BACKGROUND

10001 j Soluble zinc sails, such as zinc citrate, have been used in dentifrice compositions, see, e.g., U.S. Patent No. 6, 121 ,31 5, but may reac with common exeiptenis in dentifrice to form insoluble salts and so reduce delivery of the zinc to the tooth surface. For example, many people prefer dentifrice comprising calcium carbonate (chalk) abrasive, but zinc ions will react with calcium carbonate to form insoluble zinc carbonate, thereby reducing the delivery of the zinc to the tooth surface.

[0002j Thus, there is a need for compositions which, are able to overcome the problems with formulation zinc salts in a calcium carbonate backbone,

SUMMARY

[0003] Some embodiments of the present invention provide enhanced delivery of n~ ' ions from a zinc ion source such as ZnO and/or Zn citrate to the tooth surface using a calcium carbonate dentifrice, thus providing enhanced antibacterial efficacy and enhanced protection against erosion and hypersensitivity. The zinc ion source is incorporated in silica dentifrice stripes entrained in a calcium carbonate based dentifrice formulation, providing the benefits and consumer acceptability of a calcium carbonate dentifrice. This formulation provides enhanced delivery of zinc to the tooth surface compared to simply incorporating the zinc into She calcium carbonate dentifrice, and thus enhanced the antibacterial, aniisensitivity and antierosion benefits of the zinc. Products comprising the toothpaste and methods of making and using the dentifrice are also provided.

[0004] Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter, it should be understood thai the detailed description and specific examples, vvhiie indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the* invention. i ⁾ Ki A H J - l ⁾ DHSCRI PTION

{000$] The following description of the preferred embodiments) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses. j 0061 The invention provides, in one embodiment, formulations to enhance th delivery of Xn ^' " ions from a zinc ion source, e.g., zinc oxide and/or zinc citrate, onto hard tissue surfaces e.g., hydroxyapaiite (HAP), from a calcium carbonate dentifrice, to obtain enhanced antibacterial efficacy. Zinc, ions have good antibacterial efficacy compared to conventional chalk-based formulations, bin when zinc ions are provided in calcium carbonate formulations, we have found that the delivery of zinc to the tooth surface is relatively poor, in this formulation, a zinc ion source is incorporated in silica gel stripes entrained in a calcium carbonate based dentifrice. This formulation surprisingly enhances the delivery of zinc ion on hard tissues in the oral cavity, thus providing enhanced antibacterial benefits compared to formulations containing zinc ion sources in a calcium carbonate matrix.

}0007] The invention thus provides a toothpaste product (Product 1 } comprising

a first dentifrice comprising a calcium carbonate abrasive,

a second dentifrice comprising a zinc ion source in a gel base, and a container which holds the first dentifrice physically separate from the second dentifrice until the dentifrices are dispensed, and which, is capable of dispensing the second dentifrice as a stripe entrained in the first dentifrice.

For example. Product 1 includes, e.g.,

3 .1. Product i wherein the zinc ion source is selected from zinc oxide, zinc citrate, and

mixtures thereof.

1.2. Product 1 or 1. i wherein the amount of first dentifrice relative to ihe second dentifrice is from 3: 1 to 5: i , e.g., about 4: 1 .

i .3, Any of the foregoing products wherein the first dentifrice is substantially free of zinc, 1 ,4. Any of the foregoing products wherein the second dentifrice is substantially free of

dentifrice combined is I rum u. ->i%, e . ., 0,N- i , v f _f . . .;, s ui <i.8%

1 ,6. Any of the foregoing products wherein the second dentifrice contains zinc in an amount of 0.1 - 10%, e.g., 2 -6%, e.g. about 4%.

Any of (he foregoing products wherein the second dentifrice contains a zinc ion source selected from (i) zinc oxide in an amount of 4-6%, e.g., about 5%, and (ii) zinc oxide in an amount of 2-3%, e.g., about 2.5% and zinc citrate in an amount of 8- 12%, e.g., about 10%.

l.H. Any of the foregoing products wherein the ratio of the first dentifrice to the second

dentifrice is about 4: 1 and the second dentifrice contains about 5% zinc oxide,

1 .9. Any of the foregoing products wherein the second dentifrice contains a viscosity

modifying amount of one or more thickening agents selected from thickening silica, polyethylene glycols, polysaccharides (e.g., cellulose derivatives, for example carboxymcthyl cellulose, pol saccharide gums, for example xanlhun gum or carrageenan gum), and combinations thereof; e.g., selected from carboxymcthyi cellulose, xatrthan, thickening silica, and mixtures thereof.

