NL8903187A - ANTIBACTERIAL ANTI-PLAQUE PREPARATION. - Google Patents

Description

Title: Antibacterial anti-plaque preparation.

DESCRIPTION

The invention relates to a dental oral antibacterial anti-plaque preparation. More particularly, the invention relates to an oral dental treatment composition containing a substantially water-insoluble non-cationic antibacterial agent which provides effective plaque inhibition.

Dental plaque is a soft deposit that forms on teeth as opposed to tartar, which is a hard calcified deposit on teeth. Unlike tartar, plaque can form on any part of the tooth surface, including in particular at the gumline.

In addition to being an ugly face, dental plaque is involved in the development of gingivitis.

It is therefore particularly desirable that anti-microbial agents known to reduce plaque be included in oral preparations. Often cationic antibacterial agents have been proposed.

In addition, in U.S. Pat. No. 4,022,880 to Vinson et al., A zinc ion-providing compound as an anti-tartar agent is mixed with an antibacterial agent that effectively retards the growth of plaque bacteria. The zinc compounds disclose a wide variety of antibacterial agents including cationic materials such as guanides and quaternary ammonium compounds, as well as non-cationic compounds such as halogenated salicylic anilides and halogenated hydroxydiphenyl ethers. The non-cationic antibacterial anti-plaque compound Triclosan, a halogenated hydroxydiphenyl ether, has also been described in combination with zinc citrate trihydrate in European Patent Publication 0,161,899 to Saxton et al. Triclosan is also described in Davis European Patent Publication 0.271.332 as a component of toothpaste that contains a solvent, such as propylene glycol.

The cationic antibacterial materials such as chlorhexidine, benzthonium chloride and cetylpyridinium chloride have been thoroughly investigated as antibacterial anti-plaque agents. However, they are generally ineffective when used with anionic materials. Non-cationic antibacterial materials, on the other hand, may be compatible with anionic components in an oral preparation.

Oral preparations are normally, however, mixtures of many components and even such typically neutral materials as wetting agents can affect the properties of such preparations.

In addition, even non-cationic antibacterial agents may have limited anti-plaque effectiveness with commonly used materials such as polyphosphates, which are used as anti-tartar agents and are described together in British Patent Publication 2,200,551 to Gaffar et al. And in the European United States Patent Application No. 3951605, filed on August 25, 1989, shows that anti-plaque effectiveness is greatly enhanced by a means of enhancing antibacterial properties {AEA, standing for " antibacterial-enhancing agent ") that improves the release of said antibacterial agent to and retains it on oral surfaces and to use optimal amounts and ratios of polyphosphate and AEA.

An advantage of this invention is that it provides an oral composition in which a substantially water-insoluble non-cationic antibacterial agent and an AEA are present for the inhibition of plaque formation, the oral composition containing a liquid carrier acceptable for oral use, which the antibacterial agent allows to dissolve in an effective anti-plaque amount in the saliva.

Another advantage of this invention is that the AEA improves the delivery and retention of small but effective anti-plaque amounts of the antibacterial agent on teeth and soft tissues in the mouth.

Another advantage of this invention is that it provides an oral anti-plaque preparation that effectively reduces the incidence of gingivitis.

Further advantages of this invention will become apparent upon reading from the description below.

In accordance with certain aspects of the invention, this invention relates to an oral composition comprising an effective anti-plaque amount of a substantially water-insoluble, non-cationic antibacterial agent, about 0.005-4% by weight of an antibacterial property enhancer. enhances delivery of said antibacterial agent to and retains it on oral surfaces and a carrier acceptable for use in the mouth which enables said antibacterial agent to dissolve in an effective anti-plaque amount in the saliva, which oral preparation is essentially free of polyphosphate acting as an anti-tartar agent.

Typical examples of water-insoluble non-cationic antibacterial agents, which are particularly desirable from the standpoint of anti-plaque effectiveness, safety and formulation, are:

Halogenated diphenyl ethers: 21,4,4'-trichloro-2-hydroxydiphenyl ether (Triclosan) 2,2'-dihydroxy-5,51-dibromo diphenyl ether.

Halogenated salicylanilides: 4 ', 5-dibromosalicylanilide 3,4', 5-trichlorosalicylanilide 3,4 ', 5-tribromosalicylanilide 2,3,3', 5-tetrachlorosalicylanilide 3,3,3 ', 5-tetrachlorosalicylanilide 3.5-dibromo-3 trifluoromethyl-salicylanilide 5-n-octanoyl-3'-trifluoromethyl-salicylanilide 3,5-dibromo-41-trifluoromethyl-salicylanilide 3,5-dibromo-3'-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 its homologues, mono- and polyalkyl and aromatic halogen (e.g. F, Cl, Br, J) phenols, resorcinol and catechol and their derivatives and bisphenol compounds).

Phenol and are 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 aralkylhalophenols: methyl-p-chlorophenol ethyl-p-chlorophenol n-propyl-p-chlorophenol n-butyl-p-chlorophenol n-amy1-p-chlorophenol sec-amyl-p-chlorophenol n-hexy1 -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-arayl-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, m-dimethyl-p-chlorophenol o-phenylethyl-p-chlorophenol o-phenylethyl-m-methyl-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-methyl-p-chlorophenol 6-isopropyl-2-ethyl-3-methyl-p-chlorophenol 2-sec. amyl-3,5-dimethyl-p-chlo orphenol 2-diethylmethyl-3,5-dimethyl-p-chlorophenol 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 / in-dimethyl-o-bromophenol 2-phenylphenol 4-chloro-2-methylphenol 4-chloro-3-methylphenol 4-chloro-3,5-dimethylphenol 2,4-dichloro-3,5-dimethylphenol 3,4 5,6-tetrabromo-2-methylphenol 5-methyl-2-pentylphenol 4-isopropyl-3-methylphenol 5-chloro-2-hydroxydiphenylmethane.

Resorcinol and its derivatives: methyl resorcinol, resorcinol ethylresorcinol n-propylresorcinol n-butylresorcinol amylresorcinol n-n-n-hexylresorcinol heptylresorcinol n-octylresorcinol n-nonylresorcinol fenylresorcinol benzyl resorcinol fenylethylresorcinol fenylpropylresorcinol p-chloorbenzylresorcinol 5-chloro-2,4-dihydroxydiphenylmethane 41-chloro-2 4-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 non-cationic antibacterial agent is present in the oral composition in an effective anti-plaque amount of normally about 0.01-5% by weight, preferably about 0.03-1%, more preferably about 0.25-0% .5%, or about 0.25% to less than 0.5%, and most preferably about 0.25-0.35%, e.g. about 0.3%, in a dental care agent, or preferably about 0.03 - 0.3% by weight, most preferably about 0.03 - 0.1%, in a mouthwash or liquid dental care agent.

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%.

