WO1994026244A1 - Oral care compositions containing zinc oxide particles and sodium bicarbonate - Google Patents

Abstract

Submicron zinc oxide particles or agglomerated submicron zinc oxide particles are added to oral care compositions containing sodium bicarbonate such as tooth pastes, tooth gels, tooth powders, mouthwashes, gums, lozenges, chewable tablets or coated onto oral care accessories such as dental floss to inhibit the formation of plaque. The compositions contain a carrier and optionally other conventional ingredients.

Description

ORAL CARE COMPOSITIONS CONTAINING ZINC OXIDE

PARTICLES AND SODIUM BICARBONATE

FIELD OF THE INVENTION

The present invention relates to oral care compositions which provide anti-plague, anti-tartar, and gingivitis preventative 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 composed 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 plague, 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 irritation 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. Generally, once formed, mechanical removal 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 other users they cause sensitivity to the teeth.

Prevention of plague and gingivitis can be very important to the health of individuals. Loss of teeth and other ill affects 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 plague. In mild cases the only symptom is a slight reddening 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. Sometimes, however, over-the-counter chemotherapeutic agents such as anti-bacterial mouthwashes or toothpastes containing anti-bacterial agents are useful in preventing gingivitis in more susceptible individuals.

Many kinds of anti-bacterial agents, when incorporated 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. Toothpastes 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 reported; however, due to the unpleasant lingering taste of zinc salts, only minor levels of zinc salts have been used. Since one would expect any microbial 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 is believed that in some cases it can lead to or be a precursor to more serious gum diseases known as periodontitiε.

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 human health products. 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. 7, 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 plague 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 ,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. 4.647.452 (Ritchey et.al.) discloses a composition for retarding plaque which is a mixture of 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 as glycine in a base material such as dentifrices. U.S. 4.814.163 and U.S. 4.814.164 (Barth) disclose antitartar 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. 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. 4.170.634 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. 2, 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. 4.309.409 (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. 3.624.199 (Norfleet) discloses a stable dental cream containing hydrated alumina, calcium carbonate or an insoluble alkali 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° (e.g., trisodium phosphate) as a stabilizing agent to prevent separation of the cream. 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 a carboxylic, sulfonic, and/or phosphoric and radicals (see col. 3, line 64 to col. 4, line 63). U.S. 4.522.806 (Muhlemann et al.) disclose oral composition, such as mouthwashes and toothpastes, for inhibiting the formation of dental plaque without staining the teeth which contain a combination of an anti-bacterial pyrimidine amine base plus one or more zinc salts (see col. 5, lines 13-44) . U.S. .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 provide 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 morpholine-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.) disclose oral compositions such as dentifrices with an improved plaque efficacy provided by the inclusion of a mixture of the 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 as antiplaque/antigingivitis agents, to dental floss (see col. 12, lines 49-53). U.S. 4,952.392 (Thame) 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 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 as toothpastes, tooth gels, and tooth powders; mouthwashes, mouth sprays, irrigating solutions, cleansing drops, or foams; flavored or unflavored chewing gums; candies, preferably 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 anti-tartar effective amount of sodium bicarbonate, typically about 0.2- 98%, which amount will vary with the oral care form selected; (b) an effective amount of submicron or agglomerated submicron zinc oxide particles, which particles have a primary particle size of less than 1 micron and an agglomerated secondary particle size of 50 microns or less; and (c) 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 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, a chewing gum, a candy, a lozenge, or a chewable tablet, (a) an effective amount of sodium bicarbonate, typically 0.2-98% by weight preferably 0.5-10%; and (b) an anti-microbially effective amount or an anti-tartar effective amount of submicron zinc oxide particles or agglomerated submicron zinc oxide particles, typically 0.05-2%, preferably 0.1-1%, 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.

