Composite material with antibacterial properties and method for its production and use

Abstract

The application relates to the field of waste plastic resource utilization, and discloses a composite material with antibacterial performance and a preparation method and application thereof, the composite material comprising a crosslinked polymer and a nano metal loaded on the crosslinked polymer, wherein the crosslinked polymer is a product of crosslinked structure crosslinking of halogen-containing plastic, the structural formula of the crosslinked structure is shown as formula a, and the nano metal comprises at least one of silver, copper, zinc and aluminum, wherein m and n are each independently 1-6. The composite material provided by the application can be prepared by using waste halogen-containing plastic and cheap metal, raw material sources are wide, the cost is low, the process is simple, the operation difficulty is low, the composite material has excellent antibacterial performance and can promote wound healing, that is, the composite material provided by the application can realize safe dehalogenation of halogen-containing waste plastic while simply and efficiently synthesizing an antibacterial material, and realizes resource utilization and high-value utilization of waste halogen-containing plastic.

Description

Technical Field

[0001] This invention relates to the field of waste plastic resource utilization, specifically to a composite material with antibacterial properties, its preparation method, and its application. Background Technology

[0002] Halogenated plastics are an important class of plastic materials, widely used in industry, agriculture, construction, transportation, communications, medical care, and daily life. However, the large-scale disposal or expiration of the lifespan of halogenated plastics has caused serious waste plastic pollution. Due to the special structure of halogenated plastics, their recycling has always been very difficult. Simple incineration and landfill disposal will cause secondary environmental pollution, while pyrolysis will produce hydrogen halides, which corrode equipment and seriously threaten the safety of production facilities. Therefore, achieving safe dehalogenation of halogenated waste plastics and developing efficient recycling technologies for halogenated waste plastics are of great significance.

[0003] As people's awareness of a healthy environment increases, antibacterial materials are receiving more and more attention. Antibacterial materials are a class of novel functional materials with inherent antibacterial properties, currently used in home appliances, automobile manufacturing, and other fields. For example, CN102660114B discloses a method for preparing a novel antibacterial plastic material, which includes the following steps: 1) Impregnating muscovite powder in hydrogen peroxide; 2) Adding the treated expanded muscovite powder to a trisodium phosphate solution; 3) Dissolving by stirring, filtering, washing, and drying to obtain a solid product; 4) Adding the solid product to an AgNO3 solution and treating to obtain a silver-supported mica antibacterial powder; 5) Adding the silver-supported mica antibacterial powder obtained in step 3 to a mixed solution of a diluent and a coupling agent; 6) Stirring to obtain the novel antibacterial plastic material. However, existing technologies for preparing antibacterial materials using plastics generally suffer from drawbacks such as high operational difficulty and high cost. Furthermore, if the plastic used contains halogens, these halogens may remain in the antibacterial material, potentially causing adverse effects on the environment and human health during use.

[0004] Therefore, there is an urgent need to develop antibacterial materials and their synthesis processes that are simple to synthesize, low in cost, and capable of safely dehalogenating and recycling halogenated waste plastics at high value. Summary of the Invention

[0005] The purpose of this invention is to overcome the above-mentioned problems existing in the prior art and to provide a composite material with antibacterial properties, its preparation method, and its application.

[0006] To achieve the above objectives, a first aspect of the present invention provides a composite material with antibacterial properties, the composite material comprising a crosslinked polymer and nano-metals loaded on the crosslinked polymer, wherein the crosslinked polymer is a product of crosslinking a halogenated plastic through a crosslinked structure, and the nano-metals include at least one selected from silver, copper, zinc, and aluminum.

[0007] A second aspect of the present invention provides a method for preparing a composite material with antibacterial properties, the method comprising:

[0008] (1) In the presence of a solvent and a crosslinking catalyst, halogen-containing plastics are brought into contact with a crosslinking agent to carry out a crosslinking reaction;

[0009] (2) Loading nano-metals onto the cross-linked polymer obtained by the cross-linking reaction in step (1), wherein the nano-metals include at least one of silver, copper, zinc and aluminum.

[0010] A third aspect of the present invention provides a composite material prepared by the method described above.

[0011] A fourth aspect of the present invention provides the use of the composite material as described above in the preparation of a bactericidal formulation.

[0012] The fifth aspect of the present invention provides the use of the composite material as described above in the preparation of a medicament for promoting wound healing.

[0013] The beneficial effects obtained by the present invention through the above technical solution include at least the following:

[0014] (1) The composite material provided by the present invention has excellent antibacterial properties and can effectively kill bacteria under both dark and light conditions, and cause bacterial cells to deform or even rupture.

[0015] (2) The composite material provided by the present invention can be prepared using waste halogenated plastics and inexpensive metals. It can synthesize antibacterial materials simply and efficiently, and can also achieve safe dehalogenation of halogenated waste plastics. It is of great significance for the resource utilization and high-value utilization of waste halogenated plastics.

[0016] (3) The method for preparing composite materials provided by the present invention has a wide range of raw material sources, low cost, simple process, low operation difficulty, and is suitable for industrial promotion.

[0017] (4) The composite material provided by the present invention can promote wound healing and has the potential to be used in the preparation of antibacterial drugs. Attached Figure Description

[0018] Figure 1 Here is an image showing the morphological appearance of the PVC-DETA@CuNPs prepared in Example 1;

[0019] Figure 2This is a Fourier transform infrared spectrum image of the PVC-DETA prepared in Example 1;

[0020] Figure 3 The images show the XPS, XRD (Cu2p), and XRD spectra of PVC-DETA@CuNPs prepared in Example 1, where from left to right are the XPS spectrum, XRD (Cu2p) spectrum, and XRD spectrum.

