Zinc-based materials for caries treatment

Abstract

Compositions and methods are provided for treating dental caries in individuals and animals. The compositions may be zinc compositions of [Zn(NH3)4]F2. Also provided are methods for producing inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) on the surface of carious lesions. The deposition of inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) reduces the amount of Zn 2+ This can occur by diluting a ZnO / NH3 solution (e.g., an aqueous or alcohol-based solution) into water (e.g., deionized water). The formation of inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) can occur instantaneously upon dilution.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Applications Nos. 63 / 335,634, 63 / 479,982, and 63 / 483,493, filed on April 27, 2022, January 13, 2023, and February 6, 2023, respectively, the disclosures of which are incorporated herein by reference. Background of the Disclosure

[0002] Conventionally, the treatment of dental caries involves the use of acids produced by cariogenic bacteria in the oral cavity (mainly acid-producing and acid-resistant) to convert the biomineral hydroxyapatite (also called HAp; Ca 10 Traditionally, treatment has been achieved by surgical removal of infected tissue that has been invaded by fluoride (PO4)6(OH)2). The resulting preparation is then restored with a variety of materials. For early caries lesions, the surgical approach has been replaced by minimally invasive dentistry (MID) protocols that halt the progression of the lesion and promote remineralization to restore damaged but structurally intact dentin.

[0003] Silver diamine fluoride (SDF) has been used in MID to treat early caries. However, a significant drawback of the SDF modality is the production of deep dark stains, which are problematic in terms of esthetics and patient acceptance. It is generally accepted that SDF reacts with exposed dentin to form silver phosphate, Ag3(PO4), a semiconductor that undergoes autoreduction under visible light irradiation. As a result, neutral silver atoms are formed and aggregate into silver nanoparticles. These nanoparticles appear black because they are originally violet absorbing (yellow colloidal phase) but subsequently form aggregates that absorb broadly throughout the visible spectrum. The time course of formation of black deposits varies but occurs whenever SDF is used at the clinically recommended concentration of 38% (w / w) in water. The objectives of MID would be well served by a topical agent that is generally accepted by the parents of pediatric patients, who are probably the primary beneficiaries of SDF treatment. Unfortunately, the formation of stains (especially on anterior teeth) makes parents reluctant to accept the treatment.

[0004] To solve the staining problem, many chemical agents have been tested, including ammonium hexafluorosilicate, zinc fluoride, and potassium iodide. The application of SDF followed immediately by saturated aqueous KI solution is the clinically recommended method. However, SDF / KI precipitates have been reported to significantly reduce the bond strength of glass ionomer and composite restorations. Furthermore, even after treatment with SDF / KI, teeth have been reported to discolor within 14 days. The SDF / KI treatment option is 15 times more expensive than the SDF unit dose treatment option. Most importantly, KI is contraindicated for use during pregnancy due to its association with congenital iodine goiter. Many cautions associated with SDF suggest the need for alternatives.

[0005] ZnO has been shown to be effective against Strep. mutans. Studies have shown that ZnO is converted to hopeite in saliva and Zn 2+It acts as a reservoir for inhibiting bacterial proliferation and the progression of caries.

[0006] Water-dispersible ZnO has been reported. By providing high concentrations of antimicrobial agents, it helps to form a chemical barrier against bacterial invasion and proliferation. However, it is difficult to retain ZnO aqueous dispersions in carious tissues because there is no obvious route for the ZnO dispersion to transform into a mechanically stable mineral phase.

[0007] There are several routes to obtain the desired mineral: Zn in the form of ZnO nanoparticles; 2+ The preparation of a 1.25 M ethanol-rich solution of ZnO has been reported. ZnO nanoparticle dispersions using triethanolamine as a capping agent have also been reported. Nanoparticles have also been shown to readily aggregate in electrolyte-containing solutions, which may be important for the deposition of ZnO in dentinal tubules. Once deposited, the poorly soluble nanoparticles transform from ZnO to hopite (Zn3(PO4)2), which then deposits ZnO in the biological HAp matrix of the tubules. 2+ The incorporation of zinc has been shown to help stabilize dentin and enamel against bacterial invasion.

[0008] In one aspect, the disclosure provides a method of treating dental caries comprising application of a composition that results in the deposition of Zn3(PO)4 and / or (NH4)ZnPO4, and / or application of a fluoride-containing zinc species (e.g., [Zn(NH3)4]F2), which results in the deposition of inorganic zinc compounds.

[0009] In one aspect, the present disclosure provides a method of depositing an inorganic zinc compound. In various embodiments, the inorganic zinc compound is ZnO, Zn(OH)2, or Zn(OH)F. The inorganic zinc compound (e.g., ZnO, Zn(OH)2, or Zn(OH)F) may be deposited on the surface of a carious lesion. The deposition of the inorganic zinc compound (e.g., ZnO, Zn(OH)2, or Zn(OH)F) can be Zn 2+This can occur by diluting a ZnO / NH3 solution (e.g., an aqueous or alcohol-based solution) into water (e.g., deionized water). The formation of inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) can occur instantaneously upon dilution. [Brief description of the drawings]

[0010] For a better understanding of the nature and objects of the present disclosure, reference should be made to the following detailed description taken in conjunction with the accompanying figures.

[0011] Figure 1 shows BSE SEM micrographs of milled HAp surface samples: (A) zinc nitrate alone, (B) zinc nitrate followed by dibasic ammonium phosphate, (C) ammonium phosphate followed by zinc nitrate, and (D) control.

[0012] Figure 2 shows SEM micrographs of milled HAp surface samples accompanied by EDS data showing calcium (red) and zinc (blue): (A) zinc nitrate alone, (B) zinc nitrate followed by diammonium phosphate, (C) ammonium phosphate followed by zinc nitrate, and (D) control.

[0013] Figure 3 shows BSE SEM micrographs of dentin cross sections from tooth #2 with and without EDS data showing calcium (blue) and zinc (yellow). (A and B) Wide field 204.8 μm. The green box indicates the area selected for the narrow field image. (C and D) Narrow field 62.5 μm.

[0014] Figure 4 shows BSE SEM micrographs of dentin cross sections from tooth #3 with and without EDS data showing calcium (blue) and zinc (yellow). (A and B) Wide field 204.8 μm. The green box indicates the area selected for the narrow field image. (C and D) Narrow field 62.5 μm.

[0015] FIG. 5 shows a sample substrate consisting of ground HAp epoxy-bonded to a silicon support protected by a layer of Scotch tape.

[0016] FIG. 6 shows: (A) zinc ammonium phosphate powder, Zn(NH4)PO4; (B) ground hydroxyapatite (HAp) powder, calcium hydroxyapatite on epoxy resin; (C) HAp powder treated with zinc nitrate followed by diammonium phosphate; (D) HAp powder on epoxy resin treated with diammonium phosphate followed by zinc nitrate; (E) hopite, Zn3(PO4)2, technical grade.