The present invention also provides a process for treating an oral care accessory, such as dental floss, the bristles of a tooth brush, particularly a disposable tooth brush, and a tooth pick with a composition comprising (a) an effective amount of sodium bicarbonate, typically about 1- 50%, preferably 5-40%, by weight, (b) an anti-microbially effective amount or an anti-tartar effective amount of submicron zinc oxide particles or agglomerated submicron zinc oxide particles, typically about 0.1-20%, preferably 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 (c) 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 Chemie under the trademark SACHTOTEC® and Presperεe 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 can have a 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 about 1-5%, by weight and the amount of sodium bicarbonate is about 3-98%, preferably 10-90%, by weight. In toothpastes the amount of sodium bicarbonate is about 3-70%, preferably 10-65%, in tooth gels the amount is about 3-60%, preferably 5-35%, and in tooth powder the amount is about 20-98%, preferably above about 50%. For mouthwashes and mouth sprays, the amount of zinc oxide particles is about 0.2-2%, preferably about 0.5- 1%, by weight and the amount of sodium bicarbonate is about 1-8%, preferably about 2-5% by weight. For a chewing gum, the amount of zinc oxide particles is about 0.1-1%, preferably about 0.2-0.5%, by weight and the amount of sodium bicarbonate is about 1-20%, preferably about 5-15%, by weight. For a lozenge or a chewable tablet the amount of zinc oxide particles is about 0.05-0.5%, preferably about 0.1-0.4%, by weight and the amount of sodium bicarbonate is about 0.2-2%, preferably about 0.5-1%, by weight. For coatings for oral care accessories, the amount of zinc oxide particles is about 0.1-20%, preferably about 0.2-0.5%, by weight and the amount of sodium bicarbonate is about 1-40%, preferably about 5-15% by weight. As used herein, "carrier" refers to a vehicle which is pharmaceutically acceptable and which is suitable for use in the oral cavity.

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 dentifrices containing sodium bicarbonate, i.e., a pH of about 7.5-9.5, 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.

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 the pyrophosphate salts hydrolyze in saliva to inactive orthophosphate.

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 a sodium bicarbonate, typically about 3- 70%, preferably about 10-65%; (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 is typically about 0.1-10%, preferably about 1-5%.

In a toothpaste or tooth gel, the liquid vehicle may comprise water and humectant in an amount ranging from about 10-90%. Water comprises up to about 50%, preferably about 5-35% of the composition. However, an anhydrous toothpaste or gel can be formulated if desired. A humectant is also a desirable component in a toothpaste or gel. Typically, the humectant comprises about 5-50% of the formulation, preferably about 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 about 1 to 1.

Optional, but preferred, components which are included in the toothpastes or 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 orthophosphates, o- phosphoric acid, alkali metal glycerophosphateε, tartrates and citrates; and/or like components conventionally added to toothpastes and tooth gels. To improve clarity when the dentifrice is a gel, less sodium bicarbonate is used, typically about 3-60%, preferably about 5-35% and coarse bicarbonate crystals are chosen, preferably crystals having an average particle size of greater than 44 microns, most preferably greater than 74 microns. If a secondary abrasive is used, the abrasive selected is one which will give a clear or translucent gel. The tooth powders comprise (a) an effective amount of sodium bicarbonate, typically about 20-95%, preferably above about 50% 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 agglomerated particle size of 50 microns or less. The amount of zinc oxide particles is typically about 0.1-10%, preferably about 1-5%.

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 a 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 powers.

Preferably, the sodium bicarbonate particles have a mean particle size of about 5 to 200 microns. The bicarbonate particles may be incorporated in the dentifrice in varying amounts, depending upon the desired properties of the formulation. Higher levels of sodium bicarbonate, e.g. , about 50%, allow it to be used as the sole abrasive. Such formulations remove plaque effectively, have a desirable low abrasivity, and provide an exceptionally clean feeling to the teeth and gums after brushing. Lower levels allow the incorporation of secondary abrasives and permit the formulation of clearer gels. At very low levels, e.g., less than about 10%, the bicarbonate still provides effective buffering in the pH 7.5 to 9.5 range and enhances the clean feeling of the teeth and gums, but to a lesser degree than when high levels are used. To improve clarity when the dentifrice is a gel, less sodium bicarbonate is used, typically about 3-60%, preferably about 5-35% and coarser bicarbonate crystals are chosen, preferably crystals having an average particle size of greater than 44 microns, most preferably greater than 74 microns.

Conventional abrasives or polishing materials are also useful herein as a secondary abrasive. Conventional water-insoluble abrasives include sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, 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 admixed with the sodium bicarbonate 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 particularly 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.

Any of the foregoing water-insoluble abrasives may be present in amounts of up to about 50%, preferably in amounts up to about 20%, which amount will depend upon the amount of sodium bicarbonate used.

Suitable humectants include glycerine, propylene glycol, sorbitol, polypropylene glycol and/or polyethylene glycol (e.g., molecular weight of 400-1200) , and/or the like. Also advantageous are liquid mixtures of water, glycerine and sorbitol or mixtures with polyethylene glycol. Toothpastes and tooth gels typically contain a natural or synthetic organic thickener or gelling agent in proportions of about 0.1-10%, preferably about 0.3-2%. Suitable organic thickeners include sodium carboxymethyl cellulose, starch, gum tragacanth, carrageenan, xanthan gum, polyacrylate salts, polyvinylpyrrolidone, hydroxyethylpropyl cellulose, hydroxybutylmethyl cellulose, hydroxypropylmethyl cellulose, or hydroxyethyl cellulose, which are usually used in amounts of about 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, non-ionic or ampholytic surfactants may be used.

