Oral care products comprising tetrabasic zinc chloride and trimethylglycine

BACKGROUND

0001Dental erosion involves demineralization and damage to the tooth structure due to acid attack from nonbacterial sources. Erosion is found initially in the enamel and, if unchecked, may proceed to the underlying dentin. Dental erosion may be caused or exacerbated by acidic foods and drinks, exposure to chlorinated swimming pool water, and regurgitation of gastric acids. The tooth enamel is a negatively charged surface, which naturally tends to attract positively charged ions such as hydrogen and calcium ions, while resisting negatively charged ions such as fluoride ions. Depending upon relative pH of surrounding saliva, the tooth enamel will lose or gain positively charged ions such as calcium ions. Generally saliva has a pH between 7.2 to 7.4. When the pH is lowered and concentration of hydrogen ions becomes relatively high, the hydrogen ions will replace the calcium ions in the enamel, forming hydrogen phosphate (phosphoric acid), which damages the enamel and creates a porous, sponge-like roughened surface. If saliva remains acidic over an extended period, then remineralization may not occur, and the tooth will continue to lose minerals, causing the tooth to weaken and ultimately to lose structure.

0002Dentinal hypersensitivity is acute, localized tooth pain in response to physical stimulation of the dentine surface as by thermal (hot or cold) osmotic, tactile combination of thermal, osmotic and tactile stimulation of the exposed dentin. Exposure of the dentine, which is generally due to recession of the gums, or loss of enamel, frequently leads to hypersensitivity. Dentinal tubules open to the surface have a high correlation with dentine hypersensitivity. Dentinal tubules lead from the pulp to the cementum. When the surface cementum of the tooth root is eroded, the dentinal tubules become exposed to the external environment. The exposed dentinal tubules provide a pathway for transmission of fluid flow to the pulpal nerves, the transmission induced by changes in temperature, pressure and ionic gradients.

0003Heavy metal ions, such as zinc, are resistant to acid attack. Zinc ranks above hydrogen in the electrochemical series, so that metallic zinc in an acidic solution will react to liberate hydrogen gas as the zinc passes into solution to form di-cations, Zn²⁺. Zinc has been shown to have antibacterial properties in plaque and caries studies.

0004Soluble zinc salts, such as zinc citrate, have been used in dentifrice compositions, see, e.g., <patcit id="pcit0001" dnum="US6121315A"><text>U.S. Patent No. 6,121,315</text></patcit>, but have several disadvantages. Zinc ions in solution impart an unpleasant, astringent mouthfeel, so formulations that provide effective levels of zinc, and also have acceptable organoleptic properties, have been difficult to achieve. Finally, the zinc ions will react with anionic surfactants such as sodium lauryl sulfate, thus interfering with foaming and cleaning.

0005Tetrabasic zinc chloride (TBZC), is a zinc hydroxy compound with chemical formula Zn₅(OH)₈Cl₂·H₂O. It is also referred to as zinc chloride hydroxide monohydrate, basic zinc chloride, zinc hydroxychloride, or zinc oxychloride. It occurs naturally as the mineral simonkolleite. Unlike zinc chloride, TBZC is insoluble in water. TBZC has been suggested for use in oral care compositions, see e.g., <patcit id="pcit0002" dnum="GB2243775A"><text>GB2243775A</text></patcit>, but such formulations do not deliver zinc efficiently to the teeth due to the insolubility of TBZC.

0006<i>N,N,N-</i>trimethylglycine (TMG or glycine betaine) is a quaternary amino acid. At neural pH, the compound exists as a zwitterion, forming an inner salt between the quaternary ammonium and the carboxy portions of the molecule. In the presence of strong acids, it will form acid addition salts, e.g., hydrochloride. The compound is originally isolated from sugar beets, and is used as a dietary supplement in animal feed and as a laboratory reagent stabilizer, e.g., in polymerase chain reactions. There are reports of its use in oral care products to treat dry mouth, e.g. <patcit id="pcit0003" dnum="US6156293A"><text>US 6,156,293</text></patcit>, and in antiperspirant products, e.g. <patcit id="pcit0004" dnum="US6969510B"><text>US 6,969,510</text></patcit>.

0007<patcit id="pcit0005" dnum="WO2007063507A"><text>WO-A-2007/063507</text></patcit> discloses a dentifrice composition comprising a binder system comprising hydrophilic clay material. <patcit id="pcit0006" dnum="WO2011123123A"><text>WO-A-2011/123123</text></patcit> discloses an oral care composition.

0008While the prior art discloses the use of various oral compositions for the treatment of dentinal hypersensitivity, dental caries, and enamel erosion and demineralization, there is still a need for additional compositions and methods which provide improved performance in such treatments.

SUMMARY

0009While TBZC is substantially insoluble in prior art formulations, it has now been discovered that tetrabasic zinc chloride can form a soluble complex with TMG in both its free form and acidified form. When placed in formulation, this complex provides an effective concentration of zinc ions to the enamel and/or dentine surface, thereby protecting against erosion, reducing bacterial colonization and biofilm development, and providing enhanced shine to the teeth. Moreover, upon dilution during use, the formulation provides a precipitate which can plug the dentinal tubules, thereby reducing the sensitivity of the teeth. The tetrabasic zinc halide is thus solubilized in the formulation, but provides a zinc precipitate upon use and dilution with saliva and/or rinsing. This is unexpected, at least partially because better solubilization is generally expected with dilution. While providing efficient delivery of zinc in comparison to conventional formulations with insoluble TBZC, the formulations comprising TBZC and TMG do not exhibit the poor taste and mouthfeel, poor fluoride delivery, and poor foaming and cleaning associated with conventional zinc-based oral care products using soluble zinc salts.

0010The formation of this soluble complex is particularly surprising, as similar complexes are not formed between zinc and, for example, creatine (an amino acid with a basic guanidine moiety rather than an ammonium moiety) or cetylpyridinium chloride, or acidified forms of the two. When TMG is present in its acidified form (such as in the form of TMG hydrochloride), the soluble complex accounts for a major component of the ionic species. When TMG is used in its free form, this soluble complex can still form, but is minor amounts and rather insignificant in quantity relative to TMG monomers and oligomers. Without being bound by theory, it appears that upon combination of TBZC and trimethylglycine hydrochloride in aqueous solution, two highly soluble species are formed - a complex comprising zinc, TMG and chloride and a second complex comprising zinc and chloride. Upon further dilution of the solution, these complexes break down, and a precipitate principally comprised zinc-containing compounds (such as TBZC, zinc hydroxide).

0011The present invention provides an oral care composition according to claim 1 (for example mouthwash, oral gel or dentifrice composition), comprising a mixture of a tetrabasic zinc halide and TMG, in orally acceptable acid addition salt form. Preferred features are defined in the dependent claims. The compositions may optionally further comprise a fluoride source and or an additional phosphate source. The compositions may be formulated in a suitable oral care formulation e.g., a conventional dentifrice, oral gel or mouthwash base, e.g., comprising one or more abrasives, surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, antimicrobial agents, preservatives, flavorings, and/or colorants.

0012The invention thus provides, in one embodiment, a complex comprising TBZC and TMG, in its orally acceptable acid addition salt form, for example a zinc-TMG-HCl complex, e.g., formed by combining TBZC and trimethylglycine hydrochloride in aqueous solution.

0013The invention further provides the compositions of the invention for use to reduce and inhibit acid erosion of the enamel, reduce bacterially-generated biofilm and plaque, reduce gingivitis, inhibit tooth decay and formation of cavities, and reduce dentinal hypersensitivity. The invention further provides methods of using the compositions of the invention to whiten the teeth by imparting a coating onto the teeth, wherein the coating is whiter than the native teeth.

0014Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.

DETAILED DESCRIPTION

0015The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.

0016As used herein, "trimethylglycine" refers to <i>N,N,N-</i>trimethylglycine; and the terms may be used interchangeably herein.

