NZ236645A

NZ236645A - Oral cleaning composition containing a molecularly-dehydrated polyphosphate salt, benzoate ester and an insoluble non cationic antibacterial agent

Info

Publication number: NZ236645A
Application number: NZ23664588A
Authority: NZ
Inventors: Abdul Gaffer; Brian S Jannone; Nuran Nabi
Original assignee: Colgate Palmolive Co
Priority date: 1987-01-30
Filing date: 1988-01-07
Publication date: 1992-02-25
Also published as: NZ236642A; NZ236643A; NZ236641A; NZ238146A; NZ236644A

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £36645 •• J 2 3 6 6- Prir;:"., ' "!?.?• . , "" 2"5 FEB1992 r' ••Utider....the....RTO.vi5jQC\5....«f L. I,' tetion 23 {\). Jhe mv Regu- NO DRAW!M£$f .»,.:t c ' tr cification has been ante-dated — *■<" ) i to............ A' . v. 19 I'L \ < ' v 1 i Initials Ov-V ^ 2.*2.:t»vzS Patents Form No. 5 Number ^"2 1 DEC 1990 y v- ,<c ' •>? Pfi'i PATENTS ACT 1953 Dated COMPLETE SPECIFICATION ANTIBACTERIAL ANTIPLAQUE, ANTICALCULUS ORAL COMPOSITION We, COLGATE-PALMOLIVE COMPANY, a corporation organised under the lavis of the State of Delaware, United States of America, of 300 Park Avenue, New York, New York 10022, United States of America do hereby declare the invention for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: - 1 - 2 366^5 Has invention relates to an antibacterial antiplaque anticalculus •dentifrice composition. More particularly, it relates to a dentifrice |jcomposition containing a polyphosphate anticalculus (that is, I ll'dntitartar) agent and a compatible antibacterial agent effective to | inhibit plaque. ^ In N.Z. Patent Specification fto. 217558 to Gaffar et al; 4,515,772 to Parran et al; and 4,323,551 to Parran, oral compositions are described .which include various polyphosphate compounds. In the patent to i I j Gaffar et al, a linear polyphosphate salt is employed in t 1 • I conjunction with a fluoride ion-providing source and a synthetic linear [polymeric polycarboxylate to inhibit calculus formation. • I jj In the patents to Parran et al and to Parran water soluble . i jjdialkali metal pyrophosphate alone or mixed with tetraalkali metal •pyrophosphate is employed. ! I ;{ Oral compositions which inhibit calculus formation on dental ii ••surfaces are highly desirable since calculus Is one of the causitive ;jfactors in periodontal conditions. Thus, its reduction promotes oral {}hygiene. H I Dental plaque is a precursor of calculus. Unlike calculus, II :|however, plaque may form on any part of the tooth surface, particularly ! i including at the gingival margin. Hence, besides being unsightly, it is implicated in the occurence of gingivitis. Accordingly, it would be highly desirable to include antimicrobial agent6 which have been known to reduce plaque in oral 11 compositions containing anticalculus agents. Indeed, this has been '.described in U.S. Patent 4,022,880 to Vinson et al, wherein a compound 11providing zinc ions as an anticalculus agent is admixed with an : i ■ i (antibacterial agent effective to retard the growth of plaque bacteria. t < j A wide variety of antibacterial agents are described with the zinc -2- r'-'C ^ '3 1 MAY 1991: t 2366 '".5 compounds including cationic materials such as guanides and quaternary J ammonium compounds as well as non-cationic compounds such ae halogenated ! salicylanilldes and halogenated hydroxydiphenyl ethers. Hitherto, the cationic antibacterial materials such as chlorhexidine, benzthonium chloride and cetyl pyridinium chloride have been the subject of greatest investigation as antibacterial antiplaque agents. However, in spite of their being used in conjuction with zinc anticalculus agent, they are not effective when U6ed with anionic materials such as polyphosphate anticalculus agent. This j ineffectiveness is considered to be quite surprising as polyphosphates I are chelating agents and the chelating effect has previously been known l to increase the efficacy of cationic antibacterial agents.(see e.g. Disinfection, Sterilization and Preservation, 2nd Ed., Black, 1977, page 915 and Inhibition and Destruction of the Microbial Cell, Hugo, 1971, page 215). Indeed, quaternary ammonium compound Is present in the plaque control mouthwash containing pyrophosphate of U.S. Patent 4,323,551 and bis-biguanide antiplaque agent is suggested in the I|anticalculus pyrophosphate oral composition of U.S. Patent 4,515,772. In view of the surprising incompatibility of cationic antibacterial agents with polyphosphates present as anticalculus agents, it was quite unexpected that other antibacterial agent would be effective. It is an advantage of this invention that certain antibacterial agents are effective in anticalculus dentifrice compositions to inhibit plaque formation. It is a further advantage of this invention that a composition is provided which is effective to reduce plaque and calculus formation. It' is a further advantage of this invention that an antiplaque, r 11 anticalculus dentifrice composition