WO2014151244A1 - Compositions and methods for remineralizing tooth enamel using calcium phosphate nanoparticles - Google Patents
Compositions and methods for remineralizing tooth enamel using calcium phosphate nanoparticles Download PDFInfo
- Publication number
- WO2014151244A1 WO2014151244A1 PCT/US2014/025282 US2014025282W WO2014151244A1 WO 2014151244 A1 WO2014151244 A1 WO 2014151244A1 US 2014025282 W US2014025282 W US 2014025282W WO 2014151244 A1 WO2014151244 A1 WO 2014151244A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- priming
- tooth enamel
- composition
- calcium phosphate
- remineralizing
- Prior art date
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract description 52
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- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- 229940045872 sodium percarbonate Drugs 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- ANOBYBYXJXCGBS-UHFFFAOYSA-L stannous fluoride Chemical compound F[Sn]F ANOBYBYXJXCGBS-UHFFFAOYSA-L 0.000 description 1
- 229960002799 stannous fluoride Drugs 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 230000036347 tooth sensitivity Effects 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 229960003500 triclosan Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/70—Preparations for dentistry comprising inorganic additives
- A61K6/71—Fillers
- A61K6/74—Fillers comprising phosphorus-containing compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/15—Compositions characterised by their physical properties
- A61K6/17—Particle size
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C19/00—Dental auxiliary appliances
- A61C19/06—Implements for therapeutic treatment
- A61C19/063—Medicament applicators for teeth or gums, e.g. treatment with fluorides
Definitions
- the present invention is in the field of dental treatment compositions used to remineralize teeth and methods of remineralizing teeth.
- Tooth enamel is the hardest and most highly mineralized substance in the human body. Ninety-six percent of enamel consists of mineral, with water and organic material composing the rest. Enamel's primary mineral is hydroxyapatite, which is a crystalline calcium phosphate. Enamel is avascular and has no nerve supply within it and is not renewed, however, it is not a static tissue as it can undergo mineralization changes.
- Tooth cavities are caused when acids dissolve tooth enamel according to the following equation:
- enamel In addition to bacterial invasion, enamel is also susceptible to other destructive forces. Bruxism, also known as clenching of or grinding on teeth, destroys enamel very quickly. The wear rate of enamel, called attrition, is 8 ⁇ a year from normal factors. Other nonbacterial processes of enamel destruction include abrasion (involving foreign elements, such as toothbrushes), erosion (involving chemical processes, such as dissolving by soft drinks or lemon and other juices), and possibly abfraction (involving compressive and tensile forces).
- enamel is vulnerable to demineralization it is also capable of remineralization.
- Fluoride ions catalyze the diffusion of calcium and phosphate into the tooth surface, which in turn remineralizes the crystalline structures in a dental cavity. Fluoride mediates remineralization with fluorapatite.
- the remineralized tooth surfaces contain fluoridated hydroxyapatite and fluorapatite, which resist acid attack much better than the original tooth did. Fluoride therapy is therefore used to help prevent dental decay.
- compositions, methods, dental treatment devices, and kits for remineralizing tooth enamel using calcium phosphate nanoparticles Under very high magnification, enamel and dentin are not particularly smooth. The topography varies greatly with many areas that very small particles can become caught. A benefit of calcium phosphate nanoparticles is that these tiny particles can become entrapped in these deformities, undercuts, depressions, etc. and as such can become a nucleation site and building block for new mineral (enamel or dentin). This is dependent upon saliva and the ions present but normal saliva carries all of the ions necessary for enamel formation. Enamel simply needs attachment sites for the ions to be attracted to.
- compositions, methods and kits include a priming agent that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel and calcium phosphate nanoparticles that can enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel.
- the calcium phosphate nanoparticles can promote remineralization of tooth enamel by providing nucleation sites that attract calcium ions and phosphate ions contained in tooth saliva and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- priming and remineralizing compositions include a priming agent that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel, calcium phosphate nanoparticles that can enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel, and a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
- the priming and remineralizing composition can be applied to enamel by loading the composition onto a barrier layer, such an oral treatment strip or dental treatment tray, and placing the barrier layer with the composition over a user's teeth.
- the composition is preferably kept on the user's teeth for a time sufficient to prime the user's enamel and cause or permit calcium phosphate nanoparticles to enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel.
- the calcium phosphate nanoparticles can provide nucleation sites that attract calcium ions and phosphate ions contained in tooth saliva and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- the priming agent comprises a peroxide dental bleaching agent.
- the priming and remineralizing composition may have an acidic or neutral pH.
- the pH is acidic, it is advantageously less than about 6, preferably less than about 5.
- the priming agent comprises an acid that etches calcium ions from hydroxyapatite mineral material of tooth enamel.
- the pH is advantageously less than about 3, preferably less than about 2.
- the calcium phosphate nanoparticles in the priming and remineralizing compositions will typically have a particle size of less than 1 micron, preferably less than about 500 nm, more preferably less than about 250 nm, and most preferably less than about 100 nm.
- the calcium phosphate nanoparticles may include one or more different calcium phosphate compounds, including at least one of calcium phosphate monobasic, calcium phosphate dibasic, or calcium phosphate tribasic.
- the priming and remineralizing compositions may include a carrier that is a sticky viscous gel comprised of a polyol and a tissue adhesion agent. They may further include a fluoride salt for promoting formation of fluorapatite on or within tooth enamel. They may include potassium nitrate to reduce tooth sensitivity.
- priming and remineralizing compositions for remineralization of tooth enamel include: (1) a peroxide compound that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; (2) calcium phosphate nanoparticles; and (3) a sticky viscous gel carrier in which the peroxide compound and calcium phosphate nanoparticles are dispersed.