The preferred halogenated diphenyl ether is triclosan. The preferred phenolic compounds are phenol, thymol, eugenol, hexylresorcinol and 2,2'-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 van 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 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 O, N, S, SO, SO_, P, PO or Si or nz 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.

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.

50 butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc.

SO ^ butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

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

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

51 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 monovalent retention enhancing group is minimal, 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 be 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 repeat units, in which one or more phosphonic acid release enhancing groups are bonded 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:

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

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 polytalpha-styrene phosphonic acid) with units of formula

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:

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

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

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 the invention, the oral composition comprises a carrier acceptable for use in the mouth, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, and an antibacterial property improver having an average molecular weight of about 1000 to about 1,000. 000, containing at least one release-enhancing functional group and at least one organic retention-enhancing group, which agent with these groups is free or substantially free of water-soluble alali metal or ammonium synthetic anionic linear polymeric polycarboxylate salts of molecular weight from about 1000 to about 1,000. 000.

In another preferred embodiment, the AEA may comprise a synthetic anionic polymeric polycarboxylate. Although not used in the present invention to cooperate with polyphosphate anti-tartaric agent, synthetic anionic polymeric polycarboxylate having a molecular weight of about 1000 to about 1,000,000, preferably about 30,000 to about 500,000, has been used as an inhibitor of alkaline phosphatase enzyme for optimizing the anti-tartar activity of linear molecularly dehydrated polyphosphate salts, as described in U.S. Patent 4,627,977 to Gaffar et al. In British Patent Publication 2,200,551, the polymeric polycarboxylate is indeed disclosed as an optional ingredient in oral preparations which linear molecularly dehydrated polyphosphate salts and substantially water-insoluble non-cationic antibacterial agent. In the context of the present invention, it is further noted that such polycarboxylate significantly enhances the release and retention of the nonionic antibacterial anti-plaque agent on tooth surfaces when interacting with another ingredient (ie molecularly dehydrated polyphosphate), a ingredient with which the polymeric polycarboxylate interacts is absent; e.g. when the ingredient with which the polymeric polycarboxylate interacts is, in particular, the non-cationic antibacterial agent.

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, where they contain retention enhancing groups or by modification, can be used in the compositions and methods of the present invention and so far the quoted publications are hereby incorporated by reference.

The synthetic anionic polymeric polycarboxylates used herein are known products, which are often used in the form of their free acids or, preferably, in the form of their partially or even more completely neutralized water-soluble alkali metal (eg, potassium and most preferably sodium -) or ammonium salts. Preference is given to 1; 4 to 4: 1 copolymers of maleic anhydride or maleic acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl 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 GAP 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 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., 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 primarily a hydrocarbon with optionally halogen and O-containing substituents and bonds, such as e.g. present in ester, ether and OH groups, and is used in the compositions of the invention in amounts by weight of about 0.05-4%, preferably 0.05-3%, most preferably 0.1-2%.

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) n ~ 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.

In one aspect of the present invention, the AEA having an average molecular weight of about 1,000 to about 1,000,000 contains at least one release enhancing functional group and at least one organic retention enhancing group, which agent containing these groups is free or substantially free is of water-soluble synthetic alkali metal or ammonium anionic linear polymeric polycarboxylate salts having a molecular weight of from about 1,000 to about 1,000,000.

In the present invention, a preferred oral preparation is a dental treatment agent containing about 0.3% by weight of the antibacterial agent (e.g., triclosan) and about 1.5-2% by weight of the polycarboxylate as AEA.

Without being bound by theory, it is believed that the AEA, especially polymer AEA, is generally an anionic film-forming material, which is believed to bind to dental surfaces, forming a (continuous film over the surfaces, preventing the adhesion of bacteria to tooth surfaces It is possible that the non-cationic antibacterial agent forms a complex or other form of association with the AEA, thereby forming a film of a complex or the like over the tooth surfaces. of the AEA and the improved release and film-forming property of the AEA and the improved release and retention of the antibacterial agent on dental surfaces, thanks to the AEA, have been shown to make dental surfaces unfavorable for bacterial accumulation, in particular because the direct bacteriostatic action of the antibacterial agent controls bacterial growth, making it oral formulation by the combination of three modes of action: 1) improved release, 2) long retention time on tooth surfaces, and 3) prevention of bacterial adhesion to tooth surfaces, rendered effective in plaque reduction. Similar anti-plaque effectiveness is achieved in soft tissue in the mouth at or near the edge of the gum.

According to the present invention, the oral-acceptable carrier is effective in allowing the substantially water-insoluble non-cationic antibacterial to dissolve in saliva in an effective anti-plaque amount.

In the oral preparation, a carrier acceptable for use in the mouth comprises an aqueous phase with a wetting agent present. In a gel-shaped dental care agent, typically containing about 5-30% by weight of a siliceous polishing agent, water is normally present in an amount of at least about 3% by weight, generally about 3-35%, and the total amount of wetting agent, preferably glycerine and / or sorbitol, typically about 6.5-75 or 80% by weight of the oral gelled dental treatment composition. Reference herein to sorbitol typically refers to the material as commercially available in 70% aqueous solutions.

The gelled dental care agents, when the amount of the antibacterial agent is about 0.25-0.35 wt%, do not need any further ingredient in the oral suitable carrier to dissolve the antibacterial agent, although the presence of a such a solvent is optional. When the amount of antibacterial agent is less than about 0.25 wt%, e.g. about 0.01 to about 0.25% by weight, therefore, a dissolving agent should be present to ensure sufficient dissolution in the saliva for effective anti-plaque action. When the amount of antibacterial agent is above about 0.35 wt%, e.g. about 0.35 to about 0.5 or more, say 5%, should therefore be a solubilizing agent, otherwise a significant portion of the antibacterial agent would remain insoluble.

When the oral preparation is a dental treatment agent containing about 30-75% by weight of a dental polish acceptable for dental purposes, the presence of such a solvent is also optional.

When the oral preparation is a mouthwash or liquid dental treatment agent, the oral carrier comprises at least one ingredient from the group of surfactants, flavoring oils and non-toxic alcohols, each of which contributes to the dissolution of the antibacterial agent, and again the presence of such solvent optional.

When a solvent is present in oral compositions of the present invention, it is typically in an amount of about 0.5-20% by weight, while an amount of only about 0.5% by weight is already sufficient when the amount of the substantially water-insoluble non-cationic antibacterial agent is low, say up to about 0.3 wt%. When larger amounts, such as at least about 0.5 wt% antibacterial agent, are present and especially when a siliceous polishing agent is also present in an amount of about 5-30 wt%, it is desirable that at least about 5 wt%, normally up to about 20% by weight or more of the solvent is present. It is noted that the dental treatment agent may exhibit a tendency to separate into liquid and solid parts when more than about 5% by weight of the solvent is present.

