FIELD OF THE INVENTION The present invention relates to oral care compositions which provide anti-plaque, anti-tartar and gingivitis preventive effects. BACKGROUND OF THE INVENTION

Calculus, or tartar as it is sometimes called, is the solid, hard mass of calcified material deposited on and adhering to the surfaces of the teeth. Calculus is com¬ posed of inorganic salts which make the calculus hard and resistant. Calculus is largely calcium phosphates, mainly hydroxyapatite with varying, but small, amounts of other inorganic salts.

Although not entirely understood, the general concept is that deposits, mostly plaque, which is a sticky film of oral bacteria and their products, become calcified with the ultimate formation on the teeth of a hard mineral consisting of calcium hydroxyapatite.

As the mature calculus develops, it becomes visibly white or yellowish in color unless stained or discolored by some extraneous agent. In addition to being unsightly and undesirable from an aesthetic standpoint, the mature calculus deposits can be constant sources of irrita¬ tion of the gingiva.

Methods for chemically reducing or preventing calculus formation have been directed at affecting the process at any of several stages in its development. One approach is to develop agents which inhibit the formation of the crystalline calcium phosphate or hydroxyapatite.

A wide variety of chemical and biological agents have been suggested to retard calculus formation or to remove calculus after it is formed. The chemical approach to calculus inhibition generally involves crystal growth

inhibition which prevents the calculus from forming. Mech¬ anical removal of calculus by the dentist is necessary and is a routine dental office procedure.

The most widely used tartar control agents in dentifrices are the pyrophosphate salts. A disadvantage of pyrophosphate salts is that they cause irritation in some users and in others they cause sensitivity to the teeth.

Prevention of plaque and gingivitis can be very important to the health of individuals. Loss of teeth and other ill effects can result from poor oral health.

Gingivitis is an inflammation or soreness of the exposed gums and gingiva and is usually caused by bacteria in plaque. In mild cases the only symptom is a slight red¬ dening of the gum tissues at the tip of the gingiva. In more severe cases the reddening spreads and the gums become swollen. Sometimes the gums bleed on brushing or when probed by a dentist. In very severe cases spontaneous bleeding of the gums occurs.

Gingivitis can often be inhibited by regular, twice daily brushing with a regular toothpaste and by the use of floss to remove plaque from between teeth. Some¬ times, however, over-the-counter chemotherapeutic agents such as anti-bacterial mouthwashes or toothpastes con¬ taining anti-bacterial agents are useful in preventing gingivitis in more susceptible individuals.

Many kinds of anti-bacterial agents, when incor¬ porated into mouthwashes or dentifrices, have been found to be at least somewhat effective in preventing gingivitis. A mouthwash containing the essential oils thymol, eucalyptus, and menthol in an alcohol/water base is currently marketed and has been shown in several clinical studies to provide a significant benefit. This product, however, has an unpleasant taste which deters use. Tooth¬ pastes containing triclosan have also been shown to be effective and are available in Europe. Cationic anti¬ microbial surfactants have also been suggested as anti-

plaque/anti-gingivitis agents.

Enhancement of the activity of Triclosan and cationic anti-microbials by zinc salts has also been re¬ ported; however, due to the unpleasant lingering taste of zinc salts, only minor levels of zinc salts have been used. Since one would expect any icrobial effect of zinc salts to be due to the release of zinc ions, one would not expect insoluble zinc compounds to be effective anti-bacterials. Gingivitis is a significant disease because it iε believed that in some cases it can lead to or be a precur¬ sor to more serious gum diseases known as periodontitis.

Periodontitis is a disease which occurs below the gum line. Anaerobic bacteria collect in pockets formed between the teeth and gums, and the gums recede from teeth when serious inflammation of the gums is present, loss of alveolar bone often occurs and the patient is often at risk of loosing teeth. Periodontitis cannot generally be treated by superficial use of chemotherapeutic agents. The intervention of a dentist is required and surgery is often necessary.

Zinc oxide is used in a number of oral care products. U.S. 3.624.199 (Norfleet) discloses a stable dental cream containing hydrated alumina, calcium carbonate or an insoluble alkali metal metaphosphate as a polishing agent, benzyl alcohol as a desensitizing agent, and zinc oxide which permits dental creams containing benzyl alcohol and a major amount of the these polishing agents to be placed in unlined aluminum tubes without substantial tube swelling or corrosion (see col. 3, lines 61-69). U.S. 3.622.662 (Roberts et al.) discloses dental creams containing a polishing agent, benzyl alcohol, clove or mint flavor, and zinc oxide, zinc phosphate, or an alkali metal phosphate having a pKa of at least 7 in water at 25°C (e.g., trisodium phosphate) as a stabilizing agent to prevent separation of the cream. U.S. 3.989.814 (Cordon et al.) discloses a dentifrice possessing enhanced polishing

characteristics which contains an abrasive system of at least calcium pyrophosphate and a non-toxic zinc compound (see col. 2, lines 5-14). U.S. 4.082.841. U.S. 4.152.418. and U.S. 4.154.815 (Pader) disclose improved compositions for reducing dental plaque and calculus formation comprising zinc ions (see col. 6, lines 59 to col. 1 , line 20 of the '841 patent) and an organoleptically acceptable enzyme. U.S. 4.100.269 (Pader) discloses dentifrice and mouthwash formulations for the control of calculus which contain zinc compounds (see col. 3, lines 12-32) . U. S. 4.159.315 (Wagenknecht) discloses dental compositions for inhibiting or reducing plaque which contain zinc compounds (see col. 4, lines 25-45) . U.S. 4.339.432 and U.S. 4.425.325 (Ritchey et al.) disclose oral compositions, such as mouthwashes, containing a zinc-glycine combination as an anticalculus-antiplaque agent (see col. 3, lines 54 to col. 3, line 15 of the '432 patent, col. 2, line 62 to col. 3, line 41 of the '325 patent) . U.S. 4.647.452 (Ritchey et al.) discloses a composition for retarding plaque which is a mixture of a zinc salt (see col. 7, line 52 to col. 8, line 29) and a non-ring halogenated aromatic salicylamide of a specified structure. U.S. 4.684.528 and U. S. 4.758.439 (Godfrey) disclose formulations of zinc compounds (see col. 3, lines 47-55 of the '528 and '439 patents) with select amino acids such a glycine in a base material such as dentifrices. U.S. 4.814.163 and U.S. 4.814.164 (Barth) disclose anti-tartar mouth deodorants which contain a zinc compound (see col. 3, line 31 to col. 4, line 2 of the '163 patent and col. 3, lines 20-58 of the '164 patent), an ionone ketone terpene derivative, and a flavor, as the essential ingredients, with a gluconate salt and an acidic pH to aid in zinc solubilization, in a sugar-free carrier. U.S. 4.562.063 (Hayes et al.) discloses an astringent gel dentifrice containing a water-soluble zinc salt (see col. 3, lines 5-25) , and hydrous silica gel polishing agent compatible and substantially non-reactive with the zinc

