Dental varnish

Abstract

To provide methods for producing a dental varnish composition.SOLUTION: Provided is a method of synthesis of a dental varnish comprising: a. polymerizing dopamine; b. covalently boding the polymerized dopamine of the step (a) with a cationic polymer; c. reacting the cationic polymer with an anionic polymer; and d. crosslinking the dopamine with a metal ion.SELECTED DRAWING: Figure 9

Description

[Technical Field]

[0001] The present disclosure generally relates to dental treatment compositions, and more specifically to dental varnish compositions useful for effective fluoridation, enhanced remineralization of tooth enamel, and hypersensitivity due to occlusion of dentinal tubules. The dental varnish composition comprises a hydrogel system and at least one fluoride source, and the dental varnish is water-soluble. The hydrogel system comprises at least one polyphenol having at least one phenolic group, at least one polymer, and metal ions. The present disclosure also provides a method for producing such a dental varnish composition. [Background technology]

[0002] Caries and tooth sensitivity are two very common dental conditions. Dental varnishes, such as fluoride, are known to treat both caries and tooth sensitivity. Fluoride forms a protective layer of CaF2 on the teeth. As a result, dissolution of tooth enamel, which is primarily composed of hydroxyapatite, under acid attack is slowed by the formation of acid-resistant fluorapatite. Fluoride also accelerates the crystallization of hydroxyapatite, preventing further demineralization.

[0003] Commonly used fluoride sources are aminofluorides, stannous fluoride, sodium phosphate difluoride, sodium monofluorophosphate, and sodium fluoride. Each has its own advantages and limitations. For example, aminofluorides such as N',N'-tri-(polyoxyethylene)-N-hexadecylpropylenediamine dihydrofluoride, 9-octadecylamine hydrofluoride, hexadecylamine hydrofluoride, and bis-(hydroxyethyl)-aminopropyl-N-hydroxyethyloctadecylamine dihydrofluoride have a characteristic taste that is difficult to mask due to their cationic activity. However, even low concentrations (0.001% F) are highly effective. On the other hand, stannous fluoride is not stable in aqueous preparations, has an unpleasant metallic bitter taste, is irritating to the gums, and causes discoloration due to the deposition of Sn3F3PO4. Therefore, stannous fluoride prophylactic products have long been completely removed from the market.

[0004] Sodium fluoride (NaF) is a fluoride salt commonly used in varnish systems. Sodium fluoride has a basic pH and is chemically stable when stored in plastic or polythene containers. NaF dissolves well in water and rapidly releases very high concentrations of fluoride. Sodium fluoride provides highly reactive fluoride ions, and therefore blending with compatible abrasives is crucial to achieving caries prevention benefits. These materials are not irritating to the gums and do not cause discoloration of teeth.

[0005] On the other hand, sodium phosphate acid fluoride (APF) is composed of NaF with the addition of acid. The fluoride concentration is 1.23%, the acid is in the form of orthophosphoric acid, and the pH is 3.2. It is chemically stable when stored in plastic containers and does not cause tooth discoloration. The success of any topical fluoride additive depends on its ability to deposit fluoride ions into enamel not only as calcium fluoride but also as fluoroapatite. Compared to NaF, APF effectively stimulates the deposition of fluoroapatite on enamel by increasing the fluoride ion concentration and decreasing the pH. The increased fluoride ion concentration leads to the formation of calcium fluoride and phosphate, while the presence of acid leads to the dissolution of the outer enamel surface and the release of calcium and phosphate. Both reactions result in the formation of phosphate. Increasing the phosphate concentration shifts the reaction equilibrium to the right, in the direction in which fluorapatite and hydroxyapatite crystals are formed.

[0006] Sodium monofluorophosphate (NaMFP), unlike other ionic fluorides, consists of a covalently bonded fluoride compound and therefore cannot enter solution by dissociation. It must first be hydrolyzed by bacterial phosphatases present in saliva and dental plaque. Therefore, NaMFP releases significantly less fluoride at a much slower rate than other ionically soluble fluoride salts, such as NaF, SnF, and amino fluorides. Mechanistically, ionically bound fluoride acts by dissociation of the fluoride ion and subsequent precipitation of calcium fluoride, while the sodium monofluorophosphate ion is presumably incorporated into enamel and dentin as a complex ion.

[0007] Fluoride-containing products, such as toothpastes, fluoride trays, mouthrinses, and tablets, are typically developed for topical application in a variety of concentrations and application forms. Because fluoride uptake into enamel is a relatively slow process requiring long contact times, fluoride varnishes were developed. These are typically polymer coatings containing a fluoride source that present fluoride in close proximity to the enamel for extended periods. Varnishes offer additional advantages over other treatments: they provide extended contact time between the fluoride agent and the enamel surface, acting as a sustained-release reservoir; they increase the amount of fluoride permanently retained in the enamel; they prevent or slow the progression of caries through the formation of acid-resistant fluorapatite and / or fluorohydroxyapatite; they minimize exposure to large amounts of fluoride and are easy to apply; they are rapid, requiring no specialized prophylaxis; and they can be applied without eating or drinking. Commonly used ingredients in fluoride varnishes are sodium fluoride, rosin and / or synthetic resins, various solvents, flavoring agents, sweeteners, and pigments.

[0008] Although current varnishes have shown great success in preventing caries and tooth sensitivity, these systems have certain limitations. Traditional fluoride varnishes are made from wood rosin and synthetic resins that are partially dissolved by organic solvents. These rosin coatings are hydrophobic and do not release sufficient fluoride in an effective manner. Furthermore, solvents such as hexane or heptane are not sufficiently biocompatible. Other traditional fluoride varnishes contain polymers that dissolve in solvents such as ethyl acetate or butyl acetate. Ethyl acetate and butyl acetate are harsh to oral tissues and are poorly tolerated by patients. Furthermore, many traditional fluoride varnishes leave a long-lasting hard coat on the tooth, which must be destroyed and extracted from the tooth. Furthermore, many traditional fluoride varnishes can have a yellow color, which is aesthetically unpleasing to patients. Existing varnishes containing sodium fluoride contain little to no water (<5%). However, sodium fluoride is soluble in water, and therefore fluoride is insoluble in hydrophobic solutions, resulting in precipitation and the creation of heterogeneous mixtures, resulting in the formation of fluoride particle accumulations and irregular fluoride release. To interact with tooth enamel, the precipitated fluoride must first be dissolved by aqueous saliva (saliva normally dissolves the fluoride available at the surface of the film). Since the trapped fluoride within the film is difficult to release, slowing the release of fluoride is crucial. Another problem is that the released fluoride ions can only diffuse through the hydrophobic varnish film toward the tooth surface, resulting in most of the fluoride ions migrating into the oral cavity. This means that while known products can release large amounts of fluoride, only a small amount reaches the enamel, increasing the risk of fluorosis due to the high sodium fluoride concentrations required for adequate fluoridation. Summary of the Invention [Problem to be solved by the invention]

[0009] As discussed above, there is a continuing need for varnish systems that overcome the problems of existing varnish systems.

[0010] It is an object of the present disclosure to provide a one-component hydrogel-based varnish with controlled adhesive and gelling properties. In embodiments, the final varnish composition does not contain organic solvents.

[0011] To develop a hydrogel system based varnish complex of naturally occurring polyphenols, at least one polymer and metal ions were used to create a hydrogel system that crosslinks and rapidly adheres to the tooth enamel surface upon contact with the tooth enamel in the aqueous environment of saliva.

[0012] A first aspect of the present disclosure is a hydrogel system for use in a dental varnish composition, the hydrogel system comprising: (a) at least one polyphenol having at least one phenolic group; (b) at least one polymer comprising functional groups capable of forming hydrogen bonds with the polyphenol; and (c) metal ions.

[0013] According to one embodiment of the present disclosure, the hydrogel system is capable of forming a crosslinked film and simultaneously adhering to the tooth enamel surface.

[0014] A second aspect of the present disclosure herein is a dental varnish composition comprising a hydrogel system and at least one fluoride source, wherein the hydrogel system comprises: (a) at least one polyphenol having at least one phenolic group; (b) at least one polymer comprising a functional group capable of forming hydrogen bonds with the polyphenol; and (c) a metal ion source. The dental varnish is water-soluble.

[0015] According to one embodiment of the dental varnish composition, the at least one polyphenol is selected from the group consisting of resveratrol, tannic acid, gallic acid, isoflavones, flavonols, flavones, isoflavones, flavanones, hydroxycinnamic acids, tocopherols, anthocyanidins, procyanidins, catechins, and combinations thereof.

[0016] According to another embodiment of the dental varnish composition, the at least one polymer is selected from the group consisting of polyethylene glycol, polyethyleneimine, poly(N-isopropylacrylamide) (PNIPAM), polyacrylonitrile, polyoxazoline, poly(N-vinylpyrrolidone) (PVPON), poly(2-alkyl-2-oxazoline), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), polyvinyl alcohol, pluronic, polyacrylic acid, polymethylmethylacrylic acid, polymer. Acrylic acid, poly(vinylamine) hydrochloride, poly(L-lysine hydrobromide), poly(allylamine), poly(allylamine hydrochloride), poly(4-aminostyrene), poly(N-methylvinylamine), poly(ethylene glycol) bis(2-aminoethyl), poly(diallyldimethylammonium chloride), poly(2-vinyl-1-methylpyridinium bromide), poly(N-ethenylformamide), polyacrylamide (PAM), chitosan, poly(benzyl methacrylate), poly(isobutyl acrylate) acrylate), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(isobutyl methacrylate), poly(n-decyl acrylate), poly(ethyl acrylate), poly(glycidyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl methacrylic acid), poly(2-hydroxypropyl methacrylate), poly(lauryl acrylate), poly(octadecyl methacrylate), poly(isopropyl methacrylate), poly(β-amino ester), poly esters, polycarbophil, poly(acrylamide / acrylic acid), poly(2-ethyl-2-oxazoline), poly(hexamethylene adipamide), poly(hexamethylene sebacamide), polymethacrylamide, polyaniline, poly(2-methacryloxyethyltrimethylammonium bromide), poly(lysine), poly(N-vinylpyrrolidone), poly(lactic acid), poly(acrylic acid chloride), poly(ethylene glycol) 2-mercaptoethyl ether acetate, and mixtures thereof.

