.

[0013] Optionally, the amount of copper gluconate added in step S4 is 0.01-0.5 parts by weight.

[0014] Another object of the present invention is to provide an antibacterial wound irrigant, which is prepared by the above-mentioned method for preparing the antibacterial wound irrigant.

[0015] The beneficial effects of the present invention are: The preparation method of the antibacterial wound irrigating liquid provided by the present invention optimizes the preparation process so that the prepared antibacterial wound irrigating liquid has excellent stability; through the coordinated action of various components, the prepared irrigating liquid has a significant antibacterial effect, can effectively prevent and control wound infection, and at the same time has little irritation to wound tissue, can promote wound healing, and has good stability, making it suitable for wide clinical application. DETAILED DESCRIPTION

[0016] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, but should not be construed as limiting the present invention. All other embodiments obtained by persons of ordinary skill in the art based on the embodiments of the present invention without creative effort are intended to fall within the scope of protection of the present invention.

[0017] In order to solve the problem of poor stability of copper-based compounds in the prior art when used in irrigating solutions, the present invention provides a method for preparing an antibacterial wound irrigating solution, the preparation method comprising the following steps: S1: Mix vitamin E and glycerin according to the formula at 40-50°C to form mixture A; This step can be performed by stirring, ultrasonication, etc. to promote the mixing of vitamin E and glycerin; Vitamin E, an antioxidant used in wound irrigants, directly protects cell membrane integrity by scavenging free radicals and inhibiting lipid peroxidation, alleviating oxidative stress damage and reducing inflammatory responses. However, it has poor water solubility. Therefore, the present invention first mixes vitamin E with glycerol. This not only enhances the dispersion stability of vitamin E, but also acts as a humectant to maintain a moist microenvironment on the wound surface, promoting fibroblast migration and collagen synthesis. The two synergistically form a dual "antioxidant-moisturizing" mechanism, which can reduce the levels of inflammatory factors (such as IL-6), accelerate epithelial regeneration, reduce scar formation, and significantly improve the efficiency and quality of tissue repair. S2: Add poloxamer to water at 40-50°C according to the formula amount, stir until dissolved, add to mixture A, and then mix thoroughly by stirring, ultrasonication, homogenization, etc. to form mixture B; The water in this step is preferably purified water; this step can be performed by stirring, ultrasonication, etc. to promote the dissolution of poloxamer in water; Based on the special amphiphilic structure of poloxamer, it exhibits strong solubilization and emulsification capabilities for oily ingredients such as vitamin E, forming a highly stable emulsion system, effectively preventing component stratification and precipitation, and improving system stability; Specifically, by adding poloxamer, an oil-in-water (O / W) microemulsion is formed. The hydrophilic end of the poloxamer faces outward and dissolves in the aqueous phase, while the hydrophobic end faces inward and wraps around oily ingredients such as vitamin E, forming microemulsion droplets with uniform particle size. The steric hindrance effect prevents the droplets from aggregating and stratifying. S3: adding sodium citrate, sodium chloride, and L-menthol to water, preferably purified water, at 40-50° C. according to the formula, and stirring, ultrasonicating, or the like until completely dissolved to form a mixture C; The cooling sensation brought by L-menthol can relieve wound pain and improve comfort. Furthermore, L-menthol can disintegrate biofilms, destroying the extracellular polysaccharide matrix of bacterial biofilms, allowing antimicrobial ingredients to more easily access the bacteria themselves. It also enhances the clearance of drug-resistant bacteria by altering bacterial membrane fluidity, reversing the efflux pump mechanism of some drug-resistant bacteria, and increasing sensitivity to drug-resistant bacteria, thereby providing a supplementary antibacterial effect. S4: adding copper gluconate to mixture C according to the formula amount, preferably slowly adding copper gluconate to mixture C, stirring, ultrasonicating, etc., until completely dissolved to form mixture D; Copper gluconate releases Cu in solution 2+ , exerting its antibacterial effect through the following pathways: Destroy bacterial cell membranes: Cu 2+Binds to the negative charge on the cell membrane surface, destroying the lipid bilayer structure of the membrane and causing leakage of cell contents; Interfering with bacterial DNA replication: Cu 2+ Enters into bacteria and binds to nucleic acid, inhibiting DNA polymerase activity and blocking the synthesis of genetic material; Producing reactive oxygen species (ROS): Inducing ROS accumulation in bacteria through the Fenton reaction, oxidatively damaging proteins, lipids, and nucleic acids, leading to bacterial death; By adding copper gluconate to mixture C, citrate ions (C6H5O7 3- ) Chelated Cu 2+ After that, the positive charge is neutralized, which reduces the influence of metal ions on the stability of the system, ensures the stability of the product, makes the components evenly mixed, and is not prone to stratification and precipitation during storage and use. The stability of the system is enhanced through the synergistic effect of the components. After the reaction of sodium citrate and copper gluconate, the free Cu 2+ concentration, which reduces the cytotoxicity of the wound irrigation solution and gives the system good biocompatibility; S5: adding mixture B dropwise to mixture D to form mixture E; Preferably, in this step, the mixture B is slowly added dropwise to the mixture D, and stirred, etc., until a uniform milky white oil-in-water (O / W) microemulsion system is formed to obtain a mixture E; S6: adjusting the pH of the mixture E to 4.5-6.5, filtering the mixture through a filter to remove possible impurities; filling the filtered solution into suitable packaging, labeling it, and sterilizing it by irradiation to obtain an antibacterial wound rinse solution; Preferably, in this step, the mixture E is diluted to the target volume with purified water, the pH is adjusted to 4.5-6.5 with 1M sodium hydroxide / hydrochloric acid solution, preferably the pH is adjusted to 5.5-6.5, filtered, filled, and sterilized to obtain an antibacterial wound irrigant.