Examples of suitable anionic surfactants are the water-soluble salts of the higher alkyl sulfates such as sodium lauryl sulfate or other C₈-C₁₈ 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 substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds such as C₁₂~^ci₆ ^fattY acids, alkyl or acyl radicals, and the like. Examples of the last mentioned amides are N-lauryl sarcosinate and the sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, 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 useful herein are the condensation products of ethylene oxide with various other compounds which are reactive therewith and have long hydrophobic chains (e.g., C₁₂-C₂o 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, aspartame, D-tryptophan , dihydrochalcones, 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%, preferably about 0.02-0.1% of the composition.

Cationic anti-microbial agents such as cetyl pyridinium chloride (CPC) or benzothonium chloride are useful herein. Bis-biguanides are also effective. Such agents include chlorhexidine (1,6-bis [N⁵-p-chlorophenyl-N- biguanido]hexane) , and the soluble and insoluble salts thereof and related materials such as l,2-bis(N⁵-p- trifluoromethylphenyl-N¹-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 formulation.

Water-insoluble, non-ionic anti-microbials such as 2 ' ,4,4 '-trichloro-2-hydroxy-diphenyl ether (Triclosan) or 2,2 '-dihydroxy-5,5 '-dibromo-diphenyl ether are particularly useful herein. In addition to these halogenated diphenyl ethers, phenol and its homologs, mono- and poly-alky1 and aromatic halophenols, resorcinol and its derivatives, bisphenolic compounds and halogenated salicylanilides are also useful. These include 2-, 3-, or 4-methyl phenol; 4- ethyl phenol; 2,4-, 2,5-, 3,4-, and 2, 6-dimethylphenol; 4-n- propyl, 4-n-butyl, or 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 or 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-ethyl-3-methyl p-chlorophenol; 6-n- or 6- isopropyl-3-methyl p-chlorophenol; 2-ethyl-3-methyl or 3,5- dimethyl p-chlorophenol; 6-iso-propyl-3-methyl or 2-ethyl-3- methyl p-chlorophenol; 6-sec-butyl-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-chlorophenol; methyl, ethyl, n-propyl, n-butyl, n- or sec-amyl, or cyclohexyl p-bromophenol; tert-amyl- bro ophenol; n-hexyl o-bromophenol, n-propyl-m,m-dimethyl o- bro ophenol; 2-phenyl phenol; 4-chloro- 2- or 3-methyl phenol; 4-chloro- or 2,4-dichloro-3 ,5-dimethyl phenol; 3,4,5,6-terabromo 2-methyl phenol; 5-methyl-2-pentyl phenol; 4-isopropyl-3-methyl phenol; 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) sulphide; 4• ,5-dibromo- or 3,3' ,5-or 3,4' ,5-tribromo- salicylanilide; 3,3 ' ,5- or 3,4 ' ,5-trichlorosalicylanilide or 2,3,3 ' ,5-tetrachlorosalicylanilide; 3,5-dibromo-3 '- or 4*- trifluoromethyl salicylanilide; 5-n-octanoyl-3 ' - trifluoro ethyl salicylanilide; methyl, ethyl, propyl, or butyl p-hydroxybenzoic acid; 3,3' ,4- or 3,4,4'- trichlorocarbanilide; 3-trifluoromethyl-4 , 4 ' - dichlorocarbanilide; and like compounds. The non-ionic secondary anti-microbial agents have the advantage of not losing efficacy in the presence of anionic surfactants.

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. The pyrophosphates include mono-, di-, tri- or tetraalkali metal pyrophosphates and mixtures thereof. The preferred pyrophosphate salts include disodium pyrophosphate, dipotassiumpyrophosphate, tetrasodium pyrophosphate, and/or tetrapotassium pyrophosphate. The pyrophosphates may be employed in their anhydrous or hydrated forms. Although a particular pyrophosphate 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 both the final pH of the dentifrice and the salting-out effect of the sodium bicarbonate. If desired, pyrophosphates are added to the dentifrices in an amount 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 monofluorophosphate, and mixtures thereof are preferred.

The amount of the soluble fluoride ion source in the dentifrice is dependent on the particular compounds used and the type of dentifrice, but it must be incorporated in an effective but nontoxic 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 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%-1.20%.

