Self-adaptive anti-caries coating as well as preparation method and application thereof

Abstract

The invention relates to the technical field of oral biological materials, in particular to a self-adaptive anti-caries coating as well as a preparation method and application thereof. The coating is prepared from random and block polymers, and is specifically prepared by polymerizing acid radical-containing functional monomers, phenylboronic acid and derivatives thereof. Construction of the coating depends on specific coordination of a functional group and Ca < 2 + > in enamel, and stable anchoring on the tooth surface is achieved. The core action mechanism is to introduce phenylboronic acid groups to endow the coating with pH sensitive characteristics: in a cariogenic acid environment, biofilm formation is synergistically inhibited through a plurality of mechanisms such as physical barrier, electrostatic repulsion and inhibition of mucoprotein-mediated adhesion. According to the application, the Ca < 2 + > anchoring monomer, phenylboronic acid and the derivative thereof are copolymerized, design is carried out aiming at two key links of protein adsorption and bacterial adhesion, multi-mechanism synergy and environment dynamic response are integrated, and an integrated anti-caries effect from early intervention to long-term protection is realized.

Description

Technical Field

[0001] This application relates to the field of oral biomaterials technology, and more specifically, to an adaptive anti-caries coating, its preparation method, and its application. Background Technology

[0002] The oral environment is characterized by alternating open and closed spaces, variable temperature and humidity, diverse microorganisms, and active inflammatory factors, forming a unique dynamic ecological microenvironment. This complexity easily leads to the occurrence of various oral diseases and renders traditional treatment methods ineffective.

[0003] For example, traditional anti-caries coatings commonly use fluoride-containing materials. The mechanism involves fluoride ions reacting with hydroxyapatite in tooth enamel to form fluorapatite, thereby enhancing the tooth's resistance to acid erosion. However, these coatings lack dynamic response properties and cannot effectively remove already attached bacteria. Furthermore, salivary mucins (such as MUC5B) are important mediators of bacterial colonization, and current technologies struggle to achieve controllable removal or release regulation of them. Another example is the method of constructing biomimetic hydroxyapatite coatings, which involves grafting polymers with Ca... 2+ Coordinating groups inhibit bacterial adhesion. Although hydrophilic polymers have been widely used in the construction of antifouling surfaces, their excessive hydrophilicity leads to insufficient stability of the coating on the substrate surface, making it difficult to achieve long-term reliable antibacterial effects in the complex oral environment. Some technologies utilize the catalytic action of enzymes such as glucose oxidase and lysozyme to decompose the metabolic substrates of oral bacteria or destroy the bacterial cell wall structure, thereby achieving anti-caries effects. However, these enzymes have poor stability and are easily inactivated in the complex oral environment. Furthermore, their catalytic activity is significantly affected by environmental factors such as temperature, humidity, and pH, making it difficult to guarantee the stability of the treatment effect. Antibacterial agent loading therapy often involves loading antibacterial components such as silver ions, quaternary ammonium salts, and nano-zinc oxide into the coating matrix, utilizing the sustained-release effect of the antibacterial agent to achieve bactericidal function. While this strategy can achieve antibacterial effects in the short term, it suffers from problems such as difficulty in precisely controlling the sustained-release rate of the antibacterial agent, the potential for long-term release to induce bacterial resistance, and the possibility of high-concentration antibacterial agents causing irritation to dental tissues. Therefore, its safety and long-term effectiveness in clinical application are insufficient.

[0004] To address the aforementioned bottlenecks, it is necessary to break through the limitations of existing passive protection technologies and provide a new technological approach to solve the problems of long-term effectiveness and precision in caries prevention within the complex oral microenvironment. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the purpose of this application is to provide an adaptive anti-caries coating, its preparation method, and its application, thereby solving the problems mentioned in the background art through the following technical solutions.

[0006] The primary objective of this application is to provide an adaptive anti-caries coating, the coating being prepared from random and block polymers, the copolymer being polymerized from an acid-containing functional monomer and phenylboronic acid and its derivatives.