0017The invention therefore provides, in a first embodiment, an oral care composition (Composition 1), comprising a mixture of a tetrabasic zinc halide, e.g. tetrabasic zinc chloride (TBZC), and <i>N,N,N</i>-trimethylglycine (TMG) in orally acceptable acid addition salt form; e.g., <ul id="ul0001" list-style="none" compact="compact"><li>1.1. Composition 1 wherein the level of zinc in the formulation by weight on an elemental basis is 0.25 - 4%, e.g., 1-2%, e.g., 0.5-1.5%, e.g., about 1%.</li><li>1.2. Composition 1 or 1.1 wherein the TMG is provided in hydrochloride salt form, or where TMG is formed in situ by providing TMG and acid (such as HCl) as separate entities in molar ratios between 1:5 to 5:1 (moles of TMG vs. moles of protons released from the acid).</li><li>1.3. Any of the foregoing compositions wherein the molar ratio of TBZC to TMG is from 1:1 to 1:10, e.g., about 1:5.</li><li>1.4. Any of the foregoing compositions wherein the molar ratio of zinc to TMG is from 5:1 to 1:2, e.g., about 1:1.</li><li>1.5. Any of the foregoing compositions wherein the pH is between pH 5 and pH 6.</li><li>1.6. Any of the foregoing compositions wherein the formulation includes the step of combining TBZC and trimethylglycine hydrochloride in aqueous solution.</li><li>1.7. Any of the foregoing compositions wherein the TMG is provided in hydrohalide salt form, and the TBZC and TMG form soluble complexes selected from zinc-TMG-halide complexes, zinc-halide complexes, and mixtures thereof, e.g. wherein the halide is selected from fluoride, chloride, bromide and mixtures thereof.</li><li>1.8. Any of the foregoing compositions wherein the TMG is provided in hydrohalide salt form, and the TBZC and TMG form two soluble complexes, one having the chemical composition Zn₂O₈H₆X₂ and the other having the chemical composition Zn₂O₈H₅X₂-TMG, wherein X is selected from Cl, F, Br, and mixtures thereof.</li><li>1.9. Any of the foregoing compositions wherein the TMG is provided in hydrochloride salt form, and the TBZC and TMG form soluble complexes selected from zinc-TMG-chloride complexes, zinc-chloride complexes, and mixtures thereof.</li><li>1.10. Any of the foregoing compositions wherein the TMG is provided in hydrochloride salt form, and the TBZC and TMG form two soluble complexes, one having the chemical composition Zn₂O₈H₆Cl₂ and the other having the chemical composition Zn₂O₈H₅Cl₂-TMG.</li><li>1.11. Any of the foregoing compositions wherein a complex comprising TBZC and TMG is formed, in whole or in part, <i>in situ</i> after the composition is applied.</li><li>1.12. Any of the foregoing compositions wherein a complex comprising TBZC and TMG is formed, in whole or in part, <i>in situ</i> after the composition is formulated.</li><li>1.13. Any of the foregoing compositions comprising an acid, e.g., hydrochloric acid, e.g., such that the pH of the composition is between 5 and 6.</li><li>1.14. Any of the foregoing compositions, further comprising a basic amino acid, e.g., lysine or arginine.</li><li>1.15. Any of the foregoing compositions, in a substantially anhydrous carrier, e.g. a carrier comprising less than 10% water.</li><li>1.16. Any of the foregoing compositions in the form of a toothpaste, gel, mouthwash, powder, cream, strip, or gum.</li><li>1.17. Any of the foregoing compositions in an orally acceptable base, e.g., a mouthwash, gel, or dentifrice base.</li><li>1.18. Any of the foregoing compositions in the form of a dentifrice, e.g., wherein the TBZC and TMG are present in an effective amount, e.g., in an amount of 0.05-4% zinc by weight, e.g., about 0.5-3%, e.g. about 1% zinc by weight, in a dentifrice base.</li><li>1.19. Composition 1.1, wherein the dentifrice base comprises an abrasive, e.g., an effective amount of a silica abrasive, e.g., 10-30%, e.g., about 20%.</li><li>1.20. Composition 1 in the form of a mouthwash, e.g., wherein the TBZC is present in an effective amount, e.g., in an amount of 0.05-4% of zinc by weight, e.g., about 1% of zinc by weight.</li><li>1.21. Any of the foregoing compositions further comprising an effective amount of a fluoride ion source, e.g., providing 500 to 3000 ppm fluoride.</li><li>1.22. Any of the foregoing compositions further comprising an effective amount of fluoride, e.g., wherein the fluoride is a salt selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylendiamine-N,N,N'- tris(2-ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.</li><li>1.23. Any of the preceding compositions comprising an effective amount of one or more alkali phosphate salts, e.g., sodium, potassium or calcium salts, e.g., selected from alkali dibasic phosphate and alkali pyrophosphate salts, e.g., alkali phosphate salts selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any of two or more of these, e.g., in an amount of 1-20%, e.g., 2-8%, e.g., ca. 5%, by weight of the composition.</li><li>1.24. Any of the foregoing compositions comprising buffering agents, e.g., sodium phosphate buffer (e.g., sodium phosphate monobasic and disodium phosphate).</li><li>1.25. Any of the foregoing compositions comprising a humectant, e.g., selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, e.g. comprising at least 20%, e.g., 20-40%, e.g., 25-35% glycerin.</li><li>1.26. Any of the preceding compositions comprising one or more surfactants, e.g., selected from anionic, cationic, zwitterionic, and nonionic surfactants, and mixtures thereof, e.g., comprising an anionic surfactant, e.g., a surfactant selected from sodium lauryl sulfate, sodium ether lauryl sulfate, and mixtures thereof, e.g. in an amount of from about 0.3% to about 4.5% by weight, e.g. 1-2% sodium lauryl sulfate (SLS); and/or a zwitterionic surfactant, for example a betaine surfactant, for example cocamidopropylbetaine, e.g. in an amount of from about 0.1% to about 4.5% by weight, e.g. 0.5-2% cocamidopropylbetaine.</li><li>1.27. Any of the preceding compositions further comprising a viscosity modifying amount of one or more of polysaccharide gums, for example xanthan gum or carrageenan, silica thickener, and combinations thereof.</li><li>1.28. Any of the preceding compositions comprising gum strips or fragments.</li><li>1.29. Any of the preceding compositions further comprising flavoring, fragrance and/or coloring.</li><li>1.30. Any of the foregoing compositions comprising an effective amount of one or more antibacterial agents, for example comprising an antibacterial agent selected from halogenated diphenyl ether (e.g. triclosan), herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea-buckthorn extract), bisguanide antiseptics (e.g., chlorhexidine, alexidine or octenidine), quaternary ammonium compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine, delmopinol, salifluor, metal ions (e.g., zinc salts, for example, zinc citrate, stannous salts, copper salts, iron salts), sanguinarine, propolis and oxygenating agents (e.g., hydrogen peroxide, buffered sodium peroxyborate or peroxycarbonate), phthalic acid and its salts, monoperthalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen bromide, delmopinol, octapinol and other piperidino derivatives, nicin preparations, chlorite salts; and mixtures of any of the foregoing; e.g., comprising triclosan or cetylpyridinium chloride.</li><li>1.31. Any of the foregoing compositions comprising an antibacterially effective amount of triclosan, e.g. 0.1 -0.5%, e.g. about 0.3%.</li><li>1.32. Any of the preceding compositions further comprising a whitening agent, e.g., a selected from the group consisting of peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof.</li><li>1.33. Any of the preceding compositions further comprising hydrogen peroxide or a hydrogen peroxide source, e.g., urea peroxide or a peroxide salt or complex (e.g., such as peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or persulphate salts; for example calcium peroxyphosphate, sodium perborate, sodium carbonate peroxide, sodium peroxyphosphate, and potassium persulfate);</li><li>1.34. Any of the preceding compositions further comprising an agent that interferes with or prevents bacterial attachment, e.g., solbrol or chitosan.</li><li>1.35. Any of the preceding compositions further comprising a source of calcium and phosphate selected from (i) calcium-glass complexes, e.g., calcium sodium phosphosilicates, and (ii) calcium-protein complexes, e.g., casein phosphopeptide-amorphous calcium phosphate</li><li>1.36. Any of the preceding compositions further comprising a soluble calcium salt, e.g., selected from calcium sulfate, calcium chloride, calcium nitrate, calcium acetate, calcium lactate, and combinations thereof.</li><li>1.37. Any of the preceding compositions further comprising a physiologically or orally acceptable potassium salt, e.g., potassium nitrate or potassium chloride, in an amount effective to reduce dentinal sensitivity.</li><li>1.38. Any of the foregoing compositions further comprising an anionic polymer, e.g., a synthetic anionic polymeric polycarboxylate, e.g., wherein the anionic polymer is selected from 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer; e.g., wherein the anionic polymer is a methyl vinyl ether/maleic anhydride (PVM/MA) copolymer having an average molecular weight (M.W.) of about 30,000 to about 1,000,000, e.g. about 300,000 to about 800,000, e.g., wherein the anionic polymer is about 1-5%, e.g., about 2%, of the weight of the composition.</li><li>1.39. Any of the preceding compositions further comprising a breath freshener, fragrance or flavoring.</li><li>1.40. Any of the forgoing compositions for use to reduce and inhibit acid erosion of the enamel, clean the teeth, reduce bacterially-generated biofilm and plaque, reduce gingivitis, inhibit tooth decay and formation of cavities, and reduce dentinal hypersensitivity.</li><li>1.41. Any of the foregoing compositions produced by a process comprising the step of mixing TBZC and trimethylglycine hydrochloride in aqueous media.</li><li>1.42. Any of the foregoing compositions wherein upon dilution with water, e.g., to a level of 1% of less of zinc relative to water, a zinc precipitate, e.g. a TBZC precipitate, is formed.</li></ul>

0018Also described are methods to reduce and inhibit acid erosion of the enamel, clean the teeth, reduce bacterially-generated biofilm and plaque, reduce gingivitis, inhibit tooth decay and formation of cavities, whiten teeth, and reduce dentinal hypersensitivity, comprising applying an effective amount of a composition of the invention, e.g., any of Composition 1, <i>et seq.</i> to the teeth.

0019Also described is a method of making a composition comprising a TBZC and TMG, e.g., any of Composition 1, <i>et seq.</i> comprising the step of combining TBZC and an orally acceptable acid addition salt of TMG, e.g., TMG-HCl, in an aqueous medium.

