Composition for repairing enamel damage as well as preparation method and application of composition

Abstract

The invention provides a composition for repairing tooth enamel damage and a preparation method and application thereof, and the composition for repairing tooth enamel damage comprises the following raw materials: glaze protein, procyanidine, a calcium ion source, a phosphate ion source and an orally acceptable carrier. According to the composition provided by the invention, by combining the glaze protein, the procyanidine and a biological remineralization technology, mineralized crystals can be induced to directionally grow along the damaged hydroxyapatite surface, a firmer structure is formed, remineralization is sustainable, and enamel is helped to be better repaired.

Description

Technical Field

[0001] This invention belongs to the field of enamel restoration technology, and in particular relates to a composition for repairing enamel damage, its preparation method and application. Background Technology

[0002] Dental caries, the most prevalent oral health problem worldwide, is the leading cause of enamel loss. In the development of caries, the incidence rate in the early demineralization stage (before cavities form) is significantly higher than in late-stage caries (when definite defects have formed). Since mature enamel lacks cell regeneration capacity and cannot repair itself once damaged, early intervention is crucial for caries prevention and control. At this stage, inducing the formation of hydroxyapatite externally to fill the micropores caused by demineralization holds promise for non-surgical reversal of caries lesions.

[0003] The basic building block of glaze is the glaze column, which contains hundreds of thousands of hydroxyapatite microcrystals oriented along the c-axis. This highly ordered crystal arrangement is the structural basis for the excellent mechanical strength, wear resistance, and hardness of glaze. Given that the main component of glaze is inorganic mineral, it becomes an ideal hard tissue that can be repaired or regenerated through chemical methods rather than cellular intervention.

[0004] Biomimetic mineralization, a biologically inspired material preparation strategy, refers to the process by which inorganic ions undergo nucleation and growth under the regulation of an organic matrix (such as collagen, amelogenin, and other biomolecules), forming biominerals with multi-level ordered structures under the combined control of the chemical environment, spatial framework, and structure guidance. For example, amelogenin has been proven to effectively promote the remineralization of tooth enamel surfaces. However, existing biomimetic mineralization technologies still face problems such as limited repair efficiency and unstable effects in practical applications. Therefore, developing more efficient and controllable new strategies for enamel repair remains an important direction of current research. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a composition for repairing enamel damage, its preparation method, and its application. The composition for repairing enamel damage provided by this invention can induce mineralized crystals to grow directionally along the damaged hydroxyapatite surface, forming a more robust structure, and enabling sustainable remineralization, thus helping to better repair enamel.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: On the one hand, this application provides a composition for repairing enamel damage, characterized in that the raw materials of the composition for repairing enamel damage include amelogenin, proanthocyanidins, calcium ion source, phosphate ion source, buffer, and oral-acceptable carrier.

[0007] The applicant discovered that: in this application, amelogenin and proanthocyanidins play an outstanding synergistic role in enamel repair. Amelogenin, as a "smart template," can self-assemble into nanospheres, precisely guiding the orderly arrangement of calcium and phosphorus ions to form hydroxyapatite crystals; while proanthocyanidins act as "molecular glue," stabilizing the amelogenin template through cross-linking, enhancing its adhesion to the tooth surface, and strengthening the density and hardness of the newly formed mineral layer. The combination of the two not only simulates the natural biomineralization process, but also creates a repair layer that is thicker, harder, and closer to natural enamel than a single component through molecular-level reinforcement, achieving a unity of biomimetic repair and performance enhancement.

[0008] Furthermore, the calcium ion source includes soluble calcium salts and insoluble calcium salts; In this application, the preferred calcium ion source is a mixture of soluble and insoluble calcium salts. This is mainly because soluble calcium salts have high solubility and can provide a sufficient calcium ion source, while insoluble calcium salts can act as crystal nuclei to promote mineralization during the mineralization process. The simultaneous addition of both can better repair tooth enamel.

