N-halamine antibacterial microspheres of maleimide copolymer as well as preparation method and application of N-halamine antibacterial microspheres

Abstract

The invention discloses N-halamine antibacterial microspheres of a maleimide copolymer as well as a preparation method and application of the N-halamine antibacterial microspheres, and belongs to the technical field of antibacterial materials. The N-halamine antibacterial microspheres of the maleimide copolymer have the advantages that acylamino / imide groups can be modified into N-halamine groups with antibacterial effects after the N-halamine antibacterial microspheres of the maleimide copolymer are subjected to halogen amination by the aid of hypohalide acid salts, and the N-halamine antibacterial microspheres of the maleimide copolymer can be used for efficiently killing staphylococcus aureus and escherichia coli.

Description

Technical Field

[0001] The invention belongs to the technical field of antibacterial materials, and in particular relates to N-halamine antibacterial microspheres of maleimide copolymers and a preparation method and application thereof. Background Art

[0002] Bacterial microorganisms bring many troubles to human life in terms of drinking water pollution, food spoilage, and infection of medical supplies. Traditional antibacterial agents such as chlorine and ozone are often used in water treatment, but chlorine itself is harmful to the human body, which restricts its application; although ozone has low toxicity, it is unstable in water and its antibacterial effect is greatly reduced. In addition, nanosilver / silver ions are often added to textiles as antibacterial agents, but the high cost has a great impact on their application. Ultraviolet rays are also a widely used antibacterial method, but the application of ultraviolet rays is limited in light-proof places such as pipes and tanks. In summary, it is urgent to develop a new type of antibacterial agent that is non-toxic, highly efficient, and has a wide range of applications.

[0003] N-halamines are a class of promising antimicrobial agents. After amines, amides or imides are oxidized by hypohalites, the hydrogen attached to nitrogen is replaced by an oxidizing halogen (Cl + ,Br + , I + ) to form N-halamine. N-halamine has the same bactericidal effect as the equivalent inorganic hypohalite, and is more stable, durable, less toxic, less harmful to the human body and the environment, and can be recycled. This antibacterial agent has a significant killing effect on representative microorganisms that cause various infections, such as Staphylococcus aureus (Gram-positive bacteria), Escherichia coli (Gram-negative bacteria), methicillin-resistant Staphylococcus aureus (resistant Gram-positive bacteria), vancomycin-resistant Enterococcus (resistant Gram-positive bacteria) and Candida albicans (fungus).

[0004] Common N-haloamine polymers include those obtained by polymerizing olefinic compounds containing hydantoin structures as monomers. The hydantoin ring contains both an amide group and an imide group, so the oxidized halide ion obtained by halogenation has both stability and reactivity. CN116791231 A introduces 3-allyl-5,5-dimethylhydantoin into polyester fibers to give them antibacterial properties. In addition, other compounds containing amines, amides, and imides can also be introduced into polymers as N-halamine antibacterial polymers, such as J. Ind. Eng. Chem. 2022, 107: 249-258, curing methacrylamide / acrylic acid copolymer with epoxy resin, and introducing PET fabric to modify it for antibacterial effect; J. Ind. Text. 2015, 46 (1): 59-74, electrostatic assembly and then coating chitosan multilayer film on polyglycolide surgical suture, the amino group in chitosan has antibacterial effect after halogenation; Cellulose. 2011, 19 (1): 209-217, cross-linking amino / amide / imide compounds such as urea, barbituric acid and carbamic acid with straw cellulose to obtain antibacterial cellulose. However, when synthesizing these antibacterial polymers, the process of introducing amine-containing antibacterial units requires a relatively complex polymerization reaction or polymer chemical reaction, which brings great limitations to their application and subsequent industrial production.

[0005] The common methods for preparing polymer microspheres include emulsion polymerization, seed swelling polymerization, suspension polymerization, dispersion polymerization and precipitation polymerization. Different polymerization methods can prepare microspheres with different particle sizes and particle size distributions. The common disadvantage of these polymerization methods is that stabilizers must be added, which will have a certain impact on the physical and chemical properties of the surface of polymer microspheres. At the same time, the presence of stabilizers will also cause certain harm to the human body.

[0006] CN112574336 A discloses a method for preparing a maleimide copolymer, but the synthesized microspherical maleimide copolymer lacks antibacterial functional units and does not have antibacterial efficacy, and the non-crosslinked microspherical maleimide copolymer cannot exist stably in an aqueous solution for a long time. Summary of the invention

[0007] In order to solve the above technical problems, the present invention proposes a maleimide copolymer N-halamine antibacterial microsphere and its preparation method and application. The maleimide copolymer cross-linked microsphere of the present invention can contain maleamic acid groups and maleimide groups at the same time, and after being halogenated with hypohalite, the amide group / imide group can be modified into an N-halamine group with antibacterial effect. The polymer microsphere has a high efficiency in killing some representative bacteria.

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] One of the technical solutions of the present invention:

[0010] The present invention provides a method for preparing N-halamine antibacterial microspheres of maleimide copolymer, comprising the following steps:

[0011] Adding a comonomer, maleic anhydride, an initiator and a crosslinking agent into an organic solvent, allowing the comonomer and the maleic anhydride to undergo a self-stabilizing precipitation polymerization reaction to precipitate maleic anhydride copolymer crosslinked microspheres;

[0012] The maleic anhydride copolymer cross-linked microspheres are subjected to a gas-solid amination reaction in an ammonia atmosphere to obtain maleamic acid copolymer cross-linked microspheres, wherein the amination rate of the maleamic acid copolymer cross-linked microspheres is above 99%, and the amination rate can be increased by increasing the time of the gas-solid amination reaction;

[0013] Heating the maleamic acid copolymer cross-linked microspheres to cause an imidization reaction to occur, thereby obtaining maleimide copolymer cross-linked microspheres, wherein the imidization rate of the maleimide copolymer cross-linked microspheres is any value between 20% and 100%;

[0014] The maleimide copolymer microspheres are dispersed in a hypohalite aqueous solution for halogenation to obtain N-haloamine antibacterial microspheres of the maleimide copolymer.