1.10. Any of the foregoing products wherein the calcium carbonate abrasive in the first dentifrice is a mixture of precipitated calcium carbonate and natural calcium carbonate, e.g., in an amount of 35-45% by weight of the first dentifrice.

1.1 L Any of the foregoing products wherein the second dentifrice comprises silica abrasive, e.g. 10-40%, e.g. about 20%.

1 .12. Any of the foregoing products wherein the first dentifrice is an opaque white paste and the second abrasive is a colored translucent gel.

1 , 13, Any of the foregoing products wherein the first and/or second dentifrice comprise an effective amount of fluoride, e.g., sodium monofiuorophosphate in an amount of 0.5- 1 % by weight, of the first, and second dentifrice combined,.

1 , 14. Any of the foregoing products wherein the first dentifrice further comprises one or more of one or more of water, abrasives in addition to calcium carbonate, surfactants, foaming agents, vitamins, polymers, enzymes, humecta s, thickeners, antimicrobial agents, preservatives, flavorings, colorings and/or combinations thereof.

ί . ί ;·. Any os t.n.c foregoing products wherein the second dcrilnrice Uirther comprises one or more of on . or m re, oi wa ^' {«¾\ ab a i s other t n o k-s m carbonate, surfactants, foaming agents, vitamins, polymers, enzymes, rmmectants, thickeners, antimicrobial agents, preservatives, flavorings, colorings and/or combinations thereof

1. 16. Any of the foregoing products wherein the first dentifrice comprises one or more or all of the following ingredients: Ingredients (amounts

given as w/w% of first

dentifrice of Product 1 ) Range For example, about

Sorbitol 70 % ] 20-25 21

Xanthan j 0-0.5 0.2

Cavboxyineihyicei!ulose 0.5-1.0 0.7

Sodium Chloride 0-0,8 0.6

Sodium Saccharin | 0.25-0.45 0.3

Sodium Silicate 0 1 .5 1.2

Sodium Bicarbonate 0- 1 .0 0.6

Thickening Silica 1 -2.5 j 2.5

Calcium Carbonate 35-45 1 40

Tetnisodhun

pyrophosphate 0-1 0.5

Sodium

Moiioiluorophospiiate 0.5-1 0.76

Sodium Lauryl Sulfate

Granules 1 .2-2,5 2,2

Flavor i ~1 .5 1 «

Purified Water | 20-40 25-30, or q.s

. Any of the foregoing products wherein the second dentifrice comprises one or more or all of the following ingredients:

Amounts given as

w/w% of second

dentifrice of Product 1 !v iigc For example, about

Sorbitol 70 % 30-50 40

Xanthan 0-0.5 0.2

Carboxymethylcellulose 0.5- 1 .0 0.72

0.2.5-

Sodium Saccharin 0.45 0.27

Thickening Silica 1 -2.5

Abrasiv Silica 10- 40 20

Sodium

Mono Π uorophosphaie 0.5- 1 0.76

Sodium Lauryl Sulfate

Granules f 2-2.5 2 ?S

Flavor 1 - 1 .5 1

Purified Water 20-40 25-30, or q.s.

