An antibacterial wound irrigation solution and its preparation method

Abstract

This invention relates to the field of wound disinfection technology, and more particularly to an antibacterial wound irrigation solution and its preparation method. The preparation method includes the following steps: Vitamin E and glycerin are mixed at 40-50°C according to the prescribed amounts to form mixture A; poloxamer is added to water and stirred until dissolved, then added to mixture A to form mixture B; sodium citrate, sodium chloride, and L-menthol are added to water according to the prescribed amounts to form mixture C; copper gluconate is added to mixture C according to the prescribed amounts to form mixture D; mixture B is added dropwise to mixture D to form mixture E; the pH of mixture E is adjusted to 4.5-6.5, filtered, filled, and sterilized to obtain the antibacterial wound irrigation solution. This invention optimizes the preparation process, resulting in an antibacterial wound irrigation solution with excellent stability; and through the synergistic effect of the components, the prepared irrigation solution exhibits significant antibacterial efficacy.

Description

Technical Field

[0001] This invention relates to the field of wound disinfection technology, and in particular to an antibacterial wound irrigation solution and its preparation method. Background Technology

[0002] Currently, there are many types of wound irrigation solutions used clinically, but all have certain limitations. Common saline mainly serves to clean wounds, but its antibacterial ability is weak and it cannot effectively prevent or control wound infection. Irrigation solutions containing chemical disinfectants, although having strong antibacterial effects, are often highly irritating to wound tissues, affecting the wound healing process and potentially leading to delayed 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 and tendency to cause metal ion deposition when used in irrigation solutions limit their application. Summary of the Invention

[0004] To address the issue of poor stability of copper-based compounds in irrigation solutions in existing technologies, this 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, reducing the concentration of free copper ions and minimizing the risk of metal ion deposition. This method solves the problem of poor stability of copper-based compounds in irrigation solutions in existing technologies.

[0005] The technical solution adopted by this invention to solve its technical problem is:

[0006] A method for preparing an antibacterial wound irrigation solution includes the following steps:

[0007] S1: According to the formula amount, mix vitamin E and glycerin at 40-50℃ to form mixture A;

[0008] S2: According to the formula amount, add poloxamer to water at 40-50℃ and stir until dissolved, then add it to the mixture A to form mixture B;

[0009] S3: Add sodium citrate, sodium chloride, and L-menthol to water at 40-50℃ according to the formula to form mixture C;

[0010] S4: Add copper gluconate to mixture C according to the formula amount to form mixture D;

[0011] S5: Add mixture B to mixture D to form mixture E;

[0012] S6: Adjust the pH of the mixture E to 4.5-6.5 to obtain an antibacterial wound irrigation solution.

[0013] Optionally, the vitamin E is d-α-tocopherol.

[0014] Optionally, the poloxamer is selected from at least one of poloxamer 188, poloxamer 407, poloxamer 237, poloxamer 338, and poloxamer 124.

[0015] Optionally, the amount of vitamin E added in step S1 is 0.05-1 part by weight; the amount of glycerol added is 3-15 parts.

[0016] Optionally, the amount of poloxamer added in step S2 is 1-3 parts by weight.

[0017] Optionally, the amount of sodium citrate added in step S3 is 0.2-1.5 parts by weight.

[0018] Optionally, the amount of sodium chloride added in step S3 is 0.5-1.5 parts by weight.

[0019] Optionally, the amount of L-menthol added in step S3 is 0.01-0.5 parts by weight.

[0020] Optionally, the amount of copper gluconate added in step S4 is 0.01-0.5 parts by weight.

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

[0022] The beneficial effects of this invention are:

[0023] The method for preparing the antibacterial wound irrigation solution provided by this invention optimizes the preparation process, resulting in an antibacterial wound irrigation solution with excellent stability. Through the synergistic effect of each component, the prepared irrigation solution exhibits significant antibacterial effects, effectively preventing and controlling wound infection. At the same time, it has low irritation to wound tissue, promotes wound healing, and has good stability, making it suitable for widespread clinical application. Detailed Implementation

[0024] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0025] To address the problem of poor stability of copper-based compounds in irrigation solutions in existing technologies, this invention provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0026] S1: According to the formula amount, mix vitamin E and glycerin at 40-50℃ to form mixture A;

[0027] This step can be achieved by stirring, sonication, or other methods to help vitamin E and glycerin mix.