[0021] Figure 4 These are TEM images of PVC-DETA@CuNPs prepared in Example 1;

[0022] Figure 5 These are STEM images of PVC-DETA@CuNPs prepared in Example 1 and their corresponding Cu, N and O elements;

[0023] Figure 6 The fluorescence emission intensity of PVC-DETA@CuNPs prepared in Example 1 under different irradiation times;

[0024] Figure 7 These are four types of reactive oxygen species (ROS) after different irradiation times of PVC-DETA@CuNPs prepared in Example 1. 1 O2、·O 2- The content of H2O2 and ·OH;

[0025] Figure 8 These are E. coli cell morphology images of the blank control group, PVC-DETA, PVC-DETA@CuNPs, and PVC-DETA@CuNPs+PDT group;

[0026] Figure 9 The images show the recovery status of the mice, where (a) is a macroscopic imaging analysis of wound healing, (b) is the wound healing rate data, and (c) is the change in mouse body weight.

[0027] Figure 10 This is the plate condition after culturing bacterial residue from skin wounds in mice after the experiment;

[0028] Figure 11 It is the number of bacteria cultured from bacterial residue in skin wounds after mouse experiments;

[0029] Figure 12 These are the test results of inflammation-related hematological parameters after the mouse experiment;

[0030] Figure 13 These are the histological features of mouse wounds after staining following mouse experiments. Detailed Implementation

[0031] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0032] The first aspect of this invention provides a composite material with antibacterial properties, the composite material comprising a crosslinked polymer and a nano-metal supported on the crosslinked polymer, wherein the crosslinked polymer is a product of a halogenated plastic crosslinked via a crosslinking structure, the crosslinking structure having the structural formula shown in Formula a, and the nano-metal comprising at least one of silver, copper, zinc, and aluminum.

[0033]

[0034] Where m and n are each an integer from 1 to 6.

[0035] Due to limitations in reaction and separation conditions, the composite material provided in this invention, in addition to the crosslinking structure shown in Formula a, may inevitably contain (partial) structures of the reactants used to synthesize the crosslinked polymer, (partial) reaction byproducts, and (partial) impurities from the raw materials used to synthesize the crosslinked polymer. These structures, reaction byproducts, or impurities, being directly or indirectly connected to the crosslinking structure or difficult to completely remove during washing, will together with the crosslinking structure constitute the crosslinked polymer described in this invention.

[0036] Preferably, the N content in the crosslinked polymer is 5-90 wt% based on the total weight of the crosslinked polymer, more preferably 5-45 wt%, and even more preferably 5-15 wt%.

[0037] Preferably, the crosslinking structure content in the crosslinked polymer is 10-40 wt%; however, in order to obtain the composite material with the best antibacterial effect, the crosslinking structure content in the crosslinked polymer is preferably 15-30 wt%, such as 15 wt%, 17 wt%, 19 wt%, 21 wt%, 23 wt%, 25 wt%, 27 wt%, 29 wt%, and 30 wt%, as well as any range between any two values.

[0038] Preferably, the nano-metal has reducing properties.

[0039] Preferably, the nano-metal comprises elemental metals and / or metal oxides.

[0040] Preferably, the content of the nano-metal (calculated as metal element) is 1-30 mol relative to each kilogram of crosslinked polymer, for example, it can be 1 mol, 3 mol, 5 mol, 7 mol, 9 mol, 11 mol, 13 mol, 15 mol, 17 mol, 19 mol, 21 mol, 23 mol, 25 mol, 27 mol, 29 mol and 30 mol and any range between any two values. In order to reduce production costs while ensuring bactericidal performance, the content of the nano-metal is more preferably 1-5 mol, and even more preferably 1-3 mol.

[0041] According to the present invention, the content of the metal element relative to each kilogram of crosslinked polymer can be 2-30 mol, for example, it can be 2 mol, 5 mol, 8 mol, 11 mol, 14 mol, 17 mol, 20 mol, 23 mol, 26 mol, 29 mol and 30 mol, and any range between any two values.

[0042] According to the present invention, the content of the metal oxide is preferably 2-20 mol per kilogram of crosslinked polymer, for example, it can be 2 mol, 5 mol, 8 mol, 11 mol, 14 mol, 17 mol and 20 mol, and any range between any two values.

[0043] According to the present invention, the metallic element is preferably copper.

[0044] According to the present invention, the metal oxide is preferably cuprous oxide.

[0045] According to the present invention, the content of nano-metals in the composite material, calculated as metal elements, is 5-50 wt%, for example, it can be 5 wt%, 8 wt%, 10 wt%, 12 wt%, 13 wt%, 15 wt%, 25 wt%, 35 wt%, 45 wt%, and 50 wt%, and any range between any two values, preferably 10-30 wt%, more preferably 12-15 wt%.

[0046] According to one embodiment of the present invention, the nanometals are elemental Cu and Cu₂O, and their parameters in the product include: the lattice spacing (d) of Cu(111) is 0.208-0.23 nm, and the lattice spacing (d) of Cu₂O(111) is 0.24-0.26 nm. The lattice spacing (d) is measured by transmission electron microscopy.

[0047] To ensure that the antibacterial material has better antibacterial properties and the most stable and suitable physical properties, m and n are preferably 2.

[0048] According to the present invention, preferably, the halogenated plastic is polyhalogenated polyethylene, more preferably polyvinyl chloride (see below for details).

[0049] A second aspect of the present invention provides a method for preparing a composite material with antibacterial properties, the method comprising:

[0050] (1) In the presence of a solvent and a crosslinking catalyst, a halogenated plastic is brought into contact with a crosslinking agent to carry out a crosslinking reaction, wherein the crosslinking agent has the structure shown in formula b;

[0051]

[0052] Preferably, m and n are each independently 1-6 (integers);

[0053] (2) Loading nano-metals onto the cross-linked polymer obtained by the cross-linking reaction in step (1), wherein the nano-metals include at least one of silver, copper, zinc and aluminum.

[0054] Preferably, in step (1), the solvent can be a solvent that does not react with the reactants and can dissolve halogen-containing plastics, such as at least one of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, tetrahydronaphthalene and decahydronaphthalene, more preferably dimethyl sulfoxide.

