NZ236641A

NZ236641A - Oral cleaning composition including a linear, molecularly dehydrated polyphosphate salt, a non cationic antibacterial agent and a fluoride ion source

Info

Publication number: NZ236641A
Application number: NZ23664188A
Authority: NZ
Inventors: Abdul Gaffar; 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; NZ236645A; NZ236643A; NZ236644A; NZ238146A

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £36641 2 5 F E B 1992 '.Oil*' 'I' Under the provisions v1 Regu- NO dp,;x lation 23 (1) the Specification has been ante-dated to. ' i y it \ ii",,' 19 .L. Initials ■ Patents Form No. 5 Number V i-ti ; \ C ■ /■/ \ '(2 1 DtC|99Qr ■ PATENTS ACT 1953 Dated COMPLETE SPECIFICATION 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 - 23664 1 'Itiis invention relates to an antibacterial antiplaque anticalculus dentifrice composition. More particularly, it relates to a dentifrice composition containing a polyphosphate anticalculus (that is, : antitartar) agent and a compatible antibacterial agent effective to |Inhibit plaque. 1 In N.Z. Patent Specification No. 217558 to Gaffar et al; 4,515,772 i I j to Parran et al; and ".,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 • conjunction with a fluoride ion-providing source and a synthetic linear i : polymeric polycarboxylate to inhibit calculus formation. In the patents to Parran et al and to Parran water soluble il K . I tjdialkali metal pyrophosphate alone or mixed with tetraalkali metal : pyrophosphate is -jmployed. j Oral compositions which inhibit calculus formation on dental i i 'surfaces are higlly desirable since calculus is one of the causitive •jfactors in periocontal conditions. Thus, its reduction promotes oral jj hygiene. p || Dental plaque is a precursor of calculus. Unlike calculus, M ,jhowever, plaque ray form on any part of the tooth surface, particularly I j|including at the gingival margin. Hence, besides being unsightly, it '•is implicated in the occurence of gingivitis. j| Accordingly, it would be highly desirable to include j I antimicrobial agents which have been known to reduce plaque in oral ■ | compositions containing anticalculus agents. Indeed, this has been ij '.described in U.S. Patent 4,022,800 to Vinson et al, wherein a compound !j providing zinc ions as an anticalculus agent is admixed with an • i 'antibacterial agent effective to retard the growth of plaque bacteria. ;iA wide variety of antibacterial agents are described with the zinc -2- i. r 23664! i' canpounds Including cationic naterials such as guanides and quaternary | ammonium compounds as well as non-cationlc compounds Buch ae halogenated •I sal lcylanilides and halogenated hyd roxyd iphenyl ethers. 11 l| Hitherto, the cationic antibacterial materials such as chlorhexidine, benzthoniura chloride and cetyl pyridinium chloride have been the 6ubject of greatest Investigation as antibacterial antlplaque agents. However, in spite of their being used in conjuction with zinc anticalculus agent, they are not effective when used with anionic !i i| materials such as polyphosphate anticalculus agent. This l| ineffectiveness is considered to be quite surprising as polyphosphates '! ■i are chelating agents and the chelating effect has previously been known i 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 'I j> plaque control mouthwash containing pyrophosphate of U.S. Patent . 4,323,551 and bis-biguanide antlplaque agent is suggested in the I '{anticalculus pyrophosphate oral composition of U.S. Patent A,515,772. Ij In view of the surprising Incompatibility of cationic II antibacterial agents with polyphosphates present as anticalculus agents, it was quite unexpected that other antibacterial agent would be effective. ii ■' It is an advantage of this invention that certain antibacterial agents are effective in anticalculus dentifrice conpositions to inhibit M plaque formation. i 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 antlplaque, j| anticalculus dentifrice composition is provided which is effective to . reduce the occurence of gingivitis. t i -3- 736641 . Additional advantages of this invention will be apparent from nsideration 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 and halogenated carbanilides and a fluoride ion source. In this specification and claims "dentifrice" and "dentifrice composition" mean any toothpaste or cream or dental gel, 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 desirable from considerations of antiplaque effectiveness, safety and formulation are; Halogenated Diphenyl Ethers 2,4,4'-trichloro-2'-hydroxy-diphenyl ether (Triclosan) 2,2'-dihydroxy-5,5'-dibromo-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 2,6-Dimethyl - Phenol j|4-n-Propyl - Phenol 4-n-Butyl 4-n-Amyl A-tert-Amyl 4-n-Hexyl 4-n-Heptyl Methyl ■ Ethyl ?! 