[0015] The present invention first adds a comonomer, maleic anhydride, an initiator and a crosslinking agent into an organic solvent, so that the comonomer and maleic anhydride undergo a self-stabilizing precipitation polymerization reaction to precipitate maleic anhydride copolymer crosslinked microspheres; then the maleic anhydride copolymer crosslinked microspheres are placed in an ammonia atmosphere for gas-solid amination reaction to obtain maleamic acid copolymer crosslinked microspheres; then the maleamic acid copolymer crosslinked microspheres are placed in a confined space, and an imidization reaction is carried out under heating conditions to obtain maleimide copolymer crosslinked microspheres (i.e. maleamic acid / maleimide copolymer microspheres); finally, the maleimide copolymer crosslinked microspheres are dispersed in a hypohalite aqueous solution for halogenation to obtain N-halamine antibacterial microspheres of maleimide copolymers. The present invention can prepare N-halamine antibacterial microspheres of maleimide copolymers with good antibacterial effects without adding a surfactant, and the microspheres have a crosslinked structure and good stability in an aqueous solution. Polymer microspheres have the advantages of large specific surface area, strong adsorption, strong surface reaction ability, etc. The present invention introduces antibacterial functional groups into polymer microspheres to obtain highly effective antibacterial microspheres. The present invention adopts a self-stabilizing precipitation polymerization polymerization method, and can synthesize polymer microspheres without adding additional stabilizers. The process is simple and green. The subsequent process of introducing amine-containing antibacterial units into polymer microspheres is also simple and easy to operate, does not involve complex polymer chemical reactions, and is suitable for large-scale synthesis.

[0016] The comonomer is selected from at least one of the following monomers: (meth) acrylic monomers, styrene monomers, vinyl monomers, olefin monomers, composite monomers derived from petroleum fractionation, and composite monomers derived from coal chemical industry. Exemplarily, the comonomer is selected from at least one of the following monomers: styrene, α-methylstyrene, vinyl acetate, 1,1-diphenylethylene, isobutylene, gasoline, C4 mixture, C5 mixture, C8 mixture, C9 mixture, coumarone, and coal tar light fraction.

[0017] The crosslinking agent is selected from at least one of the following compounds: divinylbenzene, diallyl phthalate, N,N'-(4,4'-methylenediphenyl)-bismaleimide, 1,6-bismaleimide hexane, ethylene glycol diacrylate, ethylene glycol dimethacrylate and triethylene glycol dimethacrylate.

[0018] The molar ratio of the comonomer to maleic anhydride is 1:10-10:1 (i.e. 1 / 10 to 10 / 1); and / or

[0019] The amount of the organic solvent is 20-900% of the total mass of the comonomer and maleic anhydride; and / or

[0020] The amount of the initiator is 0.2-10% of the total mass of the comonomer and maleic anhydride; and / or

[0021] The amount of the cross-linking agent used is 0.1-5% of the total molar amount of maleic anhydride.

[0022] The average particle size of the maleic anhydride copolymer cross-linked microspheres is 200 nm-6 μm, preferably 400 nm-4 μm, and the particle size dispersion coefficient is preferably 1.03-1.5.

[0023] The heating temperature is 160° C.-180° C., and the reaction time is 2 h-12 h. The higher the reaction temperature and the longer the reaction time, the higher the imidization degree.

[0024] When the maleamic acid-based copolymer crosslinked microspheres are heated, the maleamic acid-based copolymer crosslinked microspheres are heated in a state of being dispersed in a dispersion medium or in a state of being a dry solid.

[0025] The concentration of the hypohalite aqueous solution is 0.5wt.%-10wt.%, preferably 3wt.%-5wt.%, the pH value is 7-8, and the reaction time of the halogen amination reaction is 10min-6h, preferably 30min-2h.

[0026] The hypohalite is selected from at least one of the following salts: NaClO, KClO, Ca(ClO)2, NaBrO, KBrO, Ca(BrO)2, NaIO, KIO and Ca(IO)2.

[0027] The second technical solution of the present invention:

[0028] The present invention also provides N-halamine antibacterial microspheres of maleimide copolymer prepared according to the method.

[0029] The third technical solution of the present invention:

[0030] The present invention also provides the use of the N-halamine antibacterial microspheres of the maleimide copolymer in the preparation of antibacterial drugs.

[0031] The N-halamine antibacterial microspheres of the maleimide copolymer of the present invention can effectively kill Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).

[0032] The fourth technical solution of the present invention:

[0033] The present invention also provides an antibacterial material, the active component of which is the N-halamine antibacterial microspheres of the maleimide copolymer.

[0034] Compared with the prior art, the present invention has the following advantages and technical effects:

[0035] The invention provides a method for preparing N-halamine cross-linked antibacterial microspheres of a maleimide copolymer. The obtained polymer microspheres can contain maleamic acid groups and maleimide groups at the same time. After being halogenated with hypohalite, the amide group / imide group can be modified into an N-halamine group with antibacterial effect. The polymer microspheres have a highly effective killing effect on some representative bacteria.

[0036] The maleic anhydride copolymer microspheres of the present invention are synthesized by a self-stabilizing precipitation polymerization method. This process is simple and efficient, the solvent is green and recyclable, the product is easy to separate, and no stabilizer needs to be added, which can greatly reduce the production cost and ensure that the product is harmless to the human body. The obtained maleic anhydride copolymer cross-linked microspheres can be subjected to gas-solid amination reaction under an ammonia atmosphere, and the reaction time is more than 12 hours, so that the amination rate is more than 99%. The temperature of the imidization reaction is usually 160°C-180°C, and the reaction time is usually 2h-12h. The higher the reaction temperature and the longer the reaction time, the higher the degree of imidization. Since the copolymer microspheres are cross-linked structures, the degree of imidization will not affect their water solubility and morphological changes in water. There is no additional solvent in the amidation and imidization process, which simplifies the process flow and reduces the environmental burden. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings:

[0038] Figure 1 Scanning electron microscope images and corresponding energy spectrum mapping images of different microspheres prepared in Example 6, wherein: a is a C5 mixture-maleic anhydride copolymer cross-linked microsphere, b is a C5 mixture-maleamic acid copolymer cross-linked microsphere, c is a maleimide copolymer cross-linked microsphere, and d is a C5 mixture-maleimide-based N-halamine cross-linked microsphere;

