Complex for blocking dentinal tubules, reagent for treating dentin hypersensitivity, and use thereof

Abstract

A complex for blocking dentinal tubules, characterized in that the complex is formed by means of polymerizing catecholamine and metal ions. The catecholamine comprises one or more of dopamine, norepinephrine, tannic acid, gallic acid, phlorotannins, phloroglucinol monomers and epigallocatechin gallate; and the metal ions comprise one or more of V 2+, Cr 2+, Cr 3+, Mn 2+, Mn 3+, Fe 2+, Fe 3+, Co 2+, Ni 2+, Cu 2+ and Sr 2+. A reagent for treating dentin allergy comprises the complex for blocking dentinal tubules, can block nearly 85% of dentinal tubules within 3 minutes, and can form a crystal structure similar to hydroxyapatite after being mineralized in vitro for 7 days. In addition, in 7-day animal experiments with SD rats, results consistent with in-vitro mineralization experiments are also observed. Moreover, the complex can not only be rapidly prepared, but also has antibacterial ability against pathogenic bacteria of dental caries, and also has good biocompatibility.

Description

A complex for blocking dentinal tubules and an agent for treating dentine hypersensitivity and applications thereof

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on October 30, 2023, with application number 202311412278.5 and invention name “A rapid dentinal tubule blocking complex and its application”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application belongs to the field of oral care technology, and specifically relates to a complex for blocking dentinal tubules and an agent for treating dentin hypersensitivity and applications thereof. Background Art

[0003] Dentin hypersensitivity (DH) manifests as severe pain. This pain is caused by the reaction of the fluid-carrying tubules (DTs) within the exposed dentin to heat, evaporation, tactile penetration, and chemical and electrical stimulation. Therefore, sealing the exposed DTs is key to reducing or curing DH.

[0004] The main sealing materials currently used in clinical practice are sealing resins, dentin adhesives, remineralization coatings, and other coatings used in clinical practice. However, most sealing materials do not produce satisfactory results. The reasons are, on the one hand, mechanical friction causes the sealing materials to fall off easily; on the other hand, the unpolymerized monomers leached from the adherent smear layer (MERs) have adverse reactions, such as hypersensitivity, estrogen activity, and changes in immune response. In addition, oral bacteria easily attach to the salivary acquired membrane (SAP) coating to form biofilms, produce toxins, and even cause chronic diseases such as pulpitis, but the antibacterial properties of desensitizing products have long been ignored. Therefore, how to achieve deep DTS sealing combined with antibacterial and remineralization and maintain stable performance is crucial for the long-term treatment of DH. Summary of the Invention

[0005] The present application aims to provide a complex for occluding dentinal tubules and an agent for treating dentin hypersensitivity, as well as their use. The complex provided herein can improve tooth hypersensitivity, rapidly and efficiently occlude dentinal tubules, exhibit antibacterial properties against caries-causing bacteria, and exhibit good biocompatibility.

[0006] To achieve the above objectives, this application provides the following technical solutions:

[0007] The present application provides a complex for blocking dentinal tubules, which is formed by polymerization of catecholamine and metal ions.

[0008] Preferably, the catecholamines include one or more of dopamine, norepinephrine, tannic acid, gallic acid, brown algae polyphenols, phloroglucinol monomers and epigallocatechin gallate.

[0009] Preferably, the metal ions include V 2+ Cr 2+ Cr 3+ 、Mn 2+ 、Mn 3+ 、Fe 2+ 、Fe 3+ 、Co 2+ 、Ni 2+ 、Cu 2+ and Sr 2+ One or more of the .

[0010] The present application also provides a method for preparing the complex for blocking dentinal tubules described in the above scheme, which comprises the following steps: mixing catecholamines and metal ions for reaction under aerobic alkaline conditions to obtain the complex for blocking dentinal tubules.

[0011] Preferably, the mixing reaction time is 1-30 min.

[0012] Preferably, the mixing reaction time is 1-5 minutes.

[0013] Preferably, the mixing reaction time is 5-10 minutes.

[0014] Preferably, the mixing reaction time is 10-15 minutes.

[0015] Preferably, the mixing reaction time is 15-20 minutes.

[0016] Preferably, the mixing reaction time is 20-25 minutes.

[0017] Preferably, the mixing reaction time is 25-30 minutes.

[0018] Preferably, the pH value of the alkaline condition is 7.4-11.

[0019] Preferably, the pH value of the alkaline condition is 8.5-10.

[0020] Preferably, the alkaline condition is 1.21 mg / mL Tris buffer.