[0009] Furthermore, the soluble calcium salt includes one or more of casein phosphopeptide-amorphous calcium phosphate, calcium gluconate, calcium citrate, calcium malate, calcium lactate, calcium glycerophosphate, calcium L-aspartate, calcium chloride, calcium nitrate, and calcium dihydrogen phosphate.

[0010] The insoluble calcium salts include one or more of tricalcium phosphate, octacalcium phosphate, calcium phosphosilicate, and hydroxyapatite.

[0011] Furthermore, the phosphate ion source includes one or more of trisodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, tripotassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium phosphate.

[0012] Further, the buffer includes one or more of HEPES buffer, MES buffer, PIPES buffer, MOPS buffer, Bicine buffer, Tris buffer, TES buffer, Tricine buffer, and sodium dihydrogen phosphate-disodium hydrogen phosphate buffer. Furthermore, the mass ratio of the amelogenin to the proanthocyanidins is 1:0.5-1.5; Specifically, the mass ratio of amelogenin to proanthocyanidins can be 1:0.5, 1:0.8, 1:1, 1:1.2, or 1:1.5. Furthermore, the molar ratio of calcium ions in the calcium ion source to phosphate ions in the phosphate ion source is 3.6-5:3; Specifically, the molar ratio of calcium ions in the calcium ion source to phosphate ions in the phosphate ion source can be 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, or 5:3. Furthermore, the mass ratio of the amelogenin to the orally acceptable carrier is 1:10-70; Specifically, the mass ratio of the amelogenin to the orally acceptable carrier can be 1:10, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, or 1:70. Furthermore, the mass ratio of the amelogenin to the calcium ions in the calcium ion source is 1:300-800; Specifically, the mass ratio of the amelogenin to the calcium ions in the calcium ion source is 1:300, 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650, 1:700, 1:750, or 1:800. Furthermore, the orally acceptable carrier includes one or more of carbomer, povidone, sodium hyaluronate, alginate, and poloxamer; Furthermore, the carrier exists in the form of a hydrogel, wherein the mass ratio of the carrier to water in the hydrogel is 1:300-1000; Specifically, the mass ratio of the carrier to water in the hydrogel can be 1:300, 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650, 1:700, 1:750, 1:800, 1:850, 1:900, 1:950, or 1:1000.

[0013] On the other hand, this application also provides a method for preparing a composition for repairing enamel damage, characterized in that the preparation method includes the following steps: Step (1): Prepare hydrogel; Step (2): Dissolve amelogenin and proanthocyanidins in buffer solution to obtain mixture 1. Then, add mixture 1 dropwise to hydrogel and shake well to obtain mixture 2. Then, add calcium ion source and phosphate ion source to mixture 2 and shake well. Adjust the pH value to 7.5±0.5 to obtain a composition for repairing tooth enamel damage.

[0014] Furthermore, the calcium ion source includes soluble calcium salts and insoluble calcium salts; Furthermore, the soluble calcium salt includes one or more of casein phosphopeptide-amorphous calcium phosphate, calcium gluconate, calcium citrate, calcium malate, calcium lactate, calcium glycerophosphate, calcium L-aspartate, calcium chloride, calcium nitrate, and calcium dihydrogen phosphate. Furthermore, the sparingly soluble calcium salt includes one or more of tricalcium phosphate, octacalcium phosphate, calcium phosphosilicate, and hydroxyapatite.

[0015] Furthermore, the phosphate ion source includes one or more of trisodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, tripotassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium phosphate. Further, the buffer solution includes one or more of HEPES buffer, MES buffer, PIPES buffer, MOPS buffer, Bicine buffer, Tris buffer, TES buffer, Tricine buffer, and sodium dihydrogen phosphate-disodium hydrogen phosphate buffer.