[0039] Figure 2 The antibacterial evaluation pictures of the plate coating counting method, wherein: a1-a6 are blank controls, b1-b6 are polymer microspheres prepared in Example 6 without N-halamination reaction (i.e., C5 mixture-maleimide copolymer cross-linked microspheres), c1-c6 are polymer microspheres prepared in Example 6 after N-halamination reaction (i.e., C5 mixture-maleimide N-halamine cross-linked microspheres), and the initial colony concentration is 10 6 CFU / mL, and the bacterial contact time was 10 min;

[0040] Figure 3 The morphologies of the uncrosslinked copolymer microspheres with a low degree of imidization prepared in Comparative Example 1 in different dispersion media, wherein: a is the morphology after dispersion in an organic solvent (methyl tert-butyl ether) for 5 min, and b is the morphology after dispersion in a NaClO aqueous solution (concentration of 3 wt.%, pH = 8) for 5 min. DETAILED DESCRIPTION

[0041] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0042] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0043] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0044] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0045] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0046] In some embodiments of the present invention, a method for preparing N-halamine antibacterial microspheres of maleimide copolymer is provided:

[0047] The comonomer, maleic anhydride, an initiator and a crosslinking agent are added into an organic solvent to make the comonomer and maleic anhydride undergo a self-stabilizing precipitation polymerization reaction to precipitate maleic anhydride copolymer crosslinked microspheres;

[0048] The maleic anhydride copolymer cross-linked microspheres are subjected to a gas-solid amination reaction in an ammonia atmosphere to obtain maleamic acid copolymer cross-linked microspheres, wherein the amination rate of the maleamic acid copolymer cross-linked microspheres is above 99%;

[0049] Heating the maleamic acid copolymer cross-linked microspheres to cause an imidization reaction to occur, thereby obtaining maleimide copolymer cross-linked microspheres, wherein the imidization rate of the maleimide copolymer cross-linked microspheres is any value between 20% and 100%;

[0050] The maleimide copolymer microspheres are dispersed in a hypohalite aqueous solution for halogenation to obtain N-halamine antibacterial microspheres of the maleimide copolymer.

[0051] The infrared spectrum peak area integration method was used to calculate the amination rate of the maleamic acid copolymer cross-linked microspheres. The specific calculation method is:

[0052]

[0053] Among them, A 1-1860 1860cm in the sample after amination -1 The characteristic peak area of ​​the anhydride group, A1-1460 1460cm in the sample after amination -1 The characteristic peak area of ​​methyl group; A 0-1860 1860 cm in the unaminated sample -1 The characteristic peak area of ​​the anhydride group, A 0-1460 1460 cm in the unaminated sample -1 The characteristic peak area of ​​methyl group.

[0054] The imidization rate of the maleimide copolymer cross-linked microspheres was calculated by the infrared spectrum peak area integration method. The specific calculation method is:

[0055]

[0056] Among them, A 1-1780 1780cm in the imidized sample -1 The characteristic peak area of ​​the imide group, A 1-1460 1460cm in the imidized sample -1 The characteristic peak area of ​​methyl group; A 2-1780 The 1780 cm-1 of the fully imidized standard sample -1 The characteristic peak area of ​​the imide group, A 2-1460 The 1460 cm-1 -1 The characteristic peak area of ​​methyl group.

[0057] In the embodiments of the present invention, there is no particular restriction on the order of adding the raw materials. The comonomer, maleic anhydride, initiator and cross-linking agent can be added to the organic solvent at the same time, can be added to the organic solvent in any order, or can be pre-formed into a mixture before adding to the organic solvent.

[0058] In the embodiment of the present invention, the average particle size of the prepared maleic anhydride copolymer cross-linked microspheres is preferably 200nm-6μm, more preferably 400nm-4μm, and the particle size dispersion index (PDI) is 1.03-1.5. PDI is an indicator to measure the uniformity of the particle size distribution of microspheres. The smaller the value, the more uniform the particle size distribution.

[0059] In the embodiment of the present invention, the reaction between the comonomer and maleic anhydride is a self-stabilizing precipitation polymerization reaction, and no additional stabilizer is required. The entire system is usually a clear and transparent reactant solution before the polymerization reaction begins, and gradually turns into a milky white polymer microsphere dispersion as the polymerization reaction proceeds.

[0060] In an embodiment of the present invention, the comonomer includes but is not limited to: (meth) acrylic acid monomers, such as methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, isopropyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acrylate, pentyl (meth) acrylate, n-hexyl (meth) acrylate, glycidyl (meth) acrylate, isobornyl (meth) acrylate, etc.; styrene monomers, such as styrene, α-methylstyrene, o-methylstyrene, p-methylstyrene, etc.; vinyl monomers, vinyl acetate, vinyl propionate, etc.; olefin monomers, such as ethylene, 1,1-diphenylethylene, propylene, isobutylene, etc.; composite monomers derived from petroleum fractionation, such as gasoline, C4 mixture, C5 mixture, C8 mixture, C9 mixture, coumarone, etc.; composite monomers derived from coal chemical industry, such as coal tar light fraction, etc. These comonomers can be used alone or in combination of two or more.

[0061] In an embodiment of the present invention, the comonomer is preferably at least one selected from styrene, α-methylstyrene, vinyl acetate, 1,1-diphenylethylene, isobutylene, gasoline, C4 mixture, C5 mixture, C8 mixture, C9 mixture, coumarone and coal tar light fraction.

[0062] There is no particular restriction on the molar ratio of the comonomer to maleic anhydride, and it can be changed according to the type of the comonomer and the desired use. Usually, the molar ratio of the comonomer to maleic anhydride (comonomer / maleic anhydride) is preferably 1 / 10 to 10 / 1, more preferably 1 / 8 to 8 / 1, more preferably 1 / 5 to 5 / 1, and even more preferably 1 / 3 to 4.5 / 1.

[0063] In an embodiment of the present invention, there is no particular restriction on the type of organic solvent. Preferably, the organic solvent is a solvent that can dissolve the comonomer and maleic anhydride, but does not dissolve the obtained maleic anhydride copolymer cross-linked microspheres. From the viewpoint of maleic anhydride copolymer microspheres that are easily available, have a high specific surface area and good monodispersity, the organic solvent is preferably selected from at least one of an ester solvent, an aromatic hydrocarbon solvent and an aromatic ether solvent.