The agent which is or may be present in saliva to dissolve the antibacterial agent may be included in the water-wetting carrier. Such solvents include wetting polyols such as propylene glycol, dipropylene 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 and benzyl benzoate. When speaking of "propylene glycol" here, it includes 1,2-propylene glycol and 1,3-propylene glycol. Significant amounts of polyethylene glycol, especially with a molecular weight of 600 or more, should be avoided because polyethylene glycol effectively inhibits the antibacterial activity of the non-cationic antibacterial agent. When polyethylene glycol (PEG) 600 e.g. together with triclosan is present in a weight ratio of triclosan: 1 PEG 600, the antibacterial activity of triclosan is reduced by a factor of about 16 compared to the value in the absence of the polyethylene glycol.

In accordance with aspects of this invention, an oral dental treatment composition may have a substantially gel-like character, such as a gelled dental treatment agent. Such gel-shaped oral preparations contain silicon-containing dental polishing material. Preferred polishing materials include crystalline silica of particle sizes up to about 5 µm, average particle size up to about 1.1 µm, and surface area up to about 50,000 cm2 / g, silica gel or colloidal silicon oxide and complex amorphous alkali metal aluminosilicate .

When visually clear or opaque gels are used, a colloidal silica polishing agent such as products marketed under the SYLOID brand such as Syloid 72 and Syloid 74, or under the brand SANTOCEL such as Santocel 100, or alkali metal aluminosilicate complexes ( ie silicon oxide combined in its matrix with alumina) are particularly useful, because they are compatible with a gel-like texture and have refractive indices close to the refractive indices of gelling liquid (usually water and / or wetting agent) commonly used in dental treatments) systems.

The polishing material is generally present in the oral dental treatment compositions, such as toothpaste or gel preparations, in weight concentrations from about 5 to about 30%.

In the aspect of this invention, wherein the oral composition is a dental treatment agent, a carrier acceptable for use in the mouth comprising an aqueous phase with a wetting agent which is preferably glycerine and / or sorbitol is present, with water normally present in an amount of about 15-35 or 40% by weight, and glycerin and / or sorbitol are typically present in a total amount of about 20-75% by weight of the oral dental treatment composition, usually in an amount of about 25- 60%. Reference herein to sorbitol again refers to the material as is normally commercially available in 70% aqueous solutions.

In this invention, the oral dental treatment composition may be primarily pasty in nature, such as a toothpaste (dental cream), although it is used when siliceous polishing agent (which is not generally the case because such material is typically not used in amounts above about 30% by weight. ) can be gel-like in character. The carrier of the oral dental treatment composition contains polishing material that is acceptable for dental purposes, examples of such polishing materials being water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dicalcium phosphate dihydrate, anhydric dicalcium phosphate, calcium carbonate, aluminum oxysodium silicate, silicate silicate. thereof, with each other or with hard polishing materials, such as calcined alumina and zirconium silicate, which material comprises the powdered thermosetting resins described in U.S. Pat. No. 3,070,510, such as melamine phenol resins and urea formaldehydes, and cross-linked polyepoxides and polyesters . Preferred polishing materials include insoluble sodium metaphosphates, dicalcium phosphate and hydrated alumina.

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 in Thorpe's Dictionary of Applied Chemistry, 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.

Hydrated alumina is an example of a polishing material that is substantially nonionic in character. Normally it has a small particle size, ie at least about 85% of the particles - is less than 20 µm and, like gibbsite, is classified (alpha-aluminum oxide trihydrate) which is normally chemically represented as Al ^ O ^. SH ^ O or Al (OH). The average particle size of gibbsite is normally about 6-9 µm. A typical grade has the following particle size distribution: size (ym) percentage <30 94 - 99 <20 85 - 93 <10 56 - 67 <5 28 - 40

The polishing material is generally present in the cream, pasty or gel formulations in amounts by weight from about 30 to about 75%.

Dental creams, dental creams or dentifrices, as well as gelled dentifrices, typically contain a natural or synthetic thickening or gelling agent in amounts from about 0.1 to about 10, preferably about 0.5 to about 5%. A suitable thickener is synthetic colloidal magnesium alkali metal silicate complex clay, e.g. is commercially available as Laponite (e.g. CP, SP 2002, D) from Laporte Industries Limited. Laponite D analysis shows, by weight, approximately the following composition: 58.00% SiO2, 25.40% MgO, 3.05% Na2O, 0.98% Li2O, and a little water and trace metals. Its actual specific gravity is 2.53 and its apparent bulk density (g / ml at 8% moisture) is 1.0.

Other suitable thickening or gelling agents, or thickeners, include Irish moss, iota carrageenan, gum tragacanth, starch, polyvinyl pyrrolidone, hydroxyethylpropyl cellulose, hydroxybutylmethyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose (e.g. available as Natrosol), polycarbonate, silica, cellulose present, colloidal silica such as the materials available as the fine powders Syloid 244 or

Sylodent 15.

In the aspect of the present invention, wherein the oral composition is a mouthwash liquid or liquid dental treatment agent that is substantially of a liquid nature, the carrier, especially in a mouthwash liquid, is normally a water-alcohol mixture. Generally, the weight ratio of water to alcohol ranges from about 1: 1 to about 20; 1, preferably about 3: 1 to 10: 1, and more preferably about 4: 1 to about 6: 1. The total amount of water-alcohol mixture in this type of composition is normally in the range of about 70 to about 99.9 wt. %. The alcohol is a non-toxic alcohol such as ethanol or isopropanol. Humectants such as glycerine and sorbitol can be present in amounts of about 10-30% by weight. Liquid dental treatments typically contain about 50 to 85% water, may contain about 0.5 to 20% by weight of non-toxic alcohol, and may also contain about 10 to 40% by weight of wetting agent, such as glycerine and / or sorbitol. Reference herein to sorbitol refers to the material normally available commercially in 70% aqueous solutions. Ethanol is the preferred non-toxic alcohol. The alcohol is believed to contribute to the dissolution of the water-insoluble non-cationic antibacterial agent as it is believed to do the flavoring oil.

As mentioned, the non-cationic antibacterial agent is substantially insoluble in water. However, in the present invention, where the AEA, such as polycarboxylate, is present in the mouthwash liquid or the liquid dental treatment agent, it is believed that the organic surfactant, the flavoring oil or the non-toxic alcohol help to dissolve the antibacterial agent thereby helps to reach soft tissue in the mouth at or near the gums as well as tooth surfaces. Organic surfactants and / or flavoring oils can also help dissolve the antibacterial agents as optional ingredients in oral dental treatments.

Organic surfactants are also used in the compositions of the present invention to achieve a stronger prophylactic action, contributing to achieving thorough and complete dispersion of the anti-plaque antibacterial agent throughout the oral cavity, and make the present compositions more cosmetically acceptable. The organic surfactant is preferably anionic, nonionic or ampholytic in character, and it is preferred that a surfactant be used which provides detergent and foaming properties to the composition. 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 which can react with them and have long hydrophobic chains (eg aliphatic chains with about 12 to 20 carbon atoms), which condensation products ("ethoxamers") hydrophilic polyoxyethylene pieces, such as condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (eg sorbitan monostearate) and polypropylene oxide (eg Pluronic materials).

