NZ236644A

NZ236644A - Oral cleaning composition containing polymeric carboxylate phosphatase inhibitor

Info

Publication number: NZ236644A
Application number: NZ23664488A
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: NZ236641A; NZ238146A; NZ236643A; NZ236642A; NZ236645A

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £36644 23 6 6 4 4 Prior*iy 1: .v.c.: ...i j OasnpWrto S,ro .1 ? r'-.-;: .. J....I....'";A".V.. / ; CiCSj.* v>J)..Ak£l.|.k. l.j.l.L# PU-il-Ci p.o. : i '[1\ 2 5 FEB 1992 o—v »£_ >4.2,Po»W..\ 2 2. Its Patents Form No. 5 PATENTS ACT 1953 COMPLETE SPECIFICATION Under the provisions of Regulation 23 (1) the tA K Specification has been ante-dated 19 Cc l r\ c>c -i ■ Initials ... k*> ,.'V Number Dated \2 IDECmO'l • . - ANTIBACTERIAL ANTIPLAQUE, ANTICALCULUS ORAL COMPOSITION We, COLGATE-PALMOLIVE COMPANY, a corporation organised under the laws 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 - j This invention relates to an antibacterial antiplaque anticalculus • dentifrice ccuposition. More particularly, it relates to a dentifrice jcomposition containing a polyphosphate antlcalculus (that is, I i jantitartar) agent and a compatible antibacterial agent effective to inhibit plaque. In N.Z. Patent Specification No. 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 ( Gaffar et al, a linear polyphosphate salt is employed in I I conjunction with a fluoride ion-providing source and a synthetic linear ;polymeric polycarboxylate to inhibit calculus formation. ■ i j In the patents to Parran et al and to Parran water soluble . I ijdlalkali metal pyrophosphate alone or mixed with tetraalkali metal :pyrophosphate is employed. j Oral compositions which inhibit calculus formation on dental .i 'surfaces are highly desirable since calculus is one of the causitive ;|factors in periodontal conditions. Thus, its reduction promotes oral jj hygiene. Dental plaque is a precursor of calculus. Unlike calculus, ,I however, plaque may form on any part of the tooth surface, particularly I j including at the gingival margin. Hence, besides being unsightly, it 'lis implicated in the occurence of gingivitis. I! Accordingly, it would be highly desirable to include j|antimicrobial agents which have been known to reduce plaque in oral ijcompositions containing antlcalculus agents. Indeed, this has been 11 .described in U.S. Patent 4,022,880 to Vinson et al, wherein a compound i]providing zinc ions as an antlcalculus agent is admixed with an ■ i ■ i 'antibacterial agent effective to retard the growth of plaque bacteria, ■i A wide variety of antibacterial agents are described with the zinc -2- ~ ■> T li 236644 t j j ccrrpounds including cationic naterials such as guanides and gusternary )| - • 11 ammonium compounds as well as non-catlonlc compounds such as halugenaced I ■1 sallcylanilldes and halogenated hydroxydiphenyl ethers. li Hitherto, the cationic antibacterial materials such as chlorhexldine, benzthonlum chloride and cetyl pyridlnlum chloride have been the subject of greatest investigation as antibacterial antlplaque agents. However, in spite of their being used in conjuctlon with zinc antlcalculus agent, they are not effective when used with anionic materials such as polyphosphate antlcalculus agent. This j| ineffectiveness is considered to be quite surprising as polyphosphates are chelating agents and the chelating effect has previously been known . I j to Increase the efficacy of cationic antibacterial agents.(see e.g. ! Disinfection, Sterilization and Preservation, 2nd Ed., Black, 1977, page !j : j 915 and Inhibition and Destruction of the Microbial Cell, Hugo, 1971, l-page 215). Indeed, quaternary ammonium compound is present in the il j i plaque control mouthwash containing pyrophosphate of U.S. Patent ! 4,323,551 and bis-blguanide antlplaque agent is suggested in the : ! !jantlcalculus pyrophosphate oral composition of U.S. Patent 4,515,772. In view of the surprising incompatibility of cationic II antibacterial agents with polyphosphates present as antlcalculus agents, 11 it was quite unexpected that other antibacterial agent would be effective. i! It is an advantage of this invention that certain antibacterial agents are effective in antlcalculus oral compositions to inhibit plaque formation. It is a further advantage of this invention that a composition t j|is provided which is effective to reduce plaque and calculus formation, ij It is a further advantage of this invention that an antlplaque, | |anticalculus dentifrice composition is provided which is effective to reduce ! the occurence of gingivitis. 73664 4 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 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 substantially water insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, halogenated salicylanilides, benzoate esters and halogenated carbanilides and a synthetic anionic polymeric polycarboxylate. 