N-halamine antibacterial microspheres of a maleimide copolymer, and a preparation method and application thereof

Abstract

The application discloses N-halamine antibacterial microspheres of a maleimide copolymer and a preparation method and application thereof, and belongs to the technical field of antibacterial materials. The maleimide copolymer crosslinked microspheres can simultaneously contain maleamic acid groups and maleimide groups, and after halogenation by a hypohalite, the amide groups / imide groups can be modified into N-halamine groups with antibacterial effects. The N-halamine antibacterial microspheres of the maleimide copolymer can efficiently kill staphylococcus aureus and escherichia coli.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of antibacterial materials, and particularly relates to N-halamine antibacterial microspheres of a maleimide copolymer and a preparation method and application thereof. BACKGROUND

[0002] Bacterial microorganisms bring many troubles to human life in aspects of drinking water pollution, food deterioration, medical product infection, etc. Traditional antibacterial agents such as chlorine and ozone are often applied to water treatment, but chlorine is harmful to human body, which restricts its application; ozone has lower toxicity, but it is unstable in water, and the antibacterial effect is greatly reduced. In addition, nano-silver / silver ions are often incorporated into textiles as antibacterial agents, but the high cost greatly affects its application. Ultraviolet is also a widely used antibacterial approach, but the application of ultraviolet is limited in light-avoiding places such as pipes and tanks. In summary, it is urgent to develop a new type of antibacterial agent which is non-toxic, high-efficiency and widely applied.

[0003] N-halamine is a promising antibacterial agent. Amine, amide or imide is oxidized by hypohalite, and the hydrogen connected to nitrogen is replaced by oxidizing halogen (Cl + , Br + , I + ) to form N-halamine. N-halamine has the same bactericidal efficacy as equivalent inorganic hypohalite salt, is more stable and durable, has lower toxicity, causes less harm to human body and environment, and can be recycled. This antibacterial agent has obvious killing effect on representative microorganisms causing various infections, such as Staphylococcus aureus (gram-positive bacteria), Escherichia coli (gram-negative bacteria), methicillin-resistant Staphylococcus aureus (drug-resistant gram-positive bacteria), vancomycin-resistant Enterococcus (drug-resistant gram-positive bacteria) and Candida albicans (fungi).

[0004] Common N-halamine polymers include those polymerized from monomers containing a hydantoin structure. The hydantoin ring contains both an amide group and an imide group, so the resulting oxidizing halogen ion after halamineation has both stability and reactivity. CN116791231 A introduces 3-allyl-5,5-dimethylhydantoin into polyester fibers to impart antibacterial properties. In addition, introducing other compounds containing amine, amide, and imide groups into polymers can also be used as N-halamine antibacterial polymers, for example, J. Ind. Eng. Chem. 2022, 107: 249-258, which cured methacrylamide / acrylic acid copolymer with epoxy resin and introduced it into PET fabric for antibacterial modification; J. Ind. Text. 2015, 46(1): 59-74, which coated a chitosan multilayer film on a polyglycolide surgical suture by electrostatic assembly, and the amino group in chitosan was halaminated to have antibacterial effect; Cellulose. 2011, 19(1): 209-217, which crosslinked urea, barbituric acid, and carbamic acid containing amino / amide / imide groups with straw cellulose to obtain antibacterial cellulose. However, when synthesizing these antibacterial polymers, the process of introducing amine-containing antibacterial units needs to go through relatively complex polymerization or polymer chemistry reactions, which greatly limits their application and subsequent industrial production.

[0005] Generally, the methods for preparing polymer microspheres include emulsion polymerization, seed swelling polymerization, suspension polymerization, dispersion polymerization, and precipitation polymerization. Different polymerization methods can produce microspheres with different particle sizes and particle size distributions. The common drawback of these polymerization methods is that a stabilizer must be added, which can affect the physical and chemical properties of the polymer microsphere surface, and the presence of the stabilizer can also be harmful to the human body.

[0006] CN112574336 A discloses a preparation method of 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

[0007] To solve the above technical problems, the present application provides a maleimide copolymer N-halamine antibacterial microsphere and its preparation method and application. The maleimide copolymer crosslinked microsphere can contain both maleamic acid groups and maleimide groups, which can be modified to N-halamine groups with antibacterial effect after hypohalite halamineation, and the polymer microsphere has a high killing effect on some representative bacteria.

[0008] To achieve the above purpose, the present application provides the following technical solutions:

[0009] One of the technical solutions of the present application is:

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

[0011] The comonomer, maleic anhydride, initiator and crosslinking agent are added into an organic solvent to make the comonomer and the maleic anhydride undergo self-stabilizing precipitation polymerization, and maleic anhydride-based copolymer crosslinked microspheres are precipitated;

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

[0013] The maleamic acid-based copolymer crosslinked microspheres are heated to undergo imidization reaction to obtain maleimide-based copolymer crosslinked microspheres, and the imidization rate of the maleimide-based copolymer crosslinked microspheres is between 20% and 100%;

[0014] The maleimide-based copolymer microspheres are dispersed in an aqueous solution of a hypohalite to undergo halogenation to obtain the N-halamine antibacterial microspheres of maleimide copolymer.