[0017] According to another embodiment of the dental varnish composition, the source of metal ions includes a source of divalent or trivalent metal ions, and mixtures thereof.

[0018] According to one embodiment of the dental varnish composition, the at least one fluoride source is selected from the group consisting of aluminum fluoride, indium fluoride, stannous fluoride, titanium fluoride, amine fluoride, sodium fluoride, sodium hydrofluorosilicate, sodium fluorosilicate, potassium fluoride, disodium monofluorophosphate, sodium acid fluoride phosphate, potassium fluoride, and mixtures thereof.

[0019] According to another embodiment of the dental varnish composition, the hydrogel system promotes increased adhesion of the varnish composition to the tooth surface.

[0020] A third aspect of the present disclosure is a method for preparing a dental varnish composition, the method comprising: (a) dissolving at least one polyphenol having at least one phenol in a solvent to form a polyphenol solution; (b) adding an antioxidant and a metal ion source to the polyphenol solution; (c) mixing the polyphenol solution with a polymer solution to form a hydrogel system; (d) removing the solvent from the hydrogel system; and (e) mixing the hydrogel system with a fluoride source to form a dental varnish.

[0021] The varnish based on the hydrogel system of the present disclosure surprisingly showed much better fluoride dissolution and higher uptake into enamel, as well as effective fluoridation and enhanced remineralization of tooth enamel.Furthermore, the varnish based on the hydrogel system of the present invention is expected to offer several advantages over existing varnishes, such as being soluble in aqueous buffer solutions at physiological pH instead of toxic organic solvents; the basic polymer system of the varnish is naturally derived and highly biocompatible / bioactive instead of being based on synthetic polymer resins; the varnish quickly adheres / crosslinks to enamel when in contact with the enamel surface in an aqueous environment; there is no need to dry the tooth surface before applying the varnish; its low viscosity allows for greater uptake of varnish components into enamel and caries; and a low concentration of fluoride is required in the varnish.

[0022] Additionally, dental varnish compositions comprising the hydrogel system of the present disclosure may be useful in occluding dentinal tubules.

[0023] According to another method of the present invention, a single-step and one-pot synthesis of a hydrogel-based dental varnish is provided. A hydrogel-based dental varnish system is provided that is capable of forming a crosslinked (cohesive) film that simultaneously adheres to an enamel surface upon contact with a moist or wet enamel surface at physiological pH and temperature.

[0024] Other aspects will be set forth in the description that follows, and in part will be obvious from the description, or may be learned by practice of the disclosure.

[0025] The above aspects, as well as other aspects, features, and advantages of the present disclosure, are described below in connection with various embodiments with reference to the accompanying figures. [Brief explanation of the drawings]

[0026] [Figure 1] FIG. 1 illustrates a single component polymer system for cohesion and adhesion. [Figure 2] FIG. 1 shows tannic acid / gallic acid / metal ion / PEG-based complexes for aggregation and adhesion. [Figure 3] FIG. 1 shows adhesion tests performed on tannic acid / gallic acid / metal ions / PEG-based hydrogel systems on wet and dry bovine teeth. [Figure 4] FIG. 1 shows pH titration of tannic acid / gallic acid / metal ion / PEG-based complexes. [Figure 5] FIG. 1 shows the adhesion of varnishes containing both stannous fluoride and sodium fluoride to wet bovine teeth stained with mustard and turmeric. [Figure 6] FIG. 1 shows the synthesis of a TA / GA / PEG system. [Figure 7] FIG. 1 shows calcium absorption by tannic acid / gallic acid / metal ions / PEG-based hydrogel systems. [Figure 8] SEM: Obstruction of dentinal tubules. [Figure 9] FIG. 1 shows an alternative single component polymer system for cohesion and adhesion. [Figure 10] FIG. 1 shows the synthesis of PAA-PEI and dopamine-based hydrogel systems. [Figure 11] FIG. 1 shows adhesion testing of varnish to hydroxyapatite discs. [Figure 12] FIG. 1 shows a remineralization test of varnish. [Figure 13] FIG. 1 shows a dentin tubule occlusion test using varnish. DETAILED DESCRIPTION OF THE INVENTION

[0027] Some of the terms used in this disclosure are defined below.

[0028] As used herein, the term "dental varnish" includes compositions that are topically applied to tooth surfaces for fluoride therapy. Typically, dental varnishes contain high concentrations of fluoride.

[0029] As used herein, the terms "tooth structure" and "tooth surface" refer to any part of an individual's teeth to which fluoride can be absorbed or bound. Thus, tooth structure and tooth surface include, but are not limited to, tooth enamel, early enamel lesions, hydroxyapatite in enamel, dentin, and cementum.

[0030] As used herein, the term "hydrogel system" refers to a physically or chemically crosslinked polymer network with a high water content.

[0031] As used herein, the term "remineralization" means the crystallization of calcium and phosphate ions into demineralized tooth enamel.

[0032] Disclosed herein are hydrogel systems, dental varnish compositions including the hydrogel systems, and methods of using the dental varnish compositions to enhance effective fluoridation and remineralization of tooth enamel, occlusion of dentinal tubules, and inhibition of dental plaque biofilm.

[0033] Hydrogel system To develop a water-soluble varnish system, a water-soluble polymer or hydrogel system must form a crosslinked film (that is cohesive with itself) and simultaneously adhere to the tooth enamel surface when the varnish comes into contact with the enamel, even under moist or wet conditions and physiological pH and temperature, all under physiological and natural conditions found in a patient's mouth, as shown in Figure 1.

[0034] Nature contains many natural substances with unexpected adhesive properties. One example of an adhesive found in nature is the adhesive protein used by mussels to adhere to rocks and stones. Therefore, to design a novel hydrogel system suitable for use in dental applications, we developed a polymer complex based on a naturally available polyphenol molecule / polymer / metal ion complex containing at least one phenolic group.

[0035] In a first aspect of the present disclosure, there is provided a hydrogel system for use in a dental varnish, comprising: The hydrogel system includes (a) at least one polyphenol having at least one phenolic group; (b) at least one polymer containing functional groups capable of forming hydrogen bonds with the polyphenol; and (c) metal ions.

[0036] In certain embodiments of the hydrogel systems disclosed herein, the at least one polyphenol is selected from the group consisting of resveratrol, tannic acid, gallic acid, isoflavones, flavonols, flavones, isoflavones, flavanones, hydroxycinnamic acids, tocopherols, anthocyanidins, procyanidins, catechins, and combinations thereof.

[0037] In certain embodiments of the hydrogel systems disclosed herein, the at least one polyphenol comprises a phenolic group selected from the group consisting of catechol, pyrogallol, and combinations thereof.

[0038] In certain embodiments of the hydrogel systems disclosed herein, the at least one polyphenol having at least one phenolic group comprises tannic acid (TA) and / or gallic acid (GA).

[0039] Similar to mussel adhesive proteins, tannic acid and gallic acid are naturally available polyphenolic molecules. The presence of di- and trihydroxyl functional groups at the meta- and para-positions of benzoic acid in tannic acid and gallic acid promotes high binding affinity to different substrates through, but not limited to, electrostatic, hydrogen bonding, and hydrophobic interactions.

[0040] The pyrogallol groups in tannic acid and gallic acid can form functional polymer adhesives through two different approaches. First, they form a three-dimensional network through intermolecular hydrogen bonding with aqueous polymer solutions. Second, the pyrogallol groups in tannic acid and gallic acid strongly cross-link with at least one metal ion by forming a robust and reversible complex with the aqueous solution of the metal ion. In the present system, both approaches to hydrogel formation are combined into one system to form a hydrogel varnish, as shown in Figure 2. The relative concentrations of PEG / TA / GA / metal ions, pH, terminal functional groups on PEG, and the number of PEG arms are factors that control the adhesive and cohesive properties of the varnish.

[0041] The molecular basis of adhesion is reversible coordination of metal oxides, π-π interactions with various synthetic polymers, and irreversible covalent bonding to any surface. In the cohesive function, catechol undergoes a pH-dependent oxidation reaction resulting in the transformation of catechol and pyrogallol / gallol to quinone. Therefore, tannic acid is a reasonable candidate for the design of hydrogel systems that can function as both adhesive and cohesive materials, depending on the external environment.

[0042] In certain embodiments of the hydrogel systems disclosed herein, the hydrogel system may include a polymer having functional groups capable of forming hydrogen bonds with polyphenols.

[0043] The functional group can be hydroxy, amine, thiol, carboxyl, carbonyl, ester, imine, amide, nitrile, or any suitable functional group capable of forming a hydrogen bond with a polyphenol, as will be understood by one of skill in the art.

[0044] In certain embodiments of the hydrogel systems disclosed herein, the at least one polymer having hydroxyl groups is polyethylene glycol or polyvinyl alcohol.