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 dehydrated" when used in connection with the polyphosphate salts in this specification and claims means the lack of at least one molecule of water in the salt's acid form. Typical examples of antibacterial agents which are particularly desirab.e from considerations of antiplaque effectiveness, safety and formulation are: Halogenated Diihenvl Ethers 2,4,4'-trichloro-2'-1 ydroxy-diphenyl ether (Triclosan) 2,2' -dihydroxy-5 , 5 ' -r.ibromo-diphenyl ether. Phenolic Compounds (including phenol and its homologs, mono-and poly-alkyl and aromatic halophenols, resorcinol and its derivatives, bisphenolic compounds and halogenated salicylanilides). Phenol and its Homologs Phenol 2 Methyl 3 Methyl 4 Methyl 4 Ethyl 2.4-Dimethyl 2.5-Dimethyl 3,4-Dimethyl Phenol Phenol Phenol Phenol Phenol Phenol Phenol © 12,6-Dimethyl - Phenol i | 4-n-Propyl - Phenol \ \ 4-n-Butyl I - Phenol I | 4-n--Aniyl - Phenol 14-tert-Amyl - Phenol 4-n-Hexyl - Phenol | ;4-n-Heptyl 1 I - Phenol Mono- and Poly-Alkyl and Aromatic Halophenols Methyl - p-Chlorophenol lEthyl < - p-Chlorophenol t 1 1 l| n-Propyl - p-Chlorophenol J n-Butyl - p-Chlorophenol 1n-Aroyl - p-Chlorophenol !sec-Amyl - p-Chlorophenol I j n-Hexyl - p-Chlorophenol i 1 Cyclohexyl - p-Chlorophenol 1 f 1 j n-Heptyl - p-Chlorophenol 1!n-Octyl - p-Chlorophenol I 23 6 6 4 i |Ethyl .! n-Propyl O-Chlorophenol '.Methyl - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chloruphenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol n-Butyl n-Amyl tert-Amyl i-i-Kaxyl n-Heptyl p-Chlorophenol o-Benzyl - p-Chlorophenol -5- i; I i jj o-Benzyl-m-methyl jjo-Benzyl-m, m-dimethyl ||o-Phenylethyl I I 11o-Phenylethyl-m-methyl lj 3-Methyl tj3,5-Dimethyl ■; 6-Kthyl-3-niethyl 6-n-Propyl-3-methyl 6-1so-Propyl-3-methyl '|2-Ethyl-3,5-dimethyl | j i|6-6ec Butyl-3-methyl ■I II 2-iso-Propyl-3,5-dimethyl - p-Chlorophenol jj6-Diethylmethyl-3-methyl - p-Chlorophenol :i6-i6o-Propyl-2-ethyl-3-nethyl - p-Chlorophenol I J j 2-sec Amyl-3,5-dimethyl - p-Chlorophenol i j 2-Diethylmethyl-3.5-diraethyl - p-Chlorophenol I 6-sec Octyl-3-methyl - p-Chlorophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - o-Bromophenol - o-Broraophenol -6- - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol !jp-Bromophenol | Methyl Ethyl n-Propyl ; |n-Butyl 'I l > n-Arayl sec-Amyl , j n-Hexyl ,; cyclohexyl j j o-Bromophenol I i tert-Amyl II n-Hexyl i 'I , I ' 1 II ♦ 1 ' I ' ' • ? 3 6 6 4 4 * i ■ I n-Propyl-m,m-Dimethyl - o-Bromophenol I t .ji-Phenyl Phenol • I li 4-chloro-2-methyl phenol I 4-ch'loro-3-methyl phenol '4-chloro-3,5-dimethyl phenol 2,4-dichloro-3,5-dimethylphenol ;3,4,5,6-terabromo-2-methylphenol i s ]!5-methyl-2-pentylphenol I | , |4-isopropyl-3-methylphenol ; 1 i 5-chloro-2-hydroxydlphenyliDthane t j ! | Resorcinol and Its Derivatives •Resorcinol 'l 'IMethyl '!Ethvl : n-1 -Propyl r -Butyl ' n- -Amyl ! i n- -Hexyl n- ! -Heptyl i n -Octyl ;ln -Nonyl !' Phenyl Benzyl - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol p-Chlorobenzyl - Resorcinol i ;5-Chloro -2,4-Dihydroxydiphenyl Methane : i 'l^'-Chloro -2,4-Dihydroxydiphenyl Methane |j 5-Brorao -2,4-Dihydroxydiphenyl Methane . I 4'-Brcno -2,4-Dihydroxydiphenyl Methane In this specification and claims where no prefix is given before 1 'hexyl'' ■ I (as in hexyl resorcinol) it is to be understood that ' *n hexyl'' is meant. -7- I! i| Phenylethyl !i iFhenylpropyl t o s a < / A ' J < ' O't -t -~s 'J | Blsphenollc Compound's j2,2'-methylene bis (4-chlorophenol) ! |2,2'-methylene bis (3,4,6-trichlorophenol) J2,2'-raethylene bis (4-chloro-6-bromophenol) bis (2-hydroxy-3,5-dichlorophenyl) sulfide bis (2-hydroxy-5-chlorobenzyl) sulfide Halogenated Sallcylanilldes j j 4 1,5-dibromosalicylanilide 3,4' ,5-trichlorosalcylanillde •I II j,3,A',5-tribromosalicylanillde 2,3,3',5-tetrachlorosalicylanilide 11 3,3' ,5- tri-chlorosalicylani lide 3,5-dibromo-3'-trifluoromethyl salicylanllide !j 5-n-ocCanoyl-3'-trifluoromethyl salicylanllide il | j 3,5-dibromo-4'-trifluoromethyl salicylanllide 'l3,5-dibromo-3'-trifluoro methyl salicylanllide (Fluocophene) Benzoic Esters Ethyl Propyl '! Butyl . Ip-Hydroxybenzoic Ac:d Methyl - p-Hydroxybenzoic Acid - p-Hydroxybenzoic Acid - p-Hydroxybenzoic Acid - p-Hydroxybenzoic Acid Halogenated Carbanilldes Il 3»4,4'-trichlorocarbanilide i i! 3-trifluoromethyl-4,4'-dichlorocarbanilide ! 3,3',4-trichlorocarbanilide H The antibacterial agent is present in the dentifrice composition in Man effective antiplaque amount, typically about 0.01-52 by weight, -8- 23664 jjpreferably about 0.03-1*. The antibacterial agent is substantially i! water-insoluble, meaning that its solubility is less than about IX by j weight in water at 25°C and may be even less than about 0.1X. If I I anionizable group Is present solubility is determined at a pH at which ionization does not occur. The preferred halogenated diphenyl ether is Triclosan. The .jpreferred phenolic compound are hexyl resorcinol, 2,2'—methylene l| bis(A-chloro-6-bromophenol) and Fluorophene. The most preferred j| antibacterial antiplaque compound is Triclosan. Triclosan is disclosed in aformentloned U.S. Patent 4,022,880 as an antibacterial agent In '•\ 1! combination with an anticalculus agent which provides zinc ions. It i6 I jjalso disclosed as an antlplaque agent in a dentifrice formulated to I I I » contain a lamellar liquid crystal surfactant phase having a lamellar ! spacing of less than 6.0 mm and which may optionally contain a zinc salt i! t: in published European Patent application 0161898 of Lane et al and in a dentifrice containg zinc citrate trlhydrate in published European Patent Application 0161899 to Saxton. 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 1 alkali metal (e.g. potassium and preferable sodium) or ammonium salt6, ! and any mixtures thereof. Representative examples include sodium |! hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium ;i j|monoacid and tetrasodium pyrophosphates and the like. Linear I 11 polyphosphates correspond to (NaP03)n where n is about 2 to about 125. 