Preparation method of multifunctional toothpaste HA material

Abstract

The application provides a preparation method of a multifunctional toothpaste HA material, and under the premise of taking double-stage hydroxyapatite as a main efficacy component of the toothpaste, the toothpaste shows excellent properties in terms of anti-cariogenic bacteria performance, bacteriostatic performance and promotion of enamel remineralization, and under the condition of taking an ionic liquid+water as an electrolyte, the electrochemical preparation of the double-stage hydroxyapatite also has the characteristics of simple process, high cost performance, non-toxicity, no environmental pollution and convenience for industrialization.

Description

TECHNICAL FIELD

[0001] The present application relates to toothpaste production technical field, in particular to a toothpaste with whitening, caries prevention, anti-allergy, anti-inflammatory and other functions and its preparation method, especially the preparation method of HA material. BACKGROUND

[0002] Toothpaste is a daily necessity for people, and its main function is to clean teeth and maintain oral health. With the continuous improvement of people's living standards, the importance of oral hygiene and its disease prevention and treatment are increasingly valued by people. Toothpaste can be divided into ordinary toothpaste and medicinal toothpaste according to its function. Medicinal toothpaste accounts for a considerable market share as an auxiliary means for preventing and treating oral diseases, and it can be further divided into caries prevention toothpaste, anti-allergy toothpaste, anti-inflammatory and hemostatic toothpaste, anti-stone toothpaste, anti-bad breath toothpaste, anti-ulcer toothpaste, etc.

[0003] In the development of oral care products, one of the development trends in recent decades is to add different active ingredients to toothpaste to achieve different effects. At present, the drugs contained in the anti-dentin sensitivity toothpaste made according to the concept of "blocking dentin tubules" mainly include fluoride, calcium oxalate, calcium carbonate-phosphate, silver chloride, silver iodide, HA, etc. Among them, HA is the main inorganic component of dental hard tissue, has good biocompatibility, non-toxicity, and no harm, etc., and can naturally repair the open dentin tubules, so it has become a research hotspot of active ingredients added in anti-sensitivity toothpaste.

[0004] Dental caries is one of the most common diseases in humans, and it ranks first in the incidence of various diseases. Dental caries is a complex biofilm-mediated chronic progressive destructive disease, mainly due to the production of acid by oral bacteria using sugar metabolism, leading to destruction of dental hard tissue. Enamel is located on the outermost layer of the tooth, which is an ordered highly mineralized mineral structure mainly composed of acellular minerals. Healthy enamel contains about 95% minerals, 1% organic matter and 4-5% water. There is a constant chemical equilibrium between the solid crystalline hydroxyapatite (HAP) in the enamel and the dissolved hydroxyapatite (free calcium and phosphate ions) in the plaque fluid. When the pH value of the plaque is lower than the critical value 5.2-5.5, net mineral crystal dissolution occurs, i.e. tooth demineralization. When the mineral dissolves, the defects in the mineral lattice increase, and the enamel surface becomes loose and porous, and the mineralization degree decreases. Enamel remineralization is the process of re-forming HAP crystals on the carious enamel surface, and the remineralization process is affected by factors such as Ca 2+ , PO4 3− , F − and pH value of the plaque in saliva. The Ca 2+And PO43- is the basis of remineralization, the higher the concentration, the more conducive to the occurrence of remineralization. The key to prevent tooth demineralization is to increase the concentration of Ca 2+ , PO4 3− ions in oral saliva, and to promote the dissolution-precipitation balance of HAP to form HAP crystals. High-activity nano-HAP not only neutralizes acidic substances in the oral cavity, but also greatly increases the concentration of Ca 2+ , PO4 3− ions in saliva, which has good remineralization effect.

[0005] HAP microparticles can be used as a bioactive additive in toothpaste, easily adsorbed and filled on the surface of carious enamel, promoting the remineralization of damaged enamel, repairing damaged enamel through daily oral care, enhancing the acid erosion resistance, and preventing caries. SUMMARY

[0006] Based on the above, the present application provides a preparation method of HA material in multifunctional toothpaste, especially by electrochemical deposition method, a two-stage hydroxyapatite is prepared in one step, the first stage is nanoscale rod-shaped strontium-containing hydroxyapatite deposited by cathode, and the second stage is micron-sized spherical shell-shaped strontium-containing hydroxyapatite deposited by collision in electrolyte. Under the premise of using two-stage hydroxyapatite as the main functional component of toothpaste, the toothpaste shows excellent properties in terms of anti-cariogenic bacteria performance, bacteriostatic performance, and promotion of enamel remineralization. Moreover, under the condition of using ionic liquid + water as electrolyte, the electrochemically prepared two-stage hydroxyapatite has the characteristics of simple process, high cost performance, non-toxicity, no environmental pollution, and easy industrialization.

[0007] The preparation method of hydroxyapatite HA material is prepared by the following steps:

[0008] (1) Mix choline chloride and malonic acid according to the ratio, heat to obtain an ionic liquid;

[0009] (2) Add deionized water to the ionic liquid obtained in step (1) according to the ratio to obtain a mixed solution;

[0010] (3) Add 2-5 g / L micron carbon spheres, 10-20 mmol / L calcium nitrate, 5-10 mmol / L dihydrogen phosphate, 1-2 mmol / L strontium chloride, 0.01 mol / L sodium chloride and 1-2 g / L EDTA to the mixed solution obtained in step (2) according to the ratio, heat to dissolve, to obtain an electrolyte;

[0011] (4) Pour the prepared electrolyte into an insulating reaction kettle, take 30CrNiMoVA steel as the cathode and Mo70Cu30 alloy as the anode, the distance between the electrodes is 30-50 mm, open the nitrogen inlet and outlet valves, pre-charge nitrogen to exhaust air for 3-5 min, close the nitrogen outlet valve, charge nitrogen to 2-3 MPa as indicated by the pressure gauge, close the nitrogen inlet valve, open the power supply, apply a bidirectional pulse power supply, the positive pulse voltage is 70-80 V, the negative pulse voltage is 10-15 V, the pulse frequency is 200-300 Hz, the duty cycle is 10-15%, the temperature is raised to 70-90 DEG C at a rate of 3-5 DEG C / min, the magnetic stirring speed is 200-300 rpm, and the time is 60-120 min;

[0012] (5) Turn off the power supply and naturally cool to room temperature;

[0013] (6) Take out the cathode and scrape the powder, and then perform ball milling treatment on the obtained powder to obtain nanoscale rod-shaped strontium-containing hydroxyapatite;

[0014] (7) Centrifuge, filter, wash and dry the micrometer carbon spheres in the electrolyte, and then perform muffle high-temperature treatment to obtain micrometer spherical shell-shaped strontium-containing hydroxyapatite.