11 t|n-Propyl ' j n-Butyl I I « n-Areyl sec-Ansyl ;j n-Hexyl !|Cyclohexyl li ! jn-Heptyl 1j n-Octyl - Phenol - Phenol - Phenol - Phenol - Phenol Mono- and Poly-Alkyi and Aromatic Halophenols - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol !l° -Chlorophenol ; j Methyl Ethyl n-Propyl n-Butyl | n-Amyl I tert-Aniyl i» n-Kexyl .1 n-Heptyl '!p-Chlorophenol jIo-Benzyl - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - o-Chlorophenol - p-Chlorophenol H 0-Benzyl-m-methyl o-Benzyl-m, m-dimethyl | o-Phenylethyl I I i|o-Phenylethyl-m-methyl I i|3-Methyl . 3,5-Dimethyl I ;•6-Ethyl-3-methyl 6-n-Propyl-3-methyl 6-lso-Propyl-3-methy1 ' 2-Ethyl-3,5-dimethyl I 6-sec Butyl-3-methyl !l |j 2-i8o-Propyl-3,5-dimethyl - p-Chloropheriol • J 6-Diethylmethyl-3-methyl - p-Chlorophenol •16-l6o-Propyl-2-ethyl-3-methyl - p-Chlorophenol i; j 2-sec Amyl-3,5-dimethyl - p-Chlorophenol I 2-Diethylmethyl-3.5-dlraethyl - p-Chlorophenol 6-sec Octyl-3-methyl - p-Chlorophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - p-Bromophenol - o-Broraophenol - o-Broraophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol - p-Chlorophenol jj p-Bromophenol • I | Methyl , Ethyl n-Propyl I n-Butyl I I n-Arayl sec-Amyl , |n-Hexyl ; ; ,j cyclohexyl • i | j o-Bromophenol l) tert-Amyl j | n-Hexyl ^•6 41 'n-Propyl-tn.m-Dlraethyl - o-Bromophenol 'J • • |2-Phenyl Phenol /■ lL-chloro-2-methyl phenol ' i II I A-ch'loro-3-methyl phenol '4-chloro-3,5-dimethyl phenol 2,4-dichloro-3,5-dimethylphenol ;3,4,5,6-terabrooo-2-methylphenol ; i jj 5-methyl-2-pentylphenol II , j A-lsopropyl-3-mechylphenol '! 5-chloro-2-hydroxydiphenylmethane —-v li JjResorcinol I l ■I Methyl Resorcinol and Its Derivatives il - Resorcinol - Resorcinol - Retorcinol - Rei orclnol - Re; orclnol - Resorcinol - Reiorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol - Resorcinol !p-Chlurobenzyl - Resorcinol ;; ;5-Chloro -2,4-Dihydroxydiphenyl Methane 'I'i'-Chloro -2,4-Dihydroxydiphenyl Methane 5-Brorao 4'-Bromo MEthvl ♦ * In-Propyl :! j j ri-Butyl ' (n-Amyl I j n-ltexyl n-Heptyl n-Octyl n-Nonyl !!Phenyl !l Benzyl jj Phenylethyl 11 Phenylpropyl i! -2,4-Dihydroxydiphenyl Methane -2,4-Dihydroxydiphenyl Metliane ;] In this specification and claims where no prefix is given before ' I ''hexyl1' (as in hexyl resorcinol) it is to be understood that ' 'n-hexyl is msant. ? f f 4 1 I! Blsphenollc Compound's 2,2'-methylene bis (4-chlorophenol) 2,2'-methylene bis (3 ,4,6-trichlorophenol) , J 2,2'-methylene bis (4-chloro-6-bromophenol) • I bis (2-hydroxy-3,5-dichlorophenyl) sulfide bis (2-hydroxy-5-chlorobenzyl) sulfide Halogenated Saltcylanilldes 41,5-dibromosalicylanilide m 3 ,4',5-trichlorosalcylanilide i | I J |j 3,4 1,5-tribromosalicylanilide : * i^.S.S'.S-tetrachlorosalicylanilide 3,3',5— trichlorosalicylanilide 3,5-dibromo-3'-trifluororaethyl salicylanilide i|5-n-octanoyl-3'-tri fluoromethyl salicylanil ide t 3,5-dibromo-4'-trifluoromethyl salicylanilide 3,5-dibromo-3'-trifluoro methyl salicylanilide (Fluocophene) ! j Halogenated CarbaniI ides . i | 3,4,4'-trichlorocarbani1ide j 3-trifluoromethy1-4,'t'-dichlorocarbanilide 1 3,31,4-trichlorocarfcini1ide The antibacterial agent is present in the ctenti fri ce cni|xfiitim in • an effective antiplaque amount, typically about 0.01-5% by weight, -8- 2366 preferably about 0.03-1%. The antibacterial agent is substantially water-insoluble, meaning that its solubility 16 less than about IX by weight in water at 2S°C and may be even less than about 0.1%. If 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 |bis(4-chloro-6-bromophenol) and Fluorophene. The most preferred |antibacterial antiplaque compound is Triclosan. Triclosan is disclosed jin aformentioned U.S. Patent A,022,880 as an antibacterial agent in | combination with an anticalculus agent which provides zinc ion6. It is also disclosed as an antiplaque agent in a dentifrice formulated to ! 