[0055] Preferably, in step (1), the crosslinking catalyst is a catalyst capable of catalyzing the reaction of halogens on plastic structural units with other organic substances. For example, it can be at least one of sodium carbonate, sodium bicarbonate, sodium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene. In order to obtain better crosslinking effect, 1,8-diazabicyclo[5.4.0]undec-7-ene is preferred.

[0056] According to the present invention, in step (1), the halogen in the halogen-containing plastic can be at least one of fluorine, chlorine, bromine and iodine. However, in order to reduce the difficulty of operation and reduce environmental pollution, the halogen is preferably chlorine.

[0057] Preferably, in step (1), the halogenated plastic is polyhalogenated ethylene, for example, it can be polyvinyl chloride and / or polyvinyl fluoride, more preferably polyvinyl chloride.

[0058] According to the present invention, the halogenated plastic may also contain structural units similar to those of polyhalogenated polyethylene, for example, the halogenated plastic may also contain polyvinylidene halide.

[0059] According to the present invention, the number average molecular weight of the halogenated plastic can be 10,000-1,000,000 g / mol, for example, it can be 10,000 g / mol, 100,000 g / mol, 200,000 g / mol, 300,000 g / mol, 400,000 g / mol, 500,000 g / mol, 600,000 g / mol, 700,000 g / mol, 800,000 g / mol, 900,000 g / mol, and 1,000,000 g / mol, or any range between any two values, preferably 10,000-500,000 g / mol. However, in order to reduce the difficulty of operation and optimize the physical properties of the antibacterial material, according to one embodiment of the present invention, the number average molecular weight of the halogenated plastic is 75,000-85,000 g / mol.

[0060] According to the present invention, the average degree of polymerization of the halogenated plastic can be 500-15000, for example, it can be any range of 500, 1500, 2500, 3500, 4500, 5500, 6500, 7500, 8500, 9500, 10500, 11500, 12500, 13500, 14500 and 15000 and any two of these values, preferably 500-5500. However, in order to reduce the difficulty of operation and optimize the physical properties of the antibacterial material, according to one embodiment of the present invention, the average degree of polymerization of the halogenated plastic is preferably 1000-1500.

[0061] According to the present invention, in order to further reduce costs, the halogenated plastic can be waste halogenated plastic. When using the waste halogenated plastic to synthesize crosslinked polymers, in order to obtain better antibacterial ability and improve the safety of the material, the waste halogenated plastic can also be pretreated to remove impurities that affect antibacterial ability and safety. The pretreatment method can be any commonly used method in the art, which will not be described in detail here.

[0062] Preferably, in order to obtain a composite material with higher antibacterial properties, m and n are 2 (that is, the crosslinking agent is diethylenetriamine).

[0063] Preferably, in step (1), the weight ratio of the halogenated plastic to the solvent is 1:(5-300), for example, it can be 1:5, 1:30, 1:60, 1:90, 1:120, 1:150, 1:180, 1:210, 1:240, 1:270 and 1:300 and any range between any two values, more preferably 1:(50-100).

[0064] Preferably, in step (1), the molar ratio of the crosslinking agent to the halogenated plastic (calculated as halogen) is 1:(0.5-10), for example, it can be 1:0.5, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 and 1:10, or any range between any two values. However, in order to further reduce the reaction cost while ensuring that the reaction proceeds fully, it is more preferably 1:(0.5-5), and even more preferably 1:(1-1.3).

[0065] Preferably, in step (1), the molar ratio of halogenated plastic to crosslinking catalyst, calculated as halogen, is (0.5-5):1, for example, it can be 0.5:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1 and 5:1 and any range between any two values. In order to obtain antibacterial materials with better bactericidal effect, it is more preferably (1-4):1, and even more preferably (1-2):1.

[0066] To ensure a more complete cross-linking reaction and reduce the formation of byproducts, the plastic can be fully dissolved in a solvent before the cross-linking reaction. The dissolution method can involve adding the plastic to the solvent, heating it, and then mixing the plastic and solvent evenly. The heating temperature can be adjusted flexibly according to the type and properties of the plastic used. According to a preferred embodiment of the present invention, the dissolution temperature is 55-65°C, and the time is 0.5-2 hours. The mixing method can be a stirring or ultrasonic method commonly used in the art to obtain a homogeneous system, which will not be elaborated here.

[0067] Preferably, in step (1), the reaction conditions can be conventionally adjusted according to the type of halogenated plastic and crosslinking agent selected, as well as the size of the reaction system. According to the present invention, the reaction temperature can be 30-120℃, for example, it can be any range of 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, 65℃, 70℃, 75℃, 80℃, 85℃, 90℃, 95℃, 100℃, 105℃, 110℃, 115℃ and 120℃, and any two of these values. However, in order to shorten the reaction time, reduce the occurrence of side reactions and obtain antibacterial materials with better bactericidal effect, it is preferred to be 50-90℃, and more preferably 55-65℃.

[0068] Preferably, in step (1), the crosslinking reaction time can be 6-48h, for example, it can be any range of 6h, 10h, 14h, 18h, 22h, 26h, 30h, 34h, 38h, 42h, 46h and 48h, and any two of these values, more preferably 12-36h, and even more preferably 20-30h.

[0069] According to the present invention, in order to allow the plastic and the crosslinking agent to react fully, the method may further include stirring during the reaction. According to some embodiments of the present invention, the stirring speed may be 100-500 rpm.

[0070] After the crosslinking reaction is completed, in order to obtain a purer crosslinking reaction product, the product can be separated and purified. The separation and purification method may include: cooling the product, then separating the solid product and washing it, wherein the cooling temperature is preferably room temperature (20-30°C); the solvent used for washing can be any solvent that can dissolve the reactants and catalyst and does not react with the product, such as at least one of deionized water, methanol and n-hexane, preferably deionized water; the number of separations and washes can be adjusted according to the actual system and conditions.

