Full-spectrum nano titanium oxide bactericide as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medical bactericides, and discloses a full-spectrum nano titanium oxide bactericide and a preparation method and application thereof.The bactericide is prepared from, by mass, 1 part of nano titanium dioxide, 0.05-0.1 part of a photocatalyst, 98.0-98.5 parts of purified water, 0.2-0.4 part of a dispersing agent, 0.05-0.2 part of a stabilizer and 0.05-0.3 part of a pH regulator; and the particle size of the nano titanium dioxide is 5-20 nm. Through design of a photocatalyst, optimization of a dispersion system and upgrading of a preparation process, breakthrough of nano TiO2 in the aspects of full-spectrum response, light storage performance and extreme environment adaptability is realized. All the components have a synergistic effect through multiple mechanisms such as electron transfer, surface protection and microenvironment regulation and control, an innovative scheme is provided for solving the application bottleneck of existing nano titanium dioxide, and the nano titanium dioxide has a wide industrialization prospect in the medical antibacterial field.

Description

Technical Field

[0001] The present invention relates to the technical field of medical fungicides, and in particular to a full-spectrum nano-titanium oxide fungicide and a preparation method and application thereof. Background Art

[0002] Nano-titanium dioxide (TiO2), also known as nano-titanium dioxide, is an inorganic nanomaterial composed of titanium and oxygen elements, and its particle size is usually between 1 and 100 nm. Due to its special nano-size effect, nano-titanium dioxide has unique physical and chemical properties, such as high specific surface area, strong adsorption capacity and excellent photocatalytic activity. These characteristics make it show great application potential in many fields. From the perspective of crystal structure, nano-titanium dioxide mainly exists in three crystal forms: anatase, rutile and brookite. Among them, anatase and rutile are the most widely used in the field of photocatalysis. There are differences in photocatalytic activity and stability between different crystal forms, which also provides a theoretical basis for its performance regulation.

[0003] The most outstanding advantage of nano-titanium dioxide is its ability to kill microorganisms across the entire spectrum. Under the action of photocatalysis, nano-titanium dioxide can produce hydroxyl radicals (-OH) and superoxide anion radicals with strong oxidizing properties. These reactive oxygen species can destroy the cell walls, cell membranes, and intracellular biomacromolecule structures of microorganisms such as bacteria, viruses, and fungi, achieving efficient inactivation of various microorganisms. It has important value in the fields of public health and biosafety. However, this material has significant limitations. Its photocatalytic activity is highly dependent on ultraviolet light excitation of a specific wavelength, and it can only respond to ultraviolet light with a wavelength less than 387.5nm. This greatly reduces its application effect under natural light or ordinary indoor environments, limiting its large-scale promotion and use.

[0004] In the medical field, the application of nano-titanium dioxide is developing in the direction of refinement and intelligence. In terms of antibacterial disinfection, its full-spectrum bactericidal properties are widely used in the surface modification of medical consumables. Through sol-gel method, chemical vapor deposition method and other technologies, nano-titanium dioxide can be evenly coated on the surface of medical catheters, syringes, and implantable medical devices to form a long-lasting antibacterial protective layer. Clinical studies have shown that the incidence of nosocomial infection of central venous catheters treated with nano-titanium dioxide is more than 30% lower than that of traditional catheters. In addition, medical textiles prepared by combining nano-titanium dioxide with fiber materials, such as surgical gowns and wound dressings, can continuously inhibit bacterial growth during wear, reducing the risk of cross-infection.

[0005] The field of tumor treatment is the forefront of the application of nano-titanium dioxide. Based on the principle of photodynamic therapy (PDT), researchers use nanotechnology to precisely control the size of nano-titanium dioxide particles to 10-50 nanometers and perform biofunctional modification on their surfaces. For example, monoclonal antibodies against specific antigens on the surface of tumor cells are used to couple nano-titanium dioxide so that it can actively target tumor tissue. Under near-ultraviolet light irradiation, the reactive oxygen species produced by nano-titanium dioxide can selectively destroy the mitochondrial membrane potential of tumor cells and induce tumor cell apoptosis. At the same time, by activating the body's immune response, it triggers a tumor-specific immune response, achieving "photodynamic-immunotherapy combined therapy." Animal experiments have shown that this method can achieve an inhibition rate of more than 70% for solid tumors such as breast cancer and liver cancer.

[0006] In drug delivery systems, nano-titanium dioxide has a high specific surface area (up to 50-200m 2 / g) and a controllable pore structure, making it an ideal drug carrier material. Using mesoporous titanium dioxide (mesoporous TiO2) as a carrier, anticancer drugs, antibiotics, etc. can be loaded through physical adsorption or chemical bonding. By introducing pH-responsive polymers or magnetic nanoparticles to functionalize it, targeted delivery and intelligent release of drugs can be achieved. For example, under the weakly acidic conditions of the tumor microenvironment, pH-responsive nano-titanium dioxide carriers can rapidly release drugs, significantly increasing the drug concentration in the tumor site while reducing toxic side effects on normal tissues.

[0007] Although nano-titanium dioxide has shown great potential in the medical field, its clinical transformation still faces technical bottlenecks. The primary difficulty is to break through the limitations of the light response range. Currently, researchers are trying to broaden its light response range to the visible light and even near-infrared light region through strategies such as metal / non-metal element doping (such as nitrogen doping, silver doping) and semiconductor composites (compounds with zinc oxide, cadmium sulfide, etc.). Secondly, the problem of maintaining activity after the light source is removed needs to be solved urgently. The research team is exploring ways to achieve the light storage properties of nano-titanium dioxide by constructing core-shell structures (such as titanium dioxide @ silicon dioxide core-shell structures) and introducing energy storage materials (such as rare earth luminescent materials), so that it can continue to exert its antibacterial and therapeutic effects under no light conditions. In addition, the long-term safety evaluation of nano-titanium dioxide in the body, the optimization of large-scale preparation processes, and other issues also require multidisciplinary collaboration to lay a solid foundation for its clinical application. Summary of the Invention

[0008] The present invention aims to provide a full-spectrum nano-titanium dioxide fungicide and its preparation method and application, so as to solve the problems of the prior art in that the light response range and light storage capacity of nano-titanium dioxide are not ideal.

[0009] To achieve the above-mentioned purpose, the present invention adopts the following technical solution: a full-spectrum nano-titanium dioxide fungicide, the raw materials of which, by mass, include 1 part of nano-titanium dioxide, 0.05-0.1 part of photocatalyst, 98.0-98.5 parts of purified water, 0.2-0.4 part of dispersant, 0.05-0.2 part of stabilizer, and 0.05-0.3 part of pH adjuster; the particle size of the nano-titanium dioxide is 5-20 nm.

[0010] Preferably, as an improvement, the photocatalyst is Ag-Cu composite nano-promoter or carbon quantum dots.

[0011] Preferably, as an improvement, the purified water is injection-grade purified water, and the dispersant is at least one of PEG-400 and Tween 80.