[0007] The second objective of this application is to provide a method for preparing the aforementioned adaptive anti-caries coating, comprising the following steps: S1, preparing an acid-containing functional monomer and phenylboronic acid and its derivatives; S2, dissolving the acid-containing functional monomer and phenylboronic acid and its derivatives obtained in step S1 in an organic solvent, adding RAFT reagent and initiator, and carrying out a polymerization reaction under an inert atmosphere to obtain a copolymer solution; S3, dialysis purifying the copolymer solution, and freeze-drying it to obtain a solid polymer; S4, dispersing the solid polymer in PBS buffer to obtain a coating dispersion, which is used for tooth coating to form an adaptive anti-caries coating.

[0008] Preferably, step S1 satisfies at least one of the following: (1) the acid radical-containing functional monomer is selected from one or more of methacryloyloxyethyl sulfobetaine (SBMA), methacryloyloxyethyl carboxybetaine (CBMA), 2-methacryloyloxyethyl phosphoric acid choline (MPC) or 2-methacryloyloxyethyl phosphate (MOEP); (2) phenylboronic acid and its derivatives are selected from one or more of 4-vinylphenylboronic acid, 2-phenylboronico-3,4-dihydropyrimidin-2(1H)-one (DHPBA) or 4-(2-methylpropenyl)carbonyloxyphenylboronic acid.

[0009] Preferably, step S2 satisfies at least one of the following: (1) the RAFT reagent is selected from one or more of dibenzyl trithiocarbonate, benzodithiobenzyl ester, 4-cyano-4-(thiobenzoyl)valerate (CPADB) or ethyl 2-methyl-2-(phenylthiocarbonylthio)propionate; (2) the initiator is one or more of azobisisobutyronitrile (AIBN), benzoyl peroxide or potassium persulfate; (3) the organic solvent is dimethyl sulfoxide, N,N-dimethylformamide, chloroform, tetrahydrofuran or acetonitrile.

[0010] Preferably, step S2 satisfies at least one of the following: (1) the ratio of the functional monomer containing the acid radical and phenylboronic acid and its derivatives is 1:0.5-1:2 by molar; (2) the molar ratio of the total concentration of the functional monomer containing the acid radical and phenylboronic acid and its derivatives to the RAFT reagent is 10:1-60:1; (3) the molar ratio of the RAFT reagent to the initiator is 1:0.5-1:2; (4) the reaction temperature of the RAFT polymerization reaction is 60℃-80℃ and the reaction time is 16h-28h.

[0011] Preferably, the dialysis purification in step S3 uses a dialysis bag with a molecular weight cutoff of 3.5 kDa, pure water as the dialysis medium, and a dialysis time of 2-3 days.

[0012] Preferably, step S4 satisfies at least one of the following: (1) the concentration of solid polymer in the coating dispersion is 0.1%-1% (w / v); (2) the coating dispersion is ultrasonically treated at 50 Hz for 10 min.

[0013] The third objective of this application is to provide a method for preventing tooth decay, wherein a coating dispersion obtained according to the above preparation method is applied to the tooth surface to form an adaptive anti-caries coating on the tooth surface.

[0014] The fourth objective of this application is to provide another method for preventing tooth decay, in which an extracted tooth is immersed in a coating dispersion prepared according to the above method for 10-20 seconds, and then naturally air-dried to form an adaptive anti-caries coating on the surface of the extracted tooth.

[0015] The fifth objective of this application is to provide an adaptive anti-caries coating for use in the preparation of dental caries prevention products.

[0016] Preferably, the dental caries prevention products are tooth coating agents, anti-caries toothpaste, or oral care products.

