AIE functionalized synergistic antibacterial modified polysaccharide material, preparation method and application

Abstract

The present invention discloses an AIE-functionalized synergistic antibacterial modified polysaccharide material, preparation method and application. First, a water-soluble AIE dye is synthesized, and a halogenated AIE dye is obtained by reacting a halogenated acetyl halide with the AIE dye. The halogenated AIE dye is then reacted with a polysaccharide / polysaccharide derivative under alkaline low-temperature conditions and purified. The obtained new material solid has strong fluorescence characteristics and can itself be fluorescently traced. In particular, the temperature-sensitive injectable AIE-modified polysaccharide aqueous solution can form a hydrogel or film through physical cross-linking. In addition, the synthesized AIE-functionalized polysaccharide material can generate active oxygen under sunlight, which can be used for wound repair, etc. together with the quaternary ammonium salt of the material itself for synergistic antibacterial properties. It has good biocompatibility and biodegradability, low preparation cost, and is green and environmentally friendly. It has broad application prospects in the field of biomedicine.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials and relates to an AIE-functionalized modified polysaccharide material, and specifically relates to an AIE-functionalized synergistic antibacterial modified polysaccharide material, a preparation method and an application thereof. Background Art

[0002] Polysaccharides are formed by the condensation and dehydration of multiple monosaccharide molecules. They are high-molecular-weight compounds formed by numerous monosaccharides linked by glycosidic bonds. They are a class of carbohydrate substances with complex and bulky molecular structures. They possess large molecular weights, high viscosity, and a multi-hydroxy structure, resulting in excellent hydrophilicity and the ability to readily form gels in water. Polysaccharides are widely distributed in nature, such as starch, cellulose, agar, hyaluronic acid, heparin, and chitin. Due to their specific biological functions, the research and application of polysaccharides and their derivatives in the fields of biomaterials and medicine have attracted increasing attention. Polysaccharides and their derivatives are rich in hydroxyl groups. Researchers have long sought to utilize these hydrophilic hydroxyl groups to modify polysaccharides and their derivatives under mild conditions, imparting specific biomedical and in vivo tracer functions without excessive degradation or changes in properties.

[0003] Luminescent materials characterized by aggregation-induced emission (AIE) have recently attracted great interest. Chromophore aggregation typically has two effects on the luminescence process: aggregation-induced quenching (ACQ) and aggregation-induced emission (AIE). Generally, organic luminescent materials exhibit strong fluorescence in dilute solutions, but exhibit weak or even no fluorescence in the aggregated state, a phenomenon known as the ACQ phenomenon. Some compound molecules emit little light in solution, but exhibit enhanced luminescence when aggregated. Because this enhanced luminescence is caused by the aggregation of compound molecules, this phenomenon is defined as "aggregation-induced emission" (AIE). Research on aggregation-induced emission (AIE) has made significant progress in the past decade. In AIE systems, the fluorescence of aggregates is often greater than the fluorescence intensity of each individual molecule. Currently, luminescent materials based on AIE molecules have great application prospects in cutting-edge scientific and technological fields such as bioimaging, ion identification, and molecular ion sensors. Grafting molecules with AIE properties onto macromolecular chains generally does not affect their AIE properties. However, like many typical organic dyes, most AIE molecules are hydrophobic and difficult to dissolve in water. Therefore, it is of great significance to combine AIE molecules with hydrophilic polysaccharide derivatives to form AIE fluorescent traceable polysaccharide derivative materials with high luminescence efficiency, high hydrophilicity, good biocompatibility and biodegradability. For example, Wang Zhengke et al. from Zhejiang University reported a series of water-soluble chitosan-based aggregation-induced emission materials. However, they used as many as five organic reaction steps to synthesize the isothiocyanate-functionalized tetraphenylethylene AIE active molecule TPE-ITC (Wang, Zhengke et al., J. Am. Chem. Soc. 135, 8238-8245. Long-term fluorescent cellular tracing by the aggregates of AIE bioconjugates). Moreover, TPE-ITC can only react with chitosan of lower molecular weight; otherwise, chitosan of higher molecular weight is insoluble in DMSO, making the reaction difficult to proceed (chitosan was degraded from 1.16 million to 56,000 before use).

