USOO7846411 B2

(12) United States Patent (10) Patent No.: US 7,846,411 B2 Tung (45) Date of Patent: Dec. 7, 2010

(54) CALCIUMPEROXYPHOSPHATES AND USE 5,902,568 A 5/1999 Ryles et al. THEREOF IN DENTAL COMPOSITIONS 5,967,155 A 10, 1999 Marcon 6,102,050 A 8, 2000 Marcon (75) Inventor: Ming Tung, Gaithersburg, MD (US) 6,221.341 B1 4/2001 Montgomery 6,290,935 B1 9, 2001 Masters et al. (73) Assignee: AR Foundation, Gaithersburg, MD 6,303,1046,419,905 B1 10/20017/2002 WinstonAlvarez Hernandezet al. (US) 6,447,757 B1 * 9/2002 Orlowski et al...... 424,53 (*) Notice: Subject to any disclaimer, the term of this 6,521,215 B2 2, 2003 Okay patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 1674 days. Zhou, et al., “Studies on regular changes of quality under different treatments between early and late cropping seasons in South-China (21) Appl. No.: 10/868,880 Indica rice'. Acta Agronomica Sinica, 2003 (vol. 29) (No. 2) 225 229. Abstract only. (Abstract from CAB Abstracts, http://www. (22) Filed: Jun. 17, 2004 cababstractsplus.org/google/abstract.asp?AcNo–20043045255, p. O O 1-2) Article: Mar. 2003.* (65) Prior Publication Data Nathanson, D., “Vital Tooth Bleaching: Sensitivity and Pulpal Con US 2005/0281759 A1 Dec. 22, 2005 siderations.” JADA, vol. 128 (1997). Attin, T. et al., “Susceptibility of Enamel Surfaces to Demineraliza tion after Application of Fluoridated Carbamide Gels.” (51) Int. Cl. Caries Res. Mar.-Apr.: Vol. 37(2 93-99 (2003 A6 IK 8/00 (2006.01) age SNSSE (2003). A6 IK 8/22 (2006.01) Such, J. E., “Peroxophosphoric & Peroxophosphates'. Mellor's A6 IK 8/24 (2006.01) Comprehensive Treatise on Inorganic and Theoretical Chemistry, A6 IK33/06 (2006.01) vol. VIII, Supp. III, Longmana, London (1971). A6 IK3I/66 (2006.01) Schumb, W.C. et al., “.” Reinhold Publishing A61O II/00 (2006.01) Corporation, New York, N.Y. (1955). (52) U.S. Cl...... 423/308; 423/299.423/309: International Search Report and Written Opinion in International 424/49; 424/53; 424/57 Application PCT/US05/13028 (Sep. 8, 2004). (58) Field of Classification Search ...... 423/308, * cited by examiner 423/309: 424/49, 53 See application file for complete search history. Primary Examiner Frederick Krass Assistant Examiner Lezah W. Roberts (56) References Cited (74) Attorney, Agent, or Firm Banner & Witcoff, LTD. U.S. PATENT DOCUMENTS (57) ABSTRACT 3,036,887 A 5, 1962 Beer et al. 3,085,856 A 4, 1963 Lake et al. peroxyphosphate compounds and dental composi 3,666,399 A * 5, 1972 Castrantas ...... 8/11 1 tions comprising these compounds that combine both whit 4,041,149 A 8, 1977 Gaffar et al...... 424,57 ening/stain removal of teeth with remineralization are dis 4,309.410 A 1, 1982 Gaffar closed. The calcium peroxyphosphate compounds are 5,037,639 A 8/1991 Tung capable of releasing, in an aqueous environment, whitening 5,624,906 A 4/1997 Vermeer and remineralization effective amounts of calcium ion, phos 5,648,064 A 7, 1997 Gaffar et al. phate ion, and active oxygen. Preferred compounds are cal 9: A "29. pe et al. cium peroxymonophosphate or calcium diperoxymonophos 5,776.437 A 7/1998 Burgess et al. phate compounds. These compounds may be used in humans 5,820,852 A 10/1998 Burgess et al. and other animals, including other mammals. 5,849,269 A 12/1998 Burgess et al. 5,851,514 A 12/1998 Hassan et al. 23 Claims, No Drawings US 7,846,411 B2 1. 2 CALCUMPEROXYPHOSPHATES AND USE phate, peroxide (carbamide), metal such as THEREOF IN DENTAL COMPOSITIONS calcium peroxide, and salts of perborate, persilicate, perphos phate, and percarbonate) and a silicate clay activator second FIELD OF THE INVENTION component, implanted with Fe ions. U.S. Pat. No. 6,521.215 describes compositions comprising a whitening agent com The present invention relates to calcium peroxyphosphate prising >10% peroxide (e.g., urea peroxide (carbamide) or compounds, methods for the preparation thereof, and the use hydrogen peroxide) and a soluble calcium phosphate rem thereof in dental compositions for whitening, mineralizing, ineralizing agent (e.g., monocalcium phosphate, anhydrous and/or fluoridating teeth. These dental compositions advan dicalcium phosphate, tricalcium phosphate, or tetracalcium tageously whiten teeth while simultaneously remineralizing 10 phosphate). U.S. Pat. No. 6,419,905 describes a dental them to prevent and/or repair weaknesses including dental bleaching composition comprising urea peroxide (carbam caries, exposed dentin tubules, and Voids resulting from stain ide), Xylitol, a potassium salt (e.g., potassium pyrophosphate removal. or potassium phosphate), and a fluoride Salt (e.g., Sodium monofluorophosphate). U.S. Pat. No. 6,221.341 describes BACKGROUND OF THE INVENTION 15 compositions for whitening teeth and/or having antimicrobial activity. These compositions comprise an acyl group (or func A tooth is comprised of an outer hard enamel protective tionally similar group) Source or precursor and a peroxide layer and an inner dentin layer. The outer enamel layer is Source or precursor (e.g., urea peroxide (carbamide), sodium naturally either opaque white or slightly off-white in color. It percarbonate, sodium perborate, calcium peroxide, magne is composed of apatite mineral crystals that are somewhat sium peroxide, or ), which react in an aque porous. Without being bound by theory, it is believed that the ous environment to generate a peroxyacid (e.g., peroxyacetic porous nature of the enamel layer permits staining agents and acid). The compositions have a pH>5.2 to avoid solubilizing discoloring Substances to permeate into the enamel and dis calcium in the tooth enamel or otherwise demineralizing the color a tooth. tooth. The peroxyacetic acid, which is unstable at this pH Dentin, the inner bony part of the tooth, contains thousands 25 range, is therefore generated in situ by the above-described of microscopic tubules. On the crown end of the tooth, the reaction. U.S. Pat. Nos. 6,102,050 and 5,967,155 describe dentin tubule ends are normally sealed by the enamel. These dental flosses that administer various compounds to inter dentin tubules pass all the way through the dentin from the proximal and subgingival dental areas for purposes Such as enamel-sealed crown end to the pulp chamber. On the root whitening, remineralization, and desensitization. In addition end of the tooth, these tubules are also sealed by a bony 30 to titanium dioxide as a whitening agent, other ingredients material called cementum. However, if either the enamel that may be incorporated into the floss include desensitizing sealed crown ends or the cementum-sealed root ends of the agents (e.g., calcium nitrate, , or dibasic dentin tubules become exposed, fluid easily travels through calcium phosphate), fluorides (e.g., calcium fluoride, sodium the tubules, causing hypersensitivity and/or pain. Undesir monofluorophosphate, aluminum mono- and di-fluorophos able exposure of dentin tubules may result from mechanical 35 phate), peroxide compounds (e.g., calcium peroxide and abrasion, caries, chemical treatment (e.g., whitening agents), Sodium carbonate peroxide), and abrading agents (e.g., cal and other factors. cium). The fluoride compounds are taught to be catalytically Plaques are a major cause of both dental decay and inflam active in remineralizing or precipitating calcium and phos matory periodontal disease. These plaques can contain 250 or phate compounds, found in Saliva, onto teeth. more separate microbial