Thickened composition comprising silver fluoride; use for disclosing caries status, desensitising teeth, preventing and treating caries

Abstract

There is provided herein a thickened dental Caries Status Disclosing Solution comprising a water-based thickened silver fluoride composition comprising a thickening agent for use in the initial application of the thickened silver fluoride composition to a carious lesion followed by the subsequent application of a reducing agent solution for the visual analysis of the status of the carious lesion wherein the water-based thickened silver fluoride composition comprises nitric acid to stabilize the water-based silver fluoride composition. The thickened dental Caries Status Disclosing Solution can also be used to treat teeth that are sensitive to at least one of heat, cold, sweet, acid and tactile pressure to thereby reduce sensitivity.

Description

[0001] THICKENED COMPOSITION COMPRISING SILVER FLUORIDE; USE FOR DISCLOSING CARIES STATUS, DESENSITISING TEETH, PREVENTING AND TREATING CARIES

[0002] The present application claims priority to US Provisional Patent Application Serial No. 63 / 578,012 filed August 22, 2023, the entire contents of which are hereby incorporated by reference in their entirety.

[0003] TECHNICAL FIELD

[0004] The present invention relates to thickened dental staining solutions hereinafter referred to as Thickened Caries Status Disclosing Compositions (TCSDC).

[0005] BACKGROUND

[0006] Commercially available carious lesion staining solutions, referred to herein as dental Caries Status Disclosing Solutions (CSDS) are presently used in dentistry to indicate caries status. See for instance, Craig et al. BMC Oral Health 2013, 13:73.

[0007] CSDS stems from early clinical use of water-based silver fluoride followed by stannous fluoride (reducing agent) wherein it was found to be a reliable indicator of lesion progression. CSDS is applied to active carious lesions in primary molars in children, root surface caries, prophylactically, on recurrent caries around restorations and crown and bridgework in the elderly.

[0008] The water-based silver fluoride is applied first to the caries lesion and then, one to three minutes later, the stannous fluoride is applied and acts as a reducing agent for the silver.

[0009] This procedure stains an active carious lesion black. If the lesion remains black over a period of time it is an indication that the caries is not progressing (i.e., the caries is arrested). However, if the lesion starts to lighten (i.e., changes from black to brown or tan), this is an indication that the caries is progressing.

[0010] As such, CSDS is a visual indicator of the status of a carious lesion; namely if it has been arrested or is still progressing.

[0011] It has been known that silver fluoride does not have long term stability in solution, so stabilizers have been used. Silver fluoride can be stabilized with ammonia, by forming silver diammine fluoride. In addition, US10,610,468B2 teaches that nitric acid can be added to stabilize the water-based silver fluoride solution.

[0012] It has also been known to treat caries with a water-based silver fluoride followed by stannous fluoride (reducing agent). See for instance, Roberts-Thomson et al., Australian Dental Journal 2019; 64: 175—180. SUMMARY AND DEFINITIONS

[0013] However, CSDS has a low viscosity, and thus is a liquid at room temperature. The present inventors have found that the application of this material must be carried out carefully as it is difficult to control the intended location of the liquid on the tooth at the time of application. If the liquid runs off the intended location on the tooth, it may come in contact with gums, other mucosal surfaces, tongue, lips, and face. Furthermore, the silver fluoride may result in the formation of silver oxide which may result in a pigmentation of the applied area. This may result in a range of brown to dark brown discoloration which is undesirable on certain affected areas, including the skin.

[0014] Accordingly, the present inventors have found that what is needed is a CSDS that has an improved viscosity which allows for a dentist to better control the application of the formulation to the intended area on the teeth as a topical composition used to test for the status of carious lesions without inadvertent extension to other oral structures or spills on the face or equipment.

[0015] It was surprisingly found that adding a thickening agent to the silver fluoride composition can meet these needs when testing for the status of carious lesions in a subject with no evidence of unintended adverse effects, while maintaining the desirable properties of the silver fluoride. These improved compositions are hereinafter referred to as Thickened Caries Status Disclosing Compositions (TCSDC).

[0016] The following sentences may be used to describe the invention.

[0017] 1. In a first aspect, the disclosure relates to a thickened silver fluoride composition for oral application, comprising silver fluoride and a thickening agent, wherein the thickening agent is present in an amount of 0.1 wt.% to 15 wt.%, based on a total weight of the thickened silver fluoride composition.

[0018] 2. The thickened silver fluoride composition of sentence 1, wherein said composition may be a thixotropic fluid and may have a viscosity of 0.02 to 500 Pa s, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, carried out at a temperature of about 23°C, and a shear rate of from 0.1 / second to 100 / second.

[0019] 3. The thickened silver fluoride composition of sentence 1 or 2, may further comprise nitric acid.

[0020] 4. The thickened silver fluoride composition of any one of sentences 1 - 3, wherein the thickening agent may be present in an amount of 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, or 1.5 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

[0021] 5. The thickened silver fluoride composition of any one of sentences 1-4, wherein the thickening agent may be a cellulose derivative (“cellulose gum”) such as carboxymethyl cellulose (CMC), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and microcrystalline cellulose; polyvinyl pyrrolidone; xanthan; an admixture of glycerin and polyacrylate; carrageenans such as iota-carrageenan, kappa-carrageenan, kappa2- carrageenan, and lambda-carrageenan; guar gum; gum karaya; gum arabic; gum tragacanth; gelatin; algin; starch; pectin; silica thickeners, such as hydrated silica and colloidal silica; and mixtures thereof .

[0022] 6. The thickened silver fluoride composition as described in any one of sentences 1-5, wherein the thickened silver fluoride composition may not contain ammonia or silver diamine fluoride.

[0023] 7. The thickened silver fluoride composition as described in any one of sentences 1-6, wherein the silver fluoride may be present in an amount of 2 wt.% to 75 wt.%, or 5 wt.% to 50 wt.%, or 25 wt.% to 45 wt.%, based on the total weight of the thickened silver fluoride composition.

[0024] 8. The thickened silver fluoride composition as described in any one of sentences 1-7, may further comprise a coloring agent.

[0025] 9. The thickened silver fluoride composition as described in any one of sentences 1-8, may further comprise a coloring agent, wherein the coloring agent may be triarylmethane dye.

[0026] 10. The thickened silver fluoride composition as described in any one of sentences 1-

[0027] 9, may further comprise a flavoring agent.

[0028] 11. The thickened silver fluoride composition as described in any one of sentences 1-

[0029] 10, wherein the thickened silver fluoride composition may be a thixotropic fluid that can undergo an isothermal gel-sol-gel transformation.

[0030] 12. The thickened silver fluoride composition as described in any one of sentences 1-

[0031] 11, wherein the thickened silver fluoride composition may have a pH of from 4.0 to 7.5, or 4.5 to 7.5, or 4.5 to 7.0, or 5.5 to 7.5, or 5.5 to 7.0, or 5.5 to 6.5, or 5.5 to 6.0. 13. The thickened silver fluoride composition as described in any one of sentences 1-

[0032] 12, wherein the viscosity of the thickened silver fluoride composition may be from 0.1 Pa-s to 500 Pa-s, at a shear rate of from 0.1 / second to 100 / second; or from 0.5 Pa-s to 450 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or from 5 Pa-s to 40 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or the viscosity is greater than 75 Pa-s, at a shear rate of 0.1 / sec, and less than 15 Pa-s, at a shear rate of 100 / sec, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, and carried out at a temperature of about 23°C.

[0033] 14. The thickened silver fluoride composition as described in any one of sentences 1-

[0034] 13, wherein the silver fluoride may be present in an amount to provide 1,000 ppm to 75,000 ppm of fluoride to the thickened silver fluoride composition, or 2,000 ppm to 60,000 ppm of fluoride to the thickened silver fluoride composition, or 5,000 ppm to 50,000 ppm of fluoride to the thickened silver fluoride composition , or greater than 10,500 ppm to 50,000 ppm fluoride to the thickened silver fluoride composition, based on the total weight of the composition; or the silver fluoride is present in an amount to provide 100 ppm to 14,000 ppm of silver to the thickened silver fluoride composition, or 200 ppm to 12,000 ppm of silver to the thickened silver fluoride composition, or 600 ppm to 10,000 ppm of silver to the thickened silver fluoride composition, or 1,800 ppm to 9,000 ppm of silver to the thickened silver fluoride composition, based on the total weight of the composition.