'I .They are generally employed in the instant oral compositions in j| approximate weight amounts of 0.1 to 7% preferably 0.1 to IX, more 1 ■'preferably 2 to 7X. When n is at least 3 in (NaP03)n, said 11 polyphosphates are glassy in character. -9- 23664 4 J Particularly desirable anticalculus agents are tetraalkali l lactal pyrophosphates, including mixtures thereof, such as tetrasodium • t * | pyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. An ! anticalculus agent comprising about 4.3Z to about IX by weight of the Jdentifrice compositions wherein the weight ratio of tetrapotassium pyrophosphate to tetrasodium pyrophosphate is from about 4.3:2.7 to liabout 6:1 is especially preferred. _! ; In order to optimize the antlcalculus effectiveness of the dentifrice I j cxaTiposition, an inhibitor against enzynu.ic hydrolysis of the polyphosphate ■ ccnprising up to 3% of a synthetic anionic polymeric polycarboxylate j having a molecular weignt of about 1,000 to about 1,000,000 and preferably about 30,000 to about 500,000 is present. In addition an amount of a fluoride i |ion source sufficient to supply 25 ppm. to 5,000 ppn. of fluoride ions may !joe present. jj The sources of fluoride ions, or fluorine-providing component, iias acid phosphatase and pyrophosphatase enzyme inhibitor component, are veil known in the art as anti-caries agents. These compounds may be j slightly' soluble in water or may be fully water-soluble. They are i . characterized by their ability to release fluoride ions in water and by ' freedom from undesired reaction with other compounds of the dentifrice i preparation. Among these materials are inorganic fluoride salts, such I ! as soluble alkali metal, alkaline earth metal salts, for example, sodium i I fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a ■ copper fluoride such as cuprous fluoride, zinc fluoride, barium I i fluoride, sodium flourosilicate, ammonium florosilicate, sodium ! fluorozirconate, 6odium fluorozirconate, sodium monofluorophosphate, il 1 aluminum mono- and di-fluorophosphate, and fluorinated sodium calcium I pyrophosphate. Alkali metal and tin fluorides, such as sodium and |jstannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred. ? I 11 236614 j The amount of fluorine-providing compound is dependent to some » j extent upon the type of compound, its solubility, and the type of dentifrice Jpreparation, but it must be a non-toxic amount, generally abut 0.005 to I about 3.OX 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 .jWeight of the preparation is considered satisfactory. Any suitable jjminimum amount of such compound may be used, but it Is preferable to |jemploy sufficient compound to release about 300 to 2,000 ppm, more preferable about 800 to about 1,500 ppm of fluoride ion. i i Typically, in the cases of alkali metal fluorides, this ■ I j!component Is present In an amount up to about 2X by weight, based on the » I ijweight of the preparation, and preferably in the range of about 0.05Z to MlZ. In the case of 6odlum monofluorophosphate, the compound may be present in an amount of about 0.1-33!, more typically about 0.76X. 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 ||ppm 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 II j|polycarboxylate6 and their complexes with various cationic germicides, Ijzinc and magnesium have been previously disclosed as antlcalculus agents • i .per se in, for example U.S. Patent No. 3,429,963 to Shedlovsky; U.S. Patent ,jNo 4,152,420 to Gaffar; U.S. Patent No. 3,956,480 to Dichter et al; U.S. jPatent No. 4,138,477 to Gaffar; and u.S. Patent No. 4,183,914 to Gaffar et 11 al. However, only in aforementioned N.Z. Patent Specification No. 217558 23 6 6 4 !I to Gatiar et al 16 there disclosed use of such polycarboxylates alone i | Jjfor 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. i I 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. ^potassium and preferably sodium) or ammonium salts. Preferred are 1:4 j|co 4:1 copolymers of maleic anhydride or acid with another polymerizable 'I !'.ethylenlcally unsaturated monomer, preferably methyl vinyl ether : i I (nialelc anhydride) having a molecular weight (M.W.) of about 30,000 to | about 1,000,000. These copolymers are available for example as Gantrez ' (AM 139 (M.W. 500,000), A.N. 119 (M.W. 250,000); and preferably S-97 i j Pharmaceutical Grade (M.W. 70,000), of GAF Corporation. The term j "synthetic" is intended to exclude known thickening or gelling agents j comprising carboxymethylcellulose and other derivatives of cellulose and i natural gums. i Other operative polymeric polycarboxylates include those ■| i disclosed in U.S. Patent No. 3,956,480 referred to above, such as the I j 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl • i ; methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being 1 | 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 ij methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or j N-vinyl-2-pyrrolidone. i j ii !! ,1 I -12- i 23664 i 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 styrene, isobutylene or ethyl vinyl lecher, polyacryllc, polyltaconic and polymalelc acids, and sulfoacryllc ^oligomers of M.W. as low as 1,000, available as Unlroyal ND-2. i | Suitable generally are polymerized olefinically or .eiiiylenlcally unsaturated carboxyllc acids containing an activated :i icarbon-to-carbon oleflnic double bond and at least one carboxyl group, 'I ithat is, an acid containing an oleflnic double bond which readily • I I Ifunctlons in polymerization because of its presence in the monomer ; i p|tnolecule either in the alpha-beta position with respect to a carboxyl jgroup or as part of a terminal methylene grouping. Illustrative of such ijacids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, ijcrotonic, beta-acryloxy propionic, sorblc, alpha-chlor6orbic, clnnamlc, •beta-6tyrilacrylic, muconic, ltaconic, citraconic, mesaconic, il Mfclutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic, l ' :i i!2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids and : I anhydrides. Other different oleflnic monomers copolymerizable with such ! | carboxyllc monomers include vinylacetate, vinyl chloride, dimethyl . | j|maleate and the like. Copolymers contain sufficient carboxyllc salt . i ijgroups for water-solubility. i! .! Also useful herein are so-called carboxyvlnyl polymers ;di.sclused as toothpaste components in U.S. 3,980,767 to Chown et al; !