Anti-caries anhydrous gel, preparation method therefor, and use thereof, and tubular Anti-caries anhydrous gel

Abstract

The present disclosure provides an anti-caries anhydrous gel, a preparation method therefor, and use thereof, and a tubular anti-caries anhydrous gel, relating to the technical field of dental gels. According to the present disclosure, polyethylene glycol and / or glycerol as well as absolute ethanol are used as an anhydrous matrix, thereby achieving coexistence of a bioactive material and a high-concentration fluorine ion source; by adding a hydrophobic copolymer as a film-forming agent, the anti-caries anhydrous gel can immediately form a layer of transparent film on the tooth surface after being applied to the teeth, so that effective components are controlled to be slowly released, thereby prolonging the action time of the anti-caries gel on the teeth, improving the remineralization effect of the anti-caries gel, and solving defects of traditional remineralization products such as dissolution after encountering saliva, which leads to short residence time on the tooth surface and thus causes local remineralization-promoting ions to be insufficient due to loss. By adding an antibacterial agent, formation of a dental plaque biofilm can be inhibited by means of the slow-release effect, thereby avoiding aggravation of white spot lesions caused by dental plaque accumulation, which is more conducive to preventing and treating orthodontic white spots during the correction treatment period.

Description

An anti-caries anhydrous gel and its preparation method and application, tubular anti-caries anhydrous gel

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] The present disclosure claims priority to application number 2024102455630 filed with the Patent Office of China on March 5, 2024, entitled “A Caries-Resistant Anhydrous Gel, Preparation Method and Application thereof, and Tubular Caries-Resistant Anhydrous Gel,” the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to the technical field of dental gels, and in particular to an anhydrous dental gel and a preparation method and application thereof, and a tubular anhydrous dental gel. Background Art

[0004] Tooth enamel, primarily composed of hydroxyapatite, is a non-cellular tissue. Once damaged, it lacks the ability to repair or regenerate. Under normal physiological conditions, demineralization and remineralization of tooth enamel are in a dynamic equilibrium. Plaque attached to the enamel surface produces acid, lowering the oral pH below a critical value, leading to an imbalance between demineralization and remineralization of the enamel crystals. Further demineralization can lead to substantial cavities, which, if left untreated, can progress to pulpitis and even apical periodontitis. Therefore, early prevention of enamel demineralization and promotion of remineralization of demineralized enamel remain hot topics and challenges in current clinical research. Numerous studies have demonstrated that the application of traditional fluoride can reverse this imbalance, promote enamel remineralization, and reduce enamel surface solubility by replacing hydroxyl groups in the hydroxyapatite structure to form fluorapatite, thereby preventing enamel demineralization. However, these approaches rely heavily on calcium and phosphate ions in the oral environment. Bioactive materials are widely used in dentistry. They rapidly release calcium, sodium, silicon, and phosphate ions upon contact with saliva or water. Combining bioactive materials with fluoride can help deliver fluoride, calcium, and phosphate ions deep into lesions, promoting remineralization.

[0005] In aqueous solution systems, soluble fluoride and calcium can directly react to form insoluble calcium and fluoride. Therefore, it is difficult for general bioactive materials and high-concentration fluoride to coexist in a water-soluble system, thereby reducing the efficacy of fluoride entering the oral environment.

[0006] Chinese patent CN102083404A discloses a composition using bioactive glass to promote fluoride absorption. Using glycerol and polyethylene glycol as solvents, the addition of bioactive glass significantly enhances fluoride absorption into artificial caries lesions on the tooth enamel surface. The bioactive glass and fluoride exhibit a synergistic relationship, providing the calcium and phosphorus required for fluoride absorption onto the tooth surface, thereby increasing its remineralization potential. A resin is also added as a film-forming agent. However, resin-based varnishes generally have a high viscosity and quickly harden when exposed to saliva. This hardens the brush head used to apply the varnish, reducing its effectiveness and protective properties.

[0007] Chinese patent CN102781410A discloses a non-aqueous dentifrice composition containing bioacceptable and bioactive glass, which exhibits improved mouthfeel, foaming, and product stability. However, this toothpaste-like dentifrice fails to form a film on the tooth surface, significantly reducing the amount of active ingredients after brushing and rinsing. Furthermore, any active substances, such as the bioactive glass, remaining in the mouth are continuously diluted and removed by saliva, leaving the tooth surface where mineralization is required. Consequently, the bioactive glass and other active ingredients remain in contact with the teeth for a short time, and the amount of active ingredients attached to the tooth surface is very low, rendering them ineffective in providing a protective effect.

[0008] Chinese patent CN115957237A discloses a dual-function tooth mineralization and antibacterial gel. Using water as a solvent, the gel's main active ingredient is spherical, hybrid amorphous calcium phosphate particles with a particle size of 30 to 40 nm, doped with various metal ions and fluoride ions. The gel exhibits both antibacterial and mineralization-promoting properties. However, the gel is water-soluble and rapidly disperses upon contact with saliva in the mouth, instantly releasing all of its active ingredients. However, as saliva flows, the active ingredients remain in the mouth for a short time, rendering them ineffective in their protective effects.

[0009] In view of this, the present disclosure is proposed. Summary of the Invention

[0010] The present invention provides an anhydrous anti-caries gel, a preparation method, and applications thereof, as well as a tubular anhydrous anti-caries gel. The anhydrous anti-caries gel provided herein can significantly promote the remineralization of tooth enamel, maintains long contact time with teeth, exhibits excellent stability, and enables rapid, static demineralization, resulting in excellent tooth protection.