[0035] 15. The thickened silver fluoride composition as described in any one of sentences 1-

[0036] 14, wherein nitric acid may be added to the thickened silver fluoride composition in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 9 months at approximately 25° C.

[0037] 16. The thickened silver fluoride composition as described in any one of sentences 1-

[0038] 15, wherein nitric acid may be added to the thickened silver fluoride composition in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 18 months at approximately 25° C.

[0039] 17. The thickened silver fluoride composition as described in any one of sentences 1-

[0040] 16, may further comprising nitric acid, wherein nitric acid may be present in an amount of approximately 0.5% - 10% weight per unit volume (w / v%), or 1 - 8 w / v%, or 3 - 5 w / v%, based on the total volume of the thickened silver fluoride composition. 18. The thickened silver fluoride composition as described in any one of sentences 1- 17, wherein the silver fluoride composition may be made by dissolving a powdered silver fluoride in water and then adding the thickening agent.

[0041] 19. The thickened silver fluoride composition as described in sentence 18, wherein the water may be ultrapure water.

[0042] 20. The thickened silver fluoride composition as described in sentence 18, wherein the water may be de-oxygenated.

[0043] 21. The thickened silver fluoride composition as described in sentence 18, wherein the water may be purged with argon gas.

[0044] 22. The thickened silver fluoride composition as described in any one of sentences 1- 17, further comprising a reducing agent.

[0045] 23. The thickened silver fluoride composition as described in sentence 22, wherein the reducing agent is present in an amount of 1 wt.% to 50 wt.%, or 5 wt.% and 40 wt.%, or 8 wt.% and 15 wt.%, based on the total weight of the thickened silver fluoride composition.

[0046] 24. The thickened silver fluoride composition as described in sentence 22, wherein the reducing agent is present in an amount of 1 w / v% to about 50 w / v%, or from about 5 w / v% to about 40 w / v%, or from about 8 w / v% to about 15 w / v%.

[0047] 25. The thickened silver fluoride composition as described in any one of sentences 22- 24, wherein the reducing agent comprises Al, Cr, Fe, Fe2+, Sn2+, or Cu+, or the reducing agent comprises Fe, Fe2+, Sn2+, or Cu+.

[0048] 26. The thickened silver fluoride composition as described in any one of sentences 22- 24, wherein the reducing agent solution comprises an inorganic metallic salt.

[0049] 27. The thickened silver fluoride composition as described in sentence 26, wherein the metallic salt is ferrous fluoride.

[0050] 28. The thickened silver fluoride composition as described in sentence 26, wherein the metallic salt is stannous fluoride.

[0051] 29. The thickened silver fluoride composition as described in any one of sentences 22- 24, wherein the reducing agent solution has a solvent comprising at least one of water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 55:45 to 95:5; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 70:30 to 95:5.

[0052] 30. The thickened silver fluoride composition as described in any one of sentences 22- 24, wherein the reducing agent solution comprises an organic reducing agent.

[0053] 31. The thickened silver fluoride composition as described in sentence 30, wherein the organic reducing agent is present in an amount of from about 1 wt.% to 50 wt.%, based on the total weight of the composition.

[0054] 32. The thickened silver fluoride composition as described in any one of sentences 30- 31, wherein the organic reducing agent comprises at least one of tannic acid, a polyphenol, a eugenol and a phenylpropanoid.

[0055] 33. The thickened silver fluoride composition as described in any one of sentences 22- 24, wherein the reducing agent solution comprises a sugar comprising at least one of an oligosaccharide, a polysaccharide, a monosaccharide and a disaccharide.

[0056] 34. The thickened silver fluoride composition as described in sentence 33, wherein the monosaccharide comprises at least one of aldoses and ketoses classes of organic chemical compounds; or wherein the monosaccharide comprises dietary monosaccharides comprising at least one of galactose, glucose and fructose; or wherein the disaccharides comprise at least one of lactose and maltose; or wherein the oligosaccharide comprises at least one of starch and starch-derivatives; or wherein the oligosaccharide comprises at least one of starch and starch-derivatives and the at least one of starch and starch-derivatives comprise at least one of glucose syrup, maltodextrin and dextrin.

[0057] 35. In a second aspect, the present invention relates to a method of forming the thickened silver fluoride composition of any one of sentences 1-34, comprising: dissolving a powdered silver fluoride in water; adding nitric acid; and then adding the thickening agent in an amount of 0.1 wt.% to 15 wt.%, based on a total weight of the thickened silver fluoride composition.

[0058] 36. In a third aspect, the present invention relates to a kit comprising two containers, wherein one of the containers comprises silver fluoride and one container comprises a reducing agent solution, wherein one or both containers comprises a thickening agent in the kit such that when contents of both containers are combined to form a thickened silver fluoride composition, the thickening agent is in an amount of 0.1 wt.% to 15 wt.%, based on a total weight of the thickened silver fluoride composition.

[0059] 37. The kit as described in sentence 36, wherein when contents of both containers are combined to form a thickened silver fluoride composition, the thickening agent is in an amount of 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, or 1.5 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

[0060] 38. The kit as described in sentence 36 or 37, wherein the reducing agent may be present in an amount of 1 wt.% to 50 wt.%, or 5 wt.% and 40 wt.%, or 8 wt.% and 15 wt.%, based on the total weight of the reducing agent solution.

[0061] 39. The kit as described in any one of sentences 36-38, wherein the reducing agent may be present in an amount of 1 w / v% to about 50 w / v%, or from about 5 w / v% to about 40 w / v%, or from about 8 w / v% to about 15 w / v%.

[0062] 40. The kit as described in any one of sentences 36-39, wherein the reducing agent may comprise Al, Cr, Fe, Fe2+, Sn2+, or Cu+; or the reducing agent may comprise Fe, Fe2+, Sn2+, or Cut

[0063] 41. The kit as described in any one of sentences 36-40, wherein the reducing agent solution may comprise an inorganic metallic salt.

[0064] 42. The kit as described in sentence 41, wherein the metallic salt may be ferrous fluoride.

[0065] 43. The kit as described in sentence 41, wherein the metallic salt may be stannous fluoride.

[0066] 44. The kit as described in any one of sentences 36-43, wherein the reducing agent solution may have a solvent comprising at least one of water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 55:45 to 95:5; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 70:30 to 95:5.

[0067] 45. The kit as described in any one of sentences 36-39, wherein the reducing agent solution may comprise an organic reducing agent. 46. The kit as described in sentence 45, wherein the organic reducing agent may be present in an amount of from about 1 wt.% to 50 wt.%, based on the total weight of the composition.

[0068] 47. The kit as described in any one of sentences 45-46, wherein the organic reducing agent may comprise at least one of tannic acid, a polyphenol, a eugenol and a phenylpropanoid.

[0069] 48. The kit as described in any one of sentences 36-39, wherein the reducing agent solution may comprise a sugar comprising at least one of an oligosaccharide, a polysaccharide, a monosaccharide and a disaccharide.

[0070] 49. The kit as described in sentence 48, wherein the monosaccharide may comprise at least one of aldoses and ketoses classes of organic chemical compounds; or wherein the monosaccharide comprises dietary monosaccharides comprising at least one of galactose, glucose and fructose; or wherein the disaccharides comprise at least one of lactose and maltose; or wherein the oligosaccharide comprises at least one of starch and starchderivatives; or wherein the oligosaccharide comprises at least one of starch and starchderivatives and the at least one of starch and starch-derivatives comprise at least one of glucose syrup, maltodextrin and dextrin.

[0071] 50. The kit as described in any one of sentences 36-49, wherein the container comprising the reducing agent solution comprises the thickening agent present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the reducing agent solution.

[0072] 51. The kit as described in any one of sentences 36-49, wherein the container comprising the silver fluoride comprises the thickening agent present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

[0073] 52. The kit as described in any one of sentences 36-49, wherein the thickening agent is only present in the container comprising the silver fluoride and the container comprising the reducing agent solution has no thickening agent.

[0074] 53. The kit as described in any one of sentences 36-49, wherein the thickening agent is only present in the container comprising the reducing agent solution and the container comprising the silver fluoride has no thickening agent. 54. The kit as described in any one of sentences 36-53, wherein the thickening agent may be a cellulose derivative (“cellulose gum”) such as carboxymethyl cellulose (CMC), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and microcrystalline cellulose; polyvinyl pyrrolidone; xanthan; an admixture of glycerin and polyacrylate; carrageenans such as iota-carrageenan, kappa-carrageenan, kappa2- carrageenan, and lambda-carrageenan; guar gum; gum karaya; gum arabic; gum tragacanth; gelatin; algin; starch; pectin; silica thickeners, such as hydrated silica and colloidal silica; and mixtures thereof.

