AU673014B2 - Antibacterial, antiplaque, anticalculus oral composition - Google Patents

Description

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AUSTRALIA

Patents Act 1990 COLGATE-PALMOLIVE COMPANY

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT

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S. S 4~ *0 *4 5* *444*5 Invention Title: ANTIBACTERLL ANITIPLAQUE, ANTICALCULUS ORAL COMPOSITION The following statement is a full description of this invention including the best method of performing it known to us:- I 4 This invention relates to an antibacterial antiplaque anticalculus oral composition. More particularly, it relates to an oral composition containing a polyphosphate anticalculuL (that is, antitartar) agent and a compatible antibacterial agent effective to inhibit plaque, wherein antiplgque effectiveness is optimized by the presence of an antibacterial-enhancing agent which enhances the delivery of said antibacterial agent to, and retention thereof on, oral surfaces.

k0 In U.S. Patents 4,627,977 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 molecularly dehydrated polyphosphate salt is employed in conjunction with a fluoride ion-providing source and a synthetic linear polymeric polycarboxylate to inhibit calculus formation. In copending European Patent Application 89 200 710.5, anticalculus effectiveness is optimized with a reduced amount of the linear molecularly dehydrated polyphosphate S salt in conjunction with the fluoride ion-providing source and increased amount of the synthetic linear polymeric polycarboxylate.

In the patents to Parran et al and to Parran, water soluble dialkali metal pyrophosphate alone or mixed with -tetraalkali metal pyrophosphate is employed.

Oral compositions which inhibit calculus formation on dental surfaces are highly desirable since calculus is one of the causative factors in periodontal conditions. Thus, its reduction promotes oral hygiene.

Dental plaque is a precursor of calculus. Unlike calculus, however, plaque may form on any part of the tooth surface, particularly including at the gingival margin.

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Hence, besides being unsightly, it is implicated in the occurrence of gingivitis.

Accordingly, it would be highly desirable to include antimicrobial agents which have been known to reduce plaque .in oral compositions containing anticalculus agents.

Indeed, this has been described in U.S. Patent 4,022,550 to Vinson et al, wherein a compound providing zinc ions as an anticalculus agent is admixed with an antibacterial agent effective to retard the growth of plaque bacteria. A wide O1 variety of antibacterial agents are described with the zinc compounds including cationic materials such as guanides and quaternary ammonium compounds as well as non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers.

Hitherto, the cationic antibacterial materials such as chlorhexidine, benzethonium chloride and cetyl pyridinium chloride have been the subject of greatest investigation as antibacterial antiplaque agents. However, in spite of their being used in conjunction with zinc anticalculus agent, they @0 are not effective when used with anionic materials such as polyphosphate anticalculus agent. This ineffectiveness is considered to be quite surprising as polyphosphates are chelating agents and the chelating effect has previously been known to increase the efficacy of cationic antibacterial agents. (see e.g. Disinfection, sterilization and Preservation, 2nd Ed., Black, 1977, Page 915 and Inhibition and Destruction of the Microbial Cell, Hugo, 1971, Page 215). Indeed, quaternary ammonium compound is present in the plaque control mouthwash containing b pyrophosphate of U.S. Patent 4,323,551 to Parran and bisbiguanide antiplaque agent is suggested in the anticalculus pyrophosphate oral composition of U.S. Patent 4,515,772- Parran et al.

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In view of the surprising incompatibility of cationic antibacterial agents with polyphosphates present as anticalculus agents, it was quite unexpected that other antibacterial agents would be effective.

It is an advantage of this invention that certain antibacterial agents are effective in anticalculus oral compositions containing a linear molecularly dehydrated polyphosphate salt, a fluoride-ion-providing source and the aforementioned antibacterial-enhancing agent to inhibit plaque formation.

.9J It is a further advantage of this invention that a composition is provided which is effective to reduce calculus formation and optimize plaque reduction.

It is a further advantage of this invention that an antiplaque, anticalculus oral composition is provided 9 9 which is effective to reduce the occurrence of gingivitis.

Additional advantages of this invention will be apparent from consideration of the following specification.

The present invention provides an oral composition 20 comprising an orally acceptable vehicle, an effective S:antiplaque amount of a substantially water insoluble antibacterial agent, an antibacterial enhancing agent (AEA) which is effective to enhance the antibacterial effect of said antibacterial agentwhich AEA has an average molecular weight of 1,000 to 1,000,000, contains at least one functional group which enhances delivery of S* antibacterial effect and at least one organic group which enhances retention of antibacterial effect, said AEA containing said groups being free from or substantially free from water soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of 1,00 to 1,000,000, and a polyphosphate anticalcu.us agent.

In accordance with certain preferred aspects this invention relates to an oral composition comprising in an i! T L fN I I 4/1 orally acceptable vehicle, an effective anticalculus amount of material comprising about 0.1-3% by weight of at least one linear molecularly dehydrated polyphosphate salt as anticalculus agent, an effective antiplaque amount of a substantially water insoluble noncationic antibacterial agent and desirably up to about 4% by weight of an antibacterial-enhancing agent which enhances the delivery of said antibacterial agent to, and retention thereof on, oral surfaces, wherein typically he weight ratio of antibacterial-enhancing agent to polyphosphate ion ranges from in excess of 0.72:1 to less than 4:1, e.g. from about 1:1 to about 3.5:1, especially from about 1.6:1 to about 2.7:1, preferably about 1.7:1 to about 2.3:1 and most preferably about 1.9:1 to about 2:1. For instance, when 2% 16* 0* f oft ft.

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P""ko" I tetrasodium pyrophosphate (TSPP), is employed (providing about 1.3% of *pyrophosphate ion) with 2.5% of the antibacterial-enhancing agent, a highly desirable weight ratio of about 1.9:1 is provided.

Typical examples of antibacteriti agents which are particularly desirable from considerations of antiplaque effectiveness, safety and formulation are: Halogienated Diphenyl Ethers 2' -trichloro-2-hydroxy-diphenyI ether (Triclosan) 2,2' -dihydroxy-5, 5'-dibromo-diphenyl ether.

