NL8903185A - ANTIBACTERIAL ANTI-PLAQUE, ANTI-DENTAL STONE PREPARATION. - Google Patents

Description

Title: Antibacterial anti-plaque, anti-tartar preparation. DESCRIPTION

This invention relates to an oral anti-bacterial anti-plaque, anti-tartar preparation. More specifically, it relates to an oral preparation containing a polyphosphate anti-tartar agent (that is, anti-calculus agent) and a compatible antibacterial agent that effectively inhibits plaque, wherein anti-plaque action is optimized by the presence of an antibacterial action-enhancing agent that enhances delivery of said antibacterial agent to and retention thereof on surfaces in the mouth.

In U.S. Patents 4,627,977 to Gaffar et al .; 4,515,772 to Parran et al .; and 4,323,551 to Parran disclose oral formulations comprising various polyphosphate compounds. In the Gaffar et al. Patent, a linear molecular dehydrated polyphosphate salt is used in conjunction with a fluoride ion providing source and a synthetic linear polymer polycarboxylate to inhibit tartar formation. In European Patent Application 89 200 710.5, also pending, anti-tartar effectiveness is optimized with a reduced amount of the linear molecular dehydrated polyphosphate salt in conjunction with the source of the fluoride ion and an increased amount of the synthetic linear polymeric polycarboxylate.

In the patents of Parran et al. And of Parran, water-soluble dialkali metal pyrosphosphate is used alone or mixed with tetra-alkali metal pyrophosphate.

Oral preparations that inhibit tartar formation on tooth surfaces are highly desirable because tartar is one of the causative factors of periodontal conditions. Therefore, the reduction of this promotes oral hygiene.

Dental plaque is a precursor to tartar. Unlike tartar, however, plaque can form on any part of the tooth surface, especially including at the gumline.

In addition to looking ugly, it is therefore implicated in the development of gingivitis.

Accordingly, it would be highly desirable to include antimicrobial agents known to reduce plaque in oral compositions containing anti-tartar agents. Indeed, this is described in U.S. Patent 4,022,550 to Vinson et al., Wherein a compound providing zinc ions as an anti-tartar agent is mixed with an antibacterial agent that effectively retards the growth of plaque bacteria. A wide 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.

To date, the cationic antibacterial materials such as chlorhexidine, benzethonium chloride and cetylpyridinium chloride have been the subject of the main research as antibacterial anti-plaque agents. However, despite their use in conjunction with zinc anti-tartaric agent, they are not effective when used with anionic materials such as polyphosphate anti-tartaric agent. This ineffectiveness is considered quite surprising because polyphosphates are chelating agents and the chelating effect was known in advance to enhance the efficacy of cationic antibacterial agents. (See, e.g., Disinfection, Sterilization and Preservation, 2nd Edition, Black, 1977, p. 915 and Inhibition and Destruction of the Microbial Cell, Hugo, 1971, p. 215. Indeed, a quaternary ammonium compound is present in the plaque control- cost effective mouthwash containing pyrophosphate of U.S. Patent No. 4,323,551 to Parran and bis-biguanide anti-plaque agent is suggested in the anti-tartar pyrophosphate oral formulation of U.S. Patent 4,515,772 to Parran et al.

In light of the surprising incompatibility of cationic antibacterial agents with polyphosphates present as anti-tartaric 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 anti-tartar oral preparations containing a linear molecularly dehydrated polyphosphate salt, a fluoride ion providing source and the aforementioned antibacterial enhancing agent to inhibit plaque formation.

It is a further advantage of this invention to provide a composition that effectively reduces tartar formation and optimizes plaque reduction.

It is a still further advantage of this invention that an anti-plaque, anti-tartar oral preparation is provided which is effective in reducing the occurrence of gingivitis.

Additional advantages of this invention will become apparent upon consideration of the following description.

In accordance with some of its aspects, this invention relates to an oral composition comprising in an orally acceptable carrier an effective anti-tartar amount of material comprising about 0.1-3 wt.% Of at least one linear molecular dehydrated polyphosphate salt as an anti-tartar. tartaric agent, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent and preferably up to about 4% by weight of an anti-bacterial enhancer which inhibits the release of said antibacterial agent and retention thereof enlarged on oral surfaces in which typically the weight ratio of polyphosphate ions to antibacterial enhancer increases from an 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 from about 1.7: 1 to about 2.3: 1, most preferably about 1.9: 1 to about 2: 1. For example, when using 2% tetrasodium pyrophosphate (TSPP) (providing about 1.3% of pyrophosphate ions) with 2.5% of the antibacterial activity-enhancing agent, a highly desirable weight ratio of about 1.9: 1 is obtained.

Typical examples of antibacterial agents that are particularly desirable from considerations of anti-plaque effectiveness, safety and formulation are:

Halogenated diphenyl ethers: 2 ', 4,4'-trichloro-2-hydroxydiphenyl ether (Triclosan) 2,2'-dihydroxy-5,5'-dibromo diphenyl ether.

Halogenated salicylanilides: 4 ', 5-dibromosalicylanilide 3,4', 5-trichlorosalicylanilide 3,4 ', 5-tribromosalicylanilide 2,3,3' / 5-tetrachlorosalicylanilide 3,3,31,5-tetrachlorosalicylanilide 3,5-dibromylethyl-3'-trifluoromilide 5-n-octanoyl-31-trifluoromethyl-salicylanilide 3,5-dibromo-41-trifluoromethyl-salicylanilide 3,5-dibromo-31-trifluoromethyl-salicylanilide (Flurophene).

Benzoic acid esters: methyl-p-hydroxybenzoic acid ester ethyl-p-hydroxybenzoic acid ester propyl-p-hydroxybenzoic acid ester buty1-p-hydroxybenzoic acid ester.

Halogenated carbanilides; 3,4,4'-trichloro-carbanilide 3-trifluoromethyl-4,4'-dichloro-carbanilide 3,3,4'-trichloro-carbanilide.

Phenolic Compounds {including phenol and are homologues, mono- and polyalkyl and aromatic halogen (e.g., F, Cl, Br, J) phenols, resorcinol and catechol and their derivatives and bisphenol compounds.

Such phenolic compounds include, inter alia: -Phenol and its homologs: phenol 2-methylphenol 3-methylphenol 4-methylphenol 4-ethylphenol 2,4-dimethylphenol 2,5-dimethylphenol 3,4-dimethylphenol 2,6-dimethylphenol 4-n-propylphenol 4-n-butylphenol 4 -n-amylphenol 4-tert-amylphenol 4-n-hexylphenol 4-n-heptylphenol 2-methoxy-4- (2-propenyl) -phenol (Eugenol) 2-isopropyl-5-methylphenyl (Thymol).