[0017] Compared with the prior art, this application has the following beneficial effects:

[0018] (1) This application provides an adaptive anti-caries coating, wherein the acid radicals contained in the adaptive anti-caries coating can react with Ca in the tooth enamel. 2+ This highly efficient combination enhances coating stability and moderately improves tooth surface hydrophilicity. Furthermore, the phenylboronic acid groups impart adaptive properties to the coating, forming an intelligent anti-caries system that dynamically adapts to the oral environment. This adaptive anti-caries coating does not directly kill bacteria; instead, it controls caries by physically inhibiting the adhesion of proteins to bacteria. This avoids the disruption of the oral microecological balance caused by traditional broad-spectrum bactericides, thus maintaining a naturally healthy oral microbiome, and significantly reduces the risk of inducing bacterial resistance. The adaptive anti-caries coating exhibits excellent biocompatibility and safety. For example, even at a polymer concentration as high as 1000 μg / mL, the hemolysis rate remains below 5%. Cytotoxicity tests show that cell proliferation rates after treatment with different concentrations of the material all exceed 80%, with some groups even exceeding 100%, far superior to traditional chemical bactericides that easily cause taste disturbances, tooth discoloration, and tissue irritation.

[0019] (2) The method for preparing the adaptive anti-caries coating provided in this application introduces Ca 2+ The preparation process is simple, yields good results, and coating is easy, making it suitable for large-scale industrial production. It is based on the strategy of combining the group and the phenylboronic acid group. Attached Figure Description

[0020] Other features, objects, and advantages of this application will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings.

[0021] Figure 1 For the random copolymer rpEA synthesized in this invention 1 H NMR spectrum;

[0022] Figure 2 For the random copolymer rpCA synthesized in this invention 1 H NMR spectrum;

[0023] Figure 3 This is a schematic diagram showing the change in water contact angle of a tooth slice coating before and after immersion in a saliva-simulated solution.

[0024] Figure 4 This is a schematic diagram illustrating the quantitative inhibitory effect of biological membranes on the surface of extracted teeth after crystal violet staining, with the PBS group serving as the control group.

[0025] Figure 5 Scanning electron microscope (SEM) images of the tooth surface in the PBS group after 120 h.

[0026] Figure 6 SEM images of the tooth surface in the rpCA group after 120 h;

[0027] Figure 7 SEM images of the tooth surface in the rpEA group after 120 h;

[0028] Figure 8 The bacterial colony count results on agar plates after 120 h are shown, with the PBS group serving as the control group.

[0029] Figure 9 This is a schematic diagram showing the cytotoxicity test results of polymers rpEA and rpCA. Detailed Implementation

[0030] The present application will be further described below with reference to specific embodiments. These embodiments are only used to more clearly illustrate the technical solutions of the present application and should not be construed as limiting the scope of protection of the present application. Anything not described in detail in this patent application is considered common knowledge in the art.

[0031] The term "and / or" as used in this application includes any and all combinations of one or more of the associated listed items. Unless otherwise stated, all parts, percentages, and ratios reported in the following examples are based on weight, and all reagents used in the examples are commercially available or synthesized by conventional methods and are ready for use without further processing, as are the instruments used in the examples. All technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this application and in its specification is for the purpose of describing particular embodiments only and is not intended to be limiting of this application.

[0032] To address the problems existing in the prior art, the strategy of this invention is to effectively block protein adsorption and the resulting bacterial adhesion during the caries process through dynamic environmental response and synergistic effects of multiple mechanisms, utilizing the electrostatic repulsion and physical barrier effects of ions, thereby inhibiting the formation of caries at its source. This adaptive anti-caries coating can respond to changes in the oral environment's pH, dynamically inhibiting bacterial adhesion, and is suitable for the prevention and control of caries.

[0033] In some embodiments, this application provides an adaptive anti-caries coating, the coating being prepared from random and block polymers, the polymers being polymerized from anodized functional monomers and phenylboronic acid and its derivatives.