[0028] Vitamin E, as an antioxidant, is used in wound irrigation solutions. It directly protects cell membrane integrity by scavenging free radicals and inhibiting lipid peroxidation, reducing oxidative stress damage and alleviating inflammatory responses. However, its water solubility is poor. Therefore, this invention first mixes vitamin E with glycerin. This enhances the dispersion stability of vitamin E, while glycerin acts as a moisturizer to maintain a moist microenvironment in the wound, promoting fibroblast migration and collagen synthesis. The two work synergistically to form a dual "antioxidant-moisturizing" mechanism, which can reduce the level of inflammatory factors (such as IL-6), accelerate epithelial regeneration, reduce scar formation, and significantly improve tissue repair efficiency and quality.

[0029] S2: According to the formula amount, add poloxamer to water at 40-50℃ and stir until dissolved. Then add it to mixture A and mix evenly through stirring, sonication, homogenization and other operations to form mixture B.

[0030] The water used in this step is preferably purified water; this step can be achieved by stirring, sonication, or other methods to dissolve poloxamer in the water.

[0031] Due to its unique amphiphilic structure, poloxamer exhibits strong solubilizing and emulsifying capabilities for oily components such as vitamin E, forming a highly stable emulsion system that effectively prevents component separation and precipitation, thereby improving the stability of the system.

[0032] Specifically, by adding poloxamer to form an oil-in-water (O / W) microemulsion, the hydrophilic end of poloxamer dissolves in the aqueous phase with the hydrophobic end facing outwards, while the hydrophobic end encapsulates oily components such as vitamin E with the inwards, forming microemulsion droplets with uniform particle size. The steric hindrance effect prevents droplet aggregation and stratification.

[0033] S3: According to the formula amount, add sodium citrate, sodium chloride, and L-menthol to water at 40-50℃, preferably to purified water, and stir and sonicate until completely dissolved to form mixture C;

[0034] The cooling sensation provided by L-menthol can relieve wound pain and improve comfort. Furthermore, L-menthol can break down biofilms and destroy the extracellular polysaccharide matrix of bacterial biofilms, making it easier for antibacterial ingredients to contact 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 playing an auxiliary antibacterial role.

[0035] S4: Add copper gluconate to mixture C according to the formula amount. It is preferable to add copper gluconate to mixture C slowly and then stir, sonicate, etc. until it is completely dissolved to form mixture D.

[0036] Copper gluconate releases Cu in solution 2+ It exerts its antibacterial effect through the following pathways:

[0037] Disruption of bacterial cell membranes: Cu 2+ It binds to the negative charge on the cell membrane surface, disrupts the lipid bilayer structure of the membrane, and leads to leakage of cell contents;

[0038] Interfering with bacterial DNA replication: Cu 2+ It enters the bacteria and binds to nucleic acids, inhibiting DNA polymerase activity and blocking the synthesis of genetic material;

[0039] Production of reactive oxygen species (ROS): ROS accumulation is induced in bacteria through the Fenton reaction, causing oxidative damage to proteins, lipids, and nucleic acids, leading to bacterial death;

[0040] By adding copper gluconate to mixture C, citrate ions (C6H5O7) 3- ) Chelating Cu 2+ Afterwards, the positive charge is neutralized, reducing the impact of metal ions on the system's stability and ensuring product stability. This ensures uniform mixing of all components, preventing stratification and precipitation during storage and use. The synergistic effect between the components enhances the system's stability. Furthermore, the reaction between sodium citrate and copper gluconate reduces the free Cu content. 2+ The concentration reduced the cytotoxicity of the wound irrigation fluid and endowed the system with good biocompatibility;

[0041] S5: Add mixture B dropwise to mixture D to form mixture E;

[0042] Preferably, in this step, mixture B is slowly dripped into mixture D, and through stirring and other operations, until a uniform milky white oil-in-water (O / W) microemulsion system is formed, resulting in mixture E;

[0043] S6: Adjust the pH of mixture E to 4.5-6.5, filter it through a filter to remove any possible impurities; fill the filtered solution into suitable packaging, affix a label, and sterilize it by irradiation to obtain an antibacterial wound irrigation solution;

[0044] Preferably, in this step, the mixture E is brought to the target volume with purified water, and the pH is adjusted to 4.5-6.5 with 1M sodium hydroxide / hydrochloric acid solution, preferably to 5.5-6.5. The solution is then filtered, filled, and sterilized to obtain an antibacterial wound irrigation solution.