Various other materials may be incorporated in the dentifrice compositions. Examples thereof are coloring and whitening agents, preservatives, silicones, and/or chlorophyll compounds. These adjutants are incorporated in the dentifrices 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 pH of the dentifrices herein range from 7.0 to 10.0, preferably from 7.5 to 9.0. The pH is preferably achieved through a proper balancing of the bicarbonate and other additives. The dentifrices herein are prepared using conventional mixing techniques and used in a conventional manner.

Mouthwashes The mouthwashes may be conveniently prepared by simply adding the zinc oxide particles and sodium bicarbonate, in no particular order, to water or a water/alcohol mixture. Optional ingredients include thickeners; humectants; 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 glycol, 1,3-butylene glycol, and mixtures thereof. Suitable thickeners, humectants, surfactants, flavoring, sweetening and/or 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) about 1-8%, preferably 2-5%, of sodium bicarbonate; (c) 0 to about 50% of a non- aqueous liquid; (d) 0 to about 20% of a humectant; (e) 0 to about 12% of a surfactant; (f) 0 to about 0.3% of a flavoring agent; and (g) the balance water to 100%. Typically, the amount of zinc oxide particles is about 0.2- 2%, preferably 0.5-1%, by weight and the amount of sodium bicarbonate is about 1-8%, preferably 2-5% by weight. Optionally, the mouthwash may contain up to 1% of an anti- caries agent and up to 0.01-0.5%, preferably 0.02-0.2% of a secondary anti-microbial agent. The preferred anti¬ microbial agents are Tricolosan 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 and an effective amount of sodium bicarbonate are 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 and the amount of sodium bicarbonate is about 1-20%, preferably 5- 15% 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 suitable 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-isoprene copolymers, polyethylene, polyisobutylene, polyvinylacetate and mixtures thereof.

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, 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% to about 75%, preferably about 45% to about

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 or potassium stearate, glyceryl triacetate, glycerin and the like, as well as natural waxes and petroleum waxes such as polyurethane waxes, paraffin waxes and microcrystalline waxes. These ingredients may be reduced in amount or, in some cases, may be eliminated entirely. When present, these ingredients are generally employed in amounts of up to about 15% by weight, preferably 3-10% by weight, of the final gum base composition. Useful flavoring agents include liquid synthetic flavoring agents and/or liguids derived from plants, leaves, flowers, fruits, and the like. Preferably, the flavoring agent is selected from spearmint oil, cinnamon oil, wintergreen oil (methylsalicylate) and peppermint oil. Also useful are artificial, natural or synthetic fruit flavors such as lemon, orange, grape, lime and other citrus flavors 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 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 derivatives; cyclamic acid and its derivatives; dipeptide sweeteners such as aspartame; dihydrochalcone compounds; sugar alcohols such as sorbitol, annitol, and xylitol, and like sweeteners. Also useful is a nonfermentable sugar substitute, i.e. , a hydrogenated starch hydrolysate described in U.S. Pat. No. Re. 26,959. Also suitable is the synthetic sweetener 3,6-dihydro-6- methyl-1,2,3-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%, preferably up to about 0.06%, by weight, and other dyes suitable for food and drug applications known as FD&C dyes. Preferably, the foregoing are water-soluble. Illustrative examples include FD&C Blue No. 2 which is the disodium compound of 5,5'- indogotindisulfonic 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 the gum base in varying 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°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, the zinc oxide particles, and sodium bicarbonate are then incorporated into the base, and mixing is thereafter continued. Finally, the sweetener is added and mixed in for an additional 1 to 10 minutes. 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, as well as center-filled gum.

Lozenges. and Chewing Tablets

As indicated herein, the zinc oxide particles and sodium bicarbonate 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 amount of sodium bicarbonate is about 0.2-2%, preferably 0.5-1%, 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, maltitol, a hydrogenated starch hydrolysate ("Lycasin") , 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, carboxymethyl 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 rinsing. 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 moles of ethylene oxide, sorbitan 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, which are 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% by weight, 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%. Suitable secondary anti-microbial agents are discussed under Dentifrices. A preferred anti-microbial agent is cetylpyridinium chloride (CPC) .

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

The dental floss is prepared by procedures well known in the art and then coated or impregnated with a suspension containing the zinc oxide particles and sodium bicarbonate. 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. The sodium bicarbonate is typically added in amounts of about 1-40%, preferably 5-15%, by weight. They are suspended in the molten polyethylene glycol.