[0034] In some embodiments, the method for preparing the above-mentioned adaptive anti-caries coating includes the following steps: S1, preparing functional monomers containing acid radicals and functional monomers containing phenylboronic acid and its derivatives; wherein, the functional monomers containing acid radicals may be selected from, but are not limited to, one or more of methacryloyloxyethyl sulfobetaine (SBMA), methacryloyloxyethyl carboxybetaine (CBMA), 2-methacryloyloxyethyl phosphoric acid choline (MPC) or 2-methacryloyloxyethyl phosphate (MOEP); phenylboronic acid and its derivatives may be selected from, but are not limited to, 4-vinylphenylboronic acid, 2-Phenylobyl-3,4-dihydropyrimidin-2(1H)-one (DHPBA) or 4-(2-methylpropenyl)carbonyloxyphenylboronic acid, or one or more thereof; S2, dissolve the anion-containing functional monomer and phenylboronic acid and its derivatives obtained in step S1 in an organic solvent, add RAFT reagent and initiator, and carry out polymerization reaction under an inert atmosphere to obtain a polymer solution; wherein, the RAFT reagent is selected from dibenzyl trithiocarbonate, benzodithiobenzyl ester, 4-cyano-4-(thiobenzoyl)valerate (CPADB) or 2-methyl-2- One or more of ethyl propionate (phenylthiocarbonylthio)propionate; one or more of azobisisobutyronitrile (AIBN), benzoyl peroxide, or potassium persulfate as the initiator; dimethyl sulfoxide, N,N-dimethylformamide, chloroform, tetrahydrofuran, or acetonitrile as the organic solvent; wherein, by molar weight, the feed ratio of the anion-containing functional monomer and phenylboronic acid and its derivatives is 1:0.5-1:2, the molar ratio of the total concentration of the anion-containing functional monomer and phenylboronic acid and its derivatives to the RAFT reagent and initiator is 10-60:1:0.5-2, and the reaction temperature is... The reaction temperature is 60℃-80℃, and the reaction time is 16h-28h; S3, the copolymer solution is purified by dialysis (dialysis bag molecular weight cutoff is 3.5kDa, dialysis medium is pure water, dialysis time is 2-3 days), and then freeze-dried to obtain solid polymer; S4, the solid polymer is dispersed in PBS buffer to obtain coating dispersion, which is used for tooth coating to form an adaptive anti-caries coating. The concentration of solid polymer in the coating dispersion is 0.1%-1% (w / v). The coating dispersion is used after being sonicated at 50Hz for 10min.

[0035] Anhydration-containing polymers form a hydration layer on the tooth surface, exhibiting excellent resistance to protein adsorption, platelet adhesion, and bacterial adhesion. Furthermore, sulfonate, phosphate, and carboxyl groups can be anchored to the tooth surface through simple coordination and electrostatic interactions. Therefore, anhydration-containing monomers are chosen for enamel anchoring. The pH-responsive boron ester bond between phenylboronic acid groups and polyols is commonly used in drug delivery and biosensing. This preparation method aims to anchor nanoparticles with phenylboronic acid groups onto the enamel surface, thereby constructing an environmentally adaptive anti-caries coating.

[0036] Anion-containing monomers can have the following structures:

[0037] .

[0038] In one embodiment, the acid-containing functional monomer is 2-methacryloyloxyethyl phosphocholine (MPC), with the following structure:

[0039] .

[0040] In one embodiment, the acid-containing functional monomer is 2-methacryloyloxyethyl phosphate (MOEP), which is prepared by demethylation of dimethyl (methacryloyloxyethyl) phosphate (DMOEP). DMOEP is synthesized by nucleophilic substitution reaction of O,O-dimethylphosphoryl chloride (DCP) and hydroxyethyl methacrylate (HEMA). The structure of MOEP is as follows:

[0041] .

[0042] In one embodiment, phenylboronic acid and its derivatives are 2-phenylboronico-3,4-dihydropyrimidin-2(1H)-one (DHPBA), synthesized from 4-formylphenylboronic acid (FPBA), thiourea, and ethylene glycol acetoacetate methacrylate (AEMA) via the Biginelli reaction. The structure of DHPBA is as follows:

[0043] .

