Nanocomposite antibacterial coating for dental materials and method for preparing the same

Abstract

The application belongs to the technical field of dental antibacterial materials, and discloses a kind of nanometer composite antibacterial coating for dental material and preparation method thereof.Method: monomer modified arginine, monomer N-isopropyl acrylamide, monomer methyl hexyl acrylate, initiator azobisdimethylamino propanamide hydrochloride, dispersing agent cetyltrimethylammonium bromide and crosslinking agent N,N-methylene bis(acrylamide) are dissolved in water, and the reaction is carried out under protective atmosphere, dialysis, to obtain nanogel dispersion;The nanogel dispersion is mixed with the nanometer zinc oxide dispersion to obtain a nanogel composite zinc oxide antibacterial coating, and a coating is formed after coating.The nanometer composite antibacterial coating for dental material has excellent retention capacity and antibacterial performance.

Description

Technical Field

[0001] This invention belongs to the technical field of dental antibacterial materials, specifically relating to a nanocomposite antibacterial coating for dental materials and its preparation method. Background Technology

[0002] Young people's love of sweets and neglect of dental health, coupled with the weakened immunity of middle-aged and elderly people, all contribute to oral diseases. Dental caries is currently the most common oral disease worldwide. Caries occurs because bacteria remaining on food debris on the tooth surface are coated by the saliva film. Salivary proteins in the saliva layer provide adhesion sites for bacteria such as Streptococcus mutans and Candida albicans. Subsequently, bacteria accumulate and multiply on the basis of early adhesions, forming an oral biofilm. Under bacterial infection, early caries manifests as demineralization of inorganic tooth structure and decomposition of organic tooth structure, eventually forming cavities. For the elderly, if dentures are not cleaned properly, bacteria can adhere to them, turning the denture support area bright red and even causing white spots in the mouth. This can cause significant damage to the oral mucosa. To address dental problems, people choose dental materials for restoration. However, dental materials can also become breeding grounds for bacteria in the oral environment, forming a bacterial film on their surface and causing harm to the oral cavity. Therefore, preparing an antibacterial coating on the surface of dental restorative materials is an effective method. Dental restorative materials themselves are stable; physical or chemical modification can actually affect their original properties. Surface coatings can effectively solve this problem. The coating does not affect the performance of the substrate and can also resist the invasion of external bacteria. By adjusting the coating preparation process parameters, the coating can be made aesthetically pleasing, safe, and easy to use. Currently, hydrogels are rapidly developing into important materials for coating preparation due to their excellent biocompatibility and drug-carrying properties. However, problems such as easy coating peeling and short service life need to be solved. Improving the coating's retention and antibacterial properties is crucial.

[0003] Studies have shown that researchers are currently attempting to achieve highly effective bactericidal effects using antibiotic-loaded antibacterial coatings. This is achieved by preparing hydrogel coatings and simultaneously immersing them in antibiotics to obtain antibacterial gel coatings. For example, patent application CN 120531942 A indicates that antibacterial properties can be imparted to hydrogel coatings by loading different amounts of the antibiotic rifampicin. The antibiotic loading in the coating can be controlled by adjusting the pH value of the antibiotic solution during adsorption, allowing for on-demand control of the antibiotic loading and related release curves in the hydrogel coating for different application scenarios. However, the overuse of antibiotics can lead to bacterial resistance, and long-term use of antibiotics can also have adverse effects on the body. Summary of the Invention

[0004] This invention addresses the problems of dental caries, oral mucosal redness and pain caused by bacterial invasion in the oral cavity by providing a nanocomposite antibacterial coating for dental materials and its preparation method. The gel coating prepared by this invention exhibits good retention properties, antibacterial properties, and biocompatibility. The antibacterial coating is used in dental restorative materials, particularly on the surface of dentures, specifically the surface of the denture that contacts the denture support area.