- dental treatment devices for priming and remineralization of tooth enamel comprises: (1) a barrier layer configured for placement over a user's tooth surfaces; and (2) a priming and remineralizing composition for remineralization of tooth enamel, the priming and remineralizing composition being composed of: (a) a priming agent that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; (b) calcium phosphate nanoparticles; and (c) a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
- methods for priming and remineralizing tooth enamel comprise: (1) priming tooth enamel for remineralization by applying a composition that chemically removes plaque, pellicle, or other organic film material from the tooth enamel and exposes hydroxyapatite mineral material of the tooth enamel; and (2) treating the tooth enamel with calcium phosphate nanoparticles to promote remineralization of the tooth enamel.
- priming tooth enamel includes chemically removing plaque, pellicle, or other organic film material from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel in order to expose hydroxyapatite mineral material in the holes, pits, undercuts, spaces or other discontinuities of the tooth enamel. This facilitates penetration and lodging of the calcium phosphate nanoparticles within the holes, pits, undercuts, spaces or other discontinuities of the tooth enamel.
- priming the tooth enamel and treating the tooth enamel with calcium phosphate nanoparticles are performed in a single step using a single priming and remineralizing composition as disclosed herein.
- priming the tooth enamel and treating the tooth enamel with calcium phosphate nanoparticles are performed in successive steps using a priming composition followed by using a remineralizing composition.
- the priming and remineralizing composition can be applied to enamel using a barrier layer, such an oral treatment strip or dental treatment tray, and placing the barrier layer with the composition over a user's teeth.
- a barrier layer such an oral treatment strip or dental treatment tray
- separate priming and remineralizing compositions can be applied to enamel using separate barrier layers, such oral treatment strips or dental treatment trays, and placing the barrier layers with the compositions over a user's teeth.
- the priming composition is preferably kept on the user's teeth for a time sufficient to prime the user's enamel.
- the remineralizing composition is preferably kept on the user's teeth for a time sufficient to cause or permit calcium phosphate nanoparticles to enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel.
- the calcium phosphate nanoparticles provide nucleation sites that attract calcium ions and phosphate ions contained in tooth saliva and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- kits for use in priming and remineralizing tooth enamel include one or more syringes or other containers for storing and dispensing a priming and remineralizing composition and one or more barrier layers for applying the priming and remineralizing composition to a user's enamel.
- example kits may include a plurality of dental treatment devices comprising barrier layers having the priming and remineralizing composition pre-loaded thereon.
- kits for use in priming and remineralizing tooth enamel comprise: (1) a priming composition that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; and (2) a remineralization composition that includes calcium phosphate nanoparticles to promote remineralization of tooth enamel.
- the priming composition may include a peroxide and/or acid priming agent that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel, particularly from within holes, pits, undercuts, spaces or other discontinuities of the tooth enamel.
- kits may further include one or more barrier layers for applying the priming composition to a user's enamel and one or more additional barrier layers for applying the remineralizing composition to a user's enamel.
- the priming and remineralizing compositions can be stored within and dispensed from containers, such as syringes.
- example kits may include a plurality of dental treatment devices comprising a plurality of different barrier layers having separate priming and remineralizing composition pre-loaded thereon.
- dental treatment compositions disclosed herein can include at least one active agent, at least one tissue adhesion (or thickening) agent, a liquid or gel solvent, carrier or vehicle into which the active agent and tissue adhesion agent are dispersed, and other components and adjuvents as desired.
- the treatment compositions can be provided in a container, such as a syringe, for placement onto a barrier layer, such as an oral treatment strip or treatment tray.
- the treatment composition may be preloaded on a barrier layer and comprise continuous or discontinuous beads or layers positioned so as to contact at least a portion of a person's tooth surfaces.
- Treatment compositions can have a consistency of a liquid, gel, sticky viscous gel, putty, or solid.
- Solids and putties can become more sticky and adhesive to teeth and/or gums when moistened with water or saliva.
- the main difference between a "gel” and a "putty” or “solid” is the level of solvent or carrier within the composition.
- the greater the concentration of solvent or carrier relative to the tissue adhesive agent the less viscous is the composition.
- the lower the concentration of solvent or carrier relative to the tissue adhesion agent the more viscous, putty-like or solid is the composition.
- Examples of active agents for oral treatment compositions include dental bleaching agents, desensitizing agents, remineralizing agents, antimicrobial agents, anti-plaque agents, anti-tartar agents, gingival soothing agents, anesthetics, anti-oxidants, and mouth freshening agents.
- dental bleaching agents include aqueous hydrogen peroxide, carbamide peroxide, metal perborates (e.g., sodium perborate), metal percarbonates (e.g., sodium percarbonate), metal peroxides (e.g. , calcium peroxide), metal chlorites and hypochlorites, peroxy acids (e.g., peroxyacetic acid), and peroxy acid salts.
- Bleaching agents within dental bleaching compositions according to the invention can have any desired concentration, e.g. , between 1-90% by weight of the dental bleaching composition.
- concentration of the dental bleaching agent can be adjusted depending on the intended treatment time for each bleaching session.
- the bleaching agent is preferably included in an amount in a range of about 1% to about 60% by weight, more preferably in a range of about 3% to about 40% by weight, and most preferably in a range of about 5% to about 30% by weight.
- Examples of desensitizing agents include potassium nitrate, other potassium salts, citric acid, citrates, and sodium fluoride.
- Examples of remineralizing agents include calcium phosphate nanoparticles, sodium fluoride, stannous fluoride, sodium monofluorophosphate, and other fluoride salts.
- Examples of antimicrobial agents and preservatives include chlorhexidine, triclosan, sodium benzoate, parabens, tetracycline, phenols, cetyl pyridinium chloride, and benzalkonium chloride.
- An example of an anti- plaque or anti-tartar agent is pyrophosphate salts.
- Examples of gingival soothing agents include aloe vera, mild potassium nitrate, and isotonic solution-forming salts.