[0016] Furthermore, the mass ratio of the amelogenin to the proanthocyanidins is 1:0.5-1.5; Specifically, the mass ratio of amelogenin to proanthocyanidins can be 1:0.5, 1:0.8, 1:1, 1:1.2, or 1:1.5. Furthermore, the molar ratio of calcium ions in the calcium ion source to phosphate ions in the phosphate ion source is 3.6-5:3; Specifically, the molar ratio of calcium ions in the calcium ion source to phosphate ions in the phosphate ion source can be 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, or 5:3. Furthermore, the mass ratio of the amelogenin to the calcium ions in the calcium ion source is 1:300-800; Specifically, the mass ratio of the amelogenin to the calcium ions in the calcium ion source is 1:300, 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650, 1:700, 1:750, or 1:800. Further, the steps for preparing the hydrogel are as follows: take 0.1-0.3 parts by weight of the carrier and slowly add it to 70-90 parts by weight of H2O under stirring. After stirring evenly, let it stand at 20-30℃ for 12-36 h. Then filter it and stop when the pH is adjusted to about 7. Then add H2O until the total mass of added H2O is 100 parts by weight to obtain the hydrogel. Furthermore, the carrier includes one or more of carbomer, povidone, sodium hyaluronate, alginate, and poloxamer; Furthermore, the mass ratio of the amelogenin to the carrier is 1:10-70; Specifically, the mass ratio of the amelogenin to the carrier can be 1:10, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, or 1:70. Furthermore, the carrier exists in the form of a hydrogel, wherein the mass ratio of the carrier to water in the hydrogel is 1:300-1000; Specifically, the mass ratio of the carrier to water in the hydrogel can be 1:300, 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650, 1:700, 1:750, 1:800, 1:850, 1:900, 1:950, or 1:1000.

[0017] Furthermore, this application also provides the use of the above-mentioned composition for repairing enamel damage in the preparation of enamel restoration products.

[0018] The beneficial effects of this invention are: This invention provides a composition for repairing tooth enamel damage, its preparation method, and its application. The raw materials of the composition include amelogenin, proanthocyanidins, a calcium ion source, a phosphate ion source, and an orally acceptable carrier. The composition provided by this invention, by combining amelogenin, proanthocyanidins, and bioremineralization technology, can induce mineralized crystals to grow directionally along the damaged hydroxyapatite surface, forming a more robust structure and enabling sustainable remineralization, thus aiding in better enamel repair. Attached Figure Description

[0019] Figure 1 Field emission scanning electron microscope (FESEM) image of the dental radiograph after treatment with the composition prepared in Example 1; Figure 2 Field emission scanning electron microscope (FESEM) image of the dental radiograph after treatment with the composition prepared in Comparative Example 1; Figure 3 Field emission scanning electron microscope (FESEM) image of the dental radiograph after treatment with the composition prepared in Comparative Example 2; Figure 4 Field emission scanning electron microscope (FESEM) image of the dental radiograph after treatment with the composition prepared in Comparative Example 3; Figure 5 This is a diagram showing the test locations when performing elemental analysis on a remineralized coating using an X-ray energy dispersive spectroscopy (EDS) analyzer. Detailed Implementation

[0020] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to limit the invention. In the description of this application, it should be understood that "and / or" describes the relationship between related objects, indicating that three relationships may exist. For example, A and / or B can represent: A alone, A and B simultaneously, or B alone. Where A and B can be singular or plural.

[0022] Example 1 This embodiment provides a composition for repairing tooth enamel damage and its preparation method, the specific steps of which are as follows: (1) Take 0.2g of carbomer and slowly add it to 80ml of ddH2O under stirring. After stirring evenly, let it stand at 25℃ for 24h. Then filter it with a 0.45μm filter. Next, add 1mol / L NaOH solution dropwise under stirring, and measure the pH while adding. Stop adding NaOH solution when the pH is about 7. Then add ddH2O to 100ml to obtain carbomer hydrogel. (2) Dissolve amelogenin and proanthocyanidins in 20 mmol / L HEPES buffer (pH about 7.4) to obtain a mixture 1 with a concentration of 2 mg / mL of amelogenin and proanthocyanidins. Then, take 0.2 mL of the above mixture 1 and add it to 5 mL of carbomer hydrogel and shake well to obtain mixture 2. Then, take KH2PO4 (3.3 mmol), calcium gluconate (5.4 mmol) and tricalcium phosphate (0.1 mmol) and add them to mixture 2. After shaking well, adjust the pH value to 7.6 with 1 mol / L NaOH solution to obtain the composition for repairing tooth enamel damage.