| :U.5. 3,935,306 to Roberts et al; U.S. 3,919,409 to Perla et al; U.S. ,j 3,911,90A to Harrison, and U.S. 3,71 1 ,604 to Colodney et al. They are commercially available for example under the trademarks Carbopol 934, •940 and 941 of B. F. Goodrich, these products consisting essentially of 'I •!a colloidally water-soluble polymer of polyacryllc acid crosslinked with :|from about 0.752 to about 2.0% of polyallyl sucrose or polyallyl I I pentaerythritol as cross linking agent. 236644 | The synthetic anionic polymeric polycar boxy late component is i . I mainly a hydrocarbon with optional halogen and O-containing Bubstituents ||and linkages as present in for example ester, ether and OH groups, and 'I il HwheA present is generally employed in the instant compositions in 'japproximate weight amounts of 0.05 to 3Z, preferably 0.05 to 22, more I j II preferably 0.1 to 2X. Amounts in the upper portions of these ranges are t i jjtypically employed in dentifrice compositions typically containing a Ijdental abrasive and used in conjunction with brushing of the teeth, e.g. j tooth pastes (including creams), gels, powders and tablets. Amounts in \ I I excess of these ranges may be employed for thickening or gelling 1 I I;purposes. li I As indicated above, these polymeric polycarboxylates have been ;! ij found to be effective inhibitors of alkaline phosphatase enzyme. Since lj this enzyme has little activity (for hydrolyzing pyrophosphate) at about ;| pH 7.0 or below, the polymeric polycarboxylate component may, if ;j desired, be omitted from dentifrice preparations formulated to operate at such i | 1i pH of 7.0 or below. Such omission however could reduce the versatility l! and anticalculus effectiveness of the present dentifrice ccirpositions over the II H broad pH range of about 4.5 to about 10. j| In oral preparations such as mouthwashes, lozenges and chewing Jlgum, the fluorine-providing compound may be typically present in an 'j amount sufficient to release up to about 500 ppm, preferably about 25 to l! about 300 ppm by weight of fluoride ion. Generally about 0.005 to about ii ,1 1.0 wt.X of such compound is present. li In certain highly preferred forms of the invention the dentifrice ii composition may be substantially liquid in character, such as a .1 mouthwash or rinse. In such a preparation the vehicle is typically a '• water-alcohol mixture desirably including a humectant as described jj below. Generally, the weight ratio of water to alcohol is in the range I II ^ 7 k k / Z1 Ij of from about 1:1 to about 20:1, preferably about 3:1 to 10:1 and rfort00 ' " ;5 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 i i • t '! from about 5.5 to 8. The pH is preferably in the range of from about 6 11 jj 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 (a6 with sodium citrate, benzoate, carbonate, or bicarbonate, i j j| disodlum hydrogen phosphate, sodium dlhydrogen phosphate, etc.). 11 In certain other desirable forms of this invention, the dentifrice composition may be substantially solid or pasty in character, such as ( toothpowder, a dental tablet, a toothpaste (dental cream) 'lor gel. The vehicle of such solid or pasty • I j| oral preparations generally contains dentally acceptable polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dlcalcium phosphate, calcium pyrophosphate, magensium orthophosphate, trimagnesiura phosphate, calcium carbonate, aluminum 6ilicate, zirconium silicate, silica, bentonite, and mixtures thereof. Other suitable polishing material include the particulate thermosetting resins described in U.S. Pat. No. 3,070,510 of Dec. 15, ;| 1962 such as melamine-, phenolic, and urea-formaldehydes, and i! • \ i| cross-linked polyepoxides and polyesters. Preferred polishing materials . ) jj include crystalline silica having particle sized of up to about 5 236 6 j-microns, a mean particle size or up tu abouc 1.1 microns, and a surface ; i Ijarea of up to about 50, 000 cm. /gnu, silica gel or colloidal silica, ijand complex amorphous alkali metal aluminosilicate. l| 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 malkali metal almuino-sllicate complexes are particularly useful, since I they have refractive indices close to the refractive indices of gelling I Ijagent-liquid (including water and/or humectant)systems commonly u6ed in i dentifices. ! Many of the so-called "water-insoluble" polishing materials are ii jjanionic in character and also include small amounts of soluble material. I I |jThus, insoluble sodium metaphosphate may be formed in any suitable 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 raetaphosphates (IMP). There 16 present therein a minor amount of soluble phosphate material as impurities, usually a few percent such as up to 42 by weight. The amount of soluble phosphate material, which is believed to include a soluble sodium triraetaphosphate in the case of insoluble metaphosphate, may be reduced or eliminated by washing with water if desired. The insoluble alkali metal metaphosphate is typically employed in powder form of a particle size such that no more than IX of | the material is larger than 37 microns. The polishing material is generally present in the solid or j I i pasty compositions in weight concentrations of about 102 to about 992. h Preferably, it is present in amounts ranging from about 10% to about 752 -16- 2366' jlin toothpaste, and from about 70X to about 99% in toothpowder. ii >| In a toothpaste, the liquid vehicle may compriae water and humectant typically in an amount ranging from about 10% to about 80% by weight of the preparation. Glycerine, propylene glycol, sorbitol, polypropylene glycol and/or polyethylene glycol (e.g. 400-600) exemplify suitable humectants/carriers. Also advantageous are liquid mixtures of j. water, glycerine and sorbitol. In clear gels where the refractive index j is an important consideration, about 3-30 wt. X of water, 0 to about 70 i! jjwt.Z of glycerine and about 20-80 wt. X of sorbitol are preferably ' employed. ii Toothpastes, creams and gels typically contain a natural or U Jsynthetic thickener or gelling agent In proportions of about 0.1 to I |about 10, preferably about 0.5 to about 5wt.