0020For example, described herein are methods to (i) reduce hypersensitivity of the teeth, (ii) to reduce plaque accumulation, (iii) reduce or inhibit demineralization and promote remineralization of the teeth, (iv) inhibit microbial biofilm formation in the oral cavity, (v) reduce or inhibit gingivitis, (vi) promote healing of sores or cuts in the mouth, (vii) reduce levels of acid producing bacteria, (viii) to increase relative levels of non-cariogenic and/or non-plaque forming bacteria, (ix) reduce or inhibit formation of dental caries, (x), reduce, repair or inhibit pre-carious lesions of the enamel, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (xi) treat, relieve or reduce dry mouth, (xii) clean the teeth and oral cavity, (xiii) reduce erosion, (xiv) whiten teeth; (xv) reduce tartar build-up, and/or (xvi) promote systemic health, including cardiovascular health, e.g., by reducing potential for systemic infection via the oral tissues, comprising applying any of Compositions 1, et seq. as described above to the oral cavity of a person in need thereof, e.g., one or more times per day. The invention further provides Compositions 1, et seq. for use in any of these methods.

0021The invention further provides the use of TBZC and TMG in free or orally acceptable salt form, e.g., trimethylglycine hydrochloride, to make an oral care composition, e.g. any of Compositions 1, et. seq..

0022Also described is the use of TBZC together with TMG in free or orally acceptable salt form to reduce and inhibit acid erosion of the enamel, clean the teeth, reduce bacterially-generated biofilm and plaque, reduce gingivitis, inhibit tooth decay and formation of cavities, and reduce dentinal hypersensitivity; (ii) the use of a zinc amino acid halide precursors selected from (a) tetrabasic zinc chloride and an amino acid halide, and/or (b) tetrabasic zinc chloride, an amino acid and optionally halogen acid in the manufacture of a composition to reduce and inhibit acid erosion of the enamel, clean the teeth, reduce bacterially-generated biofilm and plaque, reduce gingivitis, inhibit tooth decay and formation of cavities, and reduce dentinal hypersensitivity.

0023It is discovered that the interaction of the zinc and the TMG converts the insoluble TBZC to a highly soluble complex. Preferably, the TMG is in acid addition salt form, e.g. hydrochloride form. The complex is highly soluble at concentrations in water, e.g., levels corresponding to about 1% or more of zinc. But with increasing dilution in water, e.g., at concentrations of 0.1 to 1%, e.g. about 0.5%, of zinc in water, the complex disassociates, and the zinc ion in the complex reverts to insoluble forms other than zinc oxide (such as TBZC and zinc hydroxide). In experiments wherein complexes are formed using TBZC and an amino acid such as lysine or arginine, precipitation upon dilution is also observed, although at higher dilution levels, but the precipitate is zinc oxide, so the formation of a TBZC precipitate is unexpected.

0024This dynamic - reduced solubility upon increasing dilution - is unusual and unexpected. The dilution upon brushing or rinsing or combination with saliva facilitates the deposition of the zinc precipitate on the teeth with administration, which acts to occlude the dentinal tubules, thereby reducing hypersensitivity, and also providing zinc to the enamel, which reduces acid erosion, biofilm and plaque formation.

0025It will be understood that although the zinc and TMG may be primarily in the form of precursor materials (e.g. TBZC and TMG-HCl) or in the form of a complex, there may be some degree of equilibrium, so that the proportion of material which is actually in complex compared to the proportion in precursor form may vary depending on the precise conditions of formulation, concentration of materials, pH, presence or absence of water, presence or absence of other charged molecules, and so forth.

0026The actives can be delivered in the form of any oral care formulations, for example a toothpaste, gel, mouthwash, powder, cream, strip, gum, or any other known in the art.

0027If the actives are delivered in the form of a mouthwash, a person desiring the benefits rinses with the stock solution and natural dilution of the stock solution by saliva will initiate the precipitation of the zinc. Alternatively, the person can mix a stock solution with appropriate amount of an aqueous diluent (e.g. to provide a concentration of zinc relative to water of about 0.1 - 1%), and rinse with the mixture.

0028In another embodiment, the mixture is prepared and immediately transferred into a retaining tray, such as those used in holding whitening gels, and the person can wear the tray for the effective period of time. The teeth that are in contact with the mixture will be treated. For use with retaining tray, the mixture can be in the form of a low-viscosity liquid or a gel.

0029In another embodiment, the stock solution, or a mixture of stock solution with water, is applied to the teeth in a gel formulation, e.g., wherein the gel can stay on the tooth for an extended period of time for effective treatment.

0030In another embodiment, the active is provided in a toothpaste. Upon brushing, the active is diluted by saliva and water, leading to precipitation and the formation of deposits and occluding particles.

0031The rate of precipitation from the formulation can be modulated by adjusting concentration of the complex in the stock solution, and changing the ratio of the stock to water. A more diluted formula leads to faster precipitation and is thus preferred when a fast treatment is desired.

0032The benefits of the oral care compositions of the invention are numerous. By providing zinc ions and zinc containing compounds that can release zinc ions in oral cavities, the oral care compositions of the invention provide antimicrobial, antiplaque, antigingivitis, anti-malodor, anticaries, and anticalculus benefits.. The occluding particles and the surface deposits are compounds containing zinc salts which can release zinc ions into oral cavities and provide the various benefits as recognized above. The coating formed on dental surfaces due to deposition can enhance the whiteness of the dental surface, thus providing whitening benefits. Additional benefits include but are not limited to anti-attachment, anti-periodontitis and anti-bone loss, as well as promotion of wound healing.

0033A second benefit is the antierosive properties of zinc ions, which form antierosive deposits on tooth surfaces through oxidation and hydrolysis. The surface deposits, as well as the occluding particles, can react with and neutralize acids, thus protecting the dental surface from the erosive effects of the acids. It is also noted that when the surface deposits and occluding particles neutralize acids, beneficial zinc ions can be released, providing oral care benefits other than anti-erosion.

0034A third benefit is anti-sensitivity benefit as a result of the occlusion. Occlusion of dentin tubules leads to sensitivity relief.

0035A fourth benefit is the benefit associated with the TMG. The TMG, due to its zwitterionic character, provides a buffering effect, counteracting the acid which can damage the teeth and so can provide anticaries benefits. In addition, TMG has been recognized to provide relief from dry-mouth.

0036In a particular embodiment, the invention provides an ionic complex comprising TBZC, TMG and an anionic species, e.g. a halide, for example chloride. In a particular embodiment, the invention provides a complex formed by combining TBZC and TMG HCl in an aqueous media to form a complex conveniently referred to as a TBZC-TMG HCl complex.

0037In another embodiment, the invention provides oral care formulations comprising a TBZC-TMG HCl complex, e.g., compositions according to Composition 1, et seq., comprising a TBZC-TMG HCl complex e.g. in the form of a mouthrinse, a gel, a toothpaste, a cream, a powder, a strip, or a gum.

0038In one embodiment, if the desired formulation is in the form of a mouthrinse, a two-component delivery system is contemplated. The first component is a concentrated solution of the TBZC-TMG HCl complex, and the second component is substantially water. The two components are mixed by the administrator/user immediately before treatment. Alternatively, a single-component delivery system in the form of a mouthrinse is contemplated, where the system comprises a concentrated solution of the TBZC-TMG HCl complex and the diluent is supplied by the administrator/user either in the form of water naturally involved in a typical oral care treatment and/or saliva generated by the user.

0039The invention is also directed, in further embodiments, to a controlled release system and a method for delivering zinc ions and TMG over an extended period of time within oral cavities, comprising administering a composition according to Composition 1, et seq.

0040In particular embodiments, Compositions 1, et seq. provide complexes from TBZC and TMG, for example zinc-TMG-chloride complexes, and/or the TBZC and TMG in free or acid addition salt form, e.g., TMG-HCl, as complex precursors, which can react <i>in situ</i> with water to form the complexes. The <i>in situ</i> formation provides ease of formulation. In another embodiment, the water permitting formation of the complex from the precursor comes from saliva and/or rinsing water that comes into contact with the composition after application.

0041In a particular embodiment, the TMG is provided in the form of an acid addition salt, for example a hydrohalide, e.g. trimethylglycine hydrochloride, which forms a complex of complexes in aqueous media with TBZC.

0042Because the number of moles or weight percent of various zinc salts and complexes herein will vary based on the particular salt or complex form, we frequently refer herein to the amount of total zinc in the formulation by weight or by molar amount, irrespective of its salt or complex form. In some embodiments, the total amount of zinc in the composition is 0.05 to 8 % by weight of the composition. In other embodiments, the total amount of zinc is at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, or at least 1 up to 8% by weight of the composition. In other embodiments, the total amount of zinc in the composition is less than 5, less than 4, less than 3, less than 2, or less than 1 to 0.05% by weight of the composition. For example, in some embodiments, the total amount of zinc in the composition may be about 1%.

0043<i><u>Active Agents</u>:</i> The compositions of the invention may comprise various agents which are active to protect and enhance the strength and integrity of the enamel and tooth structure and/or to reduce bacteria and associated tooth decay and/or gum disease, including or in addition to the zinc - amino acid - halide complexes. Effective concentration of the active ingredients used herein will depend on the particular agent and the delivery system used. It is understood that a toothpaste for example will typically be diluted with water upon use, while a mouth rinse typically will not be. Thus, an effective concentration of active in a toothpaste will ordinarily be 5-15x higher than required for a mouth rinse. The concentration will also depend on the exact salt or polymer selected. For example, where the active agent is provided in salt form, the counterion will affect the weight of the salt, so that if the counterion is heavier, more salt by weight will be required to provide the same concentration of active ion in the final product. Arginine, where present, may be present at levels from, e.g., about 0.1 to about 20 wt %(expressed as weight of free base), e.g., about 1 to about 10 wt % for a consumer toothpaste or about 7 to about 20 wt % for a professional or prescription treatment product. Fluoride where present may be present at levels of, e.g., about 25 to about 25,000 ppm, for example about 750 to about 2,000 ppm for a consumer toothpaste, or about 2,000 to about 25,000 ppm for a professional or prescription treatment product. Levels of antibacterial agents will vary similarly, with levels used in toothpaste being e.g., about 5 to about 15 times greater than used in mouthrinse. For example, a triclosan toothpaste may contain about 0.3 wt % triclosan.