salt and alkali metal carboxymethyl cellulose. u.s. 4,562.066 (Hayes et al.) disclose an astringent dentifrice containing a water-soluble zinc salt (see col. 3, lines 31- 51) and an alkali metal onofluorophosphate and a hydrous silica gel polishing agent compatible and substantially non-reactive with both the zinc salt and alkali metal monofluorophosphate. U.S. 4.170.634 and U.S. 4.187.288 (Cordon et al.) disclose dentifrices containing at least one hard abrasive and a non-toxic zinc compound (see col. 1, line 64 to col. 2, line 7 of the '634 patent and col. 1, line 65 to col. 2, line 8 of the '288 patent). U.S. 4.455.293. U.S. 4.455.294 and U.S. 4.526.778 (Harvey et al.) disclose stable, non-gassing dentifrice formulations which contain water, a neutral siliceous polishing agent, a stabilizing amount of monofluorophosphate ion, and optionally whitening agents such as titanium dioxide or zinc oxide (see col. 5, lines 36-39 of the '293 and '778 patents and col. 5, lines 34-37 of the '294 patent). U.S. 4.459.283 (Harvey et al.) discloses dentifrices containing chloroform, a siliceous agent, a mixture of phosphate esters to reduce or prevent corrosion, and optionally a whitening agent such as titanium dioxide or zinc oxide (see col. 5, lines 46-49). U.S. 4.425.324 (Harvey) discloses a hazed toothpaste for reducing carries formation which contains a binary fluorine-providing system, a synthetic precipitated siliceous polishing agent, dicalcium phosphate as a stabilizer against gassing and color fading, and optionally an opacifying agent such as zinc oxide or preferably titanium oxide (see col. 2, line 68 to col. 3, line 2). U.S. 4.562.065 (Hayes et al.) discloses an astringent dentifrice containing a water-soluble zinc salt (see col. 3, lines 3-23) and hydrous silica gel polishing agent compatible and substantially non-reactive with the zinc sale. U.S. 4.309.409 (Coll-Palagos et al.) discloses a fluorine-containing toothpaste which contains zinc oxide, an acidic pH adjuster, optionally trimagnesium phosphate,

and an insoluble alkali metal metaphosphate and/or calcium pyrophosphate. U.S. 4.022.880 (Vinson et al.) discloses an improved dental composition for inhibiting dental plaque and calculus formation which contains a combination of zinc ions (see col. 4, lines 36-54) and a non-toxic, organoleptically acceptable anti-bacterial agent in an orally acceptable medium. U.S. 4.937.066 (Vlock) discloses an oral composition, such as mouthwashes and dentifrices, for reducing calculus formation and undesirable mouth odor which contain an ammonium or alkali metal zinc tartrate. U.S. 4.138.477 (Gaffar) discloses a composition for preventing mouth odor, plaque, calculus, caries, and periodontal disease which contains, as the essential agent, a zinc-polymer combination formed by reacting or interacting a zinc compound with an anionic polymer containing carboxylic, sulfonic, and/or phosphoric acid radicals (see col. 3, line 64 to col. 4, line 63). U.S. 4.375.968 (Manhart) discloses a two part calcium hydroxide composition for use on both hard and soft dental tissues in which zinc stearate is used as an emulsifier and zinc oxide is used as a filler (see col. 2, lines 15-28). U.S. 4.522.806 (Muhlemann et al.) disclose oral compositions, such as mouthwashes and toothpastes, for inhibiting the formation of dental plaque without staining the teeth which contain a combination of an anti-bacterial pyri idine amine base plus one or more zinc salts (see col. 5, lines 13-44) . U.S. 4.826.676 (Gioffre et al.) discloses oral fluorine- containing anticariogenic compositions containing zeolite zinc ions which are retained at advantageous levels over protracted periods of time by adjusting the pH of the composition to 9.5-11. The zeolite not only provides the desired Zn ⁺⁺ ion concentration but also is an exceptionally good abrasive and/or polishing agent. U.S. 5,059.416 (Cherukuri et al.) discloses a new delivery system for zinc compounds which comprises a zinc core material coated with a first hydrophilic coating and a second hydrophobic

coating, which system has use in a variety of products including dentifrices. U.S. 5.085.850 (Pan et al.) discloses anti-plaque compositions which contain a combination of a morpholino-amino alcohol or salt thereof and a divalent metal salt such as the salts of zinc, copper, and magnesium (see col. 4, line 64 to col. 5, line 2) . U.S. 4.863.722 (Rosenthal) discloses improved dentifrices containing zirconium silicate of a particular particle size, synthetic amorphous precipitated hydrated silica, silicon dioxide of a particular particle size, and optionally the alkali metal zinc citrate described in U.S. 4.325.939. U.S. 5.188.820 (Cummins et al.) discloses oral compositions such as dentifrices with improved plaque efficacy provided by the inclusion of a mixture of a stannous salt and a zinc salt (see col. 2, lines 20-29). U.S. 4.911.927 (Hill et al.) discloses adding various chemical agents, such as tetrasodium or tetrapotassium pyrophosphates and zinc chloride aε anti-plaque/anti- gingivitis agents, to dental floss (see col. 12, lines 49- 53) . U.S. 4.952.392 (Tha e) discloses an oral rinse for plaque reduction which contains periwinkle and zinc chloride (see col. 5, lines 37-46 and col. 6, lines 37-46) .

There is still a need for improved oral care compositions which can help prevent gingivitis and tartar and plaque build-up.

SUMMARY OF THE INVENTION

The present invention provides oral care compositions in the form of dentifrices such aε toothpastes, tooth gels, and tooth powders; mouthwashes, mouthwash sprays, irrigating solutions, cleaning drops, or foams; flavored or unflavored chewing gums; candies, preferable sugarless; chewable tablets and lozenges; and coatings for coating or impregnating dental accessories such as dental floss, tooth brush bristles, and tooth

picks. The compositions comprise (a) an anti-microbially effective amount or an anti-tartar effective amount of submicron or agglomerated submicron zinc oxide particles, typically 0.05-20%, preferably 0.1-5%, by weight, which particles have a primary particle size of less than 1 micron and an agglomerated secondary particle size of 50 microns or less; and (b) a carrier in an amount sufficient to provide the desired consistency to the oral care compositions. The present invention also provides a process for treating diseases of the oral cavity or preventing tartar formation by adding to an oral composition, selected from the group consisting of a toothpaste, a tooth gel, a tooth powder, a mouthwash, a mouth spray, an irrigating solution, cleaning drops, a foam, a chewing gum, a candy, a lozenge, a chewable tablet, or a coating for dental accessories, (a) an anti-microbially effective amount or an anti-tartar effective amount of submicron zinc oxide particles or agglomerated submicron zinc oxides particles, typically about 0.05%-20%, preferably about 0.1-5%, by weight, which particles have a primary particle size of less than 1 micron and a secondary agglomerated particle size of 50 microns or less; and (b) a carrier in an amount sufficient to provide the desired consistency to the oral care composition.

The present invention also provides a process for treating an oral care accessory, such as dental floss, the bristles of tooth brushes, particularly disposable tooth brushes, and tooth picks, with a composition comprising (a) an anti-microbially effective amount or an anti-tartar effective amount of submicron zinc oxide particles or agglomerated submicron zinc oxide particles, typically 0.1- 20%, preferably about 0.2-5%, by weight, which particles have a primary particle size of less than 1 micron and a secondary particle size of 50 microns or less; and (b) a carrier suitable for coating or impregnating the oral care

accessory. The present invention further provides oral care accessories prepared by this process.