[0011] In order to achieve the above-mentioned invention objectives, the present disclosure provides the following technical solutions:

[0012] The present disclosure provides an anhydrous caries-preventing gel, which comprises the following raw materials, calculated by weight: 1 to 20 parts of a non-aqueous matrix, 5 to 10 parts of a bioactive material, 2 to 7 parts of a fluoride ion source, 40 to 80 parts of a volatile organic solvent, 2 to 10 parts of a film-forming agent, 5 to 15 parts of a thickener, and 0.1 to 1 part of an antibacterial agent;

[0013] The non-aqueous matrix includes polyethylene glycol and / or glycerol;

[0014] The bioactive material includes one or more of regenerated silicon, bioactive glass and nano-hydroxyapatite;

[0015] The fluoride ion source includes one or more of sodium fluoride, olaflur, stannous fluoride and sodium monofluorophosphate;

[0016] The film former includes a hydrophobic polymer.

[0017] Preferably, the volatile organic solvent comprises anhydrous ethanol.

[0018] Preferably, the hydrophobic polymer includes one or more of acrylic acid (ester) / octylacrylamide copolymer, polyvinyl pyrrolidone / hexadecene copolymer, trimethylsiloxysilicate, acrylic resin and dimethylsiloxane copolymer.

[0019] Preferably, the antibacterial agent includes one or more of quaternary ammonium salt antibacterial agents, imidazole salt antibacterial agents and triclosan.

[0020] Preferably, the quaternary ammonium salt antibacterial agent includes dimethoxymethylsilylpropyl octadecyldimethylammonium chloride and / or cetylpyridinium chloride;

[0021] The imidazole salt antibacterial agent includes one or more of ketoconazole, clotrimazole, miconazole, econazole and sertaconazole.

[0022] Preferably, the preparation raw materials further include 0.5 to 2 parts of a flavor regulator.

[0023] The present disclosure also provides a method for preparing the anhydrous caries-preventing gel described in the above technical solution, comprising the following steps:

[0024] first mixing the non-aqueous matrix and the biologically active material to obtain an emulsion;

[0025] The emulsion and the fluoride ion source are mixed for a second time to obtain liquid A;

[0026] a third step of mixing the film-forming agent with the volatile organic solvent to obtain a film-forming agent solution;

[0027] fourthly mixing the film-forming agent solution with the thickener to obtain a viscous gel-like solution;

[0028] Mixing the viscous gel solution with an antibacterial agent to obtain solution B;

[0029] The liquid A and the liquid B are mixed for the sixth time to obtain an anti-caries anhydrous gel.

[0030] Preferably, the temperature of the first mixing and the second mixing are independently 45-60°C, the time is independently 30-60 min, and the speed is independently 600-1000 r / min;

[0031] The temperature of the third mixing, the fourth mixing and the sixth mixing are independently 45-60° C., the time is independently 30-60 min, and the speed is independently 1800-2200 r / min;

[0032] The fifth mixing temperature is 45-60°C, the time is 30-60 minutes, and the speed is 60-90 r / min;

[0033] The rotational viscosity of the viscous gel solution is 10,000 to 20,000 mPa·s.

[0034] The present disclosure provides the use of the anhydrous caries-preventing gel described in the above technical solution or the anhydrous caries-preventing gel prepared by the preparation method described in the above technical solution in the preparation of enamel remineralization drugs.

[0035] The present disclosure also provides a tubular anhydrous caries-preventing gel, comprising a packaging material and the anhydrous caries-preventing gel in the packaging material, wherein the packaging material comprises a rotary integrated brush pen having a cavity, and the rotary integrated brush pen is provided with a pen head; the anhydrous caries-preventing gel is the anhydrous caries-preventing gel described in the above technical solution or the anhydrous caries-preventing gel prepared by the preparation method described in the above technical solution.

[0036] The caries-preventing anhydrous gel provided by the present disclosure uses polyethylene glycol and / or glycerol and anhydrous ethanol as a matrix, achieving the coexistence of bioactive materials and a high-concentration fluoride ion source; by adding a hydrophobic copolymer as a film-forming agent, a transparent film can be immediately formed on the tooth surface after being applied to the teeth, thereby controlling the slow release of the effective ingredients, prolonging the action time of the caries-preventing gel on the teeth, and improving the remineralization effect of the caries-preventing gel, solving the defects of traditional remineralization products that dissolve after encountering saliva, have a short residence time on the tooth surface, and have insufficient local loss of remineralization-promoting ions. Moreover, the caries-preventing anhydrous gel provided by the present disclosure has good fluidity and is easy for patients with metal brackets to use. It can penetrate into places that a toothbrush cannot reach. At the same time, the antibacterial agent contained in the system can inhibit the formation of plaque biofilm through a sustained release effect, avoid the aggravation of white spot lesions caused by plaque accumulation, and is more conducive to the prevention and treatment of orthodontic white spots during the correction period, with excellent tooth protection effect.

[0037] Random mixing of the raw materials can result in poor compatibility, causing insolubility or precipitation. The preparation method provided by the present disclosure first uniformly mixes the bioactive material with a polyethylene glycol and / or glycerol anhydrous matrix of a certain viscosity to form a uniform, particle-free mixture. Otherwise, agglomeration will occur in the final system, and extending the stirring time and / or increasing the number of revolutions will not result in a uniform emulsion. If anhydrous ethanol is first mixed with the thickener, antimicrobial agent, and flavor modifier, the hydrophobic polymer film-forming agent will aggregate in the system to form a colloid and no longer dissolve or disperse. The present disclosure first dissolves the hydrophobic polymer film-forming agent in anhydrous ethanol before adding the thickener, antimicrobial agent, and flavor modifier, resulting in better dissolution and dispersion of the hydrophobic polymer film-forming agent in the system. The fluoride ion source is easily dispersed in polyethylene glycol and / or glycerol and can adjust the viscosity of liquid A, making liquid A easier to mix with liquid B, avoiding the situation where liquid A is too thick to be completely poured into liquid B, and reducing the amount of liquid A left on the wall. The preparation method provided by the present disclosure has simple process, simple operation, low energy consumption, low production cost, and is suitable for industrial production.