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! |j in published European Patent application 0161898 of Lane et al and in a i!dentifrice containg zinc citrate trihydrate in published European Patent ^Application 0161899 to Saxton. '1 The linear polyphosphate salts operative ! herein as anticalculus agents are well known, being generally employed I in the form of their wholly or partially neutralized water soluble . i | alkali metal (e.g. potassium and preferable sodium) or ammonium salts, | and any mixtures thereof. Representative examples include sodium j|hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium {[monoacid and tetrasodium pyrophosphates and the like. Linear • I II polyphosphates correspond to (NaP03)n where n is about 2 to about 125. '| , They are generally employed in the instant oral compositions in jjapproximate weight amounts of 0.1 to IX preferably 0.1 to IX, more I preferably 2 to IX. When n is at least 3 in (NaP03)n, said !jpolyphosphates are glassy in character. f 2566") j Particularly desirable anticalculus agents are tetraalkali t Itnctal pyrophosphates, including mixtures thereof, such as tetraBodium pyrophosphate, tetrapotasslum pyrophosphate and mixtures thereof. An anticalculus agent comprising about h.3X to about 7X by weight of the dentifrice compositions wherein the weight ratio of tetrapotasslum pyrophosphate to tetrasodium pyrophosphate i6 from about 4.3:2.7 to nabout 6:1 is especially preferred. . I ! In order to optimize the anticalculus effectiveness of the dentifrice j composition, an amount of a fluoride ion source sufficient to supply 25 ppm. [to 5,000 ppm. of fluoride ions as an inhibitor against enzymatic hydrolysis : jjof the polyphosphate is present. In addition 0% to 3% of a synthetic !| anionic polymeric polycarboxylatc having a molecular weight of about 1,000 i > Jlto about 1,000,000, preferably about 30,000 to 500,000, may be present. !l ! The sources of fluoride ions, or fluorine-providing component, ■ia6 acid phosphatase and pyrophosphatase enzyme inhibitor component, are liwell 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 ion6 in water and by freedom from undesired reaction with other compounds of the oral /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 as cuprous fluoride, zinc fluoride, barium fluoride, sodium flourosilicate, ammonium florosilicate, sodium fluorozirconate, sodium fluorozirconate, sodium monofluorophosphate, I] aluminum mono- and di-fluorophosphate, and fluorinated sodium calcium Hpyrophosphate. Alkali metal and tin fluorides, such as sodium and |jstannous fluorides, sodium monofluorophosphate (MFP) and mixtures [thereof, are preferred. -10- ; The amount of fluorine-providing compound is dependent to some jextent upon the type of compound, its solubility, and che type of dentifrice preparation, but it must be a non-toxic amount, generally abut 0.005 to about 3.02 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 ||minimum amount of such compound may be used, but it is preferable to jjemploy sufficient compound to release about 300 to 2,000 ppm, more . i preferable about 800 to about 1,500 ppm of fluoride ion. i i j Typically, in the cases of alkali metal fluorides, this il jjcomponent Is present in an amount up to about 2% by weight, based on the ||weight of the preparation, and preferably in the range of about 0.05X to !|IX. In the case of sodium monofluorophosphate, Che compound may be present in an amount of about 0.1-3%, more typically about 0.76Z. In dentifrice preparations such as lozenges 'and chewing gum, !the fluorine-providing compound is typically present in an amount 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 6uch compound i6 present. The synthetic anionic polymeric polycarboxylate is an inhibitor 11of alkaline phosphatase enzyme. Synthetic anionic polymeric n Jj| polycarboxylates and their complexes with various cationic germicides, I l| zinc and magnesium have been previously disclosed as anticalculus agent6 • t iper se in, for example U.S. Patent No. 3,429,963 to Shedlovsky; U.S. Patent j j No 4,152,420 to Gaffar; U.S. Patent No. 3,956,480 to Dichter et al; U.S. ; ^Patent No, 4,138,477 to Gaffar; and U.S. Patent No. 4,183,914 to Gaffar et ' S jjal. However, only in aforementioned N.Z. Patent Specification No. 217558 ! I il ii 236 £■ 5 J I!to Catiar et al 16 there disclosed use of 6uch polycarboxylates alone i for inhibiting salivary hydrolysis of pyrophosphate anticalculus agents, 