[0071] To further remove organic solvents and unreacted raw materials from the product, ultrasonic treatment can be performed during the washing process. The ultrasonic treatment method can be flexibly adjusted according to the size of the system. According to some embodiments of the present invention, the ultrasonic treatment method can be: power of 50-500w and time of 15-60min.

[0072] According to the present invention, in order to ensure complete removal of organic solvents and unreacted raw materials from the product, filtration can be performed after ultrasonic treatment. The method and number of filtrations can be adjusted according to the actual situation, which will not be elaborated here.

[0073] To further remove organic solvents from the crosslinked polymer, the crosslinked polymer can be dried after washing. The drying method can be at least one of vacuum drying, supercritical carbon dioxide drying, and freeze drying. In order to obtain a purer and more stable crosslinked polymer and to prevent the crosslinked material structure from being damaged by heat, the drying is preferably freeze drying. The freeze drying method is to use a temperature of -105°C to -80°C for 6-72 hours.

[0074] Preferably, in step (2), the amount of nano-metal used is 4-30 mol relative to each kilogram of crosslinked polymer. For example, it can be 4 mol, 5 mol, 7 mol, 9 mol, 11 mol, 13 mol, 15 mol, 17 mol, 19 mol, 21 mol, 23 mol, 25 mol, 27 mol, 29 mol, and 30 mol, or any range between any two values. In order to obtain the composite material with the most uniform metal distribution and the best bactericidal effect, the amount of nano-metal used is more preferably 20-30 mol relative to each kilogram of crosslinked polymer.

[0075] Preferably, in step (2), the nano-metal includes elemental metals and / or metal oxides with bactericidal effects.

[0076] Preferably, the nano-metal has reducing properties.

[0077] In order to improve the sterilization effect while reducing the cost, the metal element is preferably copper; the metal oxide is preferably cuprous oxide.

[0078] It is understood that the metal may also contain any metal without bactericidal effect. Regardless of whether the metal without bactericidal effect will improve or reduce the bactericidal effect, as long as it contains the metal with bactericidal effect as described above, it is within the protection scope of this invention.

[0079] Preferably, in step (2), the loaded system further contains a reducing agent. The reducing agent is a substance that can convert the metal precursor into a reducing agent, such as at least one of LiAlH4, diisobutylaluminum hydride (DIBAL), and NaBH4. To improve the reduction effect and reduce the difficulty and danger of operation, NaBH4 is more preferred.

[0080] Preferably, the weight ratio of the reducing agent to the crosslinking polymer is 1:(0.5-10), for example, it can be 1:0.5, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5 and 1:10. However, in order to further reduce costs and obtain the best antibacterial effect, it is more preferably 1:(1-6), and even more preferably 1:(3-5).

[0081] According to the present invention, in step (2), in order to disperse the nano-metal more uniformly on the crosslinked polymer, the loading is carried out in the presence of a solvent (preferably water), and the amount of the crosslinked polymer is preferably 1-10g, more preferably 1-5g, relative to 1L of solvent.

[0082] According to the present invention, the nano-metal can be directly loaded onto the cross-linked polymer in a form with bactericidal properties, or a metal precursor can be used for loading, wherein the metal precursor can react to generate a metal element and / or metal compound with bactericidal properties. To improve the loading of the nano-metal onto the cross-linked polymer, it is preferable to use a metal precursor for loading.

[0083] According to the present invention, the metal precursor is preferably a metal salt that is soluble in water, wherein the anion in the metal salt can be at least one of sulfate, phosphate, nitrate and chloride, more preferably sulfate.

[0084] According to the present invention, the amount of the metal precursor is 4-30 mol relative to each kilogram of crosslinked polymer, for example, it can be 4 mol, 5 mol, 7 mol, 9 mol, 11 mol, 13 mol, 15 mol, 17 mol, 19 mol, 21 mol, 23 mol, 25 mol, 27 mol, 29 mol and 30 mol and any range between any two values. In order to obtain a composite material with the most uniform metal distribution and the best bactericidal effect, the amount of the metal precursor is more preferably 20-30 mol relative to each kilogram of crosslinked polymer.

[0085] According to the present invention, the metal precursor may be provided in anhydrous form and / or in aqueous hydrate form, whichever is appropriate depending on the actual situation.

[0086] Preferably, the loading method includes: reducing the metal precursor in the presence of a reducing agent and a crosslinking polymer. The metal precursor can be first contacted with the reducing agent to undergo a reduction reaction before being contacted with the crosslinking polymer for loading; alternatively, the metal precursor can be first contacted with the crosslinking polymer, and then the reducing agent is added to reduce the metal precursor. However, to obtain the best bactericidal effect, the loading method is preferably to mix the metal precursor and the crosslinking polymer before adding the reducing agent to reduce the metal precursor.

[0087] To obtain antibacterial materials with a more uniform structure, the crosslinked polymer can be pre-dispersed uniformly in a solvent before loading the metal onto the crosslinked polymer. The dispersion method can be a mixing method commonly used in the art, such as stirring and ultrasound. To obtain a more uniform suspension, the dispersion method is preferably ultrasound. The ultrasound method can be: power of 50-500w, time of 0.2-2h.

[0088] According to the present invention, in order to ensure the stability of the reducing agent and prevent it from decomposing during the reduction reaction and affecting the effect of reducing the metal precursor, the loaded system may also contain an alkaline substance. The alkaline substance may be any substance that dissociates / hydrolyzes into hydroxide ions after dissolving in water and does not affect the metal loading. For example, it may be at least one of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, preferably sodium hydroxide.

[0089] According to the present invention, the weight ratio of the crosslinked polymer to the alkaline substance can be 1:(1-10), for example, it can be 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5 and 1:10, and any range between any two values. However, in order to further reduce costs and obtain the best antibacterial effect, it is more preferred to be 1:(1-6), and even more preferably 1:(3-5).