Zinc ion 0.5- 10 4% (e.g., corresponding to 5% ZnO)

Pigment j

[0008] T e invention furthef provides methods to (i) reduce hypet¾ensiUvHy of the teeth, (ii) to reduce plaque accumulation, iii) reduce or inhibit demineralizalion and promote

remmeralization of the teeth, (iv) inhibit microbial biofiim formation in the oral cavity, (v) reduce or inhibit gingivitis, (vi) promote healing of sores or cuts in the mouth, (vii) reduce levels of acid producing bacteria, (viii) to increase relative levels of non-cariogenic and/or non-plaque forming bacteria, (ix) reduce or inhibit formation, of dental caries, (x), reduce, repair or inhibit pre-carious lesions of the enamel, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (EC ), (xi) treat, relieve or reduce dry mouth, (xii) clean the teeth and oral cavity, (xiii) reduce erosion, (xiv) whiten teeth; and/or (xv) promote systemic health, including cardiovascular health, e.g., by reducing potential for systemic infection via the oral tissues, in a patient in need thereof comprising brushing the teeth with the dentifrice from Product 1. et seq,

{©009} The invention, further provides a striped toothpaste comprising a first dentifrice (e.g., as described above for Product 1 , et seq.) comprising a calcium carbonate abrasive and a second dentifrice (e.g., as described above for Product I , et seq.), comprising a sane ion source in a gel base, wherein the second dentifrice is entrained as a stripe in the first dentifrice.

(0010) The invention further provides a method of making a dentifrice comprising a first dentifrice (e.g., as described above for Product I, et seq.) comprising a calcium carbonate abrasive and a second dentifrice (e.g., as described above for Product 1, et seq..), comprising a zinc ion source in a gel base, comprising entraining the second dentifrice as a stripe in the first dentifrice.

'0()! 1 CotffoitK'rx: Containers for ispensing & striped toothpaste such as described herein, e.g..

dentifrices separate until dispensing, ulli-cham-ber containers may utilize a dual or multi- chamber uibe, These can be, for example, side by side dual chamber tubes as described in U.S. Pat. No. 1 ,894,1 15; U.S. Pal No. 3.758,520 and U.S. Pal No. 3,980,222 or concentric tubes as described in U.S. Pal No, 1,535,529; U.S. Pat. No. 1 ,639,699 and U.S. Pat. No. 1 ,699,532, and may contain a flow modifying unit in the nozzle of the tube. Exemplary containers for dispensing striped toothpastes as described are described; e.g., in US 4,969,767; US 5941420; US 6,454,130; and OS 7,617,950, the contents of which are incorporated herein by reference. (0012) Zinc and Other Active Aeents: "Zinc salts" as used herein refers to zinc ion sources, particularly soluble salts such as zinc citrate. "Zinc salts" for purposes of this application may include zinc oxide, which although not a salt in the strict chemical sense, is commonly referred to in the art as a zinc salt, for ease of reference. The amount of zinc in the formulation will typically be on the order of 0,1-2% of total zinc. Thus, for example., a formulation with 1 % XnO will have about 0.8% total zinc. The zinc ion may be provided from multiple sources, e.g., about 1% of zinc oxide or about 0,5% zinc oxide together with about 2% zinc citrate. These amounts refer to total zinc in the toothpaste. The zinc in the products of the invention is concentrated in the silica gel portion of the toothpaste, so where the silica gel portion comprises, e.g., 20% of the total toothpaste, and an overaii concentration of zinc in the toothpaste is desired to be, e.g., 1%, the silica gel portion will comprise 5% zinc,