is provided which is effective to reduce 1 ! the occurence of gingivitis. > M \ V,_ ^ 9 7 c 4 5 Additional advantages of this invention will be apparent from consideration of the following specification. In accordance with certain of its aspects this invention relates to a dentifrice composition (as herein t defined) comprising in an orally acceptable vehicle an effective anticalculus amount of material comprising at least one linear molecularly dehydrated polyphosphate salt (as herein defined) as essential anticalculus agent and an effective antiplaque amount of a susbtantially water insoluble noncationic antibacterial agent being benzoate esters. In this specification and claims "dentifrice" and "dentifrice composition" mean any toothpaste or cream or dental gel, mouthwash or rinse, toothpowder, chewing gum, or tablet or lozenge or any other preparation or composition for cleansing teeth; and the term "molecularly deiydrato-'' when used in connection with the polyphosphate salts in this specification and claims, means the lack of at least cane molecule of water in the salt's acid form. Typical examples of benzoate esters which are particularly desirable frcm considerations of antiplaque effectiveness, safety and formulation are: p-Hydroxybenzoic Acid Methyl - p-Hydroxybenzoic Acid Ethyl - p-Hydroxybenzoic Acid Propyl - p-Hydroxybenzoic Acid Butyl - p-Hydroxybenzoic Acid The antibacterial agent is present in the dentifrice ccnposition in an effective antiplaque amount, typically about 0.01-5% by weight, 2366 jpreferably about 0.03-1%. The antibacterial agent is substantially iiwater-insoluble, meaning that it6 solubility is lees than about IX by weight in water at 25°C and may be even less than about 0.1%. If anionizable group is present solubility is determined at a pH at which . I I jjionization does not occur. • The linear polyphosphate salts operative herein as anticalculus agents are well known, being generally employed in the form of their wholly or partially neutralized water soluble alkali metal (e.g. potassium and preferable sodium) or ammonium salts, | and any mixtures thereof. Representative examples include sodium 11hexametaphosphate, sodium tripolyphosphate , disodium diacid, trisodiutn ; i monoacid and tetrasodium pyrophosphates and the like. Linear polyphosphates correspond to (NaP03)n where n is about 2 to about 125. '.They are generally employed in the instant oral compositions in approximate weight amounts of 0.1 to 7Z preferably 0.1 to 7Z, more preferably 2 to 7X. When n is at least 3 in (NaP03)n, said ||polyphosphates are glassy in character. - 5 - 236 6 4 j| Particularly desirable anticalculus agents are tetraalkali 11met al pyrophosphates, Including mixtures thereof, such as tetrasodium i | pyrophosphate, tetrapotassiuni pyrophosphate and mixtures thereof. An i j anticalculus agent comprising about 4.3% to about 7X by weight of the oral compositions wherein the weight ratio of tetrapotassium pyrophosphate to tetrasodium pyrophosphate is from about 4.3:2.7 to jiabout 6:1 is especially preferred. In order to optimize the anticalculus effectiveness of the oral composition, inhibitors against enzymatic hydrolysis of the i ■polyphosphate are desirably present. Such agents are an amount of a »I |jfluoride ion source sufficient to supply 25 ppm. to 5,000 ppm. of ;i !| fluoride ions, and 0% to 37. of a synthetic anionic polymeric it ||polycarboxylate having a molecular weight of about 1,000 to about ! I !| 1,000,000, preferably about 30,000 to about 500,000. j| The sources of fluoride ions, or fluorine-providing component, ias acid phosphatase and pyrophosphatase enzyme inhibitor component, are well known in the art as anti-caries agents. These compounds may be slightly soluble in water or may be fully water-soluble. They are characterized by their ability to release fluoride ions in water and by freedom from undesired reaction with other compounds of the oral i[ , preparation. Among these materials are inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal salts, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such a6 cuprous fluoride, zinc fluoride, barium fluoride, sodium flourosilicate, ammonium florosilicate, sodium fluorozirconate, sodium fluorozirconate, sodium monofluorophosphate, aluminum mono- and di-fluorophosphate, and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as sodium and [stannous fluorides, sodium monofluorophosphate (MFP) and mixtures I thereof, are preferred. - 6 - II £ w o ^ 'J / ; The amount* of fluorine-providing compound is dependent to some • I ;jextent upon the type of compound, its solubility, and the type of dentifrice but it must be a non-toxic amount, generally abut 0.005 to about 3.0' In the preparation. In a dentifrice preparation such as dental gel, toothpaste (including cream), toothpowder, or dental tablet, an amount of such compound which releases up to about 5,000 ppm of F ion by ^weight of the preparation is considered satisfactory. Any suitable jjmlnlmum amount of such compound may be used, but it 1s preferable to jjemploy sufficient compound to release about 300 to 2,000 ppm, more preferable about 800 to about 1,500 ppm of fluoride Ion. i i 1/plcally, in the cases of alkali metal fluorides, this M jjcomponent Is present in an amount up to about 22 by weight, based on the ijwelght of the preparation, and preferably in the range of about 0.05Z to 'I 12. In the case of sodium monofluorophosphate, the compound may be present in an amount of about 0.1-32, more typically about 0.76%. In dentifrice preparations such as lozenges 'and chewing gum, !