[0045] The method for preparing the antibacterial wound irrigation solution provided by this invention optimizes the preparation process, resulting in an antibacterial wound irrigation solution with excellent stability. Through the synergistic effect of each component, the prepared irrigation solution exhibits significant antibacterial effects, effectively preventing and controlling wound infection. At the same time, it has low irritation to wound tissue, promotes wound healing, and has good stability, making it suitable for widespread clinical application.

[0046] Furthermore, the present invention preferably uses d-α-tocopherol as vitamin E; and preferably uses poloxamer selected from at least one of poloxamer 188, poloxamer 407, poloxamer 237, poloxamer 338, and poloxamer 124.

[0047] Preferably, in step S1, the amount of vitamin E added is 0.05-1 part by weight, more preferably 0.1-0.4 parts; the amount of glycerol added is 3-15 parts by weight, more preferably 5-10 parts; preferably, in step S2, the amount of poloxamer added is 1-3 parts by weight, more preferably 1.5-2 parts; preferably, the amount of water added in this step is 40-60 parts by weight, more preferably 45-55 parts. The amount of sodium citrate added in step S3 is preferably 0.2-1.5 parts by weight, more preferably 0.3-1 parts; the amount of sodium chloride added is preferably 0.5-1.5 parts, more preferably 0.7-1 parts; the amount of L-menthol added is preferably 0.01-0.5 parts, more preferably 0.02-0.1 parts; the amount of water added in this step is preferably 30-50 parts, more preferably 35-45 parts; the amount of copper gluconate added in step S4 is preferably 0.01-0.5 parts by weight, more preferably 0.01-0.08 parts.

[0048] Another object of the present invention is to provide an antibacterial wound irrigation solution, which is prepared by the method described above for preparing an antibacterial wound irrigation solution.

[0049] This antibacterial wound irrigation solution comprises the following components by weight:

[0050] Copper gluconate 0.01-0.5 parts;

[0051] Vitamin E 0.05-1 serving;

[0052] L-menthol 0.01-0.5 parts;

[0053] 3-15 parts glycerin;

[0054] 1-3 servings of polosham;

[0055] Sodium chloride 0.5-1.5 parts;

[0056] Sodium citrate 0.2-1.5 parts;

[0057] Water 77-96 parts.

[0058] The antibacterial wound irrigation solution provided by this invention has excellent stability. Through the synergistic effect of each component, the prepared irrigation solution has a significant antibacterial effect, which can effectively prevent and control wound infection. At the same time, it has low irritation to wound tissue, can promote wound healing, and has good stability, making it suitable for widespread clinical application.

[0059] Specifically, the mechanism of action of the antibacterial wound irrigation solution provided by this invention is summarized as follows:

[0060] 1. Stability Mechanism: Dual Protection of Microemulsion System and Ion Chelation

[0061] 1) Emulsifying and stabilizing effect of poloxamer:

[0062] Oil-in-water (O / W) microemulsions are formed: the hydrophilic end (polyoxyethylene chain) dissolves in the aqueous phase with the outside facing out, while the hydrophobic end (polyoxypropylene chain) encapsulates oily components such as vitamin E with the inside facing in, forming microemulsion droplets with uniform particle size (particle size < 100 nm), and preventing droplet aggregation and stratification through steric hindrance effect.

[0063] Solubilizing effect: It dissolves poorly soluble components (such as vitamin E) through micellar structure, thereby improving the clarity and stability of the system.