[0012] Preferably, as an improvement, the stabilizer is sodium citrate; the pH regulator is a weak base regulator, and the pH regulator adjusts the pH of the solution to 6.0-7.5.

[0013] Preferably, as an improvement, a method for preparing a full-spectrum nano-titanium oxide fungicide comprises the following steps:

[0014] Step 1: Dissolving and mixing raw materials: adding a dispersant and a stabilizer to purified water in a stirring state, and dissolving them to obtain System I;

[0015] Step 2: Add nano-titanium dioxide to system I and disperse it under high-speed shear conditions to obtain a milky white system II;

[0016] Step 3: Add the photocatalyst to system II and stir to obtain system III;

[0017] Step 4: Use a pH regulator to adjust the pH of system III to 6.0–7.5;

[0018] Step 5: Degassing and filtration: Stir and degas the pH-adjusted system III, and then filter to remove impurities and bacteria.

[0019] Step 6. Packaging: Filling and sealing operations are completed in a GMP Class B (ISO Class 7) clean room with an ambient temperature of 20±2°C and a relative humidity of 40–60%.

[0020] Preferably, as an improvement, in step one, the stirring speed is 150-200 rpm; in step two, the high-speed shearing speed is 300-500 rpm; in step five, the filtering method is filtration using a 0.22 μm microporous membrane.

[0021] Preferably, as an improvement, a full-spectrum nano-titanium oxide fungicide is used in the preparation of wound healing drugs.

[0022] Preferably, as an improvement, a full-spectrum nano-titanium oxide fungicide is used in the preparation of a drug for preventing skin infections.

[0023] Preferably, as an improvement, a full-spectrum nano-titanium oxide fungicide is used in the preparation of a drug for removing stubborn skin tinea and athlete's foot.

[0024] Preferably, as an improvement, a full-spectrum nano-titanium oxide bactericide is used in the preparation of an antibacterial deodorant.

[0025] The principles and advantages of this solution are as follows: In practical application, this technical solution addresses the limitations of existing nano-titanium dioxide applications in the medical field. By designing photocatalysts, optimizing the dispersion system, and upgrading the preparation process, it achieves breakthroughs in nano-titanium dioxide's full-spectrum response, light storage performance, and adaptability to extreme environments. The synergistic interaction between the components through multiple mechanisms, including electron transfer, surface protection, and microenvironmental regulation, provides an innovative solution to address the current application bottlenecks of nano-titanium dioxide and has broad industrial prospects in the medical antibacterial field. In this solution, the synergistic effect of photocatalysts is utilized in the formulation optimization of the antiseptic to expand the photoresponse range: the synergistic effect of silver (Ag) and copper (Cu) expands the photoresponse range through the surface plasmon resonance (SPR) effect. Ag nanoparticles generate SPR absorption in the visible light region of 400-500nm, exciting electrons to be injected into the TiO2 conduction band; Cu reduces the electron-hole recombination rate through energy level matching. Furthermore, carbon quantum dots (CQDs) possess unique upconversion fluorescence properties, converting infrared light into ultraviolet / visible light to excite TiO2. At the same time, the abundant oxygen-containing functional groups (such as -OH, -COOH) on the surface of CQDs are adsorbed on the surface of TiO2 through hydrogen bonding to form a charge transfer complex, which broadens the light response range. 4+ The ions form a protective layer on the surface of the nanoparticles; at the same time, their carboxylate ions can capture photogenerated holes and reduce electron-hole recombination, thereby achieving the purpose of inhibiting TiO2 agglomeration and preventing metal ion precipitation.

[0026] In summary, the full spectrum nano titanium dioxide fungicide of this technical solution has the following advantages:

[0027] 1. Full spectrum: responsive to ultraviolet light, visible light and infrared light.

[0028] 2. Photoluminescent type: Remains active after the light source is removed.

[0029] 3. Continuous and long-lasting sterilization: the bacterial count in 24 hours is 1% to 1‰ of the control group

[0030] 4. High safety: The raw materials used are food additives with no toxic side effects.

[0031] 5. High stability: with permanent storage characteristics.

[0032] 6. Resistance to extreme environments: not afraid of high heat, high cold, low oxygen, closed, humid and underwater environment. DETAILED DESCRIPTION

[0033] The following will be further described in detail by specific embodiments, but the embodiments of the present application are not limited thereto. If not specifically indicated, the technical means used in the following embodiments are conventional means known to those skilled in the art; the experimental methods used are conventional methods; the materials, reagents, etc. used can be obtained from commercial channels.

[0034] General description of the scheme:

[0035] A full-spectrum nano titanium oxide bactericide, the raw materials are calculated by mass parts, including nano titanium dioxide 1 part, photocatalyst 0.05-0.1 part, purified water 98.0-98.5 parts, dispersing agent 0.2-0.4 parts, stabilizer 0.05-0.2 parts, pH adjuster 0.05-0.3 parts.

[0036] Among them, the particle size of nano titanium dioxide is 5-20 nm, and it has full-spectrum response performance.

[0037] The photocatalyst is Ag-Cu composite nano cocatalyst or carbon quantum dots.

[0038] The purified water is injection grade purified water, which meets the standard of pharmacopoeia.

[0039] The dispersing agent is at least one of PEG-400 and Tween 80, which is used to enhance the dispersibility of TiO2 in aqueous phase.

[0040] The stabilizer is sodium citrate, which is used to inhibit the agglomeration of TiO2 and prevent the precipitation of metal ions.

[0041] The pH adjuster is a weak base adjuster, and the pH adjuster adjusts the pH of the solution to 6.0-7.5.

[0042] A preparation method of a full-spectrum nano titanium oxide bactericide, comprising the following steps:

[0043] Step one, raw material dissolution and mixing: 98.0-98.5 parts of injection grade purified water is added to a clean preparation tank, and medium speed stirring (150-200 rpm) is started, 0.2-0.4 parts of dispersing agent and 0.05-0.2 parts of stabilizer are added in turn, and stirred for 5-10 min to make them fully dissolved, forming a uniform transparent solution, obtaining system I;

[0044] Step 2: Slowly add 1 part of nano-titanium dioxide powder to the system I obtained in step 1, and continuously disperse it under high-speed shear conditions (300-500 rpm) for 20 minutes until the system becomes milky white, uniform, and has no obvious agglomeration, to obtain system II;

[0045] Step 3: Add 0.05–0.1 parts of photocatalyst to the dispersed system II and continue stirring for 10 minutes to ensure that the catalytic components are fully dispersed and enhance the photocatalytic efficiency in subsequent use to obtain system III;

[0046] Step 4: Use a pH meter to monitor the pH of System III in real time, and slowly add 0.05–0.3 parts of pH adjuster to adjust the pH value of the system to 6.0–7.5, suitable for spraying on the skin or mucous membranes;

[0047] Step 5: Degassing and filtration: Stir the mixture at a low speed (50–80 rpm) for 3–5 min to eliminate microbubbles. If necessary, filter the mixture through a 0.22 μm microporous membrane to remove impurities and bacteria.