[0005] This invention is achieved through the following technical solution:

[0006] A method for preparing a nanocomposite antibacterial coating for dental materials includes the following steps:

[0007] Monomer-modified arginine (M-Arg), monomer N-isopropylacrylamide (NIPAM), monomer hexyl methacrylate (HM), initiator azobisisobutyramidine hydrochloride (V-50), dispersant cetyltrimethylammonium bromide (CTAB), and crosslinking agent N,N-methylenebis(acrylamide) (MBA) were dissolved in water, reacted under a protective atmosphere, and dialyzed to obtain a dispersion of nanogels. The nanogel dispersion was mixed with a nano zinc oxide dispersion to obtain a nanogel composite zinc oxide antibacterial coating, which was then applied to form a coating.

[0008] The mass ratio of M-Arg:NIPAM:HM is 0.1:0.5:0.1~0.2;

[0009] The mass ratio of V-50:CTAB:MBA is 0.01:0.05:0.005;

[0010] The mass ratio of M-Arg to V-50 is 0.1:0.01.

[0011] The reaction temperature is 65~75℃; the reaction time is 7~9 h.

[0012] The volume ratio of the nanogel to the zinc oxide dispersion is 1:1;

[0013] The concentrations of both the nanogel and zinc oxide were 5 mg / mL.

[0014] The concentration of the nanogel dispersion is obtained by removing the dialysis dispersion and lyophilizing it to obtain the mass of the lyophilized product.

[0015] The coating amount of the nanocomposite antibacterial coating for dental materials is 100~300μL / cm. 2 .

[0016] After coating, dry at room temperature for 12-18 hours.

[0017] The reaction is carried out under stirring at a speed of 250-350 rpm.

[0018] The dialysis is performed using an 8000-14000 MWCO dialysis bag in water. The dialysis time is 3 days, with the water changed once a day during the dialysis period.

[0019] The coating refers to the coating applied to the surface of dental materials.

[0020] The modified arginine (M-Arg) was prepared by the following method: L-arginine was reacted with methacrylic anhydride in the presence of triethylamine using a mixed solvent of dioxane and water as the reaction medium to obtain modified arginine. The reaction was carried out at room temperature for 12-15 hours.

[0021] The specific preparation method of the modified arginine is as follows: under ice-water bath conditions, methacrylic anhydride is added dropwise to a mixed system of L-arginine, triethylamine, and a mixed solvent of dioxane and water. After the addition is complete, the reaction is carried out at room temperature.

[0022] The dripping rate is 30-60 drops / min.

[0023] After the reaction, precipitation, filtration, and drying were performed. The precipitate was formed in acetone. Vacuum drying was carried out at 25-30℃.

[0024] The molar ratio of L-arginine to methacrylic anhydride is 1:2.

[0025] The volume ratio of water to dioxane is (2.3-2.5):1.

[0026] The molar ratio of the catalyst triethylamine to the monomers (L-arginine and methacrylic anhydride) is 1:1.

[0027] The reaction is carried out under stirring at a speed of 200-300 rpm.

[0028] The dental restorative material is prepared by the following method: Bis-GMA and TEGDMA are mixed, and the initiator camphorquinone (CQ) and the co-initiator ethyl 4-N,N-dimethylaminobenzoate (4-EDMAB) are added, followed by curing under ultraviolet light.

[0029] Bisphenol A-glycidyl methacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) are composed of each other in a mass ratio of (1.9~2.1):1, preferably 2:1.

[0030] The main initiator camphorquinone (CQ) and the co-initiator ethyl 4-N,N-dimethylaminobenzoate (4-EDMAB) are composed in a mass ratio of 1:4. The main initiator accounts for 0.2% of the total monomer mass.

[0031] The curing conditions are ultraviolet light irradiation with a wavelength of 365-385 nm for 90-120 s.

[0032] The antibacterial coating of this invention has excellent retention properties on dental materials such as stainless steel, ceramics, plastics, and titanium, with an intact coating and good antibacterial effect.