Specific, but non-limiting, examples of zinc oxide particles having sub-micron average particle sizes are available from Sachtleben Che ie under the trademark SACHTOTEC® and Presperse Inc. under the trademark Finex- 25®. The SACHTOTEC® particles have an average particle size of about 0.20 micron but the particle size can be as low as 0.005-0.015 micron; the agglomerated particle size is about 5-6.5 microns. The Finex-25® particles have an average particle size of about 0.1-0.5 micron; the agglomerated particle size is about 4-5 microns.

The term "oral care compositions" refers to a product which, in the ordinary course of usage is not intentionally swallowed for the purposes of the systemic administration of therapeutic agents. Rather, the product is retained in the oral cavity for a time sufficient to contact substantially all of the dental surfaces and/or oral tissues for purposes of oral activity. As used herein, the term "effective amount" means that amount which is sufficient to achieve the desired effect or result. The amount of zinc oxide particles which is effective is that amount which provides an anti¬ microbial and/or anti-tartar effect, which will depend on the form of the oral care composition, as well as upon whether or not a secondary anti-microbial agent is used. Typically, an anti-microbially effective amount is at least about 0.01% by weight and an anti-tartar effective amount is at least about 0.8%. For dentifrices, the amount of zinc oxide particles is about 0.1-10%, preferably 1-5%, by weight. For mouthwashes, mouth sprays and the like, the amount of zinc oxide particles is about 0.2-2%, preferably about 0.5- 1%, by weight. For chewing gums, the amount of zinc oxide particles is about 0.1-1%, preferably about 0.2-0.5%, by weight. For lozenges, chewable tablets and the like, the

amount of zinc oxide particles is about 0.05-0.5%, preferably about 0.1-0.4%, by weight. For coatings for oral care accessories, the amount of zinc oxide particles is about 0.1-20%, preferably about 0.2-5%, by weight. As used herein, "carrier" refers to a vehicle which is pharmaceutically acceptable and which is suitable for use in the oral cavity.

Oral care compositions containing zinc oxide exhibit enhanced anti-plaque properties. It is believed that the zinc ions are released from zinc oxide trapped in the plaque when the bacteria in the plaque metabolize sugars and release acids. These zinc ions are believed to inhibit nucleation of calcium phosphate crystals and thus prevent tartar from forming. Zinc ions have an advantage over pyrophosphate salts in the prevention of tartar in that pyrophosphates hydrolyze in saliva to inactive orthophosphate.

One skilled in the art would expect that the zinc needs to be provided in a soluble state to be most effective; however, the more soluble zinc salts, such as zinc sulfate, while somewhat effective, have a lingering unpleasant metallic and astringent taste. At the pH of most dentifrices, zinc compounds, including zinc oxide, have minimum solubility. Thus, it is surprising that the zinc oxide particles provide the desired protection. In addition, the lingering unpleasant metallic and astringent taste of most zinc salts is absent.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Dentifrices Dentifrices are provided in the form of a toothpaste, a tooth gel, or a tooth powder.

The toothpastes and tooth gels comprise (a) an effective amount of an abrasive, typically about 5-98%, preferably about 20-95%, by weight; (b) an effective amount

of submicron zinc oxide particles or agglomerated submicron zinc oxide particles, which particles have a primary particle size of less than 1 micron and a secondary agglomerated particle size of 50 microns or less; and (c) a liquid vehicle in an amount sufficient to provide the desired consistency. The amount of zinc oxide particles iε typically about 0.1-10%, preferably about 1-5%, by weight. In a toothpaste or tooth gel, the liquid vehicle may comprise water and a humectant in an amount ranging from about 10-90% by weight. Typically, water comprises up to about 50%, preferably 5-35% of the composition. However, an anhydrous toothpaste or gel can be formulated if desired. Typically, the humectant comprises 5-50% of the formulation, preferably 5-35%. In translucent gels, where the refractive index is an important consideration, it is preferred to use higher ratios of humectant to water than in opaque pastes. For a gel the ratio of humectant to water should be above about 0.5 to 1, preferably 1 to 1.

Optional, but preferred, components which are included in the toothpastes and tooth gels are organic and/or an inorganic thickeners; surfactants; flavoring agents; sweetening agents; coloring agents or pigments; secondary anti-microbial agents; additional anti-calculus agents such as pyrophosphate salts; anti-caries agents such as soluble fluoride sources which are compatible with the zinc oxide; buffering agents such as alkali metal ortho- phosphates, o-phosphoric acid, alkali metal glycerophoε- phates, tartrates and citrates; and/or like components conventionally added to toothpastes and tooth gels. The tooth powders comprise (a) an effective amount of an abrasive, typically about 60-98%, preferably about 80%, by weight, and (b) an effective amount of submicron zinc oxide particles or agglomerated submicron zinc oxide particles, which particles have a primary particle size of less than 1 micron and a secondary particle size of 50 microns or less. The amount of zinc

oxide particles is typically about 0.1-10%, preferably about 1-5%, by weight.

Optional, but preferred, components which are included in the tooth powder are surfactants; flavoring agents; sweetening agents; secondary anti-microbial agents; secondary anti-calculus agents such as pyrophosphate salts; anti-caries agents such as soluble fluoride sources which are compatible with zinc oxide; one or more processing aids to ensure product uniformity; and like components conventionally added to tooth powders.

Useful water-insoluble abrasives include sodium metaphosphate, potassium metaphosphate, tricalcium phos¬ phate, calcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, zirconium silicate, hydrated silica, hydrated alumina, bentonite, and mixtures thereof. When the dentifrice is a gel, the abrasive used is selected from those which will give clear or translucent gels. The refractive index of the humectant-water system is matched to that of the abrasive used.

Preferred abrasive materials which may be used alone or as mixtures include hydrated silica, silica gel, or colloidal silica and complex amorphous alkali metal aluminosilicates. When visually clear gels are employed, polishing agents of hydrated or colloidal silica, alkali metal aluminosilicate complexes, and alumina are particu¬ larly useful since they have refractive indices close to the refractive indices of the gelling agent-liquid systems (including water and/or humectant) commonly used in the gels.

Suitable humectants include glycerine, propylene glycol, sorbitol, polypropylene glycol and/or polyethylene glycol (e.g., molecular weight of 400-1200). Also advanta- geous are liquid mixtures of water, glycerine and sorbitol. In translucent gels, where the refractive index iε an

important consideration, it is preferred to use higher ratios of humectant to water than in opaque pastes.

Toothpastes and tooth gels typically contain a natural or synthetic organic thickener or gelling agent in proportions of about 0.1-10%, preferably 0.3-2%. Suitable organic thickeners include sodium carboxymethyl cellulose, starch, gum tragacanth, carrageenan, xanthan gum, poly- acrylate salts, polyvinylpyrrolidone, hydroxyethylpropyl cellulose, hydroxybutylmethyl cellulose, hydroxypropyl- methyl cellulose, or hydroxyethyl cellulose, which are usually used in amounts of 0.1-2.0%. Inorganic thickeners such as hydrated silicas may also be used in amounts of about 0.5-10% or greater.