species. They use Sugars and other 40 U.S. Pat. No. 5,902,568 describes compositions compris fermentable carbohydrates to produce , which cause ing hydrogen peroxide or a precursor (e.g., Sodium perborate, demineralization of the tooth Surface, and polymers, with persilicate, percarbonate, perphosphate, calcium peroxide, or which the microbial organisms bind themselves to the tooth Sodium peroxide) and bicarbonate salt components that are Surface. In its initial stages, the formation of a carious lesion separated from one another to prevent their premature reac is not readily apparent. However, with prolonged and 45 tion prior to use. The compositions have a pH range of 9-12, repeated demineralization by plaque-created acids, a cavity based on the combined components, to increase whitening. will ultimately become visible. The hydrogen peroxide or precursor component may contain Peroxide has been used as an oxidizing agent for whitening phosphoric acid. The bicarbonate salt component may con teethas well as for the treatment of various forms of stomatitis tain a carbonate (e.g., calcium carbonate). In one or both of and gingivitis. See, e.g., U.S. Pat. No. 5,820,852. When 50 the peroxide or bicarbonate salt components, fluoride (e.g., applied for extended periods at high concentrations, oxidiz Stannous monofluorophosphate or sodium monofluorophos ing agents such as hydrogen peroxide and urea peroxide phate) may be present. U.S. Pat. No. 5,851,514 describes a (carbamide) have proven effective for removing extrinsic and whitening composition containing both a peroxide com intrinsic stains as well as for brightening the overall shade and pound (e.g., calcium peroxide, hydrogen peroxide, urea per color of teeth. Unfortunately, the bleaching process for 55 oxide (carbamide), glyceryl peroxide, or ) removing stains can simultaneously reduce the microhard and an abrasive compound (e.g., dicalcium phosphate com ness of enamel and dentin, cause post-treatment tooth sensi pounds such as dicalcium phosphate-dihydrate and anhy tivity, and/or increase tooth Susceptibility to demineraliza drous dicalcium phosphate or calcium pyrophosphate, pref tion. See Nathanson, D.; “Vital Tooth Bleaching. Sensitivity erably a high beta phase calcium pyrophosphate). U.S. Pat. and Pulpal Considerations. JADA, 128 (April 1997); and 60 No. 5,770,182 describes high viscosity sustained release den Attin, T. et al., “Susceptibility of Enamel Surfaces to Dem tal compositions for treating tooth Surfaces with whitening ineralization after Application of Fluoridated Carbamide Per agents (e.g., urea peroxide) or fluorides (e.g., Sodium fluo oxide Gels.” Caries Res. March-April; 37(2):93-9 (2003). ride). These components are included in a high viscosity Various dental products have been formulated to address matrix material (e.g., carboxypolymethylene) and are prefer plaque formation and tooth whitening. For 5, U.S. Pat. No. 65 ably applied using a dental tray. 6,290,935 describes an oral composition comprising a perox U.S. Pat. No. 5,698,182 describes a composition for whit ide first component (e.g., hydrogen peroxide, peroxydiphos ening teeth and inhibiting dental calculus comprising an anti US 7,846,411 B2 3 4 calculus phosphate salt and calcium peroxide. U.S. Pat. No. In another embodiment, the calcium peroxyphosphate 5,648,064 describes a two component dentifrice composi compound is a calcium peroxymonophosphate or calcium tion. The composition comprises a peroxygen compound first diperoxymonophosphate having Formula (I): component (e.g., hydrogen peroxide, peroxydiphosphate, urea peroxide (carbamide), calcium, sodium, strontium, and 5 CaH.(PHOS)(OH). (I) salts, and perphosphate salts) and a or a hydrate or a peroxyhydrate thereof, manganese coordination complex (e.g., manganese glucon wherein q is /2 (3y+z-X); x is from 0 to 8; y is an integer ate) second component to activate the peroxygen compound from 1 to 3; Z is from 0 to 1; x<3y; and PHOS is peroxymono and accelerate the release of active oxygen upon combining phosphate having the formula POs or diperoxymonophos with the first component. 10 phate having the formula PO, or U.S. Pat. No. 5,624,906 describes an oral hygiene compo wherein said calcium peroxyphosphate compound is a cal sition comprising a heteroatom containing alkyl aldonamide cium peroxydiphosphate or calcium diperoxydiphosphate compound (e.g., alkoxymethylgluconamide). compound having Formula (II): U.S. Pat. No. 6,303,104 describes a two-component com- 15 CaH,(DIPHOS) (II) position for whitening and remineralizing teeth. The first component contains an at least partially soluble calcium salt, or a hydrate or a peroxyhydrate thereof, which may be a soluble calcium salt (e.g., calcium chloride, wherein q is /2 (4-X); x is from 0 to 3; and DIPHOS is calcium bromide, calcium nitrate, calcium acetate, calcium peroxydiphosphate having the formula POs or diperoxy gluconate, calcium benzoate, calcium glycerophosphate, cal diphosphate having the formula P.O. cium formate, calcium fumarate, calcium lactate, calcium In yet another embodiment, the present invention is a tooth butyrate, calcium isobutyrate, calcium malate, calcium male whitening and remineralizing composition comprising any of ate, calcium propionate, or calcium Valerate) and optionally a the calcium peroxyphosphate compounds described above soluble non-calcium divalent metal salt or an anhydrous cal that releases, in an aqueous environment, calcium ions, phos cium phosphate or dicalcium phosphate abrasive. The second 25 phate ions, and active oxygen in combined effective amounts component comprises a soluble orthophosphate salt (e.g., or concentrations to achieve the dual purposes of whitening monopotassium phosphate) and optionally a fluoride Salt and remineralization. (e.g., sodium monofluorophosphate). No peroxide is men In another embodiment, the present invention is a method tioned. U.S. Pat. Nos. 5,849,269; 5,820,852; and 5,776,437 30 for whitening and remineralizing teeth. The method com describe oral compositions comprising a fluoride ion Source prises applying to the teeth a composition releases, in an (e.g., Sodium monofluorophosphate), pyrophospate (e.g., tet aqueous environment, calcium ions, orthophosphate ions, rasodium pyrophosphate, either anhydrous salt or hydrated), and active oxygen in combined tooth whitening and reminer and calcium peroxide. The oral compositions have a pH of alization effective amounts. 9.0-105. 