[0015] Firstly, the comonomer, maleic anhydride, initiator and crosslinking agent are added into an organic solvent to make the comonomer and the maleic anhydride undergo self-stabilizing precipitation polymerization, and maleic anhydride-based copolymer crosslinked microspheres are precipitated; then the maleic anhydride-based copolymer crosslinked microspheres are placed in an atmosphere of ammonia gas to undergo gas-solid amination reaction to obtain maleamic acid-based copolymer crosslinked microspheres; then the maleamic acid-based copolymer crosslinked microspheres are placed in a sealed space and subjected to imidization reaction under heating to obtain maleimide-based copolymer crosslinked microspheres (i.e. maleamic acid / maleimide-based copolymer microspheres); finally, the maleimide-based copolymer crosslinked microspheres are dispersed in an aqueous solution of a hypohalite to undergo halogenation to obtain the N-halamine antibacterial microspheres of maleimide copolymer. The present application can prepare the N-halamine antibacterial microspheres of maleimide copolymer with good antibacterial effect without adding a surfactant, and the N-halamine antibacterial microspheres of maleimide copolymer have a crosslinked structure and good stability in an aqueous solution. The polymer microspheres have the advantages of large specific surface area, strong adsorption and strong surface reaction capacity, and the present application introduces an antibacterial functional group into the polymer microspheres to obtain high-efficiency antibacterial microspheres. The present application adopts a self-stabilizing precipitation polymerization method to synthesize the polymer microspheres without adding a stabilizer, and the process is simple and green. The process of introducing an amine-containing antibacterial unit into the polymer microspheres is also simple and easy to operate, and 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, complex monomers derived from petroleum fractionation, and complex monomers derived from coal chemical industry. For example, the comonomer is selected from at least one of the following monomers: styrene, α-methylstyrene, vinyl acetate, 1,1-diphenyl ethylene, 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'-methylene diphenyl)-bismaleimide, 1,6-bismaleimide hexane, ethylene glycol diacrylate, ethylene glycol dimethacrylate, and triethylene glycol dimethacrylate.

[0018] The molar ratio of the comonomer and 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 crosslinking agent is 0.1-5% of the total moles of maleic anhydride.

[0022] The average particle size of the maleic anhydride-based copolymer crosslinked 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 degree of imidization.

[0024] The maleic amide 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 aqueous hypohalite solution is 0.5 wt.%-10 wt.%, preferably 3 wt.%-5 wt.%, the pH value is 7-8, and the reaction time of the halamine reaction is 10 min-6 h, preferably 30 min-2 h.

[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 application is:

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

[0029] The third technical solution of the present application is:

[0030] The present application also provides the application 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 application can efficiently kill S. aureus and E. coli.

[0032] The fourth technical solution of the present application is:

[0033] The present application also provides an antibacterial material, and the active ingredient of the antibacterial material is the N-halamine antibacterial microspheres of the maleimide copolymer.

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

[0035] The present application provides a preparation method of N-halamine cross-linked antibacterial microspheres of a maleimide copolymer, and the obtained polymer microspheres can simultaneously contain maleimide acid groups and maleimide groups, and after the maleimide groups are halogenated by a hypohalite, the amide groups / imide groups can be modified into N-halamine groups with antibacterial effect, and the polymer microspheres have a high efficient killing effect on some representative bacteria.

[0036] The maleic anhydride copolymer microspheres in the present application are synthesized by a self-stabilizing precipitation polymerization method, and the process is simple and efficient, the solvent is green and can be recycled, the product is easy to separate, and no stabilizer is needed, so that the production cost can be greatly reduced and the product is harmless to human body. The obtained maleic anhydride copolymer cross-linked microspheres can be subjected to a gas-solid amination reaction in an ammonia atmosphere, and the amination rate can be above 99% when the reaction time is above 12h. The temperature of the imidization reaction is usually 160-180℃, and the reaction time is usually 2-12h, and the higher the reaction temperature and the longer the reaction time, the higher the imidization degree. Since the copolymer microspheres have a cross-linked structure, the imidization degree will not affect the water solubility and the change in the morphology in water. The amide and imide processes do not need additional solvents, so that the process flow is simplified and the environmental burden is reduced. BRIEF DESCRIPTION OF DRAWINGS

[0037] The accompanying drawings, which form a part of the present application, are used to provide further understanding of the present application, and the schematic embodiments of the present application and the descriptions thereof are used to explain the present application, and do not constitute improper limitations on the present application. In the drawings:

[0038] Figure 1 Scanning electron microscope and corresponding energy spectrum mapping pictures of different microspheres prepared for Example 6, wherein: a is C5 mixture-maleic anhydride copolymer crosslinked microspheres, b is C5 mixture-maleic acid copolymer crosslinked microspheres, c is maleimide copolymer crosslinked microspheres, d is C5 mixture-maleimide N-halamine crosslinked microspheres;

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

[0040] Figure 3 Morphology of low imidization degree uncrosslinked copolymer microspheres prepared for 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 an aqueous NaClO solution (concentration of 3 wt.%, pH = 8) for 5 min. DETAILED DESCRIPTION

[0041] Various exemplary embodiments of the present application will now be described in detail, which should be considered to be illustrative of the application and not restrictive of the application. It should be understood that the detailed description and specific examples, while indicating certain embodiments of the application, are intended to be illustrative only and are not intended to limit the scope of the application.

[0042] It should be understood that the terms used in the present application are merely used to describe particular embodiments and are not intended to limit the present application. In addition, for the numerical ranges in the present application, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Each smaller range within the stated range and between any stated value or intermediate value within the stated range is also included in the present application. The upper limit and the lower limit of these smaller ranges can be independently included or excluded from the range.