Organic surfactants are useful herein to achieve increased cleaning action, to assist thorough and complete dispersion of the anti-bacterial agent throughout the oral cavity, and to improve the detergent and foaming properties of the dentifrices. Anionic, nonionic or ampholytic surfactants may be used. Examples of suitable anionic surfactants are the water-soluble salts of the higher alkyl sulfates such aε sodium lauroyl sulfate or other C ₈ -C ₁₈ alkyl sulfates, water-soluble salts of higher fatty acid monoglyceride monosulfates such as the sodium salt of the monosulfate monoglyceride of hydrogenated coconut oil fatty acids, alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxy propane sulfonate, and the sub¬ stantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds such as C ₁₂ -C ₁₆ fatty acids, alkyl or acyl radicals, and the like. Examples of the last mentioned amides are N-lauroyl sarcosinate and the sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristo.yl, or N-palmitoyl sarcosinate which should be substantially free from soap or similar higher fatty acid materials.

Other suitable surfactants include non-ionic agents such as the condensates of sorbitan monostearate with ethylene oxide, the condensates of ethylene oxide with propylene oxide, or the condensates of propylene glycol (available as Pluronics®) . Other examples of water-soluble nonionic surfactants are the condensation products of ethylene oxide with various other compounds which are reactive therewith and have long hydrophobic chains (e.g., ^C ₁₂ ~ ^C ₂₀ aliphatic chains) which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene moieties, such as condensation products of polyethylene oxide with fatty acids, fatty alcohols, fatty amides, or polyhydric alcohols (e.g., sorbitan monostearate) .

The various surfactants may be utilized alone or in admixture with one another. The total amount used is preferably about 0.05%-5%, more preferably about 0.1%-2.0%.

Sweetening agents are also useful herein. They include saccharin, sucralose, dextrose, levulose, aspar- tame, D-tryptophan, dihydrochalconeε, acesulfame, sodium cyclamate, and calcium cyclamate. They are generally used in amounts of about 0.1-4%.

Secondary anti-microbial agents can be included in the dentifrices to help inhibit plaque formation and gingivitis or to reduce mouth odor. If present, the secondary anti-microbials generally comprise about 0.01-1% by weight, preferably about 0.02-0.10%. The non-ionic secondary anti-microbial agents have the advantage of not losing efficacy in the presence of anionic surfactants.

Cationic anti-microbials such as cetyl pyridinium chloride (CPC) or benzothonium chloride are useful herein. Cetyl pyridinium chloride is preferred. Bis-biguanides are also effective. Such agents include chlorhexidine (1,6- bis- [N ⁵ -p-chlorophenyl-N-biguanidohexane) , the soluble and insoluble salts thereof and related materials such as 1,2- bis(N ⁵ -p-trifluoromethylphenyl-N ^** -biguanido)ethane which are described more fully in U.S. Pat. No. 3,923.002. U.S. Pat.

No. 3.937.807. Belgian Pat. No. 843.244. and Belgian Pat. No. 844.764. When using cationic agents, it is generally necessary to avoid using anionic surfactants in the composition. Water-insoluble, non-ionic anti-microbials such as 2' ,4,4 '-trichloro-2-hydroxy-diphenyl ether (Triclosan) and 2,2 '-dihydroxy-5,5'-dibromo-diphenyl ether are useful herein. In addition to these halogenated diphenyl ethers, phenol and its homologs, mono- and poly-alkyl and aromatic halophenols, resorcinol and its derivatives, bisphenolic compounds and halogenated salicylanilides are useful. These include: 2-, 3-, or 4-methyl phenol; 4-ethyl phenol; 2,4-, 2,5-, 3,4-, and 2,6-dimethyl phenol; 4-n-propyl, 4-n- butyl, 4-n-amyl, 4-tert-amyl, 4-n-hexyl, or 4-n-heptyl phenol; methyl, ethyl, n-propyl, n-butyl, n-amyl, n-hexyl, or cyclohexyl p-chlorophenol; n-heptyl p-chlorophenol; n-octyl o- or p-chlorophenol; o-benzyl p-chlorophenol; o-benzyl-m-methyl p-chlorophenol; o-benzyl m,m-dimethyl p-chlorophenol; o-phenylethyl p-chlorophenol; o-phenylethyl m-methyl p-chlorophenol; 3-methyl or 3,5-dimethyl p-chlorophenol; 6-ethy1-3-methyl p-chlorophenol; 6-n- or 6-isopropy1-3-methyl p-chlorophenol; 2-ethyl-3-methyl or 3,5-dimethyl p-chlorophenol; 6-iso-propyl-3-methyl or 2-ethy1-3-methyl p-chlorophenol; 6-sec-butyl or octyl-3- methyl p-chlorophenol; 2-iso-propyl-3 , 5-dimethyl p-chlorophenol; 6-diethylmethyl-3-methyl or 3,5-dimethyl p-chlorophenol; 2-sec-amyl-3,5-dimethyl p-chloro-phenol; methyl, ethyl, n-propyl, n-butyl, n- or sec-amyl, or cyclohexyl p-bromophenol; tert-amyl, n-hexyl, or n- propyl-m,m-dimethyl o-bromophenol; 2-phenyl phenol; 4- chloro- 2- or 3-methylphenol; 4-chloro- or 2,4-dichloro- 3,5-dimethylphenol; 3,4,5,6-terabromo 2-methylphenol; 5- methyl-2-pentylphenol; 4-isopropyl-3-methylphenol; 5- chloro-2-hydroxydiphenylmethane; methyl, ethyl, n-propyl, n-butyl, n-amyl, n-hexyl, n-heptyl, n-octyl, or n-nonyl resorcinol; phenyl, phenylethyl, or phenylpropyl

resorcinol; benzyl or p-chlorobenzyl resorcinol; 4- or 5- chloro-2,4-dihydroxydiphenyl methane; 4- or 5-bromo-2,4- dihydroxydiphenyl methane; 2 , 2 '-methylene bis(4- chlorophenol) ; 2 ,2 '-methylene bis(3,4,6-trichlorophenol) ; 2,2 '-methylene bis(4-chloro-6-bromophenol) ; bis(2-hydroxy- 3,5-dichlorophenyl) or bis(2-hydroxy-5-chlorobenzyl) sulfide; 4' ,5-dibromo- or 3,3' ,5- or 3,4 ^» ,5-tribromo- salicylanilide; 3,3' ,5- or 3,4' ,5- trichloro-salicylanilide or 2,3,3* ,5-tetrachloro-salicylanilide; 3,5-dibromo-3 '- or 4 '-trifluoro ethyl salicylanilide; 5-n-octanoyl- 3 '-trifluoromethyl salicylanilide; methyl, ethyl, propyl, or butyl p-hydroxy-benzoic acid; 3,3' ,4- or 3,4,4'- trichloro-carbanilide; 3-trifluoromethyl-4 , 4 ' - dichlorocarbanilide; and like phenolic compounds. A solvent, typically 1-10%, preferably 2-6%, is used with water-insoluble, non-ionic secondary microbial agents. Preferred solvents are flavor oils such as oil of wintergreen, peppermint, spearmint, sassafras, and clove. Also useful are polyethylene glycols having a molecular weight of about 200-600; (di)propylene glycols; methyl or ethyl cellosolve; olive or castor oil; amyl or ethyl acetate; glyceryl tristearate, benzyl benzoate; and mixtures thereof.