[0075] 55. The kit as described in any one of sentences 36-54, wherein only one of the two containers contains the thickening agent, and the container containing the thickening agent contains a composition which is a thixotropic fluid and has a viscosity of 0.02 Pa-s to 500 Pa s, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, carried out at a temperature of about 23°C, and a shear rate of from 0.1 / second to 100 / second.

[0076] 56. The kit as described in any one of sentences 36-55, wherein the container comprising silver fluoride also comprises nitric acid.

[0077] 57. The kit as described in any one of sentences 36-56, wherein the kit does not contain ammonia or silver diamine fluoride.

[0078] 58. The kit as described in any one of sentences 36-57, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the silver fluoride is present in an amount of 2 wt.% to 75 wt.%, or 5 wt.% to 50 wt.%, or 25 wt.% to 45 wt.%, based on the total weight of the thickened silver fluoride composition.

[0079] 59. The kit as described in any one of sentences 36-58, further comprising a coloring agent.

[0080] 60. The kit as described in any one of sentences 36-58, further comprising a coloring agent, wherein the coloring agent is triarylmethane dye.

[0081] 61. The kit as described in any one of sentences 36-60, further comprising a flavoring agent.

[0082] 62. The kit as described in any one of sentences 36-61, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the thickened silver fluoride composition is a thixotropic fluid that can undergo an isothermal gel-sol-gel transformation.

[0083] 63. The kit as described in any one of sentences 36-62, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the thickened silver fluoride composition has a pH of from 4.0 to 7.5, or 4.5 to 7.0, or 5.5 to 7.5, or 5.5 to 7.0, or 5.5 to 6.5, or 5.5 to 6.0.

[0084] 64. The kit as described in any one of sentences 36-63, wherein only one of the two containers contains the thickening agent, and the container containing the thickening agent contains a composition having a viscosity of from 0.1 Pa-s to 500 Pa-s, at a shear rate of from 0.1 / second to 100 / second; or from 0.5 Pa-s to 450 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or from 5 Pa-s to 40 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or the viscosity is greater than 75 Pa-s, at a shear rate of 0.1 / sec, and less than 15 Pa-s, at a shear rate of 100 / sec, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, and carried out at a temperature of about 23°C.

[0085] 65. The kit as described in any one of sentences 36-64, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the silver fluoride is present in an amount to provide 1,000 ppm to 75,000 ppm of fluoride to the thickened silver fluoride composition, or 2,000 ppm to 60,000 ppm of fluoride to the thickened silver fluoride composition, or 5,000 ppm to 50,000 ppm of fluoride to the thickened silver fluoride composition , or greater than 10,500 ppm to 50,000 ppm fluoride to the thickened silver fluoride composition, based on the total weight of the composition; or the silver fluoride is present in an amount to provide 100 ppm to 14,000 ppm of silver to the thickened silver fluoride composition, or 200 ppm to 12,000 ppm of silver to the thickened silver fluoride composition, or 600 ppm to 10,000 ppm of silver to the thickened silver fluoride composition, or 1,800 ppm to 9,000 ppm of silver to the thickened silver fluoride composition, based on the total weight of the composition.

[0086] 66. The kit as described in any one of sentences 36-65, wherein the container comprising the silver fluoride also comprises nitric acid in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 9 months at approximately 25° C, based on the total weight of the composition in the container comprising the silver fluoride. 67. The kit as described in any one of sentences 36-66, wherein the container comprising the silver fluoride also comprises nitric acid in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 18 months at approximately 25° C, based on the total weight of the composition in the container comprising the silver fluoride.

[0087] 68. The kit as described in any one of sentences 36-67, wherein the container comprising the silver fluoride also comprises nitric acid and wherein when contents of both containers are combined to form the thickened silver fluoride composition, the nitric acid is present in an amount of approximately 0.5% - 10% weight per unit volume (w / v%), or 1 - 8 w / v%, or 3 - 5 w / v%, based on the total volume of the thickened silver fluoride composition.

[0088] 69. In fourth aspect, the present invention may relate to a method of testing the status of a carious lesion, may comprise topically applying a therapeutically effective amount of the thickened silver fluoride composition according to any one of sentences 1-34 to a location of a carious lesion in at least one tooth.

[0089] 70. A method of testing the status of a carious lesion, may comprise accessing the kit according to any one of sentences 36-38, topically applying a therapeutically effective amount of the contents of the container comprising the silver fluoride to a location of a carious lesion in at least one tooth, then applying the contents of the container comprising the reducing agent solution to the same location, and examine the color of the location to determine the status of the carious lesion.

[0090] 71. The method of sentence 70, wherein the reducing agent solution may comprise a thickening agent.

[0091] 72. In a fifth aspect, the present invention relates to a method of densensitizing teeth, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition of any one of sentences 1-34 to a surface of at least one tooth that is sensitive to at least one of heat, cold, sweet, acid and tactile pressure to thereby reduce sensitivity.

[0092] 73. In a sixth aspect, the present invention relates to a method of densensitizing teeth, comprising accessing the kit according to any one of sentences 36-38, topically applying a therapeutically effective amount of the container comprising the silver fluoride to a location on at least one tooth that is sensitive to at least one of heat, cold, sweet, acid and tactile pressure, then applying the contents of the container comprising the reducing agent solution to the same location, to thereby reduce sensitivity.

[0093] 74. The method of sentence 73, wherein the reducing agent solution may comprise a thickening agent.

[0094] 75. In a seventh aspect, the present invention relates to a method of treating teeth, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition of any one of sentences 1-34 to a decayed portion of at least one tooth.

[0095] 76. In an eighth aspect, the present invention relates to a method of treating teeth, comprising accessing the kit according to any one of sentences 36-68, topically applying a therapeutically effective amount of the contents of the container comprising the silver fluoride to a location of a decayed portion of at least one tooth, then applying the contents of the container comprising the reducing agent solution to the same location.

[0096] 77. The method of sentence 76, wherein the reducing agent solution may comprise a thickening agent.

[0097] 78. In a ninth aspect, the present invention relates to a method of preventing caries in high-risk teeth, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition of any one of sentences 1-34 to a surface of the tooth that is at a high risk of forming a carious lesion.

[0098] 79. In a tenth aspect, the present invention relates to a method of preventing caries in high-risk teeth, comprising accessing the kit according to any one of sentences 36-68, topically applying a therapeutically effective amount of the contents of the container comprising the silver fluoride to at least one tooth having a high risk of forming a carious lesion, then applying the contents of the container comprising the reducing agent solution to the same location.

[0099] 80. The method of sentence 79, wherein the reducing agent solution may comprise the thickening agent.

[0100] 81. In an eleventh aspect, the present invention relates to a method of forming a kit, comprising forming a composition comprising silver fluoride by dissolving a powdered silver fluoride in water; adding nitric acid; and then adding a thickening agent in an amount of 0.2 wt.% to 30 wt.%, based on a total weight of the composition. 82. The method of forming the kit as described in sentence 81, may further comprise forming a reducing agent solution by combining a reducing agent with a solvent comprising at least one of water, glycerol and sorbitol; or further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising water, glycerol and sorbitol; or further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 55:45 to 95:5; or further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 70:30 to 95:5.

[0101] 83. The method of forming the kit as described in any one of sentences 36-68, wherein the thickening agent is present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

[0102] The following definitions of terms are provided in order to clarify the meanings of certain terms as used herein.

[0103] The terms “topical” and “topically” refer to application of a composition as disclosed herein to an outer surface of the teeth. If the tooth is coated with plaque, then the topical treatment includes treating the surface of the plaque. The surfaces of the teeth include the subgingival surface and the buccal surface. Also, the tooth may or may not have root surface tooth decay, and as such, the composition may be applied directly to the decayed portion of the tooth.