Mono- and polyalkyl and aralkyl halophenols; methyl-p-chlorophenol ethyl-p-chlorophenol n-propyl-p-chlorophenol n-butyl-p-chlorophenol n-amyl-p-chlorophenol sec-amyl-p-chlorophenol n-hexyl-p-chlorophenol cyclohexyl-p-chlorophenol n-heptyl-p-chlorophenol n-octyl-p-chlorophenol o-chlorophenol methyl-o-chlorophenol ethyl-o-chlorophenol n-propyl-o-chlorophenol n-butyl-o-chlorophenol n-amyl-o-chlorophenol tert- amyl-o-chlorophenol n-hexyl-o-chlorophenol n-heptyl-o-chlorophenol p-chlorophenol o-benzyl-p-chlorophenol o-benzyl-m-methyl-p-chlorophenol o-benzyl-m, diraethyl- p-chlorophenol o-phenylethyl-p-chlorophenol o-phenylethyl-m-rthiethyl-p-chlorophenol 3-methyl-p-chlorophenol 3,5-dimethyl-p-chlorophenol 6-ethyl-3-methyl-p-chlorophenol 6 -n-propyl-3-methyl-p-chlorophenol 6-isopropyl-3-methyl-p-chlorophenol 2-ethyl-3,5-dimethyl-p-chlorophenol 6-sec.butyl-3-methyl-p-chlorophenol 2 -isopropyl-3,5-dimethyl-p-chlorophenol 6-diethylmethyl-3-inethyl-p-chlorophenol 6-isopropyl-2-ethyl-3-methyl-p-chlorophenol 2-sec.amyl-3,5-dimethyl- p-chlorophenol 2-diethylmethyl-3,5-dimethyl-p-chl ear phenol 6-sec.octyl-3-methyl-p-chlorophenol p-bromophenol methyl-p-bromophenol ethyl-p-bromophenol n-propyl-p-bromophenol n-butyl-p-bromophenol n-amyl-p-bromophenol sec- amyl-p-bromophenol n-hexyl-p-bromophenol cyclohexyl-p-bromophenol o-bromophenol tert-amyl-o-bromophenol n-hexyl-o-bromophenol n-propyl-m, m-dimethyl-o-bromophenol 2-phenylphenol 4-chloro-2-methylphenol 4-chloro-3-methylphenol 4-chloro-3,5-dimethylphenoi 2,4-dichloro-3,5-dimethylphenol 3,4,5,6-tetrabromo-2-methylphenol 5-methyl -2-pentylphenol 4-isopropyl-3-methylphenol 5-chloro-2-hyaroxydiphenylmethane.

Resorcinol and its derivatives; resorcinol methylresorcinol ethylresorcinol n-propylresorcinol n-butylresorcinol n-amylresorcinol n -nexylresorcinol n-heptylresorcinol n-octylresorcinol n-nonylresorcinol-phenylresorcinol-benzyl-chloro-yl-pyl-resorcinol phenyl dihydroxydiphenylmethane 5-bromo-2,4-dihydroxydiphenylmethane 4 "-bromo-2,4-dihydroxydiphenylmethane.

Bisphenol compounds:

Bisphenol-A

2,2'-methylene-bis- (4-chlorophenol) 2,2'-methylene-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 anti-plaque amount, typically about 0.01-5% by weight, preferably about 0.03-1% by weight, most preferably about 0.25-0%, 5 wt% and most preferably about 0.25-0.35 wt%.

The antibacterial agent is essentially water insoluble, meaning that its solubility is less than about 1% by weight in water at 25 ° C and may even be less than about 0.1%. When an ionizable group is present, solubility is determined at a pH at which ionization does not occur.

The preferred halogenated diphenyl ether is triclo-san. The preferred phenolic compounds are phenol, thymol, eugenol, hexylresorcinol and 2,21-methylenebis (4-chloro-6-bromophenol). The most preferred antibacterial anti-plaque compound is triclosan. Triclosan is described in the aforementioned U.S. Pat. No. 4,022,880 as an antibacterial agent in combination with an anti-tartaric agent providing zinc ions and in German Patent Publication 3,532,860 in combination with a copper compound. It is disclosed in European Patent Publication 0 278 744 in combination with a tooth desensitizing agent, which contains a source of potassium ions. It is also described as an anti-plaque agent in a dental treatment agent having a formulation in which a lamellar liquid crystal surfactant phase is present with a lamella spacing less than 6.0 nm and which may optionally contain a zinc salt, in published European Patent Application 0,161 .898 to Lane et al. And in a dental treatment agent containing zinc citrate trihydrate, in published European Patent Application 0,161,899 to Saxton et al.

The linear molecularly dehydrated polyphosphate salts active herein as anti-tartar agents are well known, generally used in the form of a fully or partially neutralized aqueous soluble alkali metal (e.g., potassium and preferably sodium) and ammonium salts, and any mixtures thereof. Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium monoacid, and tetran sodium pyrophosphates, the corresponding potassium salts and the like. Linear polyphosphates correspond to (NaPC> 3) n where n is about 2 to about 125. In the present invention, they are used in the oral compositions in amounts by weight of approximately 0.1-3%, typically 1-2.5% and more typically 1.5-2%. When n is at least 3 in (NaPO 3) n, said polyphosphates are glassy in nature.

Particularly desirable anti-tartaric agents are tetraalkali metal pyrophosphates, including mixtures thereof, such as tetran sodium pyrophosphate, tetra potassium pyrophosphate, and mixtures thereof. Thus, the oral preparation may contain polyphosphate anti-tartaric agent which is substantially free of tetrasodium pyrophosphate or substantially free of combinations of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium to sodium pyrophosphate is 3: 1 or in excess of 3: 1. An anti-tartaric agent comprising tetrasodium pyrophosphate in about 2% by weight of the oral preparation is particularly effective.

The antibacterial property enhancing agent (AEA) that enhances the release of said antibacterial agent to and retains it on oral surfaces is used in achieving effective amounts of effective range within the range from about 0.005 to about 4 in the oral composition. wt%, preferably about 0.1 to about 3 wt%, most preferably about 0.5 to about 2.5 wt. %.

The AEA may be a simple compound, preferably a polymerizable monomer, more preferably a polymer, the latter term being used in its fully generic sense, and e.g. 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 a natural or synthetic material, and may be water-insoluble or, preferably, water-soluble (saliva) or swellable (hydratable, hydrogel-forming). It has a (weight) average molecular weight of from about 100 to about 1,000,000, preferably from about 1,000 to about 1,000,000, and most preferably from about 2,000 or 2500 to about 250,000 or 500,000.

The AEA usually contains at least one release enhancing group, which is preferably an acidic group, such as sulfone, phosphone, or more preferably phosphone or carboxyl, or a salt thereof, e.g. alkali metal or ammonium, and at least one organic retention promoting group, preferably a plurality of both the release enhancing and retention enhancing groups, the latter groups preferably having the formula - (X) -R, wherein X is 0, N, S, SO, SO, P, PO or Si or έ έ the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or inert-substituted derivatives thereof, and n is 0 or 1 or more. The "inert-substituted derivatives" mentioned above are intended to include substituents on R which are generally not hydrophilic and do not significantly enhance the desired functions of the AEA as an agent to enhance the release of the antibacterial agent to and retain it on oral surfaces. disturb, such as halogen, e.g. Cl, Br, J, and carbo and the like.