Halogienated Salicylanilides 4' 3, 2,3,3' 3,3' 3, 5-dibromo-3 '-trifluoromethyl salicylanilide ::.:5-n-octanoyl-3 '-trifluoromethyl salicylanilide 3,.irm-*trfurmty saiyanld 3, 5-dibromo-4 '-trifluoro methyl salicylanilide (lrpee Benzoic Esters Methyl p-Hydroxybenzoic Ester I Ethy yroyezcEtr Etyl p-Hydroxybenzoic Ester **Buroyl p-Hydroxybenzoic Ester :~:Halogienated Carbanilides 3; 4,4 -trichorocarbanilide 3-trifluoromethyl-4, 4'-dichlorocarbanilide R3* 3,3,4'-trichlorocarbanilide Phenolic Compounds (including phenol and its homologs, mono- and poly-alkyl and aromatic halo F, Cl, Br, p p phenols, resorcinol and catechol and their derivatives and bisphenolic compounds). Such phenolic compounds include, inter aim: Phenol and its Homologs Phenol 2 Methyl Phenol 3 Methyl Phenol 4 Methyl Phenol 4 Ethyl Phenol (0 2,4-Dimethyl Phenol Phenol 3,4 -Dimethyl Phenol 2,6-Dimethyl Phenol 4-n Propyl Phenol 4-n-Batyl Phenol 4-n-Amyl Phenol 4-tert-Amyl Phenol 4-n-Hexyl Phenol 4-n-Heptyl Phenol 2-Methoxy-4-( 2-Propenyl) -Phenol (Eugenol) 2-Isopropyl-5-Methyl Phenol CThyznol) Mono- and Poly-Alkyl and Aralkyl Halophenols

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Ethyl n-Propyl n-Butyl n-Amyl sec-Amyl n-Hexyl Q cyclohexyl n-Heptyl D-Octyl O-Chloropbeno.

Methyl p-Chlorophenol p-Chlorphenol p-Chlorophenol p-Chlorophenol p-Chlorophenol p-Chlorophenol p-Chlorophenol p-Chlorophenol p-Chlorophenol p-Chlorophenol o-Chlorophenol

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n-Butyl o-Chlorophenol ii-Aznyl o-Chlorophenol tert-Amyl o-Chlorophenol n-Hexyl o-chiorophenol nHeptyl o-Chlw~openol -Chiorophenol o-Benzyj. p-Chlorophenol o-Benzyl-m-methyl p-Chlorophenol O-Benzyl-m, in-dimethyl p-Chlorophenol o-Phenylethyl p-Chlorophenol *o-Phenylethyl-m-methyl p-Chlorophenol 3-Methyl p-Chlorophenol P-Chlorophenol *6-Ethyl-3-methyl p-Chlorophenol 6-n-Px-opyl-3-znethyl p-Chlorophenol 6-iso-propyl-3-methyl P-Chlorophenol 2-Ethyl-3, 5-dimethyl p-Chlorophenol f 6-sec Butyl-3-mdthyl P-Chlorophenol 2-iso-Propyl-3, 5-diinethyl p-Chlorophenol 6-Diethylmnethyl-3-niethyl p-Chlb:rophenol 6-iso-Propyl-2-ethyl-3-methyl p-Chliarophenol 2-sec Aznyl-3 ,5-dime thyl p-Chlorophenol 2-Diethylmethyl-3, 5-dimethyl p-Chlorophenol 6-sec Octyl-3-methyl p-Chlorophenol p-Bromophenol Methyl p-Bromophenol Ethyl p-Bromophenol 30 n-Propyl p-Bromophenol n-Butyl p-Bromophenol n-Amyl p-Bromophenol sec-Aznyl p-Bromophenol 7 n-Haxyl cyclaoxyl p-Bromopheriol p-Bromophenol o-Bromophenol.

tert-Amyl o-Bromophenol n-Hexyl o-Bromophenol n-Propyl-u,M-Dimethyl o-Bromophenol 2-Phanyl Phenol 4 -Chloro-2-methyl phenol 4 -ehloro-3-methyl phenol 4-chloro- 3, 5-dinethyl phenol 2, 4-dichloro-3,5-dimethyl phenol 3,4,5, 6-tetrabromo-2-methylphenol 5-methyl-2-pentylphenol 4 -isopropyl-3 -metbyiphenol -chloro-2-hydroxydiphenyl methane Resorcinol and Its Derivatives S S S. S S S S it C

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4: S. *O *S C Resorcinol Methyl Ethyl S n-Propyl n-Butyl n-Aznyl n-Hexyl n-Heptyl n-Octyl n-Nonyl Phenyl Benzyl Phenylethyl Phenylpropyl p-Chlorobenzyl 4' -Chioro Resorcinol Resorcinol Resorcinol -Resorcinol -Resorcinol -Resorcinol -Resorcinol Resorcinol Resorcinol Resorcinol Resorcinol Resorcinol Resorcinol Resorcinol 4-Dihydroxydiphenyl Methane 4-Dihydroxydiphenyl Methane .4*445

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.4,4 a ad -9- -2,4-Dihydroxydiphenyl Methane 4'-Bromo -2,4-Dihydroxydiphenyl Methane Bisphenolic Compounds Bisphenol A 2,2'-methylene bis (4-chlorophenol) 2,2'-methylenebis bis (3,4,6-trichlorophenol) (hexachlorophene) 2,2'-methylene bis (4-chloro-6-bromophenol) bis (2-hydroxy-3,5-dichlorophenyl) sulfide bis (2-hydroxy-5-chlorobenzyl) sulfide The antibacterial agent is present in the oral composition in an effective antiplaque amount, preferably about 0.01-5% by weight, more preferably about 0.03-1% and very preferably about 0.25-0.5% and most preferably about 15 0.25-0.35%. The antibacterial agent is substantially water-insoluble, meaning that its solubility is less than about 1% by weight in water at 25°C and may be even loss than about If an ionizable group is present solubility is determined at a pH at which ionization does not occur.