[0044] In one embodiment, when the molar ratio of MPC to DHPBA is 1:2, the random copolymer obtained in step S2 is rpCA, with the following structure:

[0045] , where n=5-50, m=5-50.

[0046] In one embodiment, when the molar ratio of MOEP to DHPBA is 1:1, the random copolymer obtained in step S2 is rpEA, with the following structure:

[0047] , where n=5-50, m=5-50.

[0048] In one embodiment, the copolymer obtained in step S2 is rpCA or rpEA, and in step S4 it is dispersed in PBS buffer at a concentration of 1% (w / v) to obtain a coating dispersion.

[0049] In some embodiments, this application provides a method for preventing tooth decay, wherein a coating dispersion prepared according to the above preparation method is applied to the tooth surface to form an adaptive anti-caries coating on the tooth surface.

[0050] In other embodiments, a method for preventing tooth decay is provided, in which an extracted tooth is immersed in a coating dispersion for 10-20 seconds and then naturally air-dried to form an adaptive anti-caries coating on the surface of the extracted tooth.

[0051] In some embodiments, this application provides the application of an adaptive anti-caries coating in the preparation of caries prevention products, wherein the caries prevention products include, but are not limited to, dental coating agents, anti-caries toothpaste, or oral care products.

[0052] Example 1

[0053] This embodiment provides an adaptive anti-caries coating, and the preparation method of the coating is as follows:

[0054] S1. Preparation of functional monomers containing acid radicals and phenylboronic acid and its derivatives

[0055] Preparation of 2-methacryloyloxyethyl phosphate choline (MOEP): In a round-bottom flask, 0.040 mol of O,O-dimethylphosphoryl chloride (DCP) and 15 mL of chloroform were added and stirred until dissolved. Then, 0.040 mol of pyridine was added. In another container, 0.010 mol of hydroxyethyl methacrylate (HEMA) was dissolved in 15 mL of chloroform. Under ice bath conditions, the HEMA solution was slowly added dropwise to the DCP mixture. After the addition was complete, stirring was continued in the ice bath for 2 h, followed by stirring at room temperature for 3 h. The reaction solution was washed five times with 0.01 M HCl, and the organic phase was separated. Chloroform was removed by rotary evaporation to obtain the intermediate dimethyl (methacryloyloxyethyl) phosphate (DMOEP). 1.3 mmol of DMOEP was dissolved in 40 mL of anhydrous chloroform, and 5.2 mmol of trimethylbromosilane (TMSBr) was slowly added dropwise in an ice bath under nitrogen protection for 3 h. The solvent was removed by rotary evaporation, and 100 mL of [amount missing] mL of [solvent missing] solution was added to the residue. The MOEP monomer is obtained by stirring the H2O / THF mixed solution overnight at room temperature and then rotary evaporating the solvent.

[0056] Preparation of 2-phenylboronyl-3,4-dihydropyrimidine-2(1H)-one (DHPBA): 4-Formylphenylboronic acid (3.0 g, 20 mmol), thiourea (1.52 g, 20 mmol), and ethylene glycol acetoacetate methacrylate (AEMA) (6.43 g, 30 mmol) were weighed in a 25 mL round-bottom flask at a feed ratio of 1:1:1.5. MgCl2 (0.57 g, 6 mmol) was weighed in the round-bottom flask as a catalyst at a ratio of AEMA:MgCl2 = 5:1. Finally, 3 mL of glacial acetic acid was added to dissolve the catalyst. The mixture was stirred at 450 r / min for 4 h in an oil bath at 100 °C. After the reaction was completed, the mixture was slowly added dropwise to cold deionized water, and the mixture was stirred continuously for 3 h to precipitate the precipitate. After filtration, the precipitate was ultrasonically washed twice with deionized water and diethyl ether / petroleum ether (4:1, v / v), centrifuged, and then rotary evaporated to obtain the DHPBA monomer.