[0021] Preferably, the aerobic condition is exposure to air.

[0022] Preferably, in the mixed solution obtained by mixing catecholamines and metal ions, the concentration of brown algae polyphenols is 0.1-5 mg / mL.

[0023] Preferably, the concentration of the brown algae polyphenols is 0.1-0.4 mg / mL.

[0024] Preferably, the concentration of the brown algae polyphenols is 0.4-0.8 mg / mL.

[0025] Preferably, the concentration of the brown algae polyphenols is 0.8-1.2 mg / mL.

[0026] Preferably, the concentration of the brown algae polyphenols is 1.2-1.6 mg / mL.

[0027] Preferably, the concentration of the brown algae polyphenols is 1.6-5 mg / mL.

[0028] Preferably, the Sr 2+ The concentration is 0.1-0.4 mg / mL.

[0029] Preferably, the Sr 2+ The concentration is 0.4-0.8 mg / mL.

[0030] Preferably, the Sr 2+ The concentration is 0.8-1.2 mg / mL.

[0031] Preferably, the Sr 2+ The concentration is 1.2-1.6 mg / mL.

[0032] Preferably, the Sr 2+ The concentration is 1.6-5mg / mL.

[0033] Preferably, the concentration of the brown algae polyphenols is 0.4 mg / mL, and the Sr 2+ The concentration is 1.6 mg / mL.

[0034] The present application also provides an agent for treating dentin hypersensitivity, comprising the complex for blocking dentinal tubules described in the above scheme or the complex for blocking dentinal tubules obtained by the preparation method described in the above scheme.

[0035] Preferably, the agent for treating dentin hypersensitivity further comprises: an effective amount of a basic amino acid in free or salt form, a fluoride salt, an anti-inflammatory compound, an anticalculus agent, a surfactant, a moisturizer, an antibacterial agent, and an antioxidant.

[0036] Preferably, the agent for treating dentin hypersensitivity is toothpaste, mouthwash or medicine.

[0037] The present application also provides the use of the reagent for treating dentin hypersensitivity described in the above scheme in the preparation of a drug for treating dentin hypersensitivity, a drug for dental caries or a drug for enamel damage.

[0038] The present application also provides a toothpaste, which includes the agent for treating dentin hypersensitivity described in the above scheme, and also includes one or more of water, abrasive, surfactant, foaming agent, vitamins, polymers, enzymes, moisturizers, thickeners, antibacterial agents, preservatives, flavorings and colorants.

[0039] This application provides a complex for occluding dentinal tubules. The complex provided in this application can occlude nearly 85% of dentinal tubules within 3 minutes. After 7 days of in vitro mineralization, it forms a crystal structure similar to hydroxyapatite. Simultaneously, a 7-day animal experiment on SD rats also observed results consistent with the in vitro mineralization experiments. Furthermore, the complex can be prepared quickly, exhibits antibacterial properties against dental caries pathogens, and exhibits good biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] FIG1 is a scanning electron micrograph of dentinal tubules blocked by different concentrations of brown algae polyphenols and strontium chloride;

[0041] Figure 2 shows field emission scanning electron micrographs of dentin slices after immersion in distilled water, PL solution, strontium chloride solution, PL@Sr, and phloroglucinol@Sr solution, and SEM images of the contents of dentinal tubules in dentin slices treated with PL@Sr after negative pressure aspiration.

[0042] Figure 3 shows the occlusion rates of PL-treated dentin slices, Sr-treated dentin slices, and PL@Sr-treated dentin slices;

[0043] Figure 4 shows the stability results of PL@Sr plugging material immersed in physiological saline for different time periods;

[0044] Figure 5 shows the mineralization results of PL@Sr-treated dentin slices. A: SEM images of the dentin surfaces of the four groups after 4 and 24 hours of remineralization. B: XRD patterns of the dentin of the four groups after remineralization.

[0045] Figure 6 shows the results of mineralization and acid corrosion resistance of PL@Sr-treated dentin slices. A: SEM images of normal dentin, PL@Sr-sealed dentin, and dentin mineralized 24 hours after sealing after 90 seconds of 5wt% citric acid corrosion. B and C are the calcium (Ca) and phosphorus (P) loss concentrations of normal dentin, PL@Sr-sealed dentin, and dentin mineralized 24 hours after sealing after 90 seconds of 5wt% (n=3) citric acid corrosion. The one-way analysis of variance showed significant differences (P<0.05).