Secondary anti-calculus agents include the soluble complex phosphate salts such as pyrophosphates, tripolyphosphates, and hexametaphosphates. They include mono-, di-, tri- or tetraalkali metal pyrophosphates and mixtures thereof. The preferred pyrophosphate salts include disodium pyrophosphate, dipotassium pyrophosphate, tetrasodium pyrophosphate, and/or tetrapotassiu pyro¬ phosphate. The pyrophosphates may be employed in their anhydrous or hydrated forms. Although a particular pyro¬ phosphate salt, e.g. , disodium pyrophosphate, may be the pyrophosphate salt initially added to the composition, the actual pyrophosphate ion present in the composition and the quantity present in the dentifrice is dependent on the

final pH of the dentifrice. If desired, pyrophosphates are added to the dentifrices in amounts from about 0.5-10%, typically 1-6%.

The dentifrices can include a water-soluble fluoride ion source which is effective both as a pyrophosphatase inhibitor and as an anti-caries agent. Suitable fluoride ion sources include inorganic fluoride salts such as soluble alkali metal or alkaline earth metal salts, e.g. , sodium fluoride, potassium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate or sodium monofluorophosphate. Alkali metal fluorides such as sodium fluoride, sodium mono- fluorophosphate, and mixtures thereof are preferred.

The amount of the soluble fluoride ion source in the dentifrice is dependent on the particular compound used and the type of dentifrice, but it must be incorporated in an effective, but non-toxic, amount, generally up to about 5.0%. Any suitable minimum amount of fluoride may be used, but it is preferable to employ a quantity sufficient to release about 50 up to about 3500 ppm, preferably about 850-1500 ppm, of fluoride ions. In the case of sodium fluoride, the fluoride ion source is present in an amount from about 0.05-0.65%, preferably about 0.18-0.35%. In the case of sodium monofluorophosphate, the amount is about 0.2-2%, more typically about 0.65%-l.20%.

Various other materials may be incorporated in the dentifrice compositions. Examples thereof are coloring and whitening agents, preservatives, silicones, and/or chlorophyll compounds. These adjuvants are incorporated in amounts which do not substantially adversely affect the properties and characteristics desired and are selected and used in effective amounts, depending upon the particular adjuvant and type of dentifrice involved.

The dentifrice compositions herein are prepared using conventional mixing techniques. They are also used in a conventional manner.

Mouthwashes The mouthwashes may be conveniently prepared by simply adding, at any convenient point of manufacture, the zinc oxide particles and sodium bicarbonate, in no particular order, to water or a water/alcohol mixture. Optional ingredients include thickeners; humectantε; anti- caries-effective fluoride compounds; secondary anti¬ microbial agents; surfactants; sweetening agents; flavoring agents; and/or coloring agents. The non-aqueous liquid may be selected from the group consisting of ethyl alcohol, propylene glycal, 1,3-butylene glycol, and mixtures thereof. Suitable thickeners, humectantε, surfactants, flavoring, sweetening and/or coloring agents, anti-caries agents, and secondary anti-microbial agents are discussed under Dentifrices.

A typical mouthwash comprises: (a) an anti- microbially effective amount or an anti-tartar effective amount of the above-described submicron or agglomerated submicron zinc oxide particles; (b) 0 to about 50% of a non-aqueous liquid; (c) 0 to about 20%, preferably 5-20% of a humectant; (d) 0 to about 12% of a surfactant; (e) 0 to about 0.3% of a flavoring agent; and (f) the balance water to 100%. Typically, the amount of zinc oxide particles is about 0.2-2%, preferably 0.5-1%, by weight. Optionally, the mouthwash may contain up to 1% of an anti-caries agent and 0.01-0.5%, preferably 0.02-0.2%, by weight of a secondary anti-microbial agent such as Triclosan or cetylpyridinium chloride (CPC) .

Gums The gum base employed will vary greatly depending on various factors such as the type of base used, the consistency desired and the other components used to make the final product. An anti-microbially effective amount or an anti-tartar effective amount of zinc oxide particles is added to the gum base. Typically, the amount of zinc oxide particles is about 0.1-1%, preferably about 0.2-0.5%, by

weight. Gum amounts of about 5-85% by weight of the final chewing gum composition are acceptable, with the preferred amounts being about 15-70% by weight. The gum base may be any water-insoluble gum base well known in the art. Illustrative examples of gum bases include both natural and synthetic elastomers and rubbers, substances of vegetable origin such as chicle, jelutong, gutta percha and crown gum, synthetic elastomers such as butadiene-styrene copolymers, isobutylene-isporene copolymers, polyethylene, poly-isobutylene, polyvinylacetate and mixtures thereof which are particularly useful.

The gum base composition may contain elastomer solvents to aid in softening the rubber component. Suitable solvents include methyl, glycerol or pentaerythritol esters of rosins or modified rosins, such as hydrogenated, dimerized or polymerized rosins or mixtures thereof, e.g., the pentaerythritol ester of partially hydrogenated wood rosin, pentaerythritol ester of wood rosin, glycerol ester of wood rosin, glycerol ester of partially dimerized rosin, glycerol ester of polymerized rosin, glycerol ester of tall oil rosin, glycerol ester of wood rosin and partially hydrogenated wood rosin and partially hydrogenated methyl ester of rosin, such as polymers of alpha-pinene or beta-pinene; terpene resins including polyterpene and mixtures thereof. The solvent may be employed in an amount ranging from about 10-75%, preferably about 45-70%, by weight of the gum base.

A variety of traditional ingredients are also used. These include plasticizers or softeners such as lanolin, stearic acid, sodium stearate, potassium stearate, glyceryl triacetate, glycerin and the like and natural waxes, petroleum waxes such as polyurethane waxes, paraffin waxes and microcrystalline waxes. These ingredientε may be reduced in amount or, in some cases, may be eliminated entirely. When present, these materials are generally employed in amounts of up to about 15% by weight,

preferably about 3-10% by weight, of the final gum base composition.

Useful flavoring agents may be chosen from synthetic flavoring liquids and/or liquids derived from plants, leaves, flowers and fruits, and combinations thereof. Preferably, the flavor component is selected from spearmint oil, cinnamon oil, oil of wintergreen (methylsalicylate) , and peppermint oil. Also useful are artificial, natural or synthetic fruit flavors such as citrus oil including lemon, orange, grape, lime and grapefruit and fruit essences including apple, strawberry, cherry, pineapple and the like.