[0015] The molar ratio of choline chloride and malonic acid is 1:2.

[0016] The amount of deionized water used in step (2) is 200-300 mL.

[0017] The size of the micrometer carbon spheres is 5-10 mu m.

[0018] The length of the nanoscale rod-shaped strontium-containing hydroxyapatite is 200-300 nm; the size of the micrometer spherical shell-shaped strontium-containing hydroxyapatite is 5-15 mu m, and the hollow size is 5-10 mu m.

[0019] The ball milling treatment uses zirconium oxide as the grinding ball and anhydrous ethanol as the medium to perform wet grinding.

[0020] The electrolyte in step (7) is centrifuged at a speed of 5000-7000 r / min.

[0021] The washing is performed by using ethanol and deionized water for multiple times in sequence, and the drying is performed at 60-70 DEG C under vacuum.

[0022] The muffle high-temperature treatment is performed by increasing the temperature to 500-550 DEG C at a rate of 5-7 DEG C / min, maintaining for 2-3 h, and naturally cooling to room temperature.

[0023] The nanoscale rod-shaped strontium-containing hydroxyapatite and the micrometer spherical shell-shaped strontium-containing hydroxyapatite are mixed at a mass ratio of 1:(2-3) and used for the preparation of toothpaste.

[0024] An anti-tooth decay whitening toothpaste composition consisting of the following ingredients in percentage by weight:

[0025] Repairing agent: nano-sized rod-shaped strontium-containing hydroxyapatite and micro-sized spherical shell-shaped strontium-containing hydroxyapatite 8-14%;

[0026] Friction agent: natural calcium carbonate 20-30%;

[0027] Friction agent: silicon dioxide 3-5%;

[0028] Binder: sodium hydroxymethyl cellulose 0.6-0.8%;

[0029] Binder: hydroxypropyl guar gum 18-20%;

[0030] Moisturizing agent: sorbitol 15-20%

[0031] Surfactant: sodium dodecyl sulfate 2.2-2.4%;

[0032] Preservative: sodium benzoate 0.3-0.5%;

[0033] Sweetener: sodium saccharin 0.1-0.3%;

[0034] Anti-allergic agent: potassium nitrate 2-4%;

[0035] Essence: fruit essence 0.8-1%;

[0036] Deionized water to 100.

[0037] Further, the mass ratio of nano-sized rod-shaped strontium-containing hydroxyapatite and micro-sized spherical shell-shaped strontium-containing hydroxyapatite is 1: (2~3).

[0038] Further, the length of the nano-sized rod-shaped strontium-containing hydroxyapatite is 200-300 nm.

[0039] Further, the size of the micro-sized spherical shell-shaped strontium-containing hydroxyapatite is 5-15 μm, and the hollow size is 5-10 μm.

[0040] The preparation method of the whitening toothpaste comprises the following steps:

[0041] (1) In a vacuum paste machine, quickly disperse sodium hydroxymethyl cellulose and hydroxypropyl guar gum into part of the sorbitol solution, add sodium saccharin, sodium nitrate deionized water solution, and high-speed stirring to form a uniform paste;

[0042] (2) Then add natural calcium carbonate, silicon dioxide, sodium dodecyl sulfate, sodium benzoate to the paste, add fruit essence and high-speed stirring, vacuum degassing to form a toothpaste base;

[0043] (3) The nanometer-sized rod-shaped strontium-containing hydroxyapatite and the micron-sized spherical shell-shaped strontium-containing hydroxyapatite are uniformly dispersed in sorbitol in a certain proportion, and then are added into the toothpaste base through high-speed stirring;

[0044] (4) Finally, the uniform toothpaste product is prepared through vacuum degassing.

[0045] The stirring speed is 200-1000 rpm, and the stirring time is 10-15 min.

[0046] The degassing time is 10-12 min, and the vacuum degree is -1±0.05 Mpa.

[0047] The toothpaste of the present application comprises repairing agent, abrasive agent, adhesive, humectant, surfactant, preservative, sweetener, anti-allergic agent, and essence. The abrasive agent requires proper fineness (generally 10-40 μm), proper hardness (Mohs hardness value 2-3, lower than tooth enamel), and abrasion value (RDA lower than 250), and the appearance is white, uniform, fine, comfortable, safe, non-toxic, chemically stable, and does not react with other components, and has low solubility.

[0048] The humectant requires hygroscopicity, can significantly reduce the freezing point of the paste, stabilize the viscosity of the paste, and has a pleasant sweet taste. The role of the humectant in the toothpaste is anti-freezing and moisture retention. Due to the hygroscopicity, the evaporation of water in the paste is slowed down. Any concentration of sorbitol solution exposed to air absorbs or releases water until the concentration reaches the equilibrium with the air humidity.

[0049] The adhesive requires a three-dimensional spatial network structure, proper viscosity and thixotropy, easy swelling and dispersion during production, no particle or lump formation, good compatibility with other raw materials, no odor, and good anti-enzyme ability.

[0050] The surfactant for toothpaste is sodium dodecyl sulfate, which is an anionic surfactant and becomes an aqueous phase after being dissolved in water. The essence is an oil phase. The two phases form an emulsion after contact and stirring, i.e. the oil is dispersed in the water. Sodium dodecyl sulfate is an excellent emulsifier, which forms a relatively firm film around the dispersed phase droplets, prevents the droplets from coalescing, and forms a stable emulsion. In addition, it can improve the surface adsorption state of the abrasive agent and improve the dispersibility.