|the fluorine-providing compound is typically present in an amount . i ||sufficient to release up to about 500 ppm, preferably about 25 to 300 |Jppm by weight of fluoride Ion. Generally about 0.005 to about 1.0 wt. X of such compound Is present. The synthetic anionic polymeric polycarboxylate is an Inhibitor ;;of alkaline phosphatase enzyme. Synthetic anionic polymeric 11 jjpolycarboxylates and their complexes with various cationic germicides, 11zinc and magnesium have been previously disclosed as anticalculus agents iper se in, for example U.S. Patent No. 3,429,963 to Shedlovsky; U.S. Patent ;|No 4,152,420 to GafEar; U.S. Patent No. 3,956,480 to Dichter et al; U.S. i; 'Patent No. 4,138,477 to Gaffar; and U.S. Patent No. 4,183,914 to Gaffar et 11 al - Hcwever, only in aforementioned N.Z. Patent Specification No. 217558 ! I il - 7 - V J 236645 to Gariar et al is there disclosed use of 6uch polycarboxylates alone for inhibiting salivary hydrolysis of pyrophosphate anticalculus agents, j much less in combination with a compound providing a source of fluoride ion. . It Is to be understood that the synthetic anionic polymeric polycarboxylates so disclosed in these several patents are operative in the compositions and methods of this invention and such disclosures are ! to that extent incorporated herein by reference thereto. The synthetic anionic polymeric polycarboxylates optionally but preferably employed herein are, as indicated above, well known, being often employed in the form of their free acids or preferably partially or more preferably fully neutralized water soluble alkali metal (e.g. jjputasslura and preferably sodium) or ammonium salts. Preferred are 1:4 ijto 4:1 copolymers of maleic anhydride or acid with another polymerizable 'I liethylenically unsaturated monomer, preferably methyl vinyl ether !j ( (maleic anhydride) having a molecular weight (M.W.) of about 30,000 to about 1,000,000. These copolymers are available for example as Gantrez (AN 139 (M.W. 500,000), A.N. 119 (M.W. 250,000); and .preferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAF Corporation. The term "synthetic" is intended to exclude known thickening or gelling agents comprising carboxymethylcellulose and other derivatives of cellulose and natural gums. Other operative polymeric polycarboxylates include those disclosed in U.S. Patent No. 3,956,480 referred to above, such as the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl ; methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA jjGrade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl j|methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. - 8 - © li !! n 23 6 6 4 Additional operative polymeric polycarboxylates disclosed in ■jabove referred to U.S. Patent No. 4,138,477 and 4,183,914, include [[copolymers of maleic anhydride with etyrene, isobutylene or ethyl vinyl f i jiether, polyacrylic, polyltaconic and polytnalelc acids, and sulfoacryllc ijoligoaers of M.W. as low as 1,000, available as Uniroyal ND-2. i j| Suitable generally are polymerized olefinically or Ielhylenically unsaturated carboxylic acids containing an activated !i icarbon-to-carbon olefinic double bond and at least one carboxyl group, 'I ,!t.hat is, an acid containing an olefinic double bond which readily ,(functions in polymerization because of its presence In the monomer ijmolecule either in the alpha-beta position with respect to a carboxyl I ,|group or as part of a terminal methylene grouping- Illustrative of such •jacids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, ilcrotonic, beta-acryloxy propionic, 6orbic, alpha-chlor6orbic, cinnamic, ■beta-styrilacrylic, muconic, itaconic, cltraconic, mesaconic, il llplutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic, ii ]!2-cyclohexylacrylic, angelic, umbellic, fumarlc, maleic acids and ll Htinhydrides. Other different olefinic monomers copolymerizable with such I • !|carboxylic monomers include vlnylacetate, vinyl chloride, dimethyl !