[0045] In certain embodiments of the hydrogel systems disclosed herein, at least one polymer comprises an amino group, including, but not limited to, poly(vinylamine) hydrochloride, poly(L-lysine hydrobromide), poly(allylamine), poly(allylamine hydrochloride), poly(4-aminostyrene), poly(N-methylvinylamine), poly(ethylene glycol) bis(2-aminoethyl), poly(N-vinylpyrrolidone), poly(2-alkyl-2-oxazolines), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), or poly(diallyldimethylammonium chloride).

[0046] In certain embodiments of the hydrogel systems disclosed herein, the at least one polymer having amide groups includes, but is not limited to, poly(N-ethenylformamide), polyacrylamide (PAM), or poly(hexamethylene adipamide), poly(hexamethylene sebacamide), polymethacrylamide, poly(N-isopropylacrylamide), and nylon.

[0047] In certain embodiments of the hydrogel systems disclosed herein, at least one polymer may have an imine group, for example, polyethyleneimine.

[0048] In certain embodiments of the hydrogel systems disclosed herein, at least one polymer may have nitrile groups, for example, polyacrylonitrile.

[0049] In certain embodiments of the hydrogel systems disclosed herein, at least one polymer may have a thiol group, for example, poly(ethylene glycol) 2-mercaptoethyl ether acetic acid.

[0050] In certain embodiments of the hydrogel systems disclosed herein, at least one polymer can have a carboxy group, for example, the polymer can be, but is not limited to, polyacrylic acid, polymethylmethacrylic acid, polymethylacrylic acid, poly(2-hydroxyethylmethacrylic acid), poly(lactic acid), and polycarbophil.

[0051] In certain embodiments of the hydrogel systems disclosed herein, the at least one polymer having ester groups includes, but is not limited to, poly(benzyl methacrylate), poly(isobutyl acrylate), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(isobutyl methacrylate), poly(n-decyl acrylate), poly(ethyl acrylate), poly(glycidyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl methacrylate), poly(lauryl acrylate), poly(octadecyl methacrylate), poly(isopropyl methacrylate), poly(β-amino esters), and polyesters.

[0052] In certain embodiments of the hydrogel systems disclosed herein, the at least one polymer can be a macromolecule such as nylon, pullulan, gellan gum, hyaluronic acid, starch, cellulose, chitosan, chitin, xanthan gum, guar gum, dextran, alginate, collagen, gelatin, lignin, carbohydrates, silk, proteins, peptides, and DNA.

[0053] In further embodiments, the polymer is selected from polyethylene glycol, polyethyleneimine, poly(N-isopropylacrylamide) (PNIPAM), polyoxazoline, poly(N-vinylpyrrolidone) (PVPON), poly(2-alkyl-2-oxazoline)s, poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), pullulan, gellan gum, hyaluronic acid, and mixtures thereof.

[0054] In certain embodiments of the hydrogel systems disclosed herein, the metal ion source includes a divalent, trivalent metal ion source, or a mixture thereof.

[0055] It will be understood that there is no particular limitation on the source of the metal ions.

[0056] Examples of suitable divalent ion sources include, but are not limited to, salts of calcium, zinc, magnesium, tin, strontium, chromium, manganese, beryllium, barium, cobalt, nickel, lead, and copper, although typically the salts are selected from the group consisting of calcium chloride, stannous fluoride, stannous chloride, zinc chloride, and the like.

[0057] Examples of suitable trivalent ion sources include, but are not limited to, salts of aluminum, iron, chromium, bismuth, manganese, cobalt, and indium, but typically the salts are selected from the group consisting of aluminum chloride, aluminum sulfate, iron chloride, iron oxide, indium fluoride, and the like.

[0058] In certain embodiments of the hydrogel systems disclosed herein, the hydrogel system further comprises an antioxidant.

[0059] The antioxidant may be selected from the group consisting of boric acid, ascorbic acid, borax, sodium tetraborate, 4,4'-biphenyldiboronic acid, benzene-1,4-diboronic acid, 2,5-thiophenediylbisboronic acid, sulfur dioxide, uric acid, tocopherol, and mixtures thereof.

[0060] In certain embodiments of the hydrogel systems disclosed herein, the hydrogel system further comprises a solvent.

[0061] The solvent is selected from the group consisting of water, ethyl alcohol, isopropanol, ethyl acetate, butyl acetate, isoamyl propionate, hexane, heptane, and mixtures thereof.

[0062] Methods for forming the hydrogel systems are also disclosed herein.

[0063] The hydrogel system of the present disclosure comprises: (a) dissolving at least one polyphenol having at least one phenol in a solvent to form a polyphenol solution; (b) adding a metal ion source and optionally an antioxidant to the polyphenol solution; (c) mixing the polyphenol solution with the polymer solution to prepare a hydrogel system; (d) removing the solvent from the hydrogel system.

[0064] In certain embodiments of the method of preparing a hydrogel system, the at least one polyphenol is selected from the group consisting of resveratrol, tannic acid, gallic acid, isoflavones, flavonols, flavones, isoflavones, flavanones, hydroxycinnamic acids, tocopherols, anthocyanidins, procyanidins, catechins, and combinations thereof.

[0065] In certain embodiments of the method of preparing the hydrogel system, the at least one polyphenol having at least one phenolic group includes tannic acid and gallic acid.

[0066] In certain embodiments of the method of preparing the hydrogel system, the tannic acid and gallic acid are dissolved in a solvent selected from the group consisting of water, ethyl alcohol, isopropanol, ethyl acetate, butyl acetate, isoamyl propionate, hexane, heptane, and mixtures thereof. In embodiments, the solvent is ethanol.

[0067] The solvent may be present in the hydrogel system in an amount of from about 0% to about 100%, for example, from about 5% to about 50%, or from about 5% to about 10%, based on the total volume of the starting reaction mixture.

[0068] In certain embodiments of the method of preparing a hydrogel system, tannic acid is present at a concentration of 0.005 g / ml to 2.8 g / ml, e.g., in the range of 0.01 g / ml to 2 g / ml or in the range of 0.1 g / ml to 0.5 g / ml, based on the total volume of the hydrogel system.

[0069] In certain embodiments of the method of preparing a hydrogel system, gallic acid is present at a concentration of 0.005 g / ml to 0.175 g / ml, e.g., in the range of 0.01 g / ml to 0.1 g / ml or in the range of 0.02 g / ml to 0.0 g / ml, based on the total volume of the hydrogel system.

[0070] In certain embodiments of the method of preparing the hydrogel system, the metal ion source includes a divalent, trivalent metal ion source, or a mixture thereof.

[0071] It will be understood that there is no particular limitation on the source of the metal ions.

[0072] Examples of suitable divalent ion sources include, but are not limited to, salts of calcium, zinc, magnesium, tin, strontium, chromium, manganese, beryllium, barium, cobalt, nickel, lead, and copper.

[0073] Examples of suitable trivalent ion sources include, but are not limited to, salts of aluminum, iron, chromium, bismuth, manganese, cobalt, and indium.

[0074] In certain embodiments of the method of preparing the hydrogel system, the source of metal ions can be aluminum chloride.

[0075] In certain embodiments of the method of preparing a hydrogel system, the metal ion source is present at a concentration of 0 g / ml to 1.0 g / ml, e.g., in the range of 0.01 g / ml to 0.5 g / ml or in the range of 0.05 g / ml to 0.1 g / ml, based on the total volume of the hydrogel system.

[0076] In certain embodiments of the method of preparing a hydrogel system, the hydrogel system further comprises an antioxidant.

[0077] The antioxidant may be selected from the group consisting of boric acid, ascorbic acid, borax, sodium tetraborate, 4,4'-biphenyldiboronic acid, benzene-1,4-diboronic acid, 2,5-thiophenediylbisboronic acid, sulfur dioxide, uric acid, tocopherol, and mixtures thereof.

[0078] In certain embodiments of the method for preparing a hydrogel system, the antioxidant may be added at a concentration of 0.01 to 10 wt % based on the total volume of the hydrogel system, such as in the range of 0.05 to 5 wt % of the total varnish, or in the range of 0.1 to 1 wt %.

[0079] In certain embodiments of the method for preparing a hydrogel system, the polymer is polyethylene glycol, polyethyleneimine, poly(N-isopropylacrylamide) (PNIPAM), polyacrylonitrile, polyoxazoline, poly(N-vinylpyrrolidone) (PVPON), poly(2-alkyl-2-oxazoline), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), polyvinyl alcohol, pluronic, polyacrylic acid, polymethylmethylacrylic acid, polymethylacrylic acid. Acrylic acid, poly(vinylamine) hydrochloride, poly(L-lysine hydrobromide), poly(allylamine), poly(allylamine hydrochloride), poly(4-aminostyrene), poly(N-methylvinylamine), poly(ethylene glycol) bis(2-aminoethyl), poly(diallyldimethylammonium chloride), poly(2-vinyl-1-methylpyridinium bromide), poly(N-ethenylformamide), polyacrylamide (PAM), chitosan, poly(benzyl methacrylate), poly(isobutyl acrylate) ), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(isobutyl methacrylate), poly(n-decyl acrylate), poly(ethyl acrylate), poly(glycidyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl methacrylic acid), poly(2-hydroxypropyl methacrylate), poly(lauryl acrylate), poly(octadecyl methacrylate), poly(isopropyl methacrylate), poly(β-amino ester), poly(ethylene glycol acrylate ... The polymer is selected from the group consisting of esters, polycarbophil, poly(acrylamide / acrylic acid), poly(2-ethyl-2-oxazoline), poly(hexamethylene adipamide), poly(hexamethylene sebacamide), polymethacrylamide, polyaniline, poly(2-methacryloxyethyltrimethylammonium bromide), poly(lysine), poly(N-vinylpyrrolidone), poly(lactic acid), poly(acrylic acid chloride), poly(ethylene glycol) 2-mercaptoethyl ether acetate, and mixtures thereof.