[0051] Hydroxyapatite (HA) is the main inorganic component of human bone and teeth. The HA synthesized in the present application has a crystal form and structure very similar to that of HAP in bone, has the function of adsorbing protein, amino acid, lipid, and dextran, and can promote the remineralization of the surface of tooth enamel and enhance the anti-caries ability of enamel. Hydroxyapatite has good biocompatibility with alveolar bone, can promote the repair of defective alveolar bone, and effectively prevents alveolar bone absorption and atrophy. Therefore, the present application uses HA as a tooth enamel remineralization material.

[0052] Both enamel and dentin can absorb strontium, and the sensitivity of dentin to strontium is far more than that of enamel. Strontium reacts with calcium carbonate in tooth to form strontium carbonate (SrCO3), and reacts with hydroxyapatite in dentin to form strontium hydroxyapatite, thereby enhancing the acid resistance of teeth. Strontium can also combine with other organic matters in dentin (such as oxyhemoglobin), penetrate into deep part of teeth, and significantly reduce the permeability of hard tissue of teeth, thereby playing an acid-resistant and desensitizing role. Based on this, strontium-doped hydroxyapatite can calm nerves and desensitize, slow down the transmission of cytoplasmic processes of odontoblast cells, and accelerate the formation of secondary dentin, thereby playing a desensitizing and analgesic role.

[0053] Based on the above, the present application uses strontium-doped hydroxyapatite as a main functional component for improving the remineralization effect of teeth. Two kinds of abrasive agents, toothpaste-grade natural calcium carbonate and silicon dioxide, are selected to improve the fineness and gloss of the paste. Sodium hydroxymethyl cellulose and hydroxypropyl guar gum are selected as binders. An anionic surfactant, sodium dodecyl sulfate, is selected as a surfactant. Sorbitol is selected as a humectant. Fruit essence and sodium saccharin are selected to improve the taste. Food-grade potassium nitrate and sodium benzoate are used as additives.

[0054] The toothpaste prepared in the embodiment of the present application is tested according to GB8372-2001. The paste is clean, uniform, fine, and normal in color and luster. The pH is 8.24. The room temperature consistency is 16 mm. The heat-resistant consistency is 17 mm. The foam volume is 152.4 mm. The stability is that the paste does not overflow the nozzle and does not separate water. The smell and color are normal. The bacterial detection is that the fecal coliform group is negative, the green pyocyanin is negative, and the staphylococcus aureus is negative, which meets the requirements of GB8372-2001.

[0055] In addition, the present application simultaneously prepares micro-nano hydroxyapatite with different morphologies by using an electrochemical method. The following steps are used to prepare the same:

[0056] (1) Chlorocholine and malonic acid are mixed according to the ratio and heated to obtain an ionic liquid;

[0057] (2) Deionized water is added to the ionic liquid obtained in step (1) according to the ratio to obtain a mixed solution;

[0058] (3) 2-5 g / L of micron carbon balls, 10-20 mmol / L of calcium nitrate, 5-10 mmol / L of phosphonium diamine, 1-2 mmol / L of strontium chloride, 0.01 mol / L of sodium chloride, and 1-2 g / L of EDTA are added to the mixed solution obtained in step (2) according to the ratio and heated to dissolve to obtain an electrolyte;

[0059] (4) Pour the prepared electrolyte into the insulating reaction kettle, take 30CrNiMoVA steel as the cathode, take Mo70Cu30 alloy as the cathode, the inter-electrode distance is 30-50mm, open the nitrogen inlet and outlet valves, pre-charge nitrogen to exhaust air for 3-5min, close the nitrogen outlet valve, charge nitrogen to 2-3Mpa as read by the pressure gauge, close the nitrogen inlet valve, open the power supply, apply a bidirectional pulse power supply, the positive pulse voltage is 70-80V, the negative pulse voltage is 10-15V, the pulse frequency is 200-300Hz, the duty cycle is 10-15%, heat to 70-90 DEG C at a rate of 3-5 DEG C / min, the magnetic stirring speed is 200-300rpm, the time is 60-120min;

[0060] (5) Close the power supply, and cool to room temperature naturally;

[0061] (6) Take out the cathode to scrape powder, and perform ball milling treatment on the obtained powder to obtain nanoscale rod-shaped strontium-containing hydroxyapatite;

[0062] (7) Centrifuge, filter the micron carbon balls in the electrolyte, and perform washing and drying treatment, and then perform muffle high-temperature treatment to obtain micron-scale spherical shell-shaped strontium-containing hydroxyapatite.

[0063] Firstly, choline chloride and malonic acid are used as ionic liquid electrolyte, which has non-volatility, low melting point (up to -100 DEG C), wide liquid range, wide electrochemical window, selective solubility and designability, but the viscosity of the electrolyte is high, therefore, deionized water is added in the ionic liquid to improve the viscosity of the electrolyte, so as to facilitate the occurrence of electrochemical deposition.