- Examples of anesthetics include benzocaine and lidocaine.
- Examples of anti-oxidants include vitamin A, vitamin C, vitamin E, other vitamins, and carotene.
- Examples of mouth freshening agents include camphor, oil of wintergreen, peppermint, spearmint, and methyl salicylate.
- Tissue adhesion agents, tackifying agents, or thickening agents can include a wide variety of hydrophilic polymers.
- hydrophilic polymers examples include polyvinyl pyrrolidone (PVP), PVP- vinyl acetate copolymers, carboxypolymethylene (e.g., CARBOPOL, sold by Novean, Inc.), polyethylene oxide (e.g., POLYOX, made by Union Carbide), polyacrylic acid polymers or copolymers (e.g., PEMULEN, sold by Novean, Inc.), polyacrylates, polyacrylamides, copolymers of polyacrylic acid and polyacrylamide, carboxymethylcellulose, carboxypropylcellulose, cellulosic ethers, polysaccharide gums, proteins, and the like.
- PVP polyvinyl pyrrolidone
- PVP- vinyl acetate copolymers examples include polyvinyl pyrrolidone (PVP), PVP- vinyl acetate copo
- PVPs examples include Kollidon 30, a polyvinyl pyrrolidone polymer sold by BASF having a molecular weight of 50,000, Kollidon VA 60, a polyvinyl pyrrolidone polymer having a molecular weight of 60,000, and Kollidon 90 F, a polyvinyl pyrrolidone polymer having a molecular weight of 1.3 million.
- the one or more tissue adhesion agents are preferably included in an amount in a range of about 1% to about 50% by weight of the treatment gel, more preferably in a range of about 3% to about 30% by weight, and most preferably in a range of about 5% to about 20% by weight.
- the one or more tissue adhesion agents are preferably included in an amount in a range of about 10% to about 90% by weight of the substantially solid treatment composition, more preferably in a range of about 20% to about 80% by weight, and most preferably in a range of about 40% to about 75% by weight.
- Liquids and gels, including sticky viscous gels may include one or more liquid or gel, solvents, carriers or vehicles into which the active agent, tissue adhesion agent, and other components are dissolved or dispersed.
- liquid or gel solvents, carriers or vehicles examples include water, alcohols (e.g., ethyl alcohol), and polyols (e.g., glycerin, sorbitol, mannitol, other sugar alcohols, propylene glycol, 1,3-propandiol, polyethylene glycol, polyethylene oxide, and polypropylene glycol).
- alcohols e.g., ethyl alcohol
- polyols e.g., glycerin, sorbitol, mannitol, other sugar alcohols, propylene glycol, 1,3-propandiol, polyethylene glycol, polyethylene oxide, and polypropylene glycol.
- the concentration of solvent, carrier or vehicle will typically be attenuated compared to treatment gels.
- volatile solvents e.g., water, alcohols, acetone, and other organic solvents.
- even treatment compositions that appear to be solid may include a significant amount of bound water (e.g., up to about 10% or more by weight of the treatment composition).
- the composition will generally include a solvent, carrier or vehicle that acts as a plasticizer or softening agent.
- Oral treatment compositions may optionally include other components as desired to yield treatment compositions having desired properties.
- bleaching agent stabilizers e.g., EDTA, salts of EDTA, citric acid and its salts, phosphoric acid and its salts, phenolphosphonic acid and its salts, gluconic acid and its salts, alkali metal pyrophosphates, alkali metal polyphosphates, and alkyl sulfates
- neutralizing agents e.g., sodium hydroxide and triethanolamine
- inorganic thickening agents e.g. , fumed silica
- colorants e.g., flavorants, sweeteners, and the like.
- compositions that are effective in remineralizing tooth enamel as well as a comparative example of a composition that is less effective in remineralizing tooth enamel.
- a toothpaste composition was prepared according to the following formulation.
- the toothpaste composition can be effective in mechanically removing plaque, pellicle and other organic film material from tooth enamel when brushed onto tooth surfaces using a toothbrush but is largely ineffective in removing plaque, pellicle and other organic film material from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel that cannot be reached by the toothbrush bristles.
- plaque, pellicle and other organic film material within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel block penetration of the hydroxyapatite nanoparticles into the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- Priming and remineralizing compositions for remineralization of tooth enamel were prepared according to the following formulations.
- the priming and remineralizing compositions of Examples 1-8 are effective in chemically removing plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- the plaque, pellicle and other organic film material otherwise residing within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel do not block penetration of the nanoparticles into the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- This renders the priming and remineralizing compositions of Examples 1-8 substantially more effective in remineralizing tooth enamel compared to the toothpaste composition of the Comparative Example.
- Priming and remineralizing compositions for remineralization of tooth enamel were prepared according to the following formulations.
- Polyethylene Glycol 300 0.00 0.00 5.40 0.00 0.00 0.00 5.50
- the priming and remineralizing compositions of Examples 9-10 and 12-15 are effective in chemically removing plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- the plaque, pellicle and other organic film material otherwise residing within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel do not block penetration of the nanoparticles into the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- This renders the priming and remineralizing compositions of Examples 9-10 and 12-15 substantially more effective in remineralizing tooth enamel compared to the toothpaste composition of the Comparative Example.
- the remineralizing composition of Example 11 is effective for use as a component within a kit or method for priming and remineralizing tooth enamel in combination with a priming composition containing an acid and/or peroxide that chemically removes plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
- compositions of the Comparative Example and Examples 1-15 is included within a kit that also includes a priming composition containing an acid and'or peroxide that chemically removes plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
Abstract
Compositions, methods, dental treatment devices, and kits for remineralizing tooth enamel employ calcium phosphate nanoparticles to promote remineralization. Priming and remineralizing compositions include a priming agent that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; calcium phosphate nanoparticles; and a carrier. Methods for remineralizing tooth enamel include priming tooth enamel by removing plaque, pellicle, or other organic film material from the tooth enamel and exposing hydroxyapatite mineral material and treating the tooth enamel with calcium phosphate nanoparticles to promote remineralization.