[0013 j The compositions of the invention may comprise various agents which are active to protect and enhance the strength and integrity of the enamel and tooth structure and/or to reduce bacteria and associated tooth decay and/or gum disease, including or in addition to the zinc ion sources. Effective concentration of the active ingredients used herein will depend on the particular agent, the delivery system used, and the exact salt or polymer selected. For example, where the active agent is provided in salt form, the counterfoil will affect the weight of the salt, so tha if the countefion is heavier, more salt by weight will, be required to provide the same concentration of active ion in the final product. In some embodiments, the dentifrice may comprise arginine, which where present, may he present at levels from, e.g., about: 0.1 to about 20 wt ^(expressed as weight of free base), e.g., about 1 to about 1 wt % for a consumer toothpaste or about 7 to about 20 wt % for a professional or prescription treatment product Fluoride where present may he presen ai levels oh e.g., about 25 to about 25,000 ppm, for example about 750 to about 2,000 ppm for a consumer toothpaste, or about 2,000 to about 25.000 ppm i r a professional or prescription treatment product Other antibacterial agents may be present in effective amounts, e .g., iriciostm may be present in a concentration of about 0.3 wt [0014] FlMQri joti So rcit: The oral care compositions may further include one or more fluoride ion sources, e.g., soluble fluoride salts. A wide variety of fluoride ion-yielding materials can be employed as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion-yielding materials are found in U.S. Pat. No. 3,535,421 , to Briner et aL; U.S. Pat. No.4,885,155, to Parran, Jr. et ah and U.S. Pat. No. 3,678.154, to idder et at Representative fluoride ion sources include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofiuorophosphate, sodium fluorosRicate, ammonium fluorosilicaie, amine fluoride, ammonium fluoride, and combinations thereof. In certain embodiments the fluoride ton source includes stannous fluoride, sodium fluoride, sodium monofl uorophosphate as well as mixtures thereof. Jn certain embodiments, the oral care composition of the invention may also contain a source of fluoride ions or fluorine-providing ingredient in. amounts sufficient to supply about 25 ppm to about 25,000 ppm of fluoride ons, generally at least about 500 ppm, e.g., about 500 to about 2000 ppm, e.g., about 1000 to about 1600 ppm, e.g., about. 1450 ppm. The appropriate level of fluoride will depend on the particular application. A toothpaste for general consumer use would typical iy have about 1000 to about 1 500 ppm, with pediatric toothpaste having somewhat less. A dentifrice or coating for professional application could have as much as about 5,000 or even about 25,000 ppm fluoride. Fluoride ion sources may be added to the compositions of the invention at a level of about 0.01 wt. % to about 10 wt, % in one embodiment or about 0.03 wt. % to about 5 wt. and in another embodiment about 0.1 wt. % to about I wt. % by weight of the composition in another

embodiment. Weights of fluoride salts to provide the appropriate level of fluoride ion will obviously vary based on the weight of the counterfoil in the salt.

{OOlSj Abrasives: The toothpastes of the invention, e.g. the toothpastes used in Product L et seq. may include silica abrasives, e.g., as a component of the silica gel portion. The calcium carbonate abrasive may include precipitated calcium carbonate (e.g. prepared from reaction of calcium oxide with water and carbon dioxide), natural refined calcium carbonate (e.g., from mineral sources), or mixt r s thereof. Natural calc- nn carbonate may have a somewhat harder., ore crystalline structure than precipitated cakuuns carbonate, and in a particular embo iment, the calcium carbonate abrasive is a mixture of the two. The calcium carbonate base portion may also comprise silica abrasives and/or additional abrasives, e.g., a calcium phosphate abrasive, e.g., tricalcium phosphate (CasCPC a), hydroxyapatite or dicalciuui

phosphate dthydrate (CaHP0 ₄ · 2¾0, also sometimes referred to herein J S DiCa!) or calcium pyrophosphate; or abrasives such as sodium metaphosphate, potassium nietaphosphate. aluminum silicate, calcined alumina, benioniie or other siliceous materials, or combinations thereof,

[0016] Foaming agents: The oral care compositions of the invention also may include an agent to increase the amount of foam that is produced when the oral cavity is brushed, illustrative examples of agents that increase the amount of loam include, but are not limited to

polyoxyethylene and certain polymers including, but not limited to, alginate polymers. The polyoxyethylene may increase the amount of foam and the thickness of the foam generated by the oral care carrier component of the present invention. Polyoxyethylene is also commonly known as polyethylene glycol ("PEG") or polyethylene oxide. The polyoxyethylen.es suitable for this invention will have a molecular weight of about 200,000 to about 7,000,000. In one embodiment the molecular weight will be about 600.000 to about 2,000,000 and in another embodiment about 800,000 to about 1,000,000. Polyox® is the trade name for the high molecular weight polyoxyethylene produced by Union Carbide► The polyoxyethylene may be present in an amount of about 1 % to about.90%, in one embodiment about 5% to about 50% and in another embodiment about 10% to about 20% by weight of the oral care carrier component of the oral care compositions of the present invention. Where present, the amount of of foaming agent in the oral care composition (i.e., a single dose) is about 0.0! to about 0,9 % by weight, about 0.05 to aboui 0.5% by weight, and in another embodiment about 0.1 to about 0.2 % by weight.