The amount of flavoring agent employed is normally a matter of preference subject to such factors as flavor type, base type, and flavor strength desired. In general, amounts of about 0.05-3.0% by weight of the final chewing gum composition are suitable, with amounts of about 0.3-2.5% being preferred and about 0.7-2.0% being most preferred. Those sweeteners well known in the art, including both natural and artificial sweeteners, may be included. The sweeteners may be sugars such as sucrose, glucose (corn syrup) , dextrose, invert sugar, fructose, and mixtures thereof, saccharine and its various compounds such as the sodium or calcium compound; cyclamic acid and its various compounds such as the sodium compound; the dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside) ; chloro derivatives of sucrose; dihydroflavinol; hydroxyguaiacol esters; L-amino dicarboxylic acid gem-diamines; L-aminodicarboxylic acid aminoalkenoic acid ester amides; and sugar alcohols such as sorbitol, sorbitol syrup, mannitol, xylitol, and like sweeteners. Also contemplated as an additional sweetener is the nonfermentable sugar substitute (hydrogenated starch hydrolysate) described in U.S. Pat. No. Re. 26.959. Also contemplated is the

synthetic sweetener 3,6-dihydro-6-methyl-l,2,3-oxathiazin- 4-one-2,2-dioxide, particularly the potassium (acesulfame- K) , sodium and calcium compounds thereof, as described in German Patent No. 2.001.017.7. The coloring agents useful herein include pigments such as titanium dioxide, which may be incorporated in amounts of up to about 1% by weight, preferably up to about 0.06% by weight. The colorants may include other dyes suitable for food, drug and cosmetic applications, known as FD&C dyes. Preferably, the foregoing materials are water-soluble. Illustrative examples include FD&C Blue No. 2 which is the disodium compound of 5,5'-indigotindisulfonic acid and FD&C Green No. 1 which is the monosodium compound of 4-[4-N-ethyl-p- sulfobenzylamino) diphenylmethylene]-[1-(N-ethyl-N-p- sulfoniumbenzyl)-2-5-cyclohexadieneimine] . A full recitation of all FD&C and D&C and their corresponding chemical structures may be found in the Kirk-Othmer Encyclopedia of Chemical Technology, Volume 5, pages 857- 884.

The chewing gum composition may additionally include fillers such as aluminum hydroxide, alumina, aluminum silicates, calcium carbonate, talc and combinations thereof. These fillers may be used in various amounts, preferably about 4-30% by weight of the final chewing gum.

A representative process for preparing a chewing gum composition is as follows. The gum base is melted at about 85° to about 90° C. , cooled to 78° C. , and placed in a pre-warmed (60° C.) standard mixing kettle equipped with sigma blades. Any emulsifier for the gum base is then added and mixed in. Next, a portion of sorbitol and any glycerin is added and mixed in for an additional 3 to 6 minutes. The mixing kettle is cooled and mannitol, and the remainder of the sorbitol and glycerin are then added and mixing is continued. At the time, the unflavored

chewing gum temperature is about 39-50°C. The flavor and zinc oxide particles may then be added and incorporated in the base, and mixing is thereafter continued. Finally, the sweetener material is added and mixed in for an additional 1 to 10 inuteε. The final gum temperature is about 39- 50°C. The chewing gum composition is then discharged from the kettle, rolled, scored and formed into the desired shape. The chewing gums may be in any form known in the art, such as stick gum, slab gum, chunk gum, shredded gum, hard-coated gum, tableted gum, aε well aε center-filled- gum.

Lozenges and Chewing Tablets As indicted herein, the zinc oxide particles may be incorporated into a variety of lozenges, chewable tablets, and even candy products in anti-microbially effective or anti-tartar effective amounts, typically about 0.05-0.5%, preferably 0.1-0.4%, by weight.

The vehicle or carrier used for the tablet or lozenge is a non-cariogenic solid, water-soluble polyhydric alcohol (polyol) such as mannitol, xylitol, sorbitol, altitol, a hydrogenated starch hydrolysate ("Lycaεin") , hydrogenated glucose, disaccharides and polysaccharides. The carrier is the major ingredient, and it is used in amounts of about 90-98% by weight of the total composition. Tableting lubricants, in minor amounts of about

0.1 - 5% by weight, may be incorporated into the tablet or lozenge formulation to facilitate their preparation. Suitable lubricants include vegetable oils such as coconut oil, magnesium stearate, aluminum stearate, talc, starch and "carbowax".

Lozenge formulations contain about 2% gum as a barrier agent to provide a shiny surface as opposed to a tablet which has a smooth finish. Suitable non-cariogenic gums include kappa carrageenan, carboxymethyl cellulose, hydroxyethyl cellulose, "Gantrez" (poly(-vinylmethyl ethermaleic anhydride)) and the like.

The lozenge or tablet may optionally be coated with a coating material such as waxes, shellac, carboxy ethyl cellulose, polyethylene/malic anhydride copolymer or kappa carrageenan to further increase the time it takes the tablet or lozenge to dissolve in the mouth. The uncoated tablet or lozenge is slow dissolving, providing a sustained release rate of active ingredients of about 3 to 5 minutes. Accordingly, the tablets or lozenges afford a longer time period of contact with the active ingredients in the mouth than a toothpaste, toothpowder or mouth rinse which is typically in contact with the mouth for only about 30-90 seconds of brushing or rinεing.

Any compatible surfactant may be incorporated in the tablet or lozenge. The surfactant provides additional detersive, foaming and anti-bacterial properties depending upon the specific type of surfactant. Suitable surfactants are described under Dentifrices.

Particularly suitable surfactants include non- ionic agents such as condensates of sorbitan monostearate with approximately 20 moleε of ethylene oxide, εorbitan diisostearate condensed with 40 moles of polyethylene glycol, condensates of ethylene oxide with propylene glycol (Pluronics*) and castor oil ester (e.g. Cremopher EL) and amphoteric agents such as quaternized imidazole derivatives available as MIRANOL ^® and MIRANOL C2M ^® . The non-ionic surfactants are preferred, particularly the condensates of sorbitan monostearate or diisostearate with 20 to 40 moles of ethylene oxide or polyethylene glycol.

The various surfactants are used in any suitable amount, generally from about 0.05-5%, preferably from about 0.5-2%, by weight.

Secondary anti-microbial agents may also be employed in amounts of about 0.01-0.1%, preferably 0.02- 0.05%, by weight. Suitable secondary anti-microbial agents are discussed under Dentifrices. A preferred secondary anti-microbial agent is cetyl pyridinium chloride (CPC) .

Minor amounts of coloring agents, dyes or ultraviolet absorberε to enhance the color and consumer acceptability may also be included in the tablets and lozenges. The tabletε and lozengeε are prepared by dry mixing or blending the ingredients with an inert carrier. The blended mixture is introduced into a tablet machine to shape the final product.

The solid dose oral preparations should be slowly dissolved in the mouth for a period of about 3 to 5 minutes, which affords long lasting activity of up to about 12 hours duration.

Dental Floss

Waxing is a conventional procedure used for coating the outer surfaces of the bundle of floss strands.

A suitable wax for use herein is a high molecular weight polyethylene glycol which is solid at room temperature.

The zinc oxide is typically added in amounts of about

0.1-20%, preferably 0.2-0.5%, by weight. It is suspended in the molten polyethylene glycol.

Alternatively, the floss can be impregnated with a molten coating composition using the procedure described in U.S. 4.411.927. The coating compositions of the '927 patent typically contain a surfactant (PLURONIC T127®) , εilicone, glycerine or εaccharin, a flavor or εorbitol, and a thickener such as methyl cellulose (Methocel) or carrageenan.

If desired, the zinc oxide particles can be suspended in alcohol and/or water and the bundle of floss strands can be dipped in the suεpension and allowed to air dry.

The following examples further illustrate the present invention, but it is understood that the invention iε not limited thereto. All amountε and proportions referred to herein and in the appended claims are by weight and temperatures are in degrees Celsius unless otherwise

indicated. Also, unless indicated otherwise, the zinc oxide particles used or suggested for use in the following examples have a primary particle size of less than 1 micron and are agglomerated to a median secondary particle size of about 4.6-6.4 microns.