[0090] According to the present invention, in order to control the rate of polymer reaction and prevent metal oxidation, the loaded system may also contain a chelating agent. The chelating agent may be a commonly used chelating agent in the art that has the functions of inhibiting oxidation reaction, promoting metal ion reaction and loading, preferably ethylenediaminetetraacetic acid and / or its salt, wherein the ethylenediaminetetraacetic acid salt includes at least one of ethylenediaminetetraacetic acid dipotassium, ethylenediaminetetraacetic acid disodium, and ethylenediaminetetraacetic acid disodium magnesium, preferably ethylenediaminetetraacetic acid disodium.

[0091] According to the present invention, the weight ratio of the crosslinking polymer to the chelating agent can be 1:(0.5-10), for example, it can be 1:0.5, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5 and 1:10 and any range between any two values, preferably 1:(2-10), more preferably 1:(1.5-2.5).

[0092] According to the present invention, in order to obtain a better loading effect, the metal precursor and optional chelating agent can be dissolved in a solvent first, and then the liquid can be contacted with the crosslinking polymer. In order to ensure that the metal precursor, optional chelating agent and crosslinking polymer are fully contacted, the liquid containing the metal precursor and chelating agent is preferably added dropwise. More preferably, the liquid can be stirred at the same time as and / or after the dropwise addition. The stirring time can be flexibly adjusted according to the size of the system and the environment. According to one embodiment of the present invention, the stirring time is 20-40 min.

[0093] According to the present invention, in order to obtain a better loading effect, the reducing agent and optional alkaline substance can be dissolved in a solvent first, and then the liquid containing the reducing agent and optional alkaline substance can be added to the system containing the crosslinking polymer, the metal precursor and optional chelating agent. The preferred method of addition is dropwise addition.

[0094] According to the present invention, the reduction reaction time is preferably 20-120 min, for example, it can be 20 min, 26 min, 32 min, 38 min, 44 min, 50 min, 56 min, 62 min, 68 min, 74 min, 80 min, 86 min, 92 min, 98 min, 104 min, 110 min, 116 min and 120 min and any range between any two values, preferably 30-100 min, more preferably 50-70 min.

[0095] According to the present invention, the temperature of the reduction reaction can be 15-40°C, for example, it can be any range of 15°C, 17°C, 19°C, 21°C, 23°C, 25°C, 27°C, 29°C, 31°C, 33°C, 35°C, 37°C, 39°C and 40°C, and any two of these values. In order to further improve the reduction effect, the temperature is preferably 20-25°C.

[0096] According to the present invention, the pressure of the reduction reaction is not strictly limited. In one embodiment of the present invention, the pressure of the reduction reaction is atmospheric pressure (0.1 MPa, absolute pressure).

[0097] According to the present invention, in order to obtain a pure composite material, the composite material obtained after loading can be filtered, washed, and dried. The pore size of the material used for filtration can be flexibly adjusted according to the material used. According to one embodiment of the present invention, the pore size of the material used for filtration is 115-125 μm. The solvent used for washing can be a solvent that does not react with the composite material and can dissolve residual substances, such as deionized water, methanol, and ethanol, preferably water and / or ethanol. Washing can be performed sequentially with water and ethanol, or with a mixture of water and ethanol. More preferably, washing is performed sequentially with water and ethanol to better remove substances other than the product. The amount of solvent used for washing is not limited, as long as substances other than the product are removed. The drying method can be a commonly used drying method in the art. To further remove the solvent used for washing, the drying method is preferably vacuum drying. The vacuum drying method preferably includes: a pressure of -0.08 MPa to -0.06 MPa (gauge pressure), a temperature of 40-70°C, and a time of 5-20 h.

[0098] According to the most preferred embodiment of the present invention, the method for preparing the composite material with antibacterial properties includes:

[0099] (1) Add diethylenetriamine and 1,8-diazabicyclo[5.4.0]undec-7-ene to a system containing polyvinyl chloride (PVC) and dimethyl sulfoxide, and react at 55-65℃ for 22-26 h. The molar ratio of the structural unit of PVC, diethylenetriamine and 1,8-diazabicyclo[5.4.0]undec-7-ene is 1:(0.8-1.3):(0.7-1). After the reaction is completed, the product is filtered, washed with water and dried to obtain the crosslinked polymer.

[0100] (2) After mixing the crosslinked polymer obtained in step (1) with CuSO4, add the chelating agent disodium ethylenediaminetetraacetate, the alkaline substance NaOH and the reducing agent NaBH4 for loading. The loading time is 0.5-1.5h. The mass ratio of the crosslinked polymer, CuSO4, disodium ethylenediaminetetraacetate, NaOH and NaBH4 is 1:(3-5):(1.8-2.2):(3-5):(3.5-5.5). After loading, the product is filtered, washed and dried.

[0101] A third aspect of the present invention provides a composite material prepared by the method described above.

[0102] A fourth aspect of the present invention provides the use of the composite material as described above in the preparation of a bactericidal formulation.

[0103] According to the present invention, the bacteria may be *Escherichia coli*. In some embodiments of the present invention, the *Escherichia coli* is designated ATCC 8099.

[0104] The fifth aspect of the present invention provides the use of the composite material as described above in the preparation of a medicament for promoting wound healing.

[0105] According to one embodiment of the present invention, the wound is infected with Escherichia coli.

[0106] According to the present invention, the method for killing bacteria or promoting wound healing may include: covering the wound surface with the preparation or drug.

[0107] According to the present invention, the method for killing bacteria or promoting wound healing preferably includes: irradiating the preparation or drug with light, preferably, the light irradiation method is: a power of 10-50 mW / cm². 2 The time is 0.5-120 minutes.

[0108] According to some embodiments of the present invention, phototreatment of the formulation or drug can promote the generation of reactive oxygen species (including...). 1 O2、·O 2-It can enhance the sterilization rate (H2O2 and ·OH), and can also further promote wound healing and reduce the number of inflammation-related cells in wound tissue.

[0109] The present invention will be described in detail below through examples. In the following examples, unless otherwise specified, the reagents and materials used are commercially available products purchased from regular chemical or biological reagent / material suppliers.