[0038] The tubular anhydrous caries-preventing gel provided by the present invention uses a packaging material with a built-in brush and controls the amount of each raw material to achieve the viscosity of the gel system. When in use, the packaging material only needs to be rotated to squeeze out the gel from the brush and directly apply it to the tooth surface. The operation is convenient and suitable for a variety of scenarios, overcoming the dependence of traditional caries-preventing gels on external brush accessories during use. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present disclosure and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without creative work.

[0040] FIG1 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Example 1;

[0041] FIG2 is the energy spectrum measurement results of calcium and phosphorus elements of the anhydrous caries-preventing gel prepared in Example 1;

[0042] FIG3 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Example 2;

[0043] FIG4 is the energy spectrum measurement results of calcium and phosphorus elements of the anhydrous caries-preventing gel prepared in Example 2;

[0044] FIG5 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Example 3;

[0045] FIG6 is the energy spectrum measurement results of calcium and phosphorus elements of the anhydrous caries-preventing gel prepared in Example 3;

[0046] FIG7 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Example 4;

[0047] FIG8 is the energy spectrum measurement results of calcium and phosphorus elements of the anhydrous caries-preventing gel prepared in Example 4;

[0048] FIG9 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Comparative Example 1;

[0049] FIG10 is the energy spectrum measurement results of calcium and phosphorus elements of the anhydrous caries-preventing gel prepared in Comparative Example 1;

[0050] FIG11 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Comparative Example 2;

[0051] FIG12 is a scanning electron microscope image of the remineralization effect of the anhydrous caries-preventing gel prepared in Comparative Example 3. DETAILED DESCRIPTION

[0052] The embodiments of the present disclosure will be described in detail below with reference to the examples. However, those skilled in the art will appreciate that the following examples are intended only to illustrate the present disclosure and should not be construed as limiting the scope of the present disclosure. Where specific conditions are not specified in the examples, the experiments were performed under conventional conditions or the conditions recommended by the manufacturer. Where the manufacturer of the reagents or instruments is not specified, all are commercially available conventional products.

[0053] The endpoints of the ranges and any values ​​disclosed in this disclosure are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed herein.

[0054] The present invention provides an anhydrous caries-preventing gel, which comprises the following raw materials, calculated by weight: 1 to 20 parts of a non-aqueous matrix, 5 to 10 parts of a bioactive material, 2 to 7 parts of a fluoride ion source, 40 to 80 parts of a volatile organic solvent, 2 to 10 parts of a film-forming agent, 5 to 15 parts of a thickener, and 0.1 to 1 part of an antibacterial agent;

[0055] The non-aqueous matrix includes polyethylene glycol and / or glycerol;

[0056] The bioactive material includes one or more of regenerated silicon, bioactive glass and nano-hydroxyapatite;

[0057] The fluoride ion source includes one or more of sodium fluoride, olaflur, stannous fluoride and sodium monofluorophosphate;

[0058] The film former includes a hydrophobic polymer.

[0059] Unless otherwise specified, the materials and equipment used in this disclosure are commercially available products in the art.

[0060] The anhydrous caries-preventing gel provided by the present invention comprises, by weight, 1 to 20 parts of a non-aqueous matrix, preferably 5 to 15 parts, and more preferably 10 parts; the non-aqueous matrix comprises polyethylene glycol and / or glycerol; the non-aqueous matrix preferably comprises 1 to 10 parts of polyethylene glycol, more preferably 3 to 7 parts, further preferably 4 to 6 parts, and most preferably 5 parts; and 1 to 10 parts of glycerol, more preferably 3 to 7 parts, further preferably 4 to 6 parts, and most preferably 5 parts. The present invention uses polyethylene glycol and / or glycerol and anhydrous ethanol as matrices and adopts an anhydrous system, so that the bioactive material releases the calcium and phosphorus ion source only after contact with saliva, significantly improving the stability of the bioactive material. At the same time, the bioactive material and the high-concentration fluoride ion source synergistically exert a remineralization effect, further improving the remineralization performance of the anhydrous caries-preventing gel.

[0061] The anhydrous caries-preventing gel provided herein comprises 5 to 10 parts by weight of a bioactive material, preferably 6 to 9 parts by weight, more preferably 7 to 8 parts by weight, and most preferably 7.5 parts by weight. In the present disclosure, the bioactive material comprises one or more of regenerated silicon, bioactive glass, and nanohydroxyapatite, preferably regenerated silicon.

[0062] In parts by mass, the caries-preventing anhydrous gel provided by the present disclosure includes 2 to 7 parts of a fluoride ion source, preferably 3 to 6 parts, and more preferably 4 to 5 parts. In the present disclosure, the fluoride ion source includes one or more of sodium fluoride, olafluan, stannous fluoride and sodium monofluorophosphate, more preferably olafluan. In the present disclosure, the olafluan is preferably used in the form of an olafluan solution, and the concentration of the olafluan solution is preferably 10 to 40 wt%, more preferably 20 to 30 wt%; the solvent in the olafluan solution is preferably propylene glycol. The present disclosure utilizes the dual effects of a fluoride ion source and a bioactive material, and releases a high concentration of a calcium and phosphorus ion source around the teeth through the bioactive material, thereby achieving rapid deposition of minerals on the enamel surface; the fluoride ion source is released by fluoride, which promotes the ordering of crystal nuclei and the formation of hydroxyapatite and even fluorapatite during the remineralization process, and the remineralization performance of the caries-preventing anhydrous gel is excellent.