35 In another embodiment, the present invention is a method for preparing any of the calcium peroxyphosphate com U.S. Pat. No. 5,330,746 describes a composition contain pounds described above. The method comprises reacting a ing either an anti-plaque agent (e.g., cetylpyridinium chlo peroxy acid with a calcium compound to produce the calcium ride) or an anti-hypersensitivity agent (e.g., a strontium salt). peroxyphosphate compound. In a preferred embodiment, the The agents are contained in a topically-applied varnish (e.g., calcium peroxyphosphate compound is a calcium peroxy a polymethacrylate) to provide their sustained release. The 40 monophosphate compound and the peroxy acid is peroxy composition may also contain an oxygenating agent (e.g., monophosphoric acid. In another preferred embodiment, the urea peroxide (carbamide), hydrogen peroxide, peroxybo calcium compound is selected from the group consisting of rate, or peroxydiphosphate). calcium carbonate, calcium bicarbonate, and calcium In view of these disclosures, there is an ongoing need in the 45 hydroxide. In another preferred embodiment, the reaction is art for compositions that can both whiten and remineralize carried out at a temperature from about -10°C. to about 20° teeth and fill voids associated with tooth decay and/or C. mechanical injury. Especially desired are compositions that These and other embodiments of the invention are dis comprise a whitening/stain removal agent (e.g., a source of cussed in the following detailed description. peroxide and/or active oxygen) with Sources of calcium ions and phosphate ions to remineralize teeth, thereby filling 50 Voids, adding strength, and reducing sensitivity. DETAILED DESCRIPTION OF THE INVENTION Calcium peroxyphosphates represent a class of com SUMMARY OF THE INVENTION pounds capable of releasing active oxygen, calcium ions, and 55 phosphate ions from a single molecule. Such compounds The present invention is directed to calcium peroxyphos provide both whitening and remineralizing components for phate compounds and methods for the preparation of these oral use. In particular, without being bound by theory, it is compounds. The present invention is also directed to dental believed that as active oxygen removes tooth stains and leaves compositions comprising calcium peroxyphosphate com behind avoid, the calcium and phosphate ions that are in close pounds and methods for using Such compositions that com 60 proximity and released from the same parent molecule pre bine tooth whitening/stain removal with remineralization to cipitate to form tooth mineral (i.e., calcium phosphate) and hinder and/or prevent degradation of the tooth structure, nor repair the Void by Such remineralization. Such calcium per mally associated with whitening. oxyphosphates should be provided in Sufficient concentration In one embodiment, therefore, the present invention is a in the oral environment to effect the desired whitening and calcium peroxyphosphate compound or a hydrate or a per 65 remineralizing of teeth without toxicity or other undesirable oxyhydrate thereof. In another embodiment, the compound effects. Such compositions may additionally containa Source further comprises hydrogen ions and/or hydroxide ions. of fluoride ions to enhance further remineralization. In this US 7,846,411 B2 5 6 manner, compositions of the present invention advanta J. E. Such, “Peroxophosphoric Acid & Peroxophosphates' in geously achieve both whitening and remineralization of teeth. MELLOR'S COMPREHENSIVE TREATISE ON INORGANIC AND THEORETI Exemplary calcium peroxyphosphate compounds of the CAL CHEMISTRY, Vol. VIII (Supp III), Longmana, London present invention include calcium peroxyphosphates, which (1971). These methods include (i) the hydrolysis of peroxy embrace calcium peroxymonophosphates, calcium peroxy diphosphate in a strong acid solution, (ii) the reaction of diphosphates, calciumperoxytriphosphates, etc. Other exem HPO, with aqueous hydrogen peroxide, and (iii) the anodic plary compounds of the present invention also include cal oxidation of PO, or P.O.'. cium diperoxyphosphates, which embrace calcium Diperoxyphosphoric acid, HPO, a starting material in the diperoxymonophosphates, calcium diperoxydiphosphates, preparation of calcium diperoxymonophosphate, is less well calcium diperoxytriphosphates, etc. Overall, compounds of 10 known than HPOs. However, this peroxy acid may be pre the present invention include the calcium salts of phosphate pared, for example, in a manner similar to that for preparation monomers, dimers, and polymers, provided that at least one of HPOs, namely by the action of hydrogen peroxide on of the phosphate structural units is oxidized to a peroxyphos either POs or pyrophosphoryl chloride (POCl). In general, phate group (e.g., POs), comprising one peroxy substituent, the use of a peroxygenated phosphoric acid starting material or to a diperoxyphosphate group (e.g., PO), comprising 15 allows for the preparation of various types of calcium peroxy two peroxy Substituents. These peroxyphosphate and diper phosphate compounds described herein. oxyphosphate groups may also be in their respective hydro Preferably, peroxymonophosphoric acid is prepared gen or dihydrogen forms. Thus, calcium peroxyphosphates according to the above-noted reaction (1) in a -immis and calcium diperoxyphosphates include calcium com cible liquid medium, Such as carbon tetrachloride, that is inert pounds having hydrogen peroxyphosphate groups (HPOs). to both the reactants and the reaction product under the con dihydrogen peroxyphosphate (H2POs), hydrogen diper ditions of use. The resulting peroxymonophosphoric acid oxyphosphate groups (HPO), and/or dihydrogen diper may thereafter be separated from the organic diluent phase by, oxyphosphate groups (HPO'). Furthermore, the calcium for example, decantation or equivalent methods. The recov peroxyphosphate and calcium diperoxyphosphate com ered peroxymonophosphoric acid is then reacted with a cal pounds of the present invention may also include hydroxyl 25 cium compound, preferably selected from the group consist (OH) groups that, in addition to the negatively charged per ing of calcium carbonate, calcium bicarbonate, calcium oxyphosphate and peroxydiphosphate groups (whether or not hydroxide, and mixtures thereof. The calcium compound in their hydrogen forms) must be charge-balanced by the may be added as a solid or a solution (e.g., an aqueous solu positive oxidation state of calcium. tion). The reaction between the peroxy acid and the calcium Other exemplary compounds of the present invention 30 compound is preferably carried out at low temperature, pref include calcium peroxymonophosphates, calcium peroxy erably from about -10°C. to about 20°C., to avoid excessive diphosphates, calcium diperoxymonophosphates, and cal loss of active oxygen through decomposition. The calcium cium diperoxydiphosphates. Preferred are calcium peroxy peroxymonophosphates generated from this reaction typi monophosphate or calcium diperoxymonophosphate cally precipitate rapidly upon mixing of the reactants. When compounds having Formula (I): 35 a solid calcium carbonate reactant is used, the rate of disso lution of this compound and the rate of evaporation of carbon CaH,(PHOS)(OH), (I) dioxide both influence the rate of product precipitation. wherein q is /2 (3y+z-X); x is from 0 to 8; y is an integer The solid product can be recovered from the liquid medium from 1 to 3; Z is from 0 to 1; x<3y; and PHOS is peroxymono described above by separation methods that include, but are phosphate having the formula POs or diperoxymonophos 40 not limited to, evaporation, filtration, and freeze-drying. phate having the formula PO, or calcium peroxydiphosphate Product purity can be increased by recrystallization or frac or calcium diperoxydiphosphate compounds having Formula tional crystallization, with either of these methods preferably (II): employing water or a mixture of water and a water-soluble CaH,(DIPHOS) (II) organic Solvent. Preferred organic solvents having some 45 water solubility and that are appropriate for this purpose wherein q is /2 (4-X); x is from 0 to 3; and DIPHOS is include Saturated aliphatic ketones (e.g., acetone) and ali peroxydiphosphate having the formula POs or diperoxy phatic alcohols (e.g., methanol, ethanol, and glycerol). The diphosphate having the formula