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. jjpolassiura and preferably sodium) or ammonium salts. Preferred are 1:4 i|to 4:1 copolymers of maleic anhydride or acid with another polymerlzable !i liethylenically unsaturated monomer, preferably methyl vinyl ether !J (raaleic 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 jj"synthetic" is intended to exclude known thickening or gelling agent6 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 i I 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 i!methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or jjN-vinyl-2-pyrrolidone. v -12- Additional operative polymeric polycarboxylates disclosed in (above referred to U.S. Patent No. 4,138,477 and 4,183,914, include jcopolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl lether, polyacrylic, polyitaconic arid polymaleic acids, and sulfoacrylic ijollgomers of M.W. as low as 1,000, available as Uniroyal ND-2. i j Suitable generally are polymerized olefinically or i; ietliylenically unsaturated carboxyllc acids containing an activated !i ■ icarbon-to-carbon olefinic double bond and at least one carboxyl group, 'I ;ithat is, an acid containing an olefinic double bond which readily Jfunctions in polymerization because of its presence in the monomer i I :j 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 ;jactds are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, ijcrotonic, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, clnnamlc, _jbeta-styrllacrylic, muconic, itaconic, citraconic, mesaconic, il !!j;lutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic, ii I!2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acid6 and 11 ! I anhydrides. Other different olefinic monomers copolymerizable with such ijcarboxylic monomers include vinylacetate, vinyl chloride, dimethyl !| !|maleate and the like. Copolymers contain sufficient carboxyllc salt .i i groups for water-solubility. i j Also useful herein are so-called carboxyvinyl polymers "'disclosed as toothpaste components in U.S. 3,980,767 to Chown et al; i| jU.S. 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. 3,711,604 to Colodney et al. They are cotnmercially available for example under the trademarks Carbopol 934, j940 and 941 of B. F. Goodrich, these products consisting essentially of 'I ;!a colloidally water-soluble polymer of polyacrylic acid crosslinked with V j|frop about 0.75/! to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent. 2366^1 i j Hie synthetic anionic polymeric polycar boxy late component is i I mainly a hydrocarbon with optional halogen and O-containing substituents ||and linkages as present in for example ester, ether and OH groups, and ;i H whert present is generally employed in the instant conposltlons in • I 'I approximate weight amounts of 0.05 to 3X, preferably 0.05 to 2Z, more j! II preferably 0.1 to 2%. Amounts in the upper portions of these ranges are i i jjtypically employed in dentifrice compositions typically containing a j dental 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 I I I j purposes. il | As indicated above, these polymeric polycarboxylates have been jj found to be effective inhibitors of alkaline phosphatase enzyme. Since II this enzyme has little activity (for hydrolyzing pyrophosphate) at about t I ! pH 7.0 or below, the polymeric polycarboxylate component: may, if » • desired, be omitted from <ctriti£ricE prepoaticns formulated to operate at such I ' pH of 7.0 or below. Such omission however could reduce the versatility 'Jand anticalculus effectiveness of the present dentifrice ccnpositions over the II !lbroad pH range of about A.5 to about 10. |j In dentifrice preparations such as lozenges and chewing gum, the fluorine-_ providing compound may be typically present in an amount sufficient to l| release up to about 500 ppm, preferably about 25 to about 300 ppm by weight 'j .of fluoride ion. Generally about 0.005 to about 1.0 wt.