Alternatively, the floss can be impregnated with a molten coating composition using the procedure described in U.S. 4.911.927. The coating compositions of the '927 patent typically contain a surfactant (PLURONIC T127) , silicone, glycerine or saccharin, a flavor or sorbitol, and a thickener such as methyl cellulose (methocel) or carrageenan. If desired, the zinc oxide particles and sodium bicarbonate can be suspended in alcohol and/or water and the bundle of floss strands can be dipped in the suspension and allowed to air dry.

The following examples further illustrate the present invention, but it is understood that the invention is not limited thereto. All amounts 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 <1 micron and the primary particles are agglomerated to a medium 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 resubmerged 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 % Plaque 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 sulfate and its 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 as 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. An additional three sets of plaque coated glass rods were treated with the above suspensions after the suspensions were filtered through a 0.45 micro meter filter unit to remove particulate zinc oxide. Distilled water was used as a control. The results are shown below.

Treatment Plaque (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 l Distilled Water 34.2 0

The treatment is expressed as concentration within the treatment suspension. The results show that the greatest anti-plague effects were observed with the unfiltered suspensions, thus indicating that the anti-plaque activity of the zinc oxide was dependent upon the presence of the 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 assay 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 mg. ) 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 expressed as concentration within the 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 suspensions. This increase in activity appears to have been somewhat additive in nature.

Example 4 To demonstrate the efficacy of a zinc oxide/sodium bicarbonate-containing toothpaste in controlling tartar, the following accelerated in-vivo tartar control clinical was performed.

Approximately 75 heavy tartar forming individuals were identified. Each subject was given a prophy and provided with a tooth shield which fit over their 6 mandibular teeth. The panel was divided into 3 groups.

Each group was supplied with one of the test dentifrices.

They were asked to clean their teeth twice daily by placing a ribbon of the toothpaste into their tooth shield and placing the shield over their front mandibular teeth. They then brushed the rest of their teeth with the test dentifrice. After removing the tooth shield they rinsed their teeth in the usual way. After two weeks the subjects returned for an examination of the level of tartar formed on the lingual side of their 6 mandibular front teeth using the

Volpe-Mannhold Index (VMI) .

The results were as follows:

Toothpaste VMI % Reduction N Regular Crest 11.46 - 24

ARM & HAMMER DENTAL CARE 7.39* 35.5% 23 Tartar Control Toothpaste (3.5% pyrophosphate ion) Toothpaste containing 59% sodium 7.50* 34.6% 26 bicarbonate and 2% agglomerated submicron zinc oxide ♦Different from regular Crest (p <0.05) The results show that the composition of the invention containing zinc oxide and sodium bicarbonate significantly inhibited tartar control formation.

Example 5

The following example shows the advantage of incorporating the agglomerated submicron zinc oxide particles into a toothpaste formulation containing sodium bicarbonate.

Arm & Hammer Dental Care toothpaste and Arm & Hammer Dental Care toothpaste containing 2% added SACHTOTEC® zinc oxide particles were mixed in water and compared for anti-plaque efficacy in an in vitro plaque growth model with SACHTOTECH® agglomerated submicron zinc oxide particles alone and chlorhexidine alone.

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 and immersed for 30 seconds in a water rinse. The rods were then resubmerged in fresh daily growth medium for 6 hours at 37°C. The rods were retreated with the anti-plaque test solutions or suspensions and 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.

Treatment % Plague Reduction

Water 0 Arm & Hammer Dental Care Toothpaste 21

Arm & Hammer Dental Care Toothpaste with 2% agglomerated Zinc Oxide Particles 70

Chlorhexidine (0.12%) 74

Agglomerated Submicron Zinc Oxide Particles (0.5%) 64

The toothpaste containing the zinc oxide particles showed statistically (p<0.05) superior anti-plague performance compared to the to zinc oxide particles alone.

The performance of the toothpaste containing the zinc oxide particles was indistinguishable from the anti-plague performance of chlorhexidine. Examples 6-12

The following are representative toothpastes containing agglomerated submicron zinc oxide particles.

Ingredients 6 ∑ JL 9 10 11 12

Zinc oxide 2.000 4.000 1.000 0.500 2.000 2.000 5.000 particles

Sodium 63.160 60.080 54.450 62.920 54.210 49.210 27.927 bicarbonate

Tetrasodium - - 5.350 - 5.350 5.350 5.350 pyro- phosphate

Calcium _ _ _ _ _ _ 10.000 pyrophos¬ phate

Sodium - 0.243 0.243 0.243 0.243 fluoride

Sodium - 0.780 0.780 - - - - monofluoro¬ phosphate

Glycerin 14.070 15.070 14.070 14.070 14.070 14.070 4.100 Polyethy- 1.000 - 1.000 1.000 - 1.000 1.000 lene glycol (PEG-8)