Examples of such retention enhancing groups are tabulated below: η X _- (X) R_ Ο --- methyl, ethyl, propyl, butyl, isobutyl, t-butyl, cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl, etc.

1 O ethoxy, benzyloxy, thioacetoxy, phenoxy, carbonethoxy, carbonbenzyloxy, etc.

N ethylamino, diethylamino, propylamido, benzylamino, benzoyl amido, phenylacetamido, etc.

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

SO butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc.

50 butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

P diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylphenylphosphinyl, etc.

PO diethylphosphienoxy, ethylvinylphosphienoxy, methylallylphosphienoxy, methylbenzylphosphienoxy, methylphenylphosphienoxy, etc.

Trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl,. dimethylvinylsilyl, dimethylallylsilyl, etc.

The release enhancing group as used herein refers to a group that attaches the AEA (which carries the antibacterial agent) or binds substantively, adhesive, cohesive or otherwise to oral (e.g., tooth and gum) surfaces, whereby the antibacterial agent is applied to such surfaces "handed in". The organic retention enhancing group, which is generally hydrophobic, attached or otherwise bound the antibacterial agent to the AEA, thereby promoting retention of the antibacterial agent to the AEA and indirectly to the oral surfaces. In some instances, attachment of the antibacterial agent occurs by physical entrapment thereof by the AEA, particularly when the AEA is a cross-linked polymer, the structure of which inherently provides additional sites for such entrapment. The presence of a higher molecular weight, hydrophobic cross-linking moiety in the cross-linked polymer further enhances the physical entrapment of the antibacterial agent in or by the cross-linked AEA polymer.

The AEA is preferably an anionic polymer comprising a chain or backbone with repeating units, each preferably having at least one carbon atom and preferably at least one directly or indirectly pendant monovalent release enhancing group, and at least one directly or indirectly pendant nonovalent retention improving group contain minimum, vicinal or less preferred, otherwise bound to atoms, preferably carbon, in the chain. The polymer, although less preferred, may contain release enhancing groups and / or retention enhancing groups and / or other divalent atoms or groups as links in the polymer chain in place of or adjacent to carbon atoms, or as cross-linking moieties.

It is noted that any examples or illustrations of AEAs given herein, which do not contain both release enhancing groups and retention enhancing groups, can be chemically modified in a known manner and that they are also preferred in order to obtain the preferred AEAs containing both types of groups and preferably contain a multiple of each of these groups. In the case of the preferred polymeric AEAs, for maximum substantivity and delivery of the antibacterial agent to oral surfaces, it is desirable that the repeating units in the polymer chain or backbone containing the acid release enhancing groups, at least about 10 wt. %, preferably at least about 50 wt%, more preferably at least about 60 wt%, to 95 or 100 wt% of the polymer.

According to a preferred embodiment of the invention, the AEA comprises a polymer with repeating units, in which one or more phosphonic acid release enhancing groups are bound to one or more carbon atoms in the polymer chain. An example of such an AEA is poly (vinyl phosphonic acid) with units of the formula:

which, however, does not contain a retention enhancing group. However, a group of the latter type would be present in poly (1-phosphonopropene) with units of the formula:

II

A preferred phosphonic acid containing AEA for use in the invention is poly (beta-styrene phosphonic acid) with units of the formula:

III

wherein Ph represents phenyl, wherein the phosphonic acid release enhancing group and the phenyl retention enhancing group are bound to vicinal carbon atoms in the chain, or a copolymer of beta-styrene phosphonic acid with vinyl phosphonyl chloride, where the units of formula III alternate or are sometimes linked with units of formula I, or poly (alpha-styrene phosphonic acid) with units of formula

IV

wherein the release and retention enhancing groups are chain-bound.

These styrene phosphonic acid polymers and their copolymers with other inert ethylenically unsaturated monomers generally have molecular weights ranging from about 2000 to about 30,000, preferably from about 2500 to about 10,000. Such "inert" monomers do not significantly interfere with the intended function of copolymers used herein as an AEA.

Other phosphon-containing polymers include, e.g. phosphonated ethylene with units of the formula:

V

where n e.g. can be an integer or have a value, giving the polymer a molecular weight of about 3000? and sodium poly (butene-4,4-diphosphonate) with units of the formula:

VI

and poly (allyl-bis (phosphonoethyl alcohol)) with units of the formula:

VII

Other phosphonated polymers, e.g. poly (allyl phosphonoacetate), phosphonated polymethacrylate, etc., and the geminal diphosphonate polymers disclosed in European Patent Publication 0,321,233 can be used herein as AEAs, provided, of course, that they contain the organic retention enhancing groups defined above or by modification.

In one aspect of this invention, the oral composition comprises an orally acceptable carrier, an agent that effectively enhances the antibacterial effect of an antibacterial agent having an average molecular weight of from about 1,000 to about 1,000,000, the oral composition contains at least one functional group that enhances the release of the antibacterial effect and at least one organic group that enhances the retention of antibacterial effects, said agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium synthetic antionic linear polymeric polycarboxylate salt with a molecular weight of about 1,000 to 1,000,000, and polyphosphate anti-tartar agent, such as a mixture of potassium and sodium salts, the ratio of potassium to sodium in said composition being in the range of to less than about 3: 1, e.g. from about 0.37 to about 1.04: 1.

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

Synthetic anionic polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnesium, have previously been described as anti-tartar agents per se, e.g. Shedlovsky U.S. Patent 3,429,963; Gaffar U.S. Patent 4,152,420; U.S. Patent 3,956,480 to Dichter et al .; Gaffar U.S. Patent 4,138,477; and U.S. Patent 4,183,914 to Gaffar et al. It should be noted that the synthetic anionic polymeric polycarboxylates disclosed in these patents, when containing retention enhancing groups or by modification, can be used in the compositions and methods according to this invention and in so far the cited publications are hereby incorporated by reference.

These synthetic anionic polymeric polycarboxylates are often used in the form of their free acids or preferably partially or even more completely neutralized water-soluble or water-swellable (hydratable, gel-forming) alkali metal (e.g., potassium and preferably sodium) or ammonium salts. Preferred are 1: 4 to 4: 1 copolymers of maleic anhydride or maleic acid with another polymerizable ethylenically unsaturated monomer, preferably methyl methyl ether / maleic anhydride having a molecular weight (M.W.) of about 30,000 to about 1,000,000, most preferably about 30,000 to about 500,000. These copolymers are e.g. available as Gantrez b.v. AN 139 (M.W. 500,000), AN 119 (M.W. 250,000); and preferably S-97 pharmaceutical grade (M.W. 70,000) from the GAF Corporation.

Other polymeric polycarboxylates useful as AEA containing retention enhancing groups or containing modification include those disclosed in U.S. Patent 3,956,480 mentioned above, such as the 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter copolymer e.g. available 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, isobutyl vinyl ether, or N-vinyl-2-pyrrolidone.