[0018] The preparation method of the antibacterial wound irrigating liquid provided by the present invention optimizes the preparation process so that the prepared antibacterial wound irrigating liquid has excellent stability; through the coordinated action of various components, the prepared irrigating liquid has a significant antibacterial effect, can effectively prevent and control wound infection, and at the same time has little irritation to wound tissue, can promote wound healing, and has good stability, making it suitable for wide clinical application.

[0019] Furthermore, in the present invention, the vitamin E is preferably d-α-tocopherol; and the poloxamer is preferably at least one selected from poloxamer 188, poloxamer 407, poloxamer 237, poloxamer 338, and poloxamer 124.

[0020] In the present invention, the amount of vitamin E added in step S1 is preferably 0.05-1 parts by weight, more preferably 0.1-0.4 parts; the amount of glycerol added is 3-15 parts, more preferably 5-10 parts; the amount of poloxamer added in step S2 is preferably 1-3 parts by weight, more preferably 1.5-2 parts; the amount of water added in this step is preferably 40-60 parts, more preferably 45-55 parts; preferably, in parts by weight, the amount of sodium citrate added in step S3 is 0.2-1.5 parts, more preferably 0.3-1 parts; the amount of sodium chloride added is 0.5-1.5 parts, more preferably 0.7-1 parts; the amount of L-menthol added is 0.01-0.5 parts, more preferably 0.02-0.1 parts; preferably, the amount of water added in this step is 30-50 parts, more preferably 35-45 parts; preferably, in parts by weight, the amount of copper gluconate added in step S4 is 0.01-0.5 parts, more preferably 0.01-0.08 parts.

[0021] Another object of the present invention is to provide an antibacterial wound irrigant, which is prepared by the above-mentioned method for preparing the antibacterial wound irrigant.

[0022] The antibacterial wound irrigant comprises the following components in parts by weight: Copper gluconate 0.01-0.5 parts; Vitamin E 0.05-1 part; L-menthol 0.01-0.5 parts; 3-15 parts of glycerin; Poloxamer 1-3 parts; 0.5-1.5 parts of sodium chloride; 0.2-1.5 parts of sodium citrate; 77-96 parts water.

[0023] The antibacterial wound irrigating solution provided by the present invention has excellent stability. Through the coordinated action of various components, the prepared irrigating solution has a significant antibacterial effect, can effectively prevent and control wound infection, and at the same time has little irritation to wound tissue, can promote wound healing, and has good stability, making it suitable for wide clinical application.