%. A suitable thickener Is ;! synthetic hectorite, a synthetic colloidal magnesium alkali metal I I j silicate complex clay available for example as Laponlte (e.g. CP, SP 2002,D) marketed by Laporte Industries Limited. Laponlte D analysis shows, approximately by weight, 58.00% S102> 25.40X MgO, 3.05% Na20, J0.98X Li20, and some water and trace metals. Its true specific gravity jl is 2.53 and it has an apparent bulk density (g./ml. at 8% moisture) of jjl.O. Other suitable thickeners include Irish moss, gum tragacanth, II !j starch, polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl ; » l! methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose 11 I (e.g. available as Natrosol), sodium carboxymethyl cellulose, and 'colloidal silica such as finely ground Syloid (e.g. 244). I • i It will be understood that, as is conventional, the dentifrice :j preparations are to be sold or otherwise distributed in suitable ii ■' labelled packages. Thus a jar of mouthrinse will have a label j| describing it, in substance, as a mouthrinse or mouthwash and having I 236 6 j! directions for its use; and a toothpaste, cream or gel will usually be II in a collapsible tube, typically aluminum, lined lead or plastic, or other squeeze, pump or pressurized dispenser for metering out the ii contents, having a label describing it, in substance, as a toothpaste, I jj gel or dental cream. ■j Organic surface-active agents are used in the compositions of • the present invention to achieve increased prophylactic action, assist II l! in achieving thorough and complete dispersion of the anticalculus agent i J throughout the oral cavity, and render the instant compositions more ' cosmetically acceptable. The organic surface-active material is ll ; preferably anionic, nonionic or ampholytlc in nature, and it is || preferred to employ as the surface-active agent a detersive material ! < jjwhich imparts to the composition detersive and foaming properties. :! Suitable examples of anionic surfactants are water-soluble salts of j higher fatty acid monoglycerlde monosulfates, such as the 6odlum salt of I the monosulfated monoglycerlde of hydrogenated coconut oil fatty acids, i i '•higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl ; sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl i I ^ sulfoacetates, higher fatty acid esters uf I,2-dlhydroxy propane | sulfonate, and the substantially saturated higher aliphatic acyl amides i j of lower aliphatic amino carboxyllc acid compounds, such as those having ! 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the i: lj like. Examples of the last mentioned amides are N-lauroyl sarcosine, ij and the 6odium, potassium, and ethanolamine salts of N-lauroyl, jj N-myristoyl, or N-palmitoyl sarcosine which should be substantially free .Ifrom soap or similar higher fatty acid material. The use of these . I . I I sarcoslnate compounds in the oral compositions of the present invention '•is particularly advantageous since these materials exhibit a prolonged ijand marked effect in the inhibition of acid formation in the oral cavity ii i ;! • t i | -18- 236644 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 poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sobitan monosterate) and polypropyleneoxide (e.g. Pluronic materials). Ic is preferred to use from about 0.05 to 52 by weight and preferably about 0.5 to 52 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 airmoniated material such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, where present, are incorporated in the preparations in amounts 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, perillartine, AMP (aspartyl phenyl alanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may together comprise from about 0.1% to 52 more of the prepara- , cion. In the preferred practice of this invention a dentifrice composition il !i 236644 l| according to this invention is preferably applied regularly 11 to dental enamel, such as every day or every second or third day or || preferably 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 week6 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 ;| 11 warm gum base or coating the outer surface of a gum base, illustrative » I • of which may be mentioned jelutone, rubber latex, vinylite resins, etc., II ;i desirably with conventional plasticizers or softeners, sugar or other 11 •I sweeteners or carbohydrates such as glucose, sorbitol and the like. li : i ^ jj The following examples are further illustrative of the nature -V ' i 11 of 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. li ■ i I! i! ii -20- <W 236 6 Example I Slurries and solutions described below are prepared to determine effectiveness in terms of minimum inhibitory concentration (MIC) of various antibacterial agents against a variety of oral bacterial organisms implicated in formation of plaque and leading to gingivitis on dental surfaces. Soft plaque contains