% of such compound ii - (j is present. • i !', i i i j i I II 23664! In certain other desirable forms of this invention, the dentifrice composition may be substantially solid or pa6ty in character, such as toothpowder, a dental tablet or a toothpaste (dental cream) or gel. The vehicle of such solid or pasty dentifrice preparations generally contains dentally acceptable polishing material. Examples of polishing materials are water-insoluble sodium metaphosphace, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magensium orthophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, zirconium silicate, silica, bentonlte, and mixtures thereof. Other suitable polishing material include the particulate thermosetting resins described in U.S. Pat. No. 3,070,510 of Dec. 15, Ij 1962 such as roelaraine-, phenolic, and urea-formaldehydes, and • I 11 cross-linked polyepoxides and polyesters. Preferred polishing materials jj include crystalline silica having particle sized of up to about 5 . i -15- 236 [•microns, a mean particle size or up tu about 1.1 microns, and a surface 11 2 j j area of up to about 50, 000 cm. /gm., silica gel or colloidal silica, pnd complex amorphous alkali metal aluminosilicate. When visually clear gels are employed, a polishing agent of colloidal silica, such a6 those sold under the trademark SYLOID aB Syloid 72 and Syloid 74 or under the trademark SANTOCEL aB Sancocel 100 .>alkali metal almuino-silicate complexes are particularly useful, since '(they have refractive indices close to the refractive indices of gelling 11 jjagent-liquid (including water and/or humectant)systems commonly used In ' i dentlfices. t Many of the so-called "water-insoluble" polishing materials are II jjanionic in character and also include small amounts of soluble material. \ I 11 Thus, 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 j a minute solubility in water, and therefore are commonly referred to as insoluble metaphosphates (IMP). There is present therein a minor amount of soluble phosphate material as impurities, usually a few percent 6uch as up to 4X by weight. The amount of soluble phosphate material, which Is believed to include a soluble sodium triraetaphosphate in the case of l|insoluble metaphosphate, may be reduced or eliminated by washing with i j !i water if desired. The insoluble alkali metal metaphosphate is typically 1 i employed in powder form of a particle size such that no more than IX of i ' the material is larger than 37 microns. ,j The polishing material Is generally present in the solid or i I ipasty compositions in weight concentrations of about 103! to about 99%. Preferably, it is present in amounts ranging from about 10% to about 75% il -16- 1 2366';] Jjln toothpaste, and from about 70% to about 99% in toothpowder. I In a toothpaste, the liquid vehicle may comprise water and humectant typically in an amount ranging from about 10% to about BOX by ijweight of the preparation. Glycerine, propylene glycol, sorbitol, polypropylene glycol and/or polyethylene glycol (e.g. 400-600) exemplify suitable humectantB/carrierB. 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. % of water, 0 to about 70 wt.% of glycerine and about 20-80 wt. % of sorbitol are preferably I employed. ;| il Toothpastes, creams and gels typically contain a natural or II |synthetic thickener or gelling agent in proportions of about 0.1 to 1 |about 10, preferably about 0.5 to about 5wt.%. A suitable thickener is I |!synthetic hectorite, a synthetic colloidal magnesium alkali metal I I 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% SiOj, 25.40% MgO, 3.05% Na20, . I ;J0.98% Li2°> and some water and trace metals. Its true specific gravity i| !,is 2.53 and It has an apparent bulk density (g./ml. at 8% moisture) of ! 1.0. Other suitable thickeners Include Irish moss, gum tragacanth, II |j6tarch, polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl I j methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose l . (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, thedervtifrice preparations are to be sold or otherwise distributed in suitable |i :ilabelled packages. || Thus a toothpaste, cream or gel will usually be in a collapsible II II ! I -17- 2366* I tube, typically aluminum, lined lead or plastic, or other squeeze, pump or pressurized dispenser for metering out the cpntents, having a label describing it, in substance, as a toothpaste, gel or dental cream. Organic surface-active agents are used in the compositions of . the present invention to achieve increased prophylactic action, assist Ij j |j 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 l! | preferably anionic, nonionic or ampholytic in nature, and it is preferred to employ as the surface-active agent a detersive material which imparts to the composition detersive and foaming