[0110] Polyvinyl chloride (PVC): Purchased from Inner Mongolia Junzheng Energy Chemical Group Co., Ltd., with a number average molecular weight of approximately 81,000 g / mol and an average degree of polymerization of approximately 1300.

[0111] Escherichia coli: ATCC 8099, purchased from Beijing BioBio Biotechnology Co., Ltd.

[0112] Example 1

[0113] 1. Synthesis of cross-linking material PVC-DETA

[0114] Weigh 3.6 g of PVC into a sealed tube and add 88 g of dimethyl sulfoxide. Tighten the cap and place the sealed tube in an oil bath. Heat and stir at 60 °C until the PVC is completely dissolved, obtaining a clear solution. Heating time is 60 min. Diethylenetriamine (57.6 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 48 mmol) are injected along the tube wall into the sealed tube. Then, tighten the cap and continue stirring at 60 °C for 24 h at 250 rpm. After the reaction stops, cool the reaction system to room temperature (25 °C) and pour the black jelly-like solid in the bottle into a vacuum filter funnel for filtration. Then, place the obtained solid product in a beaker, add 80 mL of deionized water, sonicate at 100 W for 30 min, and filter again. Repeat the filtration step 3 times to ensure complete removal of organic solvents and unreacted raw materials from the product. Finally, the obtained product was freeze-dried at -70°C for 24 hours to obtain PVC-DETA.

[0115] 2. Preparation of antibacterial material PVC-DETA@CuNPs

[0116] 0.1 g of PVC-DETA was added to 20 mL of water and sonicated at 100 W for 1 h until uniformly dispersed to obtain a sample suspension. 0.625 g of CuSO4·5H2O and 0.2025 g of disodium ethylenediaminetetraacetate (EDTA-2Na) were dissolved in 30 mL of water, and this solution was added dropwise to the sample suspension, with continuous stirring for 30 min. 20 mL of a solution containing 0.403 g of NaOH and 0.473 g of NaBH4 was gradually added dropwise to the above mixed solution. The reaction was carried out at atmospheric pressure and 22±2℃ for 60 min. The resulting suspension was filtered through 120 μm filter paper and washed successively with water and ethanol. It was then vacuum dried at -0.07 MPa and 60℃ for 12 h to obtain black crystalline PVC-DETA@CuNPs particles. Figure 1 As shown.

[0117] Test Example 1

[0118] (1) Characterization of PVC-DETA:

[0119] The nitrogen content in PVC-DETA was characterized by elemental analysis. The results showed that the nitrogen content in PVC-DETA was 10.63 wt%, and the content of crosslinking structure provided by the crosslinking agent diethylenetriamine was estimated to be 26 wt%.

[0120] Infrared characterization method: PVC-DETA and KBr were mixed and ground evenly at a weight ratio of 1:100, then pressed into tablets and their transmittance was tested using a Fourier transform infrared spectrometer.

[0121] In Fourier transform infrared characterization, primary amines (-NH2) should be within the range of 3300-3500 cm⁻¹. -1 There should be two absorption peaks within the range, but if... Figure 2 As shown, there is only one absorption peak at 3431 cm⁻¹ within this range. -1 This means that the absorption peak can only be the stretching vibration absorption peak of a secondary amine. This result indicates that -NH2 is absent in the crosslinked product, indicating that the reaction has been complete. Furthermore, the combined peak at 1629 cm⁻¹... -1 The presence of an NH absorption peak (the bending vibration absorption peak of secondary amines) and the absence of any sites in the raw materials that can react with primary amines except for chlorine sites indicate that the primary amines reacted completely with chlorine. These results combined demonstrate that PVC-DETA was successfully synthesized.

[0122] (2) Characterization of PVC-DETA@CuNPs:

[0123] PVC-DETA@CuNPs powder was ground and pressed into tablets for testing by X-ray diffraction (XRD); the sample powder was adhered to conductive adhesive and tested by in-situ X-ray photoelectron spectroscopy (XPS).

[0124] like Figure 3 As shown, via XPS ( Figure 3 Left 1) and XRD ( Figure 3 Characterization (left 2 and right 1) shows that the prepared PVC-DETA@CuNPs contain Cu and Cu2O, with the Cu content being 12.83 wt%.

[0125] TEM characterization method: PVC-DETA@CuNPs material was dispersed in ethanol, sonicated for 15 min, and then characterized by transmission electron microscopy. The lattice morphology and spacing of elemental Cu and cuprous oxide Cu₂O obtained by TEM characterization are shown below. Figure 4 As shown, the results indicate that the lattice spacing (d) of Cu(111) is 0.22 nm and the lattice spacing (d) of Cu2O(111) is 0.25 nm.

[0126] STEM characterization method: PVC-DETA@CuNPs material was dispersed in ethanol, sonicated for 15 min, and then subjected to EDS energy dispersive spectroscopy analysis using a high-angle annular dark-field scanning transmission electron microscope. For example... Figure 5 As shown (the top left image shows the HAADF results for PVC-DETA@CuNPs material, and the other three images are the elemental spectra of Cu, N, and O, respectively), the Cu, N, and O elements in PVC-DETA@CuNPs are uniformly distributed.

[0127] Test Example 2

[0128] 1. Reactive oxygen species test and bactericidal experiment:

[0129] 300 μg of PVC-DETA@CuNPs was added to 12.5 mL of 2,7-dichlorofluorescein diacetate (DCFH, 40 μM) solution, and the solution was heated using a power of 15 mW / cm². 2 Irradiation with an LED lamp was performed, and the fluorescence emission intensity of the solution at a wavelength of 524 nm was recorded after 0 min, 5 min, 10 min, 20 min, and 30 min. The results are as follows: Figure 6 As shown. Simultaneously, ESR characterization tests were used to determine the reactive oxygen species (ROS) in PVC-DETA@CuNPs after different irradiation times. 1 O2、·O 2- The contents of H2O2 and ·OH are as follows Figure 7 As shown (from left to right) 1 O2、·O 2- (Results of H2O2 and ·OH).