[0064] In an embodiment of the present invention, the ester solvent includes: butyl formate, amyl formate, propyl acetate, butyl acetate, n-amyl acetate, isoamyl acetate, benzyl acetate, phenyl acetate, ethyl butyrate, propyl butyrate, butyl butyrate, isobutyl butyrate, isoamyl butyrate, ethyl isobutyrate, ethyl isovalerate, isoamyl isovalerate, methyl benzoate, ethyl benzoate, propyl benzoate, butyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate, propyl phenylacetate, butyl phenylacetate, isoamyl phenylacetate. These ester solvents can be used alone or in combination of two or more.

[0065] In the embodiment of the present invention, the aromatic hydrocarbon solvent includes toluene, ethylbenzene, n-propylbenzene, isopropylbenzene, butylbenzene, xylene, diethylbenzene, mesitylene, cyclohexylbenzene, diphenylethane. These aromatic hydrocarbon solvents can be used alone or in combination of two or more.

[0066] In the embodiment of the present invention, the aromatic ether solvent includes anisole, phenethyl ether, phenylpropyl ether, and diphenyl ether. These aromatic ether solvents can be used alone or in combination of two or more.

[0067] In the embodiments of the present invention, from the viewpoint of simultaneously ensuring productivity and obtaining the desired maleic anhydride copolymer crosslinked microspheres, the amount of the organic solvent used is preferably 20-900 mass %, more preferably 50-800 mass %, relative to the total mass of the comonomer and maleic anhydride.

[0068] In an embodiment of the present invention, the initiator is preferably a free radical polymerization initiator. As specific polymerization initiators, there can be cited: azo initiators such as azobisisobutyronitrile (AIBN), azobisisovaleronitrile, azobisisoheptanenitrile (ABVN), dimethyl azobisisobutyrate; organic peroxide initiators can be selected from dibenzoyl peroxide (BPO), dipropylbenzene peroxide, di(2,4-dichlorobenzoyl) peroxide, dodecyl peroxide, tert-butyl peroxyneoheptanoate, tert-butyl peroxyneodecanoate, di-sec-butyl peroxydicarbonate, di(hexadecyl) dicarbonate, tert-amyl peroxyneodecanoate, tert-butyl peroxypivalate, di- (4-tert-butyl cyclohexyl ester), dicyclohexyl peroxydicarbonate, diisopropyl peroxydicarbonate, dibutyl peroxydicarbonate, di(2-ethylhexyl) peroxydicarbonate, tert-butyl peroxy-2-ethylhexanoate, ditetradecyl peroxydicarbonate, tert-butyl peroxyacetate, isopropyl peroxyneodecanoate, di-tert-butyl peroxide, cyclohexylsulfonylacetyl peroxide, dibenzoyl peroxide, diisobutyryl peroxide, 1,1,3,3-tetramethylbutyl peroxyneodecanoate, di-3-methoxybutyl peroxydicarbonate, 1,1,3,3-tetramethylbutyl peroxypivalate. These initiators can be used alone or in combination of two or more.

[0069] In the embodiments of the present invention, the amount of the initiator used is preferably 0.2-10% by mass, more preferably 0.8-6% by mass, and even more preferably 1-4.5% by mass, relative to the total mass of the comonomer and maleic anhydride.

[0070] In the embodiment of the present invention, the crosslinking agent includes but is not limited to: divinylbenzene, diallyl phthalate, N,N'-(4,4'-methylenediphenyl)-bismaleimide, 1,6-bismaleimide hexane, ethylene glycol diacrylate, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate. These crosslinking agents can be used alone or in combination of two or more.

[0071] In the embodiments of the present invention, the amount of the cross-linking agent is preferably 0.1-5%, more preferably 1-3%, relative to the total molar amount of maleic anhydride.

[0072] In the embodiments of the present invention, the polymerization temperature and time are determined according to the decomposition half-life of the initiator used. Generally, the polymerization temperature is 50°C-90°C, preferably 60°C-80°C. The polymerization time is 1h-24h, preferably 4h-12h, and more preferably 8h-12h.

[0073] In an embodiment of the present invention, the gas-solid amination reaction is carried out under vigorous stirring so that the maleic anhydride copolymer cross-linked microspheres react more evenly with ammonia. The stirring rate is 600-800r / min. There is no particular requirement for the reaction temperature of the gas-solid amination reaction, which is usually carried out at room temperature. The reaction time of the gas-solid amination reaction is usually based on the time when the reaction system no longer releases heat. In order to increase the amination rate as much as possible, the reaction time is usually more than 12h, and the preferred reaction time is 12h-60h, for example, the reaction time is 12h, 24h, 48h or 60h.

[0074] In an embodiment of the present invention, the imidization reaction temperature is 160° C.-180° C. The imidization reaction time is determined according to the desired imidization degree. Generally, the imidization reaction time is 10 min-12 h, and the corresponding imidization degree can be controlled at 20%-100%.

[0075] In the embodiment of the present invention, the hypohalite aqueous solution is prepared at a specific concentration, and the pH value of the hypohalite aqueous solution is adjusted with a dilute acid solution.

[0076] In an embodiment of the present invention, hypohalite includes but is not limited to: NaClO, KClO, Ca(ClO)2, NaBrO, KBrO, Ca(BrO)2, NaIO, KIO, Ca(IO)2. Preferably, the hypohalite selected in the embodiment is mainly NaClO. The concentration of hypohalite is 0.5wt.%-10wt.%, preferably 3wt.%-5wt.%. The dilute acid solution is selected from a dilute hydrochloric acid solution with a concentration of 0.1-1mol / L or a dilute sulfuric acid solution with a concentration of 0.1-1mol / L. The pH value of the hypohalite aqueous solution is 7-8. There is no special requirement for the halogenation reaction temperature, which is usually carried out at room temperature. The time of the halogenation reaction is usually 10min-6h, preferably 30min-2h.

[0077] Unless otherwise specified, the room temperature in the embodiments of the present invention is 25±2°C.

[0078] Unless otherwise specified, "%" in the embodiments of the present invention refers to mass percentage.

[0079] All raw materials used in the examples of the present invention are commercially available.