[0080] In further embodiments, the polymer is selected from polyethylene glycol, polyethyleneimine, poly(N-isopropylacrylamide) (PNIPAM), polyoxazoline, poly(N-vinylpyrrolidone) (PVPON), poly(2-alkyl-2-oxazolines), poly(2)-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), pullulan, gellan gum, hyaluronic acid, and mixtures thereof.

[0081] In certain embodiments of the method of preparing a hydrogel system, the polymer is present at a concentration of 0.01 g / ml to 1.0 g / ml, e.g., in the range of 0.01 g / ml to 0.5 g / ml or in the range of 0.1 g / ml to 0.5 g / ml, based on the total volume of the hydrogel system.

[0082] In certain embodiments of the method for preparing the hydrogel system, the resulting hydrogel system was centrifuged to remove the solvent from the hydrogel system.

[0083] Dental varnish composition In another aspect of the present disclosure, a dental varnish composition is provided, comprising a hydrogel system and at least one fluoride source. The dental varnish is water-soluble. The dental varnish disclosed herein does not contain an organic solvent.

[0084] As discussed above, the hydrogel system includes at least one polyphenol having at least one phenolic group, at least one polymer including functional groups capable of forming hydrogen bonds with the polyphenol, at least one polymer, and a source of metal ions.

[0085] In certain embodiments of the dental varnish compositions disclosed herein, The hydrogel system is present in a concentration of about 5% to about 95% by weight, for example, in the range of about 7% to 75% by weight, or in the range of about 10% to about 50% by weight, based on the total weight of the composition.

[0086] In certain embodiments of the dental varnish compositions disclosed herein, the fluoride source includes, but is not limited to, aluminum fluoride, indium fluoride, stannous fluoride, titanium fluoride, amine fluoride, sodium fluoride, hydrofluorosilicates, sodium fluorosilicate, potassium fluoride, disodium monofluorophosphate, sodium fluoride acid phosphate, potassium fluoride, bismuth fluoride, zirconium tetrafluoride, sodium monofluorophosphate, hexafluorosilicic acid, difluorosilane, and mixtures thereof.

[0087] In some embodiments, the amine fluoride is selected from the group consisting of N',N'-tri-(polyoxyethylene)-N-hexadecylpropylenediamine dihydrofluoride, 9-octadecylamine hydrofluoride, hexadecylamine hydrofluoride and bis-(hydroxyethyl)-aminopropyl-N-hydroxyethyloctadecylamine dihydrofluoride, olafur, amine fluoride, and decdecatafur.

[0088] In certain embodiments of the dental varnish compositions disclosed herein, the fluoride source comprises a combination of stannous fluoride and sodium fluoride.

[0089] In certain embodiments of the dental varnish compositions disclosed herein, the fluoride source is present at a concentration of about 0.01% to about 10% by weight, e.g., in the range of about 1% to about 8% by weight, or in the range of about 2% to about 7% by weight, based on the total weight of the composition.

[0090] In certain embodiments of the dental varnish compositions disclosed herein, the dental varnish releases fluoride ions at a concentration ranging from 1000 ppm to 30,000 ppm.

[0091] The fluoride ion source can be present in an amount sufficient to provide high levels of fluoride ions in the composition, such as at least about 1,000 ppm, and in some cases up to about 30,000 ppm, for example, from about 7,000 ppm to about 27,000 ppm, from about 15,000 ppm to about 25,000 ppm, or even about 22,000 or 23,000 ppm. To provide such concentrations in the optimal ppm range, the exact weight percent of the fluoride ion source in the composition can vary depending on the stoichiometric properties of different fluoride ion sources.

[0092] In certain embodiments of the dental varnish compositions disclosed herein, the dental varnish may further comprise at least one of a remineralizing agent, a flavoring agent, a thickening agent, a sweetener, an oxidizing agent, or a combination thereof.

[0093] Examples of remineralizing agents include, but are not limited to, bioactive glass, calcium phosphate sucrose, xylitol, nanohydroxyapatite, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and calcium sodium phosposilicate. The amount of remineralizing agent in a dental varnish typically comprises at least about 0.01% by weight and typically not more than 50% by weight, e.g., the range of remineralizing agent is 0.02% to 10% by weight.

[0094] Examples of flavoring agents include, but are not limited to, peppermint, watermelon, oil of wintergreen, spearmint, cherry, citric acid, orange, strawberry, vanilla, coconut, bubblegum flavoring, and mixtures thereof. Such flavoring agents may be present in the dental varnish in an amount of about 0.01% to about 5% by weight, e.g., about 0.1% to about 4% by weight, or about 0.7% to about 3% by weight.

[0095] Examples of thickening agents include, but are not limited to, fumed silica, carboxyvinyl polymers, carrageenan, karaya gum, gum arabic, and tragacanth, magnesium aluminum silicate, and are present in the dental varnish in an amount of 0.1% to 10% by weight, such as 0.5% to 8% by weight or about 1% to about 5% by weight, based on the total weight of the composition.

[0096] Examples of sweeteners include, but are not limited to, xylitol, sorbitol, sucralose, aspartame, sodium saccharin, and mixtures thereof. Such sweeteners may be present in the dental varnish in an amount of about 0.01% to about 2% by weight, e.g., about 0.05% to about 1.5% by weight, or about 0.08% to about 1% by weight.

[0097] Antioxidants include, but are not limited to, boric acid, ascorbic acid, borax, sodium tetraborate, 4,4'-biphenyldiboronic acid, benzene-1,4-diboronic acid, 2,5-thiophenediylbisboronic acid, sulfur dioxide, uric acid, tocopherol, and mixtures thereof. When present, antioxidants may be present in the dental varnish in an amount of about 0% to about 2% by weight, e.g., about 0.01% to about 1% by weight, or about 0.08% to about 1% by weight.

[0098] In certain embodiments of the dental varnish compositions disclosed herein, the pH of the composition is in the range of pH 1 to pH 8, such as in the range of 2 to 6 or in the range of 3 to 5.

[0099] Also disclosed herein is a method of preparing a dental varnish.

[0100] The dental varnishes of the present disclosure generally comprise: (a) dissolving at least one polyphenol having at least one phenol in a solvent to form a polyphenol solution; (b) adding an antioxidant and a metal ion source to the polyphenol solution; (c) mixing the polyphenol solution with the polymer solution to prepare a hydrogel system; (c) removing the solvent from the hydrogel system; (e) mixing the hydrogel system with a fluoride source to form a dental varnish.

[0101] In certain embodiments of the method of preparing a dental varnish, the polyphenol may be present in the dental varnish in an amount of about 0.01 mmol / ml to about 50 mmol / ml, e.g., about 0.05 mmol / ml to about 25 mmol / ml, or about 0.10 mmol / ml to about 10 mmol / ml, based on the total volume of the hydrogel system.

[0102] In certain embodiments of the method of preparing a dental varnish, the antioxidant may be present in the dental varnish in an amount of about 0.003 mmol / ml to about 20 mmol / ml, e.g., about 0.015 mmol / ml to about 10 mmol / ml, or about 0.03 mmol / ml to about 3 mmol / ml, based on the total volume of the hydrogel system.

[0103] In certain embodiments of the method of preparing a dental varnish, the metal ion source may be present in the dental varnish in an amount of about 0.005 mmol / ml to about 25 mmol / ml, e.g., about 0.01 mmol / ml to about 5 mmol / ml, or about 0.05 mmol / ml to about 2 mmol / ml, based on the total volume of the hydrogel system.

[0104] In certain embodiments of the method of preparing a dental varnish, the polymer may be present in the dental varnish in an amount of about 0.001 mmol / ml to about 50 mmol / ml, e.g., about 0.01 mmol / ml to about 10 mmol / ml, or about 0.010 mmol / ml to about 1.0 mmol / ml, based on the total volume of the hydrogel system.

[0105] In certain embodiments of the method of preparing a dental varnish, the fluoride source may be present in the dental varnish in an amount of about 0.01 mmol / ml to about 5 mmol / ml, e.g., about 0.005 mmol / ml to about 2.5 mmol / ml, or about 0.001 mmol / ml to about 1.0 mmol / ml, based on the total volume of the hydrogel system.

[0106] Characteristics / Applications The pyrogallol groups of TA and GA also act as Ca 2+ It has a strong affinity for ions. This strong affinity allows it to 2+ The trapping of ions can accelerate the formation of HAp crystals in the enamel and tubules. The GA / metal ion complex within the tubules led to the remineralization of HAp in the presence of saliva, and after 7 days of immersion in artificial saliva, densely packed HAp crystals with a high degree of order and uniformity were obtained. The relative concentrations of PEG / TA / GA / metal ions, pH, PEG terminal functional groups, and the number of PEG arms are factors that control the adhesive and cohesive properties of hydrogel varnishes.

[0107] In certain embodiments of the dental varnish compositions disclosed herein, the hydrogel system facilitates increased adhesion of the varnish composition to the tooth surface.

[0108] In certain embodiments of the dental varnish compositions disclosed herein, the hydrogel system promoted in situ remineralization of tooth surfaces.