[0023] Example 2 This embodiment provides a composition for repairing tooth enamel damage and its preparation method, the specific steps of which are as follows: (1) Take 0.2g of carbomer and slowly add it to 80ml of ddH2O under stirring. After stirring evenly, let it stand at 25℃ for 24h. Then filter it with a 0.45μm filter. Next, add 1mol / L NaOH solution dropwise under stirring, and measure the pH while adding. Stop adding NaOH solution when the pH is about 7. Then add ddH2O to 100ml to obtain carbomer hydrogel. (2) Dissolve amelogenin and proanthocyanidins in 20 mmol / L HEPES buffer (pH about 7.4) to obtain a mixture 1 with amelogenin and proanthocyanidin concentrations of 2 mg / mL and 1 mg / mL, respectively. Then, take 0.2 mL of the above mixture 1 and add it to 5 mL of carbomer hydrogel and shake well to obtain mixture 2. Then, take KH2PO4 (3.3 mmol), calcium gluconate (5.4 mmol) and tricalcium phosphate (0.1 mmol) and add them to mixture 2. After shaking well, adjust the pH value to 7.6 with 1 mol / L NaOH solution to obtain the composition for repairing tooth enamel damage.

[0024] Example 3 This embodiment provides a composition for repairing tooth enamel damage and its preparation method, the specific steps of which are as follows: (1) Take 0.2g of carbomer and slowly add it to 80ml of ddH2O under stirring. After stirring evenly, let it stand at 25℃ for 24h. Then filter it with a 0.45μm filter. Next, add 1mol / L NaOH solution dropwise under stirring, and measure the pH while adding. Stop adding NaOH solution when the pH is about 7. Then add ddH2O to 100ml to obtain carbomer hydrogel. (2) Dissolve amelogenin and proanthocyanidins in 20 mmol / L HEPES buffer (pH about 7.4) to obtain a mixture 1 with amelogenin and proanthocyanidin concentrations of 2 mg / mL and 3 mg / mL, respectively. Then, take 0.2 mL of the above mixture 1 and add it to 5 mL of carbomer hydrogel and shake well to obtain mixture 2. Then, take KH2PO4 (3.3 mmol), calcium gluconate (5.4 mmol) and tricalcium phosphate (0.1 mmol) and add them to mixture 2. After shaking well, adjust the pH value to 7.6 with 1 mol / L NaOH solution to obtain the composition for repairing tooth enamel damage.

[0025] Comparative Example 1 Compared with Example 1, the only difference is that only amelogenin is used, that is, the mixture 1 obtained in step (2) is an amelogenin solution with a concentration of 4 mg / mL.

[0026] Comparative Example 2 Compared with Example 1, the only difference is that only proanthocyanidins are used, that is, the mixture 1 obtained in step (2) is a proanthocyanidin solution with a concentration of 4 mg / mL.

[0027] Comparative Example 3 Compared with Example 1, the only difference is that “calcium gluconate (5.4 mmol) and tricalcium phosphate (0.1 mmol)” in step (2) is replaced with “calcium gluconate (5.5 mmol)”.

