Fluoride-containing aqueous zinc oral care composition

Abstract

A dental composition is described that includes a homogeneous solution having a zinc complex stabilized with an amine-containing ligand and a fluoride anion source. A method for treating or preventing caries activity on a tooth surface using the dental composition is also described, as are kits.

Description

【Background Art】 【0001】 Dental caries is a disease in which dental caries occurs due to interaction with acids produced by bacteria. Silver salts are known to have antibacterial properties, and fluoride salts are known to remineralize tooth surfaces. Both silver and fluoride compositions have been separately shown to help prevent and arrest caries activity. 【0002】 Silver diamine fluoride has been used to treat surfaces affected by dental caries. However, it reacts with saliva to produce silver phosphate. Silver phosphate is photosensitive and permanently stains teeth black when exposed to light. Silver fluoride (without a diamine stabilizer) is very unstable in aqueous solution and rapidly decomposes to form metallic silver. 【0003】 Zinc salts are also known to have antibacterial properties and are not photosensitive, i.e., zinc complexes do not change to black upon exposure. Zinc and fluoride together may form a promising treatment for dental caries. However, zinc fluoride, as well as other zinc complexes, do not dissolve in aqueous solutions. In fact, even when water-soluble zinc precursors are used, zinc fluoride often precipitates from the solution. 【0004】 What is needed is a method of formulating an aqueous solution of zinc and fluoride to treat caries activity. The present disclosure describes a dental composition that provides a zinc complex stabilized with an amine-containing ligand in an aqueous solution containing fluoride ions. 【Summary of the Invention】 【0005】 In one embodiment, a dental composition is described. The dental composition can include zinc carboxylate, an amine-containing ligand, a fluoride anion source effective to provide fluoride in an amount of at least 4 wt% based on the weight of the dental composition, and water. The dental composition can have a pH of at least 8 and can be a homogeneous solution at a temperature of about 20 - 25°C. 【0006】 In one embodiment, a method for treating or preventing caries activity on a tooth surface is described. The method may include providing a dental composition comprising zinc carboxylate, an amine-containing ligand, a fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, and water. The dental composition may have a pH of at least 8 and may be a homogeneous solution at a temperature of about 20-25°C. The method may include bringing the dental composition into contact with a tooth surface. 【0007】 In one embodiment, a kit is described. The kit may comprise a dental composition comprising zinc carboxylate, an amine-containing ligand, a fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, and water. The dental composition may have a pH of at least 8 and may be a homogeneous solution at a temperature of about 20–25°C. The method may comprise contacting the dental composition with a tooth surface. The kit may further comprise instructions for providing the dental composition and guiding the user to perform the method of contacting the dental composition with a tooth surface. [Modes for carrying out the invention] 【0008】 As used herein, "about" means ±10 percent of a given value. For example, about 10 means between 9 and 11. 【0009】 As used herein, "zinc carboxylate" means a zinc complex having one or more carboxylate ligands, e.g., -OC(O)-R. 【0010】 As used herein, “homogeneous solution” refers to a solution that is visually clear or permeable. No particulate matter or turbidity is observed in the homogeneous solutions described herein. Homogeneous solutions exclude dispersions, suspensions, and the like. 【0011】 Dental compositions In many embodiments, dental compositions are described. The dental composition may comprise zinc carboxylate, an amine-containing ligand, a fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, and water. The dental composition may have a pH of at least 8 and may be a homogeneous solution at a temperature of about 20–25°C. 【0012】 In some embodiments, the dental composition may essentially consist of zinc carboxylate, an amine-containing ligand, a fluoride source, and water. In fact, thickeners, silica, or polymer vehicles may not be required. 【0013】 In some embodiments, zinc carboxylate is present in an amount effective to provide about 5% to about 15% by weight of zinc relative to the weight of the dental composition. For example, zinc carboxylate can provide about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% by weight of the composition, or values ​​within any of the aforementioned ranges, such as about 8 to about 15% by weight, or about 10 to about 12% by weight. 【0014】 In some embodiments, the amine-containing ligand is present in an amount of about 5% to about 30% by weight relative to the weight of the dental composition. For example, the amine-containing ligand may be present in an amount of about 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30% by weight, or within a range of any of the aforementioned values, for example, about 8 to about 16% by weight, or about 10 to about 15% by weight. 【0015】 In some embodiments, zinc carboxylate and the amine-containing ligand are present in amounts that provide a molar ratio of about 1:2 to about 1:3. In some embodiments, the molar ratio is 1:2. In other embodiments, the molar ratio is greater than 1:2. 