[0046] Figure 7 shows the results of the friction and wear test of mineralized PL@Sr-treated dentin slices. A: Scanning electron micrographs of the wear traces of normal dentin, PL@Sr-sealed dentin, and dentin mineralized 24 hours after sealing (hereinafter referred to as the mineralized group). B: Friction coefficient and wear depth (n=3). The differences between the groups were statistically significant (p<0.05). C: Young's hardness (n=5). The differences between the groups were statistically significant (p<0.05).

[0047] Figure 8 shows the biocompatibility results of PL@Sr-treated dentin slices. A: Rhodamine fluorescence staining results after co-culture of L929 with the blank group, PL group, Sr group, and PL@Sr group for 1, 3, and 5 days. B: Cell proliferation-toxicity (CCK-8) results after co-culture of L929 with the four groups of dentin for 1, 3, and 5 days.

[0048] Figure 9 shows the antibacterial results of dentin slices after PL@Sr occlusion, A: Bacterial absorbance value of blank group, PL group, Sr group and PL@Sr group after 4 hours of incubation with Streptococcus mutans (n=3), (p<0.05), B: Bacterial count of blank group, PL group, Sr group and PL@Sr group, C: Bacterial smear of blank group, PL group, Sr group and PL@Sr group after 24 hours of incubation with Streptococcus mutans (n=3), (p<0.05);

[0049] Figure 10 shows the results of animal experiments, A: the process of animal modeling, B: the dentin surface morphology of the blank group and the PL@Sr group after 1 day and 7 days. DETAILED DESCRIPTION

[0050] The present application provides an agent for treating dentin hypersensitivity, comprising a complex for blocking dentinal tubules.

[0051] The reagent for treating dentin hypersensitivity provided in the present application preferably further comprises:

[0052] i. an effective amount of a basic amino acid in free or salt form;

[0053] ii. optionally further comprising an effective amount of fluoride; the fluoride is preferably a soluble fluoride salt.

[0054] In the present application, the basic amino acid is preferably arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutyric acid, diaminopropionic acid, salts thereof and / or combinations thereof.

[0055] In the present application, the basic amino acid preferably has the L configuration.

[0056] In the present application, the basic amino acid is preferably arginine; and the arginine is preferably L-arginine.

[0057] In the present application, the basic amino acid is preferably partially or entirely in the form of a salt; the salt of the basic amino acid preferably comprises one or more of arginine phosphate, arginine hydrochloride, arginine sulfate and arginine bicarbonate.

[0058] In the present application, the salt of the basic amino acid is preferably formed in situ in the reagent by neutralizing the basic amino acid with an acid or a salt of an acid. The salt of the basic amino acid is preferably formed by neutralizing the basic amino acid to form a premix before combining with the soluble fluoride salt.

[0059] In the present application, the fluoride salt is preferably one or more of stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (the amine fluoride is preferably N′-octadecyltrimethylenediamine-N,N,N′-tris(2-ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride and hexafluorosulfate.

[0060] In the present application, the fluoride salt is preferably a fluorophosphate.

[0061] In the present application, the fluoride salt is preferably sodium monofluorophosphate.

[0062] The agent for treating dentin hypersensitivity provided in the present application preferably further comprises one or more of abrasives and microparticles.

[0063] In the present application, the microparticles are preferably selected from one or more of sodium bicarbonate, calcium phosphate (the calcium phosphate is preferably calcium hydrogen phosphate dihydrate), calcium sulfate, precipitated calcium carbonate, silicon dioxide (the silicon dioxide is preferably hydrated silicon dioxide), iron oxide, aluminum oxide, perlite and plastic particles (the plastic particles are preferably polyethylene).

[0064] In the present application, the abrasive is preferably selected from one or more of calcium phosphate (the calcium phosphate is preferably calcium hydrogen phosphate dihydrate), calcium sulfate, precipitated calcium carbonate, silicon dioxide (the silicon dioxide is preferably hydrated silicon dioxide) and calcium pyrophosphate.

[0065] The agent for treating dentin hypersensitivity provided in the present application preferably further includes an anticalculus agent.

[0066] In the present application, the anti-stone agent is preferably a polyphosphate, and the polyphosphate is preferably a pyrophosphate, a tripolyphosphate or a hexametaphosphate; and the polyphosphate is preferably a sodium salt.

[0067] The agent for treating dentin hypersensitivity provided in the present application preferably further comprises a surfactant.

[0068] In the present application, the surfactant is preferably selected from one or both of sodium lauryl sulfate and cocamidopropyl betaine.

[0069] The agent for treating dentin hypersensitivity provided by the present application preferably further comprises an anionic surfactant.

[0070] In the present application, the anionic surfactant is preferably sodium lauryl sulfate.