[0080] The technical solution of the present invention is further illustrated by the following embodiments.

[0081] Example 1

[0082] 10.51g (0.1mol) styrene, 0.13g (0.001mol) divinylbenzene and 10g (0.102mol) maleic anhydride were dissolved in 195g ethyl butyrate, and 0.2168g azobisisobutyronitrile was added to react at 70°C for 3h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and ethyl butyrate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer cross-linked microspheres. The average particle size of the styrene-maleic anhydride copolymer cross-linked microspheres is 1μm, and the molecular weight is 15000g / mol. The styrene-maleic anhydride copolymer cross-linked microspheres are added to a flask connected to a gas storage bag, and excess ammonia is introduced. The reaction is carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction is 45min to obtain styrene-maleamic acid copolymer cross-linked microspheres. The product was analyzed by acid-base titration, and the amination rate of maleic anhydride group was 99%. The flask containing styrene-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 10 hours to obtain maleimide copolymer cross-linked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1g of maleimide copolymer cross-linked microspheres was dispersed in 10mL of NaClO aqueous solution with a concentration of 3wt.% and pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5min, and water was added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleimide N-halamine cross-linked microspheres.

[0083] The antibacterial rate of the polymer microspheres after N-halamine reaction (i.e., styrene-maleimide N-halamine cross-linked microspheres) was tested by plate coating counting method. Escherichia coli ATCC25922 (E. coli) and Staphylococcus aureus ATCC29213 (S. aureus) were selected as experimental strains, and the strain concentrations were 10 6 CFU / mL. The test was divided into three groups, namely the blank control group, the styrene-maleimide copolymer cross-linked microsphere group without N-halamination, and the styrene-maleimide N-halamine cross-linked microsphere group after N-halamination. The specific test method is as follows: weigh 45 mg of sample respectively, add 450 μL of sterile PBS solution to the sample (no sample is added to the blank control group), ultrasonically disperse for 30 minutes, and then add 50 μL of the prepared bacterial solution to the sample dispersion, and place it in a 37°C constant temperature oscillator for 10 minutes of shaking and co-cultivation. After the culture is completed, add an excess of Na2S2O3 solution to the culture solution to quench the remaining Cl +. Use sterile PBS solution to dilute the mixture 10 times continuously, take 100 μL of the dilution and evenly spread it on LB solid culture medium, place it in a 37℃ constant temperature incubator for 18 hours, take it out, take pictures and record the number of colonies. The antibacterial rate calculation formula is as follows:

[0084] Antibacterial rate (%) = (1-experimental group bacterial solution concentration / control group bacterial solution concentration) × 100%

[0085] The testing method of antibacterial rate in the subsequent embodiments is the same as this embodiment.

[0086] The experimental results show that the antibacterial rate of the microspheres against Staphylococcus aureus is ≥ 99.999%, and the antibacterial rate against Escherichia coli is ≥ 99.998%.

[0087] Example 2

[0088] 10.51g (0.1mol) styrene, 0.13g (0.001mol) divinylbenzene and 10g (0.102mol) maleic anhydride were dissolved in 195g isoamyl acetate, and 0.2168g azobisisobutyronitrile was added to react at 70°C for 3h. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer crosslinked microspheres. The average particle size of the styrene-maleic anhydride copolymer crosslinked microspheres was 1μm and the molecular weight was 15000g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres were added to a flask connected to a gas storage bag, and excess ammonia was introduced. The reaction was carried out at room temperature, and the reaction was accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction was 45min to obtain styrene-maleamic acid copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of maleic anhydride group was 99%. The flask containing styrene-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 2 hours to obtain maleamic acid / maleimide copolymer cross-linked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 80%. 1g of the above copolymer microspheres was dispersed in 10mL of NaClO aqueous solution with a concentration of 0.5wt.% and pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5min, and water was added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleamic acid / maleimide N-halamine cross-linked microspheres.

[0089] The antibacterial rate of the polymer microspheres after N-halamine reaction (ie, styrene-maleamic acid / maleimide-based N-halamine cross-linked microspheres) was tested by a plate coating counting method, and the antibacterial rate against Staphylococcus aureus was found to be ≥99.994%.

[0090] Example 3

[0091] 14.30g (0.12mol) α-methylstyrene, 0.16g divinylbenzene (0.001mol) and 12g (0.122mol) maleic anhydride were dissolved in 238g isoamyl acetate, and 0.2645g dibenzoyl peroxide was added to react at 70°C for 3h. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation for three times, and vacuum dried to constant weight to obtain α-methylstyrene-maleic anhydride copolymer crosslinked microspheres, the microsphere average particle size was 500nm, and the molecular weight was 6700g / mol. The microspheres were added to a flask connected to a gas storage bag, and excessive ammonia was introduced. The reaction was carried out at room temperature, and the reaction was accompanied by a magnetic stirrer stirring at 600-800rpm, and the reaction was 45min to obtain α-methylstyrene-maleamic acid copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of maleic anhydride group was 99%. The flask containing α-methylstyrene-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 10 hours to obtain maleimide copolymer cross-linked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1g of maleimide copolymer cross-linked microspheres was dispersed in 10mL of NaClO aqueous solution with a concentration of 3wt.% and pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5min, and water was added for washing and centrifugation three times, and vacuum dried to constant weight to obtain α-methylstyrene-maleimide N-halamine cross-linked microspheres.

[0092] The antibacterial rate of the polymer microspheres after N-halamine reaction (i.e., α-methylstyrene-maleimide N-halamine cross-linked microspheres) was tested by plate coating counting method, and the antibacterial rate against Escherichia coli was found to be ≥99.996%.