[0057] S2. Preparation of polymer rpEA: Weigh DHPBA (225.8 mg, 0.6 mmol), MOEP (334.9 mg, 0.6 mmol), CPADB (5.6 mg, 0.02 mmol), and AIBN (3.2 mg, 0.02 mmol) in 2 mL of DMF according to the molar ratio of [MOEP]:[DHPBA]:[CPADB]:[AIBN]=30:30:1:1; react at 80 °C for 18 h under a nitrogen atmosphere, and quench in an ice-water bath to obtain a copolymer solution.

[0058] S3. The copolymer solution was dialyzed with pure water for 3 days in a dialysis bag with a molecular weight cutoff (MWCO) of 3.5 kDa. After freeze-drying, the solid product rpEA was obtained. 1 H NMR was used to characterize the polymer structure, and the structure is as follows: Figure 1 As shown, in the structure, n=26.7 and m=28.2.

[0059] S4. Disperse the product rpEA in PBS at a concentration of 0.5% (w / v) and sonicate at 50 Hz for 10 min for later use.

[0060] Example 2

[0061] This embodiment provides an adaptive anti-caries coating, and the preparation method of the coating is as follows:

[0062] S1. Preparation of functional monomers containing acid radicals and phenylboronic acid and its derivatives

[0063] Purchase commercially available 2-methacryloyloxyethyl phosphocholine (MPC) product and prepare 2-phenylboronyl-3,4-dihydropyrimidine-2(1H)-one (DHPBA) according to the method of Example 1.

[0064] S2. Preparation of polymer rpCA: Weigh DHPBA (225.8 mg, 0.6 mmol), MPC (177.2 mg, 0.6 mmol), CPADB (5.6 mg, 0.02 mmol), and AIBN (3.2 mg, 0.02 mmol) in a ratio of [MPC]:[DHPBA]:[CPADB]:[AIBN]=30:30:1:1, and dissolve them completely in 2 mL of DMF; polymerize under the same conditions as in Example 1 to obtain a copolymer solution.

[0065] S3. The parameters for dialysis and drying are the same as in Example 1, yielding a solid product rpCA, which is then subjected to... 1 H NMR was used to characterize the polymer structure, and the structure is as follows: Figure 2 As shown, in the structure, n=28.1 and m=25.6.

[0066] S4. Disperse the product rpCA in PBS at a concentration of 0.5% (w / v) and sonicate at 50 Hz for 10 min for later use.

[0067] Comparative Example 1

[0068] This comparative study references traditional mainstream caries prevention technologies. Based on the core approach of existing fluoride-based caries prevention methods, it uses 1.23% sodium fluoride gel (a commercially available standard caries prevention product with a fluoride ion concentration of 12300 ppm, meeting the ADA recommended concentration) as the comparative example. The gel was evenly applied to the surface of extracted teeth, left to stand for 1 minute, and then gently rinsed off excess gel with sterile saline. The teeth were then allowed to air dry, forming a fluoride-based caries prevention coating. The core caries prevention mechanism of this coating is that fluoride ions react with hydroxyapatite in tooth enamel to form fluorapatite, which enhances the tooth's resistance to acid erosion. However, this reaction lacks dynamic responsiveness and cannot remove attached bacteria and salivary mucin.

[0069] Comparative Example 2

[0070] This comparative example uses a mainstream anti-caries product loaded with antibacterial agents. Based on existing technologies, it employs a sustained-release system loaded with antibacterial components such as silver ions and quaternary ammonium salts. The preparation method follows the core formulation of published patent CN108743679A (A Silver Ion Antibacterial and Anti-Caries Coating and Its Preparation Method). The method is as follows: 5g of hydroxypropyl methylcellulose (HPMC) is dissolved in 100mL of deionized water and stirred until transparent. 0.3g of silver nitrate powder (silver ion loading of 3wt%, consistent with the conventional loading concentration for this type of coating) is added, and the mixture is ultrasonically dispersed for 30min to obtain a silver ion antibacterial coating dispersion. The extracted tooth is immersed in the dispersion for 30s, then removed and dried in a 37℃ oven for 1h to form a silver ion-loaded antibacterial coating. The core anti-caries mechanism of this coating is that the sustained release of silver ions disrupts the bacterial cell wall structure, achieving a bactericidal effect. However, it relies on the release of antibacterial agents, easily induces drug resistance, and lacks environmental responsiveness.