[0104] There may be various ways to apply a topical paste or gel in accordance with the embodiments described herein. For example, the paste or gel may be applied to the teeth using an applicator. The applicator can be a Q-Tip® or other cotton tipped applicator, a flock tipped applicator, a micro-brush plastic filament brush, floss soaked with the inventive composition, a paper applicator, etc. In some embodiments, the patient may let the paste or gel remain on the teeth for 5 to 120 seconds per treatment. The first step of applying the thickened silver fluoride composition may take about 20 to about 60 seconds, and then the second step of applying the reducing agent solution may take about 5-30 seconds. When the chemical reaction has completed, the patient may rinse the oral cavity with water after allowing the paste or gel to sit on the teeth. For example, while keeping the lips closed, the patient may make a swishing motion to move the water around the oral cavity. The presence, absence, or state of a caries lesion can be determined by a health professional or lay person using methods that are known in the art. A person experiencing caries may not be aware of the disease. The earliest sign of a new carious lesion is the appearance of a chalky white spot on the surface of the tooth, indicating an area of demineralization of enamel. This is referred to as a white spot lesion, an incipient carious lesion or a "micro-cavity". As the lesion continues to demineralize, it can turn brown and eventually turn into a cavitation ("cavity"). Before the cavity forms, the process is reversible, but once a cavity forms, the lost tooth structure cannot be regenerated.

[0105] As used herein, the term “effective amount” or “therapeutically effective amount” means an amount of a composition comprising the silver fluoride, that is effective to reverse a disease state, arrest a disease state, slow the progression of a disease state, ameliorate a disease state, relieve symptoms of a disease state or has any other beneficial consequences for the treated subject. For example, the thickened compositions disclosed herein may have a topical therapeutic effect in inhibiting, reducing and / or preventing growth of a carious lesion. The thickened compositions disclosed herein may also have a topical therapeutic effect in inhibiting, reducing and / or preventing sensitivity to at least one of heat, cold, sweet, acid, and tactile pressure.

[0106] As used herein, the term “about” refers to an approximately + / — 10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.

[0107] The term “excipient” refers to an inactive substance that serves as a medium for the active agents and may be used in the production of a product comprising the composition to ensure the stability, efficacy, taste and appearance of the product is maintained from the time of production to when the product is consumed by the consumer.

[0108] The terms “patient,” “subject,” “individual,” and the like are used interchangeably herein, and refer to any animal amenable to the methods described herein. In some nonlimiting embodiments, the patient, subject or individual is mammal, such as a human, dog, or cat, preferably a human.

[0109] It must be noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

[0110] As used herein, unless otherwise specified, the use of the ordinal adjectives “first”, “second”, “third”, etc., to describe a common object, merely indicate that different instances of like objects are being referred to, and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking, or in any other manner.

[0111] In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word “comprise” or variations such as “comprises” or “comprising” are used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention. Also, the terms “including”, “characterized by” and “containing” are synonymous with and means “comprising”. The transitional phrase "consisting essentially of' limits the scope of a claim to the specified materials or steps and those that do not adversely materially affect the basic and novel characteristics of the claimed invention, such as would be needed for caries status evaluation or reduction of sensitivity to at least one of heat, cold, sweet, acid and tactile pressure.

[0112] DETAILED DESCRIPTION

[0113] For the purposes of promoting an understanding of the principles in accordance with the disclosure, reference will now be made to the embodiments described herein. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended. Any alterations and further modifications of the inventive features illustrated herein, and any additional applications of the principles of the disclosure as illustrated herein, which would normally occur to one, skilled in the relevant art and having possession of this disclosure, are to be considered within the scope of the disclosure.

[0114] In the embodiments that follow, there is disclosed a Thickened Caries Status Disclosing Composition (TCSDC) for carious lesions, processes for the preparation and methods of utilization thereof.

[0115] The TCSDC comprises a water-based silver fluoride composition, a thickening agent and optionally a reducing agent solution.

[0116] The TCSDC comprises a water-based silver fluoride composition for use in the initial application of the water-based silver fluoride solution to a carious lesion and is optionally followed by the subsequent application of a reducing agent solution for the visual analysis of the status of the carious lesion wherein the water-based silver fluoride composition can comprise nitric acid to stabilize the silver fluoride composition. Specifically, the water-based silver fluoride composition is firstly applied to a carious lesion. Then after a period of approximately 1 to 3 minutes, the reducing agent solution can be applied to the carious lesion to turn the lesion black.

[0117] Over a period of time, the lightening of the color of the blackened carious lesion from black to, for example, between brown and yellow, is an indication that the caries is still progressing. However, the carious lesion remaining black is an indication that the caries is arrested and is no longer progressing.

[0118] Now, as alluded to above, the water-based silver fluoride composition can be stabilized with nitric acid. The water-based silver fluoride composition stabilized in this way was surprisingly found to have an improved shelf life when compared to water-based silver fluoride without the nitric acid stabilizer. Furthermore, the water-based silver fluoride composition does not require ammonia and does not use silver diamine fluoride (SDF).

[0119] In further embodiments, the reducing agent solution has improved clarity when compared to prior art solutions.

[0120] Thickened Silver Fluoride Composition

[0121] The TCSDC comprises a thickened silver fluoride composition and optionally a (thickened) reducing agent solution.

[0122] The thickened silver fluoride composition comprises silver fluoride which can be present in a concentration of from about 2 wt.% to about 75 wt.%, or from about 5 wt.% to about 50 wt.%, or from about 25 wt.% to about 45 wt.% based on the total weight of the thickened silver fluoride composition.

[0123] It should be noted that, according to the present embodiments, the silver fluoride powder can be dissolved in water or the silver fluoride composition can be water-based, distinguishing the present water-based solution from silver diamine fluoride which is a silver fluoride powder dissolved in ammonia (a solution of water and ammonia).

[0124] The thickened silver fluoride composition can have a viscosity of 0.02 Pa-s to 500 Pa s, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, carried out at a temperature of about 23°C, and a shear rate of from 0.1 / second to 100 / second. The thickened silver fluoride composition can also be thixotropic, as such, the silver fluoride composition may have a reduced viscosity relative to an initial viscosity after a force is applied and is capable of recovering fully to its initial viscosity, after the force is removed.

[0125] The thickening agent can be present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, or 1.5 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition. The thickening agent to be used in the thickened silver fluoride composition can be a cellulose derivative (“cellulose gum”) such as carboxymethyl cellulose (CMC), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and microcrystalline cellulose; polyvinyl pyrrolidone; xanthan; an admixture of glycerin and polyacrylate; carrageenans such as iota-carrageenan, kappa-carrageenan, kappa2-carrageenan, and lambda- carrageenan; guar gum; gum karaya; gum arabic; gum tragacanth; gelatin; algin; starch; pectin; silica thickeners, such as hydrated silica and colloidal silica; and mixtures thereof.

[0126] The thickened silver fluoride composition can be a thixotropic fluid that can undergo an isothermal gel-sol-gel transformation.

[0127] The viscosity of the thickened silver fluoride composition can be from 0.1 Pa-s to 500 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or from 0.5 Pa-s to 450 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or from 5 Pa-s to 40 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or greater than 75 Pa-s, at a shear rate of 0.1 / sec, and less than 15 Pa-s, at a shear rate of 100 / sec, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, and carried out at a temperature of about 23°C.

[0128] The silver fluoride may be present in an amount to provide 1,000 ppm to 75,000 ppm fluoride to the thickened silver fluoride composition, or 2,000 ppm to 60,000 ppm fluoride to the thickened silver fluoride composition, or 5,000 ppm to 50,000 ppm fluoride to the thickened silver fluoride composition, or greater than 10,500 ppm to 50,000 ppm fluoride to the thickened silver fluoride composition, based on the total weight of the thickened silver fluoride composition; or the silver fluoride is present in an amount to provide 100 ppm to 14,000 ppm silver to the thickened silver fluoride composition, or 200 ppm to 12,000 ppm silver to the thickened silver fluoride composition, or 600 ppm to 10,000 ppm silver, or 1,800 ppm to 9,000 ppm of silver to the thickened silver fluoride composition, based on the total weight of the thickened silver fluoride composition.

[0129] Now, for the purposes of stabilizing the thickened silver fluoride composition, nitric acid can be added. The nitric acid, silver fluoride and thickening agent can be combined in any order, however, preferably, the thickening agent is added in the last step of making the thickened silver fluoride composition. Specifically, no significant deterioration of the silver ions in solution is expected to be found after 60 days at 55°C (which is considered to be equivalent to 18 months at an ambient temperature of 25° C) when a water-based silver fluoride composition is stabilized with nitric acid. As such, in embodiments, the water-based silver fluoride composition may have a shelf life of more than approximately 18 months (up to 24 months) without requiring refrigeration. In a preferred embodiment, the silver ion levels do not decrease by more than 5 wt.% over a period of at least 9 months at approximately 25° C, or the silver ion levels do not decrease by more than 5 wt.% over a period of at least 18 months at approximately 25° C.