[0093] Example 4

[0094] 12.87g (0.124mol) styrene, 0.4296g (0.0012mol) N, N'-(4, 4'-methylenediphenyl)-bismaleimide and 12.25g (0.125mol) maleic anhydride were dissolved in 227g isoamyl acetate, and 0.2525g azobisisobutyronitrile was added to react at 70°C for 3h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer cross-linked microspheres, the average particle size of the microspheres was 450nm, and the molecular weight was 20000g / mol. The microspheres were added to a flask connected to a gas storage bag, and excess ammonia was introduced. The reaction is carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction is carried out for 45min to obtain styrene-maleamic acid copolymer crosslinked microspheres. The product is analyzed by acid-base titration, and the amination rate of maleic anhydride group is 99%. The flask containing styrene-maleamic acid copolymer crosslinked microspheres is heated to 180°C and reacted for 30min to obtain maleamic acid / maleimide copolymer crosslinked microspheres. The degree of imidization is analyzed by infrared spectroscopy, and the imide conversion rate is 30%. 1g of maleimide copolymer microspheres is dispersed in 10mL, 5wt.% and pH=8 NaClO aqueous solution, and stirred at room temperature for 2h. After the reaction is completed, the product is centrifuged at a speed of 10000r / min for 5min, and water is added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleimide N-halamine crosslinked microspheres.

[0095] The antibacterial rate of the polymer microspheres after the N-halamine reaction (i.e., styrene-maleimide N-halamine cross-linked microspheres) was tested by the plate coating counting method, and the antibacterial rate against Staphylococcus aureus was ≥ 99.995%. Example 5

[0096] 10.11g (0.117mol) vinyl acetate, 0.8234g (0.0023mol) N, N'-(4, 4'-methylenediphenyl)-bismaleimide and 11.76g (0.12mol) maleic anhydride were dissolved in 164g isoamyl acetate, and 1.104g azobisisobutyronitrile was added to react at 70°C for 4h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain vinyl acetate-maleic anhydride copolymer cross-linked microspheres, the average particle size of the microspheres was 200nm, and the molecular weight was 3000g / mol. The microspheres were added to a flask connected to a gas storage bag, and excess ammonia was introduced. The reaction is carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction is carried out for 45min to obtain vinyl acetate-maleamic acid copolymer crosslinked microspheres. The product is analyzed by acid-base titration, and the amination rate of maleic anhydride group is 99%. The flask containing the vinyl acetate-maleamic acid copolymer crosslinked microspheres is heated to 180°C and reacted for 10h to obtain maleimide copolymer crosslinked microspheres. The degree of imidization is analyzed by infrared spectroscopy, and the imide conversion rate is 99%. 1g of maleimide copolymer crosslinked microspheres is dispersed in 10mL, 10wt.% and pH=7 NaClO aqueous solution, and stirred at room temperature for 2h. After the reaction is completed, the product is centrifuged at a speed of 10000r / min for 5min, and water is added for washing and centrifugation three times, and vacuum dried to constant weight to obtain vinyl acetate-maleimide N-halamine crosslinked microspheres.

[0097] The antibacterial rate of the polymer microspheres after N-halamine reaction (ie, vinyl acetate-maleimide N-halamine cross-linked microspheres) was tested by a plate coating counting method, and the antibacterial rate against Staphylococcus aureus was found to be ≥99.998%.

[0098] Example 6

[0099] 35g (0.2mol) C5 mixture, 0.358g (0.001mol) N, N'-(4,4'-methylenediphenyl)-bismaleimide and 10g (0.1mol) maleic anhydride were dissolved in 75g anisole, and 0.72g azobisisobutyronitrile was added to react at 70°C for 6h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and anisole and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain C5 mixture-maleic anhydride copolymer cross-linked microspheres, the average particle size of the microspheres was 2μm, and the molecular weight was 3500g / mol. The microspheres were added to a flask connected to a gas storage bag, and excess ammonia was introduced. The reaction was carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction was 45min to obtain C5 mixture-maleamic acid copolymer cross-linked microspheres. The product was analyzed by acid-base titration, and the amination rate of maleic anhydride group was 99%. The flask containing C5 mixture-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 10 hours to obtain maleimide copolymer cross-linked microspheres. The imidization degree was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1g of maleimide copolymer cross-linked microspheres was dispersed in 10mL of NaClO aqueous solution with a concentration of 3wt.% and pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5min, and water was added for washing and centrifugation three times, and vacuum dried to constant weight to obtain C5 mixture-maleimide N-halamine cross-linked microspheres.

[0100] The scanning electron microscope images of different microspheres prepared in Example 6 and the corresponding energy spectrum mapping images are shown in Figure 1 , where: a is C5 mixture-maleic anhydride copolymer cross-linked microspheres, b is C5 mixture-maleamic acid copolymer cross-linked microspheres, c is maleimide copolymer cross-linked microspheres, and d is C5 mixture-maleimide N-halamine cross-linked microspheres. It can be seen that the microspheres before and after modification are all regular spherical, indicating that the modification has basically no effect on the morphology of the microspheres, and the test shows that the size of the microspheres after multi-step modification is always around 1700nm. In the EDS mapping of the C5 mixture-maleimide N-halamine cross-linked microspheres, a clear spherical pattern can be observed, which also verifies the success of the halogenated modification.

[0101] The plate spread counting method (the initial colony concentration was 10 6 CFU / mL, bacterial contact time was 10 min) to test the antibacterial rate of polymer microspheres before N-halamine reaction (i.e., C5 mixture-maleimide copolymer cross-linked microspheres) and after reaction (i.e., C5 mixture-maleimide-based N-halamine cross-linked antibacterial microspheres). The results are shown in Figure 2The test showed that the antibacterial rate of the polymer microspheres before the reaction against Staphylococcus aureus and Escherichia coli was 0%, that is, the polymer microspheres before the reaction had no antibacterial ability. After the reaction, the antibacterial rate of the polymer microspheres against Staphylococcus aureus was ≥99.993%, and the antibacterial rate against Staphylococcus aureus was ≥99.995%.

[0102] Example 7

[0103] 26.67g (0.08mol) C8 mixture, 0.11g (0.001mmol) divinylbenzene and 8g (0.082mol) maleic anhydride were dissolved in 15g xylene, and 0.8667g azobisisobutyronitrile was added to react at 70°C for 6h. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5 minutes, and xylene and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain C8 mixture-maleic anhydride copolymer cross-linked microspheres, the average particle size of the microspheres was 6μm, and the molecular weight was 5000g / mol. The microspheres were added to a flask connected to a gas storage bag and an excess of ammonia was introduced. The reaction was carried out at room temperature, and the reaction was accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction was 45min to obtain C8 mixture-maleamic acid copolymer cross-linked microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride group was 99%. The flask containing the C8 mixture-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 10 hours to obtain maleimide copolymer cross-linked microspheres. The imidization degree was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1g of maleimide copolymer cross-linked microspheres was dispersed in 10mL of Ca(BrO)2 aqueous solution with a concentration of 10wt.% and pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5 minutes, and water was added for washing and centrifugation for three times, and vacuum dried to constant weight to obtain C8 mixture-maleimide N-halamine cross-linked microspheres.