Example 1 This example illustrates the surprising benefit of agglomerated submicron zinc oxide particles for use as a plaque inhibiting ingredient. The efficacy of zinc oxide particles in preventing plaque growth was compared with zinc citrate, zinc sulfate and chlorhexidine using a 3 day in vitro plaque growth model which simulates consumer use conditions. The SACHTOTEC® zinc oxide used had a primary particle size of <1 micron, typically about 0.2 micron, and the particles were agglomerated to a median secondary particle size of about 6.4 microns.

In the model, S. mutans was grown up in Brain heart infusion medium containing 3% sucrose into which glass rods were suspended. After overnight growth the glass rods with adherent plaque were immersed for 60 seconds in the anti-plaque test solutions or suspensions followed by 30 seconds in a water rinse. The rods were then resub erged in fresh daily growth medium for 6 hours at 37°C. The rods were retreated with the anti-plaque test solutions or suspensions, rinsed, and then stored overnight in saliva at 37°C. The treatment and growth cycles were repeated to complete a total of three full cycles, after which the dry weight of the plaque formed on the rods was determined. The results are shown below.

Anti-Plaque Test Solutions/Suspensions % Plague Reduction Water control 0

0.5% zinc oxide suspension 71

0.5% zinc sulfate heptahydrate solution 61 0.5% zinc citrate suspension 34

0.12% chlorhexidine solution 72

The results show the unexpected advantage of the zinc oxide particles over zinc citrate and zinc εulfate and itε equivalence to chlorhexidine. Surprisingly, the advantage of zinc oxide particles over zinc citrate and zinc sulfate is not related to the quantity of dissolved zinc ion provided. Filtered solutions of the zinc compounds showed the following level of dissolved zinc aε measured by atomic absorption:

Zinc sulfate solution 895 ppm zinc ion Zinc citrate suspension 418 ppm zinc ion

Zinc oxide suspension <0.25 ppm zinc ion

Example 2 The following in vitro plaque assay demonstrates that the anti-plaque activity of the water-insoluble zinc oxide (ZnO) particles was due to the presence of the particles in the suspension.

Three sets of glass rods (n=5) covered with plaque were treated with two aqueous suspensions containing agglomerated submicron zinc oxide particles and one aqueous suspension containing non-agglomerated ordinary zinc oxide particles having a primary particle size of about 1.9 microns. The submicron zinc oxide particles available from

Sachtleben Chemie under the trademark SACHTOTEC® had a primary particle size of less than 1 micron, typically about 0.2 micron, and a secondary agglomerated particle size of about 4.6-5.1 microns. The submicron zinc oxide particles available from Presperse Inc. under the trademark

Finex-25® had a primary particle size of about 0.1-0.5 micron, typically about 0.2 micron, and a secondary agglomerated particle size of about 4-5 microns.

Treatment Plague (mean mg.) Reduction (%.

Unfiltered ZnO

0.25% Finex-25® 20.8 46

0.25% SACHTOTEC® 23.7 36

0.25% Whittaker 66 27.5 23

Filtered ZnO

0.25% Finex-25® 33.3 3

0.25% SACHTOTEC® 33.5 2

0.25 Whittaker 66 33.7 1

Distilled Water 34.2 0

The treatment is expressed as concentration within the treatment suspension.

The results show that the greatest anti-plaque effects were observed with the unfiltered suspensions, thus indicating that the anti-plaque activity of the zinc oxide was dependent upon the presence of insoluble zinc oxide particles. It is believed that the insoluble particles are caught within the plaque and that zinc ions are subsequently released as the plaque pH decreases. The highest reductions in plaque were observed with the two agglomerated submicron zinc oxide samples (SACHTOTEC® and Finex-25®) .

Example 3 The following in vitro plaque asεay shows the effect of cetylpyridinium chloride (CPC) , an anti¬ microbial, on the anti-plaque activity of agglomerated submicron zinc oxide (ZnO) particles in an aqueous suspension. The procedure described in Example 2 was used for carrying out the assay. Treatment Plague (mean mq.) Reduction (%)

0.05% CPC 25.3 33

0.0625% ZnO 28.2 24

0.25% ZnO 20.1 50%

0.25% ZnO + 0.05% 15.4 65 0.125% ZnO + 0.05% 18.5 55

0.625% ZnO + 0.05% 20.1 50% Distilled Water 35.6 0

The treatment is ≥xpressed aε concentration within treatment solution or suspension.

The results show that the addition of the cetylpyridinium chloride to various levels of agglomerated submicron zinc oxide particles suspended in water increased

the anti-plaque activity of those suεpensions. This increase in activity appears to have been somewhat additive in nature.

Examples 4-9 The following are representative toothpastes containing agglomerated submicron zinc oxide particles:

Ingredients 4 _. 5 §_ 1_ 8. £

Zinc oxide 2.000 4.000 1.000 2.000 2.000 2.000

Calcium - 43.114 pyrophos¬ phate

Dicalcium 43.057 40.157 40.450 - 40.007 41.277 phosphate dihydrate Tetrasodium - - 5.350 - 5.350 2.000 pyrophos¬ phate

Sodium - 0.500 0.500 - monofluoro- phosphate

Sodium - 0.243 0.243 0.243 fluoride

Glycerin 24.070 34.070 20.070 25.670 21.070 4.100

Polyethylene 1.000 1.000 1.200 - 1.000 glycol

(PEG-8)

Carboxy- 1.250 0.850 0.650 0.650 0.650 0.700 methyl cellulose Water 26.315 7.315 28.180 26.115 26.880 7.280

Sodium 0.508 0.508 1.000 0.608 1.000 0.800 saccharin

Sorbitol _ _ _ _ _ 40.100

Sodium 1.000 0.800 0.300 0.900 0.500 0.800 lauryl sulfate

Sodium - - 0.300 - 0.300 lauroyl sarcosinate (30%)

Flavor 0.800 0.800 1.000 0.700 1.000 0.700

100.000 100.000 100.000 100.000 100.000 100.000

Examples 10-15 The following are representative tooth gels containing agglomerated submicron zinc oxide particles.

Ingredients .10 11 1Z 13 14 15

Zinc oxide 2.000 4.000 1.000 2.000 5.000 2.000

Tetrasodium - - 5.350 - 9.000 2.000 pyro¬ phosphate

Sodium - - 0.243 0.243 0.243 0.243 fluoride

Glycerin 17.000 46.845 17.000 28.745 14.745 24.957

Sorbitol 41.535 20.290 41.577 31.997 37.882 40.100

(10% solution)

Polyethylene 1.000 - 1.000 - - - glycol

(Sylodent

700)

Carboxy- 0.650 0.450 0.300 0.600 0.600 0.600 methyl cellulose

Water 16.110 8.110 10.875 16.110 10.875 5.275

Sodium 0.500 0.500 0.650 0.500 0.650 0.650 saccharin

Abf sive 15.000 12.000 15.000 15.000 12.000 15.000 hydrated silica

(Sylodent

700)

Thickening 4.500 6.000 5.000 3.000 7.000 6.000 silica

(Sylox 2)

Sodium 1.000 1.000 - 1.000 1.000 0.500 lauryl sulfate

Sodium - - 1.000 - - 1.670 lauroyl sarcosinate

(30%)

Ingredients 10 11 12 13 14 15

Flavor 0.700 0.800 1.000 0.800 1.000 1.000

Color 0.005 0.005 0.005 0.005 0.005 0.005

100.000 100.000 100.000 100.000 100.000 100.000

Examples 16-20 The following are representative tooth powders containing agglomerated submicron zinc oxide particles.