[0024] Specifically, the mechanism of action of the antibacterial wound irrigant provided by the present invention is summarized as follows: 1. Stability mechanism: dual protection of microemulsion system and ion chelation 1) Emulsification and stabilization effect of poloxamer: An oil-in-water (O / W) microemulsion is formed: its hydrophilic end (polyoxyethylene chain) faces outward and dissolves in the aqueous phase, while the hydrophobic end (polyoxypropylene chain) faces inward and wraps around oily ingredients such as vitamin E, forming microemulsion droplets with uniform particle size (particle size < 100 nm), preventing droplet aggregation and stratification through steric hindrance effect.

[0025] Solubilization: Dissolves insoluble components (such as vitamin E) through micelle structure, improving the clarity and stability of the system.

[0026] 2) Ion chelation of sodium citrate: Chelated Cu 2+ :Citrate ion (C6H5O7 3- ) and Cu 2+ Form a stable complex to reduce free Cu 2+ concentration, reduce the charge interference of metal ions on the system, and avoid component aggregation caused by charge repulsion.

[0027] Adjusting pH value: Acting as a buffer to maintain the acidic environment of the system (pH 4.5-6.5), on the one hand inhibiting bacterial growth (most pathogenic bacteria are suitable for a neutral environment), on the other hand stabilizing the structure of vitamin E (not easily oxidized under acidic conditions).

[0028] 2. Antibacterial mechanism: multi-component synergistic antibacterial 1) The core antibacterial effect of copper gluconate: Copper gluconate releases Cu in solution 2+ , exerting its antibacterial effect through the following pathways: Destroy bacterial cell membranes: Cu 2+ It binds to the negative charge on the cell membrane surface, destroying the lipid bilayer structure of the membrane and causing leakage of cell contents.

[0029] Interfering with bacterial DNA replication: Cu 2+ It enters the bacteria and binds to nucleic acid, inhibiting the activity of DNA polymerase and blocking the synthesis of genetic material.

[0030] Producing reactive oxygen species (ROS): The Fenton reaction induces ROS accumulation in bacteria, which oxidatively damages proteins, lipids, and nucleic acids, leading to bacterial death.

[0031] 2) Synergistic effect of poloxamer: As a nonionic surfactant, poloxamer enhances its antimicrobial effect through its amphiphilic structure: Promote copper ion penetration: its hydrophobic chain inserts into the lipid layer of bacterial membrane, increasing membrane permeability and allowing more Cu 2+ Enter the bacteria.

[0032] Stable drug release: After forming a microemulsion system, Cu is slowly released2+ , prolong the antibacterial effect time and avoid short-term high-concentration stimulation.

[0033] 3) Auxiliary antibacterial effect of L-menthol: Disintegrate biofilm: destroy the extracellular polysaccharide matrix of bacterial biofilm, making it easier for antibacterial components to access the bacteria themselves.

[0034] Enhance the clearance of drug-resistant bacteria: By changing the fluidity of bacterial membranes, reversing the efflux pump mechanism of some drug-resistant bacteria, and improving sensitivity to drug-resistant bacteria.

[0035] 3. Healing-promoting mechanism: synergistic effects of antioxidant, moisturizing and repair 1) Antioxidant protection of vitamin E (d-α-tocopherol) Scavenging free radicals: As a fat-soluble antioxidant, it directly captures excess hydroxyl radicals and superoxide anions at the wound site, reducing the damage of oxidative stress to cell membranes.

[0036] Inhibit inflammatory response: reduce the expression of pro-inflammatory factors (such as IL-6, TNF-α), reduce neutrophil infiltration, shorten the inflammatory phase, and promote the wound to enter the proliferation phase.

[0037] 2) Glycerin’s moisturizing and repairing properties Enhance the dispersibility of vitamin E: As a polar solvent, it works synergistically with poloxamer to evenly disperse vitamin E in the aqueous phase system, thereby improving bioavailability.