[0104] The antibacterial rate of the polymer microspheres after N-halamine reaction (ie, C8 mixture-maleimide N-halamine cross-linked microspheres) was tested by plate coating counting method, and the antibacterial rate against Escherichia coli was found to be ≥99.995%.

[0105] Example 8

[0106] 12.48g (0.12mol) of styrene, 0.204g (0.0012mol) of ethylene glycol diacrylate and 11.76g (0.12mol) of maleic anhydride were dissolved in 220g of isoamyl acetate, and 0.2424g of azobisisobutyronitrile was added to react at 70°C for 3h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer crosslinked microspheres. The average particle size of the styrene-maleic anhydride copolymer crosslinked microspheres is 800nm ​​and the molecular weight is 14000g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres are added to a flask connected to a gas storage bag, and excess ammonia is introduced. The reaction is carried out at room temperature, and the reaction is accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction is 45min to obtain styrene-maleamic acid copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of maleic anhydride group was 99%. The flask containing styrene-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 2 hours to obtain maleamic acid / maleimide copolymer cross-linked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 80%. 1g of the above copolymer microspheres was dispersed in 10mL, 1wt.% NaClO aqueous solution, pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5min, and water was added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleamic acid / maleimide N-halamine cross-linked microspheres.

[0107] The antibacterial rate of the polymer microspheres after N-halamine reaction (ie, styrene-maleamic acid / maleimide-based N-halamine cross-linked microspheres) was tested by a plate coating counting method, and the antibacterial rate against Staphylococcus aureus was found to be ≥99.996%.

[0108] Example 9

[0109] 8.6g (0.1mol) of vinyl acetate, 0.17g (0.001mol) of ethylene glycol diacrylate and 9.8g (0.1mol) of maleic anhydride were dissolved in 165g of isoamyl acetate, and 0.184g of azobisisobutyronitrile was added to react at 70°C for 3h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain vinyl acetate-maleic anhydride copolymer crosslinked microspheres. The average particle size of the vinyl acetate-maleic anhydride copolymer crosslinked microspheres is 400nm, and the molecular weight is 5000g / mol. The vinyl acetate-maleic anhydride copolymer crosslinked microspheres are added to a flask connected to a gas storage bag, and excess ammonia is introduced. The reaction is carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction is carried out for 45min to obtain vinyl acetate-maleamic acid copolymer crosslinked microspheres. The product is analyzed by acid-base titration, and the amination rate of maleic anhydride group is 99%. The flask containing vinyl acetate-maleamic acid copolymer crosslinked microspheres is heated to 180°C and reacted for 10h to obtain maleamic acid / maleimide copolymer crosslinked microspheres. The degree of imidization is analyzed by infrared spectroscopy, and the imide conversion rate is 99%. 1g of the above copolymer microspheres is dispersed in 10mL, 3wt.% and pH=8 NaClO aqueous solution, and stirred at room temperature for 2h. After the reaction is completed, the product is centrifuged at a speed of 10000r / min for 5min, and water is added for washing and centrifugation three times, and vacuum dried to constant weight to obtain vinyl acetate-maleamic acid / maleimide N-halamine crosslinked microspheres.

[0110] The antibacterial rate of the polymer microspheres after N-halamine reaction (ie, vinyl acetate-maleamic acid / maleimide-based N-halamine cross-linked microspheres) was tested by a plate coating counting method, and the antibacterial rate against Staphylococcus aureus was found to be ≥99.998%.

[0111] Example 10

[0112] 14.16g (0.1mol) α-methylstyrene, 0.17g ethylene glycol diacrylate (0.001mol) and 9.8g (0.1mol) maleic anhydride were dissolved in 215g isoamyl acetate, and 0.2396g dibenzoyl peroxide was added to react at 70°C for 3h. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain α-methylstyrene-maleic anhydride copolymer cross-linked microspheres, the microspheres having an average particle size of 500nm and a molecular weight of 10000g / mol. The microspheres were added to a flask connected to a gas storage bag and an excess of ammonia was introduced. The reaction was carried out at room temperature, and the reaction was accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction was 45min to obtain α-methylstyrene-maleamic acid copolymer cross-linked microspheres. The product was analyzed by acid-base titration, and the amination rate of maleic anhydride group was 99%. The flask containing α-methylstyrene-maleamic acid copolymer cross-linked microspheres was heated to 180°C and reacted for 10 hours to obtain maleimide copolymer cross-linked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1g of maleimide copolymer cross-linked microspheres was dispersed in 10mL of KClO aqueous solution with a concentration of 3wt.% and pH=8, and stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a speed of 10000r / min for 5min, and water was added for washing and centrifugation three times, and vacuum dried to constant weight to obtain α-methylstyrene-maleimide N-halamine cross-linked microspheres.

[0113] The antibacterial rate of the polymer microspheres after N-halamine reaction (i.e., α-methylstyrene-maleimide N-halamine cross-linked microspheres) was tested by plate coating counting method, and the antibacterial rate against Escherichia coli was found to be ≥99.993%.

[0114] Embodiment 11

[0115] 8.32g (0.08mol) styrene, 0.2864g (0.0008mol) N, N'-(4, 4'-methylenediphenyl)-bismaleimide and 7.84g (0.08mol) maleic anhydride were dissolved in 145g xylene, and 0.1616g benzoyl peroxide was added to react at 70°C for 3h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and xylene and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer crosslinked microspheres. The average particle size of the styrene-maleic anhydride copolymer crosslinked microspheres is 600nm, and the molecular weight is 12000g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres are added to a flask connected to a gas storage bag, and excess ammonia is passed. The reaction is carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction is carried out for 45min to obtain styrene-maleamic acid copolymer crosslinked microspheres. The product is analyzed by acid-base titration, and the amination rate of maleic anhydride group is 99%. The flask containing styrene-maleamic acid copolymer crosslinked microspheres is heated to 180°C and reacted for 10h to obtain maleamic acid / maleimide copolymer crosslinked microspheres. The degree of imidization is analyzed by infrared spectroscopy, and the imide conversion rate is 99%. 1g of the above copolymer microspheres is dispersed in 10mL, 5wt.% and pH=8 NaBrO aqueous solution, and the reaction is stirred at room temperature for 3h. After the reaction is completed, the product is centrifuged at a speed of 10000r / min for 5min, and water is added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleamic acid / maleimide N-halamine crosslinked microspheres.