properties. j Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglycerlde monosulfates, such as the sodium salt of the monosulfated monoglycerlde of hydrogenated coconut oil fatty acids, j i '! higher alkyl sulfates such as 6odlum lauryl sulfate, alkyl aryl '(sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxy propane sulfonate, and the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxyllc acid compounds, such as those having jj 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the Ijlike. Examples of the last mentioned amides are N-lauroyl sarcoslne, l|and the sodium, potassium, and ethanolamine salt6 of N-lauroyl, '•! jjN-myristoyl, or N-palmitoyl sarcoslne which should be substantially free from soap or similar higher fatty acid material. The use of these , I t « .1 sarc.osinate compounds in the dentifrice compositions of the present invention ' is particularly advantageous since these materials exhibit a prolonged \ i| and marked effect in the inhibition of acid formation in the oral cavity % ii 11 i i 2366 due Co 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 ("ethoxatners") 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). It is preferred to use from about 0.03 to 5£ 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 ammoniated material such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, where present, are incorporaced 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, peri1lartine , AMP (aspartyl phenyl alanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may together comprise from about 0.17. to 5% more of the preparation. In the preferred practice of this invention a dentifrice composition * 2166A 1 |j according to this invention is preferably applied regularly I | !j Co dental enamel, such as every day or every second or third day or jlpreferably 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 zenges, or in chewing gum or other products, e.g. by stirring into a j warm gum base or coating the outer surface of a gum base, illustrative Hi.. I! of which may be mentioned jelutone, rubber latex, vinylite resins, etc., \ |ldesirably with conventional plasticizers or softeners, sugar or other 'I •I sweeteners or carbohydrates such bs glucose, sorbitol and the like. The following examples are further Illustrative of the nature 11 of the present invention, but it is understood that the invention is not i > •■limited thereto. All amounts and proportions referred to herein and in 11 iithe appended claims are by weight. !i ii 'I -20- 236 6 ii jj Example 1 1 i r '■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 jorganisms implicated in formation of plaque and leading to gingivitis on '' 11 !dental surfaces. Soft plaque contains about 1.7 x 10 organi6m/gm. |j(net weight). The antibacterial agents are admixed with anionic ^materials, particularly anionic surface active agent often commonly ijemployed in oral compositions and polyphosphate anticalculus agent. . i jj Minimum inhibitory concentration (MIC) of antibacterial agent I I jjis used to evaluate the efficacy of the agent in vitro. MIC i6 defined .las 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 j!related to the efficacy of the dentifrice In vivo since retention and l I 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,A,A'-trichloro-2'-hydroxydiphenyl ether is indicated [ as "TCHE"; the quaternary ammonium antibacterial agents benzthonium i : chloride is indicated as "BTC"; The biguanide chlorhexidine digluconate .jis indicated as "CH", sodium lauryl sulfate is indicated as "SLS"; the t ' copolymer of maleic anhydride and methyl vinyl ether available from GAF 11 Ijcorporation as Gantrez S-97" is identified as ' Gantrez ; tetrasodium il pyrophosphate is identified as "pyrophosphate"; and sodium fluoride is \ 11identified'as "NaF". ij I I I I I I -21- 2't ~ r '■ 0 u TABLE 1 Test Solution Minimum Inhibition Concentration (MIC) in mcg/ml Bacteriodes Bacteriodes Actinobacillus Streptococcus glnglvalls lntermedlus actinomycetem- mutan6 comi tarts , 1. 0.5% TCHE and IX SLS in j water . 2. 