Description
COMPOSITIONS AND METHODS FOR REMINERALIZING TOOTH ENAMEL USING CALCIUM PHOSPHATE NANOPARTICLES
BACKGROUND OF THE INVENTION
1. The Field of the Invention
The present invention is in the field of dental treatment compositions used to remineralize teeth and methods of remineralizing teeth.
2. The Relevant Technology
Tooth enamel is the hardest and most highly mineralized substance in the human body. Ninety-six percent of enamel consists of mineral, with water and organic material composing the rest. Enamel's primary mineral is hydroxyapatite, which is a crystalline calcium phosphate. Enamel is avascular and has no nerve supply within it and is not renewed, however, it is not a static tissue as it can undergo mineralization changes.
The high mineral content of enamel also makes it susceptible to a demineralization process which often occurs as dental caries, otherwise known as cavities. Demineralization occurs for several reasons, but the most important cause of tooth decay is the ingestion of fermentable carbohydrates. Tooth cavities are caused when acids dissolve tooth enamel according to the following equation:
Caio(P04)6(OH)2(s) + 8H+(aq)→ 10Ca2+(aq) + 6HP04 ~2(aq) + 2H20(1).
Sugars from candies, soft drinks, and even fruit juices play a significant role in tooth decay, and consequently in enamel destruction. The mouth contains a great number and variety of bacteria. When sucrose, the most common of sugars, coats the surface of the mouth, some intraoral bacteria interact with it and form lactic acid, which decreases the pH in the mouth. The lower pH causes the hydroxyapatite crystals of enamel to demineralize, allowing for greater bacterial invasion deeper into the tooth. Furthermore, the most common site for the initiation of dental caries is in the deep grooves, pits, and fissures of enamel. These locations are difficult to reach with a toothbrush and allow for bacteria to reside there.
In addition to bacterial invasion, enamel is also susceptible to other destructive forces. Bruxism, also known as clenching of or grinding on teeth, destroys enamel very quickly. The wear rate of enamel, called attrition, is 8 μιη a year from normal factors. Other nonbacterial processes of enamel destruction include abrasion (involving foreign elements, such as toothbrushes), erosion (involving chemical processes, such as dissolving by soft drinks or lemon and other juices), and possibly abfraction (involving compressive
and tensile forces).
Although enamel is vulnerable to demineralization it is also capable of remineralization. One way is through the application of fluoride ions to the teeth. Fluoride ions catalyze the diffusion of calcium and phosphate into the tooth surface, which in turn remineralizes the crystalline structures in a dental cavity. Fluoride mediates remineralization with fluorapatite. The remineralized tooth surfaces contain fluoridated hydroxyapatite and fluorapatite, which resist acid attack much better than the original tooth did. Fluoride therapy is therefore used to help prevent dental decay.
Notwithstanding the foregoing, there remains a need to provide improved compositions and methods for promoting remineralization of enamel in order to increase the strength of enamel and increase resistance to caries.
BRIEF SUMMARY
Disclosed herein are compositions, methods, dental treatment devices, and kits for remineralizing tooth enamel using calcium phosphate nanoparticles. Under very high magnification, enamel and dentin are not particularly smooth. The topography varies greatly with many areas that very small particles can become caught. A benefit of calcium phosphate nanoparticles is that these tiny particles can become entrapped in these deformities, undercuts, depressions, etc. and as such can become a nucleation site and building block for new mineral (enamel or dentin). This is dependent upon saliva and the ions present but normal saliva carries all of the ions necessary for enamel formation. Enamel simply needs attachment sites for the ions to be attracted to.
These and other advantages and features of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Disclosed herein are priming and remineralizing compositions for remineralization of tooth enamel as well as methods, dental treatment devices, and kits for remineralizing tooth enamel. According to several embodiments, the compositions, methods and kits include a priming agent that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel and calcium phosphate nanoparticles that can enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel. The calcium phosphate nanoparticles can promote remineralization of tooth enamel by providing nucleation sites that attract calcium ions and phosphate ions
contained in tooth saliva and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
According to several embodiments, priming and remineralizing compositions include a priming agent that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel, calcium phosphate nanoparticles that can enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel, and a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
The priming and remineralizing composition can be applied to enamel by loading the composition onto a barrier layer, such an oral treatment strip or dental treatment tray, and placing the barrier layer with the composition over a user's teeth. The composition is preferably kept on the user's teeth for a time sufficient to prime the user's enamel and cause or permit calcium phosphate nanoparticles to enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel. The calcium phosphate nanoparticles can provide nucleation sites that attract calcium ions and phosphate ions contained in tooth saliva and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
According to one embodiment, the priming agent comprises a peroxide dental bleaching agent. When the priming agent comprises a peroxide dental bleaching agent, the priming and remineralizing composition may have an acidic or neutral pH. When the pH is acidic, it is advantageously less than about 6, preferably less than about 5. According to another embodiment, the priming agent comprises an acid that etches calcium ions from hydroxyapatite mineral material of tooth enamel. When the priming agent comprises an acid, the pH is advantageously less than about 3, preferably less than about 2.
The calcium phosphate nanoparticles in the priming and remineralizing compositions will typically have a particle size of less than 1 micron, preferably less than about 500 nm, more preferably less than about 250 nm, and most preferably less than about 100 nm. The calcium phosphate nanoparticles may include one or more different calcium phosphate compounds, including at least one of calcium phosphate monobasic, calcium phosphate dibasic, or calcium phosphate tribasic.