[0043] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as those of ordinary skill in the art to which the application relates. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the preferred methods and materials are described. All documents mentioned herein are incorporated by reference to disclose and describe in full the methods and / or materials which are described therein. In case of conflict between the content of the specification and that of any document incorporated herein by reference, the content of the specification prevails.

[0044] Many modifications and variations of the present application described in the specification are possible without departing from the scope or spirit of the application. Other implementations of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application. The specification and examples are illustrative only.

[0045] As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having" and the like are open-ended terms that are intended to permit but not limit the inclusion of elements or the number of elements, as well as the possibility that one or more other elements can be added or otherwise included.

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

[0047] The comonomer, maleic anhydride, initiator and crosslinking agent are added to an organic solvent to allow the comonomer to undergo self-stabilized precipitation polymerization with the maleic anhydride, and the maleic anhydride-based copolymer crosslinked microspheres are precipitated;

[0048] The maleic anhydride-based copolymer crosslinked microspheres are subjected to gas-solid amination reaction under an atmosphere of ammonia gas to obtain maleamic acid-based copolymer crosslinked microspheres, and the amination rate of the maleamic acid-based copolymer crosslinked microspheres is above 99%;

[0049] The maleamic acid-based copolymer crosslinked microspheres are heated to undergo imidization reaction to obtain maleimide-based copolymer crosslinked microspheres, and the imidization rate of the maleimide-based copolymer crosslinked microspheres is between any value from 20% to 100%;

[0050] The maleimide-based copolymer microspheres are dispersed in an aqueous hypohalite solution to undergo halamine reaction to obtain N-halamine antibacterial microspheres of maleimide copolymer.

[0051] The amination rate of the maleamic acid-based copolymer crosslinked microspheres is calculated by infrared spectroscopy peak area integration method, and the specific calculation method is as follows:

[0052]

[0053] wherein, A 1-1860 is the characteristic peak area of anhydride group at 1860 cm -1 in the sample after amination, and A1-1460 the area of the characteristic peak of the methyl group at 1460 cm -1 0-1860 the area of the characteristic peak of the acid anhydride group at 1860 cm -1 0-1460 the area of the characteristic peak of the methyl group at 1460 cm -1

[0054] The imidization rate of the maleimide-based copolymer crosslinked microspheres is calculated by the peak area integration method of infrared spectrum, and the specific calculation method is as follows:

[0055]

[0056] the area of the characteristic peak of the imide group at 1780 cm 1-1780 -1 1-1460 the area of the characteristic peak of the methyl group at 1460 cm -1 2-1780 the area of the characteristic peak of the imide group at 1780 cm -1 2-1460 the area of the characteristic peak of the methyl group at 1460 cm -1

[0057] In the embodiments of the present application, the order of addition of raw materials is not particularly limited, and the comonomer, maleic anhydride, initiator and crosslinking agent can be simultaneously added to the organic solvent, can be added to the organic solvent in any order, or can be pre-formed into a mixture and then added to the organic solvent.

[0058] In the embodiments of the present application, the average particle size of the prepared maleic anhydride-based copolymer crosslinked microspheres is preferably 200 nm-6 μm, more preferably 400 nm-4 μm, and the particle size dispersion coefficient (PDI) is 1.03-1.5. PDI is an index for measuring the uniformity of the particle size distribution of the microspheres, and the smaller the value, the more uniform the particle size distribution.

[0059] In the embodiments of the present application, the reaction of the comonomer with maleic anhydride is a self-stabilizing precipitation polymerization reaction, and no additional stabilizer needs to be added. The entire system is usually a clear and transparent reactant solution before the polymerization reaction begins, and gradually changes into a milky white polymer microsphere dispersion liquid as the polymerization reaction proceeds.

[0060] ​​​​​​​​In the embodiments of the present application, the comonomer includes, but is not limited to, (meth)acrylic monomers such as methyl (meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate, isopropyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, amyl (meth)acrylate, n-hexyl (meth)acrylate, glycidyl (meth)acrylate, isobornyl (meth)acrylate, and the like; styrene monomers such as styrene, a-methylstyrene, o-methylstyrene, p-methylstyrene, and the like; vinyl monomers such as vinyl acetate, vinyl propionate, and the like; olefin monomers such as ethylene, 1,1-diphenyl ethylene, propylene, isobutylene, and the like; complex monomers derived from petroleum fractionation such as gasoline, C4 mixture, C5 mixture, C8 mixture, C9 mixture, guaiazolone, and the like; complex monomers derived from coal chemical industry such as coal tar light fraction, and the like. These comonomers can be used alone or in combination of two or more.

[0061] In the embodiments of the present application, the comonomer is preferably at least one selected from the group consisting of styrene, a-methylstyrene, vinyl acetate, 1,1-diphenyl ethylene, isobutylene, gasoline, C4 mixture, C5 mixture, C8 mixture, C9 mixture, guaiazolone, and coal tar light fraction.

[0062] There is no particular limitation on the molar ratio of the comonomer to maleic anhydride, and it can be changed depending on the kind of the comonomer and the intended use. Generally, 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, still more preferably 1 / 5 to 5 / 1, and yet more preferably 1 / 3 to 4.5 / 1.