P.O. various calcium peroxyphosphate compounds described Exemplary peroxymonophosphates of the above-defined herein (e.g., calcium peroxydiphosphates, and calcium diper Formula (I) include CaFIPOs, Ca(HPOs), Ca(POs), CaFI 50 oxydiphosphates) may be prepared following analogous pro (POs), and Cas (POs).OH. Exemplary peroxydiphosphates cedures, using the appropriate starting peroxy acid. of the above-defined Formula (II) include CaFI(POs) and While the above-noted procedures may generate a single Ca(POs). calcium peroxyphosphate compound, generally a mixture of In one synthesis route in preparing calcium peroxymono compounds is obtained. For example, a mixture of the per phosphate compounds of the present invention, an initial step 55 oxygenated forms Ca(H2POs) and CaHPOs may be obtained involves the preparation of peroxymonophosphoric acid. The in the preparation of calcium peroxymonophosphates. The synthesis of peroxymonophosphoric acid may be carried out procedures described above may also yield non-peroxygen as described, for example, by Schmidlin and Massini (Ber. ated calcium phosphates such as mono- and di-calcium phos 43, 1910, page 1162) according to the reaction phates. Preferably, however, the peroxygenated forms will be POs-2H2O2+HO->2HPOs (1) 60 present, in either the impure or purified reaction products described above, in an amount of at least about 10% by However, due to the inherent safety risk of the above highly weight, and more preferably in an amount from about 10% to exothermic reaction (1), improvements in this basic synthesis about 90% by weight, relative to the total amount of peroxy route to peroxymonophosphoric acid were developed and are genated and non-peroxygenated calcium phosphates. Mix described, for example, in Can. J. Chem. 81:156-160 (2003) 65 tures of calcium peroxyphosphates and calcium phosphates and U.S. Pat. Nos. 3,036,887 and 3,085,856. Alternative may be characterized according to their overall relative methods for preparing this acid are described, for example, by amounts of calcium, phosphate, and peroxide and/or accord US 7,846,411 B2 7 8 ing to other analytically identifiable criteria, in order to help remineralizing the tooth, strengthening it, inhibiting its assess the types and relative amounts of the calcium phos decay, and/or attenuating its sensitivity. Additionally, rem phate species present. In case a mixture of various calcium ineralization, effected by the calcium and phosphate sources, peroxyphosphates or a mixture of calcium peroxyphosphates can decrease tooth porosity resulting from the stain removal and calcium phosphates is obtained, the molar average cal process. This in turn may prevent or slow the re-formation of cium to phosphate molar ratio (Ca/Pratio) of the various these a new stain within the Void and also prolong the whitening calcium compounds ranges preferably from about 0.25 to effect. Because the deposited calcium orthophosphate is itself about 1.67, depending on the relative amounts of calcium white, remineralization may further enhance whitening. Also, compounds and peroxymonophosphoric acid used in the the precipitation of calcium orthophosphate onto and/or into reaction described above. Importantly, both the peroxygen 10 the tooth surface can close pores in enamel and plug dentin ated and non-peroxygenated calcium phosphates, obtained tubules (e.g., at root ends) to reduce or eliminate post-treat from the synthesis procedures described above, may also be ment tooth sensitivity. The accompanying reduced porosity incorporated into dental compositions or restoratives as and/or plugging of dentin tubules can also generally reduce described herein without the need to segregate the peroxy tooth surface permeability and consequently minimize the genated forms. It is also possible to employ precursors of 15 undesired effect of peroxide diffusion into the tooth pulp. calcium peroxyphosphates (e.g., components comprising Associated with the present invention is the determination Sources of calcium and peroxyphosphate that react to form that Sufficiently high concentrations of calcium ions and the desired calcium peroxyphosphates) in these restorative phosphate ions are particularly effective for tooth remineral compositions, for example in separate compositions that are ization as a means to compensate for the reduction in tooth mixed before or during use. In this manner, the calcium per Surface integrity that may result from whitening or bleaching oxyphosphate compound may be generated in situ within, with active oxygen, generated according to above-noted reac and/or on the surfaces of the teeth. tions (2) and/or (3). Any of the calcium peroxyphosphates and calcium diper Compounds of the present invention typically decompose oxyphosphates described above may be in their respective in aqueous media (e.g., upon exposure to saliva) to provide hydrated or peroxyhydrated forms without adversely affect 25 tooth whitening and remineralizing at combined effective ing their ability to release calcium ions, phosphate ions, and amounts or concentrations of calcium ions, phosphate ions, peroxide. As is known in the art, hydrated or peroxyhydrated and active oxygen. By “whitening and remineralizing at com forms refer to the parent molecules having one or more water bined effective amounts' is meant that the amounts of cal molecules or hydrogen peroxide molecules, respectively, in cium ion, phosphate ion, and active oxygen together are Suf their structures. Thus, as an example, a hydrated form of 30 ficient to whiten teeth and compensate, through precipitation tricalcium peroxymonophosphate may be represented as Cas (i.e., remineralization) of calcium phosphate, for Some or all (POs).mH2O, indicating the association of “m' water mol of the void that typically accompanies the whitening or stain ecules per molecule of calcium peroxymonophosphate. Like removal process. The remineralization that is effected by wise, a peroxyhydrated form of tricalcium compounds of the present invention also refers to the peroxymonophosphate may be represented as Ca(POs). 35 strengthening of pre-existing tooth weaknesses that are not nH2O, indicating the association of “n” hydrogen peroxide associated with contemporaneous whitening or stain molecules per molecule of calcium peroxymonophosphate. removal. Typically, “m' is an integer from 0 to 5. Preferably, when used in dental compositions, compounds Advantageously, when used in dental compositions the of the present invention are present, on an anhydrous basis, in calcium peroxyphosphate compounds described above can 40 the composition in an amount of at least about 1% and pref readily provide both tooth whitening and remineralizing erably from about 3% to about 32% by weight, to provide activity, as they comprise both peroxyphosphate ions and generally effective amounts of calcium ions, phosphate ions, calcium ions in a single molecule of an ionic salt. Thus, these and active oxygen to effect the dual purposes of tooth whit compounds are capable of releasing calcium ions, phosphate ening and remineralization discussed above. Also additional ions, and active oxygen simultaneously, in close proximity, 45 Sources of peroxide, calcium salts, and phosphate salts can be and in amounts sufficient and effective for these purposes. By included. In a preferred embodiment, dental compositions of “active oxygen is meant atomic oxygen (O) that may be the