[0033] The dental nanocomposite antibacterial coating of this invention exhibits excellent retention and antibacterial properties. Due to the negative charge acquired by the substrate after plasma treatment, the positively charged nanogel can effectively interact with it electrostatically to achieve stable coating. Hydrophobic and negatively charged nano-zinc oxide can bind well with the nanogel, further enhancing its stability. Compared to pure nanogel coatings and pure zinc oxide coatings, the retention capacity of the composite coating is increased several times. Furthermore, the composite coating achieves an antibacterial rate of over 99% against common oral bacteria such as Streptococcus mutans and Candida albicans. The positive charge of modified arginine and the slow release of zinc ions from zinc oxide in the moist oral environment contribute to long-lasting bactericidal effects. The composite coating prepared by this invention requires a simple process, does not introduce toxic reagents during preparation, and has high biosafety.

[0034] Compared with the prior art, the present invention has the following beneficial effects and advantages: the nano-gel composite zinc oxide antibacterial coating of the present invention has excellent retention ability and antibacterial properties, such as: it can be completely retained in different solutions without falling off, and the antibacterial rate against common oral bacteria such as Streptococcus mutans and Candida albicans exceeds 99%; moreover, the preparation process of the present invention is simple, the biosafety is high, and the monomer price is low. Attached Figure Description

[0035] Figure 1 Particle size diagrams of TNG, ZnO, and TNG / ZnO in Examples 2, 3, and 4;

[0036] Figure 2 Original images and crystal violet staining images of the substrates and coatings of Examples 1, 2, 3, and 4 in phosphate buffer, deionized water, 75% ethanol, and physiological saline; Example 1: Control, Example 2: TNG, Example 3: ZnO, Example 4: TNG / ZnO;

[0037] Figure 3 The images show the original images of the TNG / ZnO coating's retention performance on different dental restorative material surfaces and its Rhodamine B staining images from Example 4.

[0038] Figure 4 The colony diagrams and antibacterial rates of Streptococcus mutans in Examples 1, 2, 3, and 4 are shown.

[0039] Figure 5 The colony diagrams and antibacterial rates of Candida albicans in Examples 1, 2, 3, and 4 are shown.

[0040] Figure 6 The graphs show the release curves of zinc ions in Examples 3 and 4. Detailed Implementation

[0041] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings, but the implementation and protection of the present invention are not limited thereto.

[0042] Bisphenol A-glycidyl methacrylate: Bis-GMA, Triethylene glycol dimethacrylate: TEGDMA, Camphorquinone: CQ, Ethyl 4-N,N-dimethylaminobenzoate: 4-EDMAB, Methacrylamide: MMC, L-arginine: Arg, Triethylamine: TEA; Methacrylamide-modified arginine: M-Arg; N-isopropylacrylamide: NIPAM; Hexyl methacrylate: HM; Cetyltrimethylammonium bromide: CTAB; N,N-Methylenebis(acrylamide): MBA; Azobisisobutyramidine hydrochloride: V-50; Nano zinc oxide: ZnO; Nanogel: TNG; Nanogel composite zinc oxide: TNG / ZnO.

[0043] Preparation of the dental restorative material resin substrate in Examples 1, 2, 3, and 4:

[0044] The resin is composed of Bis-GMA, TEGDMA, CQ, and 4-EDMAB in a mass percentage ratio of 33%:66%:0.2%:0.8%. Bis-GMA and TEGDMA were mixed at a mass ratio of 2:1 to form a resin prepolymer solution. After thorough mixing, CQ and 4-EDMAB were added to the resin prepolymer solution, and the mixture was stirred in the dark for 30 minutes. After thorough mixing, the mixture was poured into a silicone mold mounted on a glass slide and finally cured under light for 120 seconds to obtain pure resin.

[0045] Preparation of M-Arg in Examples 2 and 4:

[0046] 2 g of Arg L-arginine was placed in a reaction vessel, and 20 mL of deionized water and 8.5 mL of dioxane were added. The mixture was stirred until the solid was fully dissolved, and then 4.5 mL of TEA was added as a catalyst. The reaction vessel was placed in an ice-water bath, and 3 mL of MMC methacrylic anhydride was added dropwise over 15 min while stirring at 250 rpm. The ice-water bath was removed, and the reaction was carried out at room temperature with stirring at 250 rpm for 12 h. The resulting pale yellow solution was added in small amounts to 400 mL of acetone to precipitate the solid. The precipitate was then redissolved in water and precipitated again in acetone. This precipitation process was repeated twice. The solution was filtered, washed repeatedly with acetone, and filtered three times under vacuum to remove impurities. The precipitate was dried under vacuum at 25 °C for 24 h to obtain a white powder product, methacrylic anhydride-modified arginine, with a yield of approximately 70%.