[0017] FIG. 7 shows: (A) mineral formation from diammonium phosphate solution added to a thin layer of zinc solution on HAp, scale bar 5.0 μm; (B) enlarged, scale bar 1.0 μm; (C) mineral formation from zinc nitrate solution added to a thin layer of diammonium phosphate solution on HAp, scale bar 5.0 μm; (D) enlarged, scale bar 1.0 μm.

[0018] Figure 8 shows zinc ammonium phosphate powder after 11 days of exposure to (top) artificial saliva, (middle) DI water, and (bottom) Hopite count pattern 34869-ICSD.

[0019] Figure 9 shows the diffraction pattern of the powdered hopite. Below is the standard hopite and the calculated 34869-ICSD. The dashed line is the hopite soaked in water for one week, and the solid line is the hopite soaked in artificial saliva for one week.

[0020] Figure 10 shows early work on an established method for zinc iodide, and many have adopted or improved this method for the preparation of solutions containing zinc and fluoride. Dissolution in aqueous ammonia is well known and convenient. Reaction of ZnI2 and ZnBr2 with gas phase ammonia has yielded crystals that have been characterized by X-ray crystallography. More recently, a series of zinc amines have been shown to be produced by reaction of ZnF2 in supercritical ammonia.

[0021] FIG. 11 shows the formation of various zinc species from [Zn(NH3)4]F2.

[0022] Figure 12 is the powder diffraction pattern of the product ZnO obtained by adding [Zn(NH3)4]F2(alc) to water, where alc = propylene glycol.

[0023] Figure 13 is a SEM micrograph of ZnO obtained by adding [Zn(NH3)4]F2(alc) to water, where alc = propylene glycol.

[0024] Figure 14 shows mineral compounds associated with S. mutans. The goal is to convert the initial mineral to a zinc mineral source with reduced solubility and improved stability.

[0025] FIG. 15 shows that after deposition in dentin, Hopite is essentially colorless and potentially antibacterial.

[0026] FIG. 16 shows a preparation for imaging synthetic hydroxyapatite (HAp), a model of a dentinal tubule surface, with a scanning electron microscope.

[0027] FIG. 17 shows (left) X-ray diffraction and (right) scanning electron micrographs of the precipitate obtained from application of a zinc solution followed by (NH4)2HPO4(aq).

[0028] FIG. 18 shows (left) X-ray diffraction and (right) scanning electron micrographs of the precipitate from zinc phosphate soaked in water.

[0029] FIG. 19 shows the F2H 18 4 shows an ellipse plot for N4O3Zn.

[0030] Although the claimed subject matter is described in terms of specific embodiments, other embodiments, including embodiments that do not provide all of the advantages and features described herein, are also within the scope of this disclosure. Various structural, logical, and process step changes can be made without departing from the scope of the disclosure.

[0031] Ranges of values ​​are disclosed herein. The ranges are defined by lower and upper limits. Unless otherwise stated, the ranges include all values ​​up to the magnitude of the minimum value (either the lower or upper limit) and ranges between the values ​​in the stated ranges.

[0032] The present disclosure provides a safe, non-coloring (non-staining), caries (tooth decay) prevention agent that is an alternative to SDF. The agent's embodiments include antibacterial activity, the potential to occlude dentinal tubules (which may alleviate dentin hypersensitivity), and promote tissue remineralization. Zinc-based minerals are suitable for this purpose. The proposed mechanisms of antibacterial action of zinc ions include: 1) binding to microbial membranes, causing rupture and leakage of bacterial membranes; 2) prolonging the bacterial growth cycle and slowing cell division; and 3) affinity for gram-positive bacteria, including Streptococcus mutans, a key bacterium in the caries formation process.

[0033] The potential antibacterial effects of zinc deposition have been detailed in several recent studies. One study demonstrated the use of zinc phosphate as a titanium implant coating that was shown to be biocompatible, antibacterial, and promotes hydroxyapatite (Hap) formation. Another recent study demonstrated that Zn 2+ The composite and ZnO nanoparticles were shown to be active against Streptococcus mutans. Furthermore, zinc-loaded HAp nanorods were shown to exhibit antibacterial properties against several organisms, including Streptococcus mutans.

[0034] One of these is the direct delivery of zinc phosphate to dentinal tubules. Zinc phosphate has a long history in dentistry and has been considered a safe and reliable bonding agent, but has recently been replaced by modern agents with significantly improved mechanical properties and bond strength. However, zinc phosphate minerals may be effective in treating dental caries. Researchers have demonstrated that zinc phosphate coatings can improve hemocompatibility, cytocompatibility, and antibacterial activity compared to pure biodegradable zinc, which is thought to release zinc ions too quickly.

[0035] The challenge is to place zinc phosphate in dentin as an antibacterial barrier. Below we describe the deposition of zinc phosphate minerals that effectively occlude dentin tubules by crystallization at the tubule openings and aggregation of crystals within the tubules.

[0036] In one aspect, the disclosure provides a method of treating dental caries (tooth decay) comprising application of a composition that results in the deposition of Zn3(PO)4 and / or (NH4)ZnPO4, and / or application of a fluoride-containing zinc species (e.g., [Zn(NH3)4]F2), which results in the deposition of inorganic zinc compounds.

[0037] Zn3(PO)4 and / or (NH4)ZnPO4 can be formed by mixing various zinc salts and phosphate salts. For example, caries can be treated by applying a composition containing a zinc salt, followed by applying a composition containing a phosphate salt. In various other embodiments, one or more caries can be treated by applying a composition containing a phosphate salt, followed by applying a composition containing a zinc salt.

[0038] A variety of zinc salts can be used, including, for example, Zn(NO3)2, ZnSO4, Zn(OAc)2, ZnF2, ZnCl2, ZnBr2, ZnI2, [Zn(NH3)4]F2, and the like, or various combinations thereof.

[0039] A variety of phosphates can be used, including, for example, (NH4)2HPO4, (NH4)H2PO4, K3PO4, K2HPO4, KH2PO4, (NH4)2PO3F, and the like, or various combinations thereof.

[0040] Without intending to be bound by any particular theory, it is believed that when a composition containing Zn(NO3)2 is applied followed by a composition containing (NH4)2HPO4, (NH4)2ZnPO4 is the predominant species formed. Without intending to be bound by any particular theory, it is believed that when a composition containing (NH4)2HPO4 is applied followed by a composition containing Zn(NO3)2, Zn3(PO4)2 or Zn3(PO4)2·4H2O (i.e., hopeite) is the predominant species formed. Without intending to be bound by any particular theory, it is believed that (NH4)ZnPO4 is converted to hopeite over time.

[0041] In various embodiments, the composition comprises [Zn(NH3)4]F2. The composition comprising [Zn(NH3)4]F2 may further comprise a liquid medium. The liquid medium may be an alcohol (e.g., glycol, etc.) and / or water. For example, when the alcohol is glycol, the glycol may be propylene glycol. In various embodiments, when the glycol is propylene glycol, the liquid medium may further comprise water. For example, the alcohol may be ethanol or methanol. In various embodiments, when the alcohol is ethanol, the liquid medium may further comprise water. In various embodiments, when the alcohol is methanol, the liquid medium may further comprise water. The medium may further comprise ammonia. When the medium is methanol, the ammonia concentration may be 7N. When the medium is ethanol, the ammonia concentration may be 2N. When the medium is water, the ammonia concentration may be 30% (by weight) ammonia. When the medium is propylene glycol, the propylene glycol may be saturated with ammonia (at STP).