[0028] Test Analysis (1) Field emission scanning electron microscopy (FE-SEM) analysis and compositional analysis Preparation of dental radiographs: Freshly extracted human third molars (with intact crowns, no pigmentation, and no caries) were used. Slices approximately 5mm x 5mm were cut from the enamel surface of the crown. The slices were then polished sequentially with 400, 600, 800, 1000, and 1200 grit sandpaper. Next, the slices were ultrasonically cleaned for 5 minutes each with a detergent, acetone, and anhydrous ethanol, followed by rinsing three times with deionized water. To simulate acid erosion, the slices were etched with 37% phosphoric acid for 1 minute, immediately followed by rinsing with deionized water. The slices were then ultrasonically cleaned with deionized water for 5 minutes and allowed to air dry at room temperature to obtain the radiographs for later use.

[0029] Preparation of artificial saliva: The formula for artificial saliva is as follows: 0.2 mmol / L MgCl2, 1 mmol / L CaCl2·H2O, 20 mmol / L HEPES buffer, 4 mmol / L KH2PO4, 16 mmol / L KCl, 4.5 mmol / L NH4Cl, 300 p.pm NaF, 0.1 mol / L NaOH, and 0.1 mol / L HCl to adjust the pH to 7.6. Artificial saliva needs to be prepared daily and used immediately.

[0030] According to a volume ratio of V (composition):V (artificial saliva) = 1:3, the compositions prepared in Example 1 and Comparative Examples 1-3 were dispersed in artificial saliva to obtain soaking solutions. Dental slides were then taken and immersed in the aforementioned soaking solutions for 2 minutes, removed, and then immersed in artificial saliva for biomineralization at 37°C. The artificial saliva was changed daily. During the mineralization process, the dental slides were removed from the artificial saliva daily, rinsed with ultrapure water, immersed in the aforementioned soaking solution for 2 minutes, and then transferred back to the artificial saliva. This process was repeated twice daily. After 14 days, the planar morphology of the remineralized enamel coating was observed using field emission scanning electron microscopy, and elemental analysis of the remineralized coating was performed using energy dispersive X-ray spectroscopy.

[0031] Field emission scanning electron microscopy (FE-SEM) analysis and testing standard: JY / T 0584-2020. After the sample surface was plated with Pt25s, it was placed in the sample chamber of a scanning electron microscope (model: SIGMA 500) according to standard operating procedures for magnified observation of the test location (results are shown in the attached figure). Figure 1-4 The remineralized coating was subjected to elemental analysis using an X-ray energy dispersive spectroscopy (EDS) analyzer (model: 51-XMX1121), with the testing standard being GB / T 17359-2023. The test locations are shown in the attached diagram. Figure 5 The average values ​​of C, O, P and Ca elements in test locations 001-005 were calculated respectively. The detailed test results are shown in Table 1.

[0032] After dental X-rays are etched with acid, they will appear as black cavities under an electron microscope. These black cavities will be filled in after restoration, so fewer black cavities indicate a better restoration effect. Figures 1-4 It can be seen that, Figure 1 The absence of black cavities indicates that the composition described in this application can achieve a superior repair effect.

[0033] Table 1. Component Analysis Table C O P Ca Example 1 0.57 46.29 18.04 35.10 Comparative Example 1 0.57 45.69 18.22 35.52 Comparative Example 2 0.63 45.61 18.29 35.47 Comparative Example 3 0.58 45.78 18.10 35.54 Since enamel mineralization does not directly form hydroxyapatite in the early stages, but rather transforms from tricalcium phosphate (with a higher oxygen content) to octacalcium phosphate, and then finally to hydroxyapatite; simultaneously, carbonate apatite with a higher oxygen content is also formed during the mineralization process. Therefore, the formation of a mineralized layer can be determined by analyzing the oxygen content in the remineralized coating. As shown in Table 1, the elemental analysis results in Example 1 show an increased oxygen content, indicating that a mineralized layer was indeed formed compared to hydroxyapatite.