[0047] Preparation of TNG nanogels in Examples 2 and 4:

[0048] Weigh out 0.5 g of NIPAM, 0.1 g of M-Arg, 0.2 g of HM, 0.005 g of MBA, 0.01 g of V-50, and 0.05 g of CTAB into a reaction vessel, add 20 mL of deionized water and stir to dissolve. Purge the reaction solution with nitrogen gas for 30 min to remove dissolved oxygen. Then transfer the reaction to a water bath and continue purging with nitrogen gas until the temperature reaches 70 °C. Stir the system at 300 rpm for 8 h at 70 °C. After the reaction, dialyze the dispersion in 5 L of deionized water for 3 days using a dialysis bag with a molecular weight cutoff of 8000-14000 Da to remove unreacted monomers and impurities, thus obtaining a nanogel dispersion.

[0049] Example 1

[0050] The uncoated group of pure resin substrates consists of Bis-GMA, TEGDMA, CQ, and 4-EDMAB in a mass percentage ratio of 33%:66%:0.2%:0.8%.

[0051] Preparation of pure resin: 0.825 g Bis-GMA, 1.65 g TEGDMA, 0.005 g CQ and 0.02 g 4-EDMAB were mixed evenly and then loaded into a silicone mold supported by a glass plate. Finally, the mixture was photocured for 120 s to obtain pure resin.

[0052] The pure resin showed an antibacterial rate of 0% against Streptococcus mutans and Candida albicans in the oral cavity.

[0053] Example 2

[0054] Preparation of TNG coating: Dental restorative material resin substrate is prepared for use after plasma treatment; 100 μL of the prepared 5 mg / mL nanogel dispersion (TNG dispersion) is pipetted and spread evenly on the surface of the resin substrate, and the sample is transferred to a 50 ℃ oven and dried for 12 h.

[0055] The TNG coating was retained in only phosphate buffer and physiological saline in four solutions (phosphate buffer, deionized water, 75% ethanol, and physiological saline). The antibacterial rates of the TNG coating against Streptococcus mutans and Candida albicans in the oral cavity were 50.3% and 93.2%, respectively.

[0056] Example 3

[0057] Preparation of ZnO coating: The resin substrate was prepared by plasma treatment and then set aside. A 20% ZnO dispersion was prepared to a concentration of 5 mg / mL. 100 μL of the dispersion was pipetted onto the surface of the resin substrate and the sample was transferred to a 50 °C oven and dried for 12 h.

[0058] The ZnO coating completely detaches in phosphate buffer but remains intact in other solutions. The ZnO coating exhibits antibacterial rates of 99.8% against Streptococcus mutans and 95.4% against Candida albicans in the oral cavity.

[0059] Example 4

[0060] Preparation of TNG / ZnO coating: The resin substrate was prepared by plasma treatment and then set aside. A 20% ZnO dispersion (aqueous dispersion, average particle size ≤100nm) was prepared to a concentration of 5 mg / mL and then added to a 5 mg / mL TNG dispersion at a mass ratio of 1:1. The mixture was sonicated for 10 min to ensure complete mixing. 100 μL of the mixture was pipetted and spread evenly on the surface of the resin substrate. The sample was then placed in a room temperature environment (25℃) and dried for 12 h.

[0061] The TNG / ZnO coating remained intact in phosphate buffer, physiological saline, deionized water, and 75% ethanol solution. The TNG / ZnO coating exhibited an antibacterial rate of approximately greater than 99.9% against Streptococcus mutans and Candida albicans in the oral cavity.

[0062] Figure 1 The particle size distributions of TNG, ZnO, and TNG / ZnO in Examples 2, 3, and 4 are shown.