The preferred halogenated diphenyl ether is Triclosan. The preferred phenolic compounds are phenol, S' 2,2'methylene bis (4-chloro-6-bromophenol), thymol and eugenol. The most preferred antibacterial antiplaque S 25 compound is Triclosan. Triclosan is disclosed in *aforementioned U.S. Patent 4,022,880 as an antibacterial agent in combination with an anticalculus agent which I provides zinc ions and in German Patent Disclosure 35 32 860 in combination with a copper compound. 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 6.0nm and which may optionally contain a zinc salt in published European Patent Application 0161898 of Lane et al and in a dentifrice containing zinc citrate trihydrate in published European Patent Application 0161899 to Saxton.

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 oarticle size ruch The linear molecularly dehydrated polyphosphate salts operative herein as anticalculus agents are well known, being generally employed in the form of their- wholly or partially neutralized water soluble alkali metal (e.g.

potassium and preferable sodium) or ammonium salts, and any mixtures thereof. Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphates, the corresponding potassium salts and the like. Linear (0 polyphosphates correspond to (NaPO.), where n is about 2 to about 125. In the present invention, they are employed in the oral compositions in approximate weight amounts of 0.1 to 3% typically 1 to 2.5% more typically 1.5 to When n is at least 3 in NaPOa),, said polyphosphates are glassy in character.

Particularly desirable anticalculus agents are tetraalkali metal pyrophosphates, including mixtures thereof, such as tetrasodium pyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. Thus, the oral .b composition may contain polyphosphate anticalculus agent which is substantially free from tetra sodium pyrophosphate or substantially free from combination of tetra potassium pyrophosphate and tetra sodium pyrophosphate in which the ratio of potassium to sodium pyrophosphate is 3:1 or in .excess of 3:1. An anticalculus agent comprising about 2% by weight of the oral compositions of tetrasodium pyrophosphate is especially effective.

8 0. ii Ii Vi ^i .L v 1 The antibacterial-enhancing agent (AEA) which enhances delivery of said antibacterial agent to, and retention thereof on, oral surfaces, is employed in amounts effective to achieve such enhancement within the range in the oral composition of about 0.05% to about preferably about 0.12 to about more preferably about 0.5% to about by weight.

The AEA may be a simple compound, preferably a polymerizable monomer, more preferably a polymer, which latter term is entirely generic, including for example oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, cross-linked polymers and copolymers, and the like. The AEA may be natural or synthetic, and water insoluble or preferably water (saliva) soluble or swellable (hydratable, hydrogel forming). It has an (weight) average molecular weight of about 100 to about 1,000,000, preferably about 1,000 to about 1,000,000, more preferably about 2,000 or 2,5000 to about 250,000 or 500,000.

The AEA ordinarily contains at least one delivery- •enhancing group, which is preferably acidic such as 00 sulfonic, phosphinic, or more preferably phosphonic or carboxylic, or salt thereof, e.g. alkali metal or ammonium, and at least one organic retention-enhancing group, preferably a plurality of both the delivery-enhancing and retention-enhancing groups, which latter groups preferably have the formula wherein X is 0, N, S, SO, SO,, P, PO or Si or the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or their inertsubstituted derivatives, and n is zero or 1 or more. The S*0 aforesaid "inert-substituted derivatives", are intended to include substituents on R which are generally nonhydrophilic and do not significantly interfere with the 11 1;

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desired functions of the AEA as enhancing the delivery of the antibacterial agent to, and rctention thereof on, oral aurfaces such as halo, a. g. Cl, Br, 1, and carbo and the like. Illustrations of such re tention- enhancing groups are tabulated below.

n X(XR 0 methyl, ethyl, propyl, butyl, isobutyl, t-butyl cyclohexyl, allyl, benzyl, phenyl, chiorophenyl, xylyl, pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl, etc.

1 0 ethoxy, benzyloxy. thioacetoxy, phenoxy, carboethoxy, carbobenzyloxy, etc.

N ethylamino, diethylamino, propylamido, benzylamino, benzoylamido, phenylacetamido, etc.

S thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenylthioacetyl, thiobenzoyl, etc.

So butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulf oxy, etc.

SO

2 butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

P diethyiphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl.

e thy lphenylphosphinyl1, etc.

*PO diethyiphosphinoxy, ethylvinyiphosphinoxy, methylallylphosphinoxy, me thy lbenzy lphosphinoxy, methylphenylphosphinoxy, etc.

Si trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl dime thylvinyl s ilyl, dimethylallylsilyl, etc.

As employed herein, the delivery-enhancing group V refers to one which attaches or substantively, adhesively, cohesively or otherwise bonds the AEA (carrying the antibacterial agent) to oral tooth and gum) surfaces,

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thereby "delivering" the antibacterial agent to such surfaces. The organic retention-enhancing group, generally hydrophobic, attaches or otherwise bonds the antibacterial agent to the AEA, thereby promoting retention of the 12 antibacterial agent to the AEA and indirectly on the oral surfaces. In some inscances, attachment of the antibacterial agent occurs through physical entrapment thereof by the AEA, especially when the AEA is a crosslinked polymer, the structure of which inherently provides increased siZes for such entrapment. The presence of a higher molecular weight, more hydrophobic cross-linking moiety in the cross-linked polymer still further promotes the physical entrapment of the antibacterial agent to or by the cross-linked AEA polymer.

Preferably, the AEA is a anionic polymer comprising a chain or backbone containing repeating units each preferably containing at least one carbon atom and preferably at least one directly or indirectly pendent, monovalent delivery-enhancing group and at least one directly or indirectly pendent monovalent retentionenhancing group geminally, vicinally or less preferably otherwise bonded to atoms, preferably carbon, in the chain.

Less preferably, the polymer may contain delivery-enhancing groups and/or retention-enhancing groups and/or other divalent atoms or groups as links in the polymer chain S* instead of or in addition to carbon atoms, or as crosslinking moieties.

SIt will be understood that any examples or illustrations of AEA's disclosed herein which do not contain both delivery-enhancing groups and retention enhancing groups may and preferably should be chemically modified in known manner to obtain the preferred AEA' s containing both such groups and preferably a plurality each such groups.