}(H ⁾ !7] Surfactants The first and second dentifrice in the products of the invention may comprise one or more surfactants, e.g., selected from anionic, cationie, ¾witterkniic, and nonionic surfactants, and mixtures thereof, e.g., comprising an anionic surfactant, e.g.. a surfactant selected from sodium lauryl sulfate, sodium ether lauryl sulfate, and mixtures thereof, e.g. in an amount of from about 0,3% to about 4.5% by weight. The compositions useful in the invention may contain anionic surfactants, for example:

i. water-soluble salts of higher i ^' aUy ucsd monoglyceride monoouUates, such as the sodium salt of the monosulfated monoglyceride of hydvogenated coconut oil fatty acids such as sodium N-methyl N-ooto l taurate, sodium cocomonoglyceride sulfate,

it. higher alkyi sulfates, such as sodium lauryl sulfate, iil. higher alkyl-ether sulfates, e.g., of formula Ci i CH7) _lu Cf3 ₃ (OCl CH^OSOi , wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium laureth-2 sulfate (CH ₃ (CH2)i.oCH ₂ (OCH ₂ CH ₂ ) ₂ 0S0 ₃ Na).

iv. higher alkyl aryl sulfonates such as sodium dodeeyi benzene sulfonate (sodium iauryl benzene sulfonate)

v. higher alkyl sulfoaeetates, such as sodium iauryl sulfoacetate (dodeeyi sodium sulfoacetate), highe laity acid esters of 1 ,2 dihydroxy propane sulfonate, sulfoeolaurate (N-2- eihyl luurate potassium sulfacetamide) and sodium Iauryl sarcosinate.

jO .1,8} By "higher alkyl" is meant, e.g., Q-w alkyi. in particular embodiments, the anionic surfactant is selected from sodium Iauryl sulfate and sodium ether iauryl sulfate. The anionic surfactant may be present in an amount which is effective, e.g., > 0.01 % by weight of the formulation, but not at a concentration which would be irritating to the oral tissue, e.g., <10%, and optimal concentrations depend on the particular formulation and the particular surfactant. For example, concentrations used or a mouthwash are typically on the order of one tenth that used for a toothpaste, In one embodiment, the anionic surfactant is present in a toothpaste at from about 0,3% to about 4,5% by weight, e.g., about 1.5%. The compositions of the invention may optionally contain mixtures of surfactants, e.g., comprising anionic surfactants and other surfactants thai ma be anionic, eationic, zwitteriorac or nomonic. Generally, surfactants are those which are reasonably stable throughout a wide pH range. Surfactants axe described more fully, for example, in U.S. Pat. No. 3,95.9,458, to Agricola et al.; U.S. Pat. No. 3,937,807, to Hacfc!e; and U.S. Pat. No. 4,051 ,234, to Giesfce et ah hi certain embodiments, the anionic surfactants useful herein include the water-soluble salts of alkyl sulfates having about 1 to about 18 carbon atoms in the alky! radical and the water-soluble salts of sulfonated monogl ceridcs of fatty acid having about 1 0 to about 18 carbon atoms, Sodium iauryl sulfate, sodium lauroyl sarcosinate and sodium coconut irionogiyceride sulionaies are examples of anionic surfactants of this ivpe. In a afU uk ' enibodnnent, the iu i and second d nuhices oi Product i , st secj., each comprise sodium Iauryl sulfate in an amount of I -3%, e.g., about 2.25% , The surfactant or mixtures of compatible surfactants cm he present in the compositions of the present invention in about 0.1 % to about 5.0%, in another embodiment about 0.3 to about 3,0% and in another embodiment, about 0.5% to about 2.0% by weight of the total composition. 10019] Tartar control agents: In various embodiments of the present invention, the compositions comprise an aiiticalculus (tartar control) agent. Suitable aniiealeulus agents include without limitation phosphates and polyphosphates (for example pyrophosphates),

polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinc citrate tri hydrate, S polypeptides, poiyolefin sulfonates, polyolefiu phosphates, diphosphonates. The invention thus may comprise phosphate salts. In particular embodiments, these salts are alkali phosphate salts, i.e., salts of alkali metal hydroxides or alkaline earth hydroxides, for example, sodium, potassium or calcium salts. "Phosphate" as used herein encompasses orally acceptable mono- and polyphosphates, for example, hosphates, for example monomelic phosphates such as