[0130] Preferably, an aqueous solution of silver fluoride at a concentration of 10-50 w / v%, or 20-45 w / v%, or 35-45 w / v% is combined with nitric acid.

[0131] Preferably, the nitric acid comprises between 0.5% - 10% weight per unit volume (w / v%), or 1-8 w / v%, or 3 - 5 w / v% of the thickened silver fluoride composition. As such, the thickened silver fluoride composition can have a pH of approximately 4.0-6.0, 4.5 - 6.0, or 5.5 - 6.0.

[0132] The nitric acid used in the manufacture of the thickened silver fluoride composition can be 99.4 w / v% . In order to obtain a 3 w / v% solution of nitric acid, 3.02 ml of the nitric acid can be added to 100 ml of (thickened) silver fluoride composition.

[0133] Alternatively, to obtain a 5 w / v% solution of nitric acid in 100 ml of silver fluoride, 5.03 ml of 99.4% nitric acid (w / w) can be added to an aqueous silver fluoride.

[0134] The thickened silver fluoride composition may be made by dissolving powdered silver fluoride in water, adding the nitric acid solution, and then adding the thickening agent.

[0135] The water may be ultra-purified and may be de-oxygenated, such as by being purged with argon gas. Purging with argon gas removes dissolved oxygen from the water and is important for reducing the possibility of oxidation of the silver ions.

[0136] As such, in accordance with one exemplary process, the process for making the waterbased thickened silver fluoride composition can comprise adding silver fluoride powder to argon purged water. Then, nitric acid can be added followed by the cellulose derivative thickening agent. The final volume can made up by adding a small additional amount of argon purged water. This formula may be scaled to any quantity desired.

[0137] Excipients may also be included in the thickened silver fluoride composition such as a coloring agent, stabilizing agent, mixing agent, and flavoring agent in an amount of from about 0 wt.% to about 10 wt.%, based on the total weight of the thickened silver fluoride composition.

[0138] Reducing Agent Solution

[0139] The reducing agent solution can comprise a reducing agent present in an amount to provide 1 wt.% to 50 wt.%, or 5 wt.% and 40 wt.%, or 8 wt.% and 15 wt.% of reducing agent, based on the total weight of the reducing agent solution. Differing types of reducing agent solutions may be utilized as is described in further detail below.

[0140] The reducing agent solution can comprise any chemical species that "donates" an electron to the silver cation. These include Al, Cr, Fe, Fe2+, Sn2+, or Cu+or organic reducing agents, or the reducing agent can comprise Fe, Fe2+, Sn2+, or Cu+.

[0141] In this regard, a stannous fluoride (SnF2) may be present in an amount to provide from about 1 wt.% to about 50 wt.% of stannous fluoride, or from about 5 wt.% to about 40 wt.% of stannous fluoride, or from about 8 wt.% to about 15 wt.% of stannous fluoride, based on the total weight of the reducing agent solution. Alternatively, the stannous fluoride (SnF2) may be present in an amount to provide from about 1 w / v% to about 50 w / v% of stannous fluoride, or from about 5 w / v% to about 40 w / v% of stannous fluoride, or from about 8 w / v% to about 15 w / v% of stannous fluoride, and the stannous fluoride is in water, or a mixture of water and hydrophilic solvent(s), or a mixture of water and glycerol and sorbitol.

[0142] It is preferred for the reducing agent to avoid hydrolysis. If this happens, the solution may become cloudy. In order to reduce hydrolysis of the reducing agent, the reducing agent solution can be mixed and / or glycerol can be added.

[0143] It should be noted that other inorganic metallic salts may be included in the reducing agent solution such as ferrous fluoride in substantially the same concentration as the stannous fluoride, such that the ferrous fluoride may be present in an amount to provide from about 1 wt.% to about 50 wt.%, or from about 5 wt.% to 40 wt.%, or 8 wt.% to 15 wt.% of ferrous fluoride, based on the total weight of the reducing agent solution.

[0144] Furthermore, organic reducing agents may be utilized in substantially the same concentration as the stannous fluoride, such that the organic reducing agent may be present in an amount to provide from about 1 wt.% to about 50 wt.%, or from about 5 wt.% to about 40 wt.%, or from about 8 wt.% to about 15 wt.% of organic reducing agent, based on the total weight of the reducing agent solution. In these embodiments, the organic reducing agent may comprise tannic acid, polyphenol, eugenol, or any type of phenylpropanoid.

[0145] Moreover, the reducing agent solution may comprise a sugar which acts as a reducing agent on account of the free aldehyde or ketone group. Suitable examples of sugars include monosaccharides, disaccharides, oligosaccharides, and polysaccharides. The monosaccharides may comprise aldoses and ketoses or common dietary monosaccharides including galactose, glucose and fructose. The disaccharides may comprise lactose and maltose. Furthermore, the reducing agent solution may comprise oligosaccharides such as starch and starch-derivatives including glucose syrup, maltodextrin and dextrin that contain percentages of reducing sugars present in these starch derivatives called dextrose equivalent (DE).

[0146] Furthermore, polysaccharides that can be broken down into smaller units, such as glucose or maltose may be used.

[0147] A thickening agent can be present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the reducing agent solution.

[0148] The thickening agent for the reducing agent solution can be a cellulose derivative (“cellulose gum”) such as carboxymethyl cellulose (CMC), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and microcrystalline cellulose; polyvinyl pyrrolidone; xanthan; an admixture of glycerin and polyacrylate; carrageenans such as iota- carrageenan, kappa-carrageenan, kappa2-carrageenan, and lambda-carrageenan; guar gum; gum karaya; gum arabic; gum tragacanth; gelatin; algin; starch; pectin; silica thickeners, such as hydrated silica and colloidal silica; and mixtures thereof.

[0149] Excipients may also be included in the reducing agent solution such as a coloring agent, stabilizing agent, mixing agent, and flavoring agent in an amount of from about 0 wt.% to about 10 wt.% based on the total weight of the reducing agent solution.

[0150] Methods of Treatment

[0151] In an aspect of the disclosure, the status of a carious lesion can be determined by applying an effective amount of the thickened silver fluoride composition to a location of a carious lesion in a tooth, followed by applying a reducing agent solution to the same location, and examine the color of the location to determine the status of the carious lesion. The composition will stain a carious lesion black, while leaving non-carious surfaces a natural color. If there is tooth decay present on the tooth, it will also arrest the tooth decay, and form a hard outer layer on the lesion. If the hard and stained layer remains present, the lesion is not active. If that surface falls off, softens, or lightens in color, the lesion can reactivate.

[0152] Once the carious lesions are stained to form a black surface, decay will be arrested, and healthy teeth surfaces will remain unstained. The reducing agent solution can optionally be administered in a second step. If the reducing agent solution is used, the staining of the carious lesions and the arrest of the decay will happen essentially instantly. Without using the reducing agent solution, the color change will happen in about 48-72 hrs, whereas with the reducing agent solution, the color change will be done in about 20 seconds. In another aspect, the disclosure relates to densensitizing teeth, comprising administering a therapeutically effective amount of the thickened silver fluoride composition, and, optionally, the reducing agent solution to a surface of a tooth that is sensitive to at least one of heat, cold, sweet, acid and tactile pressure. The composition can occlude tubules as measured in a hydraulic conductance test. Tubules are associated with hypersensitive teeth. The composition reduces the sensitivity to at least one of heat, cold, sweet, acid and tactile pressure.

[0153] In another aspect, the disclosure relates to treating teeth, comprising applying a therapeutically effective amount of the thickened silver fluoride composition and optionally the reducing agent solution to a decayed portion of tooth.

[0154] In another aspect, the disclosure relates to preventing caries in high-risk teeth, comprising applying a therapeutically effective amount of the thickened silver fluoride composition and optionally the reducing agent solution to a surface of the tooth at a high risk of forming a carious lesion.

[0155] In all of the methods of the present disclosure, the subject treated can be a mammal; or a human, cat or dog; or preferably a human.