[0063] Figure 2The images show the original images of the substrates and coatings of Examples 1, 2, 3, and 4 in phosphate buffer, deionized water, 75% ethanol, and physiological saline, along with their crystal violet staining images. Example 1: Control; Example 2: TNG; Example 3: ZnO; Example 4: TNG / ZnO.

[0064] Figure 3 The images show the original images of the TNG / ZnO coating on different dental restorative material surfaces in Example 4, along with its Rhodamine B staining image.

[0065] Figure 4 Examples 1, 2, 3, and 4 show colony diagrams and antibacterial rates against Streptococcus mutans. Example 1: control, Example 2: TNG, Example 3: ZnO, Example 4: TNG / ZnO.

[0066] Figure 5 Examples 1, 2, 3, and 4 show colony diagrams and antibacterial rates against Candida albicans. Example 1: control, Example 2: TNG, Example 3: ZnO, Example 4: TNG / ZnO.

[0067] Figure 6 The figures show the zinc ion release curves in the coatings of Examples 3 and 4. Example 3: ZnO; Example 4: TNG / ZnO.

[0068] Depend on Figure 1 The average particle size of TNG is around 150 nm, proving the successful synthesis of nanogels through precipitation polymerization. After incorporating zinc oxide, the particle size increased to around 200 nm.

[0069] Depend on Figure 2 It can be seen that after shaking at 37 °C and 60 rpm for 24 h, the TNG coating almost completely detached in deionized water and partially detached in 75% ethanol solution; the ZnO coating completely detached in sulfate buffer solution; while the TNG / ZnO coating was completely retained in all four solutions. This is attributed to the lower critical phase transition temperature of TNG and the hydrophobic protective effect of ZnO. The positively charged TNG binds tightly to the negatively charged ZnO, and ZnO tightly protects the TNG, thus improving its retention effect.

[0070] Bis-GMA / TEGDMA resin is commonly used in dental restorations; polyethylene terephthalate (PET) plastic is a common substrate for invisible aligners; stainless steel and titanium are frequently used clinically to fabricate orthodontic archwires, brackets, and implants; zirconia ceramics are commonly used for all-ceramic crowns, veneers, and integrated brackets. Therefore, from Figure 3It can be seen that Bis-GMA / TEGDMA resin, polyethylene terephthalate, 304 stainless steel, titanium, and zirconia ceramic were selected as substrates, and TNG / ZnO coatings were applied to their surfaces, demonstrating the versatility of TNG / ZnO coatings. The TNG / ZnO coating does not alter the original color of the substrate, exhibiting good aesthetics and meeting clinical aesthetic requirements. After staining the coating with Rhodamine B solution, it was observed that the coating could achieve uniform coverage on various substrate surfaces, demonstrating excellent versatility. Therefore, TNG / ZnO coatings can be applied to the surfaces of different dental materials, adapting to different clinical scenarios and possessing broad application potential.

[0071] Depend on Figure 4 and Figure 5 It is known that TNG, due to its positively charged nature, can bind to negatively charged bacterial biofilms, resulting in antibacterial rates of 50.3% and 93.2% against Streptococcus mutans and Candida albicans, respectively. Zinc oxide, on the other hand, continuously releases positively charged zinc ions, achieving antibacterial rates of 95.5% and 99.8% against Streptococcus mutans and Candida albicans, respectively. The combination of these two compounds resulted in antibacterial rates exceeding 99.9% against both Streptococcus mutans and Candida albicans in the oral cavity, demonstrating their excellent bactericidal ability.

[0072] Depend on Figure 6 It can be seen that when Examples 3 and 4 were immersed in 5 mL of physiological saline, the extract was taken out in stages and physiological saline was added again. Finally, 1 mL was taken and diluted 10 times before measurement. As shown in the figure, the zinc ion concentration increased continuously within 72 h, and Example 4 reached 5 mg / mL within 1 h, proving its highly efficient bactericidal ability. The continuous release of zinc ions also proves that the coating has excellent long-term antibacterial function, expected to last 3-7 days.