【0016】 In some embodiments, the fluoride anion source is present in an amount that provides an effective amount of fluoride in the form of at least about 10% by weight, at least about 15% by weight, or at least about 20% by weight, relative to the weight of the dental composition. 【0017】 In some embodiments, the fluoride anion source is present in an amount that provides an effective amount of fluoride in an amount of about 4% to about 20% by weight. For example, the fluoride anion source may provide an amount of fluoride in an amount of about 4, 6, 8, 10, 12, 14, 16, or 20% by weight relative to the weight of the dental composition, or within a range of any of the aforementioned values, for example, about 14 to about 10% by weight or about 8 to about 16% by weight. 【0018】 In some embodiments, water is present in an amount of about 20% to about 50% by weight relative to the weight of the dental composition. For example, water may be present in an amount of about 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50, or within a range of any of the aforementioned values, for example, about 28 to about 50, about 36 to about 40, etc. 【0019】 In some embodiments, the pH of the dental composition may be at least 8, at least 9, at least 10, at least 11, or at least 12. In some embodiments, the dental composition may have a pH of about 8 to about 10. In some embodiments, the pH may be 9. 【0020】 Zinc Carboxylate In some embodiments, zinc carboxylate is selected from one or more of zinc citrate, zinc gluconate, zinc maleate, zinc acetate, zinc fumarate, zinc adipate, and zinc propionate. 【0021】 In some embodiments, zinc carboxylate is zinc citrate. 【0022】 Amine-containing ligands In some embodiments, the amine-containing ligand may include one or more of an amino acid and ammonia. 【0023】 In some embodiments, the amine-containing ligand may include one or more amino acids. 【0024】 In some embodiments, the amine-containing ligand is selected from one or more of histidine, isoleucine, leucine, lysine, tyrosine, tryptophan, methionine, phenylalanine, aspartic acid, glycine, arginine, glutamic acid, valine, alanine, threonine, cysteine, proline, and asparagine. 【0025】 In some embodiments, the amine-containing ligand can be arginine. 【0026】 In some embodiments, the amine-containing ligand is ammonia (H3N). 【0027】 In other embodiments, the amine-containing ligand may include an amine of the formula R3N, wherein one or more Rs are C 1~4 is alkyl. 【0028】 Fluoride anion source In some embodiments, the fluoride anion source is selected from one or more of sodium fluoride, ammonium fluoride, silver fluoride, stannous fluoride, and potassium fluoride. 【0029】 In some embodiments, the fluoride anion source is selected from one or more of ammonium fluoride, silver fluoride, stannous fluoride, and potassium fluoride. 【0030】 In other embodiments, the fluoride source is not sodium fluoride. 【0031】 In some embodiments, the fluoride anion source is ammonium fluoride. 【0032】 Methods for treating or preventing caries activity In many embodiments, methods for treating or preventing cariogenic activity on a tooth surface are described. The method may include providing a dental composition comprising zinc carboxylate, an amine-containing ligand, a fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, and water. The dental composition may have a pH of at least 8 and may be a homogeneous solution at a temperature of about 20–25°C. The method may include bringing the dental composition into contact with a tooth surface. 【0033】 In many embodiments, the dental composition may be any dental composition described herein. 【0034】 In some embodiments, the method may further include contacting the dental composition with the tooth surface for a period of about 10 seconds to about 15 minutes. For example, the dental composition may be contacted with the tooth surface for about 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, 600, 660, 720, 780, 840, or 900 seconds, or within a range of any of the aforementioned values, for example, about 30 to about 60 seconds, about 90 to about 300 seconds, etc. 【0035】 In some embodiments, the method may involve applying the dental composition using a dropper, needle, pipette, tray, or swab. 【0036】 kit In many embodiments, a kit is described. The kit comprises a dental composition comprising zinc carboxylate, an amine-containing ligand, a fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, and water. The dental composition may have a pH of at least 8 and may be a homogeneous solution at a temperature of about 20°C to 25°C. This method may involve contacting the dental composition with a tooth surface. The kit provides the dental composition and may further include instructions for guiding the user to perform the method of contacting the dental composition with a tooth surface. 【0037】 In some embodiments, the dental composition is provided as a single component. 【0038】 In other embodiments, the dental composition is provided as two or more agents. 【0039】 In some embodiments, the instructions may further guide the user to prepare dental compositions by combining two or more agents. 【0040】 In some embodiments, the dental composition may be any dental composition described herein. 