[0156] Examples

[0157] Example 1: Preparation O f Thickened Silver Fluoride Composition

[0158] Place 120 g - 150 g of AgF powder in a 500 ml - 1000 ml wide neck plastic container with a tight-fitting secure lid. Pour 250 ml - 300 ml of ultra-pure water into the container and mix until the AgF is dissolved.

[0159] Using an all-plastic filtration apparatus that has a vacuum attachment, place the filter into the filtration apparatus. Pour contents of the container into the filtration apparatus and apply the vacuum. Add 10-15 ml of 50-70% (w / w) nitric acid to the filtrate. Add sufficient carboxymethyl cellulose (CMC) to the mixture until the amount reaches 0.8 wt.% to 10 wt.% based on the total weight of the composition and mix until fully mixed.

[0160] Example 2: Preparation Of Stannous Fluoride Solution

[0161] Place 20-50 g SnF2 powder in a mixer. In a separate container, boil 100-200 mL of ultra pure water. Once it has reached 100°C, withdraw 30-70 mL and combine with the powder in the mixer. Mix until all of the powder dissolves. In an all-plastic filtration apparatus that has a vacuum attachment, pour contents of the mixing container into the filtration apparatus and apply the vacuum.

[0162] Introduce glycerol heated to 100°C. Stir in thoroughly until solution is completely clear. Then add the requisite amount of sorbitol to make a 10% w / v stannous fluoride solution. Add sufficient CMC to the mixture until the amount reaches 0.8 wt.% to 10 wt.% based on the total weight of the composition and mix until fully mixed.

[0163] Test of Thickened Caries Status Disclosing Compositions (TCSDC) on Arti ficial Dentin Caries

[0164] In order to test for staining, extracted third molar teeth are cleaned and stored in a 0.1% thymol solution and are sectioned horizontally 2 mm above the cemento-enamel junction. The dentin surface on the root-surface portion is smoothed with a series of fine wet and dry papers. A fine diamond disc is used to create shallow grooves to divide the dentin surface into two halves. One of the halves and the root area are coated with nail polish (a varnish). To produce artificial dentin caries in the uncoated areas, the teeth are immersed acidified gel was composed of 0.1 M lactic acid and gelatin using the method of Silverstone (1968) and are incubated for 14 days at 370C.

[0165] At the end of the incubation period, the uncoated dentin areas are applied with 40 wt.% thickened silver fluoride followed by 10 wt.% thickened stannous fluoride. The areas for each treatment are selected at random. Excess solution is immediately mopped up with absorbent tissue. The varnish coating on the covered dentin areas is removed and those corresponding to the previously treated sites are given a similar brief exposure to the test agents and then immediately washed. After drying, the dentine surfaces are photographed at 5X magnification.

[0166] An experiment that tests for the advantages of a thickened solution versus a thin solution is the Rheology test.

[0167] Rheology Test

[0168] Objective -

[0169] The objective of the Rheological Study of samples is to establish the similarity and differences in the viscosity and rheological behavior of two nonthickened compositions (Theoretical Example X and Y) versus the inventive thickened composition (Theoretical Gel).

[0170] Method -

[0171] Rheological evaluation of the samples can be accomplished on a TA Instruments model AR-G2 rheometer. Prior to analysis, rotational inertia and zero gap is established for each configuration. For formulations, the bob (14mm radius x 42mm length with a 120° cone angle bottom) and cup (15mm radius) configuration is used due to the moderately low viscosity. The analysis is done in step flow mode at shear rates from 0.1 to 100 (1 / sec) and temperature controlled at 25°C. The gap is 1mm. It is believed that at least 11 ml of product is required to fully submerge the bob and achieve a reliable measurement.

[0172] Due to the higher viscosity of the Theoretical Gel, a 40 mm cone (2°) and plate geometry is used The mode is the same as used for the bob and cup configuration. Enough product is placed on the lower plate to allow the gap to fill completely when closed to 1mm. Any excess is wiped from the outside of the plates prior to analysis. The temperature for the latter analysis is not controlled (estimated to be 23 °C).

[0173] Results -

[0174] Samples are run from 0.1 to 100 (1 / sec) shear rate and from 100 to 0.1 and all samples are expected to not exhibit change (memory) from the prior run. Below is a table of the expected viscosity data:

[0175] Summary -

[0176] All products are expected to demonstrate a significant Thixotropy (reduction in viscosity with increasing stress). The gel (as the name implies) has a significantly higher viscosity that facilitates application with a swab or applicator. Importantly, it can demonstrate similar shear thinning behavior.

[0177] The shear thinning behavior allows the products to flow (with stress applied). When they are in the mouth, the products exhibit lower stress and as a result, flow less and have the opportunity to adhere to the tooth surface.

[0178] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification may or may not necessarily all be referring to the same embodiment. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in each of the one or more embodiments.

[0179] Similarly, it should be appreciated that in the above description of example embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the Detailed Description of Specific Embodiments are hereby expressly incorporated into this Detailed Description of Specific Embodiments, with each claim standing on its own as a separate embodiment of this invention.

[0180] Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0181] Thus, while there has been described what are believed to be the preferred embodiments of the invention, those skilled in the art will recognize that other and further modifications may be made thereto without departing from the spirit of the invention, and it is intended to claim all such changes and modifications as falling within the scope of the invention. For example, the formulas given above are merely representative of procedures that may be used.

[0182] Although the invention has been described with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in many other forms.

[0183] INDUSTRIAL APPLICABILITY

[0184] It is apparent from the above, that the arrangements described are applicable to manufacturers of consumable dental materials.

Claims

ClaimsThe invention claimed is:

1. A thickened silver fluoride composition for oral application, comprising silver fluoride and a thickening agent, wherein the thickening agent is present in an amount of 0.1 wt.% to 15 wt.%, based on a total weight of the thickened silver fluoride composition.

2. The thickened silver fluoride composition of claim 1, wherein said composition is a thixotropic fluid and has a viscosity of 0.02 Pa-s to 500 Pa s, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, carried out at a temperature of about 23°C, and a shear rate of from 0.1 / second to 100 / second.

3. The thickened silver fluoride composition of claim 1 or 2, further comprising nitric acid.

4. The thickened silver fluoride composition of any one of claims 1 - 3, wherein the thickening agent is present in an amount of 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, or 1.5 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

5. The thickened silver fluoride composition of any one of claims 1 - 4, wherein the thickening agent is a cellulose derivative (“cellulose gum”), such as carboxymethyl cellulose (CMC), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and microcrystalline cellulose; polyvinyl pyrrolidone; xanthan; an admixture of glycerin and polyacrylate; carrageenans such as iota-carrageenan, kappa-carrageenan, kappa2- carrageenan, and lambda-carrageenan; guar gum; gum karaya; gum arabic; gum tragacanth; gelatin; algin; starch; pectin; silica thickeners, such as hydrated silica and colloidal silica; and mixtures thereof .

6. The thickened silver fluoride composition as claimed in any one of claims 1 - 5, wherein the thickened silver fluoride composition does not contain ammonia or silver diamine fluoride.

7. The thickened silver fluoride composition as claimed in any one of claims 1 - 6, wherein the silver fluoride is present in an amount of 2 wt.% to 75 wt.%, or 5 wt.% to 50 wt.%, or 25 wt.% to 45 wt.%, based on the total weight of the thickened silver fluoride composition.

8. The thickened silver fluoride composition as claimed in any one of claims 1-7, further comprising a coloring agent.

9. The thickened silver fluoride composition as claimed in any one of claims 1-8, further comprising a coloring agent, wherein the coloring agent is triarylmethane dye.

10. The thickened silver fluoride composition as claimed in any one of claims 1-9, further comprising a flavoring agent.

11. The thickened silver fluoride composition as claimed in any one of claims 1-10, wherein the thickened silver fluoride composition is a thixotropic fluid that can undergo an isothermal gel-sol-gel transformation.

12. The thickened silver fluoride composition as claimed in any one of claims 1-11, wherein the thickened silver fluoride composition has a pH of from 4.0 to 7.5, or 4.5 to 7.5, or 4.5 to 7.0, or 5.5 to 7.5, or 5.5 to 7.0, or 5.5 to 6.5, or 5.5 to 6.0.