SIn the case of the preferred polymeric AEA's, it is desirable, for maximizing substantivity and delivery of the antibacterial agent to oral surfaces, that the repeating units in the polymer chain or backbone containing the j 13 L i .iL' acidic delivery enhancing groups constitute at least about preferably at least about 50%, more'preferably at least abcut 801 up to 95% or 100% by weight of the polymer. According to a preferred embodiment of this invention, the AEA comprises a polymer containing repeating units in which one or more phosphonic acid deliveryenhancing groups are bonded to one or more carbon atoms in the polymer chain. An example of such an AefA is poly (vinyl i phosphonic acid) containing units of the formula: I -[CH 2

-CHI-

POH

2 which however does not contain a retention-enhancing group.A group of the latter type would however be present in poly (1-phosphonopropene) with units of the formula: II _1yH7H- A preferred phosphonic acid-containing AEA for use herein *is poly (beta styrene phosphonic acid) containing units of Swh". the formula: III -ICH -CH]- 2 Ph 1 4 3

H

2 wherein Ph is phenyl, the phosphonic delivery-enhancing group and the phenyl retention-enhancing group being bonded on vicinal carbon atoms in the chain, or a copolymer of beta styrene phosphonic acid with vinyl phosphonyl chloride IV -CH2 C I Ph PO3H2 hri hi hnl h hshncdlvr-nacn a in which the delivery and retention enhancing groups areI gemocinally bonded to the chain. a opoly (p a These styrene phosphonic acid polymertins and theirua S* inhaich the divery of fo ndla reIteinhanoin roups ar associa onde w to nthe chain. aoe o ol aph styrene phosphonic acid polymerg nis an therua .1 copolymers with other inert ethylenically unsaturated monomers generally have molecular weight's'in the range of about 2. 000 to about 30, 000, preferably about 2.500 to about 000. Such "inert" monomers do not signif icantly interfere, with the intended function of any copolymer employed as an AEA herein.

Other phosphonic-containing polymers include, for example, phosphonated ethylene having units of the formula.

NV -[CH 2 )zCHPO 3

H

2 1.where n1 may for example be an integer or have a value giving the polymer a molecular weight of about 3,000; and sodium poly (butene-4,4-diphosphonate) having units of the formula: VI -[ICHz C--

CH

2 CH (PO.

3 Na 2 2 and *poly (allyl bis (phosphonoethyl amine) having units of the formula: VII -[CH 2 s .Cu 2 N (P0 3

H

2 2 Other phosphonated polymers, for example poly (allyl v~phosphono acetate), phosphonated polymethacrylate, etc. and the geminal diphosphonate polymers disclosed in EP Publication 0321233 may be employed herein as AEA's, provided of course that they contain or are modified to contain the above-def ined organic retention-enhancing groups.

K1 ,"s In an aspect of this invention the oral composition comprises an orally acceptable vehicle, an agent which is effective to enhance the anti-bacterial, effect of an antibacterial agent which has an average molecular weight of about 1,000 to about 1,000,000, contains at least one functional group which enhances delivery of antibacterial effect and at least one organic group which enhances retention of antibacterial effects, said agent containing said groups being free from or substantially free from water jO soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of about 1,000 to 1,000,000, and polyphosphate anticalculus agent, such as a mixture of potassium and sodium salts, the ratio of potassium to sodium in the said composition being in the range of up to less than about 3:1, e.g. from about 0.37 to about 1.04:1.

:According to another preferred embodiment, the AEA comprises a synthetic anionic polymeric polycarboxylate which is also an inhibitor of alkaline phosphatase enzyme.

b Synthetic anionic polymeric polycarboxylates and their s complexes with various cationic germicides, zinc and magnesium have been previously disclosed as anticalculus agents per se in, for example U.S. Patent No. 3,429,963 to ~Shedlovsky; U.S. Patent 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 al.

However, only in disclosure essentially corresponding to U.S. Patent 4,627,977 to Gaffar et al is there described use of such polycarboxylates for inhibiting salivary hydrolysis D of pyrophosphate anticalculus agents 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 when containing or modified to contain the retention-enhancing groups defined above are operative as AEA's in the compositions and methods of this invention and such 16 I

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disclosures are to that extent incorporated herein by reference thereto. These synthetic anionic polymeric polycarboxylates are often employed in the form of their free acids or preferably partially or more preferably fully neutralized water soluble or water swellable (hydratable, gel/forming) alkali metal potassium and preferably sodium) or ammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether/maleic anhydride having a molecular weight of j about 30,000 to about 1,000,000. These copolymers are available for example as Gantrez e.g. AN 139 500,000), AN 119 250,000); and preferably S-97 Pharmaceutical Grade 70,000), of GAF Corporation.

Other AEA-operative polymeric polycarboxylates containing or modified to contain retention-enhancing groups include those disclosed in U.S. Patent No. 3,956,480 referred to above, such as the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, Nvinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrollidone.

Additional operative polymeric polycarboxylates disclosed in above referred to U.S. Patent No. 4,138,477 and 4,183,914, containing or modified to contain retentionenhancing groups include copolymers of maleic anhydride with 30 styrene, isobutylene or ethyl vinyl ether, polyacrylic, S: polyitaconic and polymaleic acids, and sulfoacrylic oligomers of M.W. as low as 1,000, available as Uniroyal ND- 2.

Suitable generally are polymerized retention-enhancing group-containing olefinically or ethylenically unsaturated carboxylic acids containing an activated carbon-to-carbon 17 1 olefinic double bond and at least one carboxyl group, that is, an acid containing an olefinic double bond which readily functions in polymerization because of its presence in the monomer molecule either in the alpha-beta position with respect to a carboxyl group or as part of a terminal methylene grouping. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, t0 mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymers ordinarily contain sufficient carboxylic salt groups for water-solubility.

Also useful herein are so-called carboxyvinyl polymers 2,2* disclosed as toothpaste components in U.S. 3,980,767 to Chown et al; U.S. 3,935,306 to Roberts et al; U.S. 3,919,409 to Perla et al; U.S. 3,911,904 to Harrison, and U.S.

3,711,604 to Colodney et al. They are commercially available for example under the trademarks Carbopol 934, 940 *and 941 of B. V. Goodrich, these products consisting essentially of a colloidally water-soluble polymer of polyacrylic acid crosslinked with from about 0.75% to about of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent, the cross-linked structures and linkages providing the desired retention enhancement by I hydrophobicity and/or physical entrapment of the *b antibacterial agent or the like. Polycarbophil is somewhat similar, being polyacrylic acid cross-linked with less than 0.2% of divinyl glycol, the lower proportion, molecular weight, and/or hydrophobicity of this cross-linking agent tending to provide decreased, or no, retention enhancement.