10 monobasic, dibasic or tribasic phosphate; dimeric phosphates such as pyrophosphates; and

muhimeric phosphates, e.g., sodium hexametaphosphate. In particular examples, the selected •phosphate is selected from alkali dibasic phosphate and alkali pyrophosphate salts, e.g., selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate di yd rate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium ί 5 tripoiyphosphate, and mixtures of an of two or more of these. In a particu lar embodiment, for example the compositions comprise a mixture of tetrasodium pyrophosphate (N d^O _? ), calcium pyrophosphate Ca^O _? , and sodium phosphate dibasic (r½2HP ), e.g., in. amounts of ca. 3- 4% of the sodium phosphate dibasic and ca. 0.2-1% of each of the pyrophosphates. In another embodiment, the compositions comprise a mixture of tetrasodium pyrophosphate (TSPP) and 0 sodium iripo!yphosphatc (STPP)( N sPsOjo), e.g., in proportions of ^' FSPP at about 1-2% and STPP at about 7% to about 10%. Such phosphates are provided in an amount eflective to reduce erosion of the enamel, to aid in cleaning the teeth, and/or to reduce tartar buildup on the teeth, for example in an amount of 2-20%, e.g., ca. 5-15%. by weight of the composition.

[0020) Flavoring Agents: The oral, care compositions of the invention may also include a

25 il vLinoi aji sis l¾vonng agents widen are aseu ni the ractice i t e present in ention

include* but are. not im iif to, essential oils as well as various flavoring akkhyd s, tit rs, alcohols, and similar materials. Examples of the essential oils include oils of spearmint, peppermint, wintergrceu, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, iurnon, lime, grapefruit, and orange. Also useful are such chemicals as menthol, carvooc, and anethole,

30 Certain embodiments employ the oils of peppermint and spearmint. The flavoring agent may be incorporated in the oral composition at a concentration of about 0.3 to about 5% by weight e.g. about 0.5 to about. 1 .5% by weight,

|0 21 | Polymers: The oral care compositions of the invention may also include additional polymers to adjust the viscosity of the formulation or enhance the solubility of other ingredien s. Such additional polymers include polyethylene glycols, polysaccharides (e.g., cellulose derivatives, for example carboxyniethyl cellulose (CMC), or polysaccharide gums, for example xanthan gum or carrageenan gum). Acidic polymers, for example polyaerylate gels, may be provided in the form of their free acids or partially or fully neutralized water soluble alkali metal (e.g., potassium and sodium) or ammonium salts.

[0022] Silica thickeners, which form polymeric structures or gels in aqueous media, may be present. Note that these silica thickeners are physically and functionally distinct from the particulate silica abrasives also present in the compositions, as the silica thickeners are very finely divided and provide little or no abrasive action. Other thickening agents are carboxyvinyi polymers, carrageenan, hydroxyelhyl cellulose and water soluble salts of cellulose ethers such as sodium carboxymefhyl cellulose and sodium earboxymethyi hydroxyelhyl cellulose. Natural gums such as karaya, gum arable, and gum tragacanth can also be incorporated. Colloidal magnesium aluminum silicate can also be used as component of the thickening composition to further improve the composition's texture. In -certain embodiments, thickening agents in an amount of about 0,5% to about 5.0% by weight of the total composition are used,