[0042] The composition may be applied to one or more carious tooth surfaces, and [Zn(NH3)4]F2 is formed prior to application to the tooth surface or directly to the caries. Without intending to be bound by any particular theory, it is believed that after application of [Zn(NH3)4]F2, inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) are formed over time, allowing for the sustained release of fluoride ions.

[0043] The resulting Zn-based materials (e.g., (NH4)ZnPO4, Zn3(PO4)2, Zn3(PO4)2·4H2O, [Zn(NH3)4]F2) are insoluble and have desirable crystalline and antimicrobial properties, as described in the examples presented herein.

[0044] In one aspect, the present disclosure provides a method of depositing an inorganic zinc compound. In various embodiments, the inorganic zinc compound is ZnO, Zn(OH)2, or Zn(OH)F. The inorganic zinc compound (e.g., ZnO, Zn(OH)2, or Zn(OH)F) can be deposited on the surface of a carious lesion. The deposition of the inorganic zinc compound (e.g., ZnO, Zn(OH)2, or Zn(OH)F) can be Zn 2+ This can occur by diluting a ZnO / NH3 solution (e.g., an aqueous or alcohol-based solution) into water (e.g., deionized water). The formation of inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) can occur instantaneously upon dilution.

[0045] In various embodiments, the method comprises the step of: 2+ This involves the precipitation of inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F) from solutions of their salts. Zn 2+ Non-limiting examples of salts include ZnF2, Zn(NO3)2, ZnSO4, ZnCl2, ZnBr2, ZnI2, and combinations thereof. 2+The concentration of NH3:Zn in solution can be 1 to 5M, including increments of 0.1 and ranges therebetween (e.g., 3.0M). The concentration of ammonia (NH3) can be 10 to 30% by weight (based on the combined weight of water and ammonia), including all ranges and values ​​therebetween (e.g., 10%, 20%, or 30% by weight). 2+ The molar ratio of NH3:Zn can be 1:1 to 10:1 (e.g., 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1). 2+ The molar ratio is 5.5:1.

[0046] The formation of inorganic zinc compounds is 2+ This may vary depending on the choice of solution containing NH3. For example, Zn 2+ If / NH3 is in water or propylene glycol prior to dilution, ZnO is formed upon dilution. 2+ When Zn(OH) is in ethanol and water prior to dilution, Zn(OH) is formed upon dilution. 2+ If / NH3 is in a water film before dilution, Zn(OH)F is formed upon dilution.

[0047] The formation of inorganic zinc compounds is 2+ This occurs after dilution of Zn(aq) in water (e.g., deionized water). For example, the dilution is about 20-fold (i.e., 50 μL added to 1 mL of water (e.g., deionized water) or more). The dilution in water may be performed directly on the tooth surface. For example, concentrated Zn 2+ / NH3(aq) and dilute Zn 2+ / Make the concentration of NH3(aq) at least 20 times with water.

[0048] In various embodiments, the method includes the step of: 2+Inorganic zinc compounds precipitate from a solution of salts (e.g., ZnO, Zn(OH)2, or Zn(OH)F). Non-limiting examples of alcohols include methanol, ethanol, N-propanol, isopropanol, butanol, sec-butanol, tert-butanol, propylene glycol, ethylene glycol, and combinations thereof. Zn 2+ Examples of Zn include, but are not limited to, ZnF2, Zn(NO3)2, ZnSO4, ZnCl2, ZnBr2, ZnI2, and combinations thereof. 2+ The concentration of NH3:Zn in solution may be 1 to 5M, including all 0.1 increments and ranges therebetween (e.g., 3.0M). The concentration of ammonia may be 1 to 7N, including all increments and ranges therebetween (e.g., 1, 2, 3, 4, 5, 6, or 7N). 2+ The molar ratio of NH3:Zn may be from 1:1 to 10:1, including all values ​​and ranges therebetween (e.g., 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1). In various examples, NH3:Zn 2+ The molar ratio is 5.5:1.

[0049] Zinc 2+ Dilution of / NH3 (alcohol) in water (e.g., deionized water) results in the formation of inorganic zinc compounds (e.g., ZnO, Zn(OH)2, or Zn(OH)F). For example, the dilution is about 20-fold (i.e., adding 50 μL to 1 mL of water (e.g., deionized water)).

[0050] In the formation of ZnO, Zn(OH)2 or Zn(OH)F in carious lesions, Zn 2+ / NH3(aq) or Zn 2+ / NH3(alc) may be deposited as an antibacterial agent on the carious lesion and / or as a tubule occluding agent on the carious lesion.

[0051] The compositions of the present disclosure may be applied to an individual's tooth surfaces by a variety of means: In various embodiments, the composition is applied with a brush onto / into one or more cavities.

[0052] Any method of the present disclosure can be performed on an individual in need of treatment, where the individual has one or more caries. The individual in need of treatment can be a human or a non-human mammal. Non-limiting examples of non-human mammals include cows, pigs, rats, cats, dogs, other farm animals, pets, service animals, etc.

[0053] The method steps described in the various embodiments and examples disclosed herein are sufficient to practice the method of the present invention. Thus, in one embodiment, the method consists essentially of a combination of the method steps disclosed herein, and in another embodiment, the method consists of such steps.