[0064] 2) Ion chelating effect of sodium citrate:

[0065] Chelated Cu 2+ Citrate ion (C6H5O7) 3- ) and Cu 2+ Formation of stable complexes reduces free Cu 2+ Concentration reduces the charge interference of metal ions on the system, preventing component aggregation caused by charge repulsion.

[0066] pH adjustment: As a buffer, it maintains the acidic environment of the system (pH 4.5-6.5), which on the one hand inhibits bacterial growth (most pathogens are suitable for a neutral environment), and on the other hand stabilizes the structure of vitamin E (it is not easily oxidized under acidic conditions).

[0067] 2. Antibacterial mechanism: Synergistic antibacterial action of multiple components

[0068] 1) The core antibacterial effect of copper gluconate:

[0069] Copper gluconate releases Cu in solution 2+ It exerts its antibacterial effect through the following pathways:

[0070] Disruption of bacterial cell membranes: Cu 2+ It binds to the negative charge on the cell membrane surface, disrupting the lipid bilayer structure and causing leakage of cell contents.

[0071] Interfering with bacterial DNA replication: Cu 2+ It enters the bacteria, binds to nucleic acids, inhibits DNA polymerase activity, and blocks the synthesis of genetic material.

[0072] Production of reactive oxygen species (ROS): ROS accumulates in bacteria through the Fenton reaction, causing oxidative damage to proteins, lipids, and nucleic acids, leading to bacterial death.

[0073] 2) Synergistic effect of poloxamer:

[0074] As a nonionic surfactant, poloxamer enhances its antibacterial effect through its amphiphilic structure:

[0075] Promotes copper ion permeation: Its hydrophobic chains insert into the lipid layer of the bacterial membrane, increasing membrane permeability and allowing more Cu ions to permeate. 2+ It enters the interior of bacteria.

[0076] Stable drug release: After forming a microemulsion system, Cu is released slowly. 2+ This prolongs the antibacterial effect time and avoids irritation from high concentrations in a short period of time.

[0077] 3) The auxiliary antibacterial effect of L-menthol:

[0078] Disruption of biofilms: Disrupts the extracellular polysaccharide matrix of bacterial biofilms, making it easier for antibacterial components to contact the bacteria themselves.

[0079] Enhanced clearance of drug-resistant bacteria: By altering bacterial membrane fluidity, the efflux pump mechanism of some drug-resistant bacteria is reversed, thereby increasing susceptibility to drug-resistant bacteria.

[0080] 3. Healing Mechanism: Synergistic Effects of Antioxidant, Moisturizing, and Repair

[0081] 1) Antioxidant protection of vitamin E (d-α-tocopherol)

[0082] Scavenging free radicals: As a lipid-soluble antioxidant, it directly captures excess hydroxyl radicals and superoxide anions at the wound site, reducing the damage of oxidative stress to cell membranes.

[0083] Inhibits inflammatory response: Reduces the expression of pro-inflammatory factors (such as IL-6 and TNF-α), reduces neutrophil infiltration, shortens the inflammatory phase, and promotes the wound to enter the proliferative phase.

[0084] 2) Glycerin's moisturizing and repairing properties

[0085] Enhanced vitamin E dispersibility: As a polar solvent, it works synergistically with poloxamer to ensure uniform dispersion of vitamin E in the aqueous system, thereby improving bioavailability.

[0086] Maintaining a moist microenvironment: By retaining moisture in the wound through hygroscopicity, it prevents the wound from drying out and forming scabs, reduces mechanical damage, and promotes epithelial cell migration.

[0087] 4. Biocompatibility mechanism: reducing the toxicity and irritation of metal ions.

[0088] 1) Reduce free Cu 2+ Cytotoxicity: After sodium citrate complexes with copper gluconate, it significantly reduces the amount of free Cu in solution. 2+ Concentration, avoid high concentrations of Cu 2+ It exhibits direct toxicity to fibroblasts and keratinocytes while reducing the risk of metal ion deposition.

[0089] 2) Mild pH value and non-irritating ingredients: The system pH value is controlled at 4.5-6.5 to avoid strong acid or alkaline irritation to the wound; it does not contain traditional irritating disinfectants such as alcohol and iodine, reducing damage to nerve endings in the wound.