Surfactant is normally present in amounts of about 0.5-5% by weight, preferably about 1-2.5%.

When the oral composition is a liquid dental treatment agent, the natural or synthetic thickening or gelling agent as described is normally present in amounts from about 0.1 to about 10, preferably from about 0.5 to about 5%.

In general, liquid dental treatments do not contain a polish. However, as described in U.S. Pat. No. 3,506,757 to Salzmann, about 0.3-2.0% by weight of a high molecular weight polysaccharide above 1,000,000 containing mannose, glucose, potassium glucuronate and acetyl groups in a ratio of about 2: 1: 1: 1 are used as a suspending and thickening agent in a liquid dental care agent, which also includes about 10 - 20% of a palette material such as hydrated alumina, dicalcium phosphate dihydrate, calcium pyrophosphate, insoluble sodium metaphosphate, anhydrous dicalcium phosphate , calcium carbonate, magnesium carbonate, magnesium oxide, silicon oxide, mixtures thereof and the like.

Without being bound by a theory that achieves the advantages of the invention, it is believed that an aqueous moisturizing carrier is normally solubilized in mobile phase surfactant micelles (i.e., without gelling agent and polishing agent, if present in a dental treatment composition). The mobile phase solution of the dental treatment agent can be diluted during use by saliva causing a precipitation of triclosan. Thus, it is found that even in the absence of a special solubilizing material for triclosan, when the amount of triclosan is about 0.25-0.35 wt. %, and AEA such as the polycarboxylate is present, sufficient triclosan is present to exert excellent anti-plaque action on the soft tissues at the gumline. The same remarks apply to other water-insoluble non-cationic antibacterial agents described herein.

The oral dental treatment composition may also contain a source of fluorine ions or a fluorine-providing component as an anti-caries agent in an amount sufficient to provide about 25-5000 ppm of fluoride ions. These compounds may be sparingly soluble in water or may be completely water soluble. Characteristic of these agents is their ability to release fluoride ions in water and the fact that they show virtually no undesired reaction with other compounds in the oral preparation. These materials include inorganic fluoride salts such as soluble alkali metal, alkaline earth metal salts, e.g. sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as copper (I) fluoride, zinc fluoride, barium fluoride, natriumfluorosilicaat, ammoniumfluorosilicaat, sodium fluorozirconate, ammoniumfluorozirkonaat, sodium monofluorophosphate, aluminum miniummono- and -difluorofosfaat and 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 the fluorine-providing compound depends somewhat on the type of the compound, its solubility, and the type of oral preparation, but it should be a non-toxic amount, which is generally about 0.0005 to about 3.0% in the preparation.

In a dental treatment preparation, e.g. a dental gel, an amount of such a compound which releases up to about 5000 ppm of fluorine ions based on the weight of the composition is satisfactory. Any suitable minimum amount of such a compound may be used, but it is preferred that sufficient compound be used to deliver about 300-2000 ppm, more preferably about 800 to about 1500 ppm, of fluoride ions.

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

It is noted that the oral preparations should, as usual, be sold or otherwise marketed in suitably labeled packages. A gelled tooth conditioner will usually be packaged in a compressible tube, typically of aluminum, coated lead or plastic, or other squeezable, pump or pressurized contents release device, labeled , essentially describing it as a gel-shaped dental treatment agent or the like.

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, it is believed that the flavoring oil, like the surfactant, contributes to the dissolution of the antibacterial agent, along with or even in the absence of the surfactant.

In the preferred practice of the invention, an oral composition of the present invention is preferably applied regularly to dental enamel and soft tissues in the mouth, especially at or near the edge of the gum, such as every day or every 2nd or 3rd day, or preferably 1 to 3 times a day, at a pH of about 4.5 to about 9 or 10, generally about 5.5 to about 8, preferably about 6-8, and most preferably about 6.5 to about 7.5, for at least 2 weeks up to 8 weeks or more, for life.

Even at such a pH below 5, tooth enamel is not decalcified or otherwise damaged. The pH can be adjusted with acid (e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) or buffered as with sodium citrate, benzoate, carbonate or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.

The compositions of the invention can be incorporated into lozenges, or into chewing gum or other products, e.g. by stirring in a warm gum base or by coating the outer surface of a gum base, which may be exemplified by jelutong, rubber latex, vinylite resins, etc., optionally with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates, such as glucose, 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.

Example 1

The following dental treatment agent was prepared: parts

A B

glycerin 10.00 - propylene glycol - 10.00 sorbitol (70%) 25.00 25.00 iotacarrageen 0.60 0.60

Gantrez S-97 2.00 2.00 sodium accharin 0.40 0.40 sodium fluoride 0.243 0.243 sodium hydroxide (50%) 1.00 1.00 titanium oxide 0.50 0.50 silica polishing agent (Zeodent 113) 20.00 20 .00 silica thickener (Sylox 15) 5.50 5.50 sodium lauryl sulfate 2.00 2.00 water '31.507 31.507 triclosan 0.30 0.30 flavoring oil 0.95 0.95

The above-defined dental treatment agent A delivers triclosan to the teeth and soft gum tissue essentially as well as dental treatment agent B, which contains a special triclosan solvent. In other words no special solving agent for the effectiveness of the dental treatment agent of the present invention is necessary. Furthermore, a corresponding dental treatment agent in which the Gantrez polycarbaxylate is absent delivers the triclosan much worse.

In the above example, improved results can also be achieved by replacing triclosan with other antibacterial agents described herein such as phenol, thymol, eugenol and 2,2'-methylene-bis (4-chloro-6-bromophenol) and / or by Gantrez replaced by other AEAs, such as a 1: 1 copolymer of maleic anhydride and ethyl acrylate, sulfoacryl oligomer, Carbopols (eg 934), and polymers of alpha or beta styrene phosphonic acid monomers and copolymers of these monomers with each other or with other ethylenically unsaturated polymer monomers such as vinyl phosphonic acid.