0044<i><u>Fluoride Ion Source</u>:</i> The oral care compositions may further include one or more fluoride ion sources, e.g., soluble fluoride salts. A wide variety of fluoride ion-yielding materials can be employed as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion-yielding materials are found in <patcit id="pcit0007" dnum="US3535421A"><text>U.S. Pat. No. 3,535,421, to Briner et al.</text></patcit>; <patcit id="pcit0008" dnum="US4885155A"><text>U.S. Pat. No. 4,885,155, to Parran, Jr. et al.</text></patcit> and <patcit id="pcit0009" dnum="US3678154A"><text>U.S. Pat. No. 3,678,154, to Widder et al.</text></patcit> Representative fluoride ion sources include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In certain embodiments the fluoride ion source includes stannous fluoride, sodium fluoride, sodium monofluorophosphate as well as mixtures thereof. In certain embodiments, the oral care composition of the invention may also contain a source of fluoride ions or fluorine-providing ingredient in amounts sufficient to supply about 25 ppm to about 25,000 ppm of fluoride ions, generally at least about 500 ppm, e.g., about 500 to about 2000 ppm, e.g., about 1000 to about 1600 ppm, e.g., about 1450 ppm. The appropriate level of fluoride will depend on the particular application. A toothpaste for general consumer use would typically have about 1000 to about 1500 ppm, with pediatric toothpaste having somewhat less. A dentifrice or coating for professional application could have as much as about 5,000 or even about 25,000 ppm fluoride. Fluoride ion sources may be added to the compositions of the invention at a level of about 0.01 wt. % to about 10 wt. % in one embodiment or about 0.03 wt. % to about 5 wt. %, and in another embodiment about 0.1 wt. % to about 1 wt. % by weight of the composition in another embodiment. Weights of fluoride salts to provide the appropriate level of fluoride ion will obviously vary based on the weight of the counterion in the salt.

0045In various embodiments, the amino acid is present in an amount of about 0.5 wt. % to about 20 wt. % of the total composition weight, about 0.5 wt. % to about 10 wt. % of the total composition weight, for example about 1.5 wt. %, about 3.75 wt. %, about 5 wt. %, or about 7.5 wt. % of the total composition weight in the case of a dentifrice, or for example about 0.5-2 wt. %, e.g., about 1% in the case of a mouthwash.

0046<i><u>Abrasives</u>:</i> The compositions of the invention, e.g. Composition 1 et seq. include silica abrasives, and may comprise additional abrasives, e.g., a calcium phosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂), hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate (CaHPO₄ • 2H₂O, also sometimes referred to herein as DiCal) or calcium pyrophosphate; calcium carbonate abrasive; or abrasives such as sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite or other siliceous materials, or combinations thereof.

0047Other silica abrasive polishing materials useful herein, as well as the other abrasives, generally have an average particle size ranging between about 0.1 and about 30 microns, about between 5 and about 15 microns. The silica abrasives can be from precipitated silica or silica gels, such as the silica xerogels described in <patcit id="pcit0010" dnum="US3538230A"><text>U.S. Pat. No. 3,538,230, to Pader et al.</text></patcit> and <patcit id="pcit0011" dnum="US3862307A"><text>U.S. Pat. No. 3,862,307, to Digiulio</text></patcit>. Particular silica xerogels are marketed under the trade name Syloid® by the W. R. Grace &amp; Co., Davison Chemical Division. The precipitated silica materials include those marketed by the J. M. Huber Corp. under the trade name Zeodent®, including the silica carrying the designation Zeodent 115 and 119. These silica abrasives are described in <patcit id="pcit0012" dnum="US4340583A"><text>U.S. Pat. No. 4,340,583, to Wason</text></patcit>. In certain embodiments, abrasive materials useful in the practice of the oral care compositions in accordance with the invention include silica gels and precipitated amorphous silica having an oil absorption value of less than about 100 cc/100 g silica and in the range of about 45 cc/100 g to about 70 cc/100 g silica. Oil absorption values are measured using the ASTA Rub-Out Method D281. In certain embodiments, the silicas are colloidal particles having an average particle size of about 3 microns to about 12 microns, and about 5 to about 10 microns. Low oil absorption silica abrasives particularly useful in the practice of the invention are marketed under the trade designation Sylodent XWA® by Davison Chemical Division of W.R. Grace &amp; Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silica hydrogel composed of particles of colloidal silica having a water content of 29% by weight averaging about 7 to about 10 microns in diameter, and an oil absorption of less than about 70 cc/100 g of silica is an example of a low oil absorption silica abrasive useful in the practice of the present invention.

0048<i><u>Foaming agents:</u></i> The oral care compositions of the invention also may include an agent to increase the amount of foam that is produced when the oral cavity is brushed. Illustrative examples of agents that increase the amount of foam include, but are not limited to polyoxyethylene and certain polymers including, but not limited to, alginate polymers. The polyoxyethylene may increase the amount of foam and the thickness of the foam generated by the oral care carrier component of the present invention. Polyoxyethylene is also commonly known as polyethylene glycol ("PEG") or polyethylene oxide. The polyoxyethylenes suitable for this invention will have a molecular weight of about 200,000 to about 7,000,000. In one embodiment the molecular weight will be about 600,000 to about 2,000,000 and in another embodiment about 800,000 to about 1,000,000. Polyox® is the trade name for the high molecular weight polyoxyethylene produced by Union Carbide. The polyoxyethylene may be present in an amount of about 1% to about 90%, in one embodiment about 5% to about 50% and in another embodiment about 10% to about 20% by weight of the oral care carrier component of the oral care compositions of the present invention. Where present, the amount of of foaming agent in the oral care composition (i.e., a single dose) is about 0.01 to about 0.9 % by weight, about 0.05 to about 0.5% by weight, and in another embodiment about 0.1 to about 0.2 % by weight.

0049<i><u>Surfactants</u>:</i> The compositions useful in the invention may contain anionic surfactants, for example: <ol id="ol0001" compact="compact" ol-style=""><li>i. water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids such as sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride sulfate,</li><li>ii. higher alkyl sulfates, such as sodium lauryl sulfate,</li><li>iii. higher alkyl-ether sulfates, e.g., of formula CH₃(CH₂)_mCH₂(OCH₂CH₂)_nOSO₃X, wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na).</li><li>iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate (sodium lauryl benzene sulfonate)</li><li>v. higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate.</li></ol>

0050By "higher alkyl" is meant, e.g., C_6-30 alkyl. In particular embodiments, the anionic surfactant is selected from sodium lauryl sulfate and sodium ether lauryl sulfate. The anionic surfactant may be present in an amount which is effective, e.g., > 0.01 % by weight of the formulation, but not at a concentration which would be irritating to the oral tissue, e.g., <10%, and optimal concentrations depend on the particular formulation and the particular surfactant. For example, concentrations used or a mouthwash are typically on the order of one tenth that used for a toothpaste. In one embodiment, the anionic surfactant is present in a toothpaste at from about 0.3% to about 4.5% by weight, e.g., about 1.5%. The compositions of the invention may optionally contain mixtures of surfactants, e.g., comprising anionic surfactants and other surfactants that may be anionic, cationic, zwitterionic or nonionic. Generally, surfactants are those which are reasonably stable throughout a wide pH range. Surfactants are described more fully, for example, in <patcit id="pcit0013" dnum="US3959458A"><text>U.S. Pat. No. 3,959,458, to Agricola et al.</text></patcit>; <patcit id="pcit0014" dnum="US3937807A"><text>U.S. Pat. No. 3,937,807, to Haefele</text></patcit>; and <patcit id="pcit0015" dnum="US4051234A"><text>U.S. Pat. No. 4,051,234, to Gieske et al.</text></patcit> In certain embodiments, the anionic surfactants useful herein include the water-soluble salts of alkyl sulfates having about 10 to about 18 carbon atoms in the alkyl radical and the water-soluble salts of sulfonated monoglycerides of fatty acids having about 10 to about 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinate and sodium coconut monoglyceride sulfonates are examples of anionic surfactants of this type. In a particular embodiment, the composition of the invention, e.g., Composition 1, et seq., comprises sodium lauryl sulfate.

0051The surfactant or mixtures of compatible surfactants can be present in the compositions of the present invention in about 0.1% to about 5.0%, in another embodiment about 0.3% to about 3.0% and in another embodiment about 0.5% to about 2.0% by weight of the total composition.