[0071] To further verify the technical solution of this application and its beneficial effects, Examples 1-2 and Comparative Examples 1-2 were verified.

[0072] Test Example 1: Hydrophilicity and Stability Performance Testing

[0073] The extracted teeth were cut into 5mm×5mm×2mm slices using a micro-cutting machine. The tooth slices were then immersed in the adaptive anti-caries coatings (prepared solution after ultrasound) prepared in Examples 1 and 2 for 10-20 seconds and then air-dried.

[0074] The water contact angle was measured using a contact angle meter. The angle was then remeasured after immersion in a saliva-simulated solution for 7 days.

[0075] like Figure 3As shown, the water contact angle of the dental films coated with rpEA and rpCA coatings was significantly lower than that of the PBS group (p < 0.01), indicating a significant improvement in hydrophilicity; after 7 days of immersion, the contact angle did not change significantly (p > 0.5), indicating that the coating has good wetting stability.

[0076] Experiment Example 2: Biofilm Inhibition Experiment

[0077] Intact molars were coated with a pre-existing solution of polymer materials rpEA and rpCA, and then incubated for 6 hours in 12-well plates containing saliva-simulated solution to allow salivary mucin to adhere to the tooth surface. Fresh *S. mutans* suspension was added to each well, and the plates were incubated at 37°C for 48 hours to form a biofilm. The culture medium was discarded, and the plates were gently washed with sterile PBS, followed by fixation with anhydrous methanol for 30 minutes. After washing with sterile PBS, crystal violet (0.5%, w / v) was added for staining for 20 minutes, followed by washing with sterile PBS until the solution was colorless. 33% acetic acid solution was added to each well to dissolve the biofilm, and absorbance was measured at 590 nm using a microplate reader, according to the formula… "Calculate the biofilm inhibition rate, where Ap represents the absorbance of the PBS group and A represents the absorbance of the material-coated group."

[0078] The results are as follows Figure 4 As shown, both polymer-coated groups exhibited significantly higher biofilm inhibition rates than the control group (p < 0.001), indicating that they have good anti-biofilm formation capabilities.

[0079] Experimental Example 3: Evaluation of the anti-caries performance and long-term effectiveness of tooth slices

[0080] 1. Coated tooth sections were co-incubated with *S. mutans* for 2 h, 4 h, 8 h, and 16 h, with the 16 h group included parallel groups subjected to acid treatment (pH=4.5). After washing with PBS, the sections were fixed with 2.5% glutaraldehyde, dehydrated with graded ethanol, and air-dried at room temperature. Surface morphology was observed using SEM. The results showed that after one anti-adhesion cycle, the number of bacteria adhering to the tooth surface in the coated group was significantly less than that in the PBS control group.

[0081] 2. To investigate the long-term anti-adhesion performance of the coating, the experiment was extended to 120 hours, and parallel groups were set up for periodic sampling. The experiment showed that even after 120 hours, the coating could still effectively reduce bacterial colonization on the tooth surface, such as... Figure 5-7 The SEM images are shown. Further, quantitative analysis of the samples after 120 hours was performed using agar plate colony counting. (See attached image.) Figure 8 As shown, the coating group has a significant inhibitory effect on bacterial colonization (p<0.01), which quantitatively verifies its sustained antibacterial ability.

[0082] The cytotoxicity of the materials was also evaluated, such as... Figure 9As shown, when the concentrations of rpCA and rpEA reach 1000 μg / mL, the cell proliferation rate still exceeds 80%, indicating that the invented material has good biocompatibility.