Example 2

The following liquid phase dental treatment solutions were tested for uptake and retention of triclosan on saliva-coated HA discs according to the test procedures described in Example 1 with the reported results:

Share ingredients

A B C D

sorbitol (70% solution) 30.0 30.0 30.0 30.0 glycerol 9.5 9.5 9.5 9.5 propylene glycol 0.5 0.5 0.5 0.5 SLS 20.0 20.0 20.0 20.0

NaF 0.243 0.243 0.243 0.243 flavoring oil 0.95 0.95 0.95 0.95 triclosan 0.3 0.3 0.3 0.3 water 56.507 54.507 54.507 54.507 poly (beta-styrene phosphonic acid) 2.0 poly (alpha styrene phosphonic acid) 2.0 polyvinyl alcohol 2.0

Adjusted to pH 6.5 with NaOH triclosan uptake in yg on saliva-coated HA discs 31.0 174.0 86.0 36.0

Retention of triclosan on saliva-coated HA discs after: initially 183.0 30 minutes 136.0 1 hour 105.0 3 hours 83.0

The above results show that solution (D) containing polyvinyl alcohol, not an AEA included below, gives triclosan uptake of only 36.0, which closely resembles 31.0 uptake of the control solution ( A) without additive. In contrast, solution (C) with poly (alpha-styrene-phosphonic acid) gives an uptake of 86.0, more than twice the uptake in the case of solutions (A) and (D), and solution (B) with poly (beta-styrene-phosphonic acid) ) gives an inclusion of about 5 times that of solutions (A) and (D), which further seems to indicate superior results in the case of vicinal substitution of the release enhancing group. The above results also show the surprisingly good retention of triclosan on the HA discs over time, obtained with solution (B) containing poly (beta-styrene phosphonic acid) (molecular weights about 3000-10,000).

Example 3

The effect of synthetic anionic linear polycarboxylate on the uptake, retention, and detachment of tooth surfaces of water-insoluble non-cationic antibacterial agent is assessed in vitro on a saliva-coated hydroxyapatite disc and flaked mouth epithelial cells. The in vitro assays can be correlated with in vivo release, and retention on surfaces in the mouth.

For the test of delivery of antibacterial agent to a saliva-coated hydroxyapatite disc, hydroxyapatite (HA) obtained from Monsanto Co. is washed extensively with distilled water, collected by vacuum filtration, and dried at 37 ° C overnight. The dried HA is ground to a powder with a mortar and pestle. 150.00 mg of the HA is introduced into a KBR pill mold chamber (Barnes Analytical, Stanford, CT.) And compressed at 10,000 pounds (4536 kg) for 6 minutes in a Carver Laboratory press. The resulting 13 mm discs are sintered at 800 ° C for 4 hours in a Thermolyne oven, Parafilm-stimulated whole saliva is collected in an ice-cooled glass beaker. The saliva is cleared by centrifugation at 15,000 x g (reverse gravity) for 15 minutes at 4 ° C. Sterilization of the clarified saliva is performed at 4 ° C with stirring by irradiating the sample for 1.0 hour with UV light.

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 skin of saliva is formed by incubating the disc in a water bath overnight at 37 ° C with continuous shaking. After this treatment, the saliva is removed and the disks are treated with 1.00 ml of a solution containing antibacterial agent (triclosan), dental treatment liquid phase solution and incubated in the water bath with continuous shaking at 37 ° C. After 30 minutes, the disc is transferred to a new tube and 5.00 ml of water are added, followed by gentle shaking of the disc with a Vortex. The disc is then transferred to a new tube and the washing procedure repeated twice. Finally, the disc is carefully transferred into a new tube avoiding the transfer of liquid along with the disc. Then 1.00 ml of methanol is added to the disc and shaken vigorously with a Vortex. The sample is left at room temperature for 30 minutes, during which time adsorbed tricloxan is extracted 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 liguid chromatography) vials for antibacterial agent determination. All experiments use triplicate samples.

For the test of antibacterial retention on a saliva-coated HA disk, a saliva-coated HA disk as described above is treated with dental treatment suspensions. After incubation for 30 minutes at 37 ° C, the HA disk is removed from the dental treatment suspension, washed twice with water, and then incubated again with parafilm-stimulated human whole saliva cleared by centrifugation. After incubation at 37 ° C with constant shaking for various periods, the HA disk is removed from the saliva, and the amount of antibacterial agent (triclosan) retained on the disk and released into the saliva is analyzed method using HPLC.

For the determination of antibacterial agent delivery to oral epithelial cells, the release is measured to determine the effect of PVM / MA on the delivery of antibacterial agent (triclosan) to soft tissue in the mouth from a dental treatment product. Oral epithelial cells are collected using a wooden applicator stick by gently rubbing the mucous membranes of the mouth. The cells are suspended in Resting Saliva Salts (RSS) Buffer (50 nM NaCl, 1.1 nM CaCl ^, and 0.6 nM KH ^ PO ^, pH 7.0) to 5 - 6 x 10 ^ cells / ml, where a hemocytometer is used to count the cells and are kept in ice until use. 0.5 ml of the cell suspension previously incubated in a water bath at 37 ° C is added to 0.5 ml of the test solution of antibacterial agent and incubated at 37 ° C. The antibacterial agent solution in the incubation mixture is diluted at least 10 times to decrease the surfactant concentration and prevent destruction of cell membranes by the surfactant. After a 30 minute incubation, the cells are harvested by centrifugation at 5000 rpm in the Beckman Microfuge 11 for 5 minutes. The pelleted cells are washed three times with RSS buffer and treated with 1.5 ml of methanol. The sample is mixed vigorously and analyzed for antibacterial agent by HPLC method.

Dental treatments were prepared with the following formulations: parts

A B

propylene glycol (1.2) 10.00 10.00

Iota carrageenan 0.75 0.75>

Gantrez S-97 - 2.00 titanium dioxide 0.50 0.50 sorbitol (70%) 30.00 30.00 sodium fluoride 0.332 0.332

A B

sodium saccharin 0.40 0.40 silica thickener (Sylodent 15) 3.00 3.00 silica polish (Zeodent 113) 20.00 20.00 triclosan 0.20 0.20 sodium lauryl sulfate 2.00 2.00 flavoring oil 0 .95 0.95 ethyl alcohol 1.00 1.00 water qs to 100.00 to 100.00

The incorporation of triclosan on the saliva-coated hydroxyapatite disc and on mouth epithelial cells with and without the polymeric polycarboxylate, Gantrez S-97, is listed in Table A below:

TABLE A

Dental Treatment Uptake of triclosan In ug x 10 ^ mouthwash in ug on saliva epithelial cell-coated disc A 25.0 38.0 B 54.0 96.0

These results show that the Gantrez material (present in dental treatment agent B) greatly improves the release and uptake of triclosan on the saliva-coated hydroxyapatite disc and on the exfoliated mouth epithelial cells.

Similar results are obtained when the dental agents contain 0.30 parts of triclosan.