[0063] In the embodiments of the present application, there is no particular limitation on the kind of the organic solvent. Preferably, the organic solvent is a solvent that can dissolve the comonomer and maleic anhydride but does not dissolve the resulting maleic anhydride-based copolymer crosslinked microspheres. From the viewpoint of easy availability, high specific surface area, and good monodispersity of the maleic anhydride-based copolymer microspheres, the organic solvent is preferably at least one selected from the group consisting of ester solvents, aromatic hydrocarbon solvents, and aryl ether solvents.

[0064] In the embodiments of the present application, the ester solvents include 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 embodiments of the present application, the aromatic hydrocarbon-based solvent includes toluene, ethylbenzene, n-propylbenzene, isopropylbenzene, butylbenzene, xylene, diethylbenzene, mesitylene, cyclohexylbenzene, diphenyl ethane. These aromatic hydrocarbon-based solvents can be used alone or in combination of two or more.

[0066] In the embodiments of the present application, the aromatic ether-based solvent includes anisole, phenetol, phenyl propyl ether, diphenyl ether. These aromatic ether-based solvents can be used alone or in combination of two or more.

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

[0068] In the embodiments of the present application, the initiator is preferably a radical polymerization initiator. As a specific polymerization initiator, azo-based initiators such as azobisisobutyronitrile (AIBN), azobisisoamyl nitrile, azobisisoheptyl nitrile (ABVN), dimethyl azobisvalerate; organic peroxide-based initiators can be selected from the group consisting of dibenzoyl peroxide (BPO), dicumyl peroxide, di(2,4-dichlorobenzoyl) peroxide, dilauryl peroxide, t-butyl peroxyneohexanoate, t-butyl peroxyneodecanoate, di-sec-butyl peroxydicarbonate, di(hexadecyl) peroxydicarbonate, t-amyl peroxyneodecanoate, t-butyl peroxyneopentanoate, di-(4-t-butylcyclohexyl) peroxydicarbonate, dicyclohexyl peroxydicarbonate, diisopropyl peroxydicarbonate, dibutyl peroxydicarbonate, di(2-ethylhexyl) peroxydicarbonate, t-butyl peroxy-2-ethylhexanoate, ditetradecyl peroxydicarbonate, t-butyl peroxyacetate, cumyl peroxyneodecanoate, di-t-butyl peroxide, cyclohexyl sulfonyl acetyl 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 application, the amount of the initiator is preferably 0.2 to 10 mass% and more preferably 0.8 to 6 mass% and yet more preferably 1 to 4.5 mass% with respect to the total mass of the comonomer and the maleic anhydride.

[0070] In the embodiments of the present application, the cross-linking agent includes, but is not limited to, divinylbenzene, diallyl phthalate, N,N'-(4,4'-methylene diphenyl)-bismaleimide, 1,6-bismaleimide hexane, ethylene glycol diacrylate, ethylene glycol dimethacrylate, and triethylene glycol dimethacrylate. These cross-linking agents can be used alone or in combination of two or more.

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

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

[0073] In the embodiments of the present application, the gas-solid amination reaction is carried out under vigorous stirring to make the reaction of the maleic anhydride-based copolymer cross-linked microspheres with ammonia gas more uniform. The stirring rate is 600-800r / min. The reaction temperature of the gas-solid amination reaction is not particularly required, and is generally carried out at room temperature. The reaction time of the gas-solid amination reaction is generally determined by the time when the reaction system no longer releases heat, and to improve the amination rate as much as possible, the reaction time is generally more than 12h, preferably the reaction time is 12-60h, for example, the reaction time is 12h, 24h, 48h or 60h.

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

[0075] In the embodiments of the present application, 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 the embodiments of the present application, the 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 embodiments is mainly NaClO. The concentration of the 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 aqueous hypohalite solution is 7-8. The temperature of the halamine reaction is not particularly required, and the reaction is usually carried out at room temperature. The time of the halamine reaction is usually 10min-6h, preferably 30min-2h.

[0077] Unless otherwise specified, the room temperature in the embodiments of the present application is 25±2℃.

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

[0079] The raw materials used in the embodiments of the present application are all commercially available.

[0080] The technical solutions of the present application are further illustrated by the following examples.

[0081] Example 1

[0082] Styrene-maleic anhydride copolymer crosslinked microspheres were prepared by dissolving 10.51 g (0.1 mol) of styrene, 0.13 g (0.001 mol) of divinylbenzene and 10 g (0.102 mol) of maleic anhydride in 195 g of ethyl butyrate, adding 0.2168 g of azobisisobutyronitrile and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with ethyl butyrate and petroleum ether, and centrifuged three times, and then 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 1 μm, and the molecular weight was 15,000 g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres were added to a flask connected to an air bag, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm, and the reaction was carried out for 45 min to obtain styrene-maleic amide copolymer crosslinked 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-maleic amide copolymer crosslinked microspheres was heated to 180°C and reacted for 10 h to obtain maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the maleimide copolymer crosslinked microspheres was dispersed in 10 mL of a 3 wt.% NaClO aqueous solution at pH = 8, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with water and centrifuged three times, and then vacuum dried to constant weight to obtain styrene-maleimide-based N-halamine crosslinked microspheres.