[0130] ESR characterization method: The powder samples were measured at 15 W / cm² at 0 min, 5 min, and 10 min using an electron paramagnetic resonance spectrometer. 2Measurement under LED illumination 1 O2、·O 2- The intensity of H2O2 and ·OH was used, with intensity representing content. It can be observed that the content of various active oxygens generated by PVC-DETA@CuNPs gradually increases with increasing light exposure time.

[0131] Escherichia coli was selected as the experimental strain. The indicator bacteria were cultured using the national standard method. The cultures were treated with antibacterial materials, and bacterial counts were performed to verify the bactericidal ability. A blank control group and experimental groups were set up for E. coli bactericidal experiments. The experimental groups were PVC-DETA (100 μg / mL), PVC-DETA@CuNPs (50 μg / mL), and PVC-DETA@CuNPs+PDT (50 μg / mL, irradiated with a 15mW LED lamp for 30 min). The contact time between the bactericide and bacteria was 30 min. The viable count of E. coli in each group was 10-1. 6 CFU / mL.

[0132] Sterilization rate: (Number of viable bacteria before sterilization - Number of viable bacteria after sterilization) / Number of viable bacteria before sterilization × 100%.

[0133] The sterilization rates of the blank control group, PVC-DETA, PVC-DETA@CuNPs, and PVC-DETA@CuNPs+PDT were 0%, 25.4%, 99.9%, and 100%, respectively. The PVC-DETA@CuNPs sterilization material could almost completely kill Escherichia coli at a concentration of 50 μg / mL.

[0134] The morphology of the treated E. coli is as follows Figure 8 As shown (from left to right: blank control group, PVC-DETA, PVC-DETA@CuNPs, and PVC-DETA@CuNPs+PDT), it can be observed that the morphology of E. coli in the blank control group and PVC-DETA group did not change significantly. However, the E. coli in the PVC-DETA@CuNPs and PVC-DETA@CuNPs+PDT groups exhibited disrupted bacterial shapes, with collapsed, defective, and rough surfaces, accompanied by leakage of cell contents and bacterial death.

[0135] Test Example 3

[0136] Male Kunming mice aged 4-6 weeks and weighing 26±2g were purchased from Spiefol (Beijing) Biotechnology Co., Ltd. After acclimatizing to their environment in the animal laboratory for 7 days, the mice were anesthetized with 10wt% chloral hydrate. Hair was removed from the back of the mice using depilatory cream, and a complete, uniform circular wound with a radius of approximately 2mm was made on the back of each mouse using sterile scissors. The mice were then inoculated with 10μL of Escherichia coli suspension (10... 6Mice were randomly divided into four groups of eight mice each. Before the experiment, mice were treated with phosphate-buffered saline (PBS buffer, control group), PVC-DETA, PVC-DETA@CuNPs, and PVC-DETA@CuNPs+PDT (808nm, 15mW / cm). 2 Apply the antibacterial agent to the wound surface after 30 minutes of light exposure, and feed the mice under the same conditions for 8 days. Do not apply the antibacterial agent again during the 8 days.

[0137] The mice were weighed daily, and wound healing was observed by taking digital photographs. Figure 9 As shown, the wound area was measured. The wound healing rate was calculated using the following formula, where A0 and A... t The wound areas on day 0 and day t are respectively:

[0138] Wound healing rate (%) = (1-A) t / A0)×100%.

[0139] Figure 9 (a) shows a macroscopic imaging analysis of wound healing on days 0, 3, 5, and 7 in the four treatment groups. Wounds gradually healed during treatment in all groups. Figure 9 As shown in (b), after 7 days, the wound healing rates of the control group, PVC-DETA, PVC-DETA@CuNPs, and PVC-DETA@CuNPs+PDT group were 39.6%, 49.8%, 55.5%, and 66.3%, respectively. Figure 9 (c) shows the change in mouse body weight. The results indicate that the body weight of mice in both the control and experimental groups remained stable throughout the treatment period.

[0140] After the experiment, skin tissue from the wounds was collected, and the residual colonies from the four groups were incubated in LB medium at 37°C for 12 hours, and the total colony count for each group was calculated. The results showed that the colony counts of the PVC-DETA@CuNPs and PVC-DETA@CuNPs+PDT groups were significantly lower than those of the other groups (e.g., ...). Figure 10 and Figure 11 As shown in the figure, this indicates that PVC-DETA@CuNPs itself has a strong antibacterial effect, and its antibacterial effect can be further improved under LED irradiation.

[0141] After the experiment, the following inflammation-related hematological parameters were measured using a complete blood count (CBC) instrument, including white blood cell count (WBC), lymphocytes (Lymph), and neutrophils (Gran). The results are as follows: Figure 12As shown in the figure. The results indicated that the white blood cell, neutrophil, and lymphocyte counts in the PVC-DETA@CuNPs+PDT group mice were within the normal range, but slightly decreased compared to the other three groups. This suggests that PVC-DETA@CuNPs+PDT possesses good in vivo anti-infective capabilities.

[0142] Seven days after the experiment, pathological sections of the mouse wound epidermis were prepared and fixed in 10 vol% paraformaldehyde. After paraffin embedding, sections were cut to a thickness of 4 μm and then sequentially immersed in xylene for 20 min, fresh xylene for 20 min, anhydrous ethanol for 10 min, fresh anhydrous ethanol for 10 min, 95 vol% ethanol for 5 min, 90 vol% ethanol for 5 min, 80 vol% ethanol for 5 min, 70 vol% ethanol for 5 min, and then washed with distilled water. The cell nuclei were then stained with hematoxylin: sections were stained with Harris hematoxylin for 3-8 min, washed with tap water, differentiated in 1 wt% hydrochloric acid ethanol for a few seconds, rinsed with tap water, and then blued with 0.6 wt% ammonia solution, and rinsed with running water. Finally, the cytoplasm was stained with eosin: sections were stained with eosin for 1-3 min. Dehydration and mounting: The sections were sequentially immersed in 95 vol% ethanol for 5 min, then in fresh 95 vol% ethanol for 5 min, then in anhydrous ethanol for 5 min, then in xylene I for 5 min, and finally in fresh xylene for 5 min to dehydrate until clear. The sections were then removed from the xylene and allowed to air dry slightly before mounting with neutral resin. Finally, the sections were examined under a microscope, and images were acquired and analyzed. The results are as follows: Figure 13 As shown.