[0090] This synergistic design not only overcomes the limitations of single components (such as copper ion deposition and poor water solubility of vitamin E), but also significantly improves clinical efficacy through multi-target action, combining high efficiency and safety.

[0091] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0092] Example 1

[0093] This embodiment provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0094] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0095] S2: Under heating conditions, add 2 parts of poloxamer 188 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0096] S3: Under heating conditions, add 0.6 parts sodium citrate, 0.8 parts sodium chloride, and 0.06 parts L-menthol to 40 parts purified water, and stir until completely dissolved to form mixture C. The heating temperature is 45±2℃.

[0097] S4: Slowly add 0.04 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0098] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0099] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0100] Example 2

[0101] This embodiment provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0102] S1: Under heating conditions, 0.1 parts by weight of vitamin E (d-α-tocopherol) and 5 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0103] S2: Under heating conditions, add 1.5 parts of poloxamer 188 to 38 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0104] 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 mixture C. The heating temperature is 45±2℃.

[0105] S4: Slowly add 0.08 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0106] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0107] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0108] Example 3

[0109] This embodiment provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0110] S1: Under heating conditions, 0.4 parts by weight of vitamin E (d-α-tocopherol) and 10 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0111] S2: Under heating conditions, add 2 parts of poloxamer 188 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0112] S3: Under heating conditions, add 0.3 parts sodium citrate, 0.7 parts sodium chloride, and 0.02 parts L-menthol to 40 parts purified water, and stir until completely dissolved to form mixture C. The heating temperature is 45±2℃.

[0113] S4: Slowly add 0.01 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0114] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0115] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M sodium hydroxide solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0116] Example 4

[0117] This embodiment provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0118] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0119] S2: Under heating conditions, add 2 parts of poloxamer 407 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0120] S3: Under heating conditions, add 0.6 parts sodium citrate, 0.8 parts sodium chloride, and 0.06 parts L-menthol to 40 parts purified water, and stir until completely dissolved to form mixture C. The heating temperature is 45±2℃.

[0121] S4: Slowly add 0.04 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0122] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0123] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0124] Example 5

[0125] This embodiment provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0126] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0127] S2: Under heating conditions, add 2 parts of poloxamer 338 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0128] S3: Under heating conditions, add 0.6 parts sodium citrate, 0.8 parts sodium chloride, and 0.06 parts L-menthol to 40 parts purified water, and stir until completely dissolved to form mixture C. The heating temperature is 45±2℃.

[0129] S4: Slowly add 0.04 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0130] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0131] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0132] All comparative examples in this invention are compared with Example 1.

[0133] Comparative Example 1

[0134] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0135] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0136] S2: Under heating conditions, add 2 parts of poloxamer 188 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0137] S3: Under heating conditions, add 0.8 parts sodium chloride and 0.06 parts L-menthol to 40 parts purified water, and stir until completely dissolved to form mixture C. The heating temperature is 45±2℃.

[0138] S4: Slowly add 0.04 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0139] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0140] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M sodium hydroxide solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0141] Comparative Example 2

[0142] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0143] S1: Under heating conditions, add 0.3 parts by weight of vitamin E (d-α-tocopherol) and 2 parts by weight of poloxamer 188 to 48 parts by purified water and stir until completely dissolved to form mixture A; wherein the heating temperature is 45±2℃.

[0144] S2: Add 0.6 parts sodium citrate, 0.8 parts sodium chloride, and 0.06 parts L-menthol to 40 parts purified water and stir until completely dissolved to form mixture B;

[0145] S3: Slowly add 0.04 parts of copper gluconate to mixture B and stir until completely dissolved to form mixture C;

[0146] S4: Slowly drip mixture A into mixture C, stirring until a uniform, milky white oil-in-water (O / W) microemulsion system, mixture D, is formed;

[0147] S5: Add purified water to bring the mixture D to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0148] Comparative Example 3

[0149] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0150] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0151] S2: Add 0.6 parts sodium citrate, 0.8 parts sodium chloride, and 0.06 parts L-menthol to 88 parts purified water and stir until completely dissolved to form mixture B;