[0109] In certain embodiments of the dental varnish compositions disclosed herein, the hydrogel system promoted occlusion of dentinal tubules.

[0110] The combination of TA / GA / PEG and TA / GA / metal ion complexes may be a powerful system that can be used to design much faster-reacting polymer systems with tunable cohesive and adhesive properties for dental varnishes. Furthermore, the hydrogel-based dental varnishes described herein have many advantages, including low cost, non-toxicity even after ingestion, ease of use, antioxidant, antimutagenic, anticarcinogenic, and antibacterial properties.

[0111] Single-step and one-pot synthesis In an alternative method according to the present invention, a simplified single-step and one-pot synthesis method for hydrogel-based dental varnishes has been developed. As shown in Figure 9, the hydrogel-based dental varnish system is capable of forming a crosslinked film (cohesive) that simultaneously adheres to enamel surfaces upon contact with moist or wet enamel surfaces at physiological pH and temperature. The hydrogel-forming polymer comprises a mixture of water-soluble anionic and cationic polymers and an adhesion promoter chemically and / or physically bound to the water-soluble polymer.

[0112] In this hydrogel system, interactions between the cationic polymer, anionic polymer, dopamine, and metal ions aid in film formation. The presence of dihydroxyl functional groups at the meta and para positions of the benzoic acid in dopamine promotes cohesion and adhesion through chemistry as described below;

[0113] a) Dopamine gelation (aggregation) chemistry As mentioned above, one of the key requirements for a hydrogel varnish is its ability to aggregate under physiological conditions. Under oxidizing conditions at basic pH, dopamine oxidation catalyzed by catechol oxidase with an oxidizing agent generates a quinone, which then participates in a crosslinking reaction between the quinone and adjacent dopamine molecules via a permanent aryl-aryl covalent bond (forming didopamine). This mediates intermolecular covalent crosslinking, which significantly contributes to the rapid aggregation (or gelation) of catechol-grafted polymers.

[0114] b) Adhesion chemistry of dopamine. The catechol group of dopamine is versatile and can adhere to any surface via several chemical mechanisms in a moist environment. Under reducing conditions, the catechol side chain of dopamine has a strong affinity for binding to both organic and inorganic surfaces through either covalent adhesion or strong, reversible bonding, such as hydrogen bonding in moist conditions, bidentate metal ion coordination and complexation, and π-π aromatic interactions. Catechol rapidly binds to surfaces by displacing bound water molecules from the substrate and reacting various functional groups (e.g., -NH2, -SH) via Michael addition and Schiff base reactions, and to metal ions (e.g., Fe) via chelation mechanisms. 3+ , Mg 2+ , Ca 2+ , Zn 2+ ) binds strongly to hydroxyapatite. Notably, catechol adsorbs more readily to hydroxyapatite than other agents such as alcohols, amines, and carboxylic acids, which is important for application, and also attracts calcium and phosphate ions from saliva. Therefore, the presence of catechol side chains on the polymer will effectively induce cohesion and adhesion of the polymer cross-linked gel.

[0115] In this study, a single-step and one-pot synthetic procedure was developed. To develop a hydrogel varnish using this procedure, an adhesion promoter such as dopamine was first reacted with cationic polymers of different molecular weights containing amine groups, such as branched polyethyleneimine (bPEI), by increasing the pH of deionized water (DI water) at room temperature. This dopamine-on-PEI conjugation procedure eliminates the need for expensive carbodiimide catalysts such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and cumbersome purification steps to remove unreacted reagents. After the reaction of dopamine with the cationic polymer, an anionic polymer such as polyacrylic acid was added to the reaction mixture. Next, divalent or trivalent metal ions were added to the formulation, as shown in Figure 2.

[0116] Four distinct reactions occur in the formulations of the present invention: 1. Dopamine self-polymerizes; 2. Dopamine covalently bonds with the cationic polymer polyethyleneimine (PEI) via Michael addition and Schiff base reactions; 3. The cationic polymer PEI reacts with the anionic polymer polyacrylic acid (PAA) via electrostatic interactions; and 4. The catechol groups in dopamine strongly cross-link with metal ions through the formation of robust, reversible complexes with aqueous solutions of the metal ions. The relative concentrations of PAA / bPEI / dopamine / metal ions, pH, and the molecular weights and molecular weight distributions of PAA and bPEI are factors that control the adhesive and cohesive properties of the varnish.

[0117] The varnish formulations of the present invention may include water-soluble polymers, cationic polymers, metal ions, fluoride agents, antioxidants, and may also include one or more of thickeners, tackifiers, flavoring agents, and sweeteners.

[0118] Suitable water-soluble polymers include, but are not limited to, hyaluronic acid (HA), polyacrylic acid (PAA), chitosan, hydroxypropyl methylcellulose (HPMC), polymethyl methacrylic acid, polymethyl acrylic acid, poly(isobutyl acrylate), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(isobutyl methacrylate), poly(n-decyl acrylate), poly(ethyl acrylate), poly(glycidyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl methacrylate), poly(lauryl acrylate), poly(octadecyl methacrylate), poly(isopropyl methacrylate), polyacrylamide (PAM), poly(acrylamide / acrylic acid), polyethylene glycol (PEG), PEG-modified polymers, water-soluble or partially water-soluble modified rosin, poly(N-isopropylacrylamide) (PNIPAM), polyacrylonitrile, polyoxazoline, poly(N-vinylpyrrolidone) (PVPON), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), polyvinyl alcohol, Pluronic, poly(vinylamine) hydrochloride, poly(L-lysine hydrobromide), poly(allylamine hydrochloride), poly(4-aminostyrene), poly(N-methylvinylamine), poly(2-vinyl-1-methylpyridinium bromide), poly(N-ethenylformamide), poly(benzyl methacrylate), poly(β-amino ester), polyester, poly(hexamethylene adipamide), poly(hexamethylene sebacamide), or a combination thereof. In some embodiments of the method of forming a hydrogel-forming polymer, the water-soluble polymer has a weight average molecular weight in the range of 1 kDa to about 4000 kDa, e.g., about 100 kDa to about 1500 kDa. In some embodiments of the method of forming a hydrogel-forming polymer, the water-soluble polymer is present at a concentration of about 0.01% to about 50% by weight, e.g., 0.1% to 20% by weight, or about 1% to about 10% by weight, based on the total volume of the reaction solution.

[0119] Suitable cationic polymers may include, but are not limited to, lysine, arginine, polylysine, polyarginine, linear polyethyleneimine, branched polyethyleneimine, or poly(diallyldimethylammonium chloride) (polyDADMAC), or combinations thereof. The cationic polymer has a weight average molecular weight ranging from 100 Da to about 1000 kDa, such as from about 1000 Da to about 10,000 Da. In some embodiments, the ratio of stimuli moiety cationic groups to hydrogen-forming polymer repeat unit functional groups is in the range of 1:2 to about 2:1, alternatively in the range of 1:2 to 1:1, alternatively in the range of 1:1 to 2:1, or approximately 1:1, or any value, range, or subrange therebetween.

[0120] Suitable adhesion promoters include, but are not limited to, dopamine, dopamine having an electron-withdrawing group attached to the 6-position of the dopamine aromatic ring, dopamine complexed with an electron-withdrawing group (nitro group (-NO), chloro group (-Cl), or fluoro group (-F) on the hydroxyl group of dopamine), and dihydroxyphenylalanine, norepinephrine, dihydroxyphenylserine, epinephrine, resveratrol, gallic acid, isoflavones, flavonols, flavones, isoflavones, flavanones, hydroxycinnamic acids, tocopherols, anthocyanidins, procyanidins, catechins, and combinations thereof. In some embodiments of the method for forming a hydrogel-forming polymer, the adhesion promoter is added in a molar ratio of 1:100 to 50:100 relative to the number of available functional groups on the repeat unit of the water-soluble polymer, such as a molar ratio of 30:100 relative to the number of available functional groups on the repeat unit of the water-soluble polymer.

[0121] The metal ion source is selected from the group consisting of divalent or trivalent metal ion sources and mixtures thereof. Examples of suitable divalent ion sources include, but are not limited to, salts of calcium, zinc, magnesium, tin, strontium, chromium, manganese, beryllium, barium, cobalt, nickel, lead, and copper. Examples of suitable trivalent ion sources include, but are not limited to, salts of aluminum, iron, chromium, bismuth, manganese, cobalt, and indium. In certain embodiments of the method for preparing the water-soluble composition, the metal ion source may be present in the dental composition in an amount of about 0.001 mmol / ml to about 5 mmol / ml, for example, about 0.002 mmol / ml to about 1 mmol / ml or about 0.01 mmol / ml to about 2 mmol / ml, based on the total volume of the hydrogel-forming polymer.

[0122] Suitable fluoride agents are selected from the group consisting of hydrofluoric acid, sodium fluoride, stannous fluoride, sodium phosphate, amine fluorides, fluorosilanes, and mixtures thereof. In some embodiments, the amine fluoride is selected from the group consisting of N',N'-tri-(polyoxyethylene)-N-hexadecylpropylenediamine dihydrofluoride, 9-octadecylamine hydrofluoride, hexadecylamine hydrofluoride, and bis-(hydroxyethyl)-aminopropyl-N-hydroxyethyloctadecylamine dihydrofluoride. The fluoride source is present in a concentration of about 0.01% to about 10% by weight, for example, about 1% to about 8% by weight, or about 2% to about 7% by weight, based on the total weight of the composition. The fluoride ion source may be present in an amount sufficient to provide a high level of fluoride ion in the composition, i.e., at least about 1,000 ppm, and in some cases up to 22,600 ppm. To provide such a concentration in the optimum ppm range, the exact weight percent of the fluoride ion source in the composition may vary depending on the stoichiometric properties of different fluoride ion sources.