[0063] The anhydrous caries-preventive gel provided by the present disclosure comprises 40 to 80 parts by mass of a volatile organic solvent, preferably 50 to 70 parts by mass, more preferably 60 to 65 parts by mass, and even more preferably 63 to 64 parts by mass. In the present disclosure, the volatile organic solvent preferably comprises anhydrous ethanol.

[0064] In parts by mass, the anticaries anhydrous gel provided by the present disclosure includes 2 to 10 parts of a film-forming agent, preferably 3 to 9 parts, more preferably 4 to 8 parts, and further preferably 5 to 6 parts. In the present disclosure, the film-forming agent includes a hydrophobic polymer, and the hydrophobic polymer preferably includes one or more of acrylic acid (ester) / octylacrylamide copolymer, polyvinyl pyrrolidone / hexadecene copolymer, trimethylsiloxysilicate, acrylic resin and dimethylsiloxane copolymer, more preferably acrylic acid (ester) / octylacrylamide copolymer. The present disclosure introduces a film-forming agent (hydrophobic polymer) to achieve rapid film formation through the volatilization of volatile organic solvents, thereby reducing the migration of effective ingredients, thereby controlling the slow release of fluoride ion source and bioactive materials, and prolonging the contact and action time of the anticaries anhydrous gel with teeth.

[0065] The anhydrous caries-preventive gel provided herein comprises 5 to 15 parts by weight of a thickener, preferably 6 to 12 parts, more preferably 7 to 10 parts, and even more preferably 7.5 to 8 parts. In the present disclosure, the thickener preferably comprises one or more of K30, K90, hydroxypropyl cellulose, and polyvinyl alcohol, more preferably K90.

[0066] In parts by mass, the caries-preventing anhydrous gel provided by the present disclosure includes 0.1 to 1 parts of an antibacterial agent, preferably 0.2 to 0.8 parts, more preferably 0.3 to 0.6 parts, and further preferably 0.4 to 0.5 parts. In the present disclosure, the antibacterial agent preferably includes one or more of a quaternary ammonium salt antibacterial agent, an imidazole salt antibacterial agent, and triclosan, more preferably a quaternary ammonium salt antibacterial agent. In the present disclosure, the quaternary ammonium salt antibacterial agent preferably includes dimethoxymethylsilylpropyl octadecyldimethylammonium chloride and / or cetylpyridinium chloride, more preferably cetylpyridinium chloride. In the present disclosure, the imidazole salt antibacterial agent preferably includes one or more of ketoconazole, clotrimazole, miconazole, econazole, and sertaconazole. The present disclosure effectively inhibits the formation of plaque biofilm by adding an antibacterial agent, avoids the continued erosion of the tooth mineral layer by dental plaque, and achieves rapid static demineralization.

[0067] The anhydrous caries-preventive gel provided herein preferably further comprises, by weight, 0.5 to 2 parts, preferably 0.8 to 1.8 parts, more preferably 1 to 1.5 parts, and even more preferably 1.2 to 1.5 parts of a flavor modifier. In the present disclosure, the flavor modifier preferably comprises an essence, more preferably a fruit flavor essence.

[0068] The present disclosure provides a method for preparing the anhydrous caries-preventing gel according to the above technical solution, comprising the following steps:

[0069] first mixing the non-aqueous matrix and the biologically active material to obtain an emulsion;

[0070] The emulsion and the fluoride ion source are mixed for a second time to obtain liquid A;

[0071] a third step of mixing the film-forming agent with the volatile organic solvent to obtain a film-forming agent solution;

[0072] fourthly mixing the film-forming agent solution with the thickener to obtain a viscous gel-like solution;

[0073] Mixing the viscous gel solution with an antibacterial agent to obtain solution B;

[0074] The liquid A and the liquid B are mixed for the sixth time to obtain an anti-caries anhydrous gel.

[0075] In the present disclosure, the amount of each raw material used in the preparation process of the anhydrous caries-preventing gel is the same as that of the aforementioned anhydrous caries-preventing gel, and will not be repeated here.

[0076] In the present disclosure, a non-aqueous matrix and a bioactive material are first mixed to form an emulsion. In the present disclosure, the temperature for the first mixing is preferably 45-60°C, more preferably 45-55°C, and even more preferably 45-50°C; the time for the first mixing is preferably 30-60 minutes, more preferably 30-50 minutes, and even more preferably 30-40 minutes; and the speed for the first mixing is preferably 600-1000 rpm, more preferably 600-800 rpm, and even more preferably 600-700 rpm.

[0077] After obtaining the emulsion, the present disclosure performs a second mixing of the emulsion and a fluoride ion source to obtain liquid A. In the present disclosure, the temperature of the second mixing is preferably 45 to 60° C., more preferably 45 to 55° C., and even more preferably 45 to 50° C.; the time of the second mixing is preferably 30 to 60 minutes, more preferably 30 to 50 minutes, and even more preferably 30 to 40 minutes; the rotation speed of the second mixing is preferably 600 to 1000 r / min, more preferably 600 to 800 r / min, and even more preferably 600 to 700 r / min.

[0078] The present disclosure includes a third mixing of the film-forming agent and the volatile organic solvent to obtain a film-forming agent solution. In the present disclosure, the temperature of the third mixing is preferably 45-60°C, more preferably 45-55°C, and even more preferably 45-50°C; the time of the third mixing is preferably 30-60 minutes, more preferably 30-50 minutes, and even more preferably 30-40 minutes; and the rotation speed of the third mixing is preferably 1800-2200 r / min, more preferably 1900-2100 r / min, and even more preferably 2000 r / min.