[0038] Maintain a moist microenvironment: retain moisture in the wound through hygroscopicity, prevent the wound from drying out and scabbing, reduce mechanical damage, and promote epithelial cell migration.

[0039] 4. Biocompatibility mechanism: reducing metal ion toxicity and irritation 1) Reduce free Cu 2+ Cytotoxicity: Sodium citrate complexes with copper gluconate, significantly reducing the free Cu 2+ concentration, avoid high concentration of Cu 2+ Direct toxicity to fibroblasts and keratinocytes while reducing the risk of metal ion deposition.

[0040] 2) Mild pH value and non-irritating ingredients: The system pH value is controlled at 4.5-6.5 to avoid strong acidity or alkalinity irritation to the wound; it does not contain traditional irritating disinfectants such as alcohol and iodine, reducing damage to the nerve endings of the wound.

[0041] This synergistic design not only overcomes the limitations of a single ingredient (such as copper ion deposition and poor water solubility of vitamin E), but also significantly improves clinical efficacy through multi-target effects, achieving both high efficiency and safety.

[0042] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below.

[0043] Example 1 This embodiment provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 188 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Under heating conditions, add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, and 0.06 parts of L-menthol to 40 parts of purified water, and stir until completely dissolved to form a mixture C. The heating temperature is 45±2°C. S4: Slowly add 0.04 parts of copper gluconate to mixture C, stirring until completely dissolved, to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0044] Example 2 This embodiment provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.1 parts of vitamin E (d-α-tocopherol) and 5 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 1.5 parts of poloxamer 188 was added to 38 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Under heating conditions, add 1 part sodium citrate, 1 part sodium chloride, and 0.1 part L-menthol to 50 parts purified water, and stir until completely dissolved to form a mixture C. The heating temperature is 45±2°C. S4: Slowly add 0.08 parts of copper gluconate to mixture C, stirring until completely dissolved, to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0045] Example 3 This embodiment provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.4 parts of vitamin E (d-α-tocopherol) and 10 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 188 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Under heating conditions, add 0.3 parts of sodium citrate, 0.7 parts of sodium chloride, and 0.02 parts of L-menthol to 40 parts of purified water, and stir until completely dissolved to form a mixture C. The heating temperature is 45±2°C. S4: Slowly add 0.01 parts of copper gluconate to mixture C, stirring until it is completely dissolved to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M sodium hydroxide solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0046] Example 4 This embodiment provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 407 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Under heating conditions, add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, and 0.06 parts of L-menthol to 40 parts of purified water, and stir until completely dissolved to form a mixture C. The heating temperature is 45±2°C. S4: Slowly add 0.04 parts of copper gluconate to mixture C, stirring until completely dissolved, to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0047] Example 5 This embodiment provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 338 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Under heating conditions, add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, and 0.06 parts of L-menthol to 40 parts of purified water, and stir until completely dissolved to form a mixture C. The heating temperature is 45±2°C. S4: Slowly add 0.04 parts of copper gluconate to mixture C, stirring until completely dissolved, to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0048] All comparative examples in the present invention are compared with Example 1.

[0049] Comparative Example 1 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 188 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Under heating conditions, add 0.8 parts of sodium chloride and 0.06 parts of L-menthol to 40 parts of purified water, and stir until completely dissolved to form a mixture C. The heating temperature is 45±2°C. S4: Slowly add 0.04 parts of copper gluconate to mixture C, stirring until completely dissolved, to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M sodium hydroxide solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0050] Comparative Example 2 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 2 parts of poloxamer 188, by weight, were added to 48 parts of purified water and stirred until completely dissolved to form a mixture A; wherein the heating temperature was 45±2°C; S2: Add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, and 0.06 parts of L-menthol to 40 parts of purified water and stir until completely dissolved to form a mixture B; S3: Slowly add 0.04 parts of copper gluconate to mixture B, stirring until completely dissolved, to form mixture C; S4: slowly dripping mixture A into mixture C, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture D is formed; S5: Add purified water to the mixture D to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound rinse.