[0048] Step 6. Transfer and Packaging: Transfer the resulting fungicide solution to a UV-sterilized stainless steel tank and complete aseptic filling, sealing, and labeling within 2 hours. The entire process is completed in a GMP Class B (ISO Class 7) cleanroom at an ambient temperature of 20 ± 2°C and a relative humidity of 40–60%.

[0049] Application of a full-spectrum nano-titanium oxide fungicide in the preparation of wound healing drugs.

[0050] Application of a full-spectrum nano-titanium oxide fungicide in the preparation of drugs for preventing skin infections.

[0051] The invention discloses an application of a full-spectrum nano-titanium oxide fungicide in the preparation of a medicine for removing stubborn skin ringworm and athlete's foot.

[0052] Application of a full-spectrum nano-titanium oxide bactericide in the preparation of an antibacterial deodorant.

[0053] Example 1

[0054] A full-spectrum nano-titanium oxide fungicide. The raw materials, calculated by weight, include 1 part of nano-titanium dioxide, 0.05 part of photocatalyst, 98.5 parts of purified water, 0.2 part of dispersant, 0.2 part of stabilizer, and 0.05 part of pH regulator.

[0055] Among them, the particle size of nano titanium dioxide is 5-20nm, and it has full spectrum response performance.

[0056] The photocatalyst is carbon quantum dots.

[0057] Purified water is injection grade purified water and meets pharmacopoeia standards.

[0058] The dispersant is PEG-400, which is used to enhance the dispersibility of TiO2 in the aqueous phase.

[0059] The stabilizer is sodium citrate, which is used to inhibit the agglomeration of TiO2 and prevent the precipitation of metal ions.

[0060] The pH adjuster is a weak base adjuster that adjusts the pH of the solution to 6.0–7.5.

[0061] The preparation process is the same as that in the general description of the above scheme.

[0062] Example 2

[0063] A full-spectrum nano-titanium oxide fungicide. The raw materials, calculated by weight, include 1 part of nano-titanium dioxide, 0.1 part of photocatalyst, 98.0 parts of purified water, 0.4 part of dispersant, 0.05 part of stabilizer, and 0.3 part of pH regulator.

[0064] Among them, the particle size of nano titanium dioxide is 5-20nm, and it has full spectrum response performance.

[0065] The photocatalyst is Ag-Cu composite nano-catalyst.

[0066] Purified water is injection grade purified water and meets pharmacopoeia standards.

[0067] The dispersant is Tween 80, which is used to enhance the dispersibility of TiO2 in the aqueous phase.

[0068] The stabilizer is sodium citrate, which is used to inhibit the agglomeration of TiO2 and prevent the precipitation of metal ions.

[0069] The pH adjuster is a weak base adjuster that adjusts the pH of the solution to 6.0–7.5.

[0070] The preparation process is the same as that in the general description of the above scheme.

[0071] Experimental Example 1: Test of Physical and Chemical Properties of Fungicide

[0072] The physical and chemical properties of the nano titanium dioxide fungicide prepared in Example 1 were tested. The test methods and results are as follows:

[0073] 1. Determination of pH value: The test method refers to Item 2.2.1.4 of the Technical Specification for Disinfection (2002 edition);

[0074] The test method is as follows: After shaking, take 10 mL of the nano-titanium dioxide fungicide stock solution as the test solution. Use pH test paper to determine the pH value of the test solution to be 3. Calibrate the pH meter with potassium tetrahydrogen oxalate standard buffer (pH 1.68, 25°C) and potassium hydrogen phthalate standard buffer (pH 4.00, 25°C). Immerse the electrode in the test solution and record the pH value after the displayed value stabilizes.

[0075] Three bottles of samples were taken and the test was repeated twice for each bottle. The test environment temperature was 22.9°C and the relative humidity was 62%.

[0076] The test results show that the average pH value of the nano-titanium dioxide fungicide of the present invention is 6.5.

[0077] 2. Lead content test: The test method refers to Chapter 4, 1.3 Lead (Method 1) of the "Technical Specifications for Safety of Cosmetics" (2015 edition);

[0078] The test method is:

[0079] ① Preparation of standard working curve: Prepare a standard series with lead concentrations ranging from 0 μg / L to 20.00 μg / L. Perform analysis under the set conditions to obtain a linear equation.

[0080] ② Sample Pretreatment: After shaking well, accurately transfer 1.00 mL of sample to an Erlenmeyer flask. Add several glass beads and 10.0 mL of nitric acid. Heat from low to high temperature to digest. When the volume of the digestion solution is reduced to approximately 2 mL, remove the heat source and cool. Then, add another 2.0 mL of perchloric acid and continue heating and digesting, gently shaking occasionally to ensure uniformity. Digest until white smoke appears and the digestion solution is colorless. Concentrate the digestion solution to approximately 1 mL. After cooling to room temperature, quantitatively transfer the sample to a 10 mL stoppered colorimetric tube. Rinse the Erlenmeyer flask with grade 1 water, add the washing solution to the colorimetric tube, and then dilute to the mark with grade 1 water. Mix thoroughly. Simultaneously, perform a reagent blank.

[0081] ③ Take appropriate amount of sample solution and reagent blank solution respectively, inject them into atomic absorption spectrometer to measure their absorbance, and read the corresponding lead concentration from the standard curve.

[0082] Three bottles of samples were taken and the test was repeated twice for each bottle. The test environment temperature was 21.1°C and the relative humidity was 58%.

[0083] The test results are shown in Table 1: the average lead content is 62μg / L, which meets the requirements of the enterprise standard Q / CQSM001-2023 "Disinfectants".

[0084] Table 1

[0085]

[0086] 3. Arsenic content test: The test method refers to Chapter 4, 1.4 Arsenic (Method 1) of the "Technical Specifications for Safety of Cosmetics" (2015 edition);

[0087] The test method is:

[0088] ① Preparation of standard working curve: Prepare a standard series with arsenic concentrations ranging from 0 μg / L to 20.00 μg / L. Perform analysis under the set conditions and obtain a linear equation;

[0089] ② Sample pretreatment: After shaking, accurately transfer 1.00mL of sample into a conical flask, add a few glass beads, add 10.0mL of nitric acid, let it sit for a while, heat slowly, remove the heat source after the reaction starts, and add 2.0mL of sulfuric acid after cooling slightly. Continue heating to digest. If the solution turns brown during the digestion process, add a little nitric acid to digest it. Repeat this process until the solution is clear or slightly yellow. After cooling, add 20mL of first-grade water and continue heating and boiling until white smoke is produced. Transfer the digestion solution to a 25mL stoppered colorimetric tube, wash the conical flask with first-grade water, add the washing solution into the colorimetric tube, dilute to the scale, and obtain the sample solution. Then take 10mL of the sample solution into a 25mL colorimetric tube, add 2.0mL of thiourea-ascorbic acid solution, mix well, and make a reagent blank at the same time;

[0090] ③ Take appropriate amount of sample solution and reagent blank solution respectively, inject them into atomic fluorescence spectrometer to measure their fluorescence value, and read the corresponding arsenic concentration from the standard curve;

[0091] Three bottles of samples were taken and the test was repeated twice for each bottle. The test environment temperature was 20.9°C and the relative humidity was 60%.