[0064] The electrochemical deposition process of the present application occurs on the surfaces of two substrates at the same time, one is the cathode, and the power supply is applied to the electrode, and the electrochemical hydrogen evolution reaction 2H2O+2e - →H2+2OH - occurs on the surface of the cathode, that is, the local OH - concentration on the surface of the cathode is increased, a local strong alkaline region is formed, and calcium and strontium ions are driven to the surface of the cathode under the action of the electric field, and 5Ca 2+ (Sr 2+ )+3H2PO4-+7OH -Ca5(PO4)3OH+6H2O, i.e. the over-saturation of HA on the cathode surface and the continuous growth, in order to obtain rod-like morphology, and the local OH content is controlled by applying a bipolar pulse process, the sealed hydrothermal reaction is used to improve the electrodeposition conditions, and then the rod-like HA material is obtained, and in addition, it should be explained here that the purpose of using nitrogen to evacuate before hydrothermal reaction is not to prevent oxidation, but to increase the pressure of the hydrothermal reaction kettle, and the electrodeposition is carried out at a lower temperature of 70-90 DEG C, and the HA obtained on the cathode surface needs to be taken out and scraped, and the obtained powder is ball milled to obtain nanoscale rod-like strontium-containing hydroxyapatite, and the average length of the nanoscale rod-like strontium-containing hydroxyapatite is 200-300 nm, as shown in the accompanying Figure 4 One is the surface of the carbon sphere, which needs to be treated by mixed acid high-temperature treatment to improve the water solubility of the carbon sphere, for example, a concentrated acid mixture composed of sulfuric acid and nitric acid is used for reflux treatment at a high temperature section, and impurities on the surface of the carbon sphere are effectively removed and hydrophilic groups are introduced. During stirring, the carbon sphere continuously touches the cathode, and due to the over-saturation of HA on the cathode surface and the continuous growth, Ca 2+ Sr 2+ and H 2 PO4 - exists a concentration difference and migrates to the vicinity of the cathode, touches the carbon sphere, and then is deposited on the surface of the carbon sphere, and then the micron carbon sphere in the electrolyte is centrifuged, filtered, washed and dried, and then high-temperature treatment in a muffle furnace is carried out, wherein part of oxygen needs to be blown into the muffle furnace for combustion to remove the carbon microspheres to obtain a hollow structure, and the size of the micron-scale spherical shell-shaped strontium-containing hydroxyapatite is 5-15 mu m, and the hollow size is 5-10 mu m.

[0065] The present application adopts pulse deposition, which is beneficial to less concentration difference, improves the deposition amount, and avoids the phenomenon that the hydroxyapatite cannot be completely deposited on the sphere, as shown in the accompanying Figure 3 It can be seen that, as in the preparation method of Comparative Example 1, low-viscosity electrolyte is not used, and pulse deposition is not used, and the whole sphere is not completely deposited, and there are a large number of holes.

[0066] In addition, the accompanying Figure 1 is a picture of the spherical strontium-containing hydroxyapatite before calcination, and the micron surface is uniformly deposited, and the accompanying Figure 2 is a picture of the spherical strontium-containing hydroxyapatite after calcination, and although there is partial rupture, it is only an example, which is used to illustrate the thickness and hollow structure of the deposited hydroxyapatite.

[0067] Beneficial technical effects: (1) Dental caries is an infectious disease caused by plaque deposited on the tooth surface. The adhesion of bacteria to the tooth surface is the primary condition for plaque formation. Cariogenic bacteria use food sugars to synthesize various extracellular polysaccharides, which adhere to the enamel and ferment sugars to produce organic acids. As acidic metabolites accumulate in dental plaque, they can lead to acid erosion and demineralization of the hard tissues of the tooth and the formation of caries. Therefore, the adhesion of cariogenic bacteria to the enamel surface, acid production, and synthesis of extracellular polysaccharides are important virulence factors leading to dental caries. The two-component hydroxyapatite (HA) toothpaste prepared in this invention has excellent adsorption of proteins and dextran.

[0068] (2) Two-component hydroxyapatite has the effect of promoting remineralization of enamel surface, enhancing enamel's resistance to caries, and increasing hardness.

[0069] (3) The toothpaste prepared by the present invention has a significant effect on reducing plaque index and gingivitis index. Attached Figure Description

[0070] Appendix Figure 1 Image of spherical strontium-containing hydroxyapatite before calcination.

[0071] Appendix Figure 2 Image of partially cracked spherical strontium-containing hydroxyapatite after roasting.

[0072] Appendix Figure 3 Images of spherical hydroxyapatite obtained in Example 2 and Comparative Example 1.

[0073] Appendix Figure 4 Image of rod-shaped strontium-containing hydroxyapatite. Detailed Implementation Example 1

[0074] An anti-fouling and whitening toothpaste composition, comprising the following ingredients by weight percentage:

[0075] Repair agent: 8% nano-sized rod-shaped strontium-containing hydroxyapatite and micron-sized spherical shell-shaped strontium-containing hydroxyapatite;

[0076] Friction agent: 20% natural calcium carbonate;

[0077] Friction agent: 3% silica;

[0078] Adhesive: Sodium carboxymethyl cellulose 0.6%;

[0079] Adhesive: 19% hydroxypropyl guar gum;

[0080] Moisturizer: Sorbitol 18%

[0081] Surfactant: Sodium dodecyl sulfate 2.2%;

[0082] Preservative: Sodium benzoate 0.3%;

[0083] Sweetening agent: sodium saccharin 0.1%;

[0084] Anti-allergic agent: potassium nitrate 2%;

[0085] Flavoring agent: fruit flavor 0.8%;

[0086] Deionized water to 100.

[0087] The mass ratio of the nanoscale rod-like strontium-containing hydroxyapatite and the microscale spherical shell-like strontium-containing hydroxyapatite is 1: (2).

[0088] The nanoscale rod-like strontium-containing hydroxyapatite and the microscale spherical shell-like strontium-containing hydroxyapatite are prepared by the following method:

[0089] (1) According to the proportion, mix choline chloride and malonic acid, heat to obtain an ionic liquid, and the molar ratio of choline chloride and malonic acid is 1:2.

[0090] (2) According to the proportion, add 200 mL of deionized water to the ionic liquid obtained in step (1) to obtain a mixed solution.

[0091] (3) According to the proportion, add 2 g / L of micro carbon spheres, 10 mmol / L of calcium nitrate, 5 mmol / L of diaminophosphate, 1 mmol / L of strontium chloride, 0.01 mol / L of sodium chloride and 1 g / L of EDTA to the mixed solution obtained in step (2) to heat and dissolve to obtain an electrolyte.

[0092] (4) Pour the prepared electrolyte into an insulating reaction kettle, use 30CrNiMoVA steel as the cathode, Mo 70 Cu 30 alloy as the anode, the inter-electrode distance is 30 mm, open the nitrogen inlet and outlet valves, pre-charge nitrogen to exhaust air for 3 min, close the nitrogen outlet valve, charge nitrogen to 2 Mpa as read by the pressure gauge, close the nitrogen inlet valve, open the power supply, apply a bidirectional pulse power supply, the positive pulse voltage is 70 V, the negative pulse voltage is 10 V, the pulse frequency is 200 Hz, the duty cycle is 10%, the temperature is raised to 70°C at a rate of 3°C / min, the magnetic stirring speed is 200 rpm, and the time is 60 min.