[0073] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for preparing a nanocomposite antibacterial coating for dental materials, characterized in that: Includes the following steps: Monomer-modified arginine, monomer N-isopropylacrylamide, monomer hexyl methacrylate, initiator azobisisobutyramidine hydrochloride, dispersant hexadecyltrimethylammonium bromide, and crosslinking agent N,N-methylenebis(acrylamide) were dissolved in water, reacted under a protective atmosphere, and dialyzed to obtain a dispersion of nanogel; the nanogel dispersion was mixed with a nano zinc oxide dispersion to obtain a nanogel composite zinc oxide antibacterial coating, which was then applied to form a coating. The mass ratio of modified arginine: N-isopropylacrylamide: hexyl methacrylate is 0.1:0.5:0.1~0.

2. The mass ratio of azobisisobutyramidine hydrochloride: cetyltrimethylammonium bromide: N,N-methylenebis(acrylamide) is 0.01:0.05:0.005; The mass ratio of modified arginine to azobisisobutyramidine hydrochloride is 0.1:0.01; The volume ratio of the nanogel dispersion to the zinc oxide dispersion is 1:1; The concentrations of the nanogel dispersion and the zinc oxide dispersion were both 5 mg / mL. The modified arginine was prepared by the following method: using a mixed solvent of dioxane and water as the reaction medium, L-arginine and methacrylic anhydride were reacted under the catalysis of triethylamine to obtain modified arginine; the molar ratio of L-arginine to methacrylic anhydride was 1:2; the volume ratio of water to dioxane was (2.3-2.5):1; and the molar ratio of the catalyst triethylamine to the monomer (L-arginine and methacrylic anhydride) was 1:

1.

2. The method for preparing the nanocomposite antibacterial coating for dental materials according to claim 1, characterized in that: The reaction temperature is 65~75℃; the reaction time is 7~9 h; The coating amount of the nano-gel composite zinc oxide antibacterial coating is 100~300 μL / cm. 2 .

3. The method for preparing the nanocomposite antibacterial coating for dental materials according to claim 1, characterized in that: After coating, dry at room temperature for 12-18 hours; The reaction is carried out under stirring at a speed of 250-350 rpm. The dialysis is performed in water using an 8000-14000 MWCO dialysis bag; The coating refers to the coating applied to the surface of dental materials.

4. The method for preparing the nanocomposite antibacterial coating for dental materials according to claim 1, characterized in that: The specific preparation method of the modified arginine is as follows: under ice-water bath conditions, methacrylic anhydride is added dropwise to a mixed system of L-arginine, triethylamine, and a mixed solvent of dioxane and water. After the addition is complete, the reaction is carried out at room temperature.

5. The method for preparing the nanocomposite antibacterial coating for dental materials according to claim 4, characterized in that: The dropping rate is 30-60 drops / min; the reaction is carried out at room temperature for 12-15 h. After the reaction is complete, the mixture is precipitated, filtered, and dried. The reaction is carried out under stirring at a speed of 200-300 rpm.

6. The method for preparing the nanocomposite antibacterial coating for dental materials according to claim 5, characterized in that: The precipitate is formed in acetone; the vacuum drying temperature is 25-30 ℃.

7. A nanocomposite antibacterial coating for dental materials obtained by the preparation method according to any one of claims 1 to 6.

8. The application of the nanocomposite antibacterial coating for dental materials according to claim 7, characterized in that: The dental material uses a nanocomposite antibacterial coating for dental restorative materials.

9. The application according to claim 8, characterized in that: The dental restorative materials include resin, stainless steel, ceramic, and titanium.

10. The application according to claim 9, characterized in that: The resin is prepared by the following method: bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate are mixed, and the initiator camphorquinone and the co-initiator ethyl 4-N,N-dimethylaminobenzoate are added, followed by curing under ultraviolet light. The mixture consists of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate in a mass ratio of (1.9~2.1):

1. The main initiator camphorquinone and the co-initiator ethyl 4-N,N-dimethylaminobenzoate are composed in a mass ratio of 1:4; the main initiator accounts for 0.2% of the total monomer mass. The curing conditions are ultraviolet light irradiation with a wavelength of 365-385 nm for 90-120 s.

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