[0079] After obtaining the film-forming agent solution, the present disclosure performs a fourth mixing of the film-forming agent solution and the thickener to obtain a viscous gel-like solution. In the present disclosure, the temperature of the fourth mixing is preferably 45 to 60°C, more preferably 45 to 55°C, and further preferably 45 to 50°C; the time of the fourth mixing is preferably 30 to 60 min, more preferably 30 to 50 min, and further preferably 30 to 40 min; the rotation speed of the fourth mixing is preferably 1800 to 2200 r / min, more preferably 1900 to 2100 r / min, and further preferably 2000 r / min. In the present disclosure, the rotational viscosity of the viscous gel-like solution is preferably 10000 to 20000 mPa·s, more preferably 12000 to 18000 mPa·s, and further preferably 14000 to 15000 mPa·s.

[0080] After obtaining a viscous gel-like solution, the present disclosure further comprises a fifth mixing of the viscous gel-like solution and an antibacterial agent to obtain liquid B. In the present disclosure, the temperature of the fifth mixing is preferably 45 to 60°C, more preferably 45 to 55°C, and further preferably 45 to 50°C; the time of the fifth mixing is preferably 30 to 60 minutes, more preferably 30 to 50 minutes, and further preferably 30 to 40 minutes; the rotation speed of the fifth mixing is preferably 60 to 90 r / min, more preferably 60 to 80 r / min, and further preferably 60 to 70 r / min. In the present disclosure, when the preparation raw materials further include a flavor regulator, the fifth mixing preferably comprises: a fifth mixing of the viscous gel-like solution, the flavor regulator, and the antibacterial agent.

[0081] After obtaining liquid A and liquid B, the present disclosure performs a sixth mixing of liquid A and liquid B to obtain an anhydrous caries-preventing gel. In the present disclosure, the temperature for the sixth mixing is preferably 45-60°C, more preferably 45-55°C, and even more preferably 45-50°C; the duration of the sixth mixing is preferably 30-60 minutes, more preferably 30-50 minutes, and even more preferably 30-40 minutes; and the rotation speed for the sixth mixing is preferably 1800-2200 r / min, more preferably 1900-2100 r / min, and even more preferably 2000 r / min.

[0082] Random mixing of the raw materials will result in poor compatibility, causing insolubility or precipitation. However, the preparation method provided by the present disclosure first mixes the bioactive material and a polyethylene glycol and / or glycerol anhydrous matrix with a certain viscosity evenly to form a uniform particle-free mixture. Otherwise, agglomeration will occur in the final system, and extending the stirring time and / or increasing the number of revolutions will not form a uniform emulsion. If anhydrous ethanol is first mixed with a thickener, an antimicrobial agent, and a flavor regulator, the hydrophobic polymer film-forming agent will agglomerate to form a colloid in the system and will no longer dissolve and disperse. However, the present disclosure first dissolves the hydrophobic polymer film-forming agent in anhydrous ethanol and then adds the thickener, antimicrobial agent, and flavor regulator, resulting in a good dissolution and dispersion effect of the hydrophobic polymer film-forming agent in the system. Based on the principle of compatibility, the fluoride ion source (especially olafluan solution, a mixture of olafluan and propylene glycol) mixed with polyethylene glycol and glycerin is the easiest to disperse. It can also adjust the viscosity of liquid A, making liquid A easier to mix with liquid B, avoiding the situation where liquid A is too thick to be completely poured into liquid B, and reducing the amount of liquid A left on the wall.

[0083] The present disclosure provides the use of the anhydrous caries-preventing gel described in the above technical solution or the anhydrous caries-preventing gel prepared by the preparation method described in the above technical solution in the preparation of enamel remineralization drugs.

[0084] The present disclosure provides a tubular anhydrous caries-preventing gel, comprising a packaging material and the anhydrous caries-preventing gel located in the packaging material, wherein the packaging material comprises a rotary integrated brush pen having a cavity, and the rotary integrated brush pen is provided with a pen head; the anhydrous caries-preventing gel is the anhydrous caries-preventing gel described in the above technical solution or the anhydrous caries-preventing gel prepared by the preparation method described in the above technical solution.

[0085] In the present disclosure, the method for preparing the tubular anhydrous anticaries gel preferably comprises the following steps: filling the anhydrous anticaries gel into a packaging material to obtain the tubular anhydrous anticaries gel. In the present disclosure, the filling is preferably performed using a gel filling machine.

[0086] To further illustrate the present disclosure, the anticaries anhydrous gel and its preparation method, as well as the tubular anticaries anhydrous gel are described in detail below with reference to the examples, but they should not be construed as limiting the scope of protection of the present disclosure.

[0087] Example 1

[0088] The ingredients of the anticaries anhydrous gel are prepared according to Table 1.

[0089] Preparation of Solution A: Polyethylene glycol and glycerol were added to a beaker and heated in a water bath to 45°C. Regenerated silicon was then evenly added in three portions and stirred at 600 rpm for 30 minutes to obtain a uniform emulsion free of visible particles. A 30 wt% olafluanid solution in propylene glycol was then added and stirred at 600 rpm for 30 minutes until the mixture was thoroughly mixed, yielding Solution A. Regenerated silicon is a composite of calcium, phosphorus, and silicon oxides.

[0090] Preparation of Liquid B: Add anhydrous ethanol to a stirred tank, raise the temperature to 45°C, evenly add 5 parts of acrylic acid (ester) / octylacrylamide copolymer in three portions, and disperse at a high speed of 2000 rpm for 30 minutes until the film-forming agent is completely dissolved, thereby obtaining a uniform and transparent film-forming agent solution; add K90 and disperse at a high speed of 2000 rpm for 30 minutes until the thickener is completely dissolved, thereby obtaining a uniform viscous gel-like solution with a rotational viscosity controlled between 10,000 and 20,000 mPa·s; add 1.5 parts of fragrance and 0.4 parts of antibacterial agent, and stir and mix at 60 rpm for 30 minutes until the materials are completely mixed, thereby obtaining Liquid B.