[0071] The agent for treating dentin hypersensitivity provided in the present application preferably further comprises a moisturizer; the moisturizer is preferably selected from one or more of glycerol and sorbitol.

[0072] The agent for treating dentin hypersensitivity provided in the present application preferably also includes a polymer, and the polymer is preferably selected from one or more of polyethylene glycol, polymethyl vinyl ether maleic acid copolymer and polysaccharide (the polysaccharide is preferably a cellulose derivative or polysaccharide gum; the cellulose derivative is preferably carboxymethyl cellulose; the polysaccharide gum is preferably xanthan gum or carrageenan).

[0073] The agent for treating dentin hypersensitivity provided by the present application preferably further includes an antibacterial agent, which is preferably selected from halogenated diphenyl ethers (the halogenated diphenyl ether is preferably triclosan), herbal plant extracts and essential oils (the herbal plant extracts and essential oils preferably include rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitiol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea buckthorn extract), biguanide antibacterial agents (the biguanide antibacterial agent is preferably chlorhexidine, alexidine or decanone), quaternary ammonium compounds (the quaternary ammonium compounds are preferably cetylpyridinium chloride (CPC), benzalkonium chloride, The invention also includes one or more of tetradecylpyridinium chloride (TPC), tetradecylethylpyridinium chloride (TDEPC)), phenolic antimicrobial agents, hexetidine, decanedioic acid, sanguinarine, povidone iodine, delmopinol, salifluor, metal ions (the metal ions are preferably zinc salts, tin salts, copper salts, iron salts; the zinc salts are preferably zinc citrate), sanguinarine, propolis and an oxidant (the oxidant is preferably hydrogen peroxide, buffered sodium perborate or sodium percarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfates, sodium dioctyl sulfosuccinate, salicylanilide, doxepin bromide, delmopinol, octaflurox and other piperidine derivatives, saccharococcin preparations and chlorite.

[0074] The reagents for treating dentin hypersensitivity provided in the present application preferably also include an anti-inflammatory compound, which is preferably an inhibitor of at least one host proinflammatory factor, and the host proinflammatory factor is preferably selected from matrix metalloproteinases (MMP's), cyclooxygenase (COX), PGE2, interleukin 1 (IL-1), IL-1β converting enzyme (ICE), transforming growth factor β1 (TGF-β1), inducible nitric oxide synthase (iNOS), hyaluronidase, cathepsin, nuclear factor kappa B (NF-κB), and IL-1 receptor-associated kinase (IRAK), and the anti-inflammatory compound is preferably selected from one or more of aspirin, ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, ketoprofen, piroxicam, meclofenamic acid and nordihydroguaiaretic acid.

[0075] The agent for treating dentin hypersensitivity provided in the present application preferably further includes an antioxidant, and the antioxidant is preferably selected from one or more of coenzyme Q10, PQQ, vitamin C, vitamin E, vitamin A and anethole-dithiothione.

[0076] The reagent for treating dentin hypersensitivity provided in the present application preferably also includes a whitening agent selected from whitening active substances, and the whitening active substance is preferably selected from one or more of peroxides, metal chlorites, perborates, percarbonates, perhydroxy acids and hypochlorites.

[0077] The reagent for treating dentin hypersensitivity provided in the present application preferably also includes hydrogen peroxide or a source of hydrogen peroxide, and the source of hydrogen peroxide is preferably urea peroxide, a peroxide salt or a complex (the peroxide salt is preferably peroxyphosphate, peroxycarbonate, perborate, peroxysilicate or persulfate; the complex is preferably calcium peroxyphosphate, sodium perborate, sodium peroxycarbonate, sodium peroxyphosphate and potassium persulfate), or a hydrogen peroxide polymer complex; the hydrogen peroxide polymer complex is preferably a hydrogen peroxide-polyvinylpyrrolidone polymer complex.

[0078] The reagent for treating dentin hypersensitivity provided in the present application preferably also includes calcium and phosphate sources, and the calcium and phosphate sources are preferably selected from (i) calcium-glass complex and (ii) calcium-protein complex, the calcium-glass complex is preferably calcium sodium phosphosilicate, and the calcium-protein complex is preferably casein phosphopeptide-amorphous calcium phosphate.

[0079] The agent for treating dentin hypersensitivity provided in the present application preferably further comprises a soluble calcium salt, for example, one or more selected from the group consisting of calcium sulfate, calcium chloride, calcium nitrate, calcium acetate and calcium lactate.

[0080] The agent for treating dentin hypersensitivity provided herein preferably further comprises an agent that interferes with or prevents bacterial attachment, such as ethyl paraben or chitosan.