[0004] Furthermore, polysaccharides have relatively weak hydroxyl activity, especially in aqueous systems where the presence of large amounts of water can interfere with the reaction of hydroxyl groups. Therefore, modifying the hydroxyl groups of polysaccharides is very challenging. Developing new methods to prepare AIE-functionalized, fluorescently traceable modified polysaccharide materials under mild conditions is crucial. Summary of the Invention

[0005] In view of the deficiencies in the existing technology and based on the work of predecessors, the purpose of the present invention is to provide an AIE-functionalized synergistic antibacterial modified polysaccharide material, preparation method and use, which can be widely used in the field of biomedicine.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

[0007] A method for preparing an AIE-functionalized modified polysaccharide material with synergistic antibacterial properties. This method involves reacting a compound exhibiting an AIE effect with a halogenated acetyl halide, such as bromoacetyl bromide, bromoacetyl chloride, or chloroacetyl chloride, to produce a halogenated AIE compound. The halogenated AIE compound is then grafted onto a hydrophilic polysaccharide or its derivatives to yield an AIE-functionalized modified polysaccharide.

[0008] Among them, the compound with AIE effect can be an existing compound or a self-made compound.

[0009] Preferably, the compound having the AIE effect is a water-soluble AIE dye having the general structural formula shown in Formula 1 below:

[0010]

[0011] In Formula 1, R1 is a trisubstituted nitrogen-containing group, Ar1 is a benzene ring or a naphthalene ring, Ar2 is a quaternary ammonium salt containing pyridine or quinoline, n is 0-3, and R2 is a hydroxyl group or an amino group.

[0012] Preferably, the water-soluble AIE dye is obtained by the reaction pathway of Formula 2:

[0013]

[0014] In formula 2, R1 is a trisubstituted nitrogen-containing group, Ar1 is a benzene ring or a naphthalene ring, Ar2 is a quaternary ammonium salt containing pyridine or quinoline, n is 0-3, R2 is a hydroxyl group or an amino group or a Boc-protected secondary amine group, and X is a halogen element.

[0015] Preferably, in the compound having the AIE effect:

[0016] The R1 is

[0017] The Ar1 is a benzene ring or a naphthalene ring; the Ar2 is, The nitrogen atom is connected to the side containing the double bond, and X is one of Cl, Br or I.

[0018] Preferably, the polysaccharide and its derivatives are any one of chitin, chitosan, hyaluronic acid, cellulose, starch and their carboxymethyl, hydroxyethyl, hydroxypropyl and hydroxybutyl derivatives, or a mixture thereof; the molecular weight of the polysaccharide and its derivatives is 5kDa to 1000kDa.

[0019] Preferably, the compound having the AIE effect is reacted with bromoacetyl bromide, bromoacetyl chloride or chloroacetyl chloride in a first solvent at low temperature for a certain period of time to obtain a halogenated AIE compound.

[0020] Among them, it is further preferred that the mass volume ratio of the compound having an AIE effect, bromoacetyl bromide (bromoacetyl chloride or chloroacetyl chloride), and the first solvent is 1g:(1-10)g:(50-300)ml; the first solvent is an organic solvent such as toluene or dichloromethane, the low temperature range is 0-20°C, and the reaction time is 2-24h.

[0021] Preferably, the halogenated AIE compound is reacted with a hydrophilic polysaccharide or a derivative thereof in a second solvent at low temperature for a certain period of time to obtain an AIE-functionalized modified polysaccharide.

[0022] Among them, it is further preferred that the mass volume ratio of the halogenated AIE compound, polysaccharide (or polysaccharide derivative), and solvent is 1g:(1-10)g:(50-300)ml. The second solvent is an alkaline aqueous solution that can dissolve the polysaccharide. The low temperature range here is 0-25°C, and the reaction time is 24-72h.

[0023] Preferably, the polysaccharide is a temperature-sensitive modified chitin, and the temperature-sensitive modified chitin is further preferably any one or a combination of temperature-sensitive hydroxybutyl chitosan, temperature-sensitive hydroxypropyl chitosan, temperature-sensitive hydroxyethyl chitosan or temperature-sensitive hydroxybutyl chitosan.