[0083] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., styrene-maleimide-based N-halamine crosslinked microspheres) was tested by the plate counting method. Escherichia coli (Escherichia coli ATCC25922, E. coli) and Staphylococcus aureus (Staphylococcus aureus ATCC29213, S. aureus) were selected as experimental strains, and the strain concentration was 10 6 CFU / mL. The test was divided into three groups, namely a blank control group, a styrene-maleimide copolymer crosslinked microspheres group without N-halamination, and a styrene-maleimide-based N-halamine crosslinked microspheres group after N-halamination. The specific test method is as follows: 45 mg of sample was weighed, 450 μL of sterile PBS solution was added to the sample (no sample was added to the blank control group), and the sample was ultrasonically dispersed for 30 min. Then, 50 μL of prepared bacterial solution was added to the sample dispersion, and the mixture was placed in a 37°C constant temperature oscillator for co-culture for 10 min. After the culture was completed, excess Na2S2O3 solution was added to the culture solution to quench the remaining Cl +The mixture was diluted 10 times successively with sterile PBS solution, 100 μL of the diluted solution was uniformly coated on LB solid medium, and then placed in a 37°C constant temperature incubator for 18 h. The number of colonies was recorded by taking a photograph. The antibacterial rate was calculated according to the following formula:

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

[0085] The antibacterial rate was tested in the subsequent examples according to the method of this example.

[0086] The antibacterial rate of the microspheres against Staphylococcus aureus was ≥99.999%, and the antibacterial rate against Escherichia coli was ≥99.998%.

[0087] Example 2

[0088] 10.51 g (0.1 mol) of styrene, 0.13 g (0.001 mol) of divinylbenzene and 10 g (0.102 mol) of maleic anhydride were dissolved in 195 g of isopentyl acetate, and 0.2168 g of azobisisobutyronitrile was added. The reaction was carried out at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, and then washed with isopentyl acetate and petroleum ether, and centrifuged three times. The product was 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 1 μm, and the molecular weight was 15,000 g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres were added to a flask connected with a gas storage bag, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm for 45 min to obtain styrene-maleamic acid copolymer crosslinked 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 crosslinked microspheres was heated to 180°C, and the reaction was carried out for 2 h to obtain maleamic acid / maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 80%. 1 g of the above copolymer microspheres was dispersed in 10 mL of 0.5 wt.% NaClO aqueous solution with pH = 8, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, and then washed with water and centrifuged three times. The product was vacuum dried to constant weight to obtain styrene-maleamic acid / maleimide-based N-halamine crosslinked microspheres.

[0089] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e. styrene-maleamic acid / maleimide-based N-halamine crosslinked microspheres) was tested by the plate coating counting method, and the antibacterial rate against Staphylococcus aureus was ≥99.994%.

[0090] Example 3

[0091] To 14.30 g (0.12 mol) of α-methylstyrene, 0.16 g of divinylbenzene (0.001 mol) and 12 g (0.122 mol) of maleic anhydride, 238 g of isopentyl acetate was added, and 0.2645 g of dibenzoyl peroxide was added at 70°C and reacted for 3 hours. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 rpm for 5 minutes, and isopentyl acetate and petroleum ether were added to wash and centrifuge three times, and vacuum dried to a constant weight to obtain α-methylstyrene-maleic anhydride copolymer crosslinked microspheres having an average particle size of 500 nm and a molecular weight of 6,700 g / mol. The microspheres were added to a flask connected to a gas pocket, and excess ammonia gas was introduced. The reaction was carried out at room temperature with a magnetic stirrer at 600-800 rpm, and was reacted for 45 minutes to obtain α-methylstyrene-maleamic acid copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride group was 99%. The flask containing the α-methylstyrene-maleamic acid copolymer crosslinked microspheres was heated to 180°C and reacted for 10 hours to obtain maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the maleimide copolymer crosslinked microspheres was dispersed in 10 mL of a 3 wt.% NaClO aqueous solution at pH 8, and was stirred at room temperature for 2 hours. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 rpm for 5 minutes, and was washed with water and centrifuged three times, and vacuum dried to a constant weight to obtain α-methylstyrene-maleimide-based N-halamine crosslinked microspheres.

[0092] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., α-methylstyrene-maleimide-based N-halamine crosslinked microspheres) was tested by the plate count method, and the antibacterial rate against E. coli was ≥ 99.996%.

[0093] Example 4

[0094] Styrene-maleic anhydride copolymer crosslinked microspheres were prepared by dissolving 12.87 g (0.124 mol) of styrene, 0.4296 g (0.0012 mol) of N,N'-(4,4'-methylenebisphenyl)-bismaleimide and 12.25 g (0.125 mol) of maleic anhydride in 227 g of isopentyl acetate, adding 0.2525 g of azobisisobutyronitrile and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 r / min for 5 min, washed with isopentyl acetate and petroleum ether, centrifuged three times, and vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer crosslinked microspheres having an average particle size of 450 nm and a molecular weight of 20,000 g / mol. The microspheres were added to a flask connected to a gas pocket, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm for 45 min to obtain styrene-maleamic acid copolymer crosslinked 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 crosslinked microspheres was heated to 180°C and reacted for 30 min to obtain maleamic acid / maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 30%. 1 g of the maleimide copolymer microspheres was dispersed in 10 mL of a 5 wt.% NaClO aqueous solution at pH = 8, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 r / min for 5 min, washed with water, and centrifuged three times, and vacuum dried to constant weight to obtain styrene-maleimide-based N-halamine crosslinked microspheres.