present invention further comprise a fluoride ion source, generated by the decomposition or hydrolysis of peroxyphos believed to promote or catalyze precipitation (remineraliza phate ions. As illustrated below, peroxymonophosphate ion, tion) of the calcium ions and phosphate ions released from for example, may decompose to yield phosphate and active 50 compounds of the present invention. The fluoride ion source oxygen according to the following reaction (2): may be a fluoride compound including, but not limited to, Sodium fluoride, potassium fluoride, Zinc fluoride, Stannous PO ->PO +O (2) fluoride, Zinc ammonium fluoride, Sodium monofluorophos Alternatively, and generally to a lesser extent, peroxymono phate, sodium hexafluorosilicate, potassium monofluoro phosphate ion may react with water (i.e., hydrolyze) to form 55 phosphate, laurylamine hydrofluoride, diethylaminoethyloc hydrogen peroxide, which in turn degrades to form active toylamide hydrofluoride, 1-ethanol-2-hexadecylimidazoline oxygen, as illustrated in the following reactions (3): dihydrofluoride, dodecyltrimethylammonium fluoride, tetra ethylammonium fluoride, didecyldimethylammonium fluo POs +HO->PO +HO, ride, cetylpyridinium fluoride, dilaurylmorpholinium fluo 60 ride, N-carboxymethyl-N-dodecyldiethylammonium HO-->HO+O (3) fluoride, sarcosine Stannous fluoride, glycine potassium fluo Without being bound by theory, it is believed that, as active ride, glycine hydrofluoride, Sodium monofluorophosphate oxygen is generated according to the reactions (2) and (3) and mixtures thereof. Preferred sources of fluoride ion above, a free perhydroxyl radical (HOO.) forms for brief include Sodium fluoride, potassium fluoride, Sodium monof periods of time sufficient to oxidize dental stains. At the same 65 luorophosphate, and Sodium hexafluorosilicate. If used, the time, calcium ions and phosphate ions deposit or precipitate, fluoride source is present in the composition in an amount, as calcium orthophosphate, in the void left behind, thereby based on fluorine, from about 10 ppm to about 0.5% by US 7,846,411 B2 10 weight. The carrier and optionally additives, described below, sition having an alkaline pH and the second composition may are generally present in a combined amount from about 10% comprise a compound of the present invention. In this to about 95% by weight. embodiment, an alkaline pH of the first composition refers to The decomposition of peroxymonophosphates according a pH value preferably above 8, and more preferably from to reaction (2) above, which promotes the effects of tooth about 8 to about 12, and even more preferably from about 9 to whitening and remineralization when used in dental compo about 11. The second composition comprising the calcium sitions or restoratives, increases in rate with increasing pH, peroxyphosphate preferably has a neutral pH or a slightly until a maximum decomposition rate is achieved in a pH acidic pH value (e.g., from about 3 to about 7). range of 12-13. In order to inhibit decomposition prior to use, Alternatively, the first composition may comprise an acti however, these compounds are preferably stabilized by main 10 vator (e.g., a transition metalion such as Zn") to catalyze or taining them either at a neutral pH or at a slightly acidic pH accelerate the decomposition of calcium peroxyphosphate and optionally in the presence of a stabilizer. While low pH upon contact therewith prior to or during use. The first com favors the hydrolysis of peroxyphosphate according to reac position may also optionally comprise a soluble calcium salt tion (3) above, it is believed that the extent of hydrolysis to provide an additional source of calcium. Soluble calcium becomes appreciable only under strongly acidic conditions, 15 salts include, but are not limited to, calcium sulfate (e.g., which are easily avoided. plaster of paris), calcium chloride, calcium nitrate, calcium Stabilizers for use in dental compositions comprising com acetate, calcium bromide, calcium gluconate, calcium ben pounds of the present invention include chelating agents that Zoate, calcium glycerophosphate, calcium formate, calcium can scavenge and inactivate trace metals that could otherwise fumarate, calcium lactate, calcium butyrate, calcium isobu catalyze the decomposition process. Suitable chelating tyrate, calcium malate, calcium propionate, and calcium val agents are described, for example, in U.S. Pat. No. 6,221.341. erate. Preferred soluble calcium salts include calcium chlo Metals, such as iron, manganese, and copper, and their oxides ride, calcium nitrate, calcium sulfate, and calcium acetate. are known in the art to promote the degradation of peroxide Calcium orthophosphates include, but are not limited to, through Fenton-type reactions. This particular degradation amorphous calcium phosphate (ACP), amorphous calcium mechanism is undesirable in that the hydroxyl free radical 25 phosphate fluoride (ACPF), and amorphous calcium carbon (HO.) is created and is not as effective as active oxygen ate phosphate (ACCP), which are described, for example, in generated according to reactions (2) and (3) above, in attack U.S. Pat. No. 5,037,639. ing chromogens that stain the teeth. Upon increasing the pH of the second composition and/or Stabilizers therefore include, but are not limited to, phar activating it by combining or mixing it with the first pH maceutically acceptable chelating agents such as the various 30 control composition having an alkaline pH and/or an activa amino carboxylate compounds that have the capacity to form tor, not only is active oxygen made available for whitening, metal-ligand complexes with one or more transition metal but also the released calcium ions and phosphate ions are ions in Solution. Such amino carboxylates include ethylene precipitated as calcium phosphate for remineralization. diaminetetraacetic acid (EDTA) and diethyltriaminepen Another means of realizing the goals of long-term storage of taacetic (DTPA), 1.2-bis(2-aminophenoxy)ethane-N,N,N', 35 compounds of the present invention and their activation upon N-tetraacetic acid (BAPTA), ethylene glycol-bis(2- use may be through the provision of a layered composition, aminoethyl)-N.N.N',N'-tetraacetic acid (EGTA), and other with separate layers (e.g., gel layers) being maintained under amino carboxylate compounds having one or multiple car separate conditions and/or having separate compositions as boxylate groups. Any derivative salt form of these amino described above. A further alternative method of stabilizing a carboxylate chelating agents, for example the disodium salt 40 calcium peroxyphosphate compound prior to use is to main form, may be also used, provided that some capacity remains tain it as a solid (either crystalline or amorphous) or a solid for the chelating agent to complex with free transition metal Suspended in an inert carrier, such as a polyol. The Solid form ions present. Forms of these chelating agents other than salt can then be either dissolved in a composition comprising an forms are also effective and include the various ester, anhy aqueous carrier at the point of use or applied directed to the dride, and halogenated forms of these compounds. A pre 45 surfaces of the teeth. Yet another alternative for stabilization ferred Stabilizer is EDTA. involves lyophilization of the calcium peroxymonophos As stated, calcium peroxyphosphate compounds of the phate, coupled