Further active polymeric polycarboxylates disclosed in U.S. Pat. Nos. 4,138,477 and 4,183,914 mentioned above, which contain or by retention enhancing groups, include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic, and polymaleic acids. , and sulfoacrylic oligomers with a molecular weight of e.g. only 1000, available as Uniroyal ND-2.

Generally suitable are retention enhancing groups containing polymerized olefinically or ethylenically unsaturated carboxylic acids with an activated olefinic carbon-carbon double bond that functions readily in polymerization due to its presence in the monomer molecule in the alpha-beta position relative to a carboxyl group or part of a terminal methylene group. Illustrative of such acids are acrylic, methacryl, ethacryl, alpha-chloroacryl, croton, beta-acryloxypropion, sorbine, alpha-chloro-sorbine, cinnamon, beta-styrylacryl, mucon, itacon, citracon , mesacon, glutacon, aconitine, alpha-phenylacryl, 2-benzylacryl, 2-cyclohexylacryl, ange-line, umbelline, fumar, maleic acids and anhydrides. Other olefinic monomers that can be copolymerized with such carboxyl monomers include vinyl acetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxyl salt groups for water solubility.

Also useful in the invention are so-called carboxyvinyl polymers described as toothpaste components in U.S. Patent 3,980,767 to Chown et al., U.S. Patent 3,935,306 to Roberts et al., U.S. Patent 3,919,409 to Perla et al. al., U.S. Pat. No. 3,911,904 to Harrison, and U.S. Pat. No. 3,711,604 to Colodney et al. They are e.g. commercially available under the brand names Carbopol 934, 940 and 941 from BFGoodrich, these products consisting essentially of a colloidal water-soluble polymer of polyacrylic acid cross-linked with about 0.75 to about 2.0% polyallyl sucrose or poly-allyl pentaerythritol as cross-linking agent wherein the cross-linked structure and cross-links provide the desired improvement in hydrophobicity retention and / or physical entrapment of the antibacterial agent and the like. Polycarbophil is somewhat comparable in that it is a polyacrylic acid cross-linked with less than 0.2% divinyl glycol, the lower amount, lower molecular weight and / or lower hydrophobicity of this cross-linking agent tending to provide little or no retention improvement. . An example of a more effective retention-improving cross-linking agent is 2,5-dimethyl-1,5-hexadiene.

The synthetic anionic polymeric polycarboxylate component is most often a hydrocarbon with optional halogen or O-containing substituents and bonds as present in, for example, ester, ether and OH groups, and when present it is generally used in the present compositions in weight amounts of approximate to about 4% (generally at least about 005%).

The AEA may also include natural anionic polymeric polycarboxylates containing retention enhancing groups. Carboxymethylcellulose and other binders, gums and film formers lacking the above defined release enhancing and / or retention enhancing groups do not act as AEAs.

As illustrative of AEAs containing phosphinic and / or sulfonic acid release enhancing groups, mention may be made of polymers and copolymers containing units or parts derived from the polymerization of vinyl or allylphosphine and / or sulfonic acids which, as required, 2 (or 3) carbon atom are substituted by an organic retention enhancing group, e.g. with the formula defined above - (X) -R. Mixtures of these monomers can be used, and copolymers of one or more inert polymerizable ethylenically unsaturated monomers, such as those described above with respect to the useful synthetic anionic polymeric polycarboxylates, can be used. It should be noted that in these and other polymeric AEAs useful herein, usually only one acid release enhancing group is bonded to a particular carbon or other atom in the polymer backbone or branch thereof. Polysiloxanes containing, or by modification, pendant release enhancing groups and retention enhancing groups may also be used herein as AEAs. Also effective herein as AEAs are ionomers which contain, or by modification, release and retention enhancing groups. Ionomers are described on pages 546 - 573 of the Kirk Othmer Encyclopedia of Chemical Technology, 3rd edition, Supplement Volume,

John Wiley & Sons, Ine., Copyright 1984, the description of which is incorporated herein by reference. Also effective as AEAs herein, provided they contain or by retention enhancing groups, are polyesters, polyurethanes and synthetic and natural polyamides including proteins and proteinaceous materials, such as collagen, poly (arginine) and other polymerized amino acids.

When the oral preparation is made by first dissolving the polyphosphate and antibacterial agent in a humectant and surfactant and adding the AEA, in particular the polycarboxylate, step by step, the solution becomes clear and can be typified as a " microemulsion ".

When the amount of the polycarboxylate increases so that the entire oral preparation contains at least about 2.2% by weight thereof, the solution becomes cloudy and can be typified as a "macro emulsion". In such macroemulsion type preparations, the anti-plaque effect of the antibacterial agent appears to be optimized.

A desirable weight ratio of the substantially water-insoluble non-cationic antibacterial agent to the polyphosphate anti-tartar 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 anti-tartar action of the oral preparation, inhibitors of enzymatic hydrolysis of the polyphosphate are preferably present. Such agents consist of an amount of a fluoride ion source sufficient to provide 25 ppm to 5,000 ppm of fluoride ions, and 3% or more of the synthetic anionic polymeric polycarboxylate having a molecular weight of from about 1,000 to about 1,000,000, preferably about 30,000 to about 500,000.

The sources of fluoride ions, or the fluorine-providing component, as acid phosphatase and pyrophosphatase enzyme inhibitor component are well known in the art as anti-caries agents.

These compounds can be slightly soluble in water or can be completely water-soluble. They are characterized by their ability to release fluoride ions in water and by freedom from undesired reaction with other compounds of the oral 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 copper (I) fluoride, zinc fluoride, barium fluorosulfonate, ammonium fluorosulfonate, ammonium fluorosilonium ammonium fluoride sodium monofluorophosphate, aluminum mono- and difluorophosphate, and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides, such as sodium and tin (II) fluorides, sodium monofluorophosphate (MFP) and mixtures thereof are preferred.

The amount of a fluorine-providing compound depends to some extent on the type of compound, its solubility, and the type of 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), dental powder or dental tablets, an amount of such a compound which releases up to about 5,000 ppm of fluoride ions relative to the weight of the composition is considered sufficient. Any suitable minimum amount of such a compound can be used, but it is preferable to use sufficient compound to release about 300 to 2,000 ppm, more preferably about 800 to about 1,500 ppm, of fluoride ions.

Typically, in the cases of alkali metal fluorides, this component is present in an amount of up to about 2% by weight, based on the weight of the composition, and preferably in the range of about 0.05-1% by weight. In the case of sodium monofluorophosphate, the compound may be present in an amount of about 0.1-3% by weight, more typically about 0.76%.

In oral preparations such as mouthwashes, 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 ions.

Generally, about 0.005 to about 1.0% by weight of such a compound is present.