【0041】 In some embodiments, instructions may guide the user to carry out any of the methods described herein. The present invention encompasses the following aspects. (1) A dental composition, Zinc carboxylate and Amine-containing ligands and A fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, Water and, The dental composition has a pH of at least 8, The dental composition is a homogeneous solution at a temperature of approximately 20°C to 25°C. (2) The dental composition according to item 1, comprising essentially the zinc carboxylate, the amine-containing ligand, the fluoride source, and water. (3) The dental composition according to item 1 or 2, wherein the zinc carboxylate is selected from zinc citrate, zinc gluconate, zinc maleate, zinc acetate, zinc fumarate, zinc adipate, zinc propionate, hydrates thereof, and combinations thereof. (4) The dental composition according to any one of items 1 to 3, wherein the zinc carboxylate is zinc citrate. (5) The dental composition according to any one of items 1 to 4, wherein the amine-containing ligand is selected from one or more amino acids and ammonia. (6) The dental composition according to any one of items 1 to 5, wherein the amine-containing ligand is an amino acid selected from histidine, isoleucine, leucine, lysine, tyrosine, tryptophan, methionine, phenylalanine, aspartic acid, glycine, arginine, glutamic acid, valine, alanine, threonine, cysteine, proline, asparagine, and combinations thereof. (7) The dental composition according to any one of items 1 to 6, wherein the amino acid is arginine. (8) The dental composition according to any one of items 1 to 5, wherein the amine-containing ligand is ammonia. (9) The dental composition according to any one of items 1 to 8, wherein the fluoride anion source is selected from sodium fluoride, ammonium fluoride, silver fluoride, stannous fluoride, potassium fluoride, and combinations thereof. (10) The dental composition according to any one of items 1 to 9, wherein the fluoride anion source is ammonium fluoride. (11) The dental composition according to any one of items 1 to 10, wherein the amine-containing ligand is present in an amount of about 5% to about 30% by weight relative to the weight of the dental composition. (12) The dental composition according to any one of items 1 to 11, wherein the zinc carboxylate is present in an amount effective to provide about 5% to about 15% by weight of zinc relative to the weight of the dental composition. (13) The dental composition according to any one of items 1 to 12, wherein the water is present in an amount of about 20% to about 50% by weight relative to the weight of the dental composition. (14) The dental composition according to any one of items 1 to 13, wherein the amine-containing ligand is present in an amount of about 10% to about 15% by weight relative to the dental composition, and provides a zinc:amine-containing ligand molar ratio of about 1:2 to about 1:3. (15) A method for treating or preventing caries activity on the tooth surface, To provide a dental composition as described in any of items 1 to 14, A method comprising bringing the dental composition into contact with the tooth surface. (16) The method according to item 15, further comprising bringing the dental composition into contact with the tooth surface for about 10 seconds to about 15 minutes. (17) The method according to item 14 or 15, wherein the contact includes applying the dental composition with a dropper, needle, pipette, tray, or swab. (18) It is a kit, A dental composition described in any of items 1 to 14, A set of instructions guiding the user to perform one of the methods described in items 15-17, A kit that includes this. [Examples] 【0042】 The purposes and advantages of this disclosure are further illustrated by the following examples, but the specific materials and their quantities, as well as other conditions and details described in these examples, should not be construed as unduly limiting this disclosure. These examples are for illustrative purposes only and are not intended to limit the scope of the appended claims. [Table 1] 【0043】 Examples EX1-EX10 and Comparative Examples CE1-CE4 All exemplary components were added to a plastic centrifuge tube. The composition was thoroughly mixed in a vortex mixer to form a suspension. The mixture was then heated to 60°C and mixed several times. The mixture was kept in a 60°C oven for 24 hours. The exemplary mixture was vortex-mixed several times while being heated in a 60°C oven to form a solution. Comparative example (CE) did not form a solution. Zinc citrate and potassium zinc fluoride were insoluble in the solution, and these comparative examples showed lower water solubility compared to the examples. [Table 2] [Table 3] 【0044】 Remineralization and acid resistance testing Enamel specimens were prepared from bovine teeth. Each specimen was immersed in a 0.1 M lactic acid and 0.2% carbopol (pH=5) solution at 37°C for 24 hours to induce caries lesions in the enamel. The specimens were then randomly assigned to one of three treatment solutions: artificial saliva (used as a control), or silver fluoride (SDF) solutions used as comparative solutions EX1, EX2, and EX3. A total of 10 specimens were prepared for each treatment solution. 【0045】 The test specimens were treated by applying different test solutions to enamel lesions using a mini dental brush (bush), scrubbing the lesions with the mini dental brush for 10 seconds, waiting for 1 minute, rinsing with artificial saliva, and storing in artificial saliva at 37°C for 30 minutes. The test specimens were then rinsed again with artificial saliva and placed in fresh artificial saliva at 37°C for 24 hours. 【0046】 The surface hardness (Vickers hardness scale (VHN)) of the treated specimens was measured using a Vickers hardness tool. The average VHN and standard deviation were calculated for 10 specimens per treatment. 