[0051] Comparative Example 3 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, and 0.06 parts of L-menthol to 88 parts of purified water and stir until completely dissolved to form a mixture B; S3: Slowly add 0.04 parts of copper gluconate to mixture B, stirring until completely dissolved, to form mixture C; S4: slowly dripping mixture A into mixture C, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture D is formed; S5: Add purified water to the mixture D to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M sodium hydroxide solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0052] Comparative Example 4 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 188 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Add 0.6 parts of sodium citrate and 0.8 parts of sodium chloride to 40 parts of purified water, and stir until completely dissolved to form a mixture C; S4: Slowly add 0.04 parts of copper gluconate to mixture C, stirring until completely dissolved, to form mixture D; S5: slowly adding mixture B dropwise into mixture D, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture E is formed; S6: Add purified water to make the mixture E to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M sodium hydroxide solution, filter, fill, and sterilize to obtain the antibacterial wound irrigation solution.

[0053] Comparative Example 5 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol), 8 parts of glycerol, and 2 parts of poloxamer 188, by weight, are added to 48 parts of purified water and stirred until completely dissolved to form a mixture A; wherein the heating temperature is 45±2°C; S2: Add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, and 0.06 parts of L-menthol to 40 parts of purified water and stir until completely dissolved to form a mixture B; S3: Slowly add 0.04 parts of copper gluconate to mixture B, stirring until completely dissolved, to form mixture C; S4: slowly dripping mixture A into mixture C, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture D is formed; S5: Add purified water to the mixture D to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound rinse.

[0054] Comparative Example 6 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol) and 8 parts of glycerol are mixed by stirring, by weight, to form a mixture A, wherein the heating temperature is 45±2°C; S2: Under heating conditions, 2 parts of Poloxamer 188 were added to 48 parts of purified water with stirring until completely dissolved, and then added to mixture A, and then stirred to mix evenly to form mixture B; wherein the heating temperature was 45±2°C; S3: Add 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, 0.06 parts of L-menthol, and 0.04 parts of copper gluconate to 40 parts of purified water, and stir until completely dissolved to form a mixture C; S4: slowly dripping mixture B into mixture C, stirring until a uniform milky white oil-in-water (O / W) microemulsion mixture D is formed; S5: Add purified water to the mixture D to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain the antibacterial wound rinse.

[0055] Comparative Example 7 This comparative example provides a method for preparing an antibacterial wound irrigating solution, comprising the following steps: S1: Under heating conditions, 0.3 parts of vitamin E (d-α-tocopherol), 8 parts of glycerol, 2 parts of poloxamer 188, 0.6 parts of sodium citrate, 0.8 parts of sodium chloride, 0.06 parts of L-menthol, and 0.04 parts of copper gluconate were added to 88 parts of purified water by weight, and the mixture was mixed by stirring to form a mixture A, wherein the heating temperature was 45±2°C; S2: Add purified water to the mixture A to the target volume of 1 L, adjust the pH to 5.5-6.0 with 1 M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain an antibacterial wound rinse.

[0056] The antibacterial properties and stability of the antibacterial wound irrigating solutions prepared in the above examples and comparative examples were tested using the following methods: 1. Antibacterial performance test: The antibacterial performance of the antibacterial wound irrigating solutions of the above embodiments and comparative examples was tested according to WS / T 650-2019, and the antibacterial rate was calculated; 2. Product stability: The antibacterial wound irrigants of the above embodiments and comparative examples were subjected to accelerated aging verification tests according to YY / T 0681.1-2018. The sterilized products were placed in an aging chamber at a temperature of 40°C ± 2°C and a humidity of 70% ± 5%. The accelerated aging factor (AAF) = Q10

（TAA-TRT） / 10

[0057] The test results are shown in Tables 1 and 2.

[0058]

[0059]

[0060] It can be seen from the data in Table 1 and Table 2 that the antibacterial wound irrigating solutions prepared in various embodiments of the present invention have excellent antibacterial properties and stability.

[0061] Compared with Example 1, Comparative Example 1 did not add sodium citrate, and could not form a complex with Cu²⁺. The initial concentration of free Cu²⁺ was high. Although the initial antibacterial activity was good, the stability decreased, the antibacterial durability was poor, and the metal ions were easily deposited.