Carboxy- 0.850 0.850 0.650 0.850 0.650 0.650 0.700 methyl cellulose

Water 16.112 16.112 20.100 17.609 20.877 24.877 5.280 Ingredients 6_ 1_ 8. 9 10 11 12

Sodium 1.208 1.208 1.000 0.808 0.800 0.800 1.000 saccharin

Sorbitol _ _ _ _ - - 37.100

Sodium 0.300 0.300 0.300 1.000 - 0.600 0.300 lauryl sulfate

Sodium 0.300 0.600 0.300 - 0.600 - 1.000 lauroyl sarcosinate (30%)

Flavor 1.000 1.000 1.000 1.000 1.200 1.200 1.000

100.000100.000100.000100.000100.000100.000100.000

Examples 13-19 The following are representative tooth gels containing agglomerated submicron zinc oxide particles.

Ingredients 13 14 15 16 17 18 19

Zinc oxide 2.000 4.000 1.000 2.000 2.000 2.000 2.000

Sodium 27.245 24.515 21.245 30.547 21.047 21.047 5.422 bicarbonate

Tetrasodium - - 5.350 - 5.350 9.350 2.000 pyrophos¬ phate

Sodium _ _ _ 0.243 0.243 0.243 0.243 fluoride

Sodium - 0.780 0.780 - - - - monofluoro¬ phosphate

Glycerin 17.000 17.000 16.220 14.745 14.745 14.745 9.100 Sorbitol 20.290 20.290 20.290 27.500 17.500 17.500 50.100 (10% Solution)

Polyethy- 1.000 1.000 1.000 1.000 1.000 1.000 1.000 lene glycol (PEG-8) Ingredients 13 14 15 16 17 18 19

Carboxy¬ 0.650 0.600 0.600 0. .600 0, .600 0, .600 0. .600 methyl cellulose

Water 16.810 16.810 18.360 8. .360 18. .360 18. .360 9. .080

Sodium 0.500 0.500 0.650 0. .500 0. ,650 0. .650 0. ,350 saccharin

Abrasive 8.000 8.000 8.000 8. ,000 12. ,000 8. ,000 13. 000 hydrated silica

(Sylodent

700)

Thickening 4.500 4.500 4.500 4.500 4.500 4.500 4.500 silica

(Sylox 2)

Sodium 1.000 1.000 0.500 0.500 1.000 1.000 0.500 lauryl sulfate

Sodium 0.500 0.500 1.600 lauroyl sarcosinate (30%)

Flavor 1.000 1.000 1.000 1.000 1.000 1.000 0.500

Color 0.005 0.005 0.005 0.005 0.005 0.005 0.005

100.000100.000100.000100.000100.000100.000100.000

Examples 20-25

The following are representative tooth powders containing agglomerated submicron zinc oxide particles.

Ingredients 20 21 22 23 24 25 Zinc oxide 2.000 4.000 1.000 2.000 5.000 2.000

Sodium 95.900 93.020 91.120 90.307 87.157 82.557 bicarbonate

Calcium - 5.000 pyro- phosphate Ingredients 20 21 22 23 24 25

Tetrasodium - - 5.350 - 5.350 5.350 pyro¬ phosphate

Sodium - 0.780 0.780 - monofluoro- phosphate

Sodium - 0.243 0.243 0.243 fluoride

Flavor 1.000 1.000 1.000 0.800 1.000 1.200 Sodium 0.500 0.500 0.650 0.850 0.650 0.650 saccharin

Magnesium 0.100 0.200 0.100 0.300 0.100 oxide

Sodium 0.500 0.500 - 0.500 0.500 lauryl sulfate

Abrasive hydrated silica (Sylodent

700) - - - 8.000

100.000 100.000 100.000 100.000 100.000100.000

Examples 26-31 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 a secondary anti-microbial agent. The Triclosan is blended in as is or preferably added to the flavor oil. The CPC is dissolved in the water and then added as a solution to the toothpaste or tooth gel. They are directly added to the tooth powders. Pastes Gels Powders Ingredients 26 27 28 29 30 31

Zinc oxide 2.000 2.000 0.500 0.500 2.000 2.000

Triclosan 0.500 - 0.400 - 0.600

Cetylpyri- - 0.2 - 0.3 - 0.4 dinium Chloride (CPC)

Sodium 62.500 62.500 30.000 30.000 95.900 94.400 bicarbonate Sodium 0.243 0.243 0.243 0.243 fluoride

Glycerin 14.070 14.070 14.070 14.070

Sorbitol - - 15.000 15.000

(70% solution)

Polyethyl- 1.000 1.000 1.000 1.000 ene glycol

(PEG-8)