[0092] The test results are shown in Table 2: The average arsenic content is 4.82 μg / L, which meets the requirements of the enterprise standard Q / CQSM001-2023 "Disinfectants".

[0093] Table 2

[0094]

[0095] 4. Mercury content test: The test method refers to Chapter 4, 1.2 Mercury (Method 1) of the "Technical Specifications for Safety of Cosmetics" (2015 edition);

[0096] The test method is:

[0097] ① Preparation of standard working curve: Prepare a standard series with mercury concentration ranging from 0μg / L to 2.000μg / L. Perform analysis under the set conditions and obtain a linear equation;

[0098] ② Sample pretreatment: After shaking, accurately transfer 1.00 mL of sample to a 50 mL stoppered colorimetric tube. Add 5.0 mL of nitric acid and 2.0 mL of hydrogen peroxide and mix thoroughly. Heat in a boiling water bath for 2 hours. Remove the sample and add 1.0 mL of hydroxylamine hydrochloride solution. Let stand for 20 minutes. Add grade 1 water to a volume of 25 mL. Mix thoroughly and set aside. Simultaneously, prepare a reagent blank.

[0099] ③ Take appropriate amount of sample solution and reagent blank solution respectively, inject them into atomic fluorescence photometer to measure their fluorescence values, and read the corresponding mercury concentration from the standard curve.

[0100] Three bottles of samples were taken and the test was repeated twice for each bottle. The test environment temperature was 21.1°C and the relative humidity was 58%.

[0101] The test results are shown in Table 3: the average arsenic content is 4.23 μg / L, which meets the requirements of the enterprise standard Q / CQSM001-2023 "Disinfectants".

[0102] Table 3

[0103]

[0104] Experimental Example 2: Microbial Index Detection

[0105] The test method refers to Appendix A of GB 27951-2021 "Hygienic Requirements for Skin Disinfectants".

[0106] The specific test methods are as follows:

[0107] 1. Sample Preparation: Use a sterile pipette to pipette 5.0 mL of the nano-titanium dioxide fungicide from Example 1 into 45 mL of tryptone soy broth containing a neutralizer. Vortex and mix for 20 seconds to prepare a 1:10 test solution. This solution is then diluted with physiological saline to 1:100 and 1:1000 test solutions.

[0108] 2. Total Colony Count Determination: Inoculate two sterile plates with 1.0 mL of the test solution at 1:10 or 1:100 dilutions. Also inoculate plates with the neutralizer and diluent from the same batch as the test as a negative control. Pour standard nutrient agar into each plate, allow to solidify, and then incubate at 36.0°C for 48 hours.

[0109] 3. Mold and Yeast Assay: Inoculate two sterile plates with 1.0 mL of the test solution at 1:10, 1:100, or 1:1000 dilutions. Also inoculate plates with the neutralizer and diluent from the same batch as the test sample as a negative control. Pour Sabouraud agar into each plate, allow to solidify, and then incubate at 28.0°C for 72 hours.

[0110] 4. Detection of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, and beta-hemolytic Streptococcus): Take 10 mL of the 1:10 test solution from the above 2, culture it with bacteria, and then culture it with streaking. If suspicious colonies appear, perform corresponding biochemical identification and make judgments based on the typical characteristics of each bacteria.

[0111] The test results are shown in Table 4. After testing, the total colony count, mold and yeast counts of the fungicide prepared by the present invention were all less than 10 CFU / mL, and Pseudomonas aeruginosa, Staphylococcus aureus, and beta-hemolytic Streptococcus were not detected, which complies with the provisions of GB 27951-20211 "Hygienic Requirements for Skin Disinfectants" on product microbial contamination.

[0112] Table 4

[0113] Detection indicators Standard value Measured value Total colony count (CFU / mL) ≤10 ＜10 Mold and yeast (CFU / mL) ≤10 ＜10 Pseudomonas aeruginosa Not to be detected Not detected Staphylococcus aureus Not to be detected Not detected Beta-hemolytic Streptococcus Not to be detected Not detected

[0114] Experimental Example 3 Sterility Test

[0115] The detection method refers to Appendix A of GB27951-2021 "Hygiene Requirements for Skin Disinfectants".

[0116] The test method is:

[0117] ① Sample treatment: 5.0 mL of the nano-titanium dioxide fungicide of Example 1 was taken with a sterile pipette and added to 45 mL of tryptone soy broth medium containing a neutralizer. The mixture was vortexed and mixed for 20 seconds to prepare a 1:10 test solution.

[0118] ② Sterility test: Take 7mL of the test solution and inoculate 5 aerobic-anaerobic culture tubes and 2 fungal culture tubes. Inoculate 1.0mL of the diluted Staphylococcus aureus suspension into one of the aerobic-anaerobic culture tubes containing the sample as a positive control. Take one aerobic-anaerobic culture tube and one fungal culture tube, open the lid and place them on the test bench until the sterility test of the sample is completed. Cover and incubate them together with the test sample as a negative control. Place the aerobic-anaerobic culture tubes inoculated with the disinfectant dilution solution, the positive control tubes, and the negative control tubes in a 35.0℃ constant temperature incubator at the same time. Incubate continuously for 5 days, and observe the culture results daily. Place the fungal culture tubes inoculated with the disinfectant dilution solution and the negative control tubes in a 25.0℃ constant temperature incubator at the same time. Incubate continuously for 7 days, and observe the culture results daily.

[0119] The test results show that no aerobic and anaerobic bacteria and fungi were detected in the fungicide of the present invention, which meets the requirements of sterility testing in GB27951-2021 "Hygiene Requirements for Skin Disinfectants".

[0120] Experimental Example 4: Fungicide Safety and Toxicity Test

[0121] 1. A broken skin irritation test

[0122] ①Test method reference: Item 2.3.3.3.2 of Technical Specifications for Disinfection (2002 edition).

[0123] ② Preparation of test samples: Use the nano-titanium dioxide fungicide stock solution of Example 1.

[0124] ③Test Method: 24 hours before the test, use an electric razor to remove the fur on both sides of the New Zealand rabbit spine, covering an area approximately 3cm x 3cm. The next day, before applying the test sample, clean and disinfect the exposed skin on both sides of a 2.5cm x 2.5cm area of ​​hairless skin with 75% alcohol. After the alcohol evaporates, use a syringe to create a well-shaped wound in the skin. Then, drop 0.5mL of the nano-titanium dioxide fungicide solution directly onto the 2.5cm x 2.5cm damaged area on the left side. Cover with a non-irritating plastic wrap and secure with non-irritating adhesive tape. The damaged area on the right side serves as a blank control. The application period is 4 hours. After the test, remove any remaining test sample with warm water.