[0034] (2) Vickers hardness test The effects of remineralization and enamel repair on tooth enamel were explored by detecting the change in hardness of demineralized tooth enamel before and after remineralization treatment. The specific experimental steps are as follows. A. Preparation of enamel blocks: A total of 20 human teeth with intact enamel, smooth surface, and no white spots, cracks, defects, or caries were selected. Using a high-speed bur, 20 enamel blocks were prepared from the crown portion. The sample size was approximately 4 mm × 4 mm. The surface was polished as smooth and flat as possible. Then, the above 20 samples were embedded and numbered with acrylic resin. B. Determine the initial hardness of the sample: The measurement conditions are 300 g for 15 seconds; 4 indentation points are measured for each sample, which are evenly distributed and spaced at least 1 mm apart. The distance between each indentation point and the edge of the tooth block is at least 0.5 mm. The final hardness of the sample is the average of the 4 points. The Vickers hardness range of the enamel sample is 230 HV-350 HV. C. Artificial Caries Demineralization Preparation: Twenty intact 4mm×4mm dental prostheses, prepared earlier, were placed in 250mL of artificial demineralization solution and continuously immersed in a 37℃ constant temperature shaker for 4 days to induce artificial caries. The hardness values ​​of all 20 samples were significantly reduced compared to the initial values. The 20 enamel samples were randomly divided into 4 groups: an experimental group and a control group. Artificial demineralization solution finished product (Dongguan Chuangfeng Automation Technology Co., Ltd.): pure water, CaCl2, sodium dihydrogen phosphate, acetic acid; D. Remineralization Experiment: The experimental group consisted of the composition prepared in Example 1, and the control group consisted of the compositions prepared in Comparative Examples 1-3. The samples were immersed in a soaking solution (prepared at a volume ratio of V(composition):V(artificial saliva) = 1:10) on a 37°C constant-temperature shaker for 1 hour each time, twice a day for 7 consecutive days. During the remaining time, the samples were rinsed with ultrapure water and then stored in artificial saliva (on a 37°C constant-temperature shaker). After the experiment, the samples were removed, dried, and subjected to micro-Vickers hardness testing. The results are shown in Table 2. Preparation of artificial saliva: The formula for artificial saliva is as follows: 0.2 mmol / L MgCl2, 1 mmol / L CaCl2·H2O, 20 mmol / L HEPES buffer, 4 mmol / L KH2PO4, 16 mmol / L KCl, 4.5 mmol / L NH4Cl, 300 p.pm NaF, 0.1 mol / L NaOH, and 0.1 mol / L HCl to adjust the pH to 7.6. Artificial saliva needs to be prepared daily and used immediately.

[0035] Table 2 Results of Micro Vickers Hardness Test After demineralization After remineralization Increased value Increase rate Example 1 146.32 198.32 52 35.54% Comparative Example 1 145.79 169.56 23.77 16.30% Comparative Example 2 146.78 158.60 11.82 8.05% Comparative Example 3 146.01 171.89 25.88 17.72% The experimental results above show that, compared with comparative examples 1-3, the solution provided in this application has significantly improved hardness, meaning that the product described in this application can achieve better technical results.

[0036] The above provides a detailed description of a composition for repairing enamel damage, its preparation method, and its application. Specific examples have been used to illustrate the principles and implementation methods of this application. The descriptions of the above embodiments are only for the purpose of helping to understand the technical solutions and core ideas of this application. Those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. These modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A composition for repairing tooth enamel damage, characterized in that, The raw materials of the composition for repairing enamel damage include amelogenin, proanthocyanidins, calcium ion source, phosphate ion source, buffer, and oral-acceptable carrier.

2. The composition for repairing enamel damage according to claim 1, characterized in that, The calcium ion source includes soluble calcium salts and insoluble calcium salts; Optionally, the soluble calcium salt includes one or more of casein phosphopeptide-amorphous calcium phosphate, calcium gluconate, calcium citrate, calcium malate, calcium lactate, calcium glycerophosphate, calcium L-aspartate, calcium chloride, calcium nitrate, and calcium dihydrogen phosphate, and the insoluble calcium salt includes one or more of tricalcium phosphate, octacalcium phosphate, calcium phosphosilicate, and hydroxyapatite.