[0091] Preparation of anhydrous caries-preventing gel: Liquid A was slowly added to Liquid B, and the mixture was dispersed at high speed at 45° C. and 2000 rpm for 30 min to obtain anhydrous caries-preventing gel.

[0092] Filling: Use a gel filling machine to fill the anhydrous anti-caries gel into a rotary integrated brush pen, and cover the pen head tightly to obtain a tubular anhydrous anti-caries gel.

[0093] Table 1: Composition of the anhydrous anti-caries gel formulations of the embodiments and comparative examples (parts by mass)

[0094] Examples 2 to 4

[0095] An anhydrous caries-preventing gel and a tubular anhydrous caries-preventing gel were prepared according to the method of Example 1. The composition formulas of the anhydrous caries-preventing gels in Examples 2 to 4 are shown in Table 1.

[0096] Comparative Examples 1-2

[0097] An anhydrous caries-preventing gel and a tubular anhydrous caries-preventing gel were prepared according to the method of Example 1. The composition formulas of the anhydrous caries-preventing gels in Comparative Examples 1 and 2 are shown in Table 1.

[0098] Comparative Example 3

[0099] According to the method of Example 1, an anhydrous caries-preventing gel and a tubular anhydrous caries-preventing gel were prepared. After the preparation, 10 parts of purified water were added and high-speed dispersion was carried out at 45° C. and 2000 rpm for 30 minutes to obtain an aqueous anhydrous caries-preventing gel. The composition formula is shown in Table 1.

[0100] Test Example 1

[0101] Performance test of anhydrous caries-preventing gels prepared in Examples and Comparative Examples

[0102] 1. Film formation time

[0103] Rotate the brush pen for one circle to allow the anti-caries anhydrous gel to flow out from the pen tip; use the brush head to evenly apply it on the glass slide into a 2 cm × 2 cm rectangle; then immediately place it in a 37°C constant temperature drying oven. Starting from 10 seconds, touch its surface with your hand every 5 seconds until the film is no longer sticky to your hand. This is considered film formation; determine the film-forming time of the anti-caries anhydrous gel sample based on the interval time.

[0104] 2. Film-forming effect and adhesion

[0105] Rotate the brush pen for one circle to allow the anticaries anhydrous gel to flow out from the pen tip; use the brush head to evenly apply it on a glass slide into a 2 cm × 2 cm rectangle; dry the sample at 37°C for 60 seconds to form a film; then place it in 37°C distilled water, soak it for 30 seconds, and observe the water effect of the coating; press the fixed film with your fingers. If it cannot be pushed away, it means the film has good adhesion; if it can be pushed away, it means the film has poor adhesion.

[0106] 3. Remineralization performance

[0107] 3.1 Preparation of artificial caries demineralization: A 5 mm × 5 mm intact glazed modular bovine tooth was placed in 100 mL of artificial demineralization solution (2.2 mmol / L CaCl2, 2.2 mmol / L NaH2PO4, 0.05 mmol / L acetic acid, pH 4.5, and purified water as the solvent) and immersed at a constant temperature of 37°C for 72 h to form artificial caries. The demineralization effect was observed under a scanning electron microscope.

[0108] 3.2 Remineralization experiment: The caries-preventing anhydrous gel was evenly applied to the demineralized bovine enamel surface, and then immersed in simulated saliva; twice a day for 15 days; after the experiment, the samples were taken out and observed by scanning electron microscopy to observe the mineralization of the enamel cross-section.

[0109] 4. Energy spectrum analysis

[0110] Samples after the above remineralization experiment were taken, and the mineralized surface was subjected to energy spectrum analysis, and the type of formed crystal nucleus was determined by the calcium-phosphorus ratio; a calcium-phosphorus ratio greater than 1.67 indicates that a hydroxyapatite mineralization layer is formed, and the crystal crystallinity is high and ordered; a calcium-phosphorus ratio of 1.67 indicates that a hydroxyapatite mineralization layer is formed, and the crystal crystallinity is low and disordered; a calcium-phosphorus ratio less than 1.67 indicates that no hydroxyapatite mineralization layer is formed, and the crystal is a calcium phosphate hydroxyapatite precursor.

[0111] The performance test results are shown in Table 2 and Figures 1 to 12.

[0112] Table 2 Summary of test results of anhydrous anti-caries gel performance

[0113] Figure 1 is an electron microscope scanning diagram of the remineralization effect of the anhydrous caries-prepared gel prepared in Example 1, Figure 2 is the calcium and phosphorus element spectrum measurement results of the anhydrous caries-prepared gel prepared in Example 1, Figure 3 is an electron microscope scanning diagram of the remineralization effect of the anhydrous caries-prepared gel prepared in Example 2, Figure 4 is the calcium and phosphorus element spectrum measurement results of the anhydrous caries-prepared gel prepared in Example 2, Figure 5 is an electron microscope scanning diagram of the remineralization effect of the anhydrous caries-prepared gel prepared in Example 3, Figure 6 is the calcium and phosphorus element spectrum measurement results of the anhydrous caries-prepared gel prepared in Example 3, 7 is an electron microscope scanning image of the remineralization effect of the anti-caries anhydrous gel prepared in Example 4, Figure 8 is the calcium and phosphorus element spectrum measurement results of the anti-caries anhydrous gel prepared in Example 4, Figure 9 is an electron microscope scanning image of the remineralization effect of the anti-caries anhydrous gel prepared in Comparative Example 1, Figure 10 is the calcium and phosphorus element spectrum measurement results of the anti-caries anhydrous gel prepared in Comparative Example 1, Figure 11 is an electron microscope scanning image of the remineralization effect of the anti-caries anhydrous gel prepared in Comparative Example 2, and Figure 12 is an electron microscope scanning image of the remineralization effect of the anti-caries anhydrous gel prepared in Comparative Example 3.