[0125] ④ Observation and Evaluation: Observe and score local skin reactions 1 hour, 24 hours, and 48 hours after removing the test sample. Refer to Tables 2-11 and 2-12 in Section 2.3.3, "Skin Irritation Test," of the Technical Specifications for Disinfection (2002 Edition) for scoring criteria and irritation intensity classification.

[0126] The test results are shown in Table 5: The maximum skin irritation index of the fungicide prepared in Example 1 of the present invention is 0.33 (0-<0.5), and the irritation intensity is non-irritating, which meets the requirements of the "Technical Specifications for Disinfection" (2002 edition).

[0127] Table 5

[0128]

[0129] 2. Acute oral toxicity test

[0130] ①Test method reference: Item 2.3.1 of the Technical Specifications for Disinfection (2002 edition).

[0131] ② Dosage grouping: set up a dose group of 5000 mg / kg, with 20 mice, half of them were male and half were female.

[0132] ③ Preparation of test samples: Weigh 5.00 g of the nano-titanium dioxide fungicide stock solution of Example 1, add purified water to 20 mL, and mix thoroughly to obtain a poisoning solution with a concentration of 250 mg / mL.

[0133] ④Test method: Before exposure, animals were fasted overnight with free access to water. The test sample was administered once to the animals by gavage, with an exposure volume of 0.2 mL / 10 g body weight.

[0134] ⑤Observation: After exposure, observe and record the signs of poisoning in the animals. At the end of the observation period, animals will be sacrificed and autopsied. Any abnormal tissues or organs found will be further examined by histopathology. The observation period is 14 days.

[0135] ⑥LD 50 Calculation method: Calculated according to the method in 2.3.1.5.2 "Single Maximum Limit Test" of "Technical Specifications for Disinfection" (2002 edition).

[0136] The test results are shown in Table 6: Acute oral toxicity test of the nano-titanium dioxide fungicide prepared in Example 1 of the present invention, LD 50 >5000mg / kg body weight, the toxicity level is practically non-toxic, and meets the requirements of the "Technical Specifications for Disinfection" (2002 edition).

[0137] Table 6

[0138] gender Dosage group (mg / kg) Number of animals Number of dead animals mortality rate(%) male 5000 10 0 0 female 5000 10 0 0

[0139] 3. Mouse bone marrow polychromatic erythrocyte micronucleus test

[0140] ①Test method reference: Item 2.3.8.4 of Technical Specifications for Disinfection (2002 edition).

[0141] ② Animal grouping: The acute oral toxicity test on mice showed that the LD50 of this sample was greater than 5000 mg / kg. Three dose groups were set up in the experiment, namely 5000 mg / kg, 2000 mg / kg, and 500 mg / kg. The positive control group was cyclophosphamide (40 mg / kg). The negative control group was pure water. Each group had 10 mice, and half of them were male and half were female.

[0142] ③ Sample Preparation: Weigh 5.00g, 2.00g, and 0.50g of the nano-titanium dioxide fungicide solution from Example 1, respectively, and dilute to 20mL with purified water to prepare 250mg / mL, 100mg / mL, and 25mg / mL contamination solutions. Weigh 0.020g of cyclophosphamide, dilute to 10mL with purified water, and mix thoroughly for later use.

[0143] ④ Test Method: Animals were exposed to the poison by oral gavage over a 30-hour period, with a 24-hour interval between two exposures, using an exposure volume of 0.2 mL / 10 g body weight. Samples were collected 6 hours after the second exposure.

[0144] ⑤ Sample collection and preparation: Sacrifice the animal by cervical dislocation. Remove both femurs, remove the muscle, and wipe clean of blood. Cut the femurs at both ends to expose the bone marrow cavity. Aspirate 0.1 mL of calf serum and flush the bone marrow cavity. Use the flushing solution for routine smears and allow to air dry.

[0145] ⑥ Staining: Fix the dried smear in methanol for 10 minutes, stain with Giemsa solution for 15 minutes, then rinse with pH 6.8 PBS solution and dry.

[0146] 7. Observation: Select areas with evenly distributed, intact, and appropriately stained cells and count the number of polychromatic erythrocytes (PCEs) containing micronuclei under an oil immersion lens. Count 1000 PCEs per animal. The micronucleated cell fraction refers to the number of PCEs containing micronuclei per 1000 PCEs, expressed as per thousand. Count 200 PCEs and also count the number of mature erythrocytes (NCEs) present.

[0147] The test results are shown in Table 7. In the mouse bone marrow micronucleus test induced by the test sample, there was no significant difference in the micronucleated cell rate of polychromatic erythrocytes in the animal bone marrow between the dose groups and the negative control group (p>0.05). The micronucleated cell rate in the cyclophosphamide positive control group was significantly higher than that in the negative control group (p<0.07). The PCEINCE ratio of the animal bone marrow in each dose group was greater than 0.1, indicating that the test sample had no significant inhibitory effect on the bone marrow. No significant abnormalities were observed in the animals in each dose group during the dosing period.

[0148] The bactericide of the embodiment of the present invention has no micronucleus-inducing effect on the polychromatic erythrocytes of the mouse bone marrow, which meets the requirements of the "Technical Specification for Disinfection" (2002 edition).

[0149] Table 7

[0150]

[0151] Note: The micronucleated cell rate (‰) was calculated based on the mouse unit and expressed as mean ± standard deviation. **p < 0.01, compared with the negative control group.

[0152] 4. Acute eye irritation test

[0153] ①Test method reference: Item 2.3.4 of Technical Specifications for Disinfection (2002 edition).

[0154] ② Preparation of test samples: Use the nano-titanium dioxide fungicide stock solution of Example 1.

[0155] ③Test Method: Pipette 0.1mL of the test sample and drip it into the conjunctival sac of the left eye of a New Zealand rabbit. After dripping the test sample, the eye is passively closed for 4 seconds. After 30 seconds, rinse with normal saline. The right eye is dripped with normal saline as a normal control.

[0156] ④ Observation and Evaluation: Observe the conjunctiva, iris, and cornea of ​​the New Zealand rabbits for damage and recovery at 1 hour, 24 hours, 48 ​​hours, 72 hours, 7 days, 14 days, and 21 days after eye instillation. If no irritation occurs within 72 hours, or if the eye irritation has completely recovered by the 7th or 14th day, terminate the test early. Refer to Tables 2-13 and 2-14 in Section 2.3.4, "Acute Eye Irritation Test," of the Technical Specifications for Disinfection (2002 Edition) for scoring criteria and irritation intensity classification.

[0157] The test results are shown in Table 8: The nano-titanium dioxide fungicide stock solution of Example 1 was subjected to an acute eye irritation test on New Zealand rabbits, and the injury type was non-irritating, meeting the requirements of the "Technical Specifications for Disinfection" (2002 edition).