[0054] The following description provides various embodiments of the present disclosure. Description 1 1. A method for treating one or more dental caries, comprising: i) applying a composition comprising a zinc salt to one or more caries and applying a composition comprising a phosphate to said one or more caries, wherein Zn3(PO)4 (and / or its hydrates) and / or (NH4)ZnPO4 are formed; or ii) applying a composition comprising zinc and fluoride to one or more caries (e.g., where an inorganic zinc compound is formed); The method includes: Statement 2 2. The method of claim 1, wherein applying is by applying the composition to the caries-bearing tooth surface with a brush. Statement 3 The method of claim 1 or 2, wherein the zinc salt is Zn(NO3)2, ZnSO4, Zn(OAc)2, ZnF2, ZnCl2, ZnBr2, ZnI2, Zn(NH3)4]F2, or the like, or various combinations thereof. Statement 4 The method of any one of the preceding claims, wherein the phosphate is (NH4)2HPO4, (NH4)H2PO4, K3PO4, K2HPO4, KH2PO4, (NH4)2PO3F, or the like, or various combinations thereof. Statement 5 The method of any one of the preceding statements, wherein the composition comprising a zinc salt is applied before the composition comprising a phosphate salt. Statement 6 The method of any one of the preceding statements, wherein the composition comprising a phosphate salt is applied before the composition comprising a zinc salt. Statement 7 13. The method of any one of the preceding claims, wherein the concentration of the zinc salt is 30-50 wt% (e.g., 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 wt%). Statement 8 8. The method of claim 7, wherein the concentration of the zinc salt is 35-45 wt % based on the total weight of the composition. Statement 9 9. The method of claim 8, wherein the concentration of the zinc salt is 38-43 wt %, based on the total weight of the composition. Statement 10 30. The method of any one of the preceding claims, wherein the concentration of the phosphate is 10 to 40 wt% (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 wt%) based on the total weight of the composition. Description 11 11. The method of claim 10, wherein the concentration of the phosphate is 15-35 wt % based on the total weight of the composition. Description 12 12. The method of claim 11, wherein the concentration of the phosphate is 20-30 wt % based on the total weight of the composition. Statement 13 The method of any one of the preceding statements, wherein Zn3(PO)4 (and / or its hydrates) and / or (NH4)ZnPO4 are formed. Statement 14 The method of any one of the preceding statements, wherein the composition comprising zinc and fluoride comprises [Zn(NH3)4]F2. Description 15 15. The method of claim 14, wherein the composition further comprises a liquid medium. Statement 16 16. The method of claim 15, wherein the liquid medium comprises an alcohol, a glycol, and / or water. Statement 17 17. The method of statement 16, wherein the glycol is propylene glycol. Description 18 20. The method of claim 17, wherein the composition further comprises water. Description 19 17. The method of statement 16, wherein the alcohol is methanol or ethanol. Description 20 20. The method of claim 19, wherein the alcohol is methanol. Description 21 21. The method of statement 20, wherein the composition further comprises water. Description 22 20. The method of claim 19, wherein the alcohol is ethanol. Statement 23 23. The method of statement 22, wherein the composition further comprises water. Description 24 A composition comprising [Zn(NH3)4]F2. Description 25 25. The composition of statement 24, wherein the composition further comprises a liquid medium. Statement 26 26. The composition of statement 25, wherein the liquid medium comprises an alcohol, a glycol, and / or water. Description 27 27. The composition of statement 26, wherein the glycol is propylene glycol. Description 28 28. The composition of statement 27, wherein the composition further comprises water. Description 29 27. The composition of statement 26, wherein the alcohol is methanol or ethanol. Description 30 30. The composition of statement 29, wherein the alcohol is methanol. Description 31 31. The composition of statement 30, wherein the composition further comprises water. Description 32 30. The composition of statement 29, wherein the alcohol is ethanol. Description 33 33. The composition of statement 32, wherein the composition further comprises water. Description 34 A method for preparing an inorganic zinc compound, comprising the steps of: 2+ ZnO, Zn(OH)2, and / or Zn(OH)F are formed by diluting a solution containing ZnO, Zn(OH)2, and / or Zn(OH)F. Description 35 Zinc 2+ 35. The method of claim 34, wherein the solution containing / NH3 is an aqueous ammonia solution. Description 36 Zinc 2+ 36. The method of claim 34 or 35, wherein is derived from ZnF2, Zn(NO3)2, ZnSO4, ZnCl2, ZnBr2, ZnI2, or a combination thereof. Description 37 Zinc 2+ 37. The method of any one of statements 34 to 36, wherein the concentration of is 1 to 5 M (e.g., 3 M). Description 38 38. The method of any one of statements 34 to 37, wherein the concentration of ammonia is 10 to 30% by weight based on the total weight of water and ammonia. Description 39 NH3:Zn in solution 2+ 39. The method of any one of statements 34 to 38, wherein the molar ratio of is 1:1 to 10:1. Description 40 Zinc 2+ 35. The method of claim 34, wherein the solution containing / NH3 is an alcohol-based ammonia solution. Description 41 41. The method of statement 40, wherein the alcohol of the alcohol-based ammonia solution is selected from methanol, ethanol, n-propanol, isopropanol, butanol, sec-butanol, tert-butanol, propylene glycol, ethylene glycol, and combinations thereof. Description 42 Zinc 2+ 42. The method of claim 40 or 41, wherein is derived from ZnF2, Zn(NO3)2, ZnSO4, ZnCl2, ZnBr2, ZnI2, or combinations thereof. Description 43 Zinc 2+ The method according to any one of items 34 and 40 to 42, wherein the concentration of is 1 to 5 M (e.g., 3 M). Description 44 44. The method of any one of statements 40 to 43, wherein the concentration of ammonia is 1 to 7N. Description 45 NH3:Zn in solution 2+ 45. The method of any one of statements 40 to 44, wherein the molar ratio of is 1:1 to 10:1. Description 46 Zinc 2+ 46. ​​The method of any one of statements 40 to 45, wherein the solution containing / NH3 is applied to the surface of the tooth or dental caries before dilution. Description 47 Zinc 2+47. The method according to any one of conditions 40-46, wherein the solution containing / NH3 is diluted at least 20-fold with water on the surface of the tooth or dental caries. Description 48 48. The method of any one of statements 40-47, wherein the method is carried out in the oral cavity of an individual.

[0055] The following examples are presented to illustrate the present disclosure and are not intended to be limiting in any respect. Example 1

[0056] This example provides a description of how to make and use the zinc-based materials of the present disclosure.

[0057] Dentin blocks prepared from human permanent molars were locally treated by sequential application of aqueous zinc nitrate and ammonium phosphate solutions. Field emission-scanning electron microscopy (FE-SEM) images and energy dispersive X-ray scattering (EDS) revealed widespread deposition of crystalline and colorless zinc minerals both within the dentinal tubules and on the dentin surface. Parallel experiments with XRD analysis of crushed hydroxyapatite (HAp) surfaces showed that, depending on the reaction conditions, the first mineral to be deposited was ammonium zinc phosphate (NH4)ZnPO 4、 or zinc phosphate Zn3(PO4)2. The results provide an avenue for optimizing the deposition of ionic zinc directly into the dentinal tubules of caries lesions, which could act as an antimicrobial agent to halt caries, potentially remineralize the lesions, and relieve tooth sensitivity.

[0058] Two experimental designs were used here: first, the solutions were applied to non-carious dentin and both the surface and tubule cross-sections were evaluated using SEM and EDS analysis, and second, the solutions were applied to a milled HAp coating layer on a silicon substrate and data were collected using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray powder diffraction (XRD).

[0059] Ground HAp was a gift. Zinc nitrate, Zn(NO3)2·6H2O, was purchased from Strem chemicals. Zinc phosphate, Zn3(PO4)2·xH2O, was purchased from Alfa Aesar (Lot:M09E004, x=3.64). Monobasic ammonium phosphate, (NH4)H2PO4, was purchased from Honeywell / Fluka (Lot:J0930), and dibasic ammonium phosphate, (NH4)2HPO4, was purchased from Fischer Chemicals (Lot:972377). Ammonium hydroxide, ACS (28.0–30.0% NH3), was purchased from Alfa Aesar (Lot:P05F004). Phosphate-buffered saline (PBS) was purchased from Fisher Scientific, Waltham, MA, USA. All chemicals were used as received.