Example 4

In tests with saliva-coated hydroxyapatite disks and with flaked mouth epithelial cells, which tests differ from the tests mentioned in Example 1, dental care agent B containing 2.00% Gantrez S-97 and 0.20% triclosan, 10 .00% propylene glycol and 2.00% sodium lauryl sulfate and an equivalent formulated dental treatment agent (B *> except for the presence of 0.30% triclosan, compared to a commercially available dental treatment agent (C) containing hydrated alumina polish and (a) 0.2% triclosan, (b) no Gantrez material, (c) no propylene glycol, (d) 0.5% zinc citrate, (e) 2.5% surfactants, (f) sodium monofluorophosphate and hydrated alumina polishing agent; and the dental treatment composition (C ') listed below which corresponds to the commercially available dental treatment agent C except for the presence of 0.30% triclosan:

Dental treatment agent C% sorbitol (70%) 27.00 sodium carboxymethyl cellulose 0.80 sodium monofluorophosphate 0.85 zinc citrate 0.50 sodium accharine 0.18 water 16.47 hydrated alumina polish 50.00 ethanol 0.20 sodium lauryl sulfonate 1.875 sodium dodecylbenzene sulfonate 0.625 triclosan 0.30 flavor 1.20

Since the dental agents C and C 'contain a total of 2.50% surfactant, more surfactant is available for dissolving triclosan than in the dental agents B and B' which contain 2.00%. However, the propylene glycol (which is not present in the hydrated alumina polishing agent of the dental treatments C and C ') contained in the silicon-containing polishing agent of the dental treatment agents B and B' ensures optimum dissolution of triclosan.

The advantage of the dental agents B and B '(containing propylene glycol and Gantrez) over the dental agents C and C', in the incorporation of triclosan on saliva-coated hydroxyapatite discs and flaked mouth epithelial cells is shown in Table B below demonstrated:

TABLE B

Delivery of triclosan to saliva-treated oral epithelial cell-coated hydroxyapatites in µg x 10® disc (in yg) epithelial cell dental treatment B 41.1 101.6 B * 77.4 142.0 C 20.4 61.0 C 42.6 100.0

Further experiments with dental treatment agent B '(0.3% triclosan; Gantrez; propylene glycol) in a 50% suspension of the dental treatment agent to determine the retention of triclosan on the saliva-coated hydroxyapatite disc over a period of time, allowing retention of excellent levels of triclosan, as shown in Table C below.

TABLE C

Retention of triclosan adsorption from from dental treatment suspension

Time Retention of triclosan (in minutes) (yg / disc) 0 70 30 60 60 70 120 65 180 57 240 59

These results indicate that dentifrices containing triclosan, Gantrez material and propylene glycol may provide improved triclosan release and retention on dental surfaces and soft surfaces in the oral cavity, thereby providing better anti-plaque and antibacterial effects.

Example 5

For comparison, formulations a and b below were prepared:

Dental treatment agent% a b glycerine 10.00 propylene glycol - 10.00

Iota carrageenan 0.60 0.60 sorbitol (70%) 25.00 25.00 sodium saccharin 0.40 0.40 sodium fluoride 0.243 0.243 titanium dioxide 0.50 0.50

Gantrez S-97 2.00 2.00 water 29.157 29.175

NaOH (50%) 2.00 2.00

Zeodent 113 (silica polish) 20.00 20.00

Sylodent 15 (silica thickener) 5.50 5.50 flavor 1.10 1.10 triclosan 0.50 0.50 sodium lauryl sulfate 2.00 2.00 ethanol 1.00 1.00

Formulation a is a dental treatment agent containing a Gantrez poly-carboxylate, containing 0.5% triclosan as an antibacterial anti-plaque agent, and not an oscopic agent. In formulation b, the solvent propylene glycol is present.

Formulation a gives poor delivery of triclosan to oral epithelial cells while formulation b is markedly effective.

The above results show excellent release of triclosan dental treatment agent.

Example 6

A closed study was conducted on a group of volunteers to determine the effects of certain dentifrices on impact on plaque regrowth according to the method described by Addy, Wilis and Moran, J. Clin. Perio, 1983, Vol. 10, pp. 89 - 99. The tested dental treatments included a placebo control containing no triclosan (i) and a dental treatment according to the invention containing 0.3% triclosan, 10% propylene glycol (instead of 3% polyethylene glycol 600) and 2% Gantrez S-97 and wetting agent of propylene glycol and sorbitol contained (ii).

The formulations of the dental treatments were as follows: parts (i) (ii)% placebo invention polyethylene glycol 600 3/00 glycerin 25.00 propylene glycol - 10.00 sorbitol (70%) 41.617 25.00 sodium carboxymethyl cellulose 0.35

Iota carrageenan - 0.60 sodium benzoate 0.50 sodium saccharin 0.20 0.40 sodium fluoride 0.243 0.243 silica polish (Zeodent 113) 18.00 20.00 silica thickener (Sylox 15) 5.50 5.50 water 8. 00 28.757

Gantrez S-97 - 2.00 triclosan - 0.30 titanium dioxide 0.50 0.50 sodium lauryl sulfate 1.20 2.50 flavoring 0.89 1.10 ethyl alcohol 1.00 sodium hydroxide (50%) 2.00

Regarding plaque reduction, on the teeth of the volunteers, compared to placebo (i), the invention (ii) showed a significant 20% decrease.

Since smaller amounts of propylene glycol can dissolve the 0.3% triclosan contained in toothpaste (ii), similar results are expected when the amount of propylene glycol is reduced to 0.5 parts and the amount of sorbitol is increased to 39.5 parts. Likewise, the other solvents may also effectively deliver dipropylene glycol, hexylene glycol, methyl cellosolve, ethyl cellosolve, olive oil, castor oil, petrolates, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate to soft tissues in the mouth instead of propylene glycol. Similar results are further expected also when propylene glycol or other solvents are omitted from toothpaste (ii) containing 0.3% triclosan.

Example 7

The following dental treatments according to the invention were prepared: parts

A B

glycerine - 20.00 propylene glycol 10.00 0.50 sorbitol (70%) 25.00 19.50 sodium carboxymethyl cellulose - 1.10

Iota carrageenan 0.600 sodium saccharin 0.40 0.30 sodium fluoride 0.243 0.243 silica polish (Zeodent 113) 20.00 20.00 silica thickener (Sylox 15) 5.50 3.00 water 28,757 15,307

Gantrez S-97 2.00 2.00 triclosan 0.50 0.30 titanium dioxide 0.50 0.50 sodium lauryl sulfate 2.50 2.00 flavoring 1.10 0.95 ethanol 1.00 sodium hydroxide (50%) 2.00 1.60

In the above examples, better results can also be obtained by replacing triclosan with other antibacterial agents as described herein, such as phenol, thymol, eugenol and 2,2'-methylene-bis (4-chloro-6-bromophenol) and / or by replacing Gantrez with other AEAs such as a 1: 1 copolymer of maleic anhydride and ethyl acrylate, sulfoacryloligomers, Carbopols (eg 934), polymers of mono mer alpha or beta styrene phosphonic acid and copolymers of these styrene phosphonic acid monomers with each other or with other ethylenically unsaturated polymerisable monomers such as vinyl phosphonic acid.