The priming and remineralizing compositions may include a carrier that is a sticky viscous gel comprised of a polyol and a tissue adhesion agent. They may further include a fluoride salt for promoting formation of fluorapatite on or within tooth enamel. They may include potassium nitrate to reduce tooth sensitivity.
In a preferred embodiment, priming and remineralizing compositions for remineralization of tooth enamel include: (1) a peroxide compound that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; (2) calcium phosphate nanoparticles; and (3) a sticky viscous gel carrier in which the peroxide compound and calcium phosphate nanoparticles are dispersed.
According to other embodiments, dental treatment devices for priming and remineralization of tooth enamel comprises: (1) a barrier layer configured for placement over a user's tooth surfaces; and (2) a priming and remineralizing composition for remineralization of tooth enamel, the priming and remineralizing composition being composed of: (a) a priming agent that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; (b) calcium phosphate nanoparticles; and (c) a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
According to other embodiments, methods for priming and remineralizing tooth enamel comprise: (1) priming tooth enamel for remineralization by applying a composition that chemically removes plaque, pellicle, or other organic film material from the tooth enamel and exposes hydroxyapatite mineral material of the tooth enamel; and (2) treating the tooth enamel with calcium phosphate nanoparticles to promote remineralization of the tooth enamel. In a preferred embodiment, priming tooth enamel includes chemically removing plaque, pellicle, or other organic film material from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel in order to expose hydroxyapatite mineral material in the holes, pits, undercuts, spaces or other discontinuities of the tooth enamel. This facilitates penetration and lodging of the calcium phosphate nanoparticles within the holes, pits, undercuts, spaces or other discontinuities of the tooth enamel.
According to one embodiment, priming the tooth enamel and treating the tooth enamel with calcium phosphate nanoparticles are performed in a single step using a single priming and remineralizing composition as disclosed herein. According to another embodiment, priming the tooth enamel and treating the tooth enamel with calcium
phosphate nanoparticles are performed in successive steps using a priming composition followed by using a remineralizing composition.
The priming and remineralizing composition can be applied to enamel using a barrier layer, such an oral treatment strip or dental treatment tray, and placing the barrier layer with the composition over a user's teeth. Similarly, separate priming and remineralizing compositions can be applied to enamel using separate barrier layers, such oral treatment strips or dental treatment trays, and placing the barrier layers with the compositions over a user's teeth. The priming composition is preferably kept on the user's teeth for a time sufficient to prime the user's enamel. The remineralizing composition is preferably kept on the user's teeth for a time sufficient to cause or permit calcium phosphate nanoparticles to enter into and lodge within holes, pits, undercuts, spaces or other discontinuities in tooth enamel to promote remineralization of tooth enamel. The calcium phosphate nanoparticles provide nucleation sites that attract calcium ions and phosphate ions contained in tooth saliva and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
According to several embodiment, kits for use in priming and remineralizing tooth enamel include one or more syringes or other containers for storing and dispensing a priming and remineralizing composition and one or more barrier layers for applying the priming and remineralizing composition to a user's enamel. Alternatively, example kits may include a plurality of dental treatment devices comprising barrier layers having the priming and remineralizing composition pre-loaded thereon.
According to other embodiments, kits for use in priming and remineralizing tooth enamel comprise: (1) a priming composition that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; and (2) a remineralization composition that includes calcium phosphate nanoparticles to promote remineralization of tooth enamel. The priming composition may include a peroxide and/or acid priming agent that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel, particularly from within holes, pits, undercuts, spaces or other discontinuities of the tooth enamel. When the priming agent comprises a peroxide dental bleaching agent, the priming composition may have a pH less than about 6, preferably less than about 5. When the priming agent comprises an acid, the pH is advantageously less than about 3, preferably less than about 2.
Such kits may further include one or more barrier layers for applying the priming composition to a user's enamel and one or more additional barrier layers for applying the remineralizing composition to a user's enamel. The priming and remineralizing compositions can be stored within and dispensed from containers, such as syringes. Alternatively, example kits may include a plurality of dental treatment devices comprising a plurality of different barrier layers having separate priming and remineralizing composition pre-loaded thereon.
In general, dental treatment compositions disclosed herein can include at least one active agent, at least one tissue adhesion (or thickening) agent, a liquid or gel solvent, carrier or vehicle into which the active agent and tissue adhesion agent are dispersed, and other components and adjuvents as desired. The treatment compositions can be provided in a container, such as a syringe, for placement onto a barrier layer, such as an oral treatment strip or treatment tray. Alternatively, the treatment composition may be preloaded on a barrier layer and comprise continuous or discontinuous beads or layers positioned so as to contact at least a portion of a person's tooth surfaces. Treatment compositions can have a consistency of a liquid, gel, sticky viscous gel, putty, or solid. Solids and putties can become more sticky and adhesive to teeth and/or gums when moistened with water or saliva. In some cases, the main difference between a "gel" and a "putty" or "solid" is the level of solvent or carrier within the composition. In general, the greater the concentration of solvent or carrier relative to the tissue adhesive agent, the less viscous is the composition. The lower the concentration of solvent or carrier relative to the tissue adhesion agent, the more viscous, putty-like or solid is the composition.
Examples of active agents for oral treatment compositions include dental bleaching agents, desensitizing agents, remineralizing agents, antimicrobial agents, anti-plaque agents, anti-tartar agents, gingival soothing agents, anesthetics, anti-oxidants, and mouth freshening agents. Examples of dental bleaching agents include aqueous hydrogen peroxide, carbamide peroxide, metal perborates (e.g., sodium perborate), metal percarbonates (e.g., sodium percarbonate), metal peroxides (e.g. , calcium peroxide), metal chlorites and hypochlorites, peroxy acids (e.g., peroxyacetic acid), and peroxy acid salts.