about 1.7 x 10^ organlsm/gm. ||(net weight). The antibacterial agent6 are admixed with anionic •materials, particularly anionic surface active agent often commonly 11 '! employed in oral compositions and polyphosphate anticalculus agent. i |j Minimum inhibitory concentration (MIC) of antibacterial agent l \ jj is used to evaluate the efficacy of the agent in vitro. MIC is defined ;as the minimum concentration in micrograms/ml of antibacterial agent at which the growth of bacteria i6 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 related to the efficacy of the dentifrice in vivo since retention and 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 jjas "TCHE"; the quaternary ammonium antibacterial agent6 benzthonium :{ chloride is indicated as "BTC"; The biguanide chlorhexidine dlgluconate jis indicated as "CH", sodium lauryl sulfate is indicated as "SLS"; the copolymer of maleic anhydride and methyl vinyl ether available from GAF . i 11 corporation as "Gantrez S-97" is identified as "Gantrez"; tetrasodium iipyrophosphate is identified as "pyrophosphate"; and 6odium fluoride is ll identified'as "NaF". -21- TABLE 1 23 6 6 4 Test Solution Minimum Inhibition Concentration (MIC) in mcg/ml Bacteriodes Bacteriodes Actinobacillus Streptococcus ginglvalls lntertnedlus actlnomycetem- nutans comltans , 1. 0.5% TCHE and 2.5 2.5 5.0 25.0 IX SLS in water 2. 0.52 TCHE, 2.5 2.5 5.0 25.0 12 SLS, 12 Gantrez, 22 Pyrophosphate and 0.22 NaF in water 3. 12 SLS in NE NE NE NE water A. 12 SLS, NE NE NE NE 12 Gantrez and 22 Pyrophosphate in water note: NE - not effective The results indicate that TCHE in the presence of anionic surfactant inhibited four dental plaque organisms, Bacteriodes ginglvalls , Bacteroides lntertnedlus , Actlnobaclllus actlnomycetemcomltans and Strep. mutans at 2.5 mcg/ml and 2.5 mcg/ml, 5.0 ocg/ml and 25.0 mcg/ml respectively(1). Similar antibacterial '. effect is seen in the presence of Gantrez/pyrophosphate/f luorlde(2). ! SLS per se and a combination of SLS/Gantrez/pyrophosphate/fluorlde was i|ineffective(3 and A). |] It is noteworthy that in human clinical tests with cationic I I • I antibacterial agents, 0.0752 BTC dissolved in water is effective in reducing plaque formation while 0.0752 BTC and 12 pyrosphosphate '•'dissolved in water is not. Similarly, 0.012 CH dissolved in water is |effective in reducing plaque formation while 0.012 CH and 12 sodium jj N-lauroyl sarcosinate dissolved in water i6 not. il -22- 236 6 Example 2 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 2 hours. The excess saliva is washed off with a buffer and saliva coated 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 I |adsorbed are calculated by the difference between the amount added and jthe amount left in the supernatant after the incubation with coated HA. I The table below summarizes the data. il • I ii • i i . I ; i I 11 • i i j i! II I! li ll t 236 6 TABLE 2 I! ' .Components and Concentrations 2 of TCHE Adsorbed to Coated HA i j j 0.0052 TCHE in 12 SLS 80* : i 0.01* TCHE in 12 SLS 852 ■ I j 0.0152 TCHE in 12 SLS 852 I 0.022 TCHE in 12 SLS 882 • \ !j0.0052 TCHE in 12 SLS; 0.52 802 l|Gantrez; 22 pyrophosphate/ !0.242 NaF ij0.012 TCHE " 852 •j0.0152 TCHE " 862 j0.022 TCHE " 872 i| •i The data indicates that the addition of pyrophosphate/ ii ''Gantrez/NaF does not impair adsorption of TCHE to saliva coated tooth I ■ I ; tainerals. •! -24- Example 3 236644 ii Dentifrice Compositions t | • i. I Glycerine Polyethylene Glycol 600 ..lota Carrageenan !| |Sodium Carboxymethyl Cellulose I l it Sodium Saccharin ! 1 : Sodium Cyclamate ;! •jSodium Fluoride ilDeionized water • i !jTitanium Dioxide l i HSodium Benzoate • |FD&C Blue No. 1(1% Solution) ^Sorbitol (70%) jl hGantrez S-97 j!Tetrasodium Pyrophosphate c 11Tetrapotassium Pyrophosphate Parts 15.00 5.00 0.60 0 .AO 0.243 15.08 O.AOO 19.807 8.330(*) 1.50 A.50 Preciphated Amorph. Hydrated Silica 16.00 Preciphated Amorp. Silica - containing combined alumina 'I ,i Silica Thickener i| j Flavor 'Sodium Lauryl Sulfate ii TCHE 7.00 1.10 1.20 0.50 Parts 10.20 3.00 1.00 3.00 0.243 29.907 0.50 22.50 1.00(**) 1.50 A.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 23 6 6 example 4 v | The dentifrice described in Example 3A is compared with the | 11 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 gm of each dentifrice, mixed well (jfor a couple of hours with stirring bar and centrifuged, after which the 'I supernatant is collected as aqueous extract. Antibacterial activity of j|the dentifrice extracts are evaluated on Bacteriodes glnglvalis. Results are summarized below. ' i table 3 II Inhibition of Growth of Bacteriodes Glnglvalis ij Treatment X !lExtract from dentifrice containing 100.0 :'TCHE (1:500) . i jjExtract from dentifrice without 0.0 .ITCHE (1:500) 'i 'TCHE (5.0 mcg/ml) by itself 100.0 ll I I :i These results indicate that TCHE antibacterial antiplaque agent is il • I compatible in a dentifrice composition containing anionic surfactant jplus pyrophosphate antlcalculus ingredients with enzyme inhibitors I j| Gantrez and NaF. Similar comparable effects prevail when each of hexyl ' i resorcinol, 2,2'-methylene bis(4-chloro-6-bromophenol) and Flourophene ; i .replace TCHE. j i • i i » . i II Example j Mouthrlnse i!Tetrasodium Pyrophosphate j|Gantrez S-97 Glycerine Sodium Fluoride j Pluronic F108 (Polyoxyethylene/Polyoxypropylene Block Copolymer) M TCHE Flavor Water 'I 'I il « I ^ Lozenge t ■'75-802 Sugar • i ij 1-202 Corn Syrup i j 0.1-1.0 Flavor Pa.-ts 2.00 0.25 10.00 0.05 2.00 0.10 0.40 Q.S. to 100.00 Example 6 22 Tetrasodium Pyrophosphate |0.252 Gantrez S-97 0.01 to 0.052 NaF 0.01 to 0.12 TCHE jjl to 52 Magnesium Stearate Lubricant ;i 0.01 to 0.22 Water </div>