Example 8

The following dental treatment agent was prepared: parts

A B C

alpha alumina trihydrate 48.00 48.00 48.00 propylene glycol - 0.50 0.50 sorbitol (70%) 21.70 21.70 21.70

Gantrez S-97 (13% solution) 15.00 15.00

Gantrez S-97 (powder) - - 2.00 sodium lauryl sulfate 2.00 2.13 2.13 sodium saccharin 0.30 0.30 0.30 sodium hydroxide (50%) 1.20 1.20 1.20 flavoring 0.95 0.95 0.95

Irish Moss 1.00 Sodium Carboxymethyl Cellulose - 1.00 1.00 Sodium Monofluorophosphate 0.76 0.76 0.76 Titanium Dioxide - 0.50 0.50 Triclosan 0.30 0.30 0.30 Water q.s. to q.s. to q.s. up to 100.00 100.00 100.00

The dental agents mentioned above deliver triclosan to the teeth and soft tissue areas of the gums to a considerably more effective extent than corresponding dental agents in which the Gantrez polycarboxylate is absent.

Example 9

The following dental treatments were prepared: parts of glycerine 22.00 10.00 sorbitol (70%) - 17.00 sodium carboxymethyl cellulose 1.00 1.00

Gantrez S-97 2.00 2.00 sodium saccharin 0.20 0.20 sodium benzoate 0.50 0.50 sodium monofluorophosphate 0.76 0.76 dicalcium phosphate / dihydrate 48.76 48.76 triclosan 0.30 0.30 sodium lauryl sulfate 1, 20 1.20 flavoring 0.89 0.89 water qs to q.s. up to 100.00 100.00

The dental agents mentioned above deliver triclosan to saliva-coated hydroxyapatite disks much more effectively than corresponding dental agents in which the Gantrez polycarboxylate is absent.

Example 10

The following anti-plaque dental treatment agent was prepared: parts of glycerine 15.00 propylene glycol 2.00 sodium carboxymethyl cellulose 1.50 water 24.93 vinyl methyl ether / maleic anhydride copolymer (42% solution) 4.76 sodium monofluorophosphate 0.76 sodium saccharin 0.30 insoluble sodium metaphosphate 47.00 titanium dioxide 0.50 sodium lauryl sulfate 2.00 triclosan 0.30 flavoring 0.95

In the above examples, improved results can also be achieved when triclosan is replaced by phenol, 2,21-methylene-bis (4-chloro-6-bromophenol), eugenol and thymol, and / or when Gantrez is replaced by other AEAs such as Carbopols (e.g.

934) or styrene phosphonic acid polymers with molecular weights in the range of about 3000-10,000, 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 oligomers, or a 1: 1 copolymer of maleic anhydride with ethyl acrylate.

Example 11

Triclosan containing mobile phases of dental treatment agent. Components —Composition,% (w / w )-

_______ A B

sorbitol (70%) 53.33 40.00 water 40.48 39.15

Gantrez S (15%) --- 13.33

NaOH (50%) 1.33 saccharin 0.40 0.40 sodium fluoride 0.32 0.32 flavoring oil 1.47 1.47 sodium lauryl sulfate 3.33 3.33 triclosan 0.67 0.67

The concentration of the above components is 1.33% dental treatment level in view of 25% abrasive level that may be required to make a complete dental treatment.

The above-mentioned mobile phases of the said dental treatment agent formulations are tested on saliva-coated HA discs for triclosan incorporation. The results are shown in the table below:

TABLE

Uptake of triclosan by saliva-coated hydroxyapatite (HA) discs from diluted and undiluted mobile phases of dental treatments

A B

% triclosan 0.67 Q, 67 ionic strength (M / L) (calculated) 0.375 pH 8.77.6 triclosan uptake (yg / disc), undiluted 55 122

The above results show a more than two-fold increase in triclosan uptake achieved with the B-formulation containing Gantrez relative to the A-formulation without the Gantrez.

Example 12

Concentration and uptake of triclosan by HA from supernatant of 1: 1 dental treatment / water suspensions.

Dental treatment agent, Triclosan (µg / ml) in Triclosan incorporation containing 0.5% triclo supernatant of 1: 1 µg / disc san, 2.5% sodium lauryl suspension sulfate _ 25% hydrated silica + 1.5% Gantrez S-97 1,650 52 50% alumina + 1.5% Gantrez S-97 1,905 74

Supernatants of 1: 1 dental / water suspensions of the above-mentioned dental agents are tested for the concentration of the triclosan in the supernatant and for the triclosan uptake on saliva-coated HA discs. The results indicate that the use of 50% alumina abrasive greatly increases triclosan under low 1: 1 dilution conditions (from 1650 to 1905), resulting in a significant increase in triclosan uptake (from 52 to 74).

Example 13

The mouthwash solutions below provide effective plaque reduction by increasing the absorption and retention of triclosan on surfaces in the mouth.

A B C D E

share

Gantrez S-97 0.24 0.25 0.25 0.25 0.25 glycerine 15.00 10.00 15.00 10.00 15.00 ethanol - - 12.50 12.50 - propylene glycol - 5.00 - 5.00

Pluronic F1Q8 2.00 (polyoxyethylene / polyoxypropylene block copolymer) sodium lauryl sulfate - - 0.20 0.20 0.20 triclosan 0.10 0.10 0.06 0.06 0.03 flavoring oil 0.40 0.40 0.40 0.40 0.40 water ----- q. s. to --------- 100.00 100.00 100.00 100.00 100.00

Example 14

The following liquid dental treatments are also effective in reducing plaque by increasing the absorption and retention of triclosan on surfaces in the mouth: Share

A B C

glycerine 20.00 20.0 -

Gantrez S-97 0.3 0.3 0.3 high molecular weight polysaccharide, where the molecule contains mannose, glucose, potassium glucuronate and acetyl groups in a ratio of about 2: 1: 1: 1 0.8 - 1.0 sodium benzoate 0 .5 0.5 0.5 saccharin sodium 0.5 0.5 0.5 water 61.3 73.1 71.6 sodium lauryl sulfate 3.0 3.0 3.0 insoluble sodium metaphosphate 10.0 - 10.0 anhydrous dicalcium phosphate 1.0 - 2.5 flavoring oil 2.5 2.5 2.5 ethyl alcohol - - 10.0 triclosan 0.1 0.1 0.1

In the above examples, improved results can also be achieved when triclosan is replaced by phenol, 2,2'-meth-leen-bis (4-chloro-6-bromophenol), eugenol and thymol, and / or when Gantrez is replaced by others AEAs such as carbopols (eg 934} or styrene phosphonic acid polymers with molecular weights in the range of about 3000-10,000 such as poly (beta styrene phosphonic acid}, copolymers of vinyl phosphonic acid with beta styrene phosphonic acid, and poly (alpha styrene phosphonic acid), or sulfoacryl, or sulfoacrylic) a 1: 1 copolymer of maleic anhydride with ethyl acetate.