Ingredients 16 11 13. 19 20

Zinc oxide 2.000 4.000 1.000 2.000 2.000

Dicalcium 46.400 85.400 82.900 - - phosphate dihydrate

Calcium 50.000 - - 95.657 50.000 pyrophos¬ phate

Teraεodium - - 5.350 - 5.350 pyrophos¬ phate

Sodium - 0.800 0.800 - - monofluoro¬ phosphate

Sodium - - - 0.243 0.243 fluoride

Sodium 0.400 0.300 0.650 0.500 0.650 saccharin

Magnesium 0.100 0.200 0.100 0.300 - oxide

Sodium 0.500 0.500 0.500 0.300 0.500 lauryl sulfate

Abrasive - 8.000 8.000 - 40.257 hydrated silica

(Sylodent

700)

Flavor 0.600 0.800 0.700 1.000 1.000

100.000 100.000 100.000 100.000 100.000

Examples 21-26 The following are preferred toothpastes, tooth

gels, and tooth powders containing agglomerated submicron zinc oxide particles and, 2' ,4,4'-trichloro-2-hydroxy- diphenyl ether (Triclosan) or cetylpyridinium chloride (CPC) as secondary anti-microbial agents. The Triclosan is blended in as is or preferably added to the flavor oil if a toothpaste or tooth gel is being prepared. The CPC iε dissolved in the water and added as a solution if a toothpaste or tooth gel is being prepared. They are directly added to the tooth powders.

Ingredients Pastes Gels Powders

21 22 22 24 25 26

Zinc oxide 2.000 2.000 0.500 0.500 2 .000 2.000

Triclosan 0.500 - 0.500 - 0, .500 -

Cetylpyri¬ - 0.300 - 0.300 - 0.300 dinium chloride

(CPC)

Calcium 42.007 40.464 - - 96. .257 95.957 pyrophos¬ phate

Sodium 0.243 0.243 0.243 0.243 0. .243 0.243 fluoride

Glycerin 34.070 34.070 20.355 18.705 - -

Sorbitol - - 41.577 41.577 - -

(70% solution)

Polyethylene 1.000 1.000 1.000 1.000 - - glycol

(PEG-8)

Sodium 0.850 - 0.300 0.300 - - carboxy- methyl cellulose

(9M31F)

Hydroxyethyl - 1.00 - - - - cellulose

Water 17.315 17.315 10.875 10.875 - -

Sodium 0.508 0.508 0.650 0.500 0 .300 0.300 saccharin

Ingredients Pastes Gels Powders

Magnesium 0.200 0.200 oxide

Hydrated 15.000 15.000 silica Thickening 7.000 7.000 silica

Sodium 0.800 1.000 0.500 lauryl sulfate Sodium 0.300 1.000 1.000 lauroyl sarcosinate

Pluronic 2.000 2.000

F-108 (Poloxamer

338)

FD&C Blue #1 0.033 0.033

(1% solution) FD&C Yellow 0.167 0.167

#10

Flavor 0 . 800 0 . 800 0 . 800 0 . 800

Examples 27-30 The following are representative mouth washes and a mouth spray containing agglomerated submicron zinc oxide particles.

Ingredients Mouthwashes Mouth Spray

21 23. 29 _. 30

Zinc oxide 0.50 2.00 2.00 0.15

Urea peroxide - - 40.00 -

Sodium lauryl - - 1.00 - sulfate

Glycerol 5.00 5.00 - -

Cremophor EL 0.25 0.25 - 0.50

Ethanol 0.10 - - - poloxyeth- ylene sorbitan monoleate

Ethanol - 10.00 ml.

10.00 ml. 10.00 ml.

Flavor - - 5 ml.

Aromatics, 0.10 0.10 - 0.10 saccharin

Sodium - - 0.125 ml. saccharin

Color - - q.s.

Water to 100.00 to 100.00 to 400.00 to 100.00

Propellant - - - As needed

Example 31 This example describes a representative chewing gum containing agglomerated submicron zinc oxide particles. Ingredients Parts Gum base 25

70% Aqueous sorbitol solution 11 Crystalline sorbitol NF 53

Glycerine NF 0.5

Zinc oxide 0.5 Flavor q.s.

The gum base is mixed in a small mixer and heated in a water bath at 38°C for 4 minutes. During thiε mixing the zinc oxide particleε are added. The flavor dissolved in a mixture of the glycerine and aqueous sorbitol solution is added to the gum mixture and mixing is continued for a further 2 minutes. Finally, the crystalline sorbitol is added and the mixture is heated to 43°C and cast into sticks on a flat plate. Zinc oxide is slowly released upon chewing and should become trapped in the plaque between the teeth.

Example 32-33 These examples describe a representative lozenge and chewable tablet containing agglomerated submicron zinc oxide particles. Lozenge

Ingredients Parts

Kappa carrageenan 2.000

Sorbitol 94.389

Sodium saccharin 0.150

Coconut oil 2.000

PEG-40 sorbitan diisostearate 1.000 Blue dye 0.006

Zinc oxide 0.200

High mint (80-95%) flavor 0.245

Alpha ionone 0.01

The sorbitol is thoroughly blended with the carrageenan. The zinc oxide particles and saccharin are added to, and mixed with, the sorbitol-carrageenan blend to form a powder blend. The dye is dispersed in the diisostearate surfactant and added to the powder blend. Then the coconut oil is added. The total mixture is heated to about 240°F with mixing. The mixture is cooled to 180°F and the flavor and ionone are added. The cooled mixture is molded, stored until hard, and demolded. The resulting product can be conveniently used after meals, at bedtime, and anytime.

Chewable Tablet Ingredients Parts

Wintergreen oil 0.36 Peppermint oil 0.18

Menthol 0.51

Silica (Syloid 244) 0.60

Sodium saccharin 0.18

Zinc oxide 0.18 Mannitol, USP (granular) 96.79

Calcium stearate 1.20

The flavoring oils, zinc oxide particles, and menthol are mixed and the mixture is absorbed on the silica. The remaining ingredients are then added. The mixture is blended and compressed on a 1 centimeter flat beveled edge punch to a suitable tablet thickness.

Examples 34-35 The following are representative dental flosεeε coated with a mixture containing agglomerated submicron zinc oxide particles. Ingredients 34 35

Peppermint oil NF 1.5

Clove oil NF 0.3

Sodium saccharine NF 0.2 0.2

Zinc oxide 2.0 2.0 Poyethylene glycol q.s. q.s.

First, the polyethylene glycol is melted at about

50°C and then flavor oils (if used) , sodium saccharine, and zinc oxide particles are mixed in. A preformed dental floss is passed through the molten suspension and the coated floss is then allowed to dry.

The above compositions are effective in reducing calculus and preventing gum disease and they possess acceptable organleptic properties.

In addition to the levels and combinations of ingredients shown in these examples, others can be used which are consistent with the invention disclosed and claimed herein.