[0114] Comparing Figure 3 with Figure 1 , it can be seen that the remineralization effect of the anhydrous caries-prepared gel prepared in Example 2 was inferior to that of Example 1, primarily due to the low amount of mineralized layer deposition. Its film-forming time was short, indicating that increasing the amount of film-forming agent in the anhydrous caries-prepared gel can increase the film-forming speed, but this results in poor film-forming effectiveness. The resulting film easily detaches from smooth surfaces (such as teeth), hindering the in situ release of fluoride ions and bioactive materials, and thus affecting the remineralization effect.

[0115] Comparing Figure 5 with Figure 1 shows that the remineralization effect of the anhydrous caries-preventing gel prepared in Example 3 is inferior to that of Example 1, primarily due to poorer crystallinity and larger particle size in the mineralized layer. Comparing Figure 6 with Figure 2 shows that the low calcium-phosphorus ratio indicates that the formed crystals are mostly disordered. This suggests that reducing the ratio of regenerated silicon and olafluanid, and adding excess fluoride ions, does not improve the ordered formation of crystal nuclei.

[0116] Comparing Figure 7 with Figure 1 , the remineralization effect of the anhydrous caries-preventing gel prepared in Example 4 was inferior to that of Example 1, primarily due to poor crystallinity and large particle size in the mineralized layer. Comparing Figure 8 with Figure 2 , the low calcium-phosphorus ratio indicates that the resulting crystals are essentially undesirable. This suggests that increasing the ratio of regenerated silicon to olafluanid will result in disordered deposition of excess regenerated silicon due to a lack of fluoride ion nucleation.

[0117] Comparing Figure 9 with Figure 5 shows that the remineralization effect of the anhydrous caries-prepared gel prepared in Comparative Example 1 is inferior to that of Example 3, demonstrating that the anhydrous caries-prepared gel prepared in Comparative Example 1, with only olafluanid added and no regenerated silicon, forms a very small remineralized layer, resulting in poor remineralization. A comprehensive analysis of the remineralization effects of Examples 1, 3, 4, and Comparative Example 1 shows that, as shown by comparing Figure 5 with Figure 7 in Figure 9 , the ratio of regenerated silicon to olafluanid affects the amount of remineralized layer formed. Comparing Figure 6 with Figure 8 in Figure 10 shows that the ratio of regenerated silicon to olafluanid significantly affects the orderliness of the crystal nuclei, directly influencing the remineralization effect.

[0118] Analysis of Example 1 and Comparative Example 2 shows that the film-forming effect of Comparative Example 2 is not as good as that of Example 1. As shown in Figure 11 and Figure 1, the remineralization effect of Comparative Example 2 is not as good as that of Example 1, which proves that the anhydrous caries-preventing gel prepared without adding a film-forming agent does not form a film, quickly disperses and dissolves in an aqueous solution, releases fluoride ions and bioactive materials instantly, cannot form a mineralized layer locally, and has a poor remineralization effect.

[0119] Analysis of Example 1 and Comparative Example 3 shows that the film-forming effect of Comparative Example 3 is not as good as that of Example 1; as shown in Figure 12 and Figure 1, the remineralization effect of Comparative Example 3 is not as good as that of Example 1, proving that under the condition of aqueous gel, due to the poor film-forming effect, fluoride ions and bioactive materials cannot stay and accumulate on the tooth surface for a long time, and cannot form a mineralized layer locally through remineralization.

[0120] In summary, in order to overcome the performance deficiencies of remineralization products, the present invention adopts the dual effects of amino fluoride ion source - olafluor and bioactive material - regenerated silicon. The regenerated silicon releases a high concentration of calcium and phosphorus ion source around the teeth, thereby achieving rapid deposition of minerals on the enamel surface; the release of fluoride ion source by olafluor promotes the ordering of crystal nuclei and the formation of hydroxyapatite and even fluorapatite during the remineralization process. By adjusting the ratio, the optimal crystal nucleus deposition process can be achieved.

[0121] To overcome the stability problem of bioactive materials, the present disclosure adopts an anhydrous system (the matrix is ​​glycerol, polyethylene glycol and ethanol), so that the bioactive material releases the calcium and phosphorus ion source only after contacting saliva, allowing the bioactive material and the high-concentration fluoride ion source to synergistically exert a remineralization effect.

[0122] In order to overcome the problem of short contact time with teeth, the present disclosure introduces a film-forming agent acrylic acid (ester) / octylacrylamide copolymer, which achieves rapid film formation through the volatilization of the volatile organic solvent ethanol, reduces the migration of effective ingredients, thereby controlling the slow release of fluoride ion source and bioactive materials and prolonging the action time.

[0123] In order to overcome the continued erosion of dental plaque on the mineralized layer of teeth, quaternary ammonium antibacterial agents are selected to inhibit the formation of plaque biofilm and achieve the purpose of rapid and static demineralization.

[0124] To overcome the need for external brushes during use, a packaging material with a built-in brush was chosen. By controlling the viscosity of the gel system, convenient application is achieved on the packaging material. During use, simply rotate the packaging material to squeeze the gel from the brush and apply it directly to the tooth surface. This convenient operation is suitable for a variety of scenarios.

[0125] Although the above embodiments provide a detailed description of the present disclosure, they are only part of the embodiments of the present disclosure, not all of the embodiments. People can also obtain other embodiments based on the embodiments of the present disclosure without creative work, and these embodiments all fall within the scope of protection of the present disclosure. Industrial Applicability

[0126] The present invention provides an anhydrous anti-caries gel that can prolong the effect time of the anhydrous anti-caries gel on teeth, improve the remineralization effect of the anhydrous anti-caries gel, and is applicable to a wider range of people; the preparation method of the anhydrous anti-caries gel has a simple process, simple operation, low energy consumption, low production cost, and is suitable for industrial production; the tubular anhydrous anti-caries gel is easy to use and is suitable for a variety of scenarios, overcoming the traditional dependence of the anhydrous anti-caries gel on external brush accessories during use.