|maleate and the like. Copolymers contain sufficient carboxylic salt .i ijgroups for water-solubility. ;! Also useful herein are so-called carboxyvinyl polymers •disclosed as toothpaste components in U.S. 3,980,767 to Chown et al; il |U.S. 3,935,306 to Roberts et al; U.S. 3,919,409 to Perla et al; U.S. ^3,911,904 to Harrison, and U.S. 3,711,604 to Colodney et al. They are • i comercially available for example under the trademarks Carbopol 934, 1940 and 941 of B. F. Goodrich, these products consisting essentially of a colloidally water-soluble polymer of polyacrylic acid crossllnked with from about 0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent. ii - 9 - 2366-15 ;j The synthetic anionic polymeric polycarboxylate ccrponent is i! • • : i mainly a hydrocarbon with optional halogen and O-containing eubstituents iland linkages as present in for example ester, ether and OH groups, and 'I il ' ilwhert present is generally employed In the instant compositions In |japproximate weight amounts of 0.05 to 3X, preferably 0.05 to 2Z, more ijpreferably 0.1 to 2%. Amounts in the upper portions of these ranges are > i jj typically employed in dentifrice compositions typically containing a J dental abrasive and used in conjunction with brushing of the teeth, e.g. tooth pastes (Including creams), gels, powders and tablets. Amounts in excess of these ranges may be employed for thickening or gelling jj purposes. I As indicated above, these polymeric polycarboxylates have been found to be effective inhibitors of alkaline phosphatase enzyme. Since II this enzyme has little activity (for hydrolyzing pyrophosphate) at about » I pH 7.0 or below, the polymeric polycarboxylate component may, if desired, be omitted from dentifrice preparations formulated to operate at such ! pH of 7.0 or below. Such omission however could reduce the versatility !; and anticalculus effectiveness of the present oral compositions over the j n i !jbroad pH range of about A.5 to about 10. | i j In dentifrice preparations such as mouthwashes, lozenges and chewing jjgum, the fluorine-providing compound may be typically present In an M amount sufficient to release up to about 500 ppm, preferably about 25 to '! about 300 ppm by weight of fluoride ion. Generally about 0.005 to about Jj 1.0 wt.% of such compound is present. |i In certain highly preferred forms of the invention the dentifrice ii I composition may be substantially liquid in character, such as a ;{ mouthwash or rinse. In such a preparation the vehicle is typically a j; II water-alcohol mixture desirably including a humectant as described i I jj below. Generally, the weight ratio of water to alcohol is in the range II -10" I I 2lb0~\b j! of from about 1:1 to about 20:1, preferably about 3:1 to 10:1 and more j| preferably about 4:1 to about 6:1. The total amount of water-alcohol mixture in this type of preparation is typically in the range of from about 70 to about 99.9% by weight of the preparation. The alcohol is typically ethanol or isopropanol. Ethanol is preferred. The pH of such liquid and other preparations of the Invention is generally in the range of from about 4.5 to about 9 and typically '! from about 5.5 to 8. The pH is preferably in the range of from about 6 ll j| to about 8.0. It is noteworthy that the compositions of the invention may be applied orally at a pH below 5 without substantially decalcifying or otherwise damaging dental enamel. The pH can be controlled with acid (e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) or buffered (as with sodium citrate, benzoate, carbonate, or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.). In certain other desirable forms of this invention, the dentifrice composition may be substantially 6olid or pasty in character, such as toothpowder, a dental 'tablet, toothpaste (dental cream) i |jor gel. The vehicle of such solid or pasty dentifrice i jj • preparations generally contains dentally acceptable polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magensium orthophosphate, trimagnesiura phosphate, calcium carbonate, aluminum silicate, zirconium silicate, silica, bentonite, and mixtures thereof. Other suitable polishing material include the particulate i 1 thermosetting resins described in U.S. Pat. No. 3,070,510 of Dec. 15, j| 1962 such as melamine-, phenolic, and urea-formaldehydes, and • | || cross-linked polyepoxides and polyesters. Preferred polishing materials . I :j include crystalline silica having particle sized of up to about 5 23 6 6 4 |jmicrons, a mean particle size or up tu about 1.1 microns, and a surface i' 2 Jjarea of up to about 50, 000 cm. /gm., silica gel or colloidal silica, i>nd complex amorphous alkali metal aluminosllicate. When visually clear gels are employed, a polishing agent of colloidal silica, such as those sold under the trademark SYLOID as Syloid 72 and Syloid 74 or under the trademark SANTOCEL as Santocel 100 .jalkali metal almuino-silicate complexes are particularly useful, since ■j they have refractive indices close to the refractive Indices of gelling i! |jagent-liquid (including water and/or humectant)systems commonly used in • i dentif ices. Many of the so-called "water-insoluble" polishing materials are anionic in character and also include small amounts of soluble material. I I |jThus, Insoluble