3. The composition for repairing enamel damage according to claim 1, characterized in that, The phosphate ion source includes one or more of trisodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, tripotassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium phosphate.

4. The composition for repairing enamel damage according to claim 1, characterized in that, The buffer includes one or more of the following: HEPES buffer, MES buffer, PIPES buffer, MOPS buffer, Bicine buffer, Tris buffer, TES buffer, Tricine buffer, and sodium dihydrogen phosphate-disodium hydrogen phosphate buffer.

5. The composition for repairing enamel damage according to claim 1, characterized in that, The mass ratio of amelogenin to proanthocyanidins is 1:0.5-1.5; And / or, the molar ratio of calcium ions in the calcium ion source to phosphate ions in the phosphate ion source is 3.6-5:3; And / or, the mass ratio of the amelogenin to the oral-acceptable carrier is 1:10-70; And / or, the mass ratio of the amelogenin to the calcium ions in the calcium ion source is 1:300-800.

6. The composition for repairing enamel damage according to claim 1, characterized in that, The orally acceptable carriers include one or more of carbomer, povidone, sodium hyaluronate, alginate, and poloxamer; Optionally, the carrier exists in the form of a hydrogel, wherein the mass ratio of the carrier to water in the hydrogel is 1:300-1000.

7. A method for preparing a composition for repairing tooth enamel damage, characterized in that, The preparation method includes the following steps: Step (1): Prepare hydrogel; Step (2): Dissolve amelogenin and proanthocyanidins in buffer solution to obtain mixture 1. Then, add mixture 1 dropwise to hydrogel and shake well to obtain mixture 2. Then, add calcium ion source and phosphate ion source to mixture 2 and shake well. Adjust the pH value to 7.5±0.5 to obtain a composition for repairing tooth enamel damage.

8. The method for preparing the composition for repairing enamel damage according to claim 7, characterized in that, The calcium ion source includes soluble calcium salts and insoluble calcium salts; optionally, the soluble calcium salts include one or more of casein phosphopeptide-amorphous calcium phosphate, calcium gluconate, calcium citrate, calcium malate, calcium lactate, calcium glycerophosphate, L-aspartate calcium, calcium chloride, calcium nitrate, and calcium dihydrogen phosphate. The sparingly soluble calcium salts include one or more of tricalcium phosphate, octacalcium phosphate, calcium phosphosilicate, and hydroxyapatite. The phosphate ion source includes one or more of the following: trisodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, tripotassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium phosphate. The buffer solution includes one or more of the following: HEPES buffer, MES buffer, PIPES buffer, MOPS buffer, Bicine buffer, Tris buffer, TES buffer, Tricine buffer, and sodium dihydrogen phosphate-disodium hydrogen phosphate buffer.

9. The method for preparing the composition for repairing enamel damage according to claim 7, characterized in that, The mass ratio of amelogenin to proanthocyanidins is 1:0.5-1.5; The molar ratio of calcium ions in the calcium ion source to phosphate ions in the phosphate ion source is 3.6-5:3; The mass ratio of the amelogenin to the calcium ions in the calcium ion source is 1:300-800. The steps for preparing the hydrogel are as follows: 0.1-0.3 parts by weight of carrier are slowly added to 70-90 parts by weight of H2O under stirring. After stirring evenly, the mixture is allowed to stand at 20-30℃ for 12-36 h. Then, the mixture is filtered and the pH is adjusted to about 7 before stopping. Next, H2O is added until the total mass of added H2O is 100 parts by weight to obtain the hydrogel. The carrier includes one or more of carbomer, povidone, sodium hyaluronate, alginate, and poloxamer. The mass ratio of amelogenin to the carrier is 1:10-70.

10. The use of the composition for repairing enamel damage according to any one of claims 1-6 or the composition prepared by the preparation method according to any one of claims 7-9 in the preparation of enamel repair products.

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