In certain major preferred forms of the invention, the oral composition may be of a substantially liquid nature, such as a mouthwash or mouthwash. In such a formulation, the carrier is typically a water-alcohol mixture, preferably including a wetting agent as described below. Generally, the weight ratio of water to alcohol is in the range from about 11 to about 20: 1, preferably from about 3: 1 to 10: 1, and most preferably from about 4: 1 to about 6: 1. The total amount of the water-alcohol mixture of this type of composition is typically in the range of from about 70 to about 99.9% by weight of the composition. The alcohol is typically ethanol or isopropanol. Ethanol is preferred.

The pH of such a liquid and other compositions of the invention generally ranges from about 4.5 to about 9, and typically from about 5.5 to 8. Preferably, the pH ranges from about 6 to about 8.0. It is noteworthy that the compositions of the invention can be used orally at a pH below 5 without causing significant decalcification or otherwise damage to dental enamel. The pH can be controlled with acid (e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) or buffered (such as with sodium citrate, benzoate, carbonate, or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In a certain other preferred form of this invention, the oral composition may be essentially solid or pasty in nature, such as dental powder, a dental tablet or a dentifrice, which is a toothpaste (dental cream) or gel dentifrice. The carrier of such solid or pasty oral preparations generally contains dentally acceptable polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimasium phosphate, aluminum bicarbonate, hydrated aluminum thereof. Other suitable polishing material includes the particular thermosetting resins described in U.S. Patent 3,070,510 issued December 15, 1962, such as melamine, phenolic, and urea formaldehydes, and interconnected polyepoxides and polyesters. Preferred polishing materials include crystalline silica with a particle size of up to about 5 microns, an average particle size of up to about 1.1 microns, and a surface area of up to about 50,000 cm 2 / gm, silica gel or colloidal silica, and complex amorphous alkali metal aluminum silicate.

When using clear gels on the face, a polishing agent of colloidal silica such as it is sold under the trade names SYLOID as Syloid 72 and Syloid 74 or under the trade name SANTOCEL as Santocel 100, alkali metal aluminum silicate complexes are particularly useful because they have refractive indices close by the refractive indices of gelling-fluid systems (including water and / or wetting agent) commonly used in dentifrices.

Many of the so-called "water-insoluble" polishing materials are anionic in nature and also include small amounts of soluble material. Insoluble sodium metaphosphate e.g. can be formed in any suitable manner as described by Thorpe's Dictionary of Applied Cnemistry, Vol. 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 very low water solubility and are therefore commonly referred to as insoluble metaphosphates (IMP). Therein, a minor amount of soluble phosphate material is present as impurities, usually a few percent such as up to 4% by weight. The amount of soluble phosphate material believed to include a soluble sodium trimetaphosphate in the case of insoluble metaphosphate can be reduced or removed by washing with water if desired. The insoluble alkali metal metaphosphate is normally used in the form of a powder with particle sizes such that no more than 1% of the material is greater than 37 µm.

The polishing material is generally present in solid or pasty formulations in weight concentrations from about 10% to about 99%. Preferably, it is present in amounts ranging from about 10% to about 75% in toothpaste, and from about 70 to about 99% in tooth powder. In toothpastes, when the polishing material is siliceous in nature, it is generally present in an amount of about 10-30% by weight. Other polishing materials are typically present in amounts of about 30-75% by weight.

In a toothpaste, the liquid carrier may comprise water and wetting agent typically in an amount ranging from about 10 wt% to about 80 wt% based on the weight of the composition. Glycerin, propylene glycol, sorbitol and polypropylene glycol are examples of suitable wetting agents / carriers. Liquid mixtures of water, glycerine and sorbitol also have advantages. In clear gels where the refractive index is an important consideration, about 2.5-30% by weight water, 0 to about 70% glycerine and about 20-80% by weight sorbitol are preferably used.

Toothpastes, creams and gels typically contain a natural or synthetic thickener or gelling agent in amounts from about 0.1 to about 10, preferably about 0.1 to about 5, weight percent. A suitable thickener is synthetic hectorite, a synthetic colloidal magnesium alkali metal silicate complex clay available as, for example, Laponite (e.g. CP, SP 2002, D) marketed by Laport Industries Limited. Laponite D analysis shows, in a weight-based approach, 58.00%

Si02f 25.40% MgO, 3.05% Na2O, 0.98% L12O, and a little water and trace metals. Its true specific weight is 2.53 and it has a clear bulk density (g / ml at 8% vapor) of 1.0.

Other suitable thickeners include Irish moss, iota carrageenan, gum tragacanth, starch polyvinylpyrrolidone, hydroxyethyl propyl cellulose, hydroxybutylmethyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose (e.g. as Natrosol), sodium carboxymethyl cellulose, and colloidal silica such as finely ground bromide

244). in some dentifrices prepared according to the present invention, especially when more than about 0.35 wt% of the water-insoluble antibacterial agent is used and a siliceous polishing agent is present in an amount of less than about 30 wt%, it may be desirable to add an agent that dissolves the antibacterial agent. Such solubilizers include humectant polyols such as propylene glycol, propylene glycol and hexylene glycol, cellosolves such as methyl cellosolve and ethyl cellosolve, vegetable oils and waxes containing at least about 12 straight chain carbon atoms such as olive oil, castor oil and petrolates and esters such as amyl acetate, ethyl acetate tate and benzyl benzoate.

It may be noted that, as usual, the oral preparations must be sold or otherwise distributed in suitably labeled packages. Therefore, have a mouthwash label describing it, in dust, as a mouthwash or mouthwash and with instructions for use; and a toothpaste, cream or gel will usually come in a squeezable tube, typically aluminum, lined lead or plastic, or other squeeze or pump dosers or pressurized dosers for measuring quantities, with a label describing it, in dust , like a toothpaste gel or dental cream.

Organic surfactants are used in the compositions of the present invention to obtain enhanced prophylactic action, to assist in obtaining a full and complete dispersion of the anti-tartar and anti-plaque agent through the oral cavity, and to assist the present make preparations more cosmetically acceptable. The organic surfactant is preferably anionic, nonionic or ampholytic in character, and it is preferred that a surfactant be used which gives detergent and foaming properties to the composition as a surfactant. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monoglyceride monosulfate of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecacylsulfonate sulfonate sulfonate sulfonate sulfonic sulfate 2-dihydroxypropane sulfonate, and the predominantly saturated higher aliphatic acylamides of lower aliphatic amino carboxylic acid compounds, such as those having 12-16 carbon atoms in the fatty acid, alkyl or acyl groups, and the like. Examples of the latter amides are N-lauroyl sarcosine, and the sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine, which should be essentially free of soap or similar higher fatty acid material. The use of these sarcosinate compounds in the oral compositions of the present invention is particularly advantageous because these materials exhibit a long-lasting and pronounced effect in inhibiting acid formation in the oral cavity due to carbohydrate degradation, in addition to their solubility in dental enamel in slightly reduce acidic solutions. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds that can react with them and have long hydrophobic chains (e.g., aliphatic chains with about 12 to 20 carbon atoms). which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene pieces, such as condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate) and polypropylene oxide (e.g. Pluronic materials).