【0047】 To measure the retention of surface microhardness, a demineralization challenge was created by placing the specimen in a solution of 0.1 M lactic acid and 0.2% CARBOPOL (pH=5) for 24 hours. Any increase in hardness retention was evaluated by acid loading. The sample was subjected to the demineralization solution for 24 hours. The retention of microhardness after acid loading indicates the ability of the treatment to resist demineralization. Surface microhardness was measured after acid loading. A higher microhardness value than the baseline measurement indicates remineralization of tooth enamel by the treatment. The specimen was stored in artificial saliva at 37°C for 24 hours, and then the hardness was measured. The specimen was acid-loaded with the demineralization solution, and the hardness was measured again. The higher the resistance of the enamel to loading, the better the surface microhardness value is retained. Surface microhardness was measured using the same procedure as in this baseline measurement. An increase in microhardness after treatment indicates the ability of the treatment solution to remineralize tooth enamel. [Table 4] 【0048】 Fluoride uptake test Enamel specimens were prepared from bovine teeth. Caries lesions were induced in the enamel of each specimen by immersion in a 0.1M lactic acid and 0.2% carbopol (pH=5) solution at 37°C for 24 hours. The specimens were randomly assigned to one of three treatments: artificial saliva (used as a control), or silver fluoride (SDF) treatments used as comparative EX1, EX2, and EX3. A total of 10 specimens were prepared for each treatment group. 【0049】 The test specimens were treated by applying different test treatment solutions to enamel lesions using a mini dental brush, scrubbing the lesions with the mini dental brush for 10 seconds, waiting for 1 minute, rinsing with artificial saliva, and storing in artificial saliva at 37°C for 30 minutes. The test specimens were then rinsed again with artificial saliva and placed in fresh artificial saliva at 37°C for 24 hours. 【0050】 Micro-drill biopsies were taken from each specimen, and the amount of fluoride transferred to the enamel was measured. To test the incorporation of fluoride into the teeth, the specimens were further subjected to acid loading. Acid loading was simulated by placing the specimens in a solution of 0.1 M lactic acid and 0.2% CARBOPOL (pH=5) at 37°C for 24 hours. Micro-drill biopsies were taken from each specimen, and the amount of fluoride in the enamel after acid loading was measured. μgF / cm 2 The results for the units are reported in Table 5. [Table 5] 【0051】 Examples EX11-EX13 and Comparative Example CE5 Additional examples were prepared using commercially available SDF combined with the zinc complex solution of Example EX3. The following examples illustrate the use of exemplary compositions on tooth surfaces. Bovine tooth samples were prepared in the following manner to serve as test surfaces for the treatment of the examples. Bovine teeth were held in an acrylic mold and polished with 120-grit sandpaper to expose the dentin, and then polished with 320-grit sandpaper to smooth the dentin surface. One drop of each example's composition was placed on the prepared bovine dentin surface and then cured using a 3M ELIPAR DEEPCURE-S LED curing light (available from 3M Company, St. Paul, MN, USA) at a maximum wavelength of 450 nm and an output of approximately 1500 mW / cm². 2 The samples were exposed to blue LED light for 20 seconds. Examples EX11-EX13 show that silver diamine fluoride can be used as an additional fluoride source and have the antimicrobial benefits of zinc in the composition, but the final state is not aesthetically satisfactory compared to examples such as EX3, which do not change to black when exposed. [Table 6] 【0052】 Example EX14 and Comparative Example CE6 Additional examples were prepared by combining the zinc fluoride complex of EX3 or SDF with a photocurable methacrylate mixture. [Table 7] 【0053】 Antimicrobial inhibition test To evaluate the antimicrobial performance of the examples, multi-range inhibition tests were conducted according to the following steps. Human saliva was used as the bacterial source. 1. A sterilized, 6mm diameter circular filter paper disc was used. 2. The experimental and control solutions were dispensed into standard 96-well plates during preparation for immersion of the filter paper discs. 3. Each sterile paper disc was immersed by applying 10 μL of the corresponding solution to the disc. Each sample was duplicated three times and treated similarly, and the final results were averaged. 4. The agar plate was divided into an equal number of sections according to the number of solutions to be tested. Each section was labeled with the name of the test solution. 5. Lift the lid of the agar plate and place the immersed filter paper samples onto the agar. Then, gently press down on each sample filter paper disc to ensure that it makes complete contact with the agar surface. Care was taken not to move the discs after contact with the agar surface. 6. As described above, the analyst continued to place one sample disc at a time onto the agar surface until all discs were placed on their respective sections on each agar plate. 7. Once all the discs were in place, the lid was replaced, the agar plate was inverted, and it was placed in a 37°C air incubator for 24 hours. 8. After incubation at 37°C for 24 hours, the diameter of each inhibition region was measured to the nearest millimeter using a ruler or caliper. The inhibition region was measured visually as the diameter from the edge of the last visible colony. 9. Care was taken to avoid touching the agar disc or surface during measurement. The ruler was decontaminated between each measurement. Measurements were performed in a biosafety cabinet. [Table 8] Equivalents Those skilled in the art will be able to identify or confirm, at best, numerous equivalents to the specific embodiments described herein by means of routine experiments. Such equivalents are intended to be covered by the following claims.