Claims

<div class="application article clearfix printTableText" id="claims"> ii n a Example 7 ?36644 ii '! Chewing Gum Gum base Sorbitol (70X) ; TCHE jj •• Tetrasodium Pyrophosophate ii !j Gantrez S.97 , NaF ; Glycerine .j Crystalline Sorbitol :! 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 J • This invention has been described with respect to certain i] 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 j| ijappended claims. The Carrnissioner considers that the invention described in this specification cannot be performed without substantial risk of infringement of New Zealand Patent Nos: 223125, 236641, 236642, 236643, 236645 and 238146. • i it ii ii i i -28- r> ?36644 WHAT WE CT.flTH Tfi :

1. A dentifrice composition (as herein defined - Page 4) comprising in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material comprising at least one linear molecularly dehydrated polyphosphate salt (as herein defined - Page 4); an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, halogenated salicylanilides, benzoate esters and halogenated carbanilides, in which there is present for the purpose of inhibiting hydrolysis of P-O-P bonds in the said polyphosphate salts by phosphatase enzymes in saliva to orthophosphates which are relatively ineffective as inhibitors of hydroxyapatite formation, a synthetic anionic polymeric polycarboxylate having a molecular weight of substantially 1,000 to substantially 1,000,000.

2. A dentifrice composition as claimed in claim 1 containing 0.05% to 3% by weight of the synthetic anionic polymeric polycarboxylate.

3. A dentifrice composition as claimed in claim 1 or claim 2 in which the synthetic anionic polymeric polycarboxylate is a water-soluble alkali metal or ammonium synthetic anionic polymeric polycarboxylate salt.

4. A dentifrice composition as claimed in any one of claims 1 to 3 which further contains a fluoride ion source in an amount sufficient to supply 25 ppm to 5000 ppm of fluoride ions. - 29 - ? 3 6 6 4 4

5. A dentifrice composition as claimed in claim 4 in which the aaid fluoride ion source is sodium fluoride and is in an amount sufficient to supply 300 ppm to 2,000 ppm of fluoride ions.

6. A dentifrice composition as claimed in any one of claims 1 to 5 in which the synthetic anionic polymeric polycarboxylate is present in an amount of 0.1 to 2% by weight.

7. A dentifrice composition as claimed in any one of claims 1 to 6 in which the synthetic anionic polymeric polycarboxylate is a water soluble alkali metal or ammonium salt of a copolymer of vinyl methyl ether and maleic acid or anhydride having a molecular weight of substantially 30,000 to substantially 500,000.

8. A dentifrice composition as claimed in any one of claims 1 to 6 in which the synthetic anionic polymeric polycarboxylate comprises carboxyvinyl polymers.