[0095] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., styrene-maleimide-based N-halamine crosslinked microspheres) was tested by the plate count method, and the antibacterial rate against Staphylococcus aureus was ≥99.995%.

[0096] Vinyl acetate-maleic anhydride copolymer crosslinked microspheres were obtained by dissolving 10.11 g (0.117 mol) of vinyl acetate, 0.8234 g (0.0023 mol) of N,N'-(4,4'-methylenebisphenyl)-bismaleimide and 11.76 g (0.12 mol) of maleic anhydride in 164 g of isopentyl acetate, adding 1.104 g of azobisisobutyronitrile and reacting at 70°C for 4 h. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 r / min for 5 min, washed with isopentyl acetate and petroleum ether, and centrifuged three times, and vacuum dried to constant weight to obtain the vinyl acetate-maleic anhydride copolymer crosslinked microspheres, which had an average particle size of 200 nm and a molecular weight of 3,000 g / mol. The microspheres were added to a flask connected to a gas pocket, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm for 45 min to obtain vinyl acetate-maleic amide copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride group was 99%. The flask containing the vinyl acetate-maleic amide copolymer crosslinked microspheres was heated to 180°C and reacted for 10 h to obtain maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the maleimide copolymer crosslinked microspheres was dispersed in 10 mL of a 10 wt.% NaClO aqueous solution at pH = 7, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 r / min for 5 min, washed with water and centrifuged three times, and vacuum dried to constant weight to obtain vinyl acetate-maleimide-based N-halamine crosslinked microspheres.

[0097] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., vinyl acetate-maleimide-based N-halamine crosslinked microspheres) was tested by the plate count method, and the antibacterial rate against Staphylococcus aureus was ≥99.998%.

[0098] Example 6

[0099] The C5 mixture-maleic anhydride copolymer crosslinked microspheres were prepared by dissolving 35 g (0.2 mol) of C5 mixture, 0.358 g (0.001 mol) of N,N'-(4,4'-methylene diphenyl)-bismaleimide and 10 g (0.1 mol) of maleic anhydride in 75 g of benzyl ether, adding 0.72 g of azobisisobutyronitrile and reacting at 70°C for 6 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with benzyl ether and petroleum ether, and centrifuged three times, and then dried in vacuum to constant weight to obtain the C5 mixture-maleic anhydride copolymer crosslinked microspheres, which had an average particle size of 2 μm and a molecular weight of 3,500 g / mol. The microspheres were added to a flask connected to an air bag, and excess ammonia gas was introduced. The reaction was carried out at room temperature with stirring by a magnetic stirrer at 600-800 rpm for 45 min to obtain the C5 mixture-maleamic acid copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride groups was 99%. The flask containing the C5 mixture-maleamic acid copolymer crosslinked microspheres was heated to 180°C, and the reaction was carried out for 10 h to obtain the maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the maleimide copolymer crosslinked microspheres was dispersed in 10 mL of a 3 wt.% aqueous NaClO solution at pH = 8, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with water and centrifuged three times, and then dried in vacuum to constant weight to obtain the C5 mixture-maleimide-based N-halamine crosslinked microspheres.

[0100] The scanning electron microscope and corresponding energy spectrum mapping images of the different microspheres prepared in Example 6 are shown in Figure 1 wherein: a is the C5 mixture-maleic anhydride copolymer crosslinked microspheres, b is the C5 mixture-maleamic acid copolymer crosslinked microspheres, c is the maleimide copolymer crosslinked microspheres, and d is the C5 mixture-maleimide-based N-halamine crosslinked microspheres. It can be seen that the microspheres before and after modification are regular spherical, which indicates that the modification has no effect on the morphology of the microspheres, and the test shows that the size of the microspheres is always about 1,700 nm after the multi-step modification. In the EDS mapping image of the C5 mixture-maleimide-based N-halamine crosslinked microspheres, a clear spherical pattern can be observed, which also verifies the success of the halamine modification.

[0101] The flat plate coating counting method (the initial colony concentration was 10 6 CFU / mL, and the bacteria contact time was 10 min) was used to test the antibacterial rates of the polymer microspheres before the N-halamine reaction (i.e., the C5 mixture-maleimide copolymer crosslinked microspheres) and the polymer microspheres after the reaction (i.e., the C5 mixture-maleimide-based N-halamine crosslinked antibacterial microspheres), and the results are shown in Figure 2The antibacterial rate of the polymer microspheres before reaction was 0% for both S. aureus and E. coli, i.e. the polymer microspheres before reaction had no antibacterial ability. The antibacterial rate of the polymer microspheres after reaction was ≥99.993% for S. aureus and ≥99.995% for E. coli.

[0102] Example 7

[0103] A mixture of 26.67 g (0.08 mol) of C8, 0.11 g (0.001 mmol) of divinylbenzene and 8 g (0.082 mol) of maleic anhydride was dissolved in 15 g of dimethylbenzene, and 0.8667 g of azobisisobutyronitrile was added to react at 70°C for 6 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, and dimethylbenzene and petroleum ether were added for washing and centrifugation three times, and then vacuum dried to constant weight to obtain C8-maleic anhydride copolymer crosslinked microspheres with an average particle size of 6 μm and a molecular weight of 5,000 g / mol. The microspheres were added to a flask connected with an air bag, and excess ammonia gas was introduced. The reaction was carried out at room temperature with a magnetic stirring bar at 600-800 rpm, and the reaction was carried out for 45 min to obtain C8-maleic amide copolymer crosslinked 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-maleic amide copolymer crosslinked microspheres was heated to 180°C, and the reaction was carried out for 10 h to obtain maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the maleimide copolymer crosslinked microspheres was dispersed in 10 mL of a Ca(BrO)2 aqueous solution with a concentration of 10 wt.% and pH = 8, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, and water was added for washing and centrifugation three times, and then vacuum dried to constant weight to obtain C8-maleimide group N-halamine crosslinked microspheres.