0052<i><u>Tartar control agents:</u></i> In various embodiments of the present invention, the compositions comprise an anticalculus (tartar control) agent. Suitable anticalculus agents include without limitation phosphates and polyphosphates (for example pyrophosphates), polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinc citrate trihydrate, polypeptides, polyolefin sulfonates, polyolefin phosphates, diphosphonates. The invention thus may comprise phosphate salts. In particular embodiments, these salts are alkali phosphate salts, i.e., salts of alkali metal hydroxides or alkaline earth hydroxides, for example, sodium, potassium or calcium salts. "Phosphate" as used herein encompasses orally acceptable mono- and polyphosphates, for example, P_1-6 phosphates, for example monomeric phosphates such as monobasic, dibasic or tribasic phosphate; dimeric phosphates such as pyrophosphates; and multimeric phosphates, e.g., sodium hexametaphosphate. In particular examples, the selected phosphate is selected from alkali dibasic phosphate and alkali pyrophosphate salts, e.g., selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any of two or more of these. In a particular embodiment, for example the compositions comprise a mixture of tetrasodium pyrophosphate (Na₄P₂O₇), calcium pyrophosphate (Ca₂P₂O₇), and sodium phosphate dibasic (Na₂HPO₄), e.g., in amounts of ca. 3-4% of the sodium phosphate dibasic and ca. 0.2-1% of each of the pyrophosphates. In another embodiment, the compositions comprise a mixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate (STPP)(Na₅P₃O₁₀), e.g., in proportions of TSPP at about 1-2% and STPP at about 7% to about 10%. Such phosphates are provided in an amount effective to reduce erosion of the enamel, to aid in cleaning the teeth, and/or to reduce tartar buildup on the teeth, for example in an amount of 2-20%, e.g., ca. 5-15%, by weight of the composition.

0053<i><u>Flavoring Agents</u>:</i> The oral care compositions of the invention may also include a flavoring agent. Flavoring agents which are used in the practice of the present invention include, but are not limited to, essential oils as well as various flavoring aldehydes, esters, alcohols, and similar materials. Examples of the essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful are such chemicals as menthol, carvone, and anethole. Certain embodiments employ the oils of peppermint and spearmint. The flavoring agent may be incorporated in the oral composition at a concentration of about 0.1 to about 5% by weight e.g. about 0.5 to about 1.5% by weight.

0054<i><u>Polymers</u>:</i> The oral care compositions of the invention may also include additional polymers to adjust the viscosity of the formulation or enhance the solubility of other ingredients. Such additional polymers include polyethylene glycols, polysaccharides (e.g., cellulose derivatives, for example carboxymethyl cellulose, or polysaccharide gums, for example xanthan gum or carrageenan gum). Acidic polymers, for example polyacrylate gels, may be provided in the form of their free acids or partially or fully neutralized water soluble alkali metal (e.g., potassium and sodium) or ammonium salts.

0055Silica thickeners, which form polymeric structures or gels in aqueous media, may be present. Note that these silica thickeners are physically and functionally distinct from the particulate silica abrasives also present in the compositions, as the silica thickeners are very finely divided and provide little or no abrasive action. Other thickening agents are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya, gum arabic, and gum tragacanth can also be incorporated. Colloidal magnesium aluminum silicate can also be used as component of the thickening composition to further improve the composition's texture. In certain embodiments, thickening agents in an amount of about 0.5% to about 5.0% by weight of the total composition are used.

0056The compositions of the invention may include an anionic polymer, for example in an amount of from about 0.05 to about 5%. Such agents are known generally for use in dentifrice, although not for this particular application, useful in the present invention are disclosed in <patcit id="pcit0016" dnum="US5188821A"><text>U.S. Pat. Nos. 5,188,821</text></patcit> and <patcit id="pcit0017" dnum="US5192531A"><text>5,192,531</text></patcit>; and include synthetic anionic polymeric polycarboxylates, such as 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether/maleic anhydride having a molecular weight (M.W.) of about 30,000 to about 1,000,000, most preferably about 300,000 to about 800,000. These copolymers are available for example as Gantrez. e.g., AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97 Pharmaceutical Grade (M.W. 700,000) available from ISP Technologies, Inc., Bound Brook, N.J. 08805. The enhancing agents when present are present in amounts ranging from about 0.05 to about 3% by weight. Other operative polymers include those such as the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Suitable generally, are polymerized olefinically or ethylenically unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, that is, an acid containing an olefinic double bond which readily functions in polymerization because of its presence in the monomer molecule either in the alpha-beta position with respect to a carboxyl group or as part of a terminal methylene grouping. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxylic salt groups for water-solubility. A further class of polymeric agents includes a composition containing homopolymers of substituted acrylamides and/or homopolymers of unsaturated sulfonic acids and salts thereof, in particular where polymers are based on unsaturated sulfonic acids selected from acrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropane sulfonic acid having a molecular weight of about 1,000 to about 2,000,000, described in <patcit id="pcit0018" dnum="US4842847A"><text>U.S. Pat. No. 4,842,847, Jun. 27, 1989 to Zahid</text></patcit>. Another useful class of polymeric agents includes polyamino acids containing proportions of anionic surface-active amino acids such as aspartic acid, glutamic acid and phosphoserine, e.g. as disclosed in <patcit id="pcit0019" dnum="US4866161A"><text>U.S. Pat. No. 4,866,161 Sikes et al.</text></patcit>

0057<i><u>Water</u>:</i> The oral compositions may comprise significant levels of water. Water employed in the preparation of commercial oral compositions should be deionized and free of organic impurities. The amount of water in the compositions includes the free water which is added plus that amount which is introduced with other materials.

0058<i><u>Humectants</u>:</i> Within certain embodiments of the oral compositions, it is also desirable to incorporate a humectant to prevent the composition from hardening upon exposure to air. Certain humectants can also impart desirable sweetness or flavor to dentifrice compositions. Suitable humectants include edible polyhydric alcohols such as glycerine, sorbitol, xylitol, propylene glycol as well as other polyols and mixtures of these humectants. In one embodiment of the invention, the principal humectant is glycerin, which may be present at levels of greater than 25%, e.g. 25-35% about 30%, with 5% or less of other humectants.

0059<i><u>Other- optional ingredients</u>:</i> In addition to the above-described components, the embodiments of this invention can contain a variety of optional dentifrice ingredients some of which are described below. Optional ingredients include, for example, but are not limited to, adhesives, sudsing agents, flavoring agents, sweetening agents, additional antiplaque agents, abrasives, and coloring agents. These and other optional components are further described in <patcit id="pcit0020" dnum="US5004597A"><text>U.S. Pat. No. 5,004,597, to Majeti</text></patcit>; <patcit id="pcit0021" dnum="US3959458A"><text>U.S. Pat. No. 3,959,458 to Agricola et al.</text></patcit> and <patcit id="pcit0022" dnum="US3937807A"><text>U.S. Pat. No. 3,937,807, to Haefele</text></patcit>.

0060Unless stated otherwise, all percentages of composition components given in this specification are by weight based on a total composition or formulation weight of 100%.

0061Unless otherwise specifically identified, the ingredients for use in the compositions and formulations of the present invention are preferably cosmetically acceptable ingredients. By "cosmetically acceptable" is meant suitable for use in a formulation for topical application to human skin. A cosmetically acceptable excipient, for example, is an excipient which is suitable for external application in the amounts and concentrations contemplated in the formulations of this invention, and includes for example excipients which are "Generally Recognized as Safe" (GRAS) by the United States Food and Drug Administration.

0062The compositions and formulations as provided herein are described and claimed with reference to their ingredients, as is usual in the art. As would be evident to one skilled in the art, the ingredients may in some instances react with one another, so that the true composition of the final formulation may not correspond exactly to the ingredients listed. Thus, it should be understood that the invention extends to the product of the combination of the listed ingredients.

0063As used throughout, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.

0064Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to refer to percentages by weight. The amounts given are based on the active weight of the material.

EXAMPLES

<b>Example</b> 1

0065It is shown that TBZC can react with TMG HCl and produce soluble forms of zinc species, conveniently named TBZC-TMG HCl. Surprisingly, TBZC-TMG HCl is found to produce solid material upon dilution with appropriate amount of water. The solid material is present in the form of a precipitate or flocculation, and attaches to a dental surface if the dental surface is exposed to the reaction mixture. The solid material is also expected to be attachable to the soft tissues within an oral care cavity. The ability of TBZC-TMG HCl in forming flocculation/precipitation is unique and unexpected.

0066TBZC-TMG, without the acidification, solubilizes but fails to generate precipitation/flocculation upon dilution. Therefore, where precipitation upon dilution is desired, it is preferred that acid be present, either by addition or by providing the TMG in the form of an acid addition salt. Other complexes with related structures are tested and fail to generate precipitation/flocculation with or without acidification. Among these are TBZC-cetyl pyridinium chloride (CPC), TBZC-CPC HCl (with partial HCl, meaning the molar ratios of HCl vs. CPC is less than 1), TBZC-Creatine, TBZC-Creatine HCl (both with partial HCl and equal moles of HCl).