[0158] Table 8

[0159]

[0160] The average score is the sum of 24h, 48h, and 72h divided by the number of observation time periods (3).

[0161] 5. Multiple complete skin irritation tests

[0162] ①Test method reference: Item 2.3.3.3.3 of the Technical Specifications for Disinfection (2002 edition).

[0163] ② Preparation of test samples: Use the nano-titanium dioxide fungicide stock solution of Example 1.

[0164] ③Test Method: 24 hours before the test, use an electric razor to remove the fur on both sides of the New Zealand rabbit's back spine, covering an area approximately 3 cm x 3 cm. The next day, apply 0.5 mL of the nano-titanium dioxide fungicide solution to a 2.5 cm x 2.5 cm area on the left side of the skin. The right side serves as a blank control. Four hours after application, rinse with warm water to remove any residual test sample. Apply the same method as above once daily for 14 days. Shave the fur as necessary to facilitate application of the test sample and observation of the results.

[0165] ④Observation and evaluation: Observe and score the skin reaction 24 hours after each application. The scoring criteria and irritation intensity classification refer to Table 2-11 and Table 2-12 in 2.3.3 "Skin Irritation Test" of "Technical Specifications for Disinfection" (2002 edition).

[0166] The test results are shown in Table 9: The nano-titanium dioxide fungicide solution of Example 1 was subjected to multiple complete skin irritation tests on New Zealand rabbits. The total integral average value, i.e., the irritation index, was 0.14 (0-<0.5), and the irritation intensity was non-irritating, which met the qualification requirements of the "Technical Specifications for Disinfection" (2002 edition).

[0167] Table 9

[0168]

[0169] Experimental Example 5 Verification of bactericidal effect and verification of microbial inhibition effect of bactericide

[0170] I. Experimental apparatus

[0171] 1. Example 1 nanometer titanium dioxide bactericide (liquid; active ingredient: nanometer titanium oxide, etc.).

[0172] 2. Test strain: Staphylococcus aureus (ATCC 6538), 7th generation; Pseudomonas aeruginosa (ATCC 15442), 6th generation.

[0173] 3. Neutralizing agent composition and concentration: D / E neutralizing broth.

[0174] 4. Diluent: tryptone physiological saline solution (TPS, pH 7.0).

[0175] 5. Organic interfering substance: 3% bovine serum albumin.

[0176] 6. Standard hard water (hardness 342 mg / L).

[0177] 7. Culture medium: tryptone soy agar medium.

[0178] 8. BSC-1004IA2 biological safety cabinet (No. TWS156), GSP-9270MBE incubator (No. WS147), XD861-A thermostat (No. WS051), sterile apparatus, etc.

[0179] II. Experimental method

[0180] 1. Detection basis: GB / T38502-2020 "Laboratory disinfectant bactericidal effect test method" item 5.1, item 5.4 and item 5.8.

[0181] 2. Neutralizing agent identification test: Example 1 nanometer titanium dioxide bactericide stock solution was used for the test, and the test temperature was 20°C constant temperature. The test was repeated 3 times.

[0182] 3. Bactericidal test: Example 1 nanometer titanium dioxide bactericide stock solution was used for the test, and the action time was 2.5 min, 5.0 min and 7.5 min, and the test temperature was 20°C constant temperature. The test was repeated 3 times.

[0183] 4. Detection environment temperature: 21.4°C~23.7°C, relative humidity: 50%~54%.

[0184] III. Experimental results

[0185] 1. Results of the Neutralizer Identification Test on Staphylococcus aureus The results of the neutralizer identification test using the nano-titanium dioxide fungicide stock solution of Example 1 of the present invention were shown in Table 10 below after three repeated tests at a constant temperature of 20°C.

[0186] Table 10 Neutralizer identification test results

[0187]

[0188] 2. Killing effect on Staphylococcus aureus

[0189] After three repeated tests, at a constant temperature of 20° C., the nano-titanium dioxide fungicide stock solution of Example 1 of the present invention was applied for 5.0 min. The killing logarithmic value of Staphylococcus aureus in the suspension is shown in Table 11 below.

[0190] Table 11 Killing effect of Staphylococcus aureus

[0191]

[0192] Note: There was no bacterial growth in the negative control group.

[0193] 3. Killing effect on Pseudomonas aeruginosa

[0194] After three repeated tests, at a constant temperature of 20° C., the nano-titanium dioxide fungicide stock solution of Example 1 of the present invention was applied for 5.0 min. The killing logarithmic values ​​of Pseudomonas aeruginosa in the suspension are shown in Table 12 below.

[0195] Table 12 Killing effect of Pseudomonas aeruginosa

[0196]

[0197] 4. Killing effect on Candida albicans

[0198] After three repeated tests, at a constant temperature of 20° C., the nano-titanium dioxide fungicide stock solution of Example 1 of the present invention was applied for 5.0 min. The killing logarithmic value of Candida albicans in the suspension is shown in Table 13 below.

[0199] Table 13 Killing effect of Candida albicans

[0200]

[0201]

[0202] In summary, after three repeated tests, under the constant temperature test conditions of 20°C, the D / E neutralization broth used can effectively neutralize the residual effect of the nano-titanium dioxide fungicide solution of Example 1 on Staphylococcus aureus, and the neutralizer and its neutralization product have no adverse effects on the culture medium and have little effect on the growth of Staphylococcus aureus.

[0203] After three repeated tests, under the constant temperature test conditions of 20°C, the bactericidal stock solution of Example 1 of the present invention was applied for 5.0 min, and the logarithmic killing values ​​of Staphylococcus aureus in the suspension, the logarithmic killing values ​​of Pseudomonas aeruginosa in the suspension, and the logarithmic killing values ​​of Candida albicans in the suspension all met the disinfection requirements of GB / T38502-2020 "Test Method for Laboratory Bactericidal Effect of Disinfectants", which are qualified.

[0204] 5. Skin Disinfection Field Test

[0205] The test method refers to Item 2.1.2.8 of the Technical Specifications for Disinfection (2002 edition).

[0206] After the subject's left and right inner middle forearms have been thoroughly rubbed against each other, the specification plate is placed on the surface of the inner middle section of the subject's left forearm. A sterile cotton swab is soaked in a test tube containing 10 mL of diluent, squeezed dry on the tube wall, and then rubbed back and forth horizontally 10 times and vertically 3 times within the area framed by the specification plate. The cotton swab is rotated each time it is rubbed. Aseptically cut the sampling end into the original diluent test tube, vortex and oscillate for 20 seconds, and draw 1.0 mL of the appropriate dilution sample solution to inoculate a plate in duplicate as a positive control group; use a non-woven fabric to soak the nano-titanium dioxide fungicide of Example 1 and wipe the area framed by the specification plate of the right forearm for 5.0 minutes of disinfection. Use a sterile cotton swab to soak in a test tube containing 10 mL of neutralizer solution, and sample and inoculate the right forearm in the same way as the test group; take 1.0 mL each of the neutralizer, diluent and cotton swab eluate from the same batch to inoculate a plate as a negative control group; pour TSA culture medium into each group of inoculation plates, wait for the culture medium to condense, place it in a 37.0°C incubator for 48 hours, and count the number of viable bacteria.