[0024] The present invention also protects an AIE-functionalized synergistically antibacterial modified polysaccharide material, which is prepared by any of the preparation methods described above and can be used for fluorescent tracing. It can emit fluorescence for tracing under ultraviolet light and can be excited to produce active oxygen for antibacterial and sterilization under sunlight.

[0025] The present invention also protects an AIE-functionalized synergistic antibacterial modified chitin hydrogel, wherein a halogenated AIE compound is grafted onto temperature-sensitive chitin and its derivatives to obtain an AIE-functionalized temperature-sensitive modified chitin.

[0026] The AIE-functionalized thermosensitive modified chitin is dissolved in water at low temperature to prepare an aqueous solution, and then placed above the transition temperature for spontaneous physical cross-linking to transform into an AIE-functionalized synergistically antibacterial modified chitin hydrogel, which has fluorescent tracing and synergistic antibacterial properties; if coated into a film, an AIE-functionalized synergistically antibacterial modified chitin water film is obtained.

[0027] The present invention also protects an AIE-functionalized synergistically antibacterial modified polysaccharide film. The AIE-functionalized modified polysaccharide prepared by any of the preparation methods described above is prepared into a solution and then coated into a film to obtain an AIE-functionalized synergistically antibacterial modified polysaccharide film.

[0028] The present invention also protects the application of the above-mentioned AIE functionalized synergistic antibacterial modified polysaccharide material, which is used for degradation tracing, usage tracing and antibacterial dressing in animals or humans. It emits fluorescence for tracing under ultraviolet light and is excited to produce active oxygen under sunlight for antibacterial and sterilization.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] For AIE-functionalized synergistic antibacterial modified polysaccharide materials, the present invention first prepares a water-soluble AIE dye containing a quaternary ammonium salt group, then reacts the AIE dye with a halogenated acetyl halide to obtain a halogenated AIE compound, and then grafts the bromine- or chlorine-containing AIE compound onto the hydroxyl group of the polysaccharide to obtain an AIE-functionalized modified polysaccharide. The preparation process is simple, the raw materials are readily available, and large-scale production is easy.

[0031] The modified polysaccharide prepared by the present invention has strong fluorescence characteristics, high luminous efficiency, and can itself be fluorescently traced, avoiding the phenomenon of fluorescence weakening or even quenching of traditional fluorescent small molecules at high concentrations. In particular, when using temperature-sensitive modified chitin, it can be dissolved in water at a low temperature of 0-20°C to form an aqueous solution, and then placed above the transition temperature to spontaneously physically cross-link and transform into a modified chitin hydrogel or film that can be fluorescently traced. It can emit fluorescence under ultraviolet light and can be traced, and can be excited to produce active oxygen under sunlight to kill bacteria and produce synergistic antibacterial effects, which can be used for wound repair. In addition, the modified polysaccharide has good biocompatibility and biodegradability, is simple to prepare, has low cost, is green and environmentally friendly, and can be used for degradation tracing and usage tracing in animals or humans, and has broad application prospects in the field of biomedicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The present invention is further described with reference to the accompanying drawings, but the embodiments in the accompanying drawings do not constitute any limitation to the present invention.

[0033] Figure 1 Schematic diagram of the AIE effect of the AIE dye in Example 1, wherein Figure 1 A in different tetrahydrofuran (THF) percentages (f w ) (water and THF mixture) under the fluorescence spectrum, Figure 1 B is different THF percentage (f w ) (mixture of water and THF), where I0 is the relative fluorescence intensity in pure water.

[0034] Figure 2 This is the fluorescence effect diagram of the polysaccharide hydrogel modified with AIE dye in Example 4, wherein: Figure 2 A is a photograph of the solution-gel transition of AIE-modified hydroxypropyl chitosan FHPCH and the control raw material thermosensitive hydroxypropyl chitosan HPCH under natural light and UV light (2.0 wt%, in 3 mL of water); Figure 2 B is the raw material temperature-sensitive hydroxypropyl chitosan HPCH rheological test solution-gel temperature-sensitive transition (2.0wt%), Figure 2 C is the rheological test solution-gel thermosensitive transition of AIE-modified hydroxypropyl chitosan FHPCH (2.0 wt%).