[0104] The antibacterial rate of the N-halamine polymer microspheres (i.e. C8-maleimide group N-halamine crosslinked microspheres) after reaction was tested by the plate coating counting method, and the antibacterial rate of the N-halamine polymer microspheres for E. coli was ≥99.995%.

[0105] Example 8

[0106] Styrene-maleic anhydride copolymer crosslinked microspheres were obtained by dissolving 12.48 g (0.12 mol) of styrene, 0.204 g (0.0012 mol) of ethylene glycol diacrylate and 11.76 g (0.12 mol) of maleic anhydride in 220 g of isopentyl acetate, adding 0.2424 g of azobisisobutyronitrile and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with isopentyl acetate and petroleum ether, centrifuged three times, and vacuum dried to constant weight. Styrene-maleic anhydride copolymer crosslinked microspheres were obtained. The average particle size of the styrene-maleic anhydride copolymer crosslinked microspheres was 800 nm, and the molecular weight was 14,000 g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres were added to a flask connected to an air bag, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm for 45 min to obtain styrene-maleic amide acid copolymer crosslinked 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-maleic amide acid copolymer crosslinked microspheres was heated to 180°C and reacted for 2 h to obtain maleic amide acid / maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 80%. 1 g of the above copolymer microspheres was dispersed in 10 mL of a 1 wt.% NaClO aqueous solution at pH = 8, and stirred at room temperature for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with water and centrifuged three times, and vacuum dried to constant weight to obtain styrene-maleic amide acid / maleimide-based N-halamine crosslinked microspheres.

[0107] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., styrene-maleic amide acid / maleimide-based N-halamine crosslinked microspheres) was tested by plate counting method, and the antibacterial rate against Staphylococcus aureus was ≥99.996%.

[0108] Example 9

[0109] Vinyl acetate-maleic anhydride copolymer crosslinked microspheres were obtained by dissolving 8.6 g (0.1 mol) of vinyl acetate, 0.17 g (0.001 mol) of ethylene glycol diacrylate and 9.8 g (0.1 mol) of maleic anhydride in 165 g of isopentyl acetate, adding 0.184 g of azobisisobutyronitrile and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with isopentyl acetate and petroleum ether, and centrifuged three times, and vacuum dried to constant weight to obtain the vinyl acetate-maleic anhydride copolymer crosslinked microspheres. The average particle size of the vinyl acetate-maleic anhydride copolymer crosslinked microspheres was 400 nm, and the molecular weight was 5,000 g / mol. The vinyl acetate-maleic anhydride copolymer crosslinked microspheres were added to a flask connected to a gas pocket, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm, and the reaction was carried out for 45 min to obtain vinyl acetate-maleic amide acid copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride group was 99%. The flask containing the vinyl acetate-maleic amide acid copolymer crosslinked microspheres was heated to 180°C and reacted for 10 h to obtain maleic amide acid / maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the above copolymer microspheres was dispersed in 10 mL of a 3 wt.% NaClO aqueous solution at pH = 8, and stirred at room temperature for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with water and centrifuged three times, and vacuum dried to constant weight to obtain vinyl acetate-maleic amide acid / maleimide-based N-halamine crosslinked microspheres.

[0110] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., vinyl acetate-maleic amide acid / maleimide-based N-halamine crosslinked microspheres) was tested by plate counting method, and the antibacterial rate against Staphylococcus aureus was ≥99.998%.

[0111] Example 10

[0112] The α-methylstyrene-maleic anhydride copolymer crosslinked microspheres were prepared by dissolving 14.16 g (0.1 mol) of α-methylstyrene, 0.17 g of ethylene glycol diacrylate (0.001 mol) and 9.8 g (0.1 mol) of maleic anhydride in 215 g of isopentyl acetate, adding 0.2396 g of dibenzoyl peroxide and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with isopentyl acetate and petroleum ether, centrifuged three times, and vacuum dried to constant weight to obtain the α-methylstyrene-maleic anhydride copolymer crosslinked microspheres having an average particle size of 500 nm and a molecular weight of 10,000 g / mol. The microspheres were added to a flask connected to a gas pocket, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm for 45 min to obtain the α-methylstyrene-maleic amide copolymer crosslinked microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride groups was 99%. The flask containing the α-methylstyrene-maleic amide copolymer crosslinked microspheres was heated to 180°C and reacted for 10 h to obtain the maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the maleimide copolymer crosslinked microspheres was dispersed in 10 mL of a 3 wt.% KClO aqueous solution at pH = 8, and the reaction was carried out at room temperature with stirring for 2 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with water, and centrifuged three times, and vacuum dried to constant weight to obtain the α-methylstyrene-maleimide-based N-halamine crosslinked microspheres.

[0113] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., the α-methylstyrene-maleimide-based N-halamine crosslinked microspheres) was tested by the plate counting method, and the antibacterial rate against Escherichia coli was ≥99.993%.