[0081] The agent for treating dentin hypersensitivity provided herein preferably further comprises a physiologically acceptable potassium salt, such as potassium nitrate, potassium citrate or potassium chloride, in an amount effective to reduce tooth sensitivity.

[0082] The present application provides an agent for treating dentin hypersensitivity, which is preferably: the salt of the basic amino acid is arginine bicarbonate, the fluoride is sodium monofluorophosphate, and the abrasive is precipitated calcium carbonate.

[0083] The present application provides an agent for treating dentin hypersensitivity, which is preferably: the salt of the basic amino acid is arginine bicarbonate, the fluoride is sodium monofluorophosphate, and the abrasive is silicon dioxide.

[0084] The agents for treating dentin hypersensitivity provided herein, when applied to the oral cavity, for example, by brushing, can be effective in (i) reducing or inhibiting caries formation, (ii) reducing, repairing, or inhibiting dangerous damage to tooth enamel, for example, as detected by quantitative light fluorescence (QLF) or electronic caries measurement (ECM), (iii) reducing or inhibiting demineralization and promoting tooth remineralization, (iv) reducing tooth hypersensitivity, (v) reducing or inhibiting gingivitis, (vi) promoting healing of oral ulcers or wounds, (vii) reducing the level of acid-producing bacteria, (viii) increasing the relative level of arginine-hydrolyzing bacteria, (ix) inhibiting the formation of biofilms of microorganisms in the oral cavity, (x) raising and / or maintaining the pH of dental plaque at a level of at least about pH 5.5 after sugar challenge, (xi) reducing dental plaque accumulation, (xii) reducing dry mouth, (xiii) cleaning the teeth and oral cavity, (xiv) reducing corrosion, (xv) whitening teeth, and / or (xvi) immunizing teeth against caries-causing bacteria.

[0085] The agent for treating dentin hypersensitivity provided herein is preferably in a form selected from mouthwash, toothpaste, tooth gel, tooth powder, non-abrasive gel, mousse, foam, oral spray, lozenge, oral tablet, dental tool, and pet care product.

[0086] In the present application, the agent for treating dentin hypersensitivity is more preferably toothpaste.

[0087] In the present application, when the agent for treating dentin hypersensitivity is toothpaste, the toothpaste preferably further comprises one or more of water, abrasive, surfactant, foaming agent, vitamin, polymer, enzyme, moisturizer, thickener, antibacterial agent, preservative, flavoring agent and coloring agent.

[0088] In order to further illustrate the present application, the scheme of the present application is described in detail below with reference to the accompanying drawings and embodiments, but they should not be understood as limiting the scope of protection of the present application.

[0089] Comparative Example 1

[0090] The polyphenol structure phloroglucinol monomer in brown algae polyphenols was used as comparative example 1.

[0091] Example 1

[0092] The natural polyphenols used in this application are brown algae polyphenols.

[0093] 1. Preparation of mixtures of different concentrations:

[0094] Under alkaline conditions, using Tris solution (pH = 8.5, 1.21 mg / mL), at room temperature (25°C) and aerobic conditions, different concentrations of brown algae polyphenols (0.2, 0.4, 0.8 and 1.6 mg / mL) and different concentrations of SrCl2 (0.2, 0.4, 0.8 and 1.6 mg / mL) were mixed and reacted for 3 minutes to prepare 16 complexes.

[0095] 2. Dentin tubule occlusion effect:

[0096] The prepared complex was coated on a dentin slice for 3 minutes and then rinsed with deionized water three times to obtain a PL@Sr dentin slice. The prepared dentin slice was photographed using a scanning electron microscope.

[0097] As shown in Figure 1 , the PL@Sr complex with a PL concentration of 0.4 mg / mL and a Sr concentration of 1.6 mg / mL had the best effect in blocking dentinal tubules.

[0098] Example 2

[0099] Exploring the performance of the optimal concentration PL@Sr complex

[0100] 1. Sample preparation:

[0101] 1) Blank control;

[0102] 2) Under alkaline conditions, brown algae polyphenols (0.4 mg / mL) and SrCl2 (1.6 mg / mL) were mixed in Tris solution (pH = 8.5, 1.21 mg / mL) at room temperature (25°C) and in the presence of oxygen for 3 minutes. The mixture was then applied to the dentin slides for 3 minutes and then rinsed three times with deionized water as the experimental group.