[0207] Detection environment temperature: 23.4℃, relative humidity: 54%.

[0208] The test results are shown in Table 14:

[0209] Table 14

[0210]

[0211]

[0212] Note: The negative control showed no sterile growth.

[0213] 6. Clostridium perfringens killing test

[0214] ① Preparation of bacterial suspension: Wash the freshly cultured strain with PBS and prepare 1x10 8 cfu / mL~5x10 8 cfu / mL of bacterial suspension.

[0215] ② Neutralizer: 0.03 mol / L PBS solution containing 2% Tween 80 + 1% lecithin + 0.5% sodium thiosulfate.

[0216] ③Test method: According to the second part (2.1.1.7) of the "Technical Specifications for Disinfection" (Ministry of Health 2002 edition) on suspension quantification, the nano-titanium dioxide fungicide stock solution was tested for 30 minutes and the test was repeated 3 times.

[0217] ④Test conditions: temperature: 22.0℃, relative humidity: 61.5%.

[0218] The test results show that the nano-titanium dioxide fungicide stock solution of Example 1 has a killing logarithm of Clostridium perfringens greater than 6.00 after 30 minutes of action, which meets the evaluation requirements of the quantitative bacterial killing test in Part 2 (2.1.1.7) of the "Technical Specifications for Disinfection" (Ministry of Health 2002 edition) (killing logarithm ≥ 5.00). The sample is qualified for disinfection of the tested strains.

[0219] 7. Aflatoxin Killing Test

[0220] ① Preparation of bacterial suspension: Wash the freshly cultured strain with PBS and prepare 1x10 7 cfu / mL~5x10 7 cfu / mL of fungal suspension.

[0221] ② Neutralizer: 0.03 mol / L PBS solution containing 2% Tween 80 + 1% lecithin + 0.5% sodium thiosulfate.

[0222] ③Test method: According to the "Technical Specifications for Disinfection" (Ministry of Health 2002 Edition) (2.1.1.9) suspension quantitative test, the nano titanium dioxide fungicide stock solution was tested for 30 minutes and the test was repeated 3 times

[0223] ④Test conditions: temperature: 22.0℃, relative humidity: 61.5%.

[0224] The test results show that the nano titanium dioxide fungicide stock solution of Example 1 has killing logarithmic values ​​of aflatoxin of 1.88, 1.92 and 1.99 respectively after 30 minutes of action.

[0225] 8. Vibrio vulnificus killing test

[0226] ① Neutralizer: 0.03 mol / L PBS solution containing 2% Tween 80 + 1% lecithin + 0.5% sodium thiosulfate.

[0227] ② Neutralizer identification test: According to the second part (2.1.1.5) of the "Technical Specifications for Disinfection" (Ministry of Health 2002 edition) on suspension quantification, the nano-titanium dioxide fungicide stock solution was tested with an action time of 3 minutes. The test was divided into 6 groups according to the standard requirements and repeated 3 times.

[0228] ③ Quantitative bacterial killing test: According to the suspension quantification in Part II (2.1.1.7) of the Technical Specifications for Disinfection (2002 edition of the Ministry of Health), the nano-titanium dioxide fungicide stock solution was tested for 30 minutes and the test was repeated 3 times.

[0229] ④Test conditions: ambient temperature 22.5℃, relative humidity 61.5%.

[0230] The test results showed that the neutralizer identification test showed that a 0.03 mol PBs solution containing 2% Tween 80, 1% egg citrus, and 0.5% sodium thiosulfate could effectively neutralize the bactericide of Example 1 (full-spectrum responsive titanium dioxide dressing) (effective concentration stock solution, action time 3 minutes), and the neutralizer and the neutralization product had no adverse effects on Vibrio vulnificus.

[0231] Quantitative bacterial killing test: The nano-titanium dioxide fungicide stock solution of Example 1 had a killing logarithm value of Vibrio vulnificus >6.00 after 30 minutes of action, which met the evaluation requirements of the quantitative killing test in Part 2 (2.1.1.7.7) of the "Technical Specifications for Disinfection" (Ministry of Health, 2002 edition) (killing logarithm value ≥5.00). The sample was judged to be qualified for disinfection of the tested strains under the test conditions used.

[0232] 9. Trichoderma viride killing test

[0233] ① Neutralizer: 0.03 mol / L PBS solution containing 2% Tween 80 + 1% lecithin + 0.5% sodium thiosulfate.

[0234] ② Neutralizer identification test: According to the second part (2.1.1.5) of the "Technical Specifications for Disinfection" (Ministry of Health 2002 edition) on suspension quantification, the nano-titanium dioxide fungicide stock solution was tested with an action time of 3 minutes. The test was divided into 6 groups according to the standard requirements and repeated 3 times.

[0235] ③ Fungus killing test: According to the "Technical Specifications for Disinfection" (Ministry of Health, 2002 edition) (2.1.1.9) suspension quantification, test the nano titanium dioxide fungicide stock solution, act for 2 minutes, and repeat the test 3 times.

[0236] ④Test conditions: ambient temperature 22.5℃, relative humidity 61.5%.

[0237] The test results show: Neutralizer identification test: 0.03 mol / LPBs solution containing 2% Tween 80 + 1% lecithin + 0.5% sodium thiosulfate can effectively neutralize "Example 1 bactericide (full spectrum response titanium dioxide dressing)" (action concentration stock solution, action time 3 minutes), and the neutralizer and the neutralization product have no adverse effects on viride fungus.

[0238] Fungus killing test: The nano-titanium dioxide fungicide stock solution of Example 1 was used for 30 minutes, and the logarithmic killing value of the fungus against Trichoderma viride was >5.00, which complies with the evaluation requirements of the fungus killing test in Part 2 (2.1, 1.96) of the "Technical Specifications for Disinfection" (Ministry of Health, 2002 edition) (killing logarithmic value ≥4.00). The sample was qualified for disinfection of the tested strains.

[0239] 10. Norovirus Killing Test

[0240] ① Virus Inactivation Test Method: Based on the poliovirus inactivation test in Section 2 (2.1.1.10.7) of the "Technical Specifications for Disinfection" (Ministry of Health, 2002 edition), a nano-titanium dioxide fungicide stock solution was tested for 45 minutes, repeated three times. The test temperature was 20°C ± 1°C. Physical Removal of Residual Disinfectant Identification Test: Based on the Physical Removal of Residual Disinfectant Identification Test in Section 2 (2.1.1.10.6) of the "Technical Specifications for Disinfection" (Ministry of Health, 2002 edition), a nano-titanium dioxide fungicide stock solution was tested for 5 minutes.