[0060] Stock solutions of 42% (w / w) zinc nitrate hexahydrate and 24% (w / w) diammonium phosphate were prepared in deionized (DI) water, 5 ml of each solution, for use in the experiments described below. Note that if the solutions were combined directly in equal masses, the molar ratio of reactants would be 1:1. The epoxy resin used to bond the HAp powder to the substrate was Devcon 5 Minute (登録商標)Epoxy, Clear. Artificial saliva (1700-0305) was purchased from Pickering Laboratories and used as received. Artificial Saliva 1700-0305: (Pickering Laboratories); Sodium Carboxymethylcellulose 10.00 g / L; Potassium Phosphate Monobasic 0.326 g / L; Potassium Chloride 0.625 g / L; Potassium Phosphate Dibasic 0.804 g / L; Magnesium Chloride Hexahydrate 0.059 g / L; Calcium Chloride Dehydrate 0.166 g / L; Methyl-p-hydroxybenzoate 2.00 g / L.

[0061] Synthesis of zinc ammonium phosphate Ammonium zinc phosphate (NH4)ZnPO4 was synthesized using a modification of the method of Baitahe. Briefly, 5.97 g of Zn(NO3)2·6H2O was weighed into a 40 ml beaker. To this was added 21 ml of 1M (NH4)H2PO4 with stirring, followed by 20 ml of 2M NH3 (aq, 28.0-30.0%). The resulting slurry was stirred vigorously for 15 min. The product was collected by filtration, washed with DI water, transferred to a watch glass and dried. As a modification, an aging step was added, where the product was resuspended in DI water, stirred overnight, collected by filtration, washed with acetone, then ethyl ether, and dried. The resulting powder was reasonably free-flowing. XRD analysis showed that the product scan was consistent with previously reported ammonium zinc phosphate 85444-ICSD.

[0062] Dentin samples: preparation and application of experimental solutions Ethical approval was obtained to use extracted human teeth according to the guidelines of the New York University College of Dentistry. Four human third molars were extracted and stored in 0.1% thymol solution at 4°C to prevent microbial growth after extraction. The teeth were then removed from the thymol solution and immersed in DI water for 30 minutes, followed by rinsing with DI water. The teeth were then immersed in 1X PBS, which was a solution of 10X PBS diluted with DI water. The teeth were left in the 1X PBS solution for 7 days prior to the experiment.

[0063] All teeth were cut tangentially with a Buehler Isomet diamond blade (Lake Bluff, IL, USA) approximately 1 mm deep on the occlusal surface to the tip of the shortest cusp to create a flat occlusal surface. The cusp tip was discarded. An incision was then made approximately 2 mm apically to the deepest part of the central occlusal groove to remove the occlusal enamel and expose the underlying dentin. This cut resulted in two planes on each experimentally treated tooth: 1) the intaglio surface of the 2 mm flat dentin disc, and 2) the flat occlusal surface of the bulk remainder of the tooth. The location and orientation of the cut were chosen to obtain a cross section perpendicular to the dentinal tubule direction. The smear layer was removed from all treated surfaces by applying 35% phosphoric acid (Fisher Scientific, Waltham, MA, USA) for 15 s, followed by rinsing with DI water for 15 s. Excess water was removed with a gentle stream of compressed air (5 s).

[0064] The experimental solutions were applied to three dentin discs and three corresponding occlusal surfaces of the bulk remainder of each tooth. The fourth tooth sample served as a control. Disc / Bulk 1: 42% zinc nitrate was applied to both surfaces with scrubbing for 15 seconds with a microbrush. After 2 minutes, the samples were immersed in 1X PBS. Disc / Bulk 2: 42% zinc nitrate was applied to both surfaces with scrubbing for 15 seconds. After 2 minutes, a gentle compressed air stream was applied for 5 seconds to remove visible liquid on the surfaces. Then, 24% diammonium phosphate solution was applied to both surfaces with scrubbing for 15 seconds. After 2 minutes, the samples were immersed in 1X PBS solution. Disc / Bulk 3: The same method as Disc 2 was used, except that the diammonium phosphate solution was applied first, followed by the zinc nitrate. Disc / Bulk 4: No experimental solution was applied. After removing the smear layer, the discs were immediately immersed in PBS solution.

[0065] Dentin sample: preparation for SEM and EDS analysis After 24 hours, the four flat disk samples were removed from the PBS solution and air-dried for 3 days. The flat disks were glued to aluminum stubs with carbon paint and then carbon-coated using a Desk V carbon evaporator (Denton Vacuum, LLC, Moorestown, NJ, USA). Four bulk dentin samples from each tooth were embedded in polymethylmethacrylate and then cut in a mesial-distal direction along the long axis of the tooth through the center of each tooth. This produced dentin cross-sectional samples with the tubule long axis lying in the surface plane for SEM analysis. The samples were glued to aluminum stubs with carbon paint and then carbon-coated for SEM analysis using a Desk V carbon evaporator (Denton Vacuum, LLC, Moorestown, NJ, USA). The intaglio surface of the disks was used to examine the surface of the treated dentin. The mesial-distal cut teeth of the teeth were used to examine the penetration of materials into the dentinal tubules after treatment.

[0066] Milled HAp samples: mineral formation The ground HAp-coated substrates were treated with a few drops of zinc nitrate stock solution delivered from a Pasteur pipette. The solution was gently spread to form a film on the HAp surface. After 5 min, excess solution was wiped off with a Kimwipe. A few drops of diammonium phosphate stock solution were then added to the sample and left for 3 min, after which the excess solution was wiped off and the sample was washed with DI water and dried overnight. The dried samples were characterized by SEM or XRD.

[0067] Preparation of zinc phosphate on planar substrates: preparation for SEM, EDS and XRD analysis For SEM measurements, aluminum-backed carbon tabs (Ted Pella, 16091-12) were applied to an aluminum pin stub (Ted Pella, 16111-9) platform. Powdered HAp or zinc phosphate was applied to the exposed, adhesive carbon tab surface. The solution of choice for mineral precipitation was applied to the HAp layer with a Pasteur pipette. After drying the samples in air, they were sputter-coated with gold for SEM and EDS analysis.

[0068] For XRD measurements, flat samples were prepared as surrogates for native or treated dentin surfaces. To mimic the natural surface, HAp powder was fixed with epoxy resin onto a silicon wafer (001 cut, 1 cm × 1 cm) protected with cellophane tape. To prepare the HAp substrate, liquid 5-min epoxy resin (Devcon, transparent) was placed on the tape and ground HAp was tamped onto the epoxy resin in sufficient excess to ensure that the exposed substrate surface was HAp-rich. After drying, the assembly was lightly tamped with a spatula to remove unbound HAp and then washed with DI water to further remove loosely bound HAp. The wafer was glued onto a pin stub mount. The mount with the sample was carefully fixed into the sample holder of the instrument. Samples of zinc phosphate on HAp were immersed in DI water for 1 week, after which the samples were washed with DI water, acetone, and dried. A second set of samples of zinc phosphate on HAp was immersed in artificial saliva for 1 week, after which these samples were washed with DI water, acetone, and dried prior to SEM and XRD analysis.