Bleaching agents within dental bleaching compositions according to the invention can have any desired concentration, e.g. , between 1-90% by weight of the dental bleaching composition. The concentration of the dental bleaching agent can be adjusted depending on the intended treatment time for each bleaching session. The bleaching agent is preferably included in an amount in a range of about 1% to about 60% by weight, more
preferably in a range of about 3% to about 40% by weight, and most preferably in a range of about 5% to about 30% by weight.
Examples of desensitizing agents include potassium nitrate, other potassium salts, citric acid, citrates, and sodium fluoride. Examples of remineralizing agents include calcium phosphate nanoparticles, sodium fluoride, stannous fluoride, sodium monofluorophosphate, and other fluoride salts. Examples of antimicrobial agents and preservatives include chlorhexidine, triclosan, sodium benzoate, parabens, tetracycline, phenols, cetyl pyridinium chloride, and benzalkonium chloride. An example of an anti- plaque or anti-tartar agent is pyrophosphate salts. Examples of gingival soothing agents include aloe vera, mild potassium nitrate, and isotonic solution-forming salts. Examples of anesthetics include benzocaine and lidocaine. Examples of anti-oxidants include vitamin A, vitamin C, vitamin E, other vitamins, and carotene. Examples of mouth freshening agents include camphor, oil of wintergreen, peppermint, spearmint, and methyl salicylate.
Tissue adhesion agents, tackifying agents, or thickening agents can include a wide variety of hydrophilic polymers. Examples include polyvinyl pyrrolidone (PVP), PVP- vinyl acetate copolymers, carboxypolymethylene (e.g., CARBOPOL, sold by Novean, Inc.), polyethylene oxide (e.g., POLYOX, made by Union Carbide), polyacrylic acid polymers or copolymers (e.g., PEMULEN, sold by Novean, Inc.), polyacrylates, polyacrylamides, copolymers of polyacrylic acid and polyacrylamide, carboxymethylcellulose, carboxypropylcellulose, cellulosic ethers, polysaccharide gums, proteins, and the like. Examples of PVPs include Kollidon 30, a polyvinyl pyrrolidone polymer sold by BASF having a molecular weight of 50,000, Kollidon VA 60, a polyvinyl pyrrolidone polymer having a molecular weight of 60,000, and Kollidon 90 F, a polyvinyl pyrrolidone polymer having a molecular weight of 1.3 million.
In the case where the oral treatment composition is a gel, the one or more tissue adhesion agents are preferably included in an amount in a range of about 1% to about 50% by weight of the treatment gel, more preferably in a range of about 3% to about 30% by weight, and most preferably in a range of about 5% to about 20% by weight.
In the case where the oral treatment composition is a putty or solid, the one or more tissue adhesion agents are preferably included in an amount in a range of about 10% to about 90% by weight of the substantially solid treatment composition, more preferably in a range of about 20% to about 80% by weight, and most preferably in a range of about 40% to about 75% by weight.
Liquids and gels, including sticky viscous gels, may include one or more liquid or gel, solvents, carriers or vehicles into which the active agent, tissue adhesion agent, and other components are dissolved or dispersed. Examples of liquid or gel solvents, carriers or vehicles include water, alcohols (e.g., ethyl alcohol), and polyols (e.g., glycerin, sorbitol, mannitol, other sugar alcohols, propylene glycol, 1,3-propandiol, polyethylene glycol, polyethylene oxide, and polypropylene glycol).
For solids or stiff putties, the concentration of solvent, carrier or vehicle will typically be attenuated compared to treatment gels. Where it is desired to convert a gel into a putty or solid composition, it may be advantageous to include one or more volatile solvents that can be removed by evaporation (e.g., water, alcohols, acetone, and other organic solvents). Because of the affinity of hydrophilic polymers for water, even treatment compositions that appear to be solid may include a significant amount of bound water (e.g., up to about 10% or more by weight of the treatment composition). In the case where the treatment composition has the consistency of a highly viscous or stiff putty, the composition will generally include a solvent, carrier or vehicle that acts as a plasticizer or softening agent.
Oral treatment compositions may optionally include other components as desired to yield treatment compositions having desired properties. Examples include bleaching agent stabilizers (e.g., EDTA, salts of EDTA, citric acid and its salts, phosphoric acid and its salts, phenolphosphonic acid and its salts, gluconic acid and its salts, alkali metal pyrophosphates, alkali metal polyphosphates, and alkyl sulfates), neutralizing agents (e.g., sodium hydroxide and triethanolamine), inorganic thickening agents (e.g. , fumed silica), colorants, flavorants, sweeteners, and the like.
Following are examples of compositions that are effective in remineralizing tooth enamel as well as a comparative example of a composition that is less effective in remineralizing tooth enamel.
COMPARATIVE EXAMPLE
A toothpaste composition was prepared according to the following formulation.
Calcium pyrophosphate 20.0%
Hydroxyapatite nanaoparticles 10.0%
Glycerin 20.0%
Propylene glycol 10.0%
Polyethylene glycol 5.0%
Sodium laurylsulfate 0.8%
Hydroxyethyl cellulose 0.5%
Xanthan gum 0.5%
Methyl paraben 0.1%
Sorbitol aqueous solution (70%) 3.3%
Water 29.8%
Total 100.0%
The toothpaste composition can be effective in mechanically removing plaque, pellicle and other organic film material from tooth enamel when brushed onto tooth surfaces using a toothbrush but is largely ineffective in removing plaque, pellicle and other organic film material from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel that cannot be reached by the toothbrush bristles. As a result, plaque, pellicle and other organic film material within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel block penetration of the hydroxyapatite nanoparticles into the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel. This in turn renders the toothpaste composition less effective in remineralizing tooth enamel compared to a composition that can chemically remove plaque, pellicle and other organic film material from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel and expose hydroxyapatite mineral material of the tooth enamel within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
EXAMPLES 1-8
Priming and remineralizing compositions for remineralization of tooth enamel were prepared according to the following formulations.