sodium metaphosphate may be formed in any suitable jl manner as illustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4th Edition, pp. 510-511. The forms of insoluble sodium metaphosphate known as Madrell's salt and Kurrol's salt are further examples of suitable materials. These metaphosphate salts exhibit only a minute solubility in water, and therefore are commonly referred to as insoluble metaphosphates (IMP). There 16 present therein a minor amount of soluble phosphate material as impurities, usually a few percent such as up to 4% by weight. The amount of soluble phosphate material, which is believed to include a soluble sodium triraetaphosphate in the case of IJ insoluble metaphosphate, may be reduced or eliminated by washing with l! water if desired. The insoluble alkali metal metaphosphate is typically , employed in powder form of a particle size such that no more than 1% of I 1 the material is larger than 37 microns. ,j The polishing material is generally present in the solid or '! pasty compositions in weight concentrations of about 10% to about 99%. I i jj Preferably, it is present in amounts ranging from about 10% to about 75% I I li - 12 - 2 3 6 6 < 5 in toothpaste, and from about 702 to about 992 in toothpovder. In a toothpaste, the liquid vehicle may comprise water and humectant typically in an amount ranging from about 102 to about 802 by weight of the preparation. Glycerine, propylene glycol, sorbitol, polypropylene glycol and/or polyethylene glycol (e.g. 400-600) exemplify suitable huaectants/carriers. Also advantageous are liquid mixtures of water, glycerine and sorbitol. In clear gels where the refractive index is an important consideration, about 3-30 wt. 2 of water, 0 to about 70 wt.2 of glycerine and about 20-80 wt. X of sorbitol are preferably employed. Toothpastes, creams and gels typically contain a natural or I jsynthetic thickener or gelling agent in proportions of about 0.1 to I |about 10, preferably about 0.5 to about 5wt.X. A suitable thickener is ! synthetic hectorite, a synthetic colloidal magnesium alkali metal ! silicate complex clay available for example as Laponite (e.g. CP, SP 2002,D) marketed by Laporte Industries Limited. Laponite D analysis shows, approximately by weight, 58.002 SiOj, 25.40Z MgO, 3.052 Na20, J0.982 LijO, and some water and trace metals. Its true specific gravity , is 2.53 and it has an apparent bulk density (g./ml. at 82 moisture) of 1.0. Other suitable thickeners include Irish moss, gum tragacanth, !| starch, polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl !i methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose I i (e.g. available as Natrosol), sodium carboxymethyl cellulose, and i colloidal silica such as finely ground Syloid (e.g. 244). ii It will be understood that, as is conventional, the dentifrice preparations areito be sold or otherwise distributed in suitable it ''labelled packages. Thus a jar of mouthrinse will have a label ||describing it, in substance, as a mouthrinse or mouthwash and having ' I '! - 13 - jr 11 23 6 64 jl directions for its uee; and a toothpaste, cream or gel will usually be ,i ■ ll in a collapsible tube, typically aluminum, lined lead or plastic, or » other squeeze, pump or pressurized dispenser for metering out the li 'contents, having a label describing it, in substance, as a toothpaste, gel or dental cream. jj Organic surface-active agents are used In the compositions of ■ the present invention to achieve increased prophylactic action, assist ll !| in achieving thorough and complete dispersion of the anticalculus agent throughout the oral cavity, and render the instant compositions more 'cosmetically acceptable. The organic surface-active material is || J preferably anionic, nonionlc or ampholytic in nature, and It 16 preferred to employ as the surface-active agent a detersive material j| which imparts to the composition detersive and foaming properties, l! Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the 6odium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, i > ''higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl | sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl ■ i 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 those having 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the like. Examples of the last mentioned amides are N-lauroyl sarcosine, and the sodium, potassium, and ethanolamine salts of N-lauroyl, | N-myristoyl, or N-palmitoyl sarcosine which should be substantially free I from soap or similar higher fatty acid material. The use of these I I I sarcosinate compounds in the oral compositions of the present invention is particularly advantageous since these materials exhibit a prolonged jj and marked effect in the inhibition of acid formation in the oral cavity I i - 14 - due to carbohydrate breakdown in addition to exerting some reduction in the solubility of tooth enamel in acid solutions. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydrophobic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene moieties, such as condensation products of polyCethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sobitan monosterate) and polypropyleneoxide (e.g. Pluronic materials). It is preferred to use from about 0.05 to 5% by weight and preferably about 0.5 to 5% of the foregoing surface active materials in the instant composition. Various other materials may be incorporated in the dentifrice preparations of this invention such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammoniated material such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, where present, are incorporated in the preparations inamounts which do not substantially adversely affect the properties and characteristics desired. Significant amounts of zinc, magnesium and other metal salts and materials, generally soluble, which would complex with active components of the instant invention are to be avoided. Any suitable flavoring or sweetening material may also be employed. Examples of suitable flavoring constituents are flavoring oils, e.g. oil of spearmint, pepperment, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitil, xylitol, sodium cyclamate, peri1lartine, AMP (aspartyl phenyl alanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may together comprise from about 0.1% to 5% more of the preparation . In the preferred practice of this invention a dentifrice composition I'l > • 9 2 i 6 6 s 5 :i according to thiB invention such as a mouthwash contcii.ni.ng p1 jjthfe composition of the present invention i6 prsferably applied regularly 11 'l to dental enamel, such as every day or every second or third day or if pref erably from 1 to 3 times daily, at a pH of about A.5 to about 9, generally about 5.5 to about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more up to lifetime. The compositions of this invention can be Incorporated in lozenges, or in chewing gum or other products, e.g. by stirring into a I; warm gun base or coating the outer surface of a gum base, illustrative of which may be mentioned jelutone, rubber latex, vinylite resins, etc., ji desirably with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates 6uch as glucose, sorbitol and the like. The following examples are further illustrative of the nature M of the present invention, but it is understood that the invention is not 11 ;jlimited thereto. All amounts and proportions referred to herein and in 11 .i the appended claims are by weight. Hie Exairples include compositions '• beyond the scope of the invention utilizing alternative antibacterial ]j agents. i i ii ii !! - 16 - 236 6 J Example 1 i '■ i I I I Slurries and solutions described below are prepared to determine I effectiveness in terms of minimum inhibitory concentration (MIC) of | various antibacterial agents against a variety of oral bacterial i I !organisms implicated in formation of plaque and leading to gingivitis on I * I I I |dental surfaces. Soft plaque contains about 1.7 x 10 organism/gm. jj(net weight). The antibacterial agents are admixed with anionic .'materials, particularly anionic surface active agent often commonly ||employed In oral compositions and polyphosphate anticalculus agent. | Minimum inhibitory concentration (MIC) of antibacterial agent j i6 used to evaluate the efficacy of the agent In vitro. MIC is defined ,!as the minimum concentration in micrograms/ml of antibacterial agent at i which the growth of bacteria is completely inhibited by the agent. The | smaller the MIC value the greater is the efficacy of the antibacterial ! agent to inhibit the growth of the bacteria. The in vitro MIC data is l!related to the efficacy of the dentifrice In vivo since retention and I j release of antibacterial agent into the oral cavity after toothbrushing is in the range of mcg/ml. In the Tables, following disclosure and following'Examples, the agent Triclosan, 2,4,4'-trichloro-2'-hydroxydiphenyl ether is indicated j as "TCHE"; the quaternary ammonium antibacterial agents benzthonlum j chloride is indicated as "BTC"; The biguanide chlorhexldine digluconate |jis indicated as "CH", sodium lauryl sulfate is indicated as "SLS"; the . I ' copolymer of maleic anhydride and methyl vinyl ether available from GAF . i 11 corporation as "Gantrez S-97" is identified as "Gantrez"; tetrasodium il pyrophosphate is identified as "pyrophosphate"; and sodium fluoride is j| identified a6 "NaF". ' I j I i I - 17 - J . >■* © 23 6 6 4 i TABLE 1 Test Solution Minimum Inhibition Concentration (MIC) in mcg/ml Bacterlodes Bacteriodes Actinobacillue Streptococcus glnglvalls lntermedlus actlnomycetem- nutans comitans , 1. 0.5X TCHE and IX SLS in water i 2. 