[0093] (5) Turn off the power supply and naturally cool to room temperature.

[0094] (6) Take out the cathode and scrape the powder, and then perform ball milling treatment on the obtained powder to obtain nanoscale rod-like strontium-containing hydroxyapatite.

[0095] (7) centrifuging, filtering, washing and drying the microsized carbon spheres in the electrolyte, and then carrying out muffle furnace high-temperature treatment, with the temperature raised to 500°C at a rate of 5°C / min and maintained for 2h, and then naturally cooled to room temperature, to obtain microsized spherical shell-shaped strontium-containing hydroxyapatite.

[0096] (8) mixing the strontium-containing hydroxyapatite prepared in step (6) and step (7) in proportion. Example 2

[0097] An anti-tooth decay whitening toothpaste composition consisting of the following ingredients in percentage by weight:

[0098] Repairing agent: nanosized rod-shaped strontium-containing hydroxyapatite and microsized spherical shell-shaped strontium-containing hydroxyapatite 11%;

[0099] Friction agent: natural calcium carbonate 25%;

[0100] Friction agent: silicon dioxide 4%;

[0101] Binder: sodium hydroxymethyl cellulose 0.7%;

[0102] Binder: hydroxypropyl guar gum 19%;

[0103] Moisturizing agent: sorbitol 17.5%

[0104] Surfactant: sodium dodecyl sulfate 2.3%;

[0105] Preservative: sodium benzoate 0.4%;

[0106] Sweetener: sodium saccharin 0.2%;

[0107] Anti-allergic agent: potassium nitrate 3%; Fragrance: fruit fragrance 0.9%;

[0108] Deionized water to 100.

[0109] The mass ratio of the nanosized rod-shaped strontium-containing hydroxyapatite and the microsized spherical shell-shaped strontium-containing hydroxyapatite is 1: (2.5).

[0110] The nanosized rod-shaped strontium-containing hydroxyapatite and the microsized spherical shell-shaped strontium-containing hydroxyapatite are prepared by the following method:

[0111] (1) mixing choline chloride and malonic acid in a proportion, heating to obtain an ionic liquid, and the molar ratio of choline chloride and malonic acid is 1:2.

[0112] (2) adding 250mL deionized water to the ionic liquid obtained in step (1) in a proportion to obtain a mixed solution.

[0113] (3) The prepared mixed solution is added with 3.5 g / L micro-carbon balls, 15 mmol / L calcium nitrate, 7.5 mmol / L phosphoric acid diamine, 1.5 mmol / L strontium chloride, 0.01 mol / L sodium chloride and 1.5 g / L EDTA for heating and dissolving to obtain an electrolyte.

[0114] (4) The prepared electrolyte is poured into an insulated reaction kettle, 30CrNiMoVA steel is used as a cathode, Mo 70 Cu 30 alloy is used as an anode, the inter-electrode distance is 40 mm, the nitrogen inlet and outlet valves are opened, nitrogen is pre-charged to exhaust air for 4 min, the nitrogen outlet valve is closed, nitrogen is charged until the pressure gauge reading is 2.5 MPa, the nitrogen inlet valve is closed, the power supply is turned on, a bidirectional pulse power supply is applied, the positive pulse voltage is 75 V, the negative pulse voltage is 12.5 V, the pulse frequency is 250 Hz, the duty cycle is 12.5%, the temperature is raised to 80°C at a rate of 4°C / min, magnetic stirring is performed at 250 rpm, and the time is 90 min.

[0115] (5) The power supply is turned off, and the temperature is naturally cooled to room temperature.

[0116] (6) The cathode is taken out for powder scraping, and the obtained powder is subjected to ball milling treatment to obtain nanoscale rod-shaped strontium-containing hydroxyapatite.

[0117] (7) The micro-carbon balls in the electrolyte are centrifuged and filtered, and are subjected to washing and drying treatment, and then are subjected to muffle high-temperature treatment to obtain microscale spherical shell-shaped strontium-containing hydroxyapatite, the muffle high-temperature treatment is raised to 525°C at a rate of 6°C / min, is maintained for 2.5 h, and is naturally cooled to room temperature.

[0118] (8) The strontium-containing hydroxyapatites prepared in steps (6) and (7) are mixed in proportion. Example 3

[0119] An anti-tooth decay and tooth whitening toothpaste composition, consisting of the following ingredients in percentage by weight:

[0120] Repairing agent: nanoscale rod-shaped strontium-containing hydroxyapatite and microscale spherical shell-shaped strontium-containing hydroxyapatite 14%;

[0121] Friction agent: natural calcium carbonate 30%;

[0122] Friction agent: silicon dioxide 5%;

[0123] Binder: sodium hydroxymethyl cellulose 0.8%;

[0124] Binder: hydroxypropyl guar gum 18%;

[0125] Moisturizing agent: sorbitol 18%

[0126] Surfactant: sodium dodecyl sulfate 2.4%;

[0127] Antiseptic: sodium benzoate 0.5%;

[0128] Sweetener: sodium saccharin 0.3%;

[0129] Anti-allergic agent: potassium nitrate 4%; essence: fruit essence 1%;

[0130] Deionized water to 100.

[0131] The mass ratio of the nanoscale rod-shaped strontium-containing hydroxyapatite and the micron-sized spherical shell-shaped strontium-containing hydroxyapatite is 1: (3).

[0132] The nanoscale rod-shaped strontium-containing hydroxyapatite and the micron-sized spherical shell-shaped strontium-containing hydroxyapatite are prepared by the following method:

[0133] (1) Mix choline chloride and malonic acid according to the ratio, heat to obtain an ionic liquid, and the molar ratio of choline chloride and malonic acid is 1:2.