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 (40)

An oral composition comprising an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, about 0.005-4% by weight of an antibacterial enhancing agent that inhibits the release of the antibacterial agent. improves and retention on surfaces in the mouth, and an orally acceptable carrier which can enable the antibacterial agent to dissolve in an effective anti-plaque amount in saliva, which oral composition is essentially polyphosphate anti- contains tartar agent. The oral preparation according to claim 1, wherein the oral preparation is a dental treatment agent comprising about 5-30% by weight of a silicon-containing polishing agent, and wherein the antibacterial agent is present in an amount of about 0.25-0.35% % and at least one component from the group of surfactants and flavoring oils is present. The oral preparation according to claim 1, wherein the oral preparation is a dental treatment agent comprising about 5-30% by weight of a silicon-containing polishing agent, the antibacterial agent being present in an amount of about 0.1-5% by weight and the oral preparation comprises a dissolving material in an amount sufficient to dissolve the antibacterial agent in saliva. The oral formulation of claim 3, wherein the antibacterial agent is present in an amount from about 0.05% down to about 0.25% by weight. The oral formulation of claim 3, wherein the antibacterial agent is present in an amount from above about 0.35% to about 5% by weight. The oral formulation of claim 5, wherein the antibacterial agent is present in an amount from above about 0.35% to about 0.5% by weight. The oral formulation of claim 1, wherein the oral formulation is a dental treatment agent comprising about 30-75% by weight of a water-insoluble polishing agent acceptable for dental use. The oral preparation according to claim 1, wherein the oral preparation is a mouthwash liquid or a liquid dental treatment agent and the oral acceptable carrier is an aqueous carrier, wherein at least one component from the group of surfactants, flavoring oils and non-toxic alcohols is present. Oral dental treatment composition according to any of the preceding claims, wherein surfactant is present in an amount of about 0.5-5% by weight. Oral dental treatment composition according to any of the preceding claims, wherein flavoring oil is present in an amount of about 0.1-5% by weight. The oral formulation of claim 6, wherein the formulation is a mouthwash liquid and the aqueous vehicle contains ethanol, and the weight ratio of water to ethanol is from about 1: 1 to about 20: 1. The oral formulation of claim 8, wherein the oral formulation is a liquid dental treatment agent containing about 0.3-2.0 wt% of a high molecular weight polysaccharide above 1,000,000 containing mannose, glucose, potassium glucuronate and acetyl groups in contains a ratio of about 2: 1: 1: 1, as a suspending and thickening agent, and about 10 - 20% by weight of a polishing material. An oral preparation according to any one of claims 1-8, wherein the 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 of claim 13, wherein the antibacterial agent is a halogenated diphenyl ether. The oral preparation of claim 14, wherein the halogenated diphenyl ether is 2,4,4'-trichloro-2-hydroxyphenyl ether. The oral dental treatment composition according to any one of claims 1 and 3 to 6, wherein a dissolving agent is present in an amount of about 0.5 - 50% by weight, and is selected from the group consisting of propylene glycol, dipropylene glycol, hexylene glycol , methyl cellosolve, ethyl cellosolve, vegetable oil and wax, with at least about 12 carbon atoms, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate. The oral dental treatment composition according to claim 16, wherein a solvent is propylene glycol present in an amount of about 0.5% by weight. The oral formulation of claim 1 or claim 16, wherein a polishing agent is selected which is selected from the group consisting of sodium metaphosphate, tricalcium phosphate, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagasodium bicarbonate, calcium calcium phosphate, aluminum oxide, silicon oxide, bentonite and mixtures thereof, and wherein the oral preparation is a dental treatment agent. The oral dental treatment composition of claim 18, wherein the polishing agent is dicalcium phosphate dihydrate or hydrated alumina. The oral formulation of any one of claims 1-8, wherein the anti-bacterial enhancing agent has an average molecular weight of about 100 to about 1,000,000. The oral formulation of claim 20, wherein the antibacterial enhancing agent contains at least one release enhancing functional group and at least one organic retention enhancing group. The oral formulation of claim 21, wherein the release enhancing group is an acidic group. The oral formulation of claim 22, wherein the release enhancing group is selected from a group consisting of carboxylic, phosphonic, phosphinic, and sulfonic acids, and salts thereof, as well as mixtures thereof. The oral preparation of claim 23, wherein the organic retention enhancing group has the formula - (X) n - R, wherein X represents 0, N, S, SO, SO 4, P, PO, or Si; R represents hydrophobic alkyl, alkylene, acyl, aryl, alkaryl, aralkyl, heterocyclic, or inert-substituted derivatives thereof, and n is 1 or 0. The oral composition of any one of claims 20 to 24, wherein the antibacterial enhancing agent is an anionic polymer containing a plurality of such release enhancing and retention enhancing groups. The oral formulation of claim 25, wherein the anionic polymer comprises a chain with repeating units each containing at least one carbon atom. The oral formulation of claim 26, wherein each unit contains at least one release enhancing group bonded to the same atom, a vicinal atom, or other atoms in the chain. The oral formulation of claim 23, wherein the release enhancing group is a carboxyl group or salt thereof. The oral composition of claim 28, wherein the antibacterial enhancing agent is a copolymer of maleic acid or maleic anhydride with another inert ethylenically unsaturated polymerizable monomer. The oral composition of claim 29, wherein the other monomer of the copolymer is methyl vinyl ether, in a 4: 1 to 1: 4 mole ratio with the maleic acid or maleic anhydride. The oral formulation of claim 30, wherein the copolymer has a molecular weight of about 30,000-1,000,000 and is present in an amount of about 0.1-2 wt%. The composition of claim 31, wherein the copolymer has an average molecular weight of about 70,000. The composition of claim 23, wherein the release enhancing group is a phosphonic acid group or salt thereof. The composition according to claim 33, wherein the antibacterial enhancing agent is poly (beta-styrene phosphonic acid) or poly (alpha styrene phosphonic acid) polymer or a copolymer of one of these styrene phosphonic acids with another ethylenically unsaturated monomer. --- A method of controlling plaque in the mouth, wherein an effective plaque controlling amount of a composition according to any of the preceding claims is applied to surfaces in the mouth. 36. 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 enhancing agent having an average molecular weight of about 1,000 to about 1,000. 000, which contains at least one release enhancing functional group and at least one organic retention enhancing group, which agent containing these groups is free or substantially free of water-soluble alkali metal or ammonium synthetic anionol linear polymer polycarboxylate salt having a molecular weight from about 1000 to about 1,000,000. The oral formulation of claim 36, wherein the antibacterial agent is present in an amount from about 0.25 to less than 0.5% by weight. The oral formulation of claim 36, wherein the antibacterial agent is present in an amount from about 0.25 to about 0.35% by weight. The oral formulation of claim 37, wherein the oral formulation contains a silicon-containing polishing agent. The oral formulation of claim 38, wherein the oral formulation contains a silicon-containing polishing agent.