0.5X TCHE, IX SLS, IX Gantrez, 2X Pyrophosphate and 0.2X NaF in water 2.5 2.5 2.5 2.5 5.0 5.0 25.0 25.0 i! 3. It SLS in water U. IX SLS, IX Gantrez and 'j 2X Pyrophosphate • I in water NE NE NE NE NE NE NE NE 11 11 note: NE ■ not effective The results indicate that TCHE in the presence of anionic surfactant inhibited four dental plaque organisms, Bacterlodes glnglvalls, Bacteroldes intermedlus, Actlnobaclllus actlnomycetemcomltans and Strep ■ mutans at 2.5 mcg/tnl and 2.5 mcg/ml, 5.0 mcg/ml and 25.0 mcg/ml respectively(1). Similar antibacterial Ijeffect is seen in the presence of Gantrez/pyrophosphate/fluoride(2). SLS per se and a combination of SLS/Gantrez/pyrophosphate/fluoride was ineffective(3 and 4). It is noteworthy that in human clinical tests with cationic antibacterial agents, 0.075X BTC dissolved in water is effective in reducing plaque formation while 0.075X BTC and IX pyrosphosphate j! dissolved in water is not. Similarly, 0.01X CH dissolved in water is ;Seffective in reducing plaque formation while 0.01X CH and IX sodium I N-lauroyl sarcosinate dissolved in water is not. - 18 - Example 2 23 6 6 The adsorption to and release from tooth minerals for antiplaque/ antitartar efficacy of agents is assessed by adsorption of antibacterial agent to saliva coated tooth mineral hydroxyapatite in the presence and the absence of pyrophosphate (soluble tetrasodium pyrophosphate)/Gantrez/NaF. 200 mg. of hydroxyapatite (HA) is treated with human saliva for I 2 hours. The excess saliva is washed off with a buffer and saliva coated HA is used for adsorption studies. Various concentrations of TCHE in SLS jor in SLS/pyrophosphate/Gantrez/NaF are mixed with the coated HA and I incubated at 37° for 3 hours under continuous agitation. At the end of incubation period, the mixtures are centrifuged, HA separated and the |amounts of TCHE adsorbed determined by estimating TCHE in the 'supernatant at 283nM in a Gilford spectrophotometer. The amounts |adsorbed are calculated by the difference between the amount added and i jthe amount left in the supernatant after the Incubation with coated HA. |The table below summarizes the data. I ii • i i; i M ■ i I • • ■j I! i i II |i li II - 19 - 236 6 M TABLE 2 ii' I ■ .Components and Concentrations 2 of TCHE Adsorbed to Coated HA . I jj 0.0052: TCHE in IX SLS 80% jj 0.012 TCHE in 12 SLS 85% I 0.0152 TCHE in 1% SLS 852 0.022 TCHE in 12 SLS 882 I 0.0052 TCHE in IX SLS; 0.52 802 Cantrez; 22 pyrophosphate/ 0.242 NaF | j 0.01% TCHE " 852 0.0152 TCHE " 862 10.022 TCHE " 872 II •i The data indicates that the addition of pyrophosphate/ ii MGantrez/NaF does not impair adsorption of TCHE to saliva coated tooth ;i ;minerals. i .1 ll - 20 - $ o Example 3 jjDentifrice Compositions Glycerine Polyethylene Glycol 600 , ilota Carrageenan I Sod 1 lire Carboxymethyl Cellulose 1 jjSodium Saccharin !Sodium Cyclamate Sodium Fluoride i|Deionized water i! jj Titanium Dioxide USodium Benzoate ■ j FD6C Blue No. 1(1X Solution) il ;Sorbitol (702) jl ll Gantrez S-97 jJTetrasodium Pyrophosphate i" II Tetrapotassium Pyrophosphate Parts 15.00 5.00 0.60 0.40 0.243 15.08 0.400 19.807 8.330(*) 1.50 4.50 Preciphated Amorph. Hydrated Silica 16.00 111 Preciphated Amorp. Silica |j containing combined alumina ll iSilica Thickener ; 1 Flavor • Sodium Lauryl Sulfate TCHE 7.00 1.10 1.20 0.50 Parts 10.20 3.00 23 6 6 4 5| 1.00 3.00 0.243 29.907 0.50 22.50 1.00(**) 1.50 4.50 19.50 0.95 1.20 0.50 Parts 15.00 5.00 0.60 0.40 0.243 23.657 0.50 22.50 1.00(**) 1.50 4.50 16.00 5.50 1.10 1.20 0.50 '' * liquid Ii ** powder - 21 - # 236 6 Example 4 li The dentifrice described in Example 3A is compared with the same composition except without any TCHE and with added 0.50 parts of water. Aqueous extracts of each dentifrice are prepared as follows: 50 ml of distilled water is added to 1.0 gin of each dentifrice, mixed well tjfor a couple of hours with stirring bar and centrlfuged, after which the ' I supernatant is collected as aqueous extract. Antibacterial activity of j j Che dentifrice extracts are evaluated on Bacterlodes glnglvalls. '.Results are summarized below. I 'i TABLE 3 il II Inhibition of Growth !', of Bacterlodes Glnglvalis jj Treatment X IIExtract from dentifrice containing 100.0 !'TCHE (1:500) ■j jiExtract from dentifrice without 0.0 llTCHE (1:500) !i •' TCHE (5.0 mcg/ml) by itself 100.0 •I These results indicate that TCHE antibacterial antiplaque agent is 'I compatible in a dentifrice composition containing anionic surfactant plus pyrophosphate anticalculus ingredients with enzyme inhibitors Gantrez and NaF. Similar comparable effects prevail when each of hexyl resorcinol, 2,2'-methylene bis(A-chloro-6-bromophenol) and Flourophene replace TCHE. li . i i I - 22 - example j • •Mouthrinse l| Tetrasodium Pyrophosphate Gantrez S-97 Glycerine Sodium Fluoride .! Pluronic F108 J (Polyoxyethylene/Polyoxypropylene ;j Block Copolymer) 1'TCHE Flavor Water Lozenge Parts 2.00 0.25 10.00 0.05 2.00 0.10 0.40 Q.S. to 100.00 Example 6 •i 75-802 Sugar ; I j|1-202 Corn Syrup i|0.1-1.0 Flavor ll . 22 Tetrasodium Pyrophosphate 0.252 Gantrez S-97 0.01 to 0.05% NaF 0.01 to 0.12 TCHE 1 to 52 Magnesium Stearate Lubricant ';! 0.01 to 0.22 Water I > 23 6 6 45 - 23 - </div>