Surfactant is typically present in an amount of about 0.1-5% by weight, preferably about 1-2.5%. It is noteworthy that surfactants can assist in the dissolution of non-cationic antibacterial agent thereby reducing the amount of solubilizing wetting agent required.

Various other materials can be included in the oral compositions of the invention such as whiteners, preservatives, silicones, chlorophylls and / or ammonia, such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, when present, are included in the compositions in amounts that do not substantially adversely affect the desired properties and characteristics. Significant amounts of zinc, magnesium and other metal salts and materials that are generally soluble and would complex with active components of the present invention should be avoided.

Furthermore, any suitable flavoring or sweetening material can also be used. Examples of suitable flavoring ingredients are flavoring oils, e.g. spearmint oil, peppermint, wintergreen, sassefras, cloves, sago, eucalyptus, marjoram, cinnamon, lime, and orange, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, xylitol, sodium cyclamate, perillartine, AMP (aspartylphenylalanine, methyl ester), saccharin and the like. Flavoring and sweetening agents may each, or together, preferably comprise about 0.1-5% or more of the composition. In addition, flavoring oil seems to help dissolve antibacterial agent.

In the preferred use of this invention, an oral composition of this invention, such as a mouthwash, or dentifrice containing the composition of the present invention, is preferably applied regularly to dental enamel, such as every day or every or second or third day, or preferably 1 to 3 times a day, at a pH from about 4.5 to about 9, generally about 5.5 to about 8, preferably about 6 to 8, for at least 2 weeks to 8 weeks or longer to life.

The compositions of this invention can be added in lozenges, or in chewing gum or other products, for example, by stirring in a warm gum base or coating the outer surface of a gum base, for which illustrative examples may be mentioned jelutong, rubber latex, vinylite resins, etc., preferably with conventional plasticizers and softeners, sugar or other sweeteners or the like such as glycose, sorbitol and the like.

The following examples further illustrate the present invention, but it is to be understood that the invention is not limited by the examples. All amounts mentioned herein and in the claims are by weight unless otherwise indicated.

In the following examples, the agent Triclosan, 2,4,4'-trichloro-2'-hydroxydiphenyl ether is designated "TCHE"; sodium lauryl sulfate is referred to as "SLS"; the copolymer of maleic anhydride and methyl vinyl ether available from GAF Corporation as "Gantrez S-97" is designated "Gantreztetrasodium pyrophosphate" is designated "pyrophosphate", sodium fluoride is designated "NaF".

Example I

The adsorption to and release of dental minerals for anti-plaque / anti-tartar action of agents is caused by adsorption of antibacterial agent to saliva-coated dental mineral hydroxyapatite disc in the presence of pyrophosphate and various amounts of polycarboxylate.

The formulations of the evaluated toothpastes are:

Parts by weight A B

Glycerin 10,000 10,000

Iota carrageenan 0.750 0.750

Sorbitol (70% solution) 30,000 30,000

Propylene glycol 0.500 0.500

Gantrez (13.02% solution) 19,000 15,500

Titanium dioxide 0.500 0.500

Water (deionized) 9,957 13,457

NaF 0.243 0.243

Sodium saccharin 0.300 0.300

Pyrophosphate 2,000 2,000

Sodium hydroxide (50%) 1,000 1,000

Silica polishing agent (Zeodent 113) 20,000 20,000

Silica thickener (Sylodent 15) 2,500 2,500

Flavoring oil 0.950 0.950 TCHE 0.300 0.300 SLS 2.000 2.000

Gantrez is present as A.I. in an 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 disc, hydroxyapatite (HA) obtained from the Monsanto Co., it is washed intensively with distilled water, collected by vacuum filtration, and allowed to dry overnight at 37 ° C. The dried HA is ground to a powder with a mortar and pestle. 150.00 mg of HA is compressed into a KBr pellet die (Barnes Analytical, Stanford, CT.) Chamber at 10,000 pounds (4,536 kg) in a Carver Laboratory press for 6 minutes. The resulting 13 mm slices are sintered in a Thermolyne oven for 4 hours at 800 ° C. Parafilm-stimulated whole saliva is collected in an ice-cooled beaker. The saliva is cleared by centrifugation at 15,000 g for 4 ° C. Sterilization of the clarified saliva is performed at 4 ° C with stirring by irradiating the sample with UV light for 1.0 hour.

Each sintered disc is hydrated with sterile water in a polyethylene test tube. The water is then removed and replaced with 2.00 ml of saliva. A saliva-containing web is formed by incubating the disc overnight at 37 ° C with continuous shaking in a water bath. After this treatment, the saliva is removed and the slices are treated with 1.00 ml of a solution-containing antibacterial agent (triclosan) in a dentifrice-liquid phase solution and incubated at 37 ° C with continuous shaking in a water bath. After 30 minutes, the disc is transferred to a new test tube and 5.00 ml of water is added followed by gentle shaking of the disc with a Vortex. The disc is then transferred to a new test tube and the washing procedure is repeated twice. Finally, the disc is carefully transferred into a new test tube to prevent co-transfer of any liquid along with the disc. Accordingly, 1.00 ml of methanol is added to the disk and shaken vigorously. The sample is left at room temperature for 30 minutes to extract adsorbed triclosan into 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 to HPLC (high performance liquid chromatography) vials for determination of the antibacterial agent concentration. Triplicate samples are used in all of these experiments.

The table below summarizes the data:

TABLE

Issue of TCHE to with

Toothpaste with saliva coated hydroxyapatite disc in n_g A 130 B 30

The data indicate that with an increasing amount of Gantrez (toothpaste A), there is a very large increase in release of TCHE to saliva coated dental minerals.

Example II

The following toothpaste is effective as an anti-plaque and anti-tartar preparation:

Parts by weight

Sorbitol (70%) 22.00

Irish moss 1.00

Sodium hydroxide (50%) 1.00

Gantrez (13.02% solution 19.00

Water (deionized) 2.69

Sodium monofluorophosphate 0.76

Sodium saccharin 0.30

Pyrophosphate 2.00

Hydrated alumina 48.00

Flavoring oil 0.95 TCHE 0.30 SLS 2.00

Example III

Mouth rinse water Share

Tetrasodium pyrophosphate 2.00

Gantrez S-97 2.50

Glycerin 10.00

Sodium fluoride 0.05

Sodium lauryl sulfate 0.20 TCHE 0.06

Flavoring oil 0.40

Refill water to 100.00

Example IV

Lozenge 75-80% sugar 1-20% corn syrup 0.1-1.0 flavoring oil 2% tetrasodium pyrophosphate 2.50% Gantrez S-97 0.01-0.05% NaF 0.01-0.1% TCHE

1-5% magnesium stearate lubricant 0.01-0.2% water

Example V

Chewing gum Share

Gum base 25.00

Sorbitol (70%) 17.00 TCHE 0.50-0.10

Tetrasodium pyrophosphate 2.00

Gantrez S-97 2.50

In a variant example of the previous example, Gantrez S-97 can be omitted.