[0069] Bulk mineral samples: Effects of solutions on minerals One milligram of each zinc ammonium phosphate powder (2 pcs) was suspended in approximately 1 ml DI water and 1 ml artificial saliva, respectively, and placed in a test tube sealed with a rubber stopper for 11 days. After the soaking period, the powder was resuspended by ultrasound, transferred to an Eppendorf centrifuge tube, and centrifuged at 8000 rpm for 6 min. The supernatant was discarded. To each sample, 1 ml (aliquot) of DI water was added, vortex mixed, and the centrifugation step was repeated. The supernatant was removed and the resuspension / centrifugation step was repeated. Finally, the samples were resuspended in methanol (1 ml) and then in ethyl ether (twice), with centrifugation at each step. The samples were then dried in air before being loaded into a 0.5 mm Kapton capillary and mounted on a magnetic base for powder XRD analysis.

[0070] Two samples of zinc phosphate powder (55 mg in 1 ml DI water and 60 mg in 1 ml artificial saliva) were placed in test tubes sealed with parafilm and left for one week. The samples were worked up using standard methods, dried and stored in vials. The powder samples were attached to epoxy resin on Si substrates as for HAp above.

[0071] Dentin sample SEM images and EDS analysis of dentin samples were acquired using a Hitachi S-3500N SEM (Hitachi, Tokyo, Japan) in backscattered electron (BSE) mode and a Bruker XFlash 6110 energy dispersive X-ray spectrometer (Bruker, Billerica, MA, USA), respectively. ESPRIT version 2.1 was used to acquire BSE and EDS images. All images were taken at high vacuum, 20 kV, and 15 mm working distance. For EDS images, the following settings were used in the ESPRIT software: map display filter: Smooth=7, map color mixing: Enhanced.

[0072] Powdered HAp sample SEM images and EDS analysis of HAp were obtained using a Carl-Zeiss Gemini 300 field emission scanning electron microscopy (FE-SEM) and a Bruker XFlash 6160, respectively.

[0073] Powder samples were deposited on zero-background Si substrates on a PanAnalytical X'Pert XRD instrument. All scans were performed using a curved crystal monochromator with the following settings: 45 kV, 40 mA, step size 0.013° (2θ), 99.45 seconds per step, range 10-45° (PanAnalytical, Malvern Panalytical, Almelo, The Netherlands).

[0074] XRD capillary data were collected using a Bruker D8 DISCOVER GADDS microdiffractomer equipped with a VANTEC-2000 area detector in the φ-rotation technique. X-rays generated from a sealed copper tube were monochromated by a graphite crystal and collimated with a 0.5 mm MONOCAP (λ, Cu-Kα=1.54178 Å). The sample-detector distance was 150 mm, and the exposure time was 300–1500 s / run. The sample position was adjusted by a video camera and an alignment laser, as well as by a manual control box. Data were integrated by the XRD2EVAL program in the Bruker PILOT software. Raw files were converted to UXD format by DIFFRACplus File Exchange and later analyzed by the WINPLOTR program.

[0075] Dentin disc surface samples: SEM / EDS characterization after treatment The intaglio surfaces of the disc samples were imaged in BSE mode and elemental distribution was assessed using EDS. Images were acquired at 20 kV, 15 mm working distance, and field widths of 122.88 μm and 35.84 μm. Spectra and elemental quantification were obtained for all samples. SEM BSE images are shown in Figure 1 and corresponding EDS images in Figure 2. Calcium is labelled in red and zinc in blue. Phosphorus (not shown) was detected uniformly across the field width for all samples, indicating phosphorus' presence in both the crystals and dentin.

[0076] Disk 1: 42% zinc nitrate Multiple crystal morphologies were observed (Figures 1A and 2A), with the largest crystals appearing as oval, flat, or hexagonal, up to approximately 6 μm long and 2 μm wide. Other crystals appear as minute spicules approximately 1 μm long. EDS visually confirmed the presence of zinc in both crystal species.

[0077] Disk 2: 42% zinc nitrate, followed by 24% diammonium phosphate The predominant species appears as clusters of fine spicules approximately 1 μm in length (Figures 1B and 2B). Analysis and quantification of the spectra showed that this surface had the highest relative abundance of zinc in atomic percentage.

[0078] Disk 3: 24% diammonium phosphate, followed by 42% zinc nitrate The crystal morphology was heterogeneous (Figs. 1C and 2C), appearing as fine spicules 1–2 μm in length and small flat rectangular seeds (generally ≤1 μm in their longest dimension).

[0079] Disc 4: Control Neither precipitate nor zinc was observed on the control surfaces (Figs. 1D and 2D).

[0080] Bulk dentin samples sectioned to visualize longitudinal deposition of zinc mineral: Post-processing SEM / EDS characterization The surfaces of the mesial-distal cross-section samples were imaged in BSE mode and characterized by EDS. Images were acquired at 20 kV, 15 mm working distance, and field widths of 204.8 μm and 62.46 μm for each sample. Spectra and elemental quantification were obtained for all samples. Calcium and zinc are labeled in blue and yellow, respectively. Phosphorus (not shown) was detected uniformly across the field width for all samples, indicating phosphorus presence in both crystals and dentin.

[0081] Significant amounts of intracanalicular precipitates were detected in teeth 2 and 3. Images of tooth 1 (42% zinc nitrate only) and tooth 4 (control) are not shown. Only a few crystals were detected in disk 1, with the furthest penetration being approximately 40 μm from the dentin surface. No precipitates or zinc were detected in the control.

[0082] Tooth 2: 42% zinc nitrate, followed by 24% diammonium phosphate Zinc- and phosphorus-containing crystals were found in almost all tubules down to a depth of approximately 120 μm (Figure 3). The crystal morphology seen in the narrow-field images appears to be fairly uniform throughout the sample. Most crystals are 2-3 μm in length, close to the width of the dentinal tubules in which they are embedded.

[0083] Tooth 3: 24% diammonium phosphate, followed by 42% zinc nitrate Zinc- and phosphorus-containing crystals were detected up to 50 μm from the capillary opening (Figure 4). The majority of the crystals were concentrated at the capillary mouth. The crystal species blocking the capillary opening appear to have a different morphology than the crystals inside.

[0084] HAp sample: Deposition of zinc phosphate on HAp (zinc phosphate / HAp) XRD and SEM The silicon plate was protected with adhesive tape. A thin layer of epoxy was deposited on the surface of the tape. The ground HAp was then lightly pressed onto the epoxy resin surface, and the epoxy resin was allowed to solidify for approximately 30 min (Figure 5).

[0085] Excess HAp was removed by tapping the inverted Si substrate. The presence of excess unbonded mineral after epoxy curing ensured that the reactive mineral surface was not covered by adhesive.

[0086] When a solution containing zinc is combined with a solution containing phosphate, zinc phosphate minerals are precipitated. Mineral deposition on HAp was achieved by sequential addition of 42% zinc nitrate followed by 24% diammonium phosphate (or vice versa). After addition of the zinc nitrate solution, excess liquid was wiped off with a Kimwipe, leaving a thin film of solution on the HAp. Naturally, the ammonium phosphate solution was in excess of the zinc nitrate in the liquid film. After 10 min, the liquid was wiped off again and the samples were washed with DI water and allowed to dry for at least 2 h.