[0062] Compared with Example 1, Comparative Example 2 did not add glycerol. Since Poloxamer 188 could not fully emulsify vitamin E, the vitamin E had poor dispersion and was easy to precipitate, resulting in decreased system stability.

[0063] Compared with Example 1, Comparative Example 3 did not add poloxamer. Since a stable microemulsion system could not be formed, oily ingredients such as vitamin E were easily stratified. Vitamin E spontaneously aggregated in the aqueous phase due to hydrophobic interactions to form agglomerates. The agglomerates were filtered out during the filtration step, resulting in decreased stability and antibacterial effect. After the sample was proofed, obvious stratification occurred and a uniform system could not be formed.

[0064] Compared with Example 1, Comparative Example 4 did not add L-menthol, which was unable to destroy the bacterial biofilm and provide auxiliary antibacterial effect, resulting in a decrease in the antibacterial effect.

[0065] Compared with Example 1, in Comparative Example 5, vitamin E was not mixed with glycerol alone, vitamin E was not fully dispersed by glycerol, and poloxamer 188 could not fully emulsify vitamin E, which was easily precipitated in the aqueous phase, resulting in decreased system stability.

[0066] Compared with Example 1, Comparative Example 6 directly mixed sodium citrate, sodium chloride, L-menthol, and copper gluconate. Although copper gluconate and sodium citrate were directly mixed to complex Cu²⁺, sodium citrate was not first dissolved in Mixture C, resulting in reduced complexation efficiency, slightly higher free Cu²⁺ concentration, and decreased stability.

[0067] Compared with Example 1, in Comparative Example 7, the components were directly mixed without step-by-step mixing, and an ordered microemulsion system and ion complex structure could not be formed. The synergistic effect of the components was weakened, resulting in decreased stability and antibacterial properties. In addition, some precipitation and agglomerates appeared during the proofing process. After filtration in the filtration step, water-oil stratification still existed.

[0068] With the above-described preferred embodiments of the present invention as a guide, and with reference to the above description, relevant personnel are fully capable of making various changes and modifications without departing from the technical scope of this invention. The technical scope of this invention is not limited to the contents of the specification and must be determined according to the scope of the claims.

Claims

1. A method for preparing an antibacterial wound irrigating solution, characterized in that: The steps include: S1: Mix vitamin E and glycerin according to the formula at 40-50°C to form mixture A; S2: Add poloxamer to water at 40-50°C according to the formula amount, stir until dissolved, and then add it to the mixture A to form a mixture B; S3: Add sodium citrate, sodium chloride, and L-menthol to water at 40-50°C according to the formula to form a mixture C; S4: adding copper gluconate to the mixture C according to the formula amount to form a mixture D; S5: adding the mixture B dropwise into the mixture D to form a mixture E; S6: adjusting the pH of the mixture E to 4.5-6.5 to obtain an antibacterial wound rinsing solution.

2. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: The vitamin E is d-α-tocopherol.

3. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: The poloxamer is selected from at least one of poloxamer 188, poloxamer 407, poloxamer 237, poloxamer 338, and poloxamer 124.

4. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: In terms of parts by weight, the amount of vitamin E added in step S1 is 0.05-1 parts; the amount of glycerol added is 3-15 parts.

5. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: In terms of parts by weight, the amount of poloxamer added in step S2 is 1-3 parts.

6. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: In terms of parts by weight, the amount of sodium citrate added in step S3 is 0.2-1.5 parts.

7. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: In terms of parts by weight, the amount of sodium chloride added in step S3 is 0.5-1.5 parts.

8. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: In terms of parts by weight, the amount of L-menthol added in step S3 is 0.01-0.5 parts.

9. The method for preparing the antibacterial wound irrigating solution according to claim 1, wherein: In terms of parts by weight, the amount of copper gluconate added in step S4 is 0.01-0.5 parts.

10. An antibacterial wound irrigant, characterized in that: The antibacterial wound rinsing liquid is prepared by the preparation method of any one of claims 1 to 9.

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