Claims

1. An anhydrous anti-caries gel, characterized in that: The preparation comprises the following raw materials, calculated by weight: 1 to 20 parts of a non-aqueous matrix, 5 to 10 parts of a bioactive material, 2 to 7 parts of a fluoride ion source, 40 to 80 parts of a volatile organic solvent, 2 to 10 parts of a film-forming agent, 5 to 15 parts of a thickener, and 0.1 to 1 part of an antibacterial agent; The non-aqueous matrix includes polyethylene glycol and / or glycerol; The bioactive material includes one or more of regenerated silicon, bioactive glass and nano-hydroxyapatite; The fluoride ion source includes one or more of sodium fluoride, olaflur, stannous fluoride and sodium monofluorophosphate; The film former includes a hydrophobic polymer.

2. The anhydrous caries-preventing gel according to claim 1, characterized in that: The volatile organic solvent includes anhydrous ethanol.

3. The anhydrous caries-preventing gel according to claim 1, characterized in that: The hydrophobic polymer includes one or more of acrylic acid (ester) / octylacrylamide copolymer, polyvinyl pyrrolidone / hexadecene copolymer, trimethylsiloxysilicate, acrylic resin and dimethylsiloxane copolymer.

4. The anhydrous caries-preventing gel according to claim 1, characterized in that: The antibacterial agent includes one or more of quaternary ammonium salt antibacterial agents, imidazole salt antibacterial agents and triclosan.

5. The anhydrous caries-preventing gel according to claim 4, characterized in that: The quaternary ammonium salt antibacterial agent includes dimethoxymethylsilylpropyl octadecyldimethylammonium chloride and / or cetylpyridinium chloride; The imidazole salt antibacterial agent includes one or more of ketoconazole, clotrimazole, miconazole, econazole and sertaconazole.

6. The anhydrous caries-preventing gel according to any one of claims 1 to 5, characterized in that: The preparation raw materials also include 0.5 to 2 parts of taste regulator.

7. The anhydrous caries-preventing gel according to claim 1, characterized in that: The preparation comprises the following raw materials in parts by mass: 5 to 15 parts of a non-aqueous matrix, 6 to 9 parts of a bioactive material, 3 to 6 parts of a fluoride ion source, 50 to 70 parts of a volatile organic solvent, 3 to 9 parts of a film-forming agent, 6 to 12 parts of a thickener, and 0.2 to 0.8 parts of an antibacterial agent.

8. The anhydrous caries-preventing gel according to claim 1, characterized in that: Calculated by weight, the non-aqueous matrix includes 1 to 10 parts of polyethylene glycol and 1 to 10 parts of glycerol.

9. The anhydrous caries-preventing gel according to claim 1, characterized in that: The olafluan is an olafluan solution, the solvent in the olafluan solution is propylene glycol, and the concentration of the olafluan solution is 10 to 40 wt%.

10. The anhydrous caries-preventing gel according to claim 9, characterized in that The concentration of the olafluor solution is 20-30 wt%.

11. The method for preparing the anticaries anhydrous gel according to any one of claims 1 to 10, characterized in that: The following steps are involved: first mixing the non-aqueous matrix and the biologically active material to obtain an emulsion; The emulsion and the fluoride ion source are mixed for a second time to obtain liquid A; a third step of mixing the film-forming agent with the volatile organic solvent to obtain a film-forming agent solution; fourthly mixing the film-forming agent solution with the thickener to obtain a viscous gel-like solution; Mixing the viscous gel solution with an antibacterial agent to obtain solution B; The liquid A and the liquid B are mixed for the sixth time to obtain an anti-caries anhydrous gel.

12. The preparation method according to claim 11, characterized in that The temperature of the first mixing and the second mixing are independently 45 to 60° C., the time is independently 30 to 60 min, and the speed is independently 600 to 1000 r / min; The temperature of the third mixing, the fourth mixing and the sixth mixing are independently 45-60° C., the time is independently 30-60 min, and the speed is independently 1800-2200 r / min; The fifth mixing temperature is 45-60°C, the time is 30-60 minutes, and the speed is 60-90 r / min; The rotational viscosity of the viscous gel solution is 10,000 to 20,000 mPa·s.

13. The preparation method according to claim 11, characterized in that The temperature of the first mixing and the second mixing are independently 45-55° C., the time is independently 30-50 min, and the speed is independently 600-800 r / min; The temperature of the third mixing, the fourth mixing and the sixth mixing are independently 45-55° C., the time is independently 30-50 min, and the speed is independently 1900-2100 r / min; The fifth mixing temperature is 45-55°C, the time is 30-50 minutes, and the speed is 60-80 r / min; The rotational viscosity of the viscous gel solution is 12000-18000 mPa·s.

14. Use of the anhydrous caries-preventing gel according to any one of claims 1 to 10 or the anhydrous caries-preventing gel prepared by the method according to any one of claims 11 to 13 in the preparation of a drug for tooth enamel remineralization.

15. A tubular anhydrous caries-preventing gel, comprising a packaging material and the anhydrous caries-preventing gel in the packaging material, wherein the packaging material comprises a rotary integrated brush having a cavity, and the rotary integrated brush is provided with a pen head; the anhydrous caries-preventing gel is the anhydrous caries-preventing gel according to any one of claims 1 to 10 or the anhydrous caries-preventing gel prepared by the preparation method according to any one of claims 11 to 13.

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