[0035] Figure 3 This is a graph of active oxygen produced under sunlight in Example 4, wherein Figure 3 A in the figure represents the ability of AIE dye and Bengal rose red (RB) to produce reactive oxygen species, Figure 3 B in the figure represents the reactive oxygen production ability of hydroxypropyl chitosan (HPCH) and AIE-modified hydroxypropyl chitosan (FHPCH) hydrogel.

[0036] Figure 4 The fluorescence imaging ability of the AIE-modified thermosensitive hydroxypropyl chitosan (FHPCH) and unmodified thermosensitive hydroxypropyl chitosan (HPCH) gels in Example 9 was tested in vitro, where Figure A shows in vitro fluorescence imaging images of FHPCH and HPCH (2.0 wt%, 100 μL) at different emission wavelengths, and Figure B shows the corresponding fluorescence quantitative data (Ex = 460 nm, data are mean ± SD, n = 3).

[0037] Figure 5 The fluorescence imaging ability of the AIE-modified thermosensitive hydroxypropyl chitosan (FHPCH) and unmodified thermosensitive hydroxypropyl chitosan (HPCH) gels in Example 9 was tested in vivo, where Figure A shows the in vivo fluorescence imaging images of FHPCH and HPCH (2.0 wt%, 100 μL) at different emission wavelengths, and Figure B shows the corresponding fluorescence quantitative data (Ex = 460 nm, data are mean ± SD, n = 3).

[0038] Figure 6 The AIE-modified hydroxypropyl chitosan (FHPCH) hydrogel in Example 9 was exposed to sunlight and not exposed to sunlight (“+light” in the figure indicates sunlight, with a sunlight intensity of 400 W / m 2 , sunlight for 10 min) (A) and quantitative data (B). C and D are the antibacterial effects of FHPCH on the formed Staphylococcus aureus biofilm in the absence of sunlight (C) and with sunlight (sunlight intensity 400W / m 2, 10min) after treatment (crystal violet staining images and absorbance of the corresponding solution).

[0039] Figure 7 The antibacterial wound repair effect of the AIE-modified hydroxypropyl chitosan (FHPCH) hydrogel in Example 9 on rats infected with Staphylococcus aureus after exposure to sunlight for different periods of time (photo scale: 1 cm; HE staining of the newly regenerated skin tissue after 12 days, scale bar: 200 μm). DETAILED DESCRIPTION

[0040] In order to make the present invention easier to understand, specific embodiments of the present invention will be further described below.

[0041] The present invention is further described below in conjunction with embodiments and drawings, which is intended to help better understand the content of the present invention, but the protection scope of the present invention is not limited thereto:

[0042] Example 1 Preparation of water-soluble AIE dye (TPPy-NH2)

[0043] 93 mg of 4-methylpyridine (CAS: 108-89-4) and 237 mg of N-Boc-3-aminopropyl bromide (CAS: 83948-53-2) were dissolved in 10 mL of acetonitrile and refluxed overnight. The mixture was then cooled to room temperature and centrifuged to obtain the crude product, Py-Boc. 273 mg of 4-(diphenylamino)benzaldehyde and 330 mg of Py-Boc were added to a reaction vessel. Under nitrogen, 20 mL of anhydrous ethanol and 4 drops of piperidine were added as a catalyst. The mixture was refluxed overnight. The reaction mixture was then poured into anhydrous ether for precipitation, yielding a red solid powder. The orange powder was then added to 10 mL of a 1:2 mixture of trifluoroacetic acid and dichloromethane, stirred at 0°C for 2 h, neutralized, and precipitated with ether to obtain the water-soluble AIE dye (TPPy-NH2). 1 H NMR(400MHz,DMSO-d6,δ):8.97(2H),8.21(2H),7.99(1H),7.64(2H),7.35(5H),7.15(6H),6.95(2H),4.64(2H),2.80(2H),2.21(2H).MALDI-TOF MS():calcd.for C 28 H 28 N3[M-Br] + ,406.23; found,406.17. This water-soluble solid can emit bright red fluorescence under ultraviolet light and has a typical AIE effect ( Figure 1 ).