[0083] Based on the preferred embodiments of this application, and through the above description, those skilled in the art can make various changes and modifications without departing from the technical concept of this application. The technical scope of this application is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. An adaptive anti-caries coating, the coating being prepared from random and block polymers, the polymers being polymerized from anodized functional monomers and phenylboronic acid and its derivatives.

2. A method for preparing the adaptive anti-caries coating according to claim 1, comprising the following steps: S1. Preparation of functional monomers containing acid radicals and phenylboronic acid and its derivatives; S2. Dissolve the anion-containing functional monomers and phenylboronic acid and their derivatives obtained in step S1 in an organic solvent, add RAFT reagent and initiator, and carry out polymerization reaction under an inert atmosphere to obtain a copolymer solution. S3. The copolymer solution is purified by dialysis and then freeze-dried to obtain a solid polymer. S4. The solid polymer is dispersed in PBS buffer to obtain a coating dispersion, which is used for tooth coating to form an adaptive anti-caries coating.

3. The preparation method according to claim 2, wherein step S1 satisfies at least one of the following: (1) The acid-containing functional monomer is selected from one or more of methacryloyloxyethyl sulfobetaine (SBMA), methacryloyloxyethyl carboxybetaine (CBMA), 2-methacryloyloxyethyl phosphoric acid choline (MPC) or 2-methacryloyloxyethyl phosphate (MOEP); (2) The phenylboronic acid and its derivatives are selected from one or more of 4-vinylphenylboronic acid, 2-phenylboronicoyl-3,4-dihydropyrimidin-2(1H)-one (DHPBA) or 4-(2-methylpropenyl)carbonyloxyphenylboronic acid.

4. The preparation method according to claim 2, wherein step S2 satisfies at least one of the following: (1) The RAFT reagent is selected from one or more of dibenzyl trithiocarbonate, benzodithiobenzyl ester, 4-cyano-4-(thiobenzoyl)valerate (CPADB) or ethyl 2-methyl-2-(phenylthiocarbonylthio)propionate; (2) The initiator is one or more of azobisisobutyronitrile (AIBN), benzoyl peroxide, or potassium persulfate; (3) The organic solvent is dimethyl sulfoxide, N,N-dimethylformamide, chloroform, tetrahydrofuran or acetonitrile.

5. The preparation method according to claim 2 or 4, wherein step S2 satisfies at least one of the following: (1) The ratio of the acid-containing functional monomer and the phenylboronic acid and its derivatives is 1:0.5-1:2, measured by molar. (2) The total concentration of the anion-containing functional monomer and the phenylboronic acid and its derivatives is in a molar ratio of 10:1 to 60:1 to the RAFT reagent; (3) The molar ratio of the RAFT reagent to the initiator is 1:0.5-1:2; (4) The reaction temperature of the polymerization reaction is 60℃-80℃ and the reaction time is 16h-28h.

6. The preparation method according to claim 2, wherein step S4 satisfies at least one of the following: (1) The concentration of the solid polymer in the coating dispersion is 0.1%-1% (w / v); (2) The coating dispersion was subjected to ultrasonic treatment at 50 Hz for 10 min.

7. A method for preventing tooth decay, wherein a coating dispersion obtained according to any one of the preparation methods described in claims 2-6 is applied to the tooth surface to form an adaptive anti-caries coating on the tooth surface.

8. A method for preventing tooth decay, wherein an extracted tooth is immersed in a coating dispersion obtained by any one of the preparation methods described in claims 2-6 for 10-20 seconds, and after natural air drying, an adaptive anti-caries coating is formed on the surface of the extracted tooth.

9. The application of an adaptive anti-caries coating as described in claim 1 or an adaptive anti-caries coating prepared according to any one of claims 2-6 in the preparation of dental caries prevention products, wherein the dental caries prevention products are dental coating agents, anti-caries toothpaste, or oral care products.

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