[0134] (2) Add 300 mL of deionized water to the ionic liquid obtained in step (1) according to the ratio to obtain a mixed solution.

[0135] (3) Add 5 g / L of micron carbon spheres, 20 mmol / L of calcium nitrate, 10 mmol / L of diaminophosphate, 2 mmol / L of strontium chloride, 0.01 mol / L of sodium chloride and 2 g / L of EDTA to the mixed solution obtained in step (2) according to the ratio, and heat to dissolve to obtain an electrolyte.

[0136] (4) Pour the prepared electrolyte into an insulating reaction kettle, use 30CrNiMoVA steel as the cathode, Mo 70 Cu 30 alloy as the anode, the inter-electrode distance is 50 mm, open the nitrogen inlet and outlet valve, pre-charge nitrogen to exhaust air for 3-5 min, close the nitrogen outlet valve, fill nitrogen to 3 Mpa reading on the pressure gauge, close the nitrogen inlet valve, open the power supply, apply a bidirectional pulse power supply, the positive pulse voltage is 80 V, the negative pulse voltage is 15 V, the pulse frequency is 300 Hz, the duty cycle is 15%, the temperature is raised to 90℃ at a rate of 5℃ / min, the magnetic stirring speed is 300 rpm, and the time is 120 min.

[0137] (5) Turn off the power supply and naturally cool to room temperature.

[0138] (6) Take out the cathode and scrape the powder, and then perform ball milling treatment on the obtained powder to obtain nanoscale rod-shaped strontium-containing hydroxyapatite.

[0139] (7) Centrifuging, filtering, washing and drying the microsized carbon spheres in the electrolyte, and then carrying out muffle furnace high-temperature treatment, with the temperature rising to 550°C at a rate of 7°C / min and keeping for 3h, and then naturally cooling to room temperature, to obtain microsized spherical shell-shaped strontium-containing hydroxyapatite.

[0140] (8) Mixing the strontium-containing hydroxyapatite prepared in step (6) and step (7) in proportion.

[0141] Comparative Example 1. An anti-tooth decay whitening toothpaste composition consisting of the following ingredients in percentage by weight:

[0142] Repairing agent: nanosized rod-shaped strontium-containing hydroxyapatite and microsized spherical shell-shaped strontium-containing hydroxyapatite 11%;

[0143] Friction agent: natural calcium carbonate 25%;

[0144] Friction agent: silicon dioxide 4%;

[0145] Binder: sodium hydroxymethyl cellulose 0.7%;

[0146] Binder: hydroxypropyl guar gum 19%;

[0147] Moisturizing agent: sorbitol 17.5%

[0148] Surfactant: sodium dodecyl sulfate 2.3%;

[0149] Preservative: sodium benzoate 0.4%;

[0150] Sweetener: sodium saccharin 0.2%; Anti-allergic agent: potassium nitrate 3%;

[0151] Essence: fruit essence 0.9%;

[0152] Deionized water to 100.

[0153] The mass ratio of the nanosized rod-shaped strontium-containing hydroxyapatite and the microsized spherical shell-shaped strontium-containing hydroxyapatite is 1: (2.5).

[0154] The nanosized rod-shaped strontium-containing hydroxyapatite and the microsized spherical shell-shaped strontium-containing hydroxyapatite are prepared by the following method:

[0155] (1) Mixing choline chloride and malonic acid in a proportion, heating to obtain an ionic liquid, and the molar ratio of choline chloride and malonic acid is 1:2.

[0156] (2) Adding no deionized water, i.e. 0 ml of deionized water, to the ionic liquid obtained in step (1).

[0157] (3) The mixture obtained in step (2) is added with 3.5 g / L micro-carbon balls, 15 mmol / L calcium nitrate, 7.5 mmol / L phosphoric acid diamine, 1.5 mmol / L strontium chloride, 0.01 mol / L sodium chloride and 1.5 g / L EDTA for heating and dissolving to obtain an electrolyte.

[0158] (4) The prepared electrolyte is poured into an insulated reaction kettle, 30CrNiMoVA steel is used as a cathode, Mo 70 Cu 30 alloy is used as an anode, the inter-electrode distance is 40 mm, the nitrogen inlet and outlet valves are opened, nitrogen is pre-charged to exhaust air for 4 min, the nitrogen outlet valve is closed, nitrogen is charged until the pressure gauge reading is 2.5 Mpa, the nitrogen inlet valve is closed, the power supply is turned on, a direct current power supply is applied, the voltage is 17.5 V, the temperature is raised to 80℃ at a rate of 4℃ / min, the magnetic stirring speed is 250 rpm, and the time is 90 min.

[0159] (5) The power supply is turned off, and the temperature is naturally cooled to room temperature.

[0160] (6) The cathode is taken out for powder scraping, and the obtained powder is subjected to ball milling treatment to obtain nanoscale rod-shaped strontium-containing hydroxyapatite.

[0161] (7) The micro-carbon balls in the electrolyte are centrifuged and filtered, and then subjected to washing and drying treatment, and then subjected to muffle high-temperature treatment to obtain microscale spherical shell-shaped strontium-containing hydroxyapatite, the muffle high-temperature treatment is raised to 525℃ at a rate of 6℃ / min, and maintained for 2.5 h, and then naturally cooled to room temperature.

[0162] (8) The strontium-containing hydroxyapatite obtained in step (6) and step (7) is mixed in proportion.

[0163] Comparative Example 2. An anti-tooth decay and whitening toothpaste composition consisting of the following ingredients in percentage by weight:

[0164] Repairing agent: microscale spherical shell-shaped strontium-containing hydroxyapatite 11%;

[0165] Friction agent: natural calcium carbonate 25%;

[0166] Friction agent: silicon dioxide 4%;

[0167] Binder: sodium hydroxymethyl cellulose 0.7%;

[0168] Binder: hydroxypropyl guar gum 19%;

[0169] Moisturizing agent: sorbitol 17.5%

[0170] Surfactant: sodium dodecyl sulfate 2.3%;

[0171] Preservative: sodium benzoate 0.4%;

[0172] Sweetening agent: sodium saccharin 0.2%;

[0173] Anti-allergic agent: potassium nitrate 3%; flavor: fruit flavor 0.9%;

[0174] Deionized water to 100.