[0044] Will replace Will replace Will (X=Cl, Br, I, n=0,1,2,3) or (X=Cl, Br, I, n=0,1,2,3) instead of Br(CH2)3NH2.

[0045] Similar water-soluble AIE dyes containing amino or hydroxyl groups can be obtained.

[0046] Example 2 Preparation of brominated AIE dyes.

[0047] A dye with an AIE effect and containing an amino group or a hydroxyl group is reacted with bromoacetyl bromide to obtain a brominated AIE dye.

[0048] 100 mg of the AIE dye TPPy-NH2 obtained in Example 1 was dissolved in 10 ml of dichloromethane at 5° C., and then 300 mg of bromoacetyl bromide was added dropwise to obtain a brominated AIE dye (TPPy-Br). 1 H NMR(400MHz,DMSO-d6):8.90(2H),8.52(1H),8.19(2H),7.99(1H),7.70–7.58(2H),7.50(1H) ,7.36(4H),7.16(5H),7.06–6.87(3H),4.49(2H),3.88(2H),3.13(2H),2.08(2H).MALDI-TOF MS:calcd.for C 30 H 29 BrN3O[M-Br] + ,526.15; found,526.16.MALDI-TOF MS:calcd.for C 30 H 30 Br2N3O[M+H] + ,606.07;found,606.05.

[0049] Similar halogenated products can be obtained using other halogenated acetyl halides such as bromoacetyl chloride or chloroacetyl chloride.

[0050] Example 3 Preparation of AIE dye-modified polysaccharide materials

[0051] 1g of the brominated AIE dye (TPPy-Br) obtained in Example 2 and 2g of chitin were dissolved in a 12% KOH aqueous solution and then reacted at 4°C for 24 hours. The AIE-modified chitin was dialyzed to obtain an AIE-functionalized modified chitin material, which exhibited distinct orange-red fluorescence under ultraviolet light and could generate active oxygen species in sunlight for bactericidal and antibacterial effects. Similar results were obtained by using other alkaline aqueous solutions instead of the 12% KOH aqueous solution, or by using a low temperature range of 0-20°C and a reaction time of 24-72 hours.

[0052] Other polysaccharides and their derivatives, such as chitosan, hyaluronic acid, cellulose, starch, and any of their carboxymethyl, hydroxyethyl, hydroxypropyl, and hydroxybutyl derivatives, or mixtures thereof, can be reacted with halogenated AIE dyes to produce modified polysaccharide materials that exhibit fluorescence and generate reactive oxygen species under sunlight. Using chlorinated AIE dyes instead of brominated AIE dyes can also yield AIE dye-modified polysaccharide materials.

[0053] Example 4 Preparation of AIE dye-modified polysaccharide hydrogel

[0054] Hydroxypropyl chitosan with low deacetylation degree was prepared by homogeneous method in sodium hydroxide-urea system. 2 grams of purified chitosan was weighed and stirred and dispersed in 100 grams of pre-frozen aqueous solution containing 11wt% sodium hydroxide and 4wt% urea, frozen at -20°C for 6 hours, taken out and mechanically stirred at room temperature to thaw, and then frozen and thawed twice to obtain a dissolved chitosan aqueous solution. 11.42g of propylene oxide was added to the obtained chitosan solution (100 grams, 2wt%), and the system was mechanically stirred at 2°C for 2 hours to mix the reactants. Then the temperature was raised to 5°C for 24 hours, and then raised to 15°C for 6 hours. Finally, the system was cooled to 2°C, the pH value of the system was adjusted to 7 with 3M hydrochloric acid, and the solution was dialyzed with deionized water for 7 days to remove small molecules such as urea and salts. The product was freeze-dried to obtain white spongy hydroxypropyl chitosan (HPCH) with a yield of 87%. 1 The acetylation degree and substitution degree of the product were calculated to be 0.90 and 0.85 respectively from the H NMR spectrum.