Claims

[Claim 1] A dental composition, Zinc carboxylate and Amine-containing ligands and A fluoride anion source effective in providing fluoride in an amount of at least 4% by weight relative to the weight of the dental composition, Water and, The dental composition has a pH of at least 8, The dental composition is a homogeneous solution at a temperature of 20°C to 25°C. [Claim 2] The dental composition according to claim 1, comprising the zinc carboxylate, the amine-containing ligand, the fluoride source, and water. [Claim 3] The dental composition according to claim 1, wherein the zinc carboxylate is selected from zinc citrate, zinc gluconate, zinc maleate, zinc acetate, zinc fumarate, zinc adipate, zinc propionate, hydrates thereof, and combinations thereof. [Claim 4] The dental composition according to claim 1, wherein the zinc carboxylate is zinc citrate. [Claim 5] The dental composition according to claim 1, wherein the amine-containing ligand is selected from one or more amino acids and ammonia. [Claim 6] The dental composition according to claim 1, wherein the amine-containing ligand is an amino acid selected from histidine, isoleucine, leucine, lysine, tyrosine, tryptophan, methionine, phenylalanine, aspartic acid, glycine, arginine, glutamic acid, valine, alanine, threonine, cysteine, proline, asparagine, and combinations thereof. [Claim 7] The dental composition according to claim 1, wherein the amino acid is arginine. [Claim 8] The dental composition according to claim 1, wherein the amine-containing ligand is ammonia. [Claim 9] The dental composition according to claim 1, wherein the fluoride anion source is selected from sodium fluoride, ammonium fluoride, silver fluoride, stannous fluoride, potassium fluoride, and combinations thereof. [Claim 10] The dental composition according to claim 1, wherein the amine-containing ligand is present in an amount of 5% to 30% by weight relative to the weight of the dental composition. [Claim 11] The dental composition according to claim 1, wherein the zinc carboxylate is present in an amount effective in providing 5% to 15% by weight of zinc relative to the weight of the dental composition. [Claim 12] The dental composition according to claim 1, wherein the water is present in an amount of 20% to 50% by weight relative to the weight of the dental composition. [Claim 13] The dental composition according to claim 1, wherein the amine-containing ligand is present in an amount of 10% to 15% by weight relative to the dental composition, and the zinc:amine-containing ligand molar ratio is 1:2 to 1:

3. [Claim 14] A dental composition, A zinc carboxylate present in an amount that provides 5% to 15% by weight of zinc relative to the weight of the dental composition, The dental composition contains one or more amine-containing ligands selected from ammonia and amino acids, present in an amount of 5% to 30% by weight relative to the weight of the dental composition. A fluoride anion source present in an amount effective to provide at least 4% by weight of fluoride relative to the weight of the dental composition, The dental composition comprises water present in an amount of 20% to 50% by weight relative to the weight of the dental composition, The dental composition has a pH of at least 8, The dental composition is a homogeneous solution at a temperature of 20°C to 25°C. [Claim 15] The zinc carboxylate is zinc citrate. The aforementioned amino acid is arginine. The fluoride anion source is ammonium fluoride, and The fluoride anion source is present in an amount that provides 6% to 10% by weight of fluoride. The dental composition according to claim 14, characterized by one or more of the following. [Claim 16] A dental composition comprising the zinc carboxylate, one or more amine-containing ligands, a fluoride anion source, and water, wherein the one or more amine-containing ligands include ammonia, and the fluoride anion source is ammonium fluoride, according to claim 14. [Claim 17] A dental composition according to any one of claims 1 to 16, for use in the treatment or prevention of caries activity on the tooth surface. [Claim 18] It's a kit, A dental composition according to any one of claims 1 to 16, A series of instructions guiding the user to bring the dental composition into contact with the tooth surface, A kit that includes this.

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