[0152] S3: Slowly add 0.04 parts of copper gluconate to mixture B and stir until completely dissolved to form mixture C;

[0153] S4: Slowly drip mixture A into mixture C, stirring until a uniform, milky white oil-in-water (O / W) microemulsion system, mixture D, is formed;

[0154] S5: Add purified water to bring the mixture D to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M sodium hydroxide solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0155] Comparative Example 4

[0156] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0157] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0158] S2: Under heating conditions, add 2 parts of poloxamer 188 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0159] S3: Add 0.6 parts sodium citrate and 0.8 parts sodium chloride to 40 parts purified water, and stir until completely dissolved to form mixture C;

[0160] S4: Slowly add 0.04 parts of copper gluconate to mixture C and stir until completely dissolved to form mixture D;

[0161] S5: Slowly drip mixture B into mixture D, stirring until a uniform, milky white oil-in-water (O / W) microemulsion mixture E is formed;

[0162] S6: Add purified water to bring the mixture E to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M sodium hydroxide solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0163] Comparative Example 5

[0164] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0165] S1: Under heating conditions, add 0.3 parts by weight of vitamin E (d-α-tocopherol), 8 parts by weight of glycerol, and 2 parts by weight of poloxamer 188 to 48 parts by weight of purified water and stir until completely dissolved to form mixture A; wherein the heating temperature is 45±2℃.

[0166] S2: Add 0.6 parts sodium citrate, 0.8 parts sodium chloride, and 0.06 parts L-menthol to 40 parts purified water and stir until completely dissolved to form mixture B;

[0167] S3: Slowly add 0.04 parts of copper gluconate to mixture B and stir until completely dissolved to form mixture C;

[0168] S4: Slowly drip mixture A into mixture C, stirring until a uniform, milky white oil-in-water (O / W) microemulsion system, mixture D, is formed;

[0169] S5: Add purified water to bring the mixture D to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0170] Comparative Example 6

[0171] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0172] S1: Under heating conditions, 0.3 parts by weight of vitamin E (d-α-tocopherol) and 8 parts by weight of glycerol are mixed by stirring to form mixture A, wherein the heating temperature is 45±2℃;

[0173] S2: Under heating conditions, add 2 parts of poloxamer 188 to 48 parts of purified water and stir until completely dissolved. Then add it to mixture A and mix evenly by stirring to form mixture B. The heating temperature is 45±2℃.

[0174] S3: Add 0.6 parts sodium citrate, 0.8 parts sodium chloride, 0.06 parts L-menthol, and 0.04 parts copper gluconate to 40 parts purified water and stir until completely dissolved to form mixture C;

[0175] S4: Slowly drip mixture B into mixture C, stirring until a uniform, milky white oil-in-water (O / W) microemulsion system, mixture D, is formed;

[0176] S5: Add purified water to bring the mixture D to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0177] Comparative Example 7

[0178] This comparative example provides a method for preparing an antibacterial wound irrigation solution, comprising the following steps:

[0179] S1: Under heating conditions, according to the following weight proportions, add 0.3 parts vitamin E (d-α-tocopherol), 8 parts glycerol, 2 parts poloxamer 188, 0.6 parts sodium citrate, 0.8 parts sodium chloride, 0.06 parts L-menthol, and 0.04 parts copper gluconate to 88 parts purified water, and mix them evenly by stirring to form mixture A. The heating temperature is 45±2℃.

[0180] S2: Add purified water to bring the mixture A to the target volume of 1L, adjust the pH to 5.5-6.0 with 1M dilute hydrochloric acid solution, filter, fill, and sterilize to obtain antibacterial wound irrigation solution.

[0181] The antibacterial properties and stability of the antibacterial wound irrigation solutions prepared in the above embodiments and comparative examples were tested using the following methods:

[0182] 1. Antibacterial performance test: The antibacterial performance of the antibacterial wound irrigation solutions of the above examples and comparative examples was tested in accordance with WS / T 650-2019, and the antibacterial rate was calculated.

[0183] 2. Product Stability: The antibacterial wound irrigation solutions 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℃±2℃ and a humidity of 70%±5%, and the accelerated aging factor (AAF) was calculated as Q10.