[0087] XRD data show the formation of zinc ammonium phosphate (NH4)ZnPO4 (85444-ICSD) on ground HAp (151414-ICSD) (Figure 6). Zinc ammonium phosphate peaks appear at 2θ values ​​of 14, 19, 20, 28 and 36. Other peaks belong to ground HAp, either alone or overlapping with zinc ammonium phosphate. In the reverse order of reagent addition, 24% diammonium phosphate was applied to the HAp surface, followed by 42% zinc nitrate, and the mineral product was identified as hopite Zn3(PO4)2·4H2O and its powder pattern (34869-ICSD) (Figure 6).

[0088] The corresponding SEM images of the two minerals precipitated on HAp clearly show the cauliflower-like structure of zinc ammonium phosphate and the flower-like structure of the hopeite (Fig. 7).

[0089] Fate of zinc minerals in aqueous media: Immersion of zinc ammonium phosphate in DI water and artificial saliva The key to understanding the utility of zinc phosphate in dentinal tubules is the nature of its transformation upon prolonged exposure to the ion-rich environment of saliva, as occurs in patent dentinal tubules. Zinc ammonium phosphate powder is transformed to zinc phosphate, to varying degrees, when soaked in artificial saliva and water for 11 days (Figure 8).

[0090] The peaks at 2θ: 17, 17.5, 18, and 31.8 belong to Hopite (34869-ICSD). In this immersion experiment, the change from zinc ammonium phosphate to the more stable phase, Hopite, is more pronounced in DI water but negligible in artificial saliva.

[0091] Hopite does not undergo morphological change in aqueous media. Its powder diffraction pattern is essentially unchanged except for peak broadening (Figure 9). The full width at half maximum (2θ) of the (241) peak at 31.3 was 0.368 for Hopite in DI water and 0.487 for Hopite in artificial saliva.

[0092] The Scherrer equation

number

[0093] These results support the feasibility of using zinc, known for its antibacterial properties, in caries treatment. A dentin block model was employed to study the reaction of aqueous zinc ions with aqueous phosphate ions resulting in the deposition of zinc phosphate minerals on the dentin surface and both at the opening and inside the dentinal tubules. As a result, patent tubules are rapidly obliterated. The formation and fate of the associated zinc phosphate minerals in an aqueous environment were investigated on a ground HAp surface as a dentin surrogate. This approach facilitated the analysis of the products by XRD and SEM, showing that the order of ion addition determines both the mineral composition and its area of ​​deposition.

[0094] Sequential application of aqueous zinc, followed by phosphate ions to the dentin surface results in the uptake of each solution into the tubules where they mix and deposit zinc phosphate. SEM and EDS analysis show that the sequential addition of zinc followed by phosphate produces zinc phosphate minerals in the form of 2-3 micron-scale crystals that are fairly uniformly distributed within the dentin tubules to a depth of up to 120 microns. When the phosphate solution is applied first followed by zinc (phosphate → zinc), smaller needle-like crystals are more prevalent on the dentin surface and block the tubule openings.

[0095] The mineral component surrounding dentinal tubules has been shown to be calcium-deficient carbonated HAp. For simplicity in this study, the deposition of zinc phosphate mineral obtained by combining solutions was evaluated on ground HAp matrices (which served as an analogue of the peridentinal tubule surface).

[0096] Parallel experiments using ground HAp as a dentin substitute provided insight into the conditions for mineral formation and transformation. In this system, a layer of HAp was exposed to an aqueous medium while remaining attached to an inert underlying silicon substrate by a layer of epoxy resin and adhesive tape. Application of a zinc salt solution followed by a phosphate solution (zinc → phosphate) produced a stable mineral phase, zinc ammonium phosphate, attached to the HAp. Excess zinc nitrate solution was wiped off leaving a film, so that diammonium phosphate ions were subsequently in excess. These conditions favor the formation of the observed products.

number

number

[0097] Zinc deposition and retention require different conditions than silver. Because direct uptake of zinc ions from solution by HAp is inherently low, zinc deposition is best achieved by de novo mineral formation, which is achieved by the formation of zinc phosphate. Deposition of zinc ammonium phosphate within the dentinal tubules is favored by a specific sequence of zinc → phosphate reagent addition to the dentin surface. This method produced the greatest tubule penetration depth by zinc (120 microns) and the highest density of tubule occlusion by crystals.

[0098] In aqueous solutions, zinc ammonium phosphate ((NH4)ZnPO4) transforms over time into the more stable phase, hopite (Zn3(PO4)2·4H2O) (Figure 6). This process is reduced in artificial saliva, probably because phosphate ions create an equilibrium (here, a higher ratio of phosphate to zinc favors (NH4)ZnPO4 over Zn3(PO4)2). However, in clinical applications, hopite may be the final phase and remain in the treated teeth, providing a long-term reservoir of zinc. In addition, ion exchange with calcium ions produces a calcium phosphate phase in the dentinal tubules, which may aid in the remineralization of carious tissue, a desirable outcome. These results suggest that zinc phosphate occludes dentinal tubules, increases dentin hardness, and decreases the permeability of exposed dentin. No discoloration was observed in the treated dentin in this experiment. Hopite is known to have antibacterial properties. In one application as a titanium implant coating, Hopite has been shown to be biocompatible, antibacterial, and a promoter of HAp formation.

[0099] These results show that topical application of zinc and phosphate solutions leads to mineral deposition on the dentin surface and within the dentinal tubules. Experiments on HAp surfaces allowed the identification of the deposited colorless zinc phosphate mineral as a function of the reaction stoichiometry and the nature of the mineral changes upon prolonged contact with aqueous media. The mineral formation protocol and the properties of the product may prove suitable for the treatment of caries and the relief of tooth sensitivity due to its antibacterial activity and aesthetic acceptability.

[0100] Without intending to be bound by any particular theory, it is believed that the zinc ammonium phosphate precipitate, in particular, has activity against Streptococcus mutans because it is a source of zinc ions. Furthermore, this novel zinc-based dentin treatment opens a wealth of other areas to be explored, including mechanical effects on resin adhesion, long-term color stability of dentin after application, and improved protocols for increasing crystal penetration depth and density. Example 2

[0101] The objective of this disclosure is to deposit (1) zinc phosphate, (2) zinc ammonium phosphate, and (3) zinc fluoride onto dentin. Below is a summary of the precursors and products that were produced:

number

[0102] It also provides delivery of ZnO to the dentinal tubules.

[0103] Zn in ammonia water 2+ A new method for the deposition of ZnO from salt solutions is described. Zn 2+ The salt may be, for example, ZnF2, Zn(NO3)2, ZnSO4, ZnCl2, ZnBr2, or ZnI2. The concentration of ammonia (NH3) may be 10%, 20%, or 30% by weight. Other percentages may be suitable. The ratio of NH3:Zn in solution 2+ The molar ratio may be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1 to 10:1.