2,5-dimethyl-l,5- hexadiene exemplifies a more effective retention-enhancing cross-linking agent.

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.jl I I The synthetic anionic polymeric polycarboxylate component is most often a hydrocarbon with optional halogen and 0-containing substituents and linkages as present in for example ester, ether and JH groups, and when present is generally employed in the instant compositions in approximate weight amounts of up to about 4% (generally at least about 0.05%).

The AEA may also comprise natural anionic polymeric polycarboxylates containing retention-enhancing groups.

Carboxymethyl cellulose and other binding agents, gums and film-formers devoid of the above-defined delivery-enhancing and/or retention-enhancing groups are ineffective as AEA's.

As illustrative of AEA's containing phosphinic acid and/or sulfonic acid delivery enhancing groups, there may be mentioned polymers and copolymers containing units or moieties derived from the polymerization of vinyl or allyl phosphinic and/or sulfonic acids substituted as needed on the 1 or 2 (or 3) carbon atom by an organic retentionenhancing group, for example having the formula -b defined above. Mixtures of these monomers may be employed, and copolymers thereof with one or more inert polymerizable ethylenically unsaturated monomers such as those described above with respect to the operative synthetic anionic i 4444 4 4.4.

.4 *4 4 44 4 4 l p 1 *4 4.

4 4* 4* polymeric polycarboxylates. As other polymeric AEA's operative acidic delivery-enhancing group carbon or other atom in the pol; thereon. Polysiloxanes contain pendant delivery-enhancing grou groups may also be employed as as AEA's herein are ionomers cot contain delivery- and retention are described on pages 546-573 Encyclopedia of Chemical Techno Supplement Volume, John Wiley a which description is incorporat Swill be noted, in these and herein, usually only one p is bonded to any given ymer backbone or branch ling or modified to contain ips and retention enhancing AEA's herein. Also effective ntaining or modified to i-enhancing groups. lonomers oF the Kirk-Othmer logy, third edition, nd Sons, Inc. copyright 1984, ed herein by reference. Also 1 i ~ll *t saes 1 1 I Ir I 1

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9. 09 e4t9 4. .94 C 9 *00*4* effective as AEA's herein, provided they contain or are modified to contain retention-enhancing groups, are polyesters, polyurethanes and synthetic and natural polyamoides including proteins and proteinaceous materials such as collagen, poly (argenine) and other polymerized amino acids.

When the oral preparation is made by initially dissolving the polyphosphate and the antibacterial agent in humectant and surface active agent and adding thereto the AEA, especially the polycarboxylate, incrementally, the solution becomes clear and may 'ie characterized as a "microemulsion". As the amount of the polycarboxylate increases such that the complete oral preparation contains at least about 2.2% by weight thereof, the solution becomes cloudy and may be characterized as a "macroemulsion". In such "macroemulsion" type compositions, the antiplaque effect of the antibacterial agent appears to be optimized.

A desirable weight ratio of the substantially waterinsoluble noncationic antibacterial agent to the agent to 30 the polyphosphate anticalculus agent is in excess of about 0.72:1 to less than about 4:1, e.g. from about 1:1 to about 3.5:1, especially from about 1.6:1 to about 2.7:1.

In order to optimize the anticalculus effectiveness of the oral composition, inhibitors against enzymatic hydrolysis of the polyphosphate are desirably present. Such agents are an amount of a fluoride ion source sufficient to supply 25 ppm. to 5,000 ppm. of fluoride ions, and up to 3Z or more of the synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 30 1,000,000, preferably about 30,000 to about 500,000.

The sources of fluoride ions, or fluorine-providing component, as acid phosphatase and pyrophosphattse enzyme inhibitor component, are well known in the art as anticaries agents. These compounds may be slightly soluble in water or may be fully water-soluble. They are characterized by their ability to release fluoride ions in water and by

K.

44 C C a. C a C a.

.4; M_ No 11 freedom from unidsired reaction with other compounds of the oral prepa t.ion. Among these materials are inorganic fluoride salt., .i.Lh 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 such as cuprous fluoride, zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, ammonium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate, and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as sodium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred.

The amount of fluorine-providing compourd is dependent to some extent upon the type of compound, its solubility, and the type or oral preparation, but it must be a non-toxic amount, generally about 0.005 to about 3.0% in the preparation. In a dentifrice preparation, e.g. dental gel, toothpaste (including cream), toothpowder, or dental tablet, an amount of such compound which releases up to about 5,000 ppm of F ion by weight of the preparation is considered satisfactory. Any suitable minimum amount of such compou-nd may be used, but it is preferable to employ sufficient 9, compound to release about 300 to 2,000 ppm, more preferably about 800 to about 1,500 ppm of fluoride ion.

Typically, in the cases of alkali metal fluorides, this component is present in an amount up to about 2% by weight, based on the weight of the preparation, and preferably in J the r:ange of about 0.05Z to In the case of sodium i t monofiluorophosphate, the compound may be present in an amount of about more typically about 0.76Z.

In oral preparations such as mouthwashes, lozenges and i 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 21 I 1 1 1 1 1 jl l 1 .e 9$*

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54

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pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, hydrated alumina, calcined alumina, aluminum silicate, 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, issued Dec. 15, 1962, such as melamine-, phenolic, and urea-formaldehydes, and cross-linked polyepoxides and polyesters. Preferred polishing materials include crystalline silica having ;0 particle sized of up to about 5 microns, a mean particle size of up to about 1.1 microns, and a surface area of up to about 50,000 cm.

2 silica gel or colloidal silica, and complex amorphous alkali metal aluminosilicate.

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, alkali metal aluminosilicate complexes are particularly useful, since they have refractive indices close to the refractive indices of gelling agent-liquid (including water and/or humectant) systems commonly used in dentifrices.

Many of the so-called "water-insoluble" polishing materials are anionic in character and also include small amounts of soluble material. 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 Mar 'ell's salt and Kurrol's salt are further examples of suitable materials. These 3D) metaphosphate salts exhibit only 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 such as up to 4% by weight. The amount of soluble phosphate material, which is believed to include a soluble sodium trimetaphosphate in the case of insoluble i r 23 If" -i i s 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 1% of the material is larger than 37 microns.