with reconstitution prior to use. present invention may be stabilized under neutral to slightly In the kit embodiment described previously, comprising acidic pH conditions. When used in dental compositions, two compositions, these compositions may be mixed or com these compounds can be conveniently decomposed at the 50 bined prior to application to the tooth surface, such that the time of use to effect the beneficial release of (i) active oxygen combination/application steps are performed sequentially. In for tooth whitening and (ii) calcium phosphate for tooth rem a preferred method of sequential application, for example, the ineralization. Peroxyphosphate decomposition according to compositions may be mixed and thereafter applied to the teeth reaction (2) above is achieved, for example, by increasing pH in a tray and/or mouth guard. Alternatively, the compositions or introducing activators such as catalytic amounts of trace 55 may be mixed on the teeth at the time of application (i.e., use) metal ions into the calcium peroxyphosphate composition. A to the teeth in a simultaneous manner. Thus, simultaneous further advantage associated with effecting decomposition by mixing and application includes methods wherein the first increasing pH is the simultaneous promotion, at elevated pH, composition is applied onto the Surface of the teeth (e.g., of the precipitation of calcium phosphate as tooth mineral. As applying a solution with a cotton tip) and the second compo described previously, calcium phosphate is a decomposition 60 sition is then applied and combined with the applied first product of calcium peroxymonophosphates. composition. Based on the above, a kit comprising two separate compo Simultaneous mixing and application represents a pre sitions represents a possible vehicle for employing com ferred method of teeth whitening and remineralization, par pounds of the present invention, allowing for long-term Stor ticularly when a first composition that comprises a soluble age of these compounds prior to use and activation of these 65 calcium salt is first applied to the surface of the teeth, allowing compounds at the point of use. In such an embodiment, for the applied calcium to diffuse into the teeth. After application example, the first composition may be a pH-control compo of the first composition, a second composition comprising a US 7,846,411 B2 11 12 compound of the present invention (i.e., a calcium peroxy cleaning abrasive slurry, a gel, a professional gel, a varnish, a phosphate) is thereafter applied to the teeth. In this manner, self-adhesive strip, a cream, a mouthwash, a pre- or post both within the teeth as well as on the surface of the teeth, brushing dental rinse, a dental spray, a dental cleanser, a active oxygen (obtained from the second composition) is dental floss, a dental cream, a floss product, a chewing generated for whitening or bleaching and the calcium ions gum, a lozenge, a tablet, a powder, a pumice , a poly (obtained from both compositions) and phosphate ions (ob meric compound, a carbonated Solution, an edible food prod tained from the second composition) are activated for precipi uct, and the like. Preferred forms of the compositions include tation or remineralization as calcium phosphate tooth min toothpastes, gels, professional gels, varnishes, self-adhesive eral. Preferably, the first composition is an . strips, chewing gums, powders, pumice flour, dental rinses, In another preferred embodiment, the second composition is 10 carbonated solutions, or edible food products. These and in a gel form and is applied using a tray. In other embodi other forms are known in the art and described in detail, for ments, the calcium peroxyphosphate of the second composi example, in U.S. Pat. Nos. 6,303,104 and 5,624,906. Other tion may either be suspended as a solid in a non-aqueous preferred carrier forms for Suspending calcium peroxymono medium or otherwise dissolved therein. In yet other embodi phosphate compounds include gels, chewing gums, powders, ments, the second composition may comprise a peroxyphos 15 varnishes, polymers, mouth rinses, carbonated solutions, and phate and optionally a non-peroxygenated phosphate. Such tooth dentifrices. Varnishes have been used for sustained that the soluble calcium salt of the first composition reacts release tooth fluoridation and are applicable for delivery of with the peroxyphosphate of the second composition togen the whitening and remineralization compositions of the erate a calcium peroxyphosphate compound in situ. Without present invention as well. Tooth varnishes are generally com being bound by theory, it is believed that the calcium peroxy pounds that are topically applied to teeth with a special brush, monophosphate compounds of the present invention, whether cotton, or tray and harden over a short time by contact with Supplied in a single composition, in a kit comprising two or saliva, air, or both. Varnishes typically comprise a carrier of a more compositions, or in the form of precursor components natural polymer (e.g., colophony or pine resin) or synthetic that are reacted at the point of use, can cause calcium ortho polymer (e.g., a polyurethane based resin or a polymethacry phosphate (or tooth mineral) to precipitate, both on the Sur 25 late based resin Such as polymethyl methacrylate) in alco faces of the dental tissues as well as in their interiors. holic solution. Whether a single composition, or, as described above, two Professional products, such as professional gels, are gen or more separate compositions are employed, the pH of the erally intended for application under professional Supervision compositions of the present invention may be maintained or and typically contain higher amounts of active ingredients controlled using any pH-control agents and buffer systems 30 (e.g., a calcium peroxyphosphate compound) or other whit known in the art to be suitable for oral compositions. For ening agents than those products designed for general con example, compositions for oral use may be adjusted and Sumer use. Professional gels are often applied using, for maintained at an alkaline pH, preferably at a pH from about 8 example, a tray to expose only dental Surfaces and not the to about 12, using hydroxide compounds (e.g., sodium gums or soft tissues to the compositions. This manner of hydroxide) and/or carbonate compounds (e.g., Sodium car 35 application is described, for example, in U.S. Pat. No. 6,221, bonate). Likewise, compositions may be adjusted and main 341 along with various thickeners that are advantageously tained for stabilization purposes at approximately neutral or used in compositions for Such applications. A preferred mode slightly acidic conditions, preferably at a pH from about 3 to of application, when a gel or paste is used as a carrier form about 7 using, for example, inorganic or organic acids includ (whether or not it is considered a professional product), ing phosphoric acid, benzoic acid, and/or citric acid. Alterna 40 involves the use of such a tray or mouth guard to restrict the tively, dissolved carbon dioxide, for example in a carbonated contact of the compositions to the teeth. In this type of appli Solution under pressure, may also function as a pH-control cation and also generally, it may be desirable to apply a agent as well as a carrier for calcium peroxymonophosphate composition comprising a compound of the