SE512333C2 - Antibacterial oral composition with plaque- and tartar-limiting action - Google Patents

Abstract

An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such as tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncationic antibacterial agent such as 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Triclosan). Antiplaque effectiveness is optimized by the presence of an antibacterial-enhancing agent which enhances delivery of said antibacterial agent to, and retention thereof on, oral surfaces. Suitable enhancing agents are anionic polymers such as a maleic acid-methyl vinyl ether copolymer or a polymer containing phosphonic groups. Also disclosed are compositions comprising (1) the noncationic antibacterial agent and the enhancing agent, (2) the polyphosphate anticalculus agent and the noncationic antibacterial agent and (3) the enhancing agent and polyphosphate anticalculus agent effective against any antibacterial agent.

Description

. ~ _ h * 512 333 "" 'preferably part of the tooth surface, especially including the gingival stripe.

In addition to being less visually appealing, plaques are involved in the onset of gingivitis.

Thus, it would be highly desirable to include antimicrobial agents known to reduce plaque in oral compositions containing antitartar agents.

This has actually been described in U.S. Pat. No. 4,022,550 (Vinson et al) wherein a compound which produces zinc ions such as an anti-tartar agent is mixed with an antibacterial agent which is effective in retarding 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 chlorhexydine, benzethonium chloride and cetylperydine chloride have been the subject of extensive research as antibacterial anti-plaque agents. However, because they are used together with zinc as an anti-tartar agent, they are not effective when used with anionic materials such as polyphosphate as an anti-tartar agent. This ineffectiveness is considered to be completely overriding because polyphosphates are chelating agents and the chelating effect has previously been known to increase the effectiveness of cationic antibacterial agents (see, for example, Disinfection, Sterilization and Preservation, 2nd Ed., Black, 1977, page 915 and Inhibition and Destruction of the Microbial ggll, Hugo, 1971, p. 215). Quaternary ammonium compound is actually present in the pyrophosphate-containing plaque-limiting mouthwash of U.S. Pat. No. 4,323,551 (Parran) and bisbiguanide as anti-plaque agents proposed in the oral pyrophosphate containing the anti-tartar composition of U.S. Pat. 4,515,772 (Parran et al). 512 333 'f- In view of the surprising incompatibility of the cationic antibacterial agents with polyphosphates present as anti-tartar agents, it was completely unexpected that other antibacterial agents would be effective.

An advantage of the present invention is that certain antibacterial agents are effective in oral antitartar compositions containing a linear molecularly dehydrated polyphosphate salt, a fluoride ion providing source and the above-mentioned antibacterial action enhancing agent, to inhibit plaque formation.

A further advantage of the present invention is that a composition is provided which is effective in reducing tartar formation and optimizing plaque reduction.

A further advantage of the present invention is that an oral antiplaque, antitartar composition is provided which is effective in reducing the onset of lingitis.

Additional advantages of the present invention will become apparent upon a study of the following description.

In accordance with some of its aspects, the present invention relates to an oral composition comprising, in an orally acceptable carrier, an effective amount of anti-tartar material comprising about 0.1-3% by weight of at least one linear molecularly dehydrated polyphosphate salt such as anti-tartar agent, a effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent, and preferably up to about 4% by weight of an antibacterial effect enhancing agent which improves the delivery of the antibacterial agent to and retention thereof on oral surfaces, typically the weight ratio antibacterial effect enhancing means 512 333 2 - to polyphosphate ion ranges from more than 0.72: 1 to less than 4: 1, for example from about 1: 1 to about 3.5: 1, especially from about 1.6: 1 to about 2 , 7: 1, preferably about 1.7: 1 to about 2.3: 1 and most preferably about 1.9: 1 to about 2: 1. For example, when 2% tetrasodium pyrophosphate (TSPP) is used (yielding about 1.3% pyrophosphate ion) together with 2.5% of the antibacterial efficacy agent, a highly desirable weight ratio of about 1.9: 1 is achieved.