[0123] The antioxidant may be selected from the group consisting of ascorbic acid, sodium metabisulfite, boric acid, sodium tetraborate, 4,4'-biphenyldiboronic acid, benzene-1,4-diboronic acid, 2,5-thiophenediylbisboronic acid, sulfur dioxide, uric acid, tocopherol, and mixtures thereof. The antioxidant may be present in the dental composition in an amount of about 0.005 mmol / ml to about 20 mmol / ml, e.g., about 0.025 mmol / ml to about 10 mmol / ml, or about 0.05 mmol / ml to about 5 mmol / ml, based on the total volume of the hydrogel-forming polymer.

[0124] Examples of thickeners include, but are not limited to, fumed silica, carboxyvinyl polymer, carrageenan, karaya gum, gum arabic, tragacanth, and magnesium aluminum silicate. The amount of thickener present in the dental varnish is about 0.1% to about 1.0% by weight, for example, about 0.5% to about 5.0% by weight, or about 1% to about 10% by weight.

[0125] Examples of tackifiers suitable for use herein include, but are not limited to, rosin, mastic, shellac, cellulose and cellulose derivatives, pullulan, xanthan gum, chitosan, hydroxypropyl methylcellulose (HPMC), poloxamer, and gellan gum. Such tackifiers described herein may be present in the dental varnish in an amount of about 0.01% to about 0.1% by weight, e.g., about 0.05% to about 1% by weight, or about 1% to about 10% by weight.

[0126] Examples of suitable flavoring agents include, but are not limited to, peppermint, caramel, watermelon, oil of wintergreen, spearmint, cherry, citric acid, orange, strawberry, vanilla, coconut, bubblegum flavoring, and mixtures thereof. If present, such flavoring agents may be present in the dental varnish in an amount of from about 0.001% to about 0.05% by weight, e.g., from about 0.005% to about 0.5% by weight, or from about 0.01% to about 5% by weight.

[0127] Examples of suitable sweeteners include, but are not limited to, xylitol, sorbitol, sucralose, aspartame, sodium saccharin, and mixtures thereof. Such sweeteners may be present in the dental varnish in an amount of about 0.001% to about 0.02% by weight, e.g., about 0.005% to about 0.2% by weight, or about 0.01% to about 2.0% by weight.

[0128] The synthesis of the invention herein is further illustrated by the compositions set forth in the following examples, which should not be construed as limiting the scope of the disclosure.

[0129] Working Example: 1. Synthesis of TA / GA / PEG / metal-based varnish formulations: First, a solution containing tannic acid and gallic acid (TA / GA solution) was prepared. Tannic acid (0–3.00 g) and gallic acid (0–7.00 g) were weighed and dissolved in approximately 15 mL of ethanol. After complete dissolution, approximately 35 mL of deionized water was added, along with aluminum chloride (a metal trivalent ion) (0–600 mg) and boric acid (0–500 mg). In a separate container, polyethylene glycol (PEG) (1000–10,000 Da MWCO) was prepared in deionized water by dissolving approximately 3.00 g of PEG in approximately 50 mL of deionized water. Next, the TA / GA solution and PEG solution were thoroughly mixed, and the solvent was removed by centrifugation at approximately 2000 rpm for approximately 5 minutes to collect the hydrogel system. The final color and adhesion depend on the relative ratios of gallic acid / tannic acid / PEG / aluminum chloride, pH, terminal functional groups on the PEG, and the number of PEG arms.

[0130] Various formulations of TA-PEG-based varnishes were synthesized, as shown in the table and photograph in Figure 6 .

[0131] Performance test: After incorporating TiO2 during the synthesis of TA-PEG, (V1) varnish formulation was used to test fluoride release and adhesion.

[0132] Fluoride Release: Before fluoride release, about 5 wt% NaF was mixed with TA-PEG(v1) to obtain about 22600 ppm fluoride, and fluoride release and total fluoride tests were performed.

[0133] Results: The fluoride released from TA-PEG (V1) was relatively high (19000 ppm) compared to the fluoride release from conventional varnish (12000 ppm).

[0134] Adhesion to bovine teeth: Adhesion tests were performed on wet and dry bovine teeth using the prepared formulations. The varnish-coated teeth were then incubated in water at about 37°C for about 2 hours. The results showed 45% adhesion to the wet teeth and higher adhesion to the dry teeth. The results are shown in Table 1 below. [Table 1]

[0135] Further testing was completed in which the addition of trivalent (AlCl3) and increasing the pH further improved adhesion in the same TA-PEG(V1) formulation shown in Figure 3.

[0136] Color Reduction Experiment: Next, varnishes were synthesized using a high molecular weight PEG of approximately 100 kDa instead of approximately 12 kDa PEG because high molecular weight PEG results in the precipitation of a large amount of gallic acid. Using 100 kDa PEG, gallic acid and trivalent ions (aluminum chloride) were reacted to produce a white varnish, as shown in Figure 4 (top row, left sample). However, a certain amount of TA is beneficial for the adhesion and viscosity of the final varnish formulation. Therefore, several formulations were synthesized by increasing the TA, as shown in Table 2 below. [Table 2]

[0137] pH Titration: Because the pH of the varnish formed was approximately 2, it was necessary to increase the pH without affecting the color of the final varnish formulation. Subsequently, pH titration was performed. First, the pH was increased during synthesis, but the hydrogel complex did not form due to limited hydrogen bonding between PEG and gallic acid / tannic acid. Next, after synthesizing varnishes of different compositions as listed in the table, the pH was sequentially increased and the color was observed. Figure 4 clearly shows that the pH can be increased to approximately 5-6 without significantly affecting the color of the varnish. Even approximately 50 mg or less of TA in the varnish did not cause significant browning at pH 4-5.

[0138] Synthesis of TA / GA / PEG / metal-based varnish formulations with improved adhesion, fluoride release, and fluoride uptake: Gallic acid (approximately 3 g) was dissolved in approximately 15 mL of ethanol and approximately 35 mL of deionized water. Tannic acid (approximately 5 g) and boric acid (approximately 500 mg) were dissolved in approximately 50 mL of deionized water. Separately, polyethylene glycol (12,000 Da, approximately 1.5 gm) and polyethylene glycol (20,000 Da, approximately 1.5 gm) were dissolved in approximately 50 mL of deionized water. Polyethylene glycol (100,000 Da, approximately 3 gm) was dissolved in 50 mL of deionized water. Next, approximately 9 mL of PEG (12,000 and 20,000 Da) was mixed with approximately 1 mL of PEG (100,000 Da) solution. Approximately 30 mL of GA solution was then mixed with approximately 5–10 mL of TA solution containing approximately 50–100 mg of AlCl and 50 mg of ascorbate, the pH was adjusted to approximately 4–4.5, and PEG solutions (12,000, 20,000, and 100,000 Da) were added. The final hydrogel system was collected by centrifugation at approximately 3,000 rpm for approximately 5 minutes.

[0139] Using this procedure, two varnish formulations with improved adhesion were prepared. Formulation (1) contained approximately 5 mL of TA solution and approximately 50 mg of AlCl. Formulation (2) contained approximately 10 mL of TA solution and approximately 100 mg of AlCl. Both formulations were tested for fluoride release and adhesion.

[0140] Adhesion: As described in SOP PDTM-039 Rev. 1, varnishes were applied to moist bovine teeth and incubated in artificial saliva for approximately 2 hours at approximately 34°C. The teeth were then stained with turmeric powder-containing mustard. [Table 3]

[0141] As shown in Figure 5 and Table 3 and confirmed by staining with turmeric-containing mustard sauce, Formulation 1, which contained less TA, retained approximately 48% of its adhesion to the teeth, while Formulation 2, which contained more TA, retained approximately 90% of its adhesion.

[0142] Fluoride Release: Fluoride release and total fluoride tests were then performed on both varnish formulations as shown in Table 4 below. [Table 4]

[0143] As predicted in both tests, fluoride release was nearly double that from conventional varnishes.

[0144] Fluoride uptake by enamel: For fluoride uptake experiments, normal bovine incisor enamel was embedded on the end of a Plexiglas rod (1 / 4" diameter x 2" length) using methyl methacrylate. Artificial initial lesions were then formed by immersion in approximately 0.1 M lactic acid / 0.2% Carbopol 907 saturated with calcium phosphate solution at 50% pH, at approximately room temperature, for approximately 24 hours.