0067Stable solutions of complexes are prepared and characterized. These complexes include TBZC-TMG, TBZC-TMG HCl, TBZC-CPC, TBZC-CPC HCl (partial HCl), TBZC-Creatine, and TBZC-Creatine HCl (2 types):

0068Sample 1, TBZC-TMG (not in accordance with the present invention), is prepared as follows. At room temperature, 5.5178g (0.01 mol) of TBZC powder is slowly added into 50mL of TMG solution (5.8577 g, 0.05mol of TMG in 50ml DI water). The mixture is stirred overnight for about 20 hours. Unreacted TBZC is removed by centrifuging followed by filtering through a 0.45 micron membrane. The final product is a transparent solution. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0001" num="0001"><table frame="all"><title>Table 1</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="46mm" /><colspec colnum="2" colname="col2" colwidth="31mm" /><colspec colnum="3" colname="col3" colwidth="31mm" /><thead><row><entry valign="top"><b>SAMPLE 1</b></entry><entry valign="top"><b>TBZC</b></entry><entry valign="top"><b>TMG</b></entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5178g, 0.01 mol</entry><entry>5.8577g, 0.05mol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col3" align="left">6.84</entry></row><row><entry>Zn content in solution (w/w%)</entry><entry namest="col2" nameend="col3" align="left">0.13 wt%</entry></row></tbody></tgroup></table></tables>

0069Sample 2, TBZC-TMG (not in accordance with the present invention), is prepared as follows. At room temperature, 5.5193g (0.01 mol) of TBZC powder is slowly added into 50mL of TMG solution (5.8573 g, 0.05mol of TMG in 50ml DI water). The mixture is stirred overnight for about 20 hours. Unreacted TBZC is removed by centrifuging followed by filtering through a 0.45 micron membrane. The final product is a transparent solution. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0002" num="0002"><table frame="all"><title>Table 2</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="46mm" /><colspec colnum="2" colname="col2" colwidth="29mm" /><colspec colnum="3" colname="col3" colwidth="29mm" /><thead><row><entry valign="top"><b>SAMPLE 2</b></entry><entry valign="top">TBZC</entry><entry valign="top">TMG</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5193g, 0.01mol</entry><entry>5.8573g, 0.05mol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col3" align="left">6.83</entry></row><row><entry>Zn content in solution (w/w%)</entry><entry namest="col2" nameend="col3" align="left">0.13 wt%</entry></row></tbody></tgroup></table></tables>

0070Sample 3, TBZC-TMG HCl (in accordance with the present invention), is prepared as follows. At room temperature, 5.5188g (0.01mol) of TBZC powder is slowly added into 50mL of TMG solution (7.68 g, 0.05mol of TMG HCl in 50ml DI water). The mixture is stirred overnight for about 20 hours. Unreacted TBZC is removed by centrifuging followed by filtering through a 0.45 micron membrane. The final product is a transparent solution. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0003" num="0003"><table frame="all"><title>Table 3</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="35mm" /><colspec colnum="2" colname="col2" colwidth="30mm" /><colspec colnum="3" colname="col3" colwidth="26mm" /><thead><row><entry valign="top"><b>SAMPLE 3</b></entry><entry valign="top">TBZC</entry><entry valign="top">TMG HCl</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5188g, 0.01 mol</entry><entry>7.68g, 0.05mol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col3" align="left">5.43</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col3" align="left">3.42 wt%</entry></row></tbody></tgroup></table></tables>

0071Sample 4, TBZC-TMG HCl (in accordance with the present invention), is prepared as follows. At room temperature, 5.5207g (0.01 mol) of TBZC powder is slowly added into 50mL of TMG solution (7.6804 g, 0.05mol of TMG HCl in 50ml DI water). The mixture is stirred overnight for about 20 hours. Unreacted TBZC is removed by centrifuging followed by filtering through a 0.45 micron membrane. The final product is a transparent solution. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0004" num="0004"><table frame="all"><title>Table 4</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="35mm" /><colspec colnum="2" colname="col2" colwidth="31mm" /><colspec colnum="3" colname="col3" colwidth="31mm" /><thead><row><entry valign="top"><b>SAMPLE 4</b></entry><entry valign="top">TBZC</entry><entry valign="top">TMG HCl</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5207g, 0.01 mol</entry><entry>7.6804g, 0.05mol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col3" align="left">5.79</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col3" align="left">3.77 wt%</entry></row></tbody></tgroup></table></tables>

0072Sample 5, TBZC-Creatine (not in accordance with the present invention), is prepared as follows. At room temperature, 5.5183g (0.01 mol) of TBZC powder is slowly added into 50mL of creatine monohydrate solution (7.4595 g, 0.05mol of creatine monohydrate in 50ml DI water). Sonication is employed to facilitate the dissolution. The mixture is stirred overnight for about 20 hours. Unreacted TBZC is removed by centrifuging followed by filtering through a 0.45 micron membrane. The final product is a transparent solution. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0005" num="0005"><table frame="all"><title>Table 5</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="35mm" /><colspec colnum="2" colname="col2" colwidth="30mm" /><colspec colnum="3" colname="col3" colwidth="37mm" /><thead><row><entry valign="top"><b>SAMPLE 5</b></entry><entry valign="top">TBZC</entry><entry valign="top">Creatine Monohydrate</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5183g, 0.01 mol</entry><entry>7.4595g, 0.05mol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col3" align="left">6.89</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col3" align="left">0.04 wt%</entry></row></tbody></tgroup></table></tables>

0073Sample 6, TBZC-Creatine 1/3 HCl (not in accordance with the present invention), is prepared as follows. Creatine Monohydrate is added into HCl aqueous solution with stirring at room temperature. TBZC is then added after about 15 minutes. The suspension is centrifuged at 7200rpm for 30mins followed by filtering through 0.45 micron membrane. Transparent solution is collected, and unreacted white solid is discarded. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0006" num="0006"><table frame="all"><title>Table 6</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="35mm" /><colspec colnum="2" colname="col2" colwidth="29mm" /><colspec colnum="3" colname="col3" colwidth="38mm" /><colspec colnum="4" colname="col4" colwidth="35mm" /><thead><row><entry valign="top"><b>SAMPLE 6</b></entry><entry valign="top">TBZC</entry><entry valign="top">Creatine Monohydrate</entry><entry valign="top">HCl (33 wt% solution)</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5201g, 0.01mol</entry><entry>7.4648, 0.05mol</entry><entry>1.839g, 0.0166mmol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col4" align="left">5.91</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col4" align="left">1.26 wt%</entry></row></tbody></tgroup></table></tables>

0074Sample 7, TBZC-CPC (not in accordance with the present invention), is prepared as follows. At room temperature, 5.5183g (0.01 mol) of TBZC powder is slowly added into 50mL of cetyl pyridinium chloride solution (17.8998 g, 0.05mol of cetyl pyridinium chloride in 50ml DI water). Sonication is employed to facilitate the dissolution. The mixture is stirred overnight for about 20 hours. Unreacted TBZC is removed by centrifuging followed by filtering through a 0.45 micron membrane. The final product is a transparent solution. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0007" num="0007"><table frame="all"><title>Table 7</title><tgroup cols="3"><colspec colnum="1" colname="col1" colwidth="34mm" /><colspec colnum="2" colname="col2" colwidth="29mm" /><colspec colnum="3" colname="col3" colwidth="40mm" /><thead><row><entry valign="top"><b>SAMPLE 7</b></entry><entry valign="top">TBZC</entry><entry valign="top">cetyl pyridinium chloride</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5183g, 0.01mol</entry><entry>17.8998g, 0.05mol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col3" align="left">7.48</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col3" align="left">0.03 wt%</entry></row></tbody></tgroup></table></tables>

0075Sample 8, TBZC-CPC 1/3 HCl (not in accordance with the present invention), is prepared as follows. Cetyl pyridinium chloride is added into HCl aqueous solution with stirring at room temperature. TBZC is then added after about 15 minutes. The suspension is centrifuged at 7200rpm for 30mins followed by filtering through 0.45 micron membrane. Transparent solution is collected, and unreacted white solid is discarded. Zinc concentration is determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0008" num="0008"><table frame="all"><title>Table 8</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="36mm" /><colspec colnum="2" colname="col2" colwidth="31mm" /><colspec colnum="3" colname="col3" colwidth="39mm" /><colspec colnum="4" colname="col4" colwidth="36mm" /><thead><row><entry valign="top"><b>SAMPLE 8</b></entry><entry valign="top">TBZC</entry><entry valign="top">cetyl pyridinium chloride</entry><entry valign="top">HCl (33 wt% solution)</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5199g, 0.01 mol</entry><entry>17.913g, 0.05mol</entry><entry>1.820g, 0.0164mmol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col4" align="left">6.91</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col4" align="left">0.04 wt%</entry></row></tbody></tgroup></table></tables>

0076Sample 9, TBZC-Creatine HCl (not in accordance with the present invention), with equal moles of HCl as Creatine, is prepared as follows. Creatine Monohydrate is added into HCl aqueous solution with stirring at room temperature. After complete dissolution is achieved, TBZC is added, and a suspension resulted. The suspension is centrifuged at 7200rpm for 30mins followed by filtering through 0.45 micron membrane. Transparent solution is collected, and unreacted white solid is discarded. Zinc concentration is to be determined by atomic absorption spectroscopy after acid digestion. <tables id="tabl0009" num="0009"><table frame="all"><title>Table 9</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="35mm" /><colspec colnum="2" colname="col2" colwidth="30mm" /><colspec colnum="3" colname="col3" colwidth="30mm" /><colspec colnum="4" colname="col4" colwidth="35mm" /><thead><row><entry valign="top"><b>SAMPLE 9</b></entry><entry valign="top">TBZC</entry><entry valign="top">Creatine</entry><entry valign="top">HCl (33 wt% solution)</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5201g, 0.01mol</entry><entry>7.4587g, 0.05mol</entry><entry>5.57g, 0.0504mmol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col4" align="left">5.55</entry></row><row><entry>Zn content in solution</entry><entry namest="col2" nameend="col4" align="left">TBD</entry></row></tbody></tgroup></table></tables>