Typical examples of antibacterial agents that are particularly desirable in terms of antiplatelet efficacy, safety and composition are: Halogenated diphenyl ethers 2 ', 4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan) 2,2'-dihydroxy-5,5' , dibromodiphenyl 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 -n-octanoyl-3'-trifluoromethyl salicylanilide 3,5-dibromo-4-trifluoromethyl salicylanilide 3,5-dibromo-3'-trifluoromethyl salicylanilide (Flurophene) Benzo-ester Hydrobenzyl Methyl - p Ethyl p-hydroxybenzoic ester Propyl - p-hydroxybenzoic ester Butyl p-hydroxybenzoic ester a? Semi-generated carbanilides 3,4,4'-trichlorocarbanilide 3-trifluoromethyl-4,4'-dichlorocarbanilide 3,3,4'-trichlorocarbanilide Phenolic compounds (including phenol and its homologues, mono- and poly-alkyl and aromatic halo- (eg F, Cl, Br, I.) -phenols, resorcinol and catechol and their derivatives and bisphenol compounds.) These phenol compounds include, but are not limited to: Phenol and its homologues phenol - phenol 2 methyl - phenol 3 methyl - phenol 4 methyl - phenol 4 ethyl phenol 2,4-dimethyl-phenol 2,5-dimethyl-phenol 3,4-dimethyl-phenol 2,6-dimethyl-phenol 4-n-propyl-phenol 4-n-butyl-phenol 4-n-amyl - phenol 4-tert-amyl - phenol 4-n-hexyl - phenol 4-n-heptyl - phenol 2-methoxy-4- (2-propenyl) - phenol (Eugenol) 2-isopropyl-5-methyl - phenol (Thymol ) Mono- and poly-alkyl and aralkyl halophenols methyl - p-chlorophenol ethyl - p-chlorophenol n-propyl - p-chlorophenol n-butyl - p-chlorophenol n-amyl p-chlorophenol "512 333 sec-amyl n-hexyl cyclohexyl n-heptyl n-octyl o-chlorophenol methyl ethyl n-propyl n-butyl n-amyl tert-amyl n-hexyl n-heptyl p-chlorophenol o-benzyl o-benzyl-m-methyl o-benzyl-m, m-dimethyl o-phenylethyl o-phenylethyl-m-methyl 3-methyl 3,5 -dimethyl 6-ethyl-3-methyl 6-n-propyl-3-methyl 6-isopropyl-3-methyl 2-ethyl-3,5-dimethyl 6-sec. butyl-3-methyl-2-iso-propyl-3,5-dimethyl-6-diethylmethyl-3-methyl-6-iso-propyl-2-ethyl-3-methyl 2-sec. amyl-3,5-dimethyl 2-diethylmethyl-3-5-dimethyl 6 sec. octyl-3-methyl 6-sec. octyl 3-3-methyl p-bromophenyl methyl - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - o-chlorophenol - o-chlorophenol - o-chlorophenol - o-chlorophenol - o-chlorophenol - o-chlorophenol - o-chlorophenol - o-chlorophenol -p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol -chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophenol - p-chlorophen1 - p-bromophenyl ethyl n-propyl n-butyl -amyl sec.-amyl n-hexyl cyclohyxel o-bromophenol tert.-amyl n-hexyl n-propyl-m, m-dimethyl 2-phenylphenol 4-chloro-2-methylphenol 4-chloro-3-methylphenol 4-chloro- 3,5-methylphenol 512 333 p-bromophenol p-bromophenol p-bromophenol p-bromophenol p-bromophenol p-bromophenol p-bromophenol o-bromophenol o-bromophenol o-bromophenol 2,4-dichloro-3,5-dimethylphenol -methyl -2-pentylphenol. 3,4,5,6-Tetrabromo-2-methylphenol 4-isopropyl-3-methylphenol-chloro-2-hydroxydiphenylmethane Resorcinol and its derivatives resorcinol methyl ethyl n-propyl n-butyl n-amyl n-hexyl n-heptyl n- octyl n-nonyl phenyl benzyl phenylethyl phenylpropyl resorcinol resorcinol resorcinol resorcinol resorcinol resorcinol resorcinol - resorcinol resorcinol resorcinol resorcinol resorcinol resorcinol 512 335 "[ -dihydroxydiphenylmethane -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 = (hexchlorophenol) 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 the oral composition in an effective amount of anti-plaque, typically about 0.01% by weight, preferably about 0.03-1% and very preferably about 0.25 -0.5% and most preferably about 0.25-0.35%. The antibacterial agent is substantially water insoluble, which means that its solubility is less than about 1% by weight in water at 25 ° C and may even be less than about 0.1%. If an ionizable group is present, the pH at which ionization does not occur is determined.

The preferred halogenated diphenyl ether is triclosan. The preferred phenolic compounds are phenol, 2,2'-methylene bis (4-chloro-6-bromophenol), thymol and eugenol. The most preferred antibacterial anti-plaque compound is triclosan.

The triclosan is disclosed in the aforementioned U.S. Pat. 4,022,888 as an antibacterial agent in combination with an anti-tartar agent which produces zinc ions and is disclosed in German Patent Specification D.E. 35 32 860 in combination with a copper compound. It is also disclosed as an anti-plaque agent in a dentifrice which is formulated to contain a lamellar phase comprising liquid crystal with hytactite agent, which phase has a lamellar spacing of less than 6.0 nm and which may optionally contain a zinc salt. , in the published patent application EP (Lane et al) and in a dentifrice containing the zinc citrate trihydrate, in published patent application E.P. 0161899 (Saxton).

The linear molecularly dehydrated polyphosphate salts operating as anti-tartar agents herein are well known and are widely used in the form of their fully or partially neutralized water-soluble alkali metal (eg gallium and preferably sodium) or ammonium salts and any mixtures thereof.

Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, disodium disura, trisodium monosura and tetrasodium pyrophosphates, the moss-equivalent potassium salts and the like. Linear polyphosphates correspond to (NaPO3) n, where n is about 2 to about 125. In the present invention, those in the oral compositions are used in approximate amounts by weight of 0.1 to 3%, typically 1 to 2.5% and more typically 1.5 to 2%. When n is at least 3 in (NaPO3) n, the polyphosphates are glassy in nature.