[0055] Subsequently, 1g of brominated AIE dye (TPPy-Br) and 2g of hydroxypropyl chitin were dissolved in 100g of 12% NaOH aqueous solution and then reacted at 5°C for 48h. The solution was dialyzed to obtain AIE-functionalized and thermosensitive modified hydroxypropyl chitin. The AIE-functionalized and thermosensitive modified hydroxypropyl chitin was prepared into a 2% solution. The solution had fluidity at low temperatures and could be thermosensitively transformed into a gel at body temperature. It also had obvious orange-red fluorescence under ultraviolet light ( Figure 2 ). And it can produce active oxygen under sunlight ( Figure 3 ).

[0056] Other thermosensitive polysaccharides and their derivatives, such as thermosensitive hydroxybutyl chitosan, thermosensitive hydroxypropyl chitin, thermosensitive hydroxyethyl chitin, or thermosensitive hydroxybutyl chitin, can be reacted with brominated AIE dyes to produce modified polysaccharide hydrogels that are fluorescent and capable of generating reactive oxygen species. Using chlorinated AIE dyes instead of brominated AIE dyes can also produce AIE dye-modified polysaccharide hydrogels.

[0057] Example 5: Fluorescently traceable modified polysaccharide derivatives and films thereof

[0058] The AIE-modified polysaccharide material in Example 3 was dissolved in a 20% potassium hydroxide aqueous solution at a concentration of 2%-5%. 10 ml of the solution was applied to a glass plate to form a 1 mm thin film. The glass plate was then immersed in ethanol for 6-12 hours. The obtained film, which was fluorescent and capable of producing active oxygen, was removed after being rinsed with deionized water.

[0059] Using other polysaccharides and their derivatives, AIE-modified polysaccharide material films that are fluorescent and can produce active oxygen can be produced.

[0060] Example 6 Preparation of AIE dye-modified hyaluronic acid gel

[0061] 1g of the brominated AIE dye prepared in Example 2 and 2g of hyaluronic acid were reacted in 200ml of 1% sodium hydroxide aqueous solution at 20°C for 48 hours. After neutralization, the mixture was dialyzed and lyophilized (lyophilization temperature was approximately -50°C) to obtain an AIE-modified hyaluronic acid sponge. Dissolving the AIE-modified hyaluronic acid in water or saline solution yielded a 0.5-3% fluorescently traceable viscous aqueous solution or hydrogel. The solution exhibited distinct orange-red fluorescence under ultraviolet light and produced reactive oxygen species under sunlight. Similar results were achieved using other hyaluronic acid derivatives.

[0062] Example 7 Preparation of AIE dye-modified cellulose 1g of brominated AIE dye (TPPy-Br) obtained in Example 2 and 2g of hydroxypropyl methylcellulose were dissolved in a 5% NaOH aqueous solution and then reacted at room temperature for 24h. The AIE-modified hydroxypropyl methylcellulose was dialyzed to obtain an AIE-functionalized modified cellulose material, which had obvious orange-red fluorescence under ultraviolet light and could produce active oxygen in sunlight to kill bacteria. Similar results can be obtained using other alkaline aqueous solutions, or at low temperatures in the range of 0-20°C and reaction times of 24-72h.

[0063] Similar results were obtained using other cellulose derivatives.

[0064] Example 8 Preparation of AIE dye-modified starch

[0065] 1g of the brominated AIE dye prepared in Example 2 and 2g of soluble starch were reacted in 200ml of 1% sodium hydroxide solution at 25°C for 48 hours. After neutralization, the mixture was dialyzed and lyophilized (lyophilization temperature was approximately -50°C) to obtain AIE-modified starch. This AIE-modified starch can be dissolved in water or saline to produce a viscous aqueous solution or hydrogel of appropriate concentration that can be fluorescently traced.

[0066] Similar results were obtained using other starch derivatives.

[0067] Example 9 Tracing and Wound Repair

[0068] Combined with animal experiments, the in vivo and in vitro tracing and wound repair of the AIE-modified thermosensitive hydroxypropyl chitin hydrogel prepared in Example 4 of the present invention were evaluated.

[0069] Figure 4 、 Figure 5 The fluorescence imaging ability of AIE-modified thermosensitive hydroxypropyl chitin and unmodified thermosensitive hydroxypropyl chitin gel was tested in vivo and in vitro, showing that AIE-modified thermosensitive hydroxypropyl chitin has good imaging effect both in vivo and in vitro in the red / near-infrared emission band.