The polishing material is generally present in the solid or pAsty compositions in weight concentrations of about 10% to about 99%. Preferably, it is present in amounts ranging from about 10% to about 75% in toothpaste, iO and from about 70Z to about 99% in toothpowder. In toothpastes, when the polishing material is silicious in I nature, it is generally present in amount of about 10-30% by weight. Other polishing materials are typically present in amount of about 30-75% by weight.

In a toothpaste, the liquid vehicle may comprise water and humectant typically in an amount ranging from about to about 80% by weight of the preparation. Glycerine, propylene glycol, sorbitol and polypropylene glycol exemplify suitable humectants/carriers. Also advantageous are liquid mixtures of water, glycerine and sorbitol. In clear gels where the refractive index is an important consideration, about 2.5-30 wt. of water, 0 to about wt.Z of glycerine and about 20-80 wt. of sorbitol are preferably employed.

Toothpastes, creams and gels typically contain a natural or synthetic thickener or gelling agent in •proportions of about 0.1 to about 10, preferably about to about 5 wt. A suitable thickener is synthetic 0 ii hectorite, a synthetic colloidal magnesium alkali metal j 3 silicate complex clay available for example as Laponite CP, SP 2002, D) marketed by Laporte Industries Limited. Laponite D analysis shows, approximately by weight, 58.00% SiO 2 25.40% MgO, 3.05% Na 2 O, 0.98% Li 2 O, and some water and trace metals. Its true specific gravity is 2.53 and it has an apparent bulk density at 8% moisture) of 24 l w :i

S

S^ yA l Ocher suitable thickeners include Irish moss, iota carrageenan, gum tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutyl mnthyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g.

available as Natrosol), sodium carboxymethyl cellulose, and colloidal silica such as finely ground Syloid 244).

In some dentifrices prepared in accordance with the present invention particularly when more than about 0.35% by weight of the water insoluble antibacterial agent is employed and a siliceous polishing agent is present in amount of less than about 30% by !;eight, it may be desirable to include an agent which dissolves the antibacterial agent. Such solubilizing j agents include humectant polyols such propylene glycol, dipropylene glycol and hexylene glycol, cellosolves such as methyl cellosolve and ethyl cellosolve, vegetable oils and waxes containing at least about 12 carbons in a straight chain such as olive oil, castor oil and petrolatum and esters such as amyl acetate, ethyl acetate and benzyl benzoate.

oC It will be understood that, as is conventional, the oral preparations are to be sold or otherwise distributed in suitable labelled packages. Thus, a jar of mouthrinse will have a label describing it, in substance, as a mouthrinse or mouthwash and having directions for its use; and a toothpaste, cream or gel will usually be in a collapsible Stube, typically aluminum, lined lead or plastic, or other Ssqueeze, pump or pressurized dispenser for metering out the contents, having a label describing it, in substance, as a toothpaste, gel or dental cream.

D0 Organic surface-active agents are used in the 'compositions of the present invention to achieve increased prophylactic action, assist in achieving thorough and complete dispersion of the anticalculus agent and antiplaque agent throughout the oral cavity, and render the instant compositions more cosmetically acceptable. The organic surface-active material is preferably anionic, nonionic or i l 1 1

Z

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. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2-dihydroxy propane sulfonate, and the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid i compounds, such as those having 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the like. Examples of the last mentioned amides are N-lauroyl sarcosine, and the sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine which should be substantially free from soap or similar higher fatty acid material. The use of these sarcosinate compounds in the S -0 •oral compositions of the present invention is particularly advantageous since these materials exhibit a prolonged a marked effect in the inhibition of acid formation in the oral cavity due to carbohydrates breakdown in addition to r 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 i* various reactive hydrogen-containing compounds reactive f therewith having long hydrophobic chains aliphatic chains of about 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain hydrophilic polyoxyethyle-2 moieties, such'as condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols sorbitan monostearate) and polypropyleneoxide Pluronic materials)..

Surface active agent is typically present in amount of about 0.1-5% by weight, preferably about It is 26 z noteworthy, that surface active agent may assist in the dissolving of the noncationic antibacterial agent and thereby diminish the amount of solubilizing humectant' needed.

Various other materials may be incorporated in the oral preparations of this invention such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammizoniated material such as urea, diammonium phosphate, and f mixtures thereof. These adjuvants, where present, are I, 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, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, 2b cinnamon, lemon, and orange, and methyl salicylate.

Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartine, AMP (aspartyl phenyl alanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may each or together comprise from about 0. 1% to 5% more of the preparation. Moreover, flavor oil appears to aid the dissolving of the antibacterial agent.

In the preferred practice of this invention an oral composition according to this invention such as a mouthwash I :b or dentifrice containing the composition of the present invention is preferably applied regularly 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 4.5 to about 9, generally about 5.5 to about. 8, preferably about 6 to 8, forq at least 2 weeks up to 8 weeks or more up to lifetime.

The compositions of this invention can be incorporated 27 wso r in lozenges, or in chewing gum or other products, e.g. by stirring into a warm gum base or coating the outer surface of a gum base, illustrative of which may be mentioned jelutong, rubber latex, vinylite resins, etc., desirably with conventional plasticizers or softeners, sugar or other sweeteners or such as glucose, sorbitol and the like.

The following examples are further illustrative of the nature of'the present invention, but it is understood that the invention is not limited thereto. All amounts and 1D proportions referred to herein and in the appended claims are by weight unless otherwise indicated.

In the following Examples, the agent Triclosan, 2,4,4'trichloro-2'-hydroxydiphenyl ether is indicated as "TCHE"; sodium lauryl sulfate is indicated as "SLS"; the copolymer of rjaleic anhydride and methyl vinyl ether available from GAF Corporation as "Gantrez S-97" is identified as "Gantrez"; tetrasodium pyrophosphate is identified as "pyrophosphate"; and sodium fluoride is identified as "NaF".

o.Q Example 1 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 disk in the presence of pyrophosphate and differing amounts of polycarboxylate.

28..