Sodium 0.850 - 0.700 0.700 carboxy¬ methyl cellulose

(9M31F)

Hydroxy- - 1.000 - methyl cellulose

Water 15.423 14.581 22.187 21.087

Sodium 1.208 0.500 1.000 0.500 0.500 0.500 saccharin Magnesium - 0.500 0.500 oxide

Hydrated - - 12.500 12.500 silica

Sodium 0.300 - 0.300 - 0.500 lauryl sulfate Sodium 1.000 1.000 1.000 1.000 - 1.000 lauryl sarcosinate

Pluronic - 2.000 - 2.000 F-108

(Poloxamer 338)

FD&C Blue - - 0.033 0.033

#1 (1% solution)

FD&C Yellow - - 0.167 0.167 #10

Flavor 0.906 0.906 0.900 0.900 1.000 1.000

Examples 31-33

The following are representative mouthwashes and a mouth spray containing agglomerated submicron zinc oxide particles.

Ingredients Mouthwjishes Mouth Sprav

31 3_2 3_3

Zinc oxide 0.50 0.20 0.15

Sodium 5.00 2.00 2.50 bicarbonate

Sodium fluoride 0.05 - -

Glycerol 5.00 5.00 -

Cremophor EL 0.25 0.25 ■0.50

Cetylpyridinium chloride (CPC) - 0.05 -

Ethanol poloxyethylene sorbitan monooleate 0.10 - -

Ethanol - 10.00 10.00 ml.

Aromatics, 0.10 0.10 0.10 saccharin Ingredients Mouthwashes Mouth Spray

21 3_2 33

Water to 100.00 to 100.00 to 100.00

Propellant - - as needed

Example 34 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

Sodium bicarbonate 10 . , 0

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 this mixing the zinc oxide particles and sodium bicarbonate 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 and bicarbonate are slowly released upon chewing and should become trapped in the plaque between the teeth.

Suitable gums may also be prepared using sugar in place of the sorbitol solution. It is recognized, however, that a chewing gum free of sugar provides a poorer environment for the formation of dental plaque. Examples 35-36

These examples describe a representative chewable tablet containing agglomerated submicron zinc oxide particles.

Lozenge Ingredients Parts

Kappa carrageenan 2.000

Sorbitol 93.389

Sodium saccharin 0.150 Coconut oil 2.000

PEG-40 Sorbitan diisostearate 1.000

Blue dye 0.006

Zinc oxide 0.200

Sodium bicarbonate 1.000 High mint (85-95%) flavor 0.245

Alpha ionone 0.01

The sorbitol is thoroughly blended with the Kappa 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 sodium bicarbonate 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, anywhere.

Chewable Tablet Ingredients Parts

Wintergreen oil 0.33

Peppermint oil 0.17

Menthol 0.47

Silica (Syloid 244) 0.55 Sodium saccharin 0.17

Sodium bicarbonate 7.76

Zinc oxide 0.17

Mannitol, USP (granular) 89.27

Calcium stearate 1.11

The flavor oils, zinc oxide particles, sodium bicarbonate, 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 37-38

The following are representative dental flosses coated with a mixture containing agglomerated submicron zinc oxide particles.

Ingredients 37 38 Peppermint oil NF 1.5

Clove oil NF 0.3

Sodium saccharine NF 0.2 0.2

Zinc oxide 2.0 2.0

Sodium bicarbonate 10.0 10.0 Polyethylene glycol (PEG- q.s. q.ε,

First, the polyethylene glycol is melted at about 50°C and then the flavor oils (if used) , sodium saccharine, zinc oxide particles, and sodium bicarbonate are mixed in. Preformed dental floss is then passed through the molten suspension and the coating on the floss is then allowed to harden.

The above oral compositions are effective in reducing calculus and preventing gum disease. In addition, they possess acceptable organoleptic 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.

Claims

WHAT IS CLAIMED IS:

1. An oral care composition comprising: a. about 0.2-98% sodium bicarbonate; b. an anti-microbially effective amount or an anti-tartar 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 carrier in an amount sufficient to provide the desired consistency to the oral care composition.

2. The composition of Claim 1, wherein the oral care composition is selected from the group consisting of a toothpaste, a tooth gel, a tooth powder, a mouthwash, a mouth spray, a chewing gum, a lozenge, a chewable tablet and a coating.