[0241] ②Test conditions: ambient temperature 22.0℃, relative humidity 62.0%.

[0242] The test results show that the nano titanium dioxide fungicide stock solution of Example 1 was used for 45 minutes, and the experiment was repeated 3 times. Its average inactivation logarithm value for norovirus GV type (Raw264.7 cell line) was >4.05.

[0243] 11. Poliovirus Killing Test

[0244] ①Test method: Technical Specifications for Disinfection (2002 edition) 2.1.1.10.

[0245] ② Action concentration: the original sample of Example 1 (full illumination).

[0246] ③Laboratory ambient temperature: 20-22°C, laboratory ambient humidity: 50-53%.

[0247] ④ Neutralizer identification test grouping:

[0248] (1) Disinfectant + virus suspension;

[0249] (2) (disinfectant + virus suspension) + neutralizer;

[0250] (3) Neutralizer + virus suspension;

[0251] (4) (disinfectant + neutralizer) + virus suspension;

[0252] (5) Virus suspension;

[0253] (6) Cells not inoculated with virus.

[0254] The bactericide (full spectrum responsive titanium dioxide dressing) of Example 1 was exposed to light for 5 minutes at a test temperature of 19-21° C. The test was repeated 3 times.

[0255] Inactivation test: When the cells are cultured to a fully grown monolayer, a disinfection experiment is performed; the polio virus stored at low temperature is melted in a water bath and placed on ice for later use; the disinfectant to be tested is taken and placed in a 20℃±1℃ water bath for later use; 100μL of organic interfering substance is mixed with 100uL of the original virus, and the mixture is placed in a 20℃±1℃ water bath for 5 minutes, and 0.8mL of the disinfectant to be tested is added, and the mixture is immediately mixed and the time is recorded. After the prescribed time, 0.1mL is immediately taken out and added to the neutralizer and mixed. In the positive (virus) control group test, sterile deionized water is used instead of the disinfectant. The virus titer is determined for each group separately, and the endpoint dilution method can be used. The test is repeated 3 times.

[0256] Test results:

[0257] 1. The neutralizing agent identification test showed that the 2x D / E neutralization broth can effectively neutralize the inactivation effect of the bactericidal agent (full spectrum responsive titanium dioxide-dressing) of Example 1 (full illumination) on the poliovirus type I vaccine strain. The neutralizing agent and the neutralization product had no adverse effects on the poliovirus type I vaccine strain and the culture medium, indicating that the neutralizing agent is suitable for the poliovirus type I vaccine strain inactivation test.

[0258] 2. According to the Technical Specifications for Disinfection (2002 edition), the bactericidal agent (full spectrum responsive titanium dioxide-dressing) of Example 1 was exposed to light for 30 minutes, and the average logarithmic inactivation value of the poliovirus type I vaccine strain was >4.00, which meets the requirements of the Technical Specifications for Disinfection (2002 edition).

[0259] Experimental Example 6: Storage Stability Verification of Fungicide

[0260] ① Test method: GB / T 38502-2020 "Test method for the bactericidal effect of disinfectants in laboratories", item 5.1 and 5.8, and "Technical Specification for Disinfection" (2002 edition), item 2.2.3.3.

[0261] ② The fungicide prepared in Example 1 was placed in a constant temperature incubator at 37.0° C. for 90 days and then taken out for testing.

[0262] Sterilization test: The above-mentioned fungicide stock solution was used for 2.5 minutes, 5.0 minutes and 7.5 minutes at a constant temperature of 20°C. The test was repeated three times.

[0263] The detection environment temperature is 23.5℃-24.9℃, and the relative humidity is 50%-4%.

[0264] Test results: After three repeated tests, the fungicide obtained in Example 1 was stored at a constant temperature of 37.0°C for 90 days, and the killing logarithm of Candida albicans in the suspension after 5 minutes was greater than 4.0, which is in line with the "Technical Specifications for Disinfection" (2002 edition) that the sample is valid for 2 years in the village.

[0265] The above is only an embodiment of the present invention, and the common knowledge such as the specific technical solutions and / or characteristics in the solution are not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the description can be used to interpret the content of the claims.

Claims

1. A full-spectrum nano-titanium oxide fungicide, characterized by: The raw materials, calculated by mass, include 1 part of nano titanium dioxide, 0.05-0.1 part of photocatalyst, 98.0-98.5 parts of purified water, 0.2-0.4 parts of dispersant, 0.05-0.2 parts of stabilizer, and 0.05-0.3 parts of pH regulator; the particle size of the nano titanium dioxide is 5-20 nm.

2. A full-spectrum nano-titanium oxide fungicide according to claim 1, characterized in that: The photocatalyst is Ag-Cu composite nano-promoter or carbon quantum dots.

3. A full-spectrum nano-titanium oxide fungicide according to claim 2, characterized in that: The purified water is injection-grade purified water, and the dispersant is at least one of PEG-400 and Tween 80.

4. The full-spectrum nano-titanium oxide fungicide according to claim 3, characterized in that: The stabilizer is sodium citrate; the pH regulator is a weak base regulator, and the pH regulator adjusts the pH of the solution to 6.0-7.

5.

5. The method for preparing a full-spectrum nano-titanium oxide fungicide according to any one of claims 1 to 4, characterized in that: The steps include: Step 1: Dissolving and mixing raw materials: adding a dispersant and a stabilizer to purified water in a stirring state, and dissolving them to obtain System I; Step 2: Add nano-titanium dioxide to system I and disperse it under high-speed shear conditions to obtain a milky white system II; Step 3: Add the photocatalyst to system II and stir to obtain system III; Step 4: Use a pH regulator to adjust the pH of system III to 6.0–7.5; Step 5: Degassing and filtration: Stir and degas the pH-adjusted system III, and then filter to remove impurities and bacteria. Step 6. Packaging: Filling and sealing operations are completed in a GMP Class B (ISO Class 7) clean room with an ambient temperature of 20±2°C and a relative humidity of 40–60%.

6. The method for preparing a full-spectrum nano-titanium oxide fungicide according to claim 5, characterized in that: In step 1, the stirring speed is 150-200 rpm; in step 2, the high-speed shearing speed is 300-500 rpm; in step 5, the filtration method is to use a 0.22 μm microporous membrane filtration.

7. Use of a full-spectrum nano-titanium oxide fungicide according to any one of claims 1 to 4 in the preparation of wound healing drugs.

8. Use of a full-spectrum nano-titanium oxide fungicide according to any one of claims 1 to 4 in the preparation of a drug for preventing skin infections.

9. Use of a full-spectrum nano-titanium oxide fungicide according to any one of claims 1 to 4 in the preparation of a drug for eliminating stubborn skin tinea and athlete's foot.

10. Use of a full-spectrum nano-titanium oxide fungicide according to any one of claims 1 to 4 in the preparation of a broad-spectrum antibacterial agent.

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