[0103] 3) Under alkaline conditions, brown algae polyphenols (0.4 mg / mL) were polymerized in Tris solution (pH = 8.5, 1.21 mg / mL) at room temperature (25°C) and in the presence of oxygen for 3 minutes. The mixture was then applied to the dentin slides for 3 minutes and rinsed three times with deionized water as a control group.

[0104] 4) Under alkaline conditions, SrCl2 (1.6 mg / mL) was applied to the dentin slices using Tris solution (pH = 8.5, 1.21 mg / mL) at room temperature (25°C) and in the presence of oxygen. The slices were then rinsed three times with deionized water as a control group.

[0105] 5) Phloroglucinol monomer, a polyphenol structure in brown algae polyphenols, was selected as a control. Phloroglucinol@Sr complex was prepared at the optimal concentration combination as described for the experimental group. After coating on the dentin slide for 3 minutes, it was rinsed with deionized water three times as a control group.

[0106] The dentin slices were immersed in distilled water, PL solution, phloroglucinol@Sr solution, strontium chloride solution, and PL@Sr for 3 minutes, respectively. Images of the prepared dentin slices were then captured using field emission scanning electron microscopy. The PL@Sr-treated dentin slices were then subjected to negative pressure aspiration, and the surface morphology of the dentinal tubule contents was captured using scanning electron microscopy. As shown in Figure 2, the phloroglucinol@Sr complex exhibited a good plugging effect on the dentin slices, but not as good as PL@Sr. The results after negative pressure aspiration of PL@Sr indicate that the PL@Sr complex maintained its intact structure under negative pressure. The pore size of the dentin slices and the amount of PL@Sr complex aspirated under negative pressure indicate that PL@Sr exhibited excellent plugging effects.

[0107] 2. Relative dentinal tubule occlusion rate calculation experiment:

[0108] Blank, PL, Sr, and PL@Sr dentin slides were examined under a scanning electron microscope (SEM). Scans were taken at 1000x magnification, and the area of ​​unblocked dentinal tubules was counted using Image J. The calculation formula was: relative dentinal tubule opening rate = sample dentinal tubule opening area / blank dentinal tubule blocking area × 100%, and relative dentinal tubule blocking rate = (1 - relative dentinal tubule opening rate) × 100%. The results are shown in Figure 3.

[0109] According to Figure 3 , the blocking rate of the PL@Sr complex is as high as 85%, which is much better than the blocking effects of PL and Sr.

[0110] 3. Blockage stability test:

[0111] Dentin samples prepared from the blank group, PL group, Sr group, phloroglucinol@Sr, and PL@Sr groups were placed in a 50-mL clean beaker. Simulated saliva was poured into each group and replaced every 2 days. The dentin samples were taken out at 4, 8, 12, 24, 72, 120, and 168 hours, respectively, and ultrasonically cleaned with pure water for 30 seconds. After drying, their surface morphology was observed under a scanning electron microscope, as shown in Figure 4.

[0112] According to Figure 4, the SEM surface morphology of the PL@Sr coating after being placed in physiological saline for 4h, 8h, 12h, 24h, 72h, 120h, and 168h, the plugging material gradually dissolved with the extension of the immersion time, and the plugging material was completely dissolved after 168h.

[0113] 4. Dentin mineralization test:

[0114] Dentin sections prepared as described above were placed at the bottom of a sealed beaker containing 50 mL of mineralization solution. The beaker was placed in a 37°C incubator. Samples were randomly removed from each group at regular intervals (4 and 24 hours). All recovered dentin sections were gently sonicated in pure water for 2 minutes, rinsed with running deionized water, and air-dried. Scanning electron microscopy and X-ray diffraction were performed to characterize the solution. The mineralization solution consisted of 18.2 mM CaCl₂, 2H₂O, 5.6 mM K₂HPO₄-3H₂O, 1 ppm NaF, 0.14 mM NaCl, 2 mM HCl, and 83 mM Tris. The pH of the solution was adjusted to 6.5 ± 0.1 using 10 mM Tris buffer.

[0115] As shown in Figure 5, the SEM results of the dentin surface of the four groups after 4h and 24h of dentin remineralization are shown in Figure 5A. The diffraction peaks in the XRD pattern in Figure 5B match the hydroxyapatite (JCPDS No.09-4032) card. The characteristic peaks of hydroxyapatite are at 32.2°, 39.8° and 46.7°, corresponding to the (002), (211), (112), (310) and (222) crystal planes, respectively.