9. A dentifrice composition as claimed ir any one of claims 1 to 6 in which the synthetic anionic polymeryc polycarboxylate comprises a colloidally water soluble polymer of polyacrylic acid crosslinked with 0.75 to 2% by weight of polyallyl sucrose or polyallyl pentaerythritol as crosslinking agent.

10. A dentifrice composition as claimed in any one of claims 1 to 9 in which the said polyphosphate salt is present in an amount of 0.1-7% by weight. 9 3664 4

11. A dentifrice composition as claimed in any one of the preceding claims in which the said antibacterial agent is present in an amount of 0.01-5% by weight.

12. A dentifrice composition as claimed in any one of claims 1 to 11 in which the said antibacterial agent is a halogenated diphenyl ether.

13. A dentifrice composition as claimed in claim 12 in which the halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxy-diphenyl ether.

14. A dentifrice composition as claimed in any one of claims 1 to 11 in which the said antibacterial agent is a phenolic compound.

15. A dentifrice composition as claimed in claim 14 in which the said phenolic compound is phenol or a homolog thereof (as herein defined - Page 4).

16. A dentifrice composition as claimed in claim 14 in which the said phenolic compound is a mono- or poly- alkyl halophenol or an aromatic halophenol.

17. A dentifrice composition as claimed in claim 14 in which the said phenolic compound is resorcinol or a derivative thereof (as herein defined - Page 7).

18. A dentifrice composition as claimed in claim 17 in which the said resorcinol derivative is hexyl resorcinol. ? 3 6 6 4 4

19. A dentifrice composition as claimed in claim 14 in which the said phenolic compound is a bisphenolic compound.

20. A dentifrice composition claimed in claim 19 in which the said bisphenolic compound is 2,2'-methylene bis(4-chloro-6-bromophenol).

21. A dentifrice composition as claimed in any one of claims 1 to 11 in which the said phenolic compound is a halogenated salicylanilide.

22. A dentifrice composition as claimed in claim 21 in which the said halogenated salicylanilide is 3,5-dibromo-3'- trifluoromethyl salicylanilide.

23. A dentifrice composition as claimed in any one of claims 1 to 11 in which the said antibacterial agent is a benzoate ester.

24. A dentifrice composition as claimed in any one of claims 1 to 11 in which the said antibacterial agent is a halogenated carbanilide.

25. A dentifrice composition as claimed in any one of the preceding claims in which the said polyphosphate salt is selected from the group consisting of water soluble alkali metal and ammonium pyrophosphates, tripolyphosphates and hexairetaphosphates.

26. A dentifrice composition as claimed in claim 25 wherein said tripolyphosphate is sodium tripolyphosphate.

27. A dentifrice composition as claimed in claim 25 wherein said hexametaphosphate is sodium hexametaphosphate.

28. A dentifrice composition as claimed claim 25 in which the said polyphosphate salt is at least one water soluble tetraalkali metal pyrophosphate.

29. A dentifrice composition as claimed in any one of the preceding claims in which the said dentifrice composition further contains a dentally acceptable water insoluble polishing agent and the said dentifrice composition is a toothpowder, dental tablet or toothpaste.

30. A dentifrice composition as claimed in claim 29 in which the said dentifrice composition contains substantially 10-80% by weight of a liquid phase comprising water and humectant, substantially 0.1-10% by weight of a gelling agent and substantially 10-75% by weight of the said polishing agent and the said dentifrice composition is a toothpaste or dental gel.

31. A dentifrice composition as claimed in either one of claims 29 or 30 in which the said polishing material is a silica polishing material.

32. A dentifrice composition as claimed in claim 29 in which the said dentifrice composition contains substantially 70-99% by weight of the said polishing material and the said dentifrice composition is a toothpowder. ?3664 4

33. A dentifrice composition as claimed in any one of claims 1 to 28 in which the said dentifrice composition contains substantially 70-99.9% by weight of a mixture of water and alcohol in a weight ratio of from substantially 1:1 to substantially 20:1 and the said dentifrice composition is a mouth rinse.

34. A dentifrice composition as claimed in claim 33 in which the said alcohol is ethanol.

35. A dentifrice composition as claimed in any one of claims 1 to 28 in which the said dentifrice composition is in the form of a lozenge.

36. A dentifrice composition claimed in any one of claims 1 to 28 in which the said dentifrice composition is in the form of a chewing gum.

37. A dentifrice composition as claimed in claim 1 in the form of a toothpaste or gel comprising in an orally acceptable vehicle, 10 to 75% by weight of a dentally acceptable water insoluble polishing agent, an effective anticalculus amount of 2 to 7% by weight of at least one water soluble linear molecularly dehydrated tetraalkali metal pyrophosphate salt and an effective antiplaque amount of 0.03-1% by weight of 2,4,4'-trichloro-2'-hydroxydipheny1 ether as a substantially water insoluble noncationic antibacterial agent in which there is present for the purpose of inhibiting hydrolysis of P-O-P bonds in the said 736644 pyrophosphate salt by phosphatase enzymes in saliva to orthophosphates which are relatively ineffective as inhibitors of hydroxyapatite formation, 0.05 to 3% by weight of a synthetic anionic polymeric polycarboxylate having a molecular weight of substantially 1,000 to 1,000,000, and a fluoride ion source in an eimount sufficient to supply 25 ppm to 5000 ppm of fluoride ion. west-walker. McCABE •/ /' /> pen -A ' ' 1k* ,'/1;J attorneys for the applicant </div>