0077Attempts are made to prepare TBZC-CPC HCl (not in accordance with the present invention), with equal moles of HCl as CPC. Cetyl Pyrindium is added into HCl aqueous solution under stirring at temperature, and white suspension is formed (it does not totally dissolve after being stirred for 15mins). Then TBZC is added. After being stirring for a while, the mixture became "soft solid" which is not able to be stirred anymore. The experiment is then abandoned. <tables id="tabl0010" num="0010"><table frame="all"><title>Table 10</title><tgroup cols="4"><colspec colnum="1" colname="col1" colwidth="30mm" /><colspec colnum="2" colname="col2" colwidth="29mm" /><colspec colnum="3" colname="col3" colwidth="40mm" /><colspec colnum="4" colname="col4" colwidth="35mm" /><thead><row><entry valign="top"><b>SAMPLE 10</b></entry><entry valign="top">TBZC</entry><entry valign="top">cetyl pyridinium chloride</entry><entry valign="top">HCl (33 wt% solution)</entry></row></thead><tbody><row><entry>Amount added</entry><entry>5.5174g, 0.01mol</entry><entry>17.913g, 0.05mol</entry><entry>5.66g, 0.0511 mmol</entry></row><row><entry>pH of final solution</entry><entry namest="col2" nameend="col4" align="left">Not applicable.</entry></row><row><entry>Zn content</entry><entry namest="col2" nameend="col4" align="left">Not applicable.</entry></row></tbody></tgroup></table></tables>

0078For the preparation involving CPC HCl (TBZC-CPC 1/3 HCl, Sample 8), HCl is added in 1:3 molar ratios (HCl : CPC). When HCl is added in equal number of moles as CPC, the reaction mixture is a thick slurry and no liquid can be extracted.

0079For the preparations involving Creatine HCl, two types are made. A first type involved use of HCl in 1:3 molar ratios to creatine and the sample is coded TBZC-Creatine 1/3 HCl, i.e., Sample 6. A second type involved use of HCl in 1:1 molar ratio to creatine and the sample is coded TBZC-Creatine HCl, i.e, Sample 9.

0080Each complex is evaluated for its ability and rate to form precipitation or flocculation upon dilution. For this analysis, samples with various dilution ratios (for example, 2x through 32x) are prepared and kept at 37°C. The samples are monitored periodically and their efficiency of generating precipitation/flocculation are recorded.

0081Dilutions experiments indicate that TBZC-TMG HCl is the only one capable of generating precipitation/flocculation, and thus is preferred for depositing solid particles on dentine surface. Rate of flocculation/precipitation depends on the dilution ratio, which is related to the initial zinc concentration at the time water is mixed with the stock solutions in desired proportions.

0082A first dilution experiment is carried out using the batch of sample TBZC-TMG HCl with a zinc concentration of 3.77 wt%. Dilutions are prepared with initial zinc concentrations (prior to precipitation) at 0.118 wt%, 0.236 wt%, 0.471 wt%, 0.628 wt%, 0.942 wt% and 1.88 wt%. The diluted samples are kept at 37°C, and the rates at which flocculation/precipitation occurred are monitored. Dilutions with initial zinc concentrations at 0.471 wt%, 0.628 wt% and 0.942 wt% are able to generate some visible flocculation within a couple of minutes from the time point when the stock solution is mixed with water. One hour from mixing, visible flocculation are observed in dilutions with initial zinc concentrations of 0.236 wt%, 0.471 wt%, 0.628 wt%, and 0.942 wt%. After 20 hours, flocculation and precipitation could be observed in all samples.

0083A second dilution experiment is carried out using the batch of sample TBZC-TMG HCl with a zinc concentration of 3.42 wt%. Dilutions are prepared with initial zinc concentrations at with initial zinc concentrations of 0.107 wt% and 0.214 wt% fail to generate any visible amounts of flocculation/precipitation, even after 24 hours of incubation.

0084Preparations that generate flocculation/precipitation can be utilized to deposit active agents onto oral surfaces, including dental and mucosal surfaces. In this regard, dilutions with initial zinc concentrations between about 0.118 wt% through about 1.88 wt% relative to water can be utilized. In an actual formulation, of course, the concentration of zinc in the formulation would be lower than the dilution concentration relative to water, because the total formulation would comprise components in addition to water. Preparations at the low and high ends of the concentration spectrum tend to require longer hours of treatment and are not among the most reliable in producing precipitation/flocculation. Dilutions with initial zinc concentrations between about 0.236 wt% and about 0.942 wt% relative to water are preferred due to their ability to generate precipitation/flocculation within one hour. Dilutions with initial zinc concentration between about 0.471 wt% and about 0.942 wt% relative to water are more preferred due to their ability to generate flocculation within a couple of minutes from the onset of dilution.

0085Preparations that do not generate flocculation/precipitation discernible to the naked eyes may also be used for depositing active agents onto oral surfaces. The failure to generate noticeable flocculation/precipitation may be due to unfavorable dilution ratio or inadequate treatment duration. However, the preparations may still be able to generate particles, such as colloidal particles. While these particles do not form precipitates within the treatment duration, they may form surface deposits onto oral surfaces. In this regard, the operable ranges of dilution ratios and/or treatment durations are wider than what can be directly inferred from the above-mentioned dilution experiments.

0086TBZC-TMG-HCl provides relatively high levels of solubilized zinc, as seen from the data for samples 3 and 4 above, and moreover provides precipitation/flocculation upon dilution.

0087The other samples are diluted and fail to generate precipitation/flocculation with or without acidification. The ability of TBZC-TMG HCl in generating flocculation/precipitation, unique among the formulations tested, is unexpected. The presence of an anion, e.g., from a TMG acid addition salt form, or provided separately as an acid, enhances performance in this respect. The TBZC-CPC and TBZC-CPC 1/3 HCl samples does not exhibit precipitation upon dilution, suggesting that the ability to form flocculation/precipitation is not common to every structure containing a quaternary amine moiety. The TBZC-Creatine, TBZC-Creatine 1/3 HCl and TBZC-Creatine HCl samples also do not exhibit precipitation upon dilution, suggesting that the ability to form flocculation/precipitation is not common to all structures with strongly basic moieties. The failure with TBZC-Creatine 1/3 HCl, which has a substantial zinc loading and a pH value essentially the same as the TBZC-TMG-HCl, further attests to the uniqueness of TBZC-TMG-HCl. It is also surprising that TBZC-TMG (without acidification) does not work in producing precipitates. Without acidification, it can be seen that TMG has a very limited ability to solubilize TBZC. In addition, TMG is primarily present in TBZC-TMG as its monomer and oligomers, instead of being in complex with the zinc-containing ions as seen with TBZC-TMG-HCl.

<i>Example 2</i>

0088TBZC-TMG-HCl complex solutions as described in the preceding example are shown to be effective in occluding dentinal tubules when applied to the teeth and diluted to trigger precipitation. This deposition and tubule occlusion should reduce sensitivity and furthermore provides a reservoir of zinc to help protect the enamel against erosion and bacterial colonization.

0089Thin slices of human dentin sections are prepared following established procedures from whole human teeth. The dentine slices are prepared by cutting human tooth into thin dentine sections of about 800 microns in thickness, designating a test side, sanding said test side using a sandpaper of about 600 grit, polishing said test side using a Buehler polishing cloth and 5 micron Buehler aluminum oxide, acid-etching said dentine section in 1 % (by weight) citric acid solution for about 20 seconds, sonicating said dentine section for 10 minutes, and storing said dentine section in phosphate buffered saline (PBS, pH 7.4, Gibco Cat. No. 10010).

0090The thin slices of human dentin sections are first imaged on the confocal microscope for baseline characterization. Top view images are taken in XYZ mode, and side view images are taken in XZY mode. Typical images are taken with a 50x objective lens, and with x4 zoom (digital magnification). When a more global view is desired at lower magnification, the images are taken at x1 or x1.6 zoom for top view images and x1.6 zoom for side view images.

0091The thin slices of human dentin sections are then treated using the respective treatment solutions. The stock solutions of TBZC-TMG HCl (with 3.42 wt% of zinc) are first mixed in a vial with the appropriate amount of water in 1:3 ratios by volume, yielding a 0.855 wt% starting zinc concentration. Within seconds, the dentin slice is added to the vial and the vial is capped and stored in an incubator at 37°C for 1 hour for treatment. At the conclusion of the treatment, the vial is removed from the incubator, and the liquid and precipitate, if any, are removed using a pipettor. The dentine disc is rinsed for 4 times, each time using 1 mL of PBS (pH=7.4) solution. The dentine disc is dried using a tissue.

0092The treated thin slices are examined under the confocal microscope for signs of occlusion and deposition on the surface. Repeat treatments are made on the treated discs using the same treatment procedure as the prior treatment. Confocal images are taken to monitor the progress of additional occlusion and deposition after one or more repeat treatments.

0093TBZC-TMG HCl, as documented by confocal images, is shown to substantially completely occlude the dentin tubules and form a substantially complete coverage on the surface of the dentin slice, after the 1 hour treatment.