[0116] 5. Remineralized dentin acid erosion test:

[0117] Mineralized dentin slices were immersed in a 5% citric acid solution for 90 seconds to evaluate their acid resistance. Remineralized dentin was coated with nail polish (candyMoyo, China) for 24 hours to block the dentin outside the remineralized surface (exposed surface area 4 mm × 4 mm). The remineralized dentin was then immersed in 2 mL of 5% citric acid solution for 90 seconds. After acid etching, the dentin was immersed in an Eppendorf tube containing 1 mL of deionized water for 2 minutes to remove residual calcium and phosphate ions. It was then immersed in another Eppendorf tube containing 1 mL of fresh deionized water for 2 minutes. The 2 mL citric acid solution and 2 mL of deionized water were collected, and calcium and phosphate ion concentrations were measured by inductively coupled plasma atomic emission spectrometry (ICP-OES). The surface morphology of the acid-etched dentin was observed using scanning electron microscopy. Healthy dentin and PL@Sr dentin served as controls (Figure 6).

[0118] According to Figure 6, Figure 6A shows the SEM surface morphology of normal dentin, PL@Sr-sealed dentin, and dentin mineralized for 24 hours after sealing, after 90 seconds of 5wt% citric acid corrosion. The mineralized dentin after sealing was obviously corroded. Figure 6B and Figure 6C show that the mineralized dentin after sealing had obvious calcium and phosphorus losses after 90 seconds of citric acid corrosion.

[0119] 6. Friction and wear test of remineralized dentin:

[0120] The friction coefficient and wear depth of the remineralized dentin (24h) group and the coating group were measured using a friction and wear tester. At room temperature, under a normal load of 1.5N, the wear depth was 1mm.s -1 Reverse sliding tests were performed using a 3mm long track at a sliding speed of 1000 nm and a 30s cycle. The coefficient of friction, z-axis, and z-depth parameters were evaluated for each group (n = 3). Wear traces of the specimens after the reverse sliding tests were analyzed using a field emission scanning electron microscope. The coefficient of friction and wear depth were calculated using RTEC Viewer software. Healthy dentin served as the control group. The results are shown in Figure 7.

[0121] According to Figure 7 , basic toothbrushing with repeated friction had no significant effect on the remineralization of PL@Sr-sealed dentin and dentine; moreover, correct toothbrushing did not lead to remineralization of PL@Sr coating and dentine.

[0122] 7. Explore the biocompatibility of different components:

[0123] L929 cells were used as experimental materials and CCK-8 (cell counting kit-8) detection was performed to quantitatively detect the number of cell growth, and the OD values ​​were measured at 1, 3, and 5 days respectively. At the same time, fluorescence staining was used to observe cell morphology, and fluorescence photos were taken after culturing for 1, 3, and 5 days respectively. The results are shown in Figure 8.

[0124] As shown in Figure 8, there was no significant difference in OD values ​​among the four groups on the 3rd and 5th days (P>0.05), indicating that the PL@Sr group had good biocompatibility.

[0125] 8. Investigate the in vitro antibacterial performance of different components:

[0126] The anti-Streptococcus mutans performance of the prepared dentin sealing mixture was evaluated by turbidity method and plate coating method. The results are shown in Figure 9.

[0127] As shown in Figure 9 , the PL group, Sr group, and PL@Sr group all have the ability to inhibit mutans Streptococcus, among which the PL@Sr group has the best ability.

[0128] 9. Animal Experimentation

[0129] Twelve male Sprague-Dawley rats, approximately four weeks old and weighing approximately 150 g, were randomly divided into four groups (blank group on day 1, blank group on day 7, PL@Sr group on day 1, and PL@Sr group on day 7), with three rats in each group. An in vivo model was successfully established by intraperitoneal injection of 2.5% sodium pentobarbital. After anesthesia took effect, the Sprague-Dawley rats were immobilized in a supine position. Hooks were removed to expose the maxillary first molars bilaterally, and the teeth were evenly abraded approximately 1 mm with a ball drill. The PL@Sr group brushed their teeth twice daily for 3 minutes each time. The blank group brushed their teeth twice daily with saline. The Sprague-Dawley rats were sacrificed on day 1 and day 7, respectively. After ultrasonic cleaning with saline for 60 seconds, the specimens were removed and dried. The surface morphology of the maxillary first molars was observed under a scanning electron microscope (Figure 10).

[0130] According to Figure 10, PL@Sr has a good dentinal tubule blocking effect in vivo.

[0131] Although the above embodiment provides a detailed description of the present application, it is only a part of the embodiments of the present application, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present application.