[0145] All specimens (normal and lesioned) were preheated to 37°C. Then, a thin layer of varnish was applied to cover the specimen. After approximately 1 minute at approximately 37°C, all specimens were air-dried and reweighed to determine the amount of varnish used on each. None of the test varnishes were forcibly removed. Based on these weights, an attempt was made to balance the amount of varnish (±10%). While varnish could be added to lower weight specimens, it was not possible to remove varnish from heavier specimens. To mimic the effect on potentially lesioned areas in the oral cavity adjacent to the varnished area, one lesioned specimen (inside the rod) was mounted alongside the varnished normal specimen. Next, each pair of specimens was immersed in artificial saliva containing mucin (approximately 10 ml) for approximately 5 minutes with constant, gentle agitation (approximately 130 rpm) to simulate the natural removal of varnish from the oral cavity. After approximately 5 minutes, the specimens were placed in fresh artificial saliva. To mimic the release of fluoride from the varnish and subsequent swallowing, the artificial saliva was changed frequently during the initial approximately 4-hour soak. The specimens were then again placed in fresh artificial saliva containing mucin for approximately 15 minutes, 30 minutes, 1 hour, and 4 hours. After the approximately 4-hour fresh saliva change, the specimens were left in the artificial saliva for an additional approximately 20 hours. After approximately 24 hours (total) of constant, gentle agitation (approximately 130 rpm) at approximately room temperature, any visible varnish was brushed or scraped off the surface of the normal specimens. No KOH immersion was performed. All specimens (normal and lesioned) were rinsed with deionized water. One layer of enamel was then removed from each specimen (normal and lesioned) by immersing each specimen (separately) in approximately 0.5 ml of approximately 1.0 N HClO₄ for approximately 15 seconds. A sample of each etching solution was then buffered with TISAB to a pH of approximately 5.2 (0.25 ml sample, 0.5 ml TISAB, and 0.25 ml 1N NaOH) and the fluoride content was determined by comparison with a similarly prepared standard curve (1 ml std and 1 ml TISAB).

[0146] Results: At 24 hours, the tannic acid / gallic acid / PEG-based hydrogel varnish promoted 1000 ppm fluoride uptake into diseased enamel and 5500 ppm fluoride uptake into normal enamel.

[0147] Remineralization: Calcium absorption by hydrogel-based formulations The catechol / pyrogallol moieties of tannic acid and gallic acid strongly bind various metal ions, such as calcium, which can accelerate tooth remineralization through the coprecipitation of calcium and phosphate ions from oral saliva to form hydroxyapatite. Current varnish systems on the market lack the characteristics of in situ biomimetic remineralization. The tannic acid / gallic acid / polymer / metal ion-based hydrogel varnish system not only possesses the characteristics of rapid fluoride release and uptake, but also promotes in situ biomimetic remineralization by absorbing calcium from the surrounding saliva.

[0148] The hydrogel-based formulations were prepared as follows. First, a solution containing tannic acid and gallic acid (TA / GA solution) was prepared. Tannic acid (4.00 gm) and gallic acid (7.0 gm) were weighed and dissolved in 40 ml of ethanol. After complete dissolution, 60 ml of deionized water and 300 mg of aluminum chloride (trivalent metal ion) were added to the solution. In a separate container, a mixture of polyethylene glycol (PEG) (4000 Da, 1.5 gm) and polyethylene glycol (PEG) (12000 Da, 1.5 gm) was prepared in 100 ml of deionized water. The TA / GA solution and the PEG solution were then thoroughly mixed, and the solvent was removed by centrifugation at 3000 rpm for 5 minutes. The precipitate was collected and used for calcium absorption experiments.

[0149] The hydrogel-based formulations were applied to glass slides and then incubated in 25 mM calcium chloride solution for 30 minutes, or as a control, in deionized water for 30 minutes.

[0150] Results: In deionized water without CaCl, the glass slide coated with the hydrogel-based formulation was transparent. However, when the glass slide was incubated in deionized water containing 25 mM CaCl, the glass slide coated with the hydrogel-based formulation turned whitish in color, clearly indicating the absorption of CaCl by the hydrogel-based formulation immersed in the CaCl solution (Figure 7).

[0151] 2. Dentin tubule blockage Bovine teeth were tested for dentin tubule occlusion using a scanning electron microscope. Samples were prepared according to a procedure using deionized water to condition the treated specimens. Test dentin matrices were prepared and stored in thymol solution at 5°C. The matrices were examined using a light microscope at 200x magnification to confirm that the tubules were visible and suitable for use.

[0152] The prepared bovine tooth samples were removed from the deionized water and rinsed with fresh deionized water. Excess water was blotted from the sample surface. While the tooth was still wet, a thin layer of varnish was applied to the test side of the tooth using an applicator brush. After allowing the treated sample to sit for 1 minute, half of the sample was rinsed with tap water at a moderate flow rate for 10 seconds to remove any varnish that had not adhered to the sample. After application of the varnish, the sample was placed in artificial saliva at room temperature for 2 hours without agitating the artificial saliva.

[0153] After immersion, the samples were removed, gently rinsed with deionized water, and air-dried for a minimum of two hours to remove all water. The samples were then placed in a 50°C oven overnight to dry. The dried samples were coated with evaporated carbon and viewed under a scanning electron microscope (SEM) to compare the control and treated sides.

[0154] SEM micrographs (Figure 8) showed tubule occlusion on the varnished side in all samples tested compared to the control. Both the washed and unwashed hydrogel varnishes met the proposed acceptance criteria and are considered to effectively occlude dentinal tubules under the conditions of this study.

[0155] 3. Bactericidal and biofilm-inhibiting Tannic acid / gallic acid, a naturally occurring, water-soluble, phenol-rich polymer, contains sugar esters, primarily glucose, and phenolic carboxylic acids, such as gallic acid and hexahydroxydipenoic acid. Several reports have demonstrated that tannic acid / gallic acid possesses antibacterial and bactericidal activity and inhibits biofilm production and accumulation by a variety of Gram-positive and Gram-negative bacteria, including oral bacteria such as Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, and Streptococcus mutans. Hertel et al. (Caries Res. 2017, 51, pp. 34–45) investigated the effect of tannic acid on the protective properties of in situ-formed pellicles. Tannic acid significantly improved the anti-erosive properties of pellicles in a pH-dependent manner. Bacterial adhesion and glucan formation on enamel were also significantly reduced after rinsing with tannic acid, as examined by fluorescence microscopy.

[0156] In another study, Payne et al. (Infect Immun. 2013, 81, pp. 496-504) showed that tannic acid inhibits biofilm formation of Staphylococcus aureus through a mechanism dependent on the putative transglycosylase IsaA and reduced pharyngeal colonization in an animal model. Shao et al. (J Food Sci. 2015, 80, M1299-305) and Kang et al. (J Microbiol. 2008, 46, pp. 744-50) evaluated gallic acid against Escherichia coli (Gram-negative), cariogenic Streptococcus mutans (Gram-positive), and periodontal pathogens under various conditions, including nutrient levels, temperatures (25°C and 37°C), and incubation times (24 and 48 hours). Gallic acid significantly affected the growth curves of both test strains at 25°C and 37°C. Nutrient levels, temperature, and treatment time affected the inhibitory activity of GA on both growth and biofilm formation of the tested pathogens.

[0157] The catechol and pyrogallol hydroxyl groups of tannic and gallic acids may be related to their relative toxicity to microorganisms, as they can penetrate and interact with lipid bilayers, causing leakage and aggregation of intramembrane materials. They can also interact with bacterial proteins and cell wall structures, causing damage to the cell membrane, reducing membrane fluidity, and inhibiting nucleic acid synthesis, cell wall synthesis, or energy metabolism. In addition to their destructive activity against bacteria, "softer" activities are also known, leading to biofilm suppression by affecting bacterial regulatory mechanisms such as quorum sensing or other global regulatory systems.

[0158] It is predicted that hydrogel-based varnishes may exhibit antibacterial activity and result in the inhibition of dental plaque biofilm and accumulation of various gram-positive and gram-negative bacteria.

[0159] The following example provides the bactericidal and biofilm-inhibiting properties of a tannic acid / gallic acid-based hydrogel varnish, useful for validating it against Escherichia coli, a widely used and simple model bacterium.

[0160] To evaluate the bactericidal and biofilm-inhibiting properties of the varnish, Escherichia coli was cultured on varnish-coated enamel-like hydroxyapatite discs and bacterial cell viability, growth rate, and biofilm formation were compared with control discs (without varnish).The antibacterial properties of the hydrogel varnish were then tested against Streptococcus mutans by measuring the bactericidal activity, growth rate, and biofilm formation of oral bacteria in the presence of the varnish.

[0161] Synthesis of varnish formulations tested for adhesion and F release using one-pot and single-step methods: In one example, a dental varnish for bonding to enamel was synthesized using a one-pot, single-step method. First, 280 mg of polyacrylic acid (PAA) was dissolved in 5.0 ml of DI water, and the pH was adjusted to approximately 8.5-9.0 using 8 N NaOH and concentrated HCl (concentrated hydrochloric acid). In a separate container, 115 mg of dopamine was dissolved in 5 ml of DI water, and 1 ml of polyethyleneimine (PEI, 1200 Da) and 2 ml of polyethyleneimine (PEI, 600 Da) were added to the dopamine solution and allowed to react at room temperature for 15 minutes. Next, the PAA solution was mixed with the PEI / dopamine solution. 0.5 ml of arginine (70 mg in DI water), 0.5 ml of AlF3 (32 mg / ml in DI water), 0.875 ml of hydrofluoric acid (48-51%), and 1 ml of borax buffer (pH 8.3) were added to the formulation and mixed thoroughly. Finally, 0.5 ml of AlCl3 (360 mg in DI water) and 0.4 gm of PEI (10000 Da) were added and the pH was adjusted to about 7.75.

[0162] Fluoride Release: Using the procedures described above, various combinations of formulations were then synthesized and tested for fluoride release, as shown in Table 5. [Table 5]

[0163] 0.02-0.05 g of varnish was applied evenly to a glass slide without thick areas and transferred to small cups. 10 ml of deionized water was added to each cup, ensuring that the varnished area was covered with water. F ion release was performed for 2 hours at 34°C to simulate the oral environment. All samples were prepared in duplicate. After 2 hours, 10 ml of the solution was transferred to a small plastic beaker containing 10 ml of TISABII and mixed with a magnetic stirrer. F ion measurements were performed by inserting a probe into the sample while gently stirring (Table 6). [Table 6]

[0164] As predicted in both tests, fluoride release was nearly double that from conventional varnishes.