0094Baseline images indicate open tubules and clean surface between the openings. Upon a single treatment, significant tubule occlusion can be observed, as well as substantial deposition between the tubule openings. Two spots are examined under the confocal microscope. At the first spot, both side view and top view images indicated presence of deposition and occlusion, as confirmed on images taken at lower resolution (showing larger area). At the second spot, almost complete surface deposition and occlusion are observed.

0095Upon the second treatment, more significant tubule occlusion and surface deposition are observed. Side view images indicate complete coverage on the surface, including tubule openings. Top view images indicate substantially complete surface coverage and tubule occlusion, except in isolated patches. A side view image shows a flare of surface deposit extending upward from the baseline (either the dentine surface or the top surface of the deposits in adjacent area) for a height of about 10 microns.

0096After the third treatment, substantial surface deposition and tubule occlusion are observed. Both the top view and side view images indicate some patches of open dentine surface and tubules, but the coverage is substantial nonetheless. It is also worth noting that the tubules that seemed open are likely still blocked at a depth that eludes the confocal images.

0097The significant increase in deposition/occlusion with repeated treatments, particularly from the first treatment to the second treatment, suggests that the surface of the dentine disc is conditioned by prior treatments and may receive more deposits/occludants during subsequent treatments. The result from the third treatment might indicate a point of saturation. In contrast, repeated treatments using TBZC-TMG fail to generate surface deposits or tubule occlusion visible in confocal images.

0098The treatment duration can be reduced from the one hour period used in this assay. As noted previously in the dilution experiments, TBZC-TMG HCl preparation with initial zinc concentrations in the range of about 0.45 wt% and about 0.95 wt% in water produces visible amounts of flocculation/precipitation within minutes from initial mixing of water and the stock solution. Also, in the 1-hour treatment study, cloudiness is observed in the solution (with 0.855 wt% initial zinc concentration in water) within one minute from mixing water and the stock solution. Therefore, these short treatment durations e.g. 1 minute or less can be employed. These short treatment periods enable many delivery platforms that are not practical with the 1-hour treatment, such as toothpaste and mouthrinse. Any potential reduction in efficacy in depositing particles is compensated by more repeated treatments. For example, the treatment regimen can comprise 3 or more treatments, each lasting about 1 to 2 minutes.

0099Treated dentine discs are also characterized using ESCA (Electron Spectroscopy for Chemical Analysis) to ascertain the presence and nature of zinc, as well as the presence of TMG. In addition, free-standing precipitates from TBZC-TMG HCl dilutions are prepared and characterized using ESCA.

0100The compositions of the precipitates were examined both as free-standing entities and as a coating on the dentine surface, using ESCA. The data suggest that the precipitates comprise a combination of zinc containing compounds and varying amounts of betaine.

0101ESCA analysis is conducted on precipitates from TBZC-TMG HCl dilutions, both as prepared and after rinsing with deionized water. Both samples contain significant amounts of Cl (chlorine). The rinsed sample is composed of TBZC, Zn(OH)₂, as well as other zinc species, and no TMG is found in the rinsed sample. The as-prepared sample contains a mixture of TBZC and Zn(OH)₂, as well as other zinc species. In addition, the as-prepared sample contained small amounts of TMG. ZnO does not appear as a primary form of zinc in either the rinsed or as-prepared precipitates, which is in contrast to experiments with TBZC-amino acid complexes.

0102ESCA results also indicate the presence of Zn-containing compounds (phosphate as well as at least one more form of Zn-containing compound) on the dentine disc treated with TBZC-TMG HCl. Zn is detected at significant levels (15.07 vs. 0 from baseline). Phosphorus (P) is also detected at levels significantly higher than for untreated disks (8.75 vs. 1.92 or 2.09 from baseline), suggesting that at least some Zn is present as a phosphorus-containing compound on the surface. The Zn peaks are not consistent with Zn in the form of Zn₃(PO₄)₂. Thus the data suggest that Zn is present as a phosphate, but not orthophosphate. The relative amounts of Zn and P also suggest that at least one more form of Zn is present on the disk, in addition to phosphate. The data do not suggest the presence of ZnO.

0103ESCA analysis does not show the presence of TMG on the dentine disc treated with TBZC-TMG HCl. Nitrogen (N) atom was also detected on the surface of the disks at levels lower than those for untreated disks (3.55 vs. 13.77 or 14.51 from baseline), reflecting the Zn coating on the surface. The nitrogen detected is probably from the dentin, since it is present in an uncharged state. TMG nitrogen would be detected as N⁺ on the surface, and its presence is not apparent. SIMS analysis fails to indicate any TMG. ESCA detects chemical compositions on the external surface of the depositing particles and TMG may be present under the external surface, thus eluding detection. Differential in the organic contents between surface layer and the bulk of the deposit is observed with TBZC-amino acid preparations and such differential could be reasonably expected in the case of TBZC-TMG. This differential can be attributed to depletion of organic contents from the surface layer upon rinsing. The absence of TMG in the rinsed precipitates and the presence of TMG in the as-prepared precipitates are supportive of this notion.

0104TBZC-TMG in the absence of anion does not provide significant deposits to dentin following dilution, in contrast to TBZC-TMG HCl. ESCA analysis shows the presence of only minor amount of zinc-containing compound, and no TMG on the dentine surface treated with TBZC-TMG. The C, O and N levels are similar to those for untreated disks indicating little deposition on the surface. Zn is detected at a low level, indicating minor uptake from the treatment. P is detected at a slightly elevated level relative to untreated disks, suggesting that Zn may be present on the surface as a phosphate. The Zn peaks are not consistent with Zn being present as Zn₃(PO₄)₂, however. The Zn peaks also indicate that Zn is not present as ZnO. SIMS analysis fails to discover any TMG. Thus where deposition of the zinc upon dilution is desired, anion may be provided as acid addition salt or as added acid approximately equimolar to TMG.

Example 3

0105Test dentifrice according to the present invention and comprising TBZC-TMG HCl, 1450 ppm fluoride, and phosphates is prepared as follows: <tables id="tabl0011" num="0011"><table frame="all"><title>Table 11</title><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="44mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><thead><row><entry valign="top"><b>Ingredient</b></entry><entry align="center" valign="top"><b>Wt %</b></entry></row></thead><tbody><row><entry>PEG600</entry><entry align="center">3</entry></row><row><entry>CMC-7</entry><entry align="center">0.65</entry></row><row><entry>Xanthan</entry><entry align="center">0.2</entry></row><row><entry>Sorbitol</entry><entry align="center">27</entry></row><row><entry>Glycerin</entry><entry align="center">20</entry></row><row><entry>Saccharin</entry><entry align="center">0.3</entry></row><row><entry>Tetrasodium pyrophosphate</entry><entry align="center">0.5</entry></row><row><entry>Calcium pyrophosphate</entry><entry align="center">0.25</entry></row><row><entry>Sodium phosphate dibasic</entry><entry align="center">3.5</entry></row><row><entry>Sodium fluoride</entry><entry align="center">0.32</entry></row><row><entry>Titanium dioxide</entry><entry align="center">0.5</entry></row><row><entry>Abrasive silica</entry><entry align="center">8</entry></row><row><entry>Thickener silica</entry><entry align="center">8</entry></row><row><entry>TMG-HCl</entry><entry align="center">5</entry></row><row><entry>Sodium lauryl sulfate</entry><entry align="center">1.5</entry></row><row><entry>Flavoring</entry><entry align="center">1.2</entry></row><row><entry>TBZC</entry><entry align="center">2</entry></row><row><entry>Water</entry><entry align="center">QS</entry></row></tbody></tgroup></table></tables>

<i>Example 4</i>

0106A stable mouthwash formulation according to the present invention is provided as follows: <tables id="tabl0012" num="0012"><table frame="all"><title>Table 12</title><tgroup cols="2"><colspec colnum="1" colname="col1" colwidth="39mm" /><colspec colnum="2" colname="col2" colwidth="14mm" /><thead><row><entry valign="top"><b>Ingredient</b></entry><entry align="center" valign="top"><b>Wt %</b></entry></row></thead><tbody><row><entry>Sorbitol</entry><entry align="center">7.5</entry></row><row><entry>Glycerin</entry><entry align="center">7.5</entry></row><row><entry>Propylene glycol</entry><entry align="center">7</entry></row><row><entry>Sodium saccharin</entry><entry align="center">0.02</entry></row><row><entry>Citric acid (anhydrous)</entry><entry align="center">0.05</entry></row><row rowsep="0"><entry>TBZC</entry><entry align="center">2</entry></row><row><entry>TMG HCl</entry><entry align="center">5</entry></row><row><entry>Flavor /dye</entry><entry align="center">0.12</entry></row><row><entry>Potassium sorbate</entry><entry align="center">0.05</entry></row><row><entry>Cocamidopropyl betaine</entry><entry align="center">1</entry></row><row><entry>Water</entry><entry align="center">QS</entry></row></tbody></tgroup></table></tables>

0107While the invention has been described with respect to specific examples including presently preferred modes of carrying out the invention, those skilled in the art will appreciate that there are numerous variations and permutations of the above described systems and techniques. It is to be understood that other embodiments may be utilized and structural and functional modifications may be made without departing from the scope of the present invention. Thus, the scope of the invention should be construed broadly as set forth in the appended claims.