[0116] The antibacterial rate of the polymer microspheres after N-halamine reaction (ie, styrene-maleamic acid / maleimide-based N-halamine cross-linked microspheres) was tested by a plate coating counting method, and the antibacterial rate against Staphylococcus aureus was found to be ≥99.992%.

[0117] Comparative Example 1

[0118] 13g styrene and 12.25g maleic anhydride were dissolved in 227g isoamyl acetate, and 0.2525g dibenzoyl peroxide was added to react at 70°C for 3h. After the reaction, the product was centrifuged at a speed of 10000r / min for 5 minutes, and isoamyl acetate and petroleum ether were added for washing and centrifugation three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer microspheres, the average particle size of which was 800nm ​​and the molecular weight was 65000g / mol. The microspheres were added to a flask connected to a gas storage bag and an excess of ammonia was introduced. The reaction was carried out at room temperature, accompanied by stirring with a magnetic stirrer at 600-800rpm, and the reaction was carried out for 45min to obtain styrene-maleamic acid copolymer microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride group was 99%. The flask containing the styrene-maleamic acid copolymer microspheres was heated to 180°C and reacted for 1h to obtain maleimide copolymer microspheres. The imidization degree was analyzed by infrared spectroscopy, and the imide conversion rate was 50%.

[0119] The morphology of the uncrosslinked copolymer microspheres with low imidization degree prepared in Comparative Example 1 in different dispersion media was tested. Figure 3 It was found that the maleimide copolymer microspheres were water-soluble when the imidization degree was low and they were not cross-linked, so they could not be dispersed well in water. After adding them to a NaClO aqueous solution (concentration of 3wt.%, pH=8), they lost their microsphere morphology. This is because the microspheres were not cross-linked and the imidization degree was low. After being dispersed in water for 5 minutes, they almost dissolved, and the spherical morphology was destroyed, making them unable to disperse.

[0120] The cross-linked microspheres prepared in Example 4 have a lower imidization conversion rate, which can be dispersed in water at a lower degree of imidization. Compared with the uncross-linked microspheres in Comparative Example 1, the uncross-linked microspheres cannot be dispersed in water when the degree of imidization is lower than 50%, which reflects the good stability of the cross-linked microspheres of the present invention in aqueous solution.

[0121] From the above content, it can be seen that the present invention provides a kind of N-halamine antibacterial microspheres of maleimide copolymer, which adopts the polymerization method of self-stabilizing precipitation polymerization to synthesize polymer cross-linked microspheres without adding additional stabilizers, and the process is simple and green. The subsequent process of introducing amine-containing antibacterial units into the polymer cross-linked microspheres is also simple and easy to operate, does not involve complex polymer chemical reactions, and is suitable for large-scale synthesis. The N-halamine antibacterial microspheres of maleimide copolymer have a cross-linked structure and can maintain good stability in aqueous solution.

[0122] The above are only preferred specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A method for preparing N-halamine antibacterial microspheres of maleimide copolymer, characterized in that: The following steps are involved: Adding a comonomer, maleic anhydride, an initiator and a crosslinking agent into an organic solvent, allowing the comonomer and the maleic anhydride to undergo a self-stabilizing precipitation polymerization reaction to precipitate maleic anhydride copolymer crosslinked microspheres; The maleic anhydride copolymer cross-linked microspheres are subjected to a gas-solid amination reaction in an ammonia atmosphere to obtain maleamic acid copolymer cross-linked microspheres, wherein the amination rate of the maleamic acid copolymer cross-linked microspheres is above 99%; Heating the maleamic acid copolymer cross-linked microspheres to cause an imidization reaction to occur, thereby obtaining maleimide copolymer cross-linked microspheres, wherein the imidization rate of the maleimide copolymer cross-linked microspheres is 20%-100%; The maleimide copolymer microspheres are dispersed in a hypohalite aqueous solution for halogenation to obtain N-halamine antibacterial microspheres of the maleimide copolymer.

2. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The comonomer is selected from at least one of the following monomers: (meth)acrylic monomers, styrene monomers, vinyl monomers, olefin monomers, complex monomers derived from petroleum fractionation, and complex monomers derived from coal chemical industry.

3. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The crosslinking agent is selected from at least one of the following compounds: divinylbenzene, diallyl phthalate, N,N'-(4,4'-methylenediphenyl)-bismaleimide, 1,6-bismaleimide hexane, ethylene glycol diacrylate, ethylene glycol dimethacrylate and triethylene glycol dimethacrylate.

4. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The molar ratio of the comonomer to maleic anhydride is (1:10) to (10:1); and / or The amount of the organic solvent is 20-900% of the total mass of the comonomer and maleic anhydride; and / or The amount of the initiator is 0.2-10% of the total mass of the comonomer and maleic anhydride; and / or The amount of the cross-linking agent used is 0.1-5% of the total molar amount of maleic anhydride.

5. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The average particle size of the maleic anhydride copolymer cross-linked microspheres is 200nm-6μm.

6. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The heating temperature is 160°C-180°C.

7. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The hypohalite is selected from at least one of the following salts: NaClO, KClO, Ca(ClO)2, NaBrO, KBrO, Ca(BrO)2, NaIO, KIO and Ca(IO)2.

8. A maleimide copolymer N-halamine antibacterial microsphere, characterized in that: Prepared according to the method according to any one of claims 1 to 7.

9. Use of the N-halamine antibacterial microspheres of the maleimide copolymer according to claim 8 in the preparation of antibacterial drugs.

10. An antibacterial material, characterized in that: The active ingredient is the N-halamine antibacterial microspheres of the maleimide copolymer described in claim 8.

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