(0023} The compositions of the invention may include an anionic polymer, for example in an amount of .from about 0,05 to about 5%, e.g., in the silica gel portion of the toothpaste. Such agents are known generally tor use in dentifrice, although not for this particular application, useful in the present invention are disclosed in U.S. Pat. Mos. 5,188,821 and 5,192,531 ; and include synthetic anionic polymeric polycarboxylates, such as 1 :4 to 4: 1 copolymers of nialeic anhydride or acid with another po!ymerizable ethyicnicaliy unsaturated monomer., preferably methyl vinyl ether/m»ici(; anhydride havijig a moleeuiai weight (M.W.) oi about 30,000 to about 1,000,000. most preferably about 300,000 to about 800,000, These copolymers are available for example as G i rcz. e.g., ΛΝ 139 (M.W. 500,000), AM 1 19 (M.W. 250,000) and preferably S-97 Pharmaceutical Grade (M.W. 700,000) available from ISP Technologies, Inc., Bound Brook, N.J. 08805.. The enhancing agents when present are present in amounts ranging from about 0.05 to about 3% by weight Other operative polymers include those such as the 3 :1 copolymers of maleic anhydride. with ethyl acryiate, hydroxyethyl methacfylate. N-vinyl-2-pyrolljdone, or ethylene, the latter being available for example as Monsanto EM A No. 1 103, M.W. 1 0,000 and BMA Oracle 61 , and 1 :1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acryiate, i so butyl vinyl ether or N-vinyl-2-p ^' yriOlidone. Suitable generally, are polymerized o!eimiea!ly or ethylenicaily unsatu ated carboxylic acids containing an activated carbon-to-carbon olefinie double bond and at least one carboxyl group, that is, an acid containing an olefinie double bond which readily functions in polymerization because of its presence in the monomer molecule either in the alpha-beta position with respect to a carboxyl group or as part of a. terminal methylene grouping, illustrative of such acids are acrylic, methacry!ic, ethacrylic, a!pha-chloroacry!ic, crotonie, beta-acryioxy propionic, sorbic, alpha-chlorsorbic, cinnamie, beta- styry (acrylic, muconic, itaconic, cilraconic, mesacomc, glutaconie, aconitie, a!pha-phenylacrylic, 2-benzyl acrylic, 2-eyclohexyiaer lic, angelic, umbellic, fumarie, maleic acids and anhydrides. Oilier different olefinie monomers oopolymerizable with such carboxylic monomers include vinyiacetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxylic salt groups for water-solubility. A further class of polymeric agents includes a composition containing homopoiyniers of substituted aery (amides and/or homopolymers of unsaturated ulfonic acids and salts thereof, in particular where polymers are based on unsaturated sulfonic acids selected from acrylamidoalykane sulfonic acids such as 2-acryIamide 2 methyl propane sulfonic acid having a molecular weight of about 1 ,000 to about 2,000,000, described in U.S. Pat, No. 4,842,847, Jun. 27, 19 9 to Zahid. Another useful class of polymeric agents includes polyaanno acids containing proportions of anionic surface-active amino acids such as asparlic acid, glutamic acid and phosphosenne, e.g. as disclosed in U.S. Pat. No.

4,866,161 Sikes et al.

[Θ024| Water; The oral compositions may comprise significant levels of water. Water employed i the preparation oi ^'' commercial oral compositions should ^' be deionized and free oi organic impurities. The amount oi water m the compositions included the fr e water which is added plus that amount which is introduced with other materials.

[0025] umccttmis: Within certain embodiments of the oral compositions, it is also desirable to incorporate a humectant to prevent the composition from hardening upon exposure to air.

Certain humeetaius can also impart desirable sweetness or flavor to dentifrice compositions. Suitable humectants include edible polyhydric alcohols such as glycerine, sorbitol, xylitol. propylene glycol as well as other polyols and mixtures of these humeelants. in one embodiment of the invention, the principal humectan is glycerin, which may be present at levels of greater than 25%, e.g. 25-35% about 30%, with 5% or less of other humectants.

[0026] Other optional ingredients: In addition to the above-described components, the embodiments of this invention can contain a variety of optional dentifrice ingredients some of which are described below. Optional ingredients include, for example, but are not limited to, adhestves, sudsing agents, flavoring agents, sweetening agents, additional antiplaque agents, abrasives, and coloring agents. These and other optional components- are further described in U.S. Pat. No. 5,004,597, to Majeti; U.S. Pat. No. 3,959,458 to Agrieola et al. and U.S. Pat. No. 3,937,807, to Haefele, ail being incorporated herein by reference.

{0027) Unless stated otherwise, all percentages of composition components given in this specification are by weight based on a total composition or formulation weight of 100%, in the case, of Product. 1, et seq., the total composition or formulation weight is the weight of the first and second dentifrices combined.