[0165] Adhesion: Next, adhesion tests were performed on enamel-like hydroxyapatite discs. However, before applying the varnish formulation containing the stimuli or the control varnish formulation, the hydroxyapatite discs were incubated in deionized water for 1–2 hours. The prepared varnish (S43) was then applied to the wet hydroxyapatite discs and allowed to bond to the discs for approximately 2–3 minutes. As a control, the wet hydroxyapatite discs did not accept the varnish formulation, confirming that the Alcian blue dye was absorbed by the varnish, not the hydroxyapatite discs.

[0166] Next, both the control and sample hydroxyapatite discs were immersed separately in the artificial saliva solution. After incubation at approximately 37°C for 2 hours, the hydroxyapatite discs were washed with deionized water and then air-dried. Finally, the hydroxyapatite discs were stained with Alcian blue dye (pH 1.5-2.0). Referring to Figure 3, the hydroxyapatite discs without varnish were nearly white, with only a few areas of blue staining. Figure 3 also shows that the hydroxyapatite discs with varnish showed strong, uniform blue staining of the hydroxyapatite disc, indicating that the varnish was adhered to the hydroxyapatite disc.

[0167] Remineralization: Calcium absorption by hydrogel-forming polymer formulations In one example, a dental varnish composition promoted in situ biomimetic remineralization by absorbing calcium from surrounding saliva. First, 280 mg of polyacrylic acid (PAA) was dissolved in 5.0 ml of DI water, and the pH was adjusted to approximately 8.5-9.0 using 8N NaOH and concentrated HCl (concentrated hydrochloric acid). In a separate container, 115 mg of dopamine was dissolved in 5 ml of DI water, and 1 ml of polyethyleneimine (PEI, 1200 Da) and 2 ml of polyethyleneimine (PEI, 600 Da) were mixed with the dopamine solution and allowed to react at room temperature for 15 minutes. Next, the PAA solution was mixed with the PEI / dopamine solution. 0.5 ml of arginine (70 mg in DI water), 0.5 ml of AlF3 (32 mg / ml in DI water), 0.875 ml of hydrofluoric acid (48-51%), and 1 ml of borax buffer (pH 8.3) were added to the formulation and mixed thoroughly.

[0168] Finally, 0.5 ml of AlCl3 (360 mg in DI water) and 0.4 gm of PEI (10,000 Da) were added, and the pH was adjusted to approximately 7.75. The prepared varnish formulation was applied to a glass slide, which was then incubated in phosphate-buffered saline (PBS) (1X, pH 7.4) for 15 minutes and in 25 mM calcium chloride solution for an additional 30 minutes. As a control, another glass slide containing the prepared varnish formulation was incubated in DI water for approximately 45 minutes.

[0169] Referring to Figure 4, the glass slides from the control remained opaque after 45 minutes of incubation. In contrast, as shown in Figure 4, the glass slides incubated in PBS and calcium chloride became whitish upon full incubation for 45 minutes, clearly indicating the absorption of Ca and phosphate by the varnish immersed in CaCl2 solution.

[0170] Synthesis of varnishes for testing fluoride uptake by enamel:

[0171] In one example, a dental varnish for F uptake was synthesized. First, 280 mg of polyacrylic acid (PAA) was dissolved in 10 ml of DI water, and the pH was adjusted to approximately 8.5–9.0 using 0.5 ml of arginine (70 mg in DI water), 0.5 ml of AlF3 (32 mg / ml in DI water), and 8 N NaOH and concentrated HCl (concentrated hydrochloric acid). In a separate container, 1 ml of polyethyleneimine (PEI, 1200 Da), 2 ml of polyethyleneimine (PEI, 600 Da), and 150 mg of dopamine were dissolved in 5 ml of borax buffer. Next, the PAA solution was mixed with the PEI / dopamine solution. 1.0 ml of hydrofluoric acid (48–51%) and 0.5 ml of AlCl3 (320 mg in DI water) were added, and the pH was adjusted to approximately 7.75.

[0172] For fluoride uptake experiments, normal bovine incisor enamel was embedded on the end of a Plexiglas rod (1 / 4" diameter x 2" long) using methyl methacrylate. Artificial initial lesions were then formed in it by immersion in a 0.1 M lactic acid / 0.2% Carbopol 907 solution 50% saturated with calcium phosphate, pH 5.0, for 24 hours at room temperature. All specimens (normal and lesioned) were preheated to 37°C. Varnish was then applied so that a thin layer covered the specimen. After 1 minute at 37°C, all specimens were air-dried and reweighed to determine the amount of varnish used on each. None of the test varnishes were forcibly removed. Based on these weights, an attempt was made to balance the amount of varnish (±10%). Varnish could be added to the lower weight specimens, but not removed from the heavier ones. To mimic the effect on intraoral lesion areas that may be adjacent to the varnish application area, the varnish was applied to the specimens. One lesioned specimen (inside the rod) was mounted alongside a normal specimen covered with varnish. Each pair of specimens was then immersed in artificial saliva containing mucin (10 ml) for 5 minutes with constant gentle agitation (130 rpm) to simulate the natural removal of varnish from the oral cavity. After 5 minutes, the specimens were placed in fresh artificial saliva. The artificial saliva was frequently changed during the first 4 hours of immersion to mimic the release of fluoride from the varnish and subsequent swallowing. The specimens were placed in fresh artificial saliva containing mucin for 15 minutes, 30 minutes, 1 hour, and 4 hours. After the 4-hour fresh saliva exchange, they were left in the AS for an additional 20 hours. They were left in the artificial saliva for a total of 24 hours. After 24 hours (total) with constant gentle agitation (130 rpm) at room temperature, any visible varnish was brushed or scraped off the surface of the normal specimens. No KOH immersion was performed. All specimens (normal and lesioned) were rinsed with DI water. Next, one layer of enamel was removed from each specimen (normal and lesioned) by immersion in 0.5 ml of 1.0 N HClO₄ for 15 seconds (separately).Samples of each etching solution were then buffered to pH 5.2 with TISAB (0.25 ml sample, 0.5 ml TISAB, and 0.25 ml 1N NaOH), and the fluoride content was determined by comparison with a similarly prepared standard curve (1 ml standard and 1 ml TISAB). The uptake of F by enamel from NMS2 was approximately 2500 ppm.

[0173] Synthesis of varnishes for testing dentinal tubule occlusion. In one example, a dental varnish for bonding to enamel was synthesized using a one-pot, single-step method. First, 280 mg of polyacrylic acid (PAA) was dissolved in 5.0 ml of DI water, and the pH was adjusted to approximately 8.5-9.0 using 8 N NaOH and concentrated HCl (concentrated hydrochloric acid). In a separate container, 115 mg of dopamine was dissolved in 5 ml of DI water, and 1 ml of polyethyleneimine (PEI, 1200 Da) and 2 ml of polyethyleneimine (PEI, 600 Da) were added to the dopamine solution and allowed to react at room temperature for 15 minutes. Next, the PAA solution was mixed with the PEI / dopamine solution. 0.5 ml of arginine (70 mg in DI water), 0.5 ml of AlF3 (32 mg / ml in DI water), 0.875 ml of hydrofluoric acid (48-51%), and 1 ml of borax buffer (pH 8.3) were added to the formulation and mixed thoroughly. Finally, 0.5 ml of AlCl3 (360 mg in DI water) and 0.4 gm of PEI (10000 Da) were added and the pH was adjusted to about 7.75.

[0174] Next, using the procedure described above, various combinations of formulations were synthesized and tested for occlusion testing (Table 7). [Table 7]

[0175] Bovine teeth were tested for dentin tubule occlusion using a scanning electron microscope. Samples were prepared according to a procedure using DI water to condition the treated specimens. Test dentin matrices were prepared and stored in thymol solution at 5°C. The matrices were examined using a light microscope at 200x magnification to confirm that the tubules were visible and suitable for use.

[0176] The prepared bovine tooth samples were removed from the deionized water and rinsed with fresh deionized water. Excess water was blotted from the sample surface. While the tooth was still wet, a thin layer of varnish was applied to the test side of the tooth. This was done using an applicator brush. After allowing the treated sample to sit for 1 minute, the sample was rinsed with tap water at a moderate flow rate for 10 seconds to remove any varnish that had not adhered to the sample. After application of the varnish, the sample was placed in artificial saliva (AS) for 2 hours at room temperature without agitating the AS.

[0177] After immersion, the samples were removed, gently rinsed with deionized water, and air-dried for a minimum of two hours to remove all water. The samples were then placed in a 50°C oven overnight to dry. The dried samples were coated with evaporated carbon and viewed under a scanning electron microscope (SEM) to compare the control and treated sides.

[0178] SEM micrographs (Figure 5) showed tubule occlusion on the varnished side. Hydrogel varnish formulations S43 and S46 met the proposed acceptance criteria and are considered to effectively occlude dentinal tubules under the conditions of this study.

[0179] Those skilled in the art will understand that various modifications can be made to the illustrated embodiments and descriptions herein without departing from the spirit and scope of the present disclosure, and all such modifications within the spirit and scope of the present disclosure are intended to be covered by the appended claims.

Claims

[Claim 1] 1. A method for synthesizing a dental varnish, comprising: a. polymerizing dopamine; b. covalently attaching the polymerized dopamine of step a using a cationic polymer; c. reacting the cationic polymer with an anionic polymer; and d. cross-linking said dopamine with a metal ion.

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