[0104] Zn in alcoholic ammonia 2+ A new method for the precipitation of ZnO from a solution of a salt is described. The alcohol can be methanol, ethanol, n-propanol, isopropanol, butanol, sec-butanol, tert-butanol, propylene glycol, or ethylene glycol. Zn 2+The salt may be, for example, ZnF2, Zn(NO3)2, ZnSO4, ZnCl2, ZnBr2, or ZnI2. The concentration of ammonia (NH3) may be 1N, 2N-N. Other concentrations may also be suitable. The ratio of NH3:Zn in solution 2+ The molar ratio may be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1 to 10:1.

[0105] The formation of ZnO is due to the 2+ This occurs when a / NH3(aq) solution is diluted with deionized water. The dilution is approximately 20-fold, i.e. 50 microliters of solution is added to 1 ml of deionized water.

[0106] The formation of ZnO is 2+ This occurs when the / NH3(alc) solution is diluted with deionized water. The dilution is approximately 20 times, i.e. 50 microliters of alcohol solution is added to 1 ml of deionized water.

[0107] Zinc 2+ / NH3(aq) or Zn 2+ Formation of ZnO in carious lesions when / NH3(alc) was deposited in the lesions as an antibacterial agent.

[0108] Zinc 2+ / NH3(aq) or Zn 2+ Formation of ZnO in carious lesions when / NH3(alc) was deposited in the lesions as a tubule occluding agent. Example 4

[0109] The following data is F2H 18 Derived from the crystallographic information file for N4O3Zn. TIFF2025514216000005.tif203164

[0110] [Table 1]

[0111] [Table 2]

[0112]

Table 3

[0113]

Table 4

[0114]

Table 5

[0115]

Table 6

[0116]

Table 7

[0117]

Table 8

[0118]

Table 9-1

Table 9-2

Table 9-3

Table 9-4

Table 9-5

Table 9-6

Table 9-7

Table 9-8

Table 9-9

Table 9-10

Table 9-11

Table 9-12

Table 9-13

Table 9-14

Table 9-15

Table 9-16

Table 9-17

Table 9-18

Table 9-19

Table 9-20

Table 9-21

Table 9-22

Table 9-23

Table 9-24

Table 9-25

Table 9-26

Table 9-27

Table 9-28

Table 9-29

Table 9-30

Table 9-31

Table 9-32

Table 9-33

Table 9-34

Table 9-35

Table 9-36

Table 9-37

Table 9-38

Table 9-39

Table 9-40

[0119] Although the present disclosure has been described with respect to one or more particular embodiments and / or examples, it will be understood that other embodiments and / or examples of the present disclosure may be made without departing from the scope of the present disclosure.

Claims

1. It is a treatment for dental caries, (1) Zn 3 (PO) 4 (and / or its hydrate) and / or (NH 4 )ZnPO 4 A composition containing a zinc salt and a composition containing a phosphate, which are applied to the caries to form the caries, or (2) A composition comprising zinc and fluoride to be applied to the caries. A therapeutic agent characterized by containing the following:

2. The therapeutic agent according to claim 1, wherein the composition is applied to the surface of a carious tooth with a brush.

3. The zinc salt is Zn(NO 3 ) 2 , ZnSO 4 , Zn(OAc) 2 , ZnF 2 , ZnCl 2 , ZnBr 2 , ZnI 2 , [Zn(NH 3 ) 4 F 2 or any combination thereof, the therapeutic agent according to claim 1.

4. Phosphates, (NH 4 ) 2 Hpo 4 , (NH 4 )H 2 PO 4 , K 3 PO 4 , K 2 Hpo 4 , KH 2 PO 4 , (NH 4 ) 2 PO 3 The therapeutic agent according to claim 1, which is F, or any combination thereof.

5. A composition containing a zinc salt is applied before a composition containing a phosphate, or The therapeutic agent according to claim 1, wherein the composition containing the phosphate is applied before the composition containing the zinc salt.

6. The therapeutic agent according to claim 1, wherein the concentration of the zinc salt is 30 to 50 wt% of the total weight of the composition.

7. The therapeutic agent according to claim 1, wherein the concentration of phosphate is 10 to 40 wt% of the total weight of the composition.

8. Zn 3 (PO) 4 (and / or its hydrate) and / or (NH 4 )ZnPO 4 A therapeutic agent according to claim 1 for forming [a certain substance].

9. A composition containing zinc and fluoride, [Zn(NH 3 ) 4 ]F 2 A therapeutic agent according to claim 1, comprising:

10. The therapeutic agent according to claim 9, wherein the composition further comprises at least one liquid medium selected from the group consisting of alcohol, glycol, and water.

11. [Zn(NH 3 ) 4 ]F 2 A composition containing the following:

12. The composition according to claim 11, further comprising at least one liquid medium selected from the group consisting of alcohol, glycol, and water.

13. A composition for preparing an inorganic zinc compound, The composition is Zn 2+ / NH 3 It is in the form of a solution containing, which is diluted with water, Here, an inorganic zinc compound is formed by the aforementioned dilution, and this inorganic zinc compound is ZnO, Zn(OH) 2 A composition which is , and / or Zn(OH)F.

14. Zn 2+ / NH 3 The composition according to claim 13, wherein the solution containing is an aqueous ammonia solution.

15. Zn 2+ The composition according to claim 13, wherein the concentration of is 1 to 5 M.

16. The composition according to claim 13, wherein the ammonia concentration is 10 to 30% by weight relative to the total weight of water and ammonia.

17. NH in solution 3 : Zn 2+ The composition according to claim 13, wherein the molar ratio of the components is 1:1 to 10:

1.

18. Zn 2+ / NH 3 The composition according to claim 13, wherein a solution containing is applied to the surface of a tooth or the surface of a dental caries before dilution.

19. The composition according to claim 13, wherein the dilution is performed in the oral cavity of an individual.

20. The composition according to claim 13, wherein the solution contains [Zn(NH3)4]2+.

21. The composition according to claim 13, wherein the solution containing Zn²⁺ / NH₃ is an alcohol-based ammonia solution.

22. The composition according to claim 21, wherein the alcohol in the alcohol-based ammonia solution is selected from methanol, ethanol, N-propanol, isopropanol, butanol, sec-butanol, tert-butanol, propylene glycol, ethylene glycol, and combinations thereof.

23. The composition according to claim 21, wherein the concentration of Zn²⁺ is 1 to 5 M.

24. The composition according to claim 21, wherein the ammonia concentration is 1 to 7 N.

25. The composition according to claim 21, wherein the molar ratio of NH3 to Zn2+ in the solution is 1:1 to 10:

1.

26. The composition according to claim 13, wherein the dilution is at least 20 times or about 20 times.

27. ​​The composition according to claim 13, wherein Zn²⁺ is obtained from Zn(NO₃)₂, ZnSO₄, Zn(OAc)₂, ZnF₂, ZnCl₂, ZnBr₂, ZnI₂, or any combination thereof.

28. A composition applied to individual teeth to alleviate tooth hypersensitivity, The composition is Zn 2+ / NH 3 It is in the form of a solution containing, which is diluted with water, The aforementioned dilution results in the formation of an inorganic zinc compound on or inside the tooth. The inorganic zinc compound is ZnO, Zn(OH) 2 , and / or Zn(OH)F A composition characterized by the following.

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