13. The thickened silver fluoride composition as claimed in any one of claims 1-12, wherein a viscosity of the thickened silver fluoride composition is from 0.1 Pa-s to 500 Pa-s, at a shear rate of from 0.1 / second to 100 / second; or from 0.5 Pa-s to 450 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or from 5 Pa-s to 40 Pa-s, and a shear rate of from0.1 / second to 100 / second; or the viscosity is greater than 75 Pa-s, at a shear rate of 0.1 / sec, and less than 15 Pa-s, at a shear rate of 100 / sec, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, and carried out at a temperature of about 23°C.

14. The thickened silver fluoride composition as claimed in any one of claims 1-13, wherein the silver fluoride is present in an amount to provide 1,000 ppm to 75,000 ppm of fluoride to the thickened silver fluoride composition, or 2,000 ppm to 60,000 ppm of fluoride to the thickened silver fluoride composition, or 5,000 ppm to 50,000 ppm of fluoride to the thickened silver fluoride composition , or greater than 10,500 ppm to 50,000 ppm fluoride to the thickened silver fluoride composition, based on the total weight of the composition; or the silver fluoride is present in an amount to provide 100 ppm to 14,000 ppm of silver to the thickened silver fluoride composition, or 200 ppm to 12,000 ppm of silver to the thickened silver fluoride composition, or 600 ppm to 10,000 ppm of silver to the thickened silver fluoride composition, or 1,800 ppm to 9,000 ppm of silver to the thickened silver fluoride composition, based on the total weight of the composition.

15. The thickened silver fluoride composition as claimed in any one of claims 1-14, wherein nitric acid is added to the thickened silver fluoride composition in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 9 months at approximately 25° C, based on the total weight of the composition.

16. The thickened silver fluoride composition as claimed in any one of claims 1-15, wherein nitric acid is added to the thickened silver fluoride composition in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 18 months at approximately 25° C, based on the total weight of the composition.

17. The thickened silver fluoride composition as claimed in any one of claims 1-16, further comprising nitric acid, wherein nitric acid is present in an amount of approximately 0.5% - 10% weight per unit volume (w / v%), or 1 - 8 w / v%, or 3 - 5 w / v%, based on the total volume of the thickened silver fluoride composition.

18. The thickened silver fluoride composition as claimed in any one of claims 1-17, wherein the silver fluoride composition is made by dissolving a powdered silver fluoride in water and then adding the thickening agent.

19. The thickened silver fluoride composition as claimed in claim 18, wherein the water is ultrapure water.

20. The thickened silver fluoride composition as claimed in claim 18, wherein the water is de-oxygenated.

21. The thickened silver fluoride composition as claimed in claim 18, wherein the water is purged with argon gas.

22. The thickened silver fluoride composition as claimed in any one of claims 1-17, further comprising a reducing agent.

23. The thickened silver fluoride composition as claimed in claim 22, wherein the reducing agent is present in an amount of 1 wt.% to 50 wt.%, or 5 wt.% and 40 wt.%, or 8 wt.% and 15 wt.%, based on the total weight of the thickened silver fluoride composition.

24. The thickened silver fluoride composition as claimed in claim 22, wherein the reducing agent is present in an amount of 1 w / v% to about 50 w / v%, or from about 5 w / v% to about 40 w / v%, or from about 8 w / v% to about 15 w / v%.

25. The thickened silver fluoride composition as claimed in any one of claims 22-24, wherein the reducing agent comprises Al, Cr, Fe, Fe2+, Sn2+, or Cu+, or the reducing agent comprises Fe, Fe2+, Sn2+, or Cu+.

26. The thickened silver fluoride composition as claimed in any one of claims 22-24, wherein the reducing agent solution comprises an inorganic metallic salt.

27. The thickened silver fluoride composition as claimed in claim 26, wherein the metallic salt is ferrous fluoride.

28. The thickened silver fluoride composition as claimed in claim 26, wherein the metallic salt is stannous fluoride.

29. The thickened silver fluoride composition as claimed in any one of claims 22-24, wherein the reducing agent solution has a solvent comprising at least one of water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 55:45 to 95:5; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 70:30 to 95:5.

30. The thickened silver fluoride composition as claimed in any one of claims 22-24, wherein the reducing agent solution comprises an organic reducing agent.

31. The thickened silver fluoride composition as claimed in claim 30, wherein the organic reducing agent is present in an amount of from about 1 wt.% to 50 wt.%, based on the total weight of the composition.

32. The thickened silver fluoride composition as claimed in any one of claims 30-31, wherein the organic reducing agent comprises at least one of tannic acid, a polyphenol, a eugenol and a phenylpropanoid.

33. The thickened silver fluoride composition as claimed in any one of claims 22-24, wherein the reducing agent solution comprises a sugar comprising at least one of an oligosaccharide, a polysaccharide, a monosaccharide and a disaccharide.

34. The thickened silver fluoride composition as claimed in claim 33, wherein the monosaccharide comprises at least one of aldoses and ketoses classes of organic chemical compounds; or wherein the monosaccharide comprises dietary monosaccharides comprising at least one of galactose, glucose and fructose; or wherein the disaccharides comprise at least one of lactose and maltose; or wherein the oligosaccharide comprises at least one of starch and starch-derivatives; or wherein the oligosaccharide comprises at least one of starch and starch-derivatives and the at least one of starch and starch-derivatives comprise at least one of glucose syrup, maltodextrin and dextrin.

35. A method of forming the thickened silver fluoride composition of any one of claims 1-34, comprising: dissolving a powdered silver fluoride in water; adding nitric acid; and then adding the thickening agent in an amount of 0.1 wt.% to 15 wt.%, based on the total weight of the thickened silver fluoride composition.

36. A kit comprising two containers, wherein one container comprises silver fluoride and one container comprises a reducing agent solution, wherein one or both containers comprises a thickening agent in the kit such that when contents of both containers are combined to form a thickened silver fluoride composition, the thickening agent is in an amount of 0.1 wt.% to 15 wt.%, based on a total weight of the thickened silver fluoride composition.

37. The kit as claimed in claim 36, wherein when contents of both containers are combined to form a thickened silver fluoride composition, the thickening agent is in an amount of 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, or 1.5 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

38. The kit as claimed in claim 36 or 37, wherein the reducing agent is present in an amount of 1 wt.% to 50 wt.%, or 5 wt.% and 40 wt.%, or 8 wt.% and 15 wt.%, based on the total weight of the reducing agent solution.

39. The kit as claimed in any one of claims 36-38, wherein the reducing agent is present in the reducing agent solution in an amount of 1 w / v% to about 50 w / v%, or from about 5 w / v% to about 40 w / v%, or from about 8 w / v% to about 15 w / v%.

40. The kit as claimed in any one of claims 36-39, wherein the reducing agent comprises Al, Cr, Fe, Fe2+, Sn2+, or Cu+, or the reducing agent comprises Fe, Fe2+, Sn2+, or Cut41. The kit as claimed in any one of claims 36-40, wherein the reducing agent solution comprises an inorganic metallic salt.

42. The kit as claimed in claim 41, wherein the metallic salt is ferrous fluoride.

43. The kit as claimed in claim 41, wherein the metallic salt is stannous fluoride.

44. The kit as claimed in any one of claims 36-43, wherein the reducing agent solution has a solvent comprising at least one of water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 55:45 to 95:5; or the reducing agent solution comprises water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 70:30 to 95:5.

45. The kit as claimed in any one of claims 36-39, wherein the reducing agent solution comprises an organic reducing agent.

46. The kit as claimed in claim 45, wherein the organic reducing agent is present in an amount of from about 1 wt.% to 50 wt.%, based on the total weight of the thickened silver fluoride composition.

47. The kit as claimed in any one of claims 45-46, wherein the organic reducing agent comprises at least one of tannic acid, a polyphenol, a eugenol and a phenylpropanoid.

48. The kit as claimed in any one of claims 36-39, wherein the reducing agent solution comprises a sugar comprising at least one of an oligosaccharide, a polysaccharide, a monosaccharide and a disaccharide.

49. The kit as claimed in claim 48, wherein the monosaccharide comprises at least one of aldoses and ketoses classes of organic chemical compounds; or wherein the monosaccharide comprises dietary monosaccharides comprising at least one of galactose, glucose and fructose; or wherein the disaccharides comprise at least one of lactose and maltose; or wherein the oligosaccharide comprises at least one of starch and starchderivatives; or wherein the oligosaccharide comprises at least one of starch and starchderivatives and the at least one of starch and starch-derivatives comprise at least one of glucose syrup, maltodextrin and dextrin.