[0114] Example 11

[0115] Styrene-maleic anhydride copolymer crosslinked microspheres were obtained by dissolving 8.32 g (0.08 mol) of styrene, 0.2864 g (0.0008 mol) of N,N'-(4,4'-methylenebisphenyl)-bismaleimide and 7.84 g (0.08 mol) of maleic anhydride in 145 g of xylene, adding 0.1616 g of benzoyl peroxide and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 r / min for 5 min, washed with xylene and petroleum ether, and centrifuged 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 600 nm, and the molecular weight was 12,000 g / mol. The styrene-maleic anhydride copolymer crosslinked microspheres were added to a flask connected to a gas pocket, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm, and the reaction was carried out for 45 min to obtain styrene-maleic amide acid copolymer crosslinked 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-maleic amide acid copolymer crosslinked microspheres was heated to 180°C and reacted for 10 h to obtain maleic amide acid / maleimide copolymer crosslinked microspheres. The degree of imidization was analyzed by infrared spectroscopy, and the imide conversion rate was 99%. 1 g of the above copolymer microspheres was dispersed in 10 mL of a 5 wt.% NaBrO aqueous solution at pH = 8, and the reaction was carried out at room temperature with stirring for 3 h. After the reaction was completed, the product was centrifuged at a rotation speed of 10,000 r / min for 5 min, washed with water and centrifuged three times, and vacuum dried to constant weight to obtain styrene-maleic amide acid / maleimide-based N-halamine crosslinked microspheres.

[0116] The antibacterial rate of the N-halamine reacted polymer microspheres (i.e., styrene-maleic amide acid / maleimide-based N-halamine crosslinked microspheres) was tested by plate counting method, and the antibacterial rate against Staphylococcus aureus was ≥99.992%.

[0117] Comparative Example 1

[0118] Styrene-maleic anhydride copolymer microspheres were prepared by dissolving 13 g of styrene and 12.25 g of maleic anhydride in 227 g of isopentyl acetate, adding 0.2525 g of dibenzoyl peroxide, and reacting at 70°C for 3 h. After the reaction was completed, the product was centrifuged at a speed of 10,000 r / min for 5 min, washed with isopentyl acetate and petroleum ether, and centrifuged three times, and then vacuum dried to constant weight to obtain styrene-maleic anhydride copolymer microspheres with an average particle size of 800 nm and a molecular weight of 65,000 g / mol. The microspheres were added to a flask connected to an air bag, and excess ammonia gas was introduced. The reaction was carried out at room temperature with magnetic stirring at 600-800 rpm for 45 min to obtain styrene-maleamic acid copolymer microspheres. The product was analyzed by acid-base titration, and the amination rate of the maleic anhydride groups was 99%. The flask containing the styrene-maleamic acid copolymer microspheres was heated to 180°C and reacted for 1 h to obtain maleimide copolymer microspheres. The degree of imidization 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 was tested in different dispersion media, and the results are shown in Figure 3 It was found that the maleimide copolymer microspheres were water-soluble when the degree of imidization was low and the microspheres were not crosslinked, and therefore they could not be well dispersed in water. When they were added to an aqueous NaClO solution (concentration of 3 wt.%, pH = 8), the spherical morphology was lost. This was because the microspheres were not crosslinked and the degree of imidization was low, and they almost dissolved in water after being dispersed for 5 min, and the spherical morphology was destroyed and could not be dispersed.

[0120] The crosslinked microspheres prepared in Example 4 had a low imidization conversion rate, and they could be dispersed in water at a low degree of imidization. Compared with the uncrosslinked microspheres in Comparative Example 1, the uncrosslinked microspheres could not be dispersed in water when the degree of imidization was less than 50%, which demonstrated the good stability of the crosslinked microspheres in aqueous solution.

[0121] As can be seen from the above, the present application provides a maleimide copolymer N-halamine antibacterial microsphere, which is synthesized by a self-stabilizing precipitation polymerization method without additional stabilizers, and the process is simple and green. The process of introducing an amine-containing antibacterial unit into the polymer crosslinked microspheres is also simple and easy to operate, and does not involve complex polymer chemical reactions, which is suitable for large-scale synthesis. The maleimide copolymer N-halamine antibacterial microsphere has a crosslinked structure and can maintain good stability in an aqueous solution.

[0122] The above merely describes the preferred embodiments of the present application, but the protection scope of the present application is not limited thereto, and any person skilled in the art can easily think of changes or replacements within the technical scope disclosed by the present application, which should be covered in the protection scope of the present application. Therefore, the protection scope of the present application should be subject to 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, so that the comonomer and the maleic anhydride undergo a self-stabilized 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 greater than 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% to 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 olefin monomers.

3. The method for preparing N-halamine antibacterial microspheres of maleimide copolymer according to claim 1, characterized in that: The comonomer is selected from vinyl monomers.

4. 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, complex monomers derived from petroleum fractionation, and complex monomers derived from coal chemical industry.

5. 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.

6. 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.

7. 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 200 nm-6 μm.

8. 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.

9. 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.

10. A maleimide copolymer N-halamine antibacterial microsphere, characterized in that: Prepared according to the method according to any one of claims 1 to 9.

11. Use of the N-halamine antibacterial microspheres of the maleimide copolymer according to claim 10 in the preparation of antibacterial drugs.

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

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