[0175] Micron-sized spherical shell-shaped strontium-containing hydroxyapatite is prepared by the following method:

[0176] (1) According to the proportion, mix choline chloride and malonic acid, heat to obtain an ionic liquid, and the molar ratio of choline chloride and malonic acid is 1:2.

[0177] (2) According to the proportion, add 250 mL of deionized water to the ionic liquid obtained in step (1) to obtain a mixed solution.

[0178] (3) According to the proportion, add 3.5 g / L of micron carbon balls, 15 mmol / L of calcium nitrate, 7.5 mmol / L of diaminium hydrogen phosphate, 1.5 mmol / L of strontium chloride, 0.01 mol / L of sodium chloride and 1.5 g / L of EDTA to the mixed solution obtained in step (2) to dissolve and heat to obtain an electrolyte.

[0179] (4) Pour the prepared electrolyte into an insulating reaction kettle, use 30CrNiMoVA steel as the cathode, Mo 70 Cu 30 Alloy as the anode, the inter-electrode distance is 40 mm, open the nitrogen inlet and outlet valve, pre-charge nitrogen to exhaust air for 4 min, close the nitrogen outlet valve, fill nitrogen to the pressure gauge reading is 2.5 Mpa, close the nitrogen inlet valve, open the power supply, apply a bidirectional pulse power supply, the positive pulse voltage is 75V, the negative pulse voltage is 12.5V, the pulse frequency is 250Hz, the duty cycle is 12.5%, the temperature is raised to 80℃ at 4℃ / min, the magnetic stirring speed is 250rpm, and the time is 90 min.

[0180] (5) Turn off the power, and naturally cool to room temperature.

[0181] (6) Centrifuge, filter the micron carbon balls in the electrolyte, and perform washing and drying treatment, then perform muffle high temperature treatment to obtain micron-sized spherical shell-shaped strontium-containing hydroxyapatite, and the muffle high temperature treatment is raised to 525℃ at 6℃ / min, kept for 2.5h, and naturally cooled to room temperature.

[0182] Comparative Example 3. An anti-tooth decay and whitening toothpaste composition consisting of the following ingredients by weight percentage:

[0183] Repairing agent: nanoscale rod-shaped strontium-containing hydroxyapatite 11%;

[0184] Friction agent: natural calcium carbonate 25%;

[0185] Friction agent: Silica 4%;

[0186] Binder: Sodium hydroxymethyl cellulose 0.7%;

[0187] Binder: Hydroxypropyl guar gum 19%;

[0188] Moisturizer: Sorbitol 17.5%

[0189] Surfactant: Sodium dodecyl sulfate 2.3%;

[0190] Preservative: Sodium benzoate 0.4%;

[0191] Sweetener: Sodium saccharin 0.2%;

[0192] Anti-allergic agent: Potassium nitrate 3%;

[0193] Essence: Fruit essence 0.9%;

[0194] Deionized water to 100.

[0195] Nano-sized rod-shaped strontium-containing hydroxyapatite.

[0196] The nano-sized rod-shaped strontium-containing hydroxyapatite and the micro-sized spherical shell-shaped strontium-containing hydroxyapatite are prepared by the following method:

[0197] (1) According to the proportion, mix choline chloride and malonic acid, heat to obtain an ionic liquid, and the molar ratio of choline chloride and malonic acid is 1:2.

[0198] (2) According to the proportion, add 250 mL of deionized water to the ionic liquid obtained in step (1) to obtain a mixed solution.

[0199] (3) According to the proportion, add 3.5 g / L of micron carbon balls, 15 mmol / L of calcium nitrate, 7.5 mmol / L of diaminophosphate, 1.5 mmol / L of strontium chloride, 0.01 mol / L of sodium chloride and 1.5 g / L of EDTA to the mixed solution obtained in step (2) to heat and dissolve to obtain an electrolyte.

[0200] (4) Pour the prepared electrolyte into an insulating reaction kettle, use 30CrNiMoVA steel as the cathode, Mo 70 Cu 30The alloy is an anode, the inter-electrode distance is 40 mm, the nitrogen inlet and outlet valves are opened, nitrogen is pre-charged to evacuate air for 4 min, the nitrogen outlet valve is closed, nitrogen is charged until the pressure gauge reading is 2.5 MPa, the nitrogen inlet valve is closed, the power is turned on, a bidirectional pulse power is applied, the positive pulse voltage is 75 V, the negative pulse voltage is 12.5 V, the pulse frequency is 250 Hz, the duty cycle is 12.5%, the temperature is increased to 80°C at a rate of 4°C / min, the magnetic stirring speed is 250 rpm, and the time is 90 min.

[0201] (5) The power is turned off, and the temperature is naturally cooled to room temperature.

[0202] (6) The cathode is taken out and the powder is scraped, and the obtained powder is subjected to ball milling treatment to obtain nanoscale rod-shaped strontium-containing hydroxyapatite.

[0203] The toothpaste obtained in Example 2 and Comparative Examples 1-3 is subjected to adsorption testing.

[0204]

[0205] The adsorption testing is mainly based on the adsorption of saliva proteins. The cell-free whole saliva subjected to centrifugal treatment is taken, and the toothpaste obtained in Example 2 and Comparative Examples 1-3 is taken 1.5 g, the original saliva protein amount is 9780 μg / mL, the adsorption time is 8 min, the temperature is 36.5°C, the stirring speed is 3000 rpm, and the adsorption results are shown in the table.

[0206] The polysaccharide testing is performed by preparing a 1 mg / L dextran solution, and then putting the toothpaste obtained in Example 2 and Comparative Examples 1-3 into the solution, the adsorption time is 8 min, the temperature is 36.5°C, the stirring speed is 3000 rpm, and the adsorption results are shown in the table.