Example
Component (Mass%)
1 2 3 4 5 6 7 8
Water 22.90 22.90 22.90 22.90 22.90 22.90 22.90 10.00
Sodium Hydroxide 2.90 2.90 2.90 2.90 2.90 2.90 2.90 1.50
Potassium Hydroxide 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
Sodium Fluoride 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.00
Potassium Nitrate 0.50 0.50 0.50 0.50 0.50 0.50 0.50 3.00
Nano Calcium Phosphate 0.10 0.50 5.00 10.00 5.00 10.00 2.50 1.00
Polyethylene Glycol 300 5.50 5.50 5.50 5.50 5.50 5.50 5.50 0.00
Glycerin 24.65 24.25 19.75 14.75 29.75 24.75 22.25 62.00
Carbomer 6.80 6.80 6.80 6.80 6.80 6.80 6.80 3.50
Silicon Dioxide 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
Xylitol 15.00 15.00 15.00 15.00 5.00 5.00 15.00 0.00
Carbamide Peroxide 20.50 20.50 20.50 20.50 20.50 20.50 20.50 20.50
Hydrogen Peroxide 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
EDTA 0.30 0.30 0.30 0.30 0.30 0.30 0.30 0.30
Flavor 0.60 0.60 0.60 0.60 0.60 0.60 0.60 0.60
Color 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
The priming and remineralizing compositions of Examples 1-8 are effective in chemically removing plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel. As a result, the plaque, pellicle and other organic film material otherwise residing within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel do not block penetration of the nanoparticles into the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel. This in turn renders the priming and remineralizing compositions of Examples 1-8 substantially more effective in remineralizing tooth enamel compared to the toothpaste composition of the Comparative Example.
EXAMPLES 9-15
Priming and remineralizing compositions for remineralization of tooth enamel were prepared according to the following formulations.
Example
Component (Mass%)
9 10 11 12 13 14 15
Water 30.00 22.20 25.50 22.90 40.00 37.00 22.90
Sodium Hydroxide 2.30 2.20 1.60 2.90 0.00 0.00 2.90
Potassium Hydroxide 0.00 0.00 0.00 0.00 8.25 12.25 0.00
Sodium Fluoride 0.00 0.25 1.10 0.25 0.25 0.25 0.25
Potassium Nitrate 5.00 0.00 3.00 1.00 0.50 0.50 0.50
Nano Calcium Phosphate 2.00 0.50 1.00 2.00 3.00 3.00 0.50
Polyethylene Glycol 300 0.00 0.00 5.40 0.00 0.00 0.00 5.50
Glycerin 35.70 49.75 48.90 23.75 0.00 0.00 34.75
Carbomer 4.20 0.00 3.00 6.80 1.10 1.10 6.80
Silicon Dioxide 0.00 0.00 0.00 0.00 6.50 8.50 0.00
Xylitol 5.50 0.00 10.00 5.00 0.00 0.00 15.00
Carbamide Peroxide 0.00 7.50 0.00 35.00 0.00 0.00 10.50
Hydrogen Peroxide 15.00 13.00 0.00 0.00 40.00 37.00 0.00
EDTA 0.30 0.30 0.00 0.30 0.30 0.30 0.10
Flavor 0.00 0.30 0.50 0.30 0.00 0.00 0.30
Color 0.00 0.00 0.00 0.00 0.10 0.10 0.00
Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0
The priming and remineralizing compositions of Examples 9-10 and 12-15 are effective in chemically removing plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel. As a result, the plaque, pellicle and other organic film material otherwise residing within holes, pits, undercuts, spaces or other discontinuities in the tooth
enamel do not block penetration of the nanoparticles into the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel. This in turn renders the priming and remineralizing compositions of Examples 9-10 and 12-15 substantially more effective in remineralizing tooth enamel compared to the toothpaste composition of the Comparative Example.
The remineralizing composition of Example 11 is effective for use as a component within a kit or method for priming and remineralizing tooth enamel in combination with a priming composition containing an acid and/or peroxide that chemically removes plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
Example 16
Any of the compositions of the Comparative Example and Examples 1-15 is included within a kit that also includes a priming composition containing an acid and'or peroxide that chemically removes plaque, pellicle and other organic film material from tooth enamel, including from within holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
Claims
What is claimed is:
I. A priming and remineralizing composition for remineralization of tooth enamel, comprising:
a priming agent that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; calcium phosphate nanoparticles; and
a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
2. A priming and remineralizing composition as in claim 1, wherein the priming agent comprises a peroxide dental bleaching agent.
3. A priming and remineralizing composition as in claim 2, wherein the composition has a pH of less than about 6.
4. A priming and remineralizing composition as in claim 2, wherein the composition has a pH of less than about 5.
5. A priming and remineralizing composition as in claim 1, wherein the priming agent comprises an acid that etches calcium ions from hydroxyapatite mineral material of tooth enamel.
6. A priming and remineralizing composition as in claim 5, wherein the composition has a pH of less than about 3.
7. A priming and remineralizing composition as in claim 5, wherein the composition has a pH of less than about 2.
8. A priming and remineralizing composition as in claim 1, wherein the calcium phosphate nanoparticles have a particle size of less than 1 micron.
9. A priming and remineralizing composition as in claim 1, wherein the calcium phosphate nanoparticles have a particle size of less than about 500 nm.
10. A priming and remineralizing composition as in claim 1, wherein the calcium phosphate nanoparticles have a particle size of less than about 250 nm.
I I. A priming and remineralizing composition as in claim 1, wherein the calcium phosphate nanoparticles have a particle size of less than about 100 nm.