0.5% TCHE, 17. SLS, 1Z Gantrez, 2X Pyrophosphate and 0.22 NaF in water 2.5 2.5 2.5 2.5 5.0 5.0 25.0 25.0 l! NE NE NE NE NE NE NE NE 3. It SLS in |! water ij U. 1% SLS, IX Gantrez and Ij 2X Pyrophosphate 'I in water I! note: NE ■ not effective The results indicate that TCHE in the presence of anionic | surfactant inhibited four dental plaque organisms, Bacteriodes ginglvalis, Bacteroldes lntermedlus, Actinobacillus actlnumycetemcomltans and Strep. mutans at 2.5 mcg/ml and 2.5 mcg/ml, 5.0 mcg/ml and 25.0 mcg/ml respectively(1). Similar antibacterial effect is seen in the presence of Gantrez/pyrophosphate/fluoride(2). SLS per se and a combination of SLS/Gantrez/pyrophosphate/fluoride was 'l inef fective(3 and A). It is noteworthy that in human clinical tests with cationic antibacterial agents, 0.075% BTC dissolved in water is effective in reducing plaque formation while 0.075% BTC and 1% pyrosphosphate !dissolved in water is not. Similarly, 0.01% CH dissolved in water is effective in reducing plaque formation while 0.01% CH and 1% sodium N-lauroyl sarcosinate dissolved in water i6 not. -22- Example 2 2 36 6 The adsorption ,to and release from tooth minerals for antlplaque/ antltartar 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 tetrasodlum J pyrophosphate)/Gantrez/NaF. Jj 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 HA I '•is used for adsorption studies. Various concentrations of TCHE in SLS :|or in SLS/pyrophosphate/Gantrez/NaF are mixed with the coated HA and •I I incubated at 37s for 3 hours under continuous agitation. At the end of j incubation period, the mixtures are centrifuged, HA separated and the i j 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 II j the amount left in the supernatant after the incubation with coated HA. .The table below summarizes the data. j! i« ii ii !! ii > i il ■I i i il ii 11 ii ii t 236 r* ) 0 TABLE 2 Components and Concentrations 2 of TCHE Adsorbed to Coated HA 0.0052 TCHE In 12 SLS ' 802 0.012 TCHE in 12 SLS 852 0.0152 TCHE in 12 SLS 852 \ 0.022 TCHE in 12 SLS 1 882 0.0052 TCHE in 12 SLS; 0.52 Gantrez; 22 pyrophosphate/ 10.242 NaF 802 0.012 TCHE 852 j 0.0152 TCHE " 862 I j0.022 TCHE 1 872 1 The data indicates li that the addition of pyrophosphate/ 1 M Gantrez/NaF does not impair • j adsorption of TCHE to saliva coated tooth • 1 • tainerals. -24- 1 o --S Example 3 jjDentifrice Compositions Glycerine Polyethylene Glycol 600 .tlola Carrageenan |Sodium Carboxymethyl Cellulose i i I j|Sodium Saccharin iSodium Cyclamate ;! ijSodium Fluoride t|Deionized water i! iiTitanium Dioxide FD&C Blue No. 1(12 Solution) ! Sorbitol (7051) ij Il Gantrez S-97 j!Tetrasodium Pyrophosphate 11 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 'j Preciphated Amorp. Silica |j containing combined alumina .Silica Thickener ! | Flavor Sodium Lauryl Sulfate TCHE 7.00 1.10 1.20 0.50 236 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 •I * liquid il ** powder -25- 23 R ;■} I! - example 4 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 gm of each dentifrice, mixed well ' i ' ,jfor a couple of hours with stirring bar and centrifuged, after which the supernatant i6 collected as aqueous extract. Antibacterial activity of jjthe dentifrice extracts are evaluated on Bacteriodes glnglvalls. -Results are summarized below. 'j TABLE 3 il ■ i ij Treatment Inhibition of Growth of Bacteriodes Glnglvalls ||Extract from dentifrice containing 100.0 !' TCHE (1:500) il "Extract from dentifrice without 0.0 !!TCHE (1:500) || '■' TCHE (5.0 mcg/ml) by itself 100.0 il ! I •I These results indicate that TCHE antibacterial antiplaque agent is |l :|| compatible In a dentifrice composition containing anionic surfactant piu6 pyrophosphate anticalculus Ingredients with enzyme inhibitors Gantrez and NaF. Similar comparable effects prevail when each of hexyl • i ^resorcinol, 2,2'-methylene bis(4-chloro-6-bromophenol) and Flourophene .replace TCHE. i! Ii . i -26- </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 236641 Example 5 Lozenge i i 75-802 Sugar i | 1-20% Corn Syrup j 0.1-1.0 Flavor . 2% Tetrasodium Pyrophosphate 0.25% Gantrez S-97 0.01 to 0.05% NaF 0.01 to 0.1% TCHE 1 to 5% Magnesium Stearate Lubricant !0.01 to 0.22 Water il t! i t I i I Example 6 il n '■•J Chewing Gum Gum base Sorbitol (70%) ; TCHE l| " Tetrasodium Pyrophosophate Ij !j Gantrez S.97 , NaF Glycerine ,j Crystalline Sorbitol II j| Flavor and Water Parte 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 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 ll [jappended claims. The Cormdssioner considers that the invention described in this specification cannot be performed without substantial risk of infringement 736641 WHAT WE rr.ftTM TS?