[0070] Figure 6 It shows that the AIE-modified thermosensitive hydroxypropyl chitosan has a good synergistic antibacterial effect due to the presence of quaternary ammonium salt in the hydrogel and the excellent ROS production efficiency.

[0071] Figure 7 It shows that AIE-modified thermosensitive hydroxypropyl chitin hydrogel can significantly improve the wound repair ability.

[0072] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A method for preparing an AIE-functionalized synergistic antibacterial modified polysaccharide material, characterized by: The method uses a compound having an AIE effect to react with bromoacetyl bromide, bromoacetyl chloride or chloroacetyl chloride to obtain a halogenated AIE compound, and then grafts the halogenated AIE compound onto a hydrophilic polysaccharide and its derivatives to obtain an AIE-functionalized modified polysaccharide. The compound having the AIE effect is a water-soluble AIE dye having the general structural formula shown in Formula 1 below: Formula 1 In formula 1, Ar1 is a benzene ring or a naphthalene ring, n is 0-3, and R2 is an amino group; R1 is 、 、 、 or ; Ar2 is 、 、 、 or , wherein the nitrogen atom is attached to the side away from the double bond, and X is one of Cl, Br or I; The polysaccharide and its derivatives are any one of chitin, chitosan, hyaluronic acid, cellulose, starch and their carboxymethyl, hydroxyethyl, hydroxypropyl and hydroxybutyl derivatives, or a mixture thereof; the molecular weight of the polysaccharide and its derivatives is 5 kDa to 1000 kDa.

2. The method for preparing the modified polysaccharide material according to claim 1, wherein: The water-soluble AIE dye is obtained by the reaction pathway of the following formula 2: Formula 2 In Formula 2, Ar1, Ar2, R2, n and R1 are as defined in claim 1, R'2 is a Boc-protected secondary amine group, and X' is a halogen element.

3. The method for preparing the modified polysaccharide material according to claim 1, wherein: The compound having the AIE effect reacts with bromoacetyl bromide, bromoacetyl chloride or chloroacetyl chloride in a solvent at 0-20° C. for 2-24 h to obtain a halogenated AIE compound; The halogenated AIE compound reacts with a hydrophilic polysaccharide or its derivative in a solvent at 0-25°C for 24-72 hours to obtain an AIE-functionalized modified polysaccharide; The mass volume ratio of the halogenated AIE compound, polysaccharide, and solvent is 1 g: (1-10) g: (50-300) ml, and the solvent is an alkaline aqueous solution that can dissolve the polysaccharide.

4. The method for preparing the modified polysaccharide material according to claim 1, wherein: The polysaccharide is a temperature-sensitive modified chitin, and the AIE-functionalized temperature-sensitive modified chitin is obtained. The temperature-sensitive modified chitin is any one or a combination of temperature-sensitive hydroxypropyl chitin, temperature-sensitive hydroxyethyl chitin or temperature-sensitive hydroxybutyl chitin.

5. A modified polysaccharide material with AIE functionalization and synergistic antibacterial properties, characterized in that: The preparation method is described in any one of claims 1 to 4.

6. A modified chitin hydrogel with AIE functionalization and synergistic antibacterial properties, characterized in that: The AIE-functionalized thermosensitive modified chitin prepared by the preparation method of claim 4 is dissolved in water at low temperature to prepare an aqueous solution, and then placed above the transition temperature for spontaneous physical cross-linking to transform into a modified chitin hydrogel that can be fluorescently traced.

7. A modified polysaccharide film with AIE functionalization and synergistic antibacterial properties, characterized in that: The AIE-functionalized modified polysaccharide prepared by the preparation method according to any one of claims 1 to 4 is prepared into a solution and then coated into a film to obtain an AIE-functionalized synergistic antibacterial modified polysaccharide film.

8. An application of the AIE functionalized synergistic antibacterial modified polysaccharide material according to claim 5, characterized in that: Used for preparing degradation tracers, usage tracer preparations and antibacterial dressings in animals or humans.

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