12. A priming and remineralizing composition as in claim 1, wherein the calcium phosphate nanoparticles comprise at least one of calcium phosphate monobasic, calcium phosphate dibasic, or calcium phosphate tribasic.
13. A priming and remineralizing composition as in claim 1, wherein the carrier is a sticky viscous gel comprised of a polyol and a tissue adhesion agent.
14. A priming and remineralizing composition as in claim 1, further comprising a fluoride salt.
15. A priming and remineralizing composition as in claim 1, further comprising potassium nitrate.
16. A dental treatment device for priming and remineralization of tooth enamel, comprising:
a barrier layer configured for placement over a user's tooth surfaces; and a priming and remineralizing composition for remineralization of tooth enamel, the priming and remineralizing composition being composed of:
a priming agent that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel;
calcium phosphate nanoparticles; and
a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
17. A method for remineralization of tooth enamel, comprising:
priming tooth enamel for remineralization by applying a composition that removes plaque, pellicle, or other organic film material from the tooth enamel and exposes hydroxyapatite mineral material of the tooth enamel; and
treating the tooth enamel with calcium phosphate nanoparticles to promote remineralization of the tooth enamel.
18. A method as in claim 17, wherein priming the tooth enamel comprises applying an acidic or peroxide composition to the tooth enamel.
19. A method as in claim 18, wherein priming the tooth enamel is performed chemically without scrubbing or brushing the acidic or peroxide composition on the tooth enamel.
20. A method as in claim 18, wherein the acidic or peroxide composition removes mineral ions from the hydroxyapatite mineral material of the tooth enamel.
21. A method as in claim 18, wherein the acidic or peroxide composition removes calcium ions from the hydroxyapatite mineral material of the tooth enamel.
22. A method as in claim 17, wherein the acidic or peroxide composition further removes phosphate ions from the hydroxyapatite mineral material of the tooth enamel.
23. A method as in claim 17, wherein priming the tooth enamel comprises exposing or opening up holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
24. A method as in claim 23, wherein treating the tooth enamel includes causing or allowing at least a portion of the calcium phosphate nanoparticles to enter and become lodged within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
25. A method as in claim 24, wherein the calcium phosphate nanoparticles promote remineralization of the tooth enamel by providing nucleation sites that attract calcium ions and phosphate ions in tooth saliva contacting the tooth enamel and promote growth of additional hydroxyapatite mineral material within the holes, pits, undercuts, spaces or other discontinuities in the tooth enamel.
26. A method as in claim 17, wherein priming the tooth enamel and treating the tooth enamel with calcium phosphate nanoparticles are performed in a single step using a single priming and remineralizing composition.
27. A method as in claim 17, wherein priming the tooth enamel and treating the tooth enamel with calcium phosphate nanoparticles are performed in successive steps using a priming composition followed by using a remineralizing composition.
28. A kit for remineralization of tooth enamel, comprising:
one or more syringes or other containers for storing and dispensing a priming and remineralizing composition; and
one or more barrier layers for applying the priming and remineralizing composition to a user's enamel.
29. A kit for remineralization of tooth enamel, comprising a plurality of dental treatment devices, each dental treatment device comprising:
a barrier layer; and
a priming and remineralizing composition pre-loaded thereon, the priming and remineralizing composition comprising:
a priming agent that removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel;
calcium phosphate nanoparticles; and
a carrier in which the priming agent and calcium phosphate nanoparticles are dispersed.
30. A kit for remineralization of tooth enamel, comprising:
a priming composition that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; and
a remineralization composition that includes calcium phosphate nanoparticles to promote remineralization of tooth enamel.
31. A kit as in claim 30, wherein the priming composition is a peroxide composition comprising a peroxide dental bleaching agent and having a pH of less than about 6.
32. A kit as in claim 30, wherein the priming composition is a peroxide composition comprising a peroxide dental bleaching agent and having a pH of less than about 5.
33. A kit as in claim 30, wherein the priming composition is an acidic composition having a pH of less than about 3.
34. A kit as in claim 30, wherein the priming composition is an acidic composition having a pH of less than about 2.
35. A kit as in claim 30, wherein the remineralization composition comprises the calcium phosphate nanoparticles dispersed in a sticky viscous gel carrier.
36. A kit as in claim 35, wherein the sticky viscous gel carrier comprises a polyol and a tooth adhesion agent.
37. A kit as in claim 30, further comprising a first syringe in which the priming composition is stored and a second syringe in which the remineralization composition is stored.
38. A kit as in claim 37, further comprising a plurality of barrier layers for separately applying the priming and remineralization compositions to a user's tooth enamel.
39. A kit for remineralization of tooth enamel, comprising:
a first dental treatment device comprising a first barrier layer and a priming composition on the first barrier layer that chemically removes plaque, pellicle, or other organic film material from tooth enamel and exposes hydroxyapatite mineral material of tooth enamel; and
a second dental treatment device comprising a second barrier layer and a remineralization composition on the second barrier layer that includes calcium phosphate nanoparticles to promote remineralization of tooth enamel.
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US201361798119P | 2013-03-15 | 2013-03-15 | |
US61/798,119 | 2013-03-15 |
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PCT/US2014/025282 WO2014151244A1 (en) | 2013-03-15 | 2014-03-13 | Compositions and methods for remineralizing tooth enamel using calcium phosphate nanoparticles |
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EP3229783A4 (en) * | 2014-12-09 | 2018-08-08 | Belmont University | Pharmaceutical semi-solid gels with entrapped calcium phosphate nanoparticles |
EP3513777A1 (en) * | 2018-01-22 | 2019-07-24 | Ivoclar Vivadent AG | Method for the remineralisation of teeth |
EP3865112A1 (en) * | 2020-02-13 | 2021-08-18 | Xi'an University of Science and Technology | Method for making composition for enamel regeneration |
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