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) and an effective antiplaque amount of a substantially water insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds and halogenated carbanilides, and sufficient fluoride ion source to release up to 5000 ppm of fluoride ion provided that when the fluoride ion source is sodium fluoride it is not present in an amount of 0.22% by weight and when the fluoride ion source is sodium monofluorophosphate it is not present in an amount of 0.80% by weight.

2. A dentifrice composition as claimed in claim 1, wherein when the fluoride ion source is sodium fluoride it is present in an amount in excess of 0.22% by weight and when the fluoride ion source is sodium monofluorophosphate it is present in an amount in excess of 0.80% by weight.

3. A dentifrice composition as claimed in either of claims 1 and 2, wherein the fluoride ion source is sufficient to release 300 to 2000 ppm of fluoride ion.

4. A dentifrice composition as claimed in any one of the preceding claims in which the fluoride ion source is sodium fluoride present in an amount of at least 0.24% by weight. - 28 -

5. A dentifrice composition as claimed in claim 3 wherein the fluoride source is sodium fluoride and is present in an amount in excess of 0.24% by weight.

6. A dentifrice composition as claimed in any one of claims 1 to 4 in the form of a dental gel, toothpaste, toothcream, toothpowder, or dental tablet.

7. A dentifrice composition as claimed in any one of the preceding claims in which the said polyphosphate salt is present in an amount of 0.1-7% by weight.

8. A dentifrice composition as claimed in claim 7 in which said polyphosphate salt is present in an amount of 2 to 7% by weight.

9. 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.

10. A dentifrice composition as claimed in any one of the preceding claims in which the said antibacterial agent is a halogenated diphenyl ether.

11. A dentifrice composition as claimed in claim 10 in which the halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxy-diphenyl ether. 29 ?3t'641

12. A dentifrice composition as claimed in any one of claims 1 to 9 in which the said antibacterial agent is a phenolic compound.

13. A dentifrice composition as claimed in claim 12 in which the said phenolic compound is phenol or a homolog thereof (as herein defined - Page 4).

14. A dentifrice composition as claimed in claim 12 in which the said phenolic compound is a mono- or poly-alkyl halophenol or an aromatic halophenol.

15. A dentifrice composition as claimed in claim 12 in which the said phenolic compound is resorcinol or a derivative thereof (as herein defined - Page 7).

16. A dentifrice composition as claimed in claim 15 in which the said resorcinol derivative is hexyl resorcinol.

17. A dentifrice composition as claimed in claim 12 in which the said phenolic compound is a bisphenolic compound.

18. A dentifrice composition claimed in claim 17 in which the said bisphenolic compound is 2,2'-methylene bis(4-chloro-6-bromophenol) .

19. A dentifrice composition as claimed in any one of claims 1 to 9 in which the said antibacterial agent is a halogenated carbanilide.

20. 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 or ammonium pyrophosphates, tripolyphosphates and hexametaphosphates.

21. A dentifrice composition as claimed in claim 20 wherein the said polyphosphate is sodium tripolyphosphate.

22. A dentifrice composition as claimed in claim 20 wherein the said hexametaphosphate is sodium hexametaphosphate.

23. A dentifrice composition as claimed in claim 20 in which the said polyphosphate salt is at least one water soluble tetraalkali metal pyrophosphate.

24. A dentifrice composition as claimed in any one of claims 1 to 11, or any one of claims 20 to 23 when dependent thereon in which the said antibacterial agent is substantially 0.03-1% by weight of 2,4,4'-trichloro-2'-hydroxy-diphenyl ether.

25. A dentifrice composition as claimed in claim 20 or claim 24 in which the said polyphosphate salt is a mixture of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in an amount of 4.3 to 7% by weight.

26. A dentifrice composition as claimed in claim 20 or claim 24 in which the said polyphosphate salt is a mixture of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in a weight ratio of from 4.3:2.7 to 6:1. 236641

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

28. A dentifrice composition as claimed in claim 27 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.

29. A dentifrice composition as claimed in either one of claims 27 or 28 in which the said polishing agent is a silica polishing material.

30. A dentifrice composition as claimed in claim 27 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.

31. A dentifrice composition as claimed in any one of claims 1 to 5 or any one of claims 7 to 26 when dependent thereon in which the said dentifrice composition is a lozenge.

32. A dentifrice composition claimed in any one of claims 1 to 5 or any one of claims 7 to 26 when dependent thereon in which the said dentifrice composition is a chewing gum. west-walker. mccabe per. -v (Ljltx- s cJI ttufi-f • , attorneys foti the applicant </div>