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The formiulati~ons of the toothpastes evaluated are: Parts bv Weieht lycerine 10.000 10.000 ota-carrageenan 0.750 0.750 ~orbitol (70% solution) 30.000 30.000 'ropylene Glycol 0.500 0.500 ;antez (13.02% solution) 19.000 15.500 itaniun dioxide 0.500 0.500 ate: (deionized) 9.957 13.457 0.243 0.243 odium~ saccharine 0.300 0.300 yrophosphate 2.000 2.000 odium hydroxide 1.000 1.000 Silica polishing agent (Zeodent 113) Silica Thickener (Sylodent !5) Flavor oil

TCHE

SLS

p p S C

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20.000 2.500 0.950 0.300 2.000 20. 000 2.500 0.950 0.300 2.000 Gancrez is present as A. I. in amount of 2.5 parts in toothpaste A and 2.0 parts in toothpaste B.

For the test of delivery of antibacterial agent to a saliva coated hydroxyapatite disk, hydroxtapatite (HA) obtained from the Monsanto Co. is washed extensively with distilled water, collected by vacuum filtration, and permizted to dry overnight at 37'C. The dried HA is ground into a powder with a mortar and pestle. 150.00 mgs of HA are placed into the chamber of a K~r pellete die (Barnes .)Analytical, Stanford, CT.) and compressed for 6 minuues at 10,000 pounds in a Carver Laboratory press. The resulting 13 mmdisks are sintered for 4 hours at 800"C in a Thermolyne furnace. Parafilm stimulated whole saliva is collected into a ice-chilled glass beaker. The saliva is clarified by centrifugation at 15,000 Xg (times gravity) 29

A

ma f aM for 15 minutes at 4°C. Sterilization of the clarifiedsaliva is done at 4"C with stirring by irradiation of the sample with UV light for 1.0 hour.

Each sintered disk is hydrated with sterile water in a polyethylene test tube. The water is then removed and replaced with 2.00 ml of saliva. A salivary pellicle is formed by incubating the disk overnight at 37"C with continuous shaking in a water bath. After this treatment, the saliva is removed and the disks are treated with 1.00 ml I of a solution containing antibacterial agent (triclosan) in a dentifrica liquid phase solution and incubated at 37°C with continuous shaking in the water bath. After minutes, the disk is transferred into a new tube and 5.00 ml of water are added followed by shaking the disk gently with a Vortex. The disk is then transferred into a new tube and the washing procedure repeated twice. Finally, the disk is transferred carefully into a new tube to avoid co-transfer i of any liquid along with the disk. Then 1.00 ml of methanol is added to the disk and shaken vigorously with a Vortex.

The sample is left at room temperature for 30 minutes to extract adsorbed triclosan in the methanol. The methanol is then aspirated and clarified by centrifugation in a Beckman Microfuge 11 at 10,000 rpm for 5 minutes. After this treatment, the methanol is transferred into HPLC(high *4 e S" performance liquid chromatography) vials for determination Sof antibacterial agent concentration. Triplicate samples are used in all experiments.

M The Table below summarizes the data: Table Delivery of TCHE to .b Toothpaste Saliva Coated Hydroxyapatite Disc in Micrograms A 130 B The data indicates that with the increasing amount of Gantrpz (Toothpaste A) there is a very great increase in delivery of TCHE to saliva coated tooth minerals.

i o 1 1 t i' I 1 i 1 "r "1 Example 2 The following toothpaste is effective as an antiplaque and anticalculus composition: Sorbitol (70%) Irish Moss Sodium Hydroxide (50%) Gantrez (13.02% solution) Water (deionized) O0 Sodium Monofluorophsophate Sodium saccharine Pyrophosphate Hydrated alumina Flavor oil

TCHE

SLS

Parts by Weight 22.00 1.00 1.00 19,00 2.69 0.76 0.30 2.00 48.00 0.95 0.30 2.00 i

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Example 3 Mouthrinse Tetrasodium Pyrophosphate Gantrez S-97 Glycerine Sodium Fluoride Sodium Lauryl Sulfate

TCHE

Flavor oil Water Parts 2.00 2.50 10.00 0.05 0.20 0.06 0.40 Q.S. to 100.00 4" 1-11 'd I:a Example 4 Lozenge 75-80% Sugar 1-20% Corn Syrup 0.1-1.0 Flavor Oil 2% Tetrasodium Pyrophosphate 2.50% Gantrez S-97 0.01 to 0.05% NaF 0.01 to 0.1% TCHE to 1 to 5% Magnesium Stearate Lubricant 0.01 to 0.2% Water Example Chewing Gum Gum Base Sorbitol (70%)

TCHE

Tetrasodium Pyrophosphate Gantrez S.97 Parts 25.00 17.00 0.50 to 0.10 2.00 2.50 *004 0 In a variant Example of the foregoing Example, Gantrez S-97 can be omitted.

Example 6

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0 04 *0404 Chewing Gum Gum Base

TCHE

Gantrez NaF Glycerine Crystalline Sorbitol Tetrasodium Pyrophosphate Flavor Oil and Water Parts 30.00 0.50 2.00 0.05 0.50 53.00 2.00 O.S. to 100.00 In the foregoing Examples improved results are also achievable when TCHE is replaced with each of phenol, 2,2'methylene bis(4-chloro-6-Bromophenol), eugenol and thymol, and/or when Gantrez is replaced by other AEA's such as 32 -e II Carbopols 934), or styrene phosphonic acid polymers having molecular weights within the range of about 3,000 to 10,000 such as poly (beta-styrenephosphonic acid), copolymers of vinyl phosphonic acid with betaatyrenephosphonic acid, and poly (alpha-styrenephosphonic acid), or sulfoacrylic oligomers, or a 1:1 copolymer of maleic anhydride with ethyl acrylate.

Likewise similar results are achieved when pyrophosphate (tetrasodium pyrophosphate) is replaced by tetrasodium pyrophosphate and tetrapotassium pyrophosphate, with the weight ratio of potassium to sodium being a) 0.37:1 b) 1.04:1; c) 3:1; and 3.5:1.

This invention has been described with respect to certain 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 appended laims.