3. The composition of Claim 2, further comprising a secondary abrasive, a secondary anti-microbial agent, a sweetening agent, a flavoring agent, and/or a colorant; and wherein the carrier is water and/or an alcohol, a gum base, a solid, water-soluble polyhydric alcohol, and/or a humectantp; and wherein the amount of zinc oxide particles is about 0.05-20%, by weight

4. The composition of Claim 2, wherein the oral care composition is the toothpaste, the tooth gel, or the tooth powder; and wherein the amount of zinc oxide particles is about 0.1-10%

5. The composition of Claim 4, further comprising about 1-10% of a secondary abrasive; about 5-50% of a humectant as a liquid vehicle; about 0.5-1% of an organic or inorganic thickener for the toothpaste or tooth gel; about 0.1-2.5% of a surfactant; about 0.1-2% of a flavoring agent; about 0.1-2% of a sweetening agent; an effective amount of an anti-caking agent for the tooth powder; an effective amount of an anti-calculus agent, and/or an effective amount of an anti-caries agent.

6. The composition of Claim 5, wherein the secondary abrasive is selected from the group consisting of sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, 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; wherein the humectant is sorbitol and/or polyethylene glycol; wherein the thickener is carboxymethyl cellulose; wherein the surfactant is sodium lauryl sulfate and sodium lauroyl surcosinate; wherein the sweetening agent is sodium saccharin; where the anti-calculus agent is one or more pyrophosphate salts present in an amount sufficient to provide at least 1.5% pyrophosphate ions; and wherein the anti-caries agent is a fluoride ion source present in an amount capable of providing about 50-3500 ppm of fluoride ions.

7. The composition of Claim 2, wherein the oral care composition is in the form of a mouthwash or a mouth spray; wherein the amount of zinc oxide particles are about 0.2-2% by weight; and wherein the amount of sodium bicarbonate is about 1-8% by weight.

8. The composition of Claim 7, further comprising a secondary anti-microbial agent and wherein the amount of zinc oxide particles is about 0.5-1% by weight and wherein the amount of sodium bicarbonate particles is about 2-5% by weight.

9. The composition of Claim 2, wherein the oral care composition is in the form of a chewing gum; wherein the amount of zinc oxide particles is about 0.1-1%; and wherein the amount of sodium bicarbonate is about 1-20% by weight.

10. The composition of Claim 9, wherein the amount of zinc oxide particles is about 0.2-0.5% by weight and wherein the amount of sodium bicarbonate is about 5-15% by weight.

11. The composition of Claim 2, wherein the oral care composition is in the form of a lozenge or chewable tablet; wherein the amount of zinc oxide particles is about 0.05-0.5% by weight; and wherein the amount of sodium bicarbonate is about 0.2-2% by weight.

12. The composition of Claim 11, wherein the amount of zinc oxide particles is about 0.1-0.4% by weight and wherein the amount of sodium bicarbonate is about 0.5-1% by weight.

13. The composition of Claim 2, wherein the oral care composition is the coating, which coating is for use on a dental floss or a toothpick; wherein the amount of zinc oxide particles is about 0.1-20%; and wherein the amount of sodium bicarbonate is about 1-40%.

14. The composition of Claim 13, wherein the amount of zinc oxide particles is about 0.2-0.5% by weight; wherein the amount of sodium bicarbonate is about 5-15% by weight; and wherein the carrier is a polyethylene glycol which is solid at room temperature.

15. A process for treating diseases of the oral cavity or preventing tartar formation by adding to an oral care composition an effective amount of sodium bicarbonate and an anti-microbially effective amount or an anti-tartar 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.

16. The process of Claim 15, wherein the oral care composition is selected from the group consisting of a mouthwash, a mouth spray, a chewing gum and a candy, a lozenge, or a chewable tablet; wherein the amount of sodium bicarbonate is about 0.2-98% and wherein the amount of zinc oxide particles is about 0.05-2%.

17. The process of Claim 16, wherein the composition is the toothpaste, the tooth gel, or the tooth powder; wherein the amount of sodium bicarbonate is about 10-65% in the toothpaste or tooth gel and above about 50% in the tooth powder; and wherein the amount of zinc oxide particles is about 1-5%.

18. A process for treating an oral care accessory, which comprises the step of coating or impregnating the oral care accessory with a composition comprising (a) an effective amount of sodium bicarbonate; (b) an anti- microbially effective amount or an anti-tartar 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 coating material.

19. The process of Claim 18, wherein the oral care accessory is selected from the group consisting of a dental floss, a tooth brush bristle, or a tooth pick; wherein the amount of sodium bicarbonate is about 1-50%; wherein the amount of zinc oxide particles is about 0.1- 20%; and wherein the coating material is a polyethylene glycol which is solid at room temperature.

20. The oral care accessory prepared by the process of Claim 19.