[0143] The control group showed severe abnormalities in skin tissue structure, with an intact epidermis, a thin and homogeneous stratum spinosum, and no observed necrosis or cell degeneration. Dermal collagen fibrosis showed a limited number of fibroblasts (blue arrows) and a small number of newly formed blood vessels (orange arrows). Inflammatory cell infiltration was clearly visible in the squamous epithelial cells. The PVC-DETA group showed moderate abnormalities in skin tissue structure, with an intact epidermis, a thin and homogeneous stratum spinosum, and no observed cell necrosis or degeneration. Dermal collagen fibrosis was significant, with a large number of fibroblasts present (as shown by blue arrows). In addition, a small number of inflammatory cells were infiltrated in the tissue (as shown by black arrows).

[0144] For PVC-DETA@CuNPs, the skin tissue structure showed slight abnormalities. The epidermis was intact, and the stratum spinosum was thin and homogeneous, without necrotic or degenerated cells. The collagen fibers in the dermis were neatly and tightly arranged, and numerous skin appendages were also observed. Sebaceous glands are indicated by red arrows. Histological analysis revealed inflammatory cell infiltration, as indicated by black arrows.

[0145] The skin tissue structure in the PVC-DETA@CuNPs+PDT group appeared histologically normal, with an intact epidermis and a thin, homogeneous stratum spinosum, showing no signs of cell necrosis or degeneration. The collagen fibers in the dermis were neatly and tightly arranged, with abundant skin appendages. Sebaceous glands are indicated by red arrows. No inflammatory cell infiltration was observed in the tissue. These results indicate that PVC-DETA@CuNPs can effectively promote the healing of bacterial-infected wounds under LED light.

[0146] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A composite material with antibacterial properties, characterized in that, The composite material comprises a crosslinked polymer and nano-metals supported on the crosslinked polymer, wherein the crosslinked polymer is a product of a halogenated plastic crosslinked via a crosslinking structure, the structural formula of which is shown in Formula a, and the nano-metals include at least one selected from silver, copper, zinc, and aluminum. Where m and n are each independently 1-6.

2. The composite material according to claim 1, wherein, The N content in the crosslinked polymer is 5-90 wt% based on the total weight of the crosslinked polymer; Preferably, the cross-linked polymer contains 10-40 wt% cross-linked structures; Preferably, the nano-metal has reducing properties; Preferably, the nano-metal comprises elemental metals and / or metal oxides; Preferably, the content of the nano-metal is 1-30 mol relative to each kilogram of crosslinked polymer; Preferably, m and n are 2; Preferably, the halogenated plastic is polyhalogenated polyethylene, more preferably polyvinyl chloride.

3. A method for preparing a composite material with antibacterial properties, characterized in that, The method includes: (1) In the presence of a solvent and a crosslinking catalyst, a halogenated plastic is brought into contact with a crosslinking agent to carry out a crosslinking reaction, wherein the crosslinking agent has the structure shown in formula b; Where m and n are each independently 1-6; (2) Loading nano-metals onto the cross-linked polymer obtained by the cross-linking reaction in step (1), wherein the nano-metals include at least one of silver, copper, zinc and aluminum.

4. The method according to claim 3, wherein, In step (1), the solvent is at least one of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, tetrahydronaphthalene, and decahydronaphthalene, preferably dimethyl sulfoxide; Preferably, in step (1), the crosslinking catalyst is selected from sodium carbonate, sodium bicarbonate, sodium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene, more preferably 1,8-diazabicyclo[5.4.0]undec-7-ene; Preferably, in step (1), the halogenated plastic is polyhalogenated polyethylene, more preferably polyvinyl chloride; Preferably, m and n are 2.

5. The method according to claim 3, wherein, In step (1), the weight ratio of the halogenated plastic to the solvent is 1:(5-300), preferably 1:(50-100); Preferably, in step (1), the molar ratio of the crosslinking agent to the halogenated plastic (calculated as halogen) is 1:(0.5-10), more preferably 1:(0.5-5); Preferably, in step (1), the molar ratio of halogenated plastic to crosslinking catalyst, calculated as halogen, is (0.5-5):1, more preferably (1-4):

1.

6. The method according to claim 3, wherein, In step (1), the temperature of the crosslinking reaction is 30-120℃, preferably 50-90℃; And / or, in step (1), the crosslinking reaction time is 6-48h, preferably 12-36h.

7. The method according to claim 3, wherein, In step (2), the amount of the nano-metal is 4-30 mol relative to each kilogram of crosslinked polymer, preferably 20-30 mol; Preferably, the nano-metal has reducing properties; Preferably, the nano-metal comprises elemental metals and / or metal oxides.

8. The method according to claim 3, wherein, In step (2), the system of the load also contains a reducing agent; Preferably, the reducing agent is at least one of LiAlH4, diisobutylaluminum hydride and NaBH4, more preferably NaBH4; Preferably, the weight ratio of the reducing agent to the crosslinking polymer is 1:(0.5-10), more preferably 1:(1-6); Preferably, the loading method includes: reducing the metal precursor in the presence of a reducing agent and a crosslinking polymer.

9. The composite material prepared by the method according to any one of claims 3-8.

10. Use of the composite material according to any one of claims 1, 2 and 9 in the preparation of a bactericidal formulation.

11. Use of the composite material according to any one of claims 1, 2 and 9 in the preparation of a medicament for promoting wound healing.

12. The application according to claim 10 or 11, wherein, The method for killing bacteria or promoting wound healing includes: irradiating the preparation or drug with light.

Images