Example VI

Chewing gum Share

Gum base 30r00 TCHE 0.50

Gantrez 2.00

NaP 0.05

Glycerin 0.50

Crystalline sorbitol 53.00

Tetrasodium pyrophosphate 2.00

Add flavoring oil and water to 100.00

In the preceding examples, improved results are also obtained when TCHE is replaced by each of the group consisting of phenol, 2,2'-methylene bis (4-chloro-6-bromophenol), eugenol and thymol, and / or when Gantrez is replaced by other AEAs such as Carbopols (eg 934), or styrene phosphonic acid polymers with molecular weights in the range of about 3,000 to 10,000 such as poly (beta styrene phosphonic acid), copolymers of vinyl phosphonic acid with beta styrene phosphonic acid, and poly (alpha styrene phosphonic acid), or sulfoacrylic acid a 1: 1 copolymer of maleic anhydride with ethyl acrylate.

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

The invention has been described with reference to certain preferred embodiments, and it will be appreciated that modifications and variations thereof, which are obvious to those skilled in the art, are within the scope of this application and the scope of the accompanying claims.

Claims (58)

An oral composition comprising, in an orally acceptable carrier, an effective anti-tartar amount of a material comprising about 0.1-3% by weight of at least one linear molecular dehydrated polyphosphate salt as an anti-tartar agent, an effective anti-tartaric agent. plaque amount of a substantially water-insoluble non-cationic antibacterial agent and up to about 4% by weight of an antibacterial activity-enhancing agent which increases the release of said antibacterial agent and its adhesion to oral surfaces, the weight ratio of polyphosphate ion to the antibacterial activity-enhancing agent ranges from about 1.6: 1 to about 2.7: 1. Oral preparation according to claim 1, wherein said antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated salicyl anilides, benzoic esters, halogenated carbanilides and phenolic compounds. The oral preparation according to claim 1, wherein said antibacterial agent is a halogenated diphenyl ether. An oral preparation according to claim 3, wherein said halogenated ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. Oral preparation according to claim 1, wherein said antibacterial agent is a phenolic compound. Oral preparation according to claim 5, wherein said phenolic compound is selected from the group consisting of phenol, thymol, eugenol and 2,2'-methylene bis (4-chloro-6-bromophenol), The oral formulation of claim 2, wherein said antibacterial agent is present in an amount of about 0.01-5% by weight. The oral formulation of claim 7, wherein said amount of the antibacterial agent is about 0.25-0.5%. The oral preparation of claim 1, wherein said linear molecularly dehydrated polyphosphate salt is an alkali metal pyrophosphate in an amount of about 1-2.5% by weight. The oral preparation of claim 9, wherein said alkali metal pyrophosphate is tetrasodium pyrophosphate. The oral formulation of any one of claims 1-10, wherein the weight ratio of the polyphosphate ion to the antibacterial activity-enhancing agent is about 1.7: 1 to about 2.3: 1. The oral formulation of any one of claims 1-11, wherein said carrier comprises water, wetting agent and a gelling agent, said oral formulation contains a dentally acceptable water-insoluble polishing agent and is a dentifrice. The oral formulation of any one of claims 1-11, wherein said carrier comprises water and a non-toxic alcohol and said oral formulation is a mouthwash. The oral formulation of any one of claims 1 to 13, wherein said antibacterial activity enhancing agent has an average molecular weight of from about 1,000 to about 1,000,000. The oral formulation of claim 14, wherein said antibacterial activity-enhancing agent contains at least one release-enhancing functional group and contains at least one organic retention-enhancing group. The oral formulation of claim 15, wherein said release enhancing group is an acidic group. The oral formulation of claim 16, wherein said release enhancing group is selected from the group consisting of carboxylic, phosphonic, phosphinic and sulfonic acids, and their salts, and mixtures thereof. The oral preparation of claim 17, wherein said organic retention enhancing group comprises the formula - (A) nR, wherein X is O, N, S, SO, SO2, PO or Si, R hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic or their inert-substituted derivatives, and η is 1 or 0. The oral preparation of claim 17 and the preceding claims, wherein said antibacterial enhancing agent is an anionic polymer containing more than one release-enhancing and organic retention-enhancing groups. The oral formulation of claim 19, wherein said anionic polymer is a chain containing repeating units, each comprising at least one carbon atom. The oral preparation of claim 20, wherein each unit contains at least one release-enhancing group and at least one organic retention-enhancing group bonded to the same or neighboring or other atoms in the chain. The oral formulation of claim 17, wherein the release enhancing group comprises a carboxylic group or a salt thereof. The oral composition of claim 22, in the preceding claims, wherein the antibacterial enhancing agent is a copolymer of maleic acid or anhydride with another ethylenically unsaturated polymerizable monomer or a salt thereof. The oral formulation of claim 23, wherein said other monomer is methyl vinyl ether in a 4: 1 to 1: 4 molar ratio with the maleic acid or anhydride. The oral formulation of any of claims 24, wherein said copolymer has a molecular weight of about 30,000-1,000,000. The formulation of claim 25, wherein the copolymer has an average molecular weight of about 70,000. The composition of claim 17, wherein the release enhancing group comprises a phosphonic acid group or salt thereof. The composition of claim 27, wherein the antibacterial activity-enhancing agent is poly (beta-styrene-phosphonic acid), poly (alpha-styrene-phosphonic acid) or a copolymer of either styrene-phosphonic acid with the other or with another inert polymerizable ethylenically unsaturated monomer or its salts. The composition of claim 28, wherein said antibacterial activity enhancing agent has a molecular weight of from about 1,000 to about 30,000. An oral preparation according to any one of claims 1-29, containing a fluoride ion supplying source. A method of controlling oral plaque comprising applying a plaque-controlling amount of a composition to oral surfaces as defined in any of claims 1-30. 32. Oral composition comprising an orally acceptable carrier, an agent that effectively enhances the antibacterial activity of an antibacterial agent, which has an average molecular weight of from about 1,000 to about 1,000,000, contains at least one functional group that releases the antibacterial effect. and contains at least one organic group which enhances the retention of the antibacterial effect, said agent containing said groups free of or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer carboxylate salt having a molecular weight of from about 1,000 to about 1,000. 000, and a polyphosphate anti-tartaric agent, wherein said polyphosphate anti-tartaric agent is a mixture of potassium and sodium salts, the ratio of potassium to sodium in said composition being in the range from less than about 3: 1. The oral formulation of claim 32, wherein said amount of potassium to sodium is from about 0.37: 1 to about 1.04: 1. The oral composition of claim 32, wherein said release enhancing group is selected from the group consisting of phosphonic, phosphinic and sulfonic acids, and their salts and mixtures thereof. The oral preparation of claim 33, wherein said organic group which enhances the retention comprises the formula - (X) n R, wherein X 0, N, S, SO, SO 2, PO or Si, R is a hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic or their inert-substituted derivatives, and η is 1 or 0. 