0028] Unless otherwise specifically identified, the ingredients for use in the compositions and formulations of the present, invention are preferably cosmetically acceptable ingredients. By "cosmetically acceptable ^' ' is meant suitable for use in a formulation for topical application to uman skin. A cosmetically acceptable excipient, for example, is an exeipieitt which is suitable for external application in the amounts and concentrations contemplated in the formuiations of this invention, and includes for example excipients which are "Generally Recognized as Safe ^1* (G AS) by 1he United Stales Fond and Drug Administration,

[0029] The compositions and formuiations as provided herein are described and claimed with reference to their ingredients, as is usual in the art. As would be evident to one skilled in the art, the ingredients may in some instances react with one another, so that the true composition of the final tormu ^' ftion may -not corr spond exactly to the ingredients listed, i bus, it should he

Understood that the invention extends .> (he pr doci of ih c mbi fion of the listed ingredients _* |003(l| As used throughout ranges are used as shorthand for describing each and every valu that is within the range. Any value within the range can be selected as the termi nus of the range, hi addition, all references cited herein are hereby incorporated by referenced in their entireties. In the- event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls. [0031 j Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to reier to percentages by weight. The amoiints given are based on die active weight of the materia!.

EXAMPLES

Example I

j0032] The following test formulations are prepared:

(i) a white active salt dentifrice base, comprising calcium carbonate abrasive but no zinc;

(ii) the dentifrice base of (i) modified to include 1% zinc oxide,

(iii) the dentifrice base of (i) modified to include 0.5% zinc oxide and 2% zinc citrate, and

(iv) a dual component dentifrice which is 80% a dentifrice base (corresponding to the first dentifrice on Product 1 , supra) having substantially the same as (i) and 20% a gel dentifrice stripe (corresponding to the second dentifrice of Produc I , supra) without calcium carbonate but with 5% zinc oxide, i.e, having the same total amount of zinc oxide as (ii), but in the silica gel rather than in the calcium carbonate base.

The specific ingredienis of (lie test formulations are as set forth in Table 1 ;

Example 2

fO«33| The. lo ihpasics f iix mpfe i are e-va uaiet.! a* follows:

1. Saliva is collected from 4 healthy volunteers and pooled together as inoculum,

2. Sterile HAP disks arc incubated under anaerobic conditions at 37 X for 24 hours with 1 ml. of sterile arlifida! saliva (with 0.01% sucrose) and I ml of pooled saliva in a 24 well inicroplate. 3. Freshly prepared treatment solution 1 part dentifrice: 2 parts distilled water is added to the well and allowed to contact with the MAP disk for 10 minutes.

4. The liquid phase is removed and replaced by 2 ml of sterile artificial saliva.

5. The disks are treated in triplicates for each control and test dentifrice for 8 days

6. At intervals of 2, 4 and 8 days the discs are collected aseptically and transferred into pre- redueed thioglycollate medium.

7. 0.01ml of the dilution 10-4, 1 -5 and 10-6 are plated in triplicate for each disk on the following media;

a) Neomycin -Vancomycin (HV) Agar for Total Gram negative Anaerobes.

8. Plates are surface spread using a sterile spreader and incubated anaerobieally @37°C for 72 hours before counting the colonies.

9. The pH is monitored for the entire period of the st udy using the liquid phase.

Plate counts are recorded in log reduction as in Table 2:

Table 2: Averase Log C U ral

}<)034] It is observed that the localization of ZnO in the silica stripe further enhances the bacterial reduction attributes of a calcium carbonate dentifrice.

?0035) ANOVA done for the dais at 95% sign ficance lev l a* set forth in Table 3.

Table 3 : Descriptive Statistics

CAS w/1%ZnO 7.260 ! 0.026 i 0.07.8 - 21__ 10.062 5.830 0.030 0.089 ZnO + 2% Zn Cit i 7.315 I 0.041 I 0.123 6.458 0.036 JX1(½ 5.693 0.032 0.095

Table 4; Significance table

j 036 j Statistical analysis further confirms the difference in efficacy observed.