50. The kit as claimed in any one of claims 36-49, wherein the container comprising the reducing agent solution comprises the thickening agent present in an amount of from 0.5wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the reducing agent solution.

51. The kit as claimed in any one of claims 36-49, wherein the container comprising the silver fluoride comprises the thickening agent present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

52. The kit as claimed in any one of claims 36-49, wherein the thickening agent is only present in the container comprising the silver fluoride and the container comprising the reducing agent solution has no thickening agent.

53. The kit as claimed in any one of claims 36-49, wherein the thickening agent is only present in the container comprising the reducing agent solution and the container comprising the silver fluoride has no thickening agent.

54. The kit as claimed in any one of claims 36-53, wherein the thickening agent is a cellulose derivative (“cellulose gum”) such as carboxymethyl cellulose (CMC), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and microcrystalline cellulose; polyvinyl pyrrolidone; xanthan; an admixture of glycerin and polyacrylate; carrageenans such as iota-carrageenan, kappa-carrageenan, kappa2-carrageenan, and lambda- carrageenan; guar gum; gum karaya; gum arabic; gum tragacanth; gelatin; algin; starch; pectin; silica thickeners, such as hydrated silica and colloidal silica; and mixtures thereof.

55. The kit as claimed in any one of claims 36-54, wherein only one of the two containers contains the thickening agent, and the container containing the thickening agent contains a composition which is a thixotropic fluid and has a viscosity of 0.02 Pa-s to 500 Pa s, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, carried out at a temperature of about 23°C, and a shear rate of from 0.1 / second to 100 / second.

56. The kit as claimed in any one of claims 36-55, wherein the container comprising silver fluoride also comprises nitric acid.

57. The kit as claimed in any one of claims 36-56, wherein the kit does not contain ammonia or silver diamine fluoride.

58. The kit as claimed in any one of claims 36-57, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the silver fluorideis present in an amount of 2 wt.% to 75 wt.%, or 5 wt.% to 50 wt.%, or 25 wt.% to 45 wt.%, based on the total weight of the thickened silver fluoride composition.

59. The kit as claimed in any one of claims 36-58, further comprising a coloring agent.

60. The kit as claimed in any one of claims 36-58, further comprising a coloring agent, wherein the coloring agent is triarylmethane dye.

61. The kit as claimed in any one of claims 36-60, further comprising a flavoring agent.

62. The kit as claimed in any one of claims 36-61, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the thickened silver fluoride composition is a thixotropic fluid that can undergo an isothermal gel-sol-gel transformation.

63. The kit as claimed in any one of claims 36-62, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the thickened silver fluoride composition has a pH of from 4.0 to 7.5, or 4.5 to 7.0, or 5.5 to 7.5, or 5.5 to 7.0, or 5.5 to 6.5, or 5.5 to 6.0.

64. The kit as claimed in any one of claims 36-63, wherein only one of the two containers contains the thickening agent, and the container containing the thickening agent contains a composition having a viscosity of from 0.1 Pa-s to 500 Pa-s, at a shear rate of from 0.1 / second to 100 / second; or from 0.5 Pa-s to 450 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or from 5 Pa-s to 40 Pa-s, and a shear rate of from 0.1 / second to 100 / second; or the viscosity is greater than 75 Pa-s, at a shear rate of 0.1 / sec, and less than 15 Pa-s, at a shear rate of 100 / sec, as measured by a TA AR-G2 rheometer with a 40 mm cone and plate, and carried out at a temperature of about 23°C.

65. The kit as claimed in any one of claims 36-64, wherein when contents of both containers are combined to form the thickened silver fluoride composition, the silver fluoride is present in an amount to provide 1,000 ppm to 75,000 ppm of fluoride to the thickened silver fluoride composition, or 2,000 ppm to 60,000 ppm of fluoride to the thickened silver fluoride composition, or 5,000 ppm to 50,000 ppm of fluoride to the thickened silver fluoride composition , or greater than 10,500 ppm to 50,000 ppm fluoride to the thickened silver fluoride composition, based on the total weight of the composition; or the silver fluoride ispresent in an amount to provide 100 ppm to 14,000 ppm of silver to the thickened silver fluoride composition, or 200 ppm to 12,000 ppm of silver to the thickened silver fluoride composition, or 600 ppm to 10,000 ppm of silver to the thickened silver fluoride composition, or 1,800 ppm to 9,000 ppm of silver to the thickened silver fluoride composition, based on the total weight of the composition.

66. The kit as claimed in any one of claims 36-65, wherein the container comprising the silver fluoride also comprises nitric acid in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 9 months at approximately 25° C, based on the total weight of the composition in the container comprising the silver fluoride.

67. The kit as claimed in any one of claims 36-66, wherein the container comprising the silver fluoride also comprises nitric acid in a sufficient quantity to substantially stabilize the silver fluoride such that the silver ion levels do not decrease by more than 5 wt.% over a period of at least 18 months at approximately 25° C, based on the total weight of the composition in the container comprising the silver fluoride.

68. The kit as claimed in any one of claims 36-67, wherein the container comprising the silver fluoride also comprises nitric acid and wherein when contents of both containers are combined to form the thickened silver fluoride composition, the nitric acid is present in an amount of approximately 0.5% - 10% weight per unit volume (w / v%), or 1 - 8 w / v%, or 3 - 5 w / v%, based on the total volume of the thickened silver fluoride composition.

69. A method of testing the status of a carious lesion, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition according to any one of claims 1-34 to a location of a carious lesion in at least one tooth.

70. A method of testing the status of a carious lesion, comprising accessing the kit according to any one of claims 36-68, topically applying a therapeutically effective amount of the contents of the container comprising the silver fluoride to a location of a carious lesion in at least one tooth, then applying the contents of the container comprising the reducing agent solution to the same location, and examine the color of the location to determine the status of the carious lesion.

71. The method of claim 70, wherein the reducing agent solution comprises a thickening agent.

72. A method of densensitizing teeth, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition of any one of claims 1-34 to a surface of at least one tooth that is sensitive to at least one of heat, cold, sweet, acid and tactile pressure to thereby reduce sensitivity.

73. A method of densensitizing teeth, comprising accessing the kit according to any one of claims 36-68, topically applying a therapeutically effective amount of the container comprising the silver fluoride to a location on at least one tooth that is sensitive to at least one of heat, cold, sweet, acid and tactile pressure, then applying the contents of the container comprising the reducing agent solution to the same location, to thereby reduce sensitivity.

74. The method of claim 73, wherein the reducing agent solution comprises a thickening agent.

75. A method of treating teeth, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition of any one of claims 1-34 to a decayed portion of at least one tooth.

76. A method of treating teeth, comprising accessing the kit according to any one of claims 36-68, topically applying a therapeutically effective amount of the contents of the container comprising the silver fluoride to a location of a decayed portion of at least one tooth, then applying the contents of the container comprising the reducing agent solution to the same location.

77. The method of claim 76, wherein the reducing agent solution comprises a thickening agent.

78. A method of preventing caries in high-risk teeth, comprising topically applying a therapeutically effective amount of the thickened silver fluoride composition of any one of claims 1-34 to a surface of the tooth that is at a high risk of forming a carious lesion.

79. A method of preventing caries in high-risk teeth, comprising accessing the kit according to any one of claims 36-68, topically applying a therapeutically effective amount of the contents of the container comprising the silver fluoride to at least one tooth having a high risk of forming a carious lesion, then applying the contents of the container comprising the reducing agent solution to the same location.

80. The method of claim 79, wherein the reducing agent solution comprises the thickening agent.

81. A method of forming a kit, comprising forming a composition comprising silver fluoride by dissolving a powdered silver fluoride in water; adding nitric acid; and then adding a thickening agent in an amount of 0.2 wt.% to 30 wt.%, based on a total weight of the composition.

82. The method of forming the kit as claimed in claim 81, further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising at least one of water, glycerol and sorbitol; or further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising water, glycerol and sorbitol; or further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 55:45 to 95:5; or further comprising forming a reducing agent solution by combining a reducing agent with a solvent comprising water, glycerol and sorbitol and the glycerol: sorbitol volume ratio is 70:30 to 95:5.

83. The method of forming the kit as claimed in any one of claims 36-68, wherein the thickening agent is present in an amount of from 0.5 wt.% to 12 wt.%, or 0.8 wt.% to 10 wt.%, based on the total weight of the thickened silver fluoride composition.

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