Claims

<div class="application article clearfix printTableText" id="claims"> t II I! Example 7 23 6 6' ' i Chewing Gum Gum base Sorbitol (70X) .! TCHE 'Tetrasodium Pyrophosophate jj Gantrez S.97 i 1 . NaF ;Glycerine ,j Crystalline Sorbitol ;j Flavor and Water Parts 25.00 17.00 0.50 to 0.10 2.00 0.25 0.05 0.50 53.00 Q.S. to 100.00 This invention has been described with respect to certain il preferred embodiments and It will be understood that modifications and variations thereof obvious to those skilled in the art are to be included within the purview of this application and the scope of the l| i| appended claims. - 24 - WHAT WE CLAIM IS:

1. A dentifrice composition (as herein defined - Page 4) comprising in an orally acceptable vehicle an effective anticalculus amount of an anticalculus material comprising at least one linear molecularly dehydrated polyphosphate salt (as herein defined - Page 4) and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial agent which is a benzoate ester.

2. A dentifrice composition as claimed in claim 1 wherein the anticalculus material is a mixture of tetrasodium pyrophosphate and tetrapotassium pyrophosphate salts.

3. A dentifrice composition as claimed in claim 1 wherein the anticalculus material is at least one wholly or partially neutralized water-soluble alkali metal or ammonium tripolyphosphate or hexametaphosphate salt.

4. A dentifrice composition as claimed in claim 1 which further comprises sodium fluoride as a fluoride ion source in an amount sufficient to supply 25 to 5000 ppm of fluoride ion.

5. A dentifrice composition as claimed in any one of the preceding claims wherein the anticalculus material is present in an amount of between 2% and 7% by weight.

6. A dentifrice composition as claimed in either of claims 4 or 5 wherein the fluoride ion source is present in an amount of at least 0.24% by weight. - 25 - ? 3 f 6 4 5

7. A dentifrice composition as claimed in any one of the preceding claims wherein the benzoate ester is present in an amount of between 0.01 and 5% by weight.

8. A dentifrice composition as claimed in any one of the preceding claims wherein the anticalculus material is present in an amount of between 4.3 and 7% by weight.

9. A dentifrice composition as claimed in claim 2 or any one of claims 5 to 7 when dependent on claim 2 wherein the tetrapotassium pyrophosphate and the tetrasodium pyrophosphate are present in a weight ratio of from 4.3:2.7 to 6:1.

10. The dentifrice composition as claimed in claim 3 wherein the anticalculus material is present in an amount of substantially 0.1 to 7% by weight and the antibacterial agent is present in an amount of substantially 0.01 to 5% by weight.

11. The dentifrice composition as claimed in claim 10 wherein the anticalculus material is sodium tripolyphosphate.

12. The dentifrice composition as claimed in claim 10 wherein the anticalculus material is sodium hexametaphosphate.

13. The dentifrice composition as claimed in any one of the preceding claims which further contains a dentally acceptable water-insoluble polishing agent and the dentifrice composition is a tooth powder, dental tablet or toothpaste. 236645

14. The dentifrice composition as claimed in claim 13 wherein the dentifrice composition contains substantially 10 to 80% by weight of a liquid phase comprising water and humectant, substantially 0.1 to 10% by weight of a gelling agent and substantially 10 to 75% by weight of the polishing agent and the dentifrice composition is a toothpaste or gel.

15. The dentifrice composition as claimed in either one of claims 13 or 14 wherein the polishing agent is a silica polishing material.

16. The dentifrice composition as claimed in claim 13 wherein the dentifrice composition contains 70 to 99% by weight of the polishing material and the dentifrice composition is a toothpowder.

17. The dentifrice composition as claimed in any one of claims 1 to 12 wherein the dentifrice composition contains substantially 70 to 99.9% by weight of a mixture of water and alcohol in a weight ratio of from substantially 1:1 to substantially 20:1 and the dentifrice composition is a mouth rinse.

18. The dentifrice composition as claimed in claim 17 wherein the alcohol is ethanol.

19. The dentifrice composition as claimed in any one of claims 1 to 12 wherein the dentifrice composition is in the form of a lozenge. 236645

20. The dentifrice composition as claimed in any one of claims 1 to 12 wherein the dentifrice composition is in the form of a chewing gum. V7EST-WALKER, McCABE per. vL attorneys for the applicant </div>