S

4 4 S S i ii 33

Claims (11)

1. An oral composition comprising an orally acceptable vehicle, an effective antiplaque amount of a substantially water insoluble noncationic antibacterial agent, an antibacterial enhancing agent (AEA) which is effective to enhance the anti-bacterial effect of said antibacterial agent which AEA has an average molecular weight of 1,000 to 1,000,000, contains at least one functional group which enhances delivery of antibacterial effect and at least one organic group which enhances retention of antiba-:terial effect, said AEA containing said groups being free from or substantially free from water soluble alkali metal or ammonium synthetic anionic linear polyme. polycarboxylate salt having a molecular weight of 1,000 to 1,000,000, and 15 a polyphosphate anticalculus agent, the said polyphosphate anticalculus agent being a mixture of potassium and sodium salts, the ratio of potassium to sodium in the said composition being below 3:1.

2. The oral composition claimed in Claim 1 wherein said S 20 ratio of potassium to sodium is from 0.37:1 to 1.04:1.

3. The oral composition claimed in Claim 1 wherein said group which enhances delivery is selected from the group consisting of phosphonic, phosphinic and sulfonic acids, and their salts, and mixtures thereof. 25 4. The oral composition claimed in Claim 2 wherein said organic group which enhances retention comprises the formula wherein X is O, N, S, SO, S0 2 PO or Si, R is hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic, or their inert-substituted j derivatives, and n is 1 or zero. An oral composition comprising an orally acceptable vehicle, an effective antiplaque amount of a substantially water insoluble antibacterial agent, an antibacterial enhancing agent (AEA) which is effective to enhance the antibacterial effect of said antibacterial agent, which pi 4 f r WS i 1 .ss i, a~ 35 *49) S 9 a 4 wr 4, 9e *9Sr 9 £4 9 it V AEA has an average molecular weight of 1,000 to 1,000,000, contains at least one functional group which enhances delivery of antibacterial effect and at least one organic group which enhances retention of antibacterial effect, said AEA containing said groups being free from or substantially free from water soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of 1,000 to 1,000,000, and a polyphosphate anticalculus agent. 10 6. The oral composition claimed in Claim 5 wherein said group which enhances delivery is selected from the group consisting of phosphonic, phosphinic and sulfonic acids, and their salts, and mixtures thereof.

7. The oral composition claimed in Claim 6 wherein said 15 organic retention enhancing group comprises the formula wherein X is 0, N, S, SO, SO2, PO or Si, R is hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic, or their inert-substituted derivatives, and n is 1 or zero. 20 8. An oral composition comprising an orally acceptable vehicle, an effective antiplaque amount of a substantially water insoluble noncationic antibacterial agent, an antibacterial-enhancing agent (AEA) which has an average molecular weight of 1,000 to 1,000,000, which AEA contains at least one delivery enhancing functional group and at least one organic retention enhancing group, said AEA containing said groups being free from or substantially free from water soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of 1,000 to 1,000,000, and polyphosphate anticalculus agent.

9. An oral composition comprising an orally acceptable vehicle, an effective antiplaque amount of a substantially water insoluble antibacterial agent, an antibacterial enhancing agent (AEA) which is effective to enhance the ji i i i ii r; ir i! u r i: j i i:k r i fri 1 44 i- ,-r 36 ltt 4 t 4r. r C 4 r c antibacterial effect of said antibacterial agent and which AEA has an average molecular weight of 1,000 to 1,000,000, and contains at least one functional group which enhances delivery of antibacterial effect and at least one organic group which enhances retention of antibacterial effect, said AEA containing said groups being free from or substancially free from water soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of 1,000 to 1,000,000, and a polyphosphate anticalculus agent where the weight ratio of polyphosphate from said anticalculus agent to said antibacterial agent ranges from in excess of 0.71:1 to less than 4:1.

10. The oral composition claimed in Claim 9 wherein said 15 weight ratio is from 1:1 to 3.5:1.

11. The oral composition claimed in Claim 9 wherein said weight ratio is from 1.6:1 to 2.7:1.

12. An oral composition comprising an orally acceptable vehicle, an effective antiplaque amount of a substantially water insoluble noncationic antibacterial agent, an antibacterial-enhancing agent (AEA) which has an average molecular weight of 1,000 to 1,000,000, and contains at least one delivery enhancing functional group and at least one organic retention enhancing group, said AEA containing said groups being free from or substantially free from water soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of 1,000 to 1,000,000, and a polyphosphate anticalculus agent, with the proviso that the composition is free from or substantially free from tetrasodium pyrophosphate anticalculus agent.

13. An oral composition comprising an orally acceptable vehicle, an effective antiplaque amount of a substantially water insoluble noncationic antibacterial agent, antibacterial-enhancing agent (AEA) which has an average I f1 i 1 j *0 I 0 44 4 r* 44 04 0 0i iir~ Ir i /1 It -:z I 37 molecular weight of 1,000 to 1,000,000, and contains at least one delivery enhancing functional group and at least one organic retention enhancing group, said AEA containing said groups being free from or substantially free from water soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of 1,000 to 1,000,000, and a polyphosphate anticalculus agent with the proviso that the composition is free from or substantially free from combination of tetra potassium pyrophosphate and tetra sodium pyrophosphate in which the ratio of potassium to sodium ',pyrophosphate is 3:1 or in excess of 3:1.

14. The oral composition claimed in claim 1 wherein said substantially water insoluble non-cationic antibacterial agent is present in an amount of from 0.25% to 0.35%. The oral composition claimed in claim 12 wherein said substantially water insoluble noncationic antibacterial agent is present in an amount of from 0.25% to 0.35%.

16. The oral composition claimed in claim 13 wherein said substantially water insoluble noncationic antibacterial c agent is present in an amount of from 0.25% to 0.35%. DATED this 21st day of June 1995 SCOLGATE-PALMOLIVE COMPANY Patent Attorneys for the Applicant: 1 F.B. RICE CO. L V jp'ii} An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such es tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncationic antibacterial agent such as 2,4,4' trichloro- efiectiveness is optimized by the presence of an antibacterial-enhancing agent which enhances delivery of a said antibacterial agent to, and retention thereof on, oral surfaces. I* An .a c s s aei e u loeg r ceig g:cnann oyhsht