36. An oral composition comprising an orally acceptable carrier, an agent effective in enhancing the antibacterial effect of an antibacterial agent having an average molecular weight of from about 1,000 to about 1,000,000, at least one of which releases the antibacterial effect. and contains at least one organic group which enhances the retention of the antibacterial effect, said agent containing said groups and being free or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt with a molecular weight of about 1,000 to about 1,000 .000 and polyphosphate anti-tartar agent. The oral formulation of claim 36, wherein said release enhancement is selected from the group consisting of phosphonic, phosphinene sulfonic acids, and their salts, and mixtures thereof. The oral preparation of claim 37, wherein said organic retention enhancing group comprises the formula - (X) n R, wherein X is o, N, S, SO, SO 2, PO or Si, R hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic, or their inert-substituted derivatives, and η is 1 or 0. 39. An oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, an antibacterial enhancer, having an average molecular weight of from about 1,000 to about 1,000. 000, contains at least one release-enhancing functional group and contains at least one organic retention-enhancing group, said agent containing said groups is free of or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight from about 1,000 to about 1,000. 000, and polyphosphate anti-tartar agent. 40. An oral composition comprising an orally acceptable carrier, an agent effective to enhance the antibacterial effect of the antibacterial agent, having an average molecular weight of from about 1,000 to about 1,000,000, containing at least one functional group that delivers the release of enhances the antibacterial effect and at least one organic group which enhances the retention of the antibacterial effect, said agent containing said groups free or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt with a molecular weight of about 1,000 to about 1,000. 000, and a polyphosphate anti-tartaric agent where the weight ratio of the polyphosphate of said polyphosphate anti-tartaric agent to said antibacterial agent ranges from in excess of 0.72: 1 to less than 4: 1. The oral formulation of claim 40, wherein said weight ratio is from about 1: 1 to about 3.5: 1. The oral formulation of claim 40, wherein said weight ratio is from 1.6: 1 to about 2.7: 1. 43. An oral composition comprising an orally acceptable carrier, an agent effective in enhancing the antibacterial effect of an antibacterial agent having an average molecular weight of from about 1,000 to about 1,000,000, containing at least one functional group that releases the enhances antibacterial effect and contains at least one organic group which enhances the retention of the antibacterial effect, and polyphosphate anti-tartar agent, provided that the composition is free of or substantially free of tetrasodium pyrophosphate. 44. An oral composition comprising an orally acceptable carrier, an agent effective in enhancing the antibacterial effect of an antibacterial agent having an average molecular weight of from about 1,000 to about 1,000,000, at least one functional group that delivers the release of the enhances antibacterial effect and contains at least one organic group which enhances the retention of the antibacterial effect, and polyphosphate anti-tartar agent, provided that the composition is free of or substantially free of a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium until sodium pyrophosphate is 3: 1 or in excess of 3: 1. 45. Oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent and polyphosphate anti-tartar agent, with the proviso that the composition is free of or substantially free of tetrasodium pyrophosphate. . 46. Oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent and polyphosphate anti-tartar agents, provided that the composition is free of or substantially free of a combination of tetra potassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium to sodium pyrophosphate is 3: 1 or in excess of 3: 1. 47. An oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, an antibacterial enhancing agent having an average molecular weight of about 1,000 to about 1,000,000, contains at least one release-enhancing functional group and contains at least one organic retention-increasing group, said agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight from about 1,000 to about 1,000,000, and polyphosphate anti-tartar agent, with the proviso that the composition is free of or substantially free of tetrasodium pyrophosphate. 48. An oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, an antibacterial enhancing agent having an average molecular weight of 1,000 to about 1,000,000. contains at least one release-enhancing functional group and contains at least one organic retention-enhancing group, said agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of about 1,000 up to about 1,000,000 and polyphosphate anti-tartar agent with the proviso that the composition is free of or substantially free of a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium to sodium pyrophosphate is 3: 1 or in excess of 3: 1 . 49. An oral composition comprising an orally acceptable carrier and an agent that effectively enhances the antibacterial effect of an antibacterial agent having an average molecular weight of 1,000 to about 1,000,000, containing at least one functional group that enhances the release of the antibacterial effect, and contains at least one organic group, which increases the retention of the antibacterial effect, said agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight of about 1,000 to about 1,000 .000, and a polyphosphate anti-tartaric agent, wherein said preparation contains potassium and sodium salts or ions, the ratio of potassium to sodium in said preparation being in the range of less than 3: 1. The oral composition of claim 48, wherein said potassium to sodium ratio is from about 0.37: 1 to about 1.04: 1. 51. An oral composition comprising an orally acceptable carrier, a substantially water-insoluble non-cationic antibacterial agent in an amount of about 0.25-0.35%, and a polyphosphate anti-tartar agent. 52. An oral composition comprising an orally acceptable carrier, a substantially water-insoluble non-cationic antibacterial agent in an amount of 0.25-0.35% and a polyphosphate anti-tartar agent, said polyphosphate anti-tartar agent being a mixture. of potassium and sodium salts, the ratio of potassium in said composition being in the range of less than about 3: 1. The oral formulation of claim 51, wherein said ratio is from about 0.35: 1 to about 1.04: 1. 54. Oral preparation comprising an orally acceptable carrier, a substantially water-insoluble non-cationic antibacterial agent in an amount of about 0.25-0.35% and a polyphosphate anti-tartar agent, provided that the preparation is free of or virtually free of tetrasodium pyrophosphate. 55. Oral preparation comprising an orally acceptable carrier, a substantially water-insoluble non-cationic antibacterial agent in an amount of about 0.25-0.35%, and a polyphosphate anti-tartar agent, provided that the composition is free of or is practically free from a combination of tetrasodium pyrophosphate and tetra potassium pyrophosphate in which the ratio of potassium to sodium pyrophosphate is 3: 1 or in excess of 3: 1. 56. An oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, an antibacterial enhancer agent having an average molecular weight of from about 1,000 to about 1,000,000, contains at least one release-enhancing functional group and contains at least one organic retention-enhancing group, said agent containing said groups being free of and substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt of molecular weight from about 1,000 to about 1,000,000, and a polyphosphate anti-tartar agent wherein the polyphosphate anti-tartar agent is a mixture of potassium and sodium salts, the ratio of potassium to sodium in said composition being in the range of less than 3: 1 . The oral formulation of claim 55, wherein said ratio is from about 0.37: 1 to about 1.04: 1. 58. An oral composition comprising an orally acceptable carrier, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent and an antibacterial activity-enhancing agent having an average molecular weight of from about 1,000 to about 1,000,000 containing at least one release-enhancing functional group and containing at least one organic retention-enhancing group, said agent-containing said groups being free of or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymer polycarboxylate salt having a molecular weight from about 1,000 to about 1,000,000, said composition containing potassium and sodium salts or ions, the ratio of potassium to sodium in said composition being in the range of 0.37: 1 to 1.04: 1.