Claims

1. A complex for blocking dentinal tubules, characterized in that: Formed by polymerization of catecholamines and metal ions; The catecholamines include one or more of dopamine, norepinephrine, tannic acid, gallic acid, brown algae polyphenols, phloroglucinol monomers and epigallocatechin gallate; The metal ions include V 2+ Cr 2+ Cr 3+ , Mn 2+ , Mn 3+ , Fe 2+ , Fe 3+ 、Co 2+ 、Ni 2+ , Cu 2+ and Sr 2+ One or more of the .

2. The complex for blocking dentinal tubules according to claim 1, characterized in that: The catecholamine is brown algae polyphenol.

3. The complex for blocking dentinal tubules according to claim 1 or 2, characterized in that: The metal ion is Sr 2+ .

4. The method for preparing the complex for blocking dentinal tubules according to any one of claims 1 to 3, characterized in that: The steps are: under aerobic alkaline conditions, catecholamines and metal ions are mixed and reacted to obtain the complex used for blocking dentinal tubules.

5. The preparation method according to claim 4, characterized in that: The mixing reaction time is 1-30 min.

6. The preparation method according to claim 4 or 5, characterized in that: The alkaline condition has a pH value of 7.4-11.

7. The preparation method according to claim 4, characterized in that: In the mixed solution obtained by mixing the catecholamine and the metal ion, the concentration of the catecholamine is 0.1-5 mg / mL; And / or, the concentration of the metal ions is 0.1-5 mg / mL.

8. An agent for treating dentin hypersensitivity, characterized in that: The invention comprises the complex for blocking dentinal tubules according to any one of claims 1 to 3 or the complex for blocking dentinal tubules obtained by the preparation method according to any one of claims 4 to 7.

9. The agent for treating dentin hypersensitivity according to claim 8, characterized in that Also includes: Effective amounts of basic amino acids in free or salt form, fluoride salts, anti-inflammatory compounds, anticalculus agents, surfactants, moisturizers, antimicrobial agents, antioxidants.

10. The agent for treating dentin hypersensitivity according to claim 9, characterized in that: The basic amino acid is arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutyric acid, diaminopropionic acid, salts thereof and / or combinations thereof.

11. The agent for treating dentin hypersensitivity according to claim 9, characterized in that The fluoride salt is one or more of stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, titanium fluoride and hexafluorosulfate.

12. The agent for treating dentin hypersensitivity according to claim 8 or 9, characterized in that: It also includes one or more of abrasives and particles.

13. The agent for treating dentin hypersensitivity according to claim 8 or 9, characterized in that: Also included are whitening agents selected from whitening actives.

14. The agent for treating dentin hypersensitivity according to claim 8 or 9, characterized in that: Also included is hydrogen peroxide or a source of hydrogen peroxide, wherein the source of hydrogen peroxide is urea peroxide, a peroxide salt or complex, or a hydrogen peroxide polymer complex.

15. The agent for treating dentin hypersensitivity according to claim 9 or 12, characterized in that: It also includes a polymer, which is selected from one or more of polyethylene glycol, polymethyl vinyl ether maleic acid copolymer and polysaccharide.

16. The agent for treating dentin hypersensitivity according to claim 9, characterized in that Also included is a calcium and phosphate source selected from the group consisting of a calcium-glass complex and a calcium-protein complex.

17. The agent for treating dentin hypersensitivity according to claim 9 or 12, characterized in that: Soluble calcium salts are also included.

18. The agent for treating dentin hypersensitivity according to claim 9, characterized in that Also included are agents that interfere with or prevent bacterial attachment.

19. The agent for treating dentin hypersensitivity according to claim 9 or 12, characterized in that: Also included are physiologically acceptable potassium salts.

20. The agent for treating dentin hypersensitivity according to claim 9, characterized in that The agent for treating dentin hypersensitivity is a toothpaste, a mouthwash, a medicine, a tooth gel, a tooth powder, a non-abrasive gel, a mousse, a foam, an oral spray, a lozenge, an oral tablet, a dental tool or a pet care product.

21. Use of the agent for treating dentin hypersensitivity according to any one of claims 8 to 20 in the preparation of a drug for treating dentin hypersensitivity.

22. Use of the agent for treating dentin hypersensitivity according to any one of claims 8 to 20 in the preparation of a drug for treating dental caries.

23. Use of the agent for treating dentin hypersensitivity according to any one of claims 8 to 20 in the preparation of a drug for treating tooth enamel damage.

24. A toothpaste comprising the agent for treating dentin hypersensitivity according to any one of claims 8 to 20, and further comprising one or more of water, abrasive, surfactant, foaming agent, vitamin, polymer, enzyme, humectant, thickener, antibacterial agent, preservative, flavoring agent and coloring agent.

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