[0207] The hardness testing is performed by using the toothpaste obtained in Example 2 and Comparative Examples 1-3 to test the artificial caries enamel surface, the testing cycle is two weeks, and the testing is performed twice a day. The microhardness testing is performed by using a full-automatic microhardness tester from Leica, Germany, the load is 50 g, the action time is 10 s, a rhombic indentation is formed, the diagonal line length is measured, and the value is converted into a Vickers hardness value, the unit is 9.81 MPa, the same tooth surface is repeatedly tested three times in the same way, and the average value is taken. The teeth for the hardness testing are derived from human extracted malposed teeth.

[0208] The gingival index and plaque index of the volunteers before and after brushing teeth by using the toothpaste of the examples and the comparative examples are detected according to the Loe & Silness standard. The plaque index of Example 2 is reduced from 1.86±0.33 to 0.23±0.41, and the gingival index is reduced from 2.36±0.35 to 0.51±0.39. The plaque index of Comparative Example 1 is reduced from 1.82±0.35 to 0.53±0.36, and the gingival index is reduced from 2.32±0.41 to 0.71±0.36.

[0209] There are some proteins, amino acids and lipids related to dental plaque formation in oral cavity, especially glucosyltransferase and its synthesized glucan, which play an important role in the process of plaque formation and caries development. The two-component hydroxyapatite of the present application has the effect of adsorbing and removing the components of proteins, amino acids, lipids and glucan of dental plaque on the surface of teeth. Based on the above tests, it can be concluded that the two forms of hydroxyapatite, nanoscale rod-shaped strontium-containing hydroxyapatite and microscale spherical shell-shaped strontium-containing hydroxyapatite, have good curative effect in preventing and treating dental problems, especially in preventing caries, anti-sensitivity, anti-inflammation and remineralization. After testing, the effect of single form of hydroxyapatite is not as good as that of two-component hydroxyapatite.

[0210] The above description is only the preferred embodiment of the present application, and is not intended to limit the other forms of the present application. Any person skilled in the art can use the disclosed technical content to make changes or modifications to equivalent embodiments. However, any simple modification, equivalent change and modification made to the above embodiments without departing from the technical solution of the present application, according to the technical essence of the present application, still belongs to the protection scope of the technical solution of the present application.

Claims

1. A method for the preparation of a multi-functional toothpaste HA material, characterized by It is prepared by the following steps: (1) mixing choline chloride and malonic acid according to the ratio, heating to obtain an ionic liquid; (2) adding deionized water to the ionic liquid obtained in step (1) according to the ratio to obtain a mixed solution; (3) adding 2-5 g / L micron carbon balls, 10-20 mmol / L calcium nitrate, 5-10 mmol / L diaminophosphate, 1-2 mmol / L strontium chloride, 0.01 mol / L sodium chloride and 1-2 g / L EDTA to the mixed solution obtained in step (2) according to the ratio, heating and dissolving to obtain an electrolyte; (4) The prepared electrolyte is poured into an insulating reaction kettle, 30CrNiMoVA steel is used as the cathode, Mo 70 Cu 30 alloy is used as the anode, the inter-electrode distance is 30-50 mm, the nitrogen inlet and outlet valves are opened, nitrogen is pre-charged to exhaust air for 3-5 min, the nitrogen outlet valve is closed, nitrogen is charged until the pressure gauge reading is 2-3 Mpa, the nitrogen inlet valve is closed, the power is turned on, a bidirectional pulse power is applied, the positive pulse voltage is 70-80 V, the negative pulse voltage is 10-15 V, the pulse frequency is 200-300 Hz, the duty cycle is 10-15%, the temperature is raised to 70-90℃ at a rate of 3-5℃ / min, magnetic stirring is performed at 200-300 rpm, and the time is 60-120 min. (5) turn off the power and cool to room temperature naturally; (6) take out the cathode and scrape the powder, and then perform ball milling treatment on the obtained powder to obtain nanoscale rod-shaped strontium-containing hydroxyapatite; (7) centrifuge and filter the micron carbon balls in the electrolyte, and then perform washing and drying treatment, and then perform muffle high temperature treatment to obtain micron-scale spherical shell-shaped strontium-containing hydroxyapatite.

2. A method for preparing HA material in a multi-functional toothpaste according to claim 1, characterized in that The molar ratio of choline chloride and malonic acid is 1:

2.

3. A method for preparing HA material in a multi-functional toothpaste as claimed in claim 1, characterized in that The amount of deionized water used in step (2) is 200-300 mL.

4. A method for preparing HA material in a multi-functional toothpaste as claimed in claim 1, characterized in that The size of the micron carbon balls is 5-10 μm.

5. The method for preparing HA material in a multifunctional toothpaste as described in claim 1, characterized in that... The length of the nanoscale rod-shaped strontium-containing hydroxyapatite is 200-300 nm; the size of the micron-scale spherical shell-shaped strontium-containing hydroxyapatite is 5-15 μm, and the hollow size is 5-10 μm.

6. The method for preparing HA material in a multifunctional toothpaste as described in claim 1, characterized in that... The ball milling treatment uses zirconia as the grinding ball and anhydrous ethanol as the medium to perform wet grinding.

7. The method for preparing HA material in a multifunctional toothpaste as described in claim 1, characterized in that... The electrolyte in step (7) is centrifuged at a speed of 5000-7000 r / min.

8. The method for preparing HA material in a multifunctional toothpaste as described in claim 1, characterized in that... The washing is multiple washing with ethanol and deionized water in sequence, and the drying is vacuum drying at 60-70°C.

9. The method for preparing HA material in a multifunctional toothpaste as described in claim 1, characterized in that... The muffle high temperature treatment is to increase the temperature to 500-550°C at a rate of 5-7°C / min, maintain for 2-3 h, and then cool to room temperature naturally.

10. The method for preparing HA material in a multifunctional toothpaste as described in claim 1, characterized in that... The nanoscale rod-shaped strontium-containing hydroxyapatite and the micron-scale spherical shell-shaped strontium-containing hydroxyapatite are mixed at a mass ratio of 1:(2-3) and used for the preparation of toothpaste.

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