（TAA-TRT） / 10

[0184] The test results are shown in Tables 1 and 2.

[0185]

[0186]

[0187] As can be seen from the data in Tables 1 and 2, the antibacterial wound irrigation solutions prepared in each embodiment of the present invention all have excellent antibacterial properties and stability.

[0188] Compared with Example 1, Comparative Example 1 did not add sodium citrate, so it could not form a complex with Cu²⁺. The initial concentration of free Cu²⁺ was high. Although the initial antibacterial properties were good, the stability decreased, the antibacterial durability was poor, and metal ions were easy to deposit.

[0189] Compared with Example 1, Comparative Example 2 did not add glycerin. As a result, poloxamer 188 could not fully emulsify vitamin E, leading to poor dispersibility of vitamin E and easy precipitation, which in turn reduced the stability of the system.

[0190] Compared with Example 1, Comparative Example 3 did not add poloxamer. As a result, a stable microemulsion system could not be formed, and oily components such as vitamin E were prone to separation. Vitamin E spontaneously aggregated in the aqueous phase due to hydrophobic interactions, forming agglomerates. The agglomerates were filtered out during the filtration step, resulting in a decrease in stability and antibacterial effect. After the sample was prepared, there was obvious separation and a uniform system could not be formed.

[0191] Compared with Example 1, Comparative Example 4 did not add L-menthol, which could not destroy the bacterial biofilm and thus could not provide auxiliary antibacterial effects, resulting in a decrease in antibacterial efficacy.

[0192] Compared with Example 1, Comparative Example 5 did not mix vitamin E with glycerol separately, so vitamin E was not sufficiently dispersed by glycerol. Poloxamer 188 could not fully emulsify vitamin E, and it was easy to precipitate in the aqueous phase, resulting in a decrease in system stability.

[0193] Compared with Example 1, Comparative Example 6 directly mixed sodium citrate, sodium chloride, L-menthol, and copper gluconate. Although the direct mixing of copper gluconate and sodium citrate could complex Cu²⁺, the sodium citrate was not first dissolved in mixture C, resulting in a lower complexation efficiency, a slightly higher concentration of free Cu²⁺, and decreased stability.

[0194] Compared with Example 1, Comparative Example 7 directly mixed the components without stepwise mixing, which failed to form an ordered microemulsion system and ion complex structure. The synergistic effect of the components was weakened, resulting in a decrease in stability and antibacterial properties. Furthermore, some precipitates and agglomerates appeared during the sampling process, and water-oil separation still existed after filtration.

[0195] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A method for preparing an antibacterial wound irrigation solution, characterized in that, Includes the following steps: S1: According to the formula amount, mix vitamin E and glycerin at 40-50℃ to form mixture A; S2: According to the formula amount, add poloxamer to water at 40-50℃ and stir until dissolved, then add it to the mixture A to form mixture B; S3: Add sodium citrate, sodium chloride, and L-menthol to water at 40-50℃ according to the formula to form mixture C; S4: Add copper gluconate to mixture C according to the formula amount to form mixture D; S5: Add mixture B to mixture D to form mixture E; S6: Adjust the pH of the mixture E to 4.5-6.5 to obtain an antibacterial wound irrigation solution.

2. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, The vitamin E mentioned is d-α-tocopherol.

3. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, 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 irrigation solution as described in claim 1, characterized in that, The amount of vitamin E added in step S1 is 0.05-1 part by weight; the amount of glycerol added is 3-15 parts.

5. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, The amount of poloxamer added in step S2 is 1-3 parts by weight.

6. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, The amount of sodium citrate added in step S3 is 0.2-1.5 parts by weight.

7. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, The amount of sodium chloride added in step S3 is 0.5-1.5 parts by weight.

8. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, The amount of L-menthol added in step S3 is 0.01-0.5 parts by weight.

9. The method for preparing the antibacterial wound irrigation solution as described in claim 1, characterized in that, The amount of copper gluconate added in step S4 is 0.01-0.5 parts by weight.

10. An antibacterial wound irrigation solution, characterized in that, The antibacterial wound irrigation solution is prepared by the method described in any one of claims 1-9.

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