present invention compounds. and one or more additional compositions in one or more Compositions comprising compounds of the present 45 repetitive steps in a predetermined order (e.g., application of invention may further comprise any carrier (e.g., a polyol) a composition comprising a readily available calcium ion known in the art and/or discussed hereinafter. In a preferred Source or a phosphate ion Source, followed by application of embodiment, an aqueous polyol carrier in the form of a gel is a composition comprising a calcium peroxyphosphate com used. Such carriers and carrier forms are preferred, for pound). In this manner and as described above, compounds of example, for providing a calcium peroxymonophosphate gel 50 the present invention may be stabilized, for example, by long Solution. In general, carriers should be substantially toxico term storage at neutral or slightly acidic pH and may there logically benign. Such carriers include polyols which after be activated at the time of use by mixing with a separate include, but are not limited to, Sorbitol, propylene glycol, composition at alkaline pH. As stated previously, another glycerol, lactitol, Xylitol, polypropylene glycols, polyethyl method of stabilizing the calcium peroxyphosphate com ene glycols, and hydrogenated corn syrup. Oil-based carriers 55 pounds prior to use is to maintain them as a solid (either may also be used, especially when combined with a surfactant crystalline or amorphous) or a Solid Suspended in an inert capable of emulsifying compositions upon contact with carrier, Such as a polyol. Otherwise, the compounds may also water. Such oils include vegetable oils, mineral oils, and be dissolved or Suspended in a nonaqueous carrier Such as essential oils, in addition to their higher molecular weight glycerol. Dissolved or Suspended compounds of the present counterpart and esters. Essential oils have antiseptic 60 invention and their respective carriers can be applied directly and antimicrobial effects, and include thymol, menthol, euca onto the teeth. Solid forms of these compounds may be dis lyptol, and eugenol. Aqueous, alcohol (e.g., ethanol), and Solved in an aqueous or nonaqueous carrier media at the point nonaqueous polyol (e.g., glycerol) carriers may also be used ofuse, just prior to application. in combination. The carrier may be in the form of a paste or gel, where the The carrier used in compositions of the present invention 65 carrier is used in a multi-layer delivery system with two or may be in any conventional form, including, but not limited more distinct compositions contained in separate layers. In to, a toothpaste, a prophylactic paste, a tooth polish, a tooth this manner, it is also possible to obtain a striped product, US 7,846,411 B2 13 14 wherein colorants of contrasting colors are incorporated in EXAMPLE 1. the distinct layer compositions, with the colorants being phar macologically and physiologically non-toxic in the amounts Preparation of Calcium Peroxymonophoshpate used. Colorants used for this particular embodiment include both pigments and dyes, as described, for example, in U.S. 5 A 9.9 gram sample of phosphorus pentoxide powder was Pat. No. 6,290,935. The use of colorants for distinct compo Suspended in 68 g of carbon tetrachloride and cooled in an ice sition layers is not only aesthetically pleasing in many cases bath under vigorous stirring. To this suspension, 5.3 ml of but also, where it is desired to mix the compositions thor 70% aqueous hydrogen peroxide was added dropwise at rate oughly before use, provides a visual indication of how uni of 3 drops per second. The mixture was stirred for 3 hrs after formly mixed the compositions are. 10 the hydrogen peroxide addition. The mixture over time With respect to the various carrier forms described above, formed separate organic and aqueous peroxymonophospho a plurality of conventional packaging methods and dispens ric acid layers. Five milliliters of the acid layer was obtained ing containers may be employed and are described, for by decanting. To half of this inorganic concentrated peroxy example, in U.S. Pat. No. 6,303,104. Preferred dispensing monophosphoric acid, calcium carbonate slurry was added containers include tubes, pumps, Syringes, and other contain 15 slowly in an ice bath and under stirring, until the pH of the ers Suitable for dispensing a paste, gel, liquid or slurry. solution was 1.7. This solution was then lyophilized. The Another preferred dispensing system is provided in U.S. Pat. resulting solid comprised calcium peroxymonophosphates No. 5,902,568, which discloses a pump dispenser having with a Ca/P ratio of 0.28 and possibly additionally contained compartments for separately storing components and a means non-peroxygenated calcium phosphate compounds. The pre for combining the components as unmixed streams prior to pared calcium peroxymonophosphate had a distinct X-ray use. In another embodiment, the dispensing container may powder diffraction pattern, different from that corresponding separate the carrier from the active ingredients and may addi to calcium phosphate. The d-space for 010 was in the range of tionally combine these shortly before use. 12.5 to 12.9A, compared to 11.7 A corresponding to calcium Regardless of the carrier, the compositions may contain phosphate. The calcium peroxymonophosphates also exhib one or more conventional additives described, for example, in 25 ited a peroxide IR peak of 785 cm', which was absent from U.S. Pat. Nos. 6,303,104; 6,290,935; 6,221,341; 5,902,568; the corresponding calcium phosphates. and 5,624,906. Such additives include, but are not limited to, Surfactants (e.g., anionic, cationic, nonionic, and Zwitterionic EXAMPLE 2 Surfactants), coSurfactants or cleansing agents, soaps, ing agents, Sweetening agents, aroma agents, astringents, 30 Calcium carbonate slurry was added slowly, under stirring, anti-plaque agents, anti-calculus agents, anti-bacterial agents to the other half of the inorganic concentrated peroxymono (e.g., cetyl pyridinium chloride), preservatives, sudsing phosphoric acid layer as described in the Example 1, until the agents, humectants, thickening agents (including inorganic pH of solution was 3.5. This solution was then lyophilized. thickeners such as hydrated silica), binding agents or cothick The solid comprised calcium peroxymonophosphates with a eners, coloring or other whitening agents, abrasive polishing 35 Ca/P ratio of 0.5 and possibly additionally contained non agents, alcohols, buffering agents, alkali metal halide salts, peroxygenated calcium phosphate compounds such as dical desensitizing agents, healing agents, other preventative caries cium phosphate dihydrate and monocalcium phosphate agents, vitamins, amino acids, proteins, opacifiers, antibiot monohydrate. The prepared calcium peroxymonophosphate ics, anti-enzymes, enzymes, other oxidizing agents, antioxi has a distinct x-ray powder diffraction pattern different from dants, and water. When used, these additives are present in 40 that corresponding to calcium phosphate. The d-space for 010 amounts that do not substantially adversely affect the desired was 12 A, compared to 11.7 A for calcium phosphate. The stain removal and remineralizing capabilities of compounds calcium peroxymonophosphates also exhibited a peroxide IR of the present invention as discussed above. The particular peak of 785 cm', which was absent from the corresponding amounts of the additives used will depend upon the type and simple calcium phosphates. form of the carrier. 45 All references cited in this specification, including without limitation, all papers, publications, patents, patent applica EXAMPLE 3 tions, presentations, texts, reports, manuscripts, brochures, Alternate Preparation of Calcium books, journal articles, periodicals, and the like, are hereby Peroxymonophosphate incorporated by reference into this specification in their 50 entireties. The discussion of the references herein is intended merely to Summarize the assertions made by their authors and Suspend 2.22 grams of calcium hydroxide in 50 ml of no admission is made that any reference constitutes prior art. water. To this Suspension, slowly add 2.28 grams of concen Applicant reserves the right to challenge the accuracy and trated peroxymonophosphoric acid, to be prepared as pertinence of the cited references. In view of the above, it will 55 described in Example 1, in order to precipitate calcium per be seen that several advantages of the invention are achieved oxymonophosphate. Filter the resulting slurry and wash it and other advantageous results obtained. with distilled water. The solid to be recovered is a basic It is intended that all matter contained in this application, calcium peroxymonophosphate, possibly also containing one including all theoretical mechanisms and/or modes of inter or more calcium phosphate compounds. action described above, are illustrative only and not limiting 60 in any way the scope of the present invention or the appended EXAMPLE 4 claims. The following examples are set forth as representative of Preparation of Calcium Peroxydiphosphate the present invention. These examples are not to be construed as limiting the scope of the invention as these and other 65 Dissolve 3.46 grams of potassium peroxydiphosphate in equivalent embodiments will be apparent in view of the 10 ml of water. To this solution, add 2.94 grams of calcium present disclosure and appended claims. chloride dihydrate under stirring, in order to precipitate cal US 7,846,411 B2 15 16 cium peroxydiphosphate. Filter the resulting slurry and wash 11. A tooth whitening an remineralizing kit comprising: it with distilled water. The solid to be recovered contains (a) a pH-control composition having an alkaline pH, and calcium peroxydiphosphate. (b) the composition of claim 4 having a neutral or acidic pH. EXAMPLE 5 5 12. The kit of claim 11, wherein said pH-control compo sition comprises a soluble calcium salt. Preparation of Calcium Diperoxymonophosphate 13. The kit of claim 11, wherein said pH-control compo sition is an aqueous solution. Prepare diperoxymonophosphoric acid by the action of 14. A method for whitening and remineralizing teeth, said hydrogen peroxide on pyrophosphoryl chloride. Maintain 10 method comprising applying to said teetha composition com this inorganic diperoxymonophosphoric acid in an ice bath prising the compound of claim 1 or a hydrate or a peroxyhy under stirring and slowly add a calcium carbonate slurry until drate thereof that releases, in an aqueous environment, cal the pH of the resulting solution is 3.3 and calcium diperoxy cium ions, phosphate ions, and active oxygen in a combined monophosphate precipitates. Filter the resulting slurry and whitening and remineralizing effective amount. then wash it with distilled water. The solid to be recovered 15 15. The method of claim 14, wherein said composition is contains calcium diperoxymonophosphates and possibly also applied using a tray. contains one or more calcium phosphate compounds. 16. A method for whitening and remineralizing teeth, said What is claimed is: method comprising contacting said teeth with a dental restor 1. A calcium peroxyphosphate compound or a hydrate or a ative comprising: peroxyhydrate thereof, wherein said calcium peroxyphos (a) the calcium peroxyphosphate compound of claim 1 or a phate compound is a calcium peroxymonophosphate or a hydrate or a peroxyhydrate thereof, and calcium diperoxymonophosphate compound in Solid form (b) a carrier for Suspending said calcium peroxyphosphate and having Formula (I): compound, said hydrate or said peroxyhydrate thereof, CaH,(PHOS)(OH), (I) wherein said carrier is selected from the group consist 25 ing of agel, a chewing gum, a powder, a varnish, a mouth or a hydrate or a peroxyhydrate thereof, rinse, a nonaqueous medium, and a carbonated solution, wherein q is /2 (3y+z-X); x is from 0 to 8; y is an integer wherein, during said contacting, active oxygen is released from 1 to 3; Z is from 0 to 1; x<3y; and PHOS is peroxy to whiten said teeth and calcium phosphate is precipi monophosphate having the formula POs or diperoxy tated to remineralize said teeth. monophosphate having the formula PO. 30 17. A method for preparing the calcium peroxyphosphate 2. The calcium peroxyphosphate compound of claim 1, compound of claim 1 or a hydrate or a peroxyhydrate thereof, wherein said compound is a calcium peroxymonophosphate said method comprising: compound. (a) reacting a peroxy acid with a calcium compound to 3. The compound of claim 2, wherein said compound is yield said calcium peroxyphosphate compound. selected from the group consisting of CaFIPOs, Ca(H2POs), 35 18. The method of claim 17, wherein said calcium peroxy Ca(POs), CaH(POs), Cas(POs).OH, and hydrates and phosphate compound is calcium peroxymonophosphate and peroxyhydrates thereof. said peroxy acid is peroxymonophosphoric acid. 4. A tooth whitening and remineralizing composition com 19. The method of claim 17, wherein said calcium com prising the calcium peroxyphosphate compound of claim 1 or pound is selected from the group consisting of calcium car a hydrate or a peroxyhydrate thereofthat releases, in an aque 40 bonate, calcium bicarbonate, and calcium hydroxide. ous environment, calcium ions, phosphate ions, and active 20. The method of claim 17, wherein said reacting step (a) oxygen in a combined tooth whitening and remineralizing is carried out at a temperature from about -10°C. to about 20° effective amount. C. 5. The composition of claim 4, wherein said composition 21. The method of claim 17, further comprising, after said further comprises a pH-control agent. 45 reacting step (a): 6. The composition of claim 5, wherein said pH-control (b) recovering said calcium peroxyphosphate compound agent is a hydroxide compound and said composition has an by a separation method selected from the group consist alkaline pH. ing of evaporation, filtration, and freeze drying. 7. The composition of claim 5, wherein said pH-control 22. The method of claim 21, further comprising, after said agent is carbon dioxide and said composition has an acidic 50 recovering step (b): pH. (c) purifying said calcium peroxyphosphate compound by 8. The composition of claim 4, further comprising a fluo recrystallization or fractional crystallization from water ride ion Source. or a mixture of water and a water-soluble organic Sol 9. The composition of claim 8, wherein said fluoride ion Vent. Source is selected from the group consisting of Sodium fluo 55 23. The method of claim 22, wherein said water-soluble ride, potassium fluoride, monofluorophosphate, hexafluoro organic solvent is a Saturated aliphatic ketone or an aliphatic silicate, and mixtures thereof alcohol. 10. The composition of claim 4, further comprising a polyol carrier in a gel form.