Particularly desirable antitartar agents are tetraalkali metal pyrophosphates including mixtures thereof, such as tetrasodium pyrophosphate, tetra potassium pyrophosphate and mixtures thereof. Thus, the oral composition may contain a polyphosphate comprising anti-tartar agent which is substantially free of tetrasodium pyrophosphate or substantially free of combination of tetrachotassium pyrophosphate and tetrasodium pyrophosphate wherein the ratio of potassium to sodium pyrophosphate is 3: An anti-tartar agent comprising about 2% by weight of the oral compositions, of tetrasodium pyrophosphate, is particularly effective.

The antibacterial effect enhancing agent (AEA), which improves the release of the antibacterial agent to and retention thereof on oral surfaces, is utilized in amounts effective to achieve such improvement, within the range of the oral composition of about 0. 05% to about 4%, preferably about 0.1% to about 3%, more preferably about 0.5% to about 2.5% by weight.

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

AEA usually contains at least one release enhancing group which is preferably acidic, such as a sulfone group, phosphine group or preferably phosphone or carboxyl group, or salt thereof, for example alkali metal or ammonium salt, and at least one organic retention enhancing group, preferably a plurality of both release agents and the retention enhancing groups, the latter groups preferably having the formula - (X) n R wherein X is O, N, S, SO, SO 2, P, PO or Si or the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl , aralkyl, heterocyclic or their inert-substituted derivatives, and n is zero or 1 or more. The above-mentioned "inert-substituted derivatives" are intended to include substituents on R which are generally non-hydrophilic and do not significantly interfere with the desirable functions of AEA to enhance the delivery of the antibacterial agent to, and remain therein, oral surfaces. , such as halo, for example Cl, Br, I and carbo and the like. Illustrations of such retention-enhancing groups are given in the table below. - (x) nR SO SO 2 PO Si Methyl, ethyl, propyl, butyl, isobutyl, t-butyl, cyclohexyl allyl, benzyl, phenyl, chlorophenyl, xyxyl, pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl etc. phenoxy, carboethoxy , ethoxy, benzyloxy, thioacetoxy, carbobenzyloxy etc. , allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc. diethylphosphinyl, etylvinylfosfinyl, etylallyl- phosphinyl, etylbenzylfosfinyl, etc. etylfenylfosfinyl dietylfosfinoxi, etylvinylfosfinoxi, metylallylfosfinoxi, metylbenzylfosfinoxi, etc. metylfenylfosfinoxi trimethylsilyl, dimetylbutylsilyl, dimetylbenzyl- silyl, dimethylvinylsilyl, dimenylallylsilyl etc. "s 512 335" As used herein, the release enhancing group refers to one which adheres or substantially adhesively, co. hesitantly or otherwise binds AEA (which carries this antibacterial agent) to oral surfaces (e.g., gum and gum surfaces) and thereby "delivers" the antibacterial agent to these surfaces. The organic retention enhancing group, which is generally hydrophobic, attaches or otherwise binds the antibacterial agent to the AEA, thereby promoting retention of the antibacterial agent at this AEA and indirectly on the oral surfaces. In some cases, the attachment of the antibacterial agent occurs by physical retention thereof with said AEA, especially when AEA is a crosslinked polymer, the structure of which by its nature provides extended sites for such retention. The presence of a higher hydrophobic crosslinking group of higher molecular weight in the crosslinked polymer further favors the physical retention of the antibacterial agent at or with the crosslinked AEA polymer.

Preferably, AEA is an anionic polymer comprising a chain or backbone containing repetitive moieties each of which preferably contains at least one carbon atom and preferably at least one directly or indirectly attached monovalent release enhancing group and at least one directly or indirectly attached monovalent retention enhancing group is geminally vicinally or less preferably otherwise attached to atoms, preferably carbon in the chain. Less preferably, the polymer may contain release enhancing groups and / or retention enhancing groups and / or other divalent atoms or groups as linkers in the polymer chain instead of or in addition to carbon atoms, or as crosslinking groups.

It should be understood that any examples or illustrations of AEA materials disclosed herein which do not contain both release enhancing groups and retention enhancing groups may and should be chemically modified to obtain the preferred AEA materials containing both of these groups and preferably a plurality of each of these groups. In the case of the preferred polymeric AEA materials, it is desirable, to maximize the substantivity and delivery of the antibacterial agent to oral surfaces, that the repetitive moieties in the polymer chain or backbone containing the acidic delivery enhancing groups be at least about 10%, preferably at least about 50%, more preferably at least about 80% up to 95% or 100% by weight of the polymer.

According to a preferred embodiment of the present invention, the AEA material comprises a polymer containing repetitive moieties in which one or more phosphonic acid including release enhancing groups is attached to one or more carbon atoms in the polymer chain. An example of such an AEA material is poly (vinylphosphonic acid) containing units of the formula: I - (cH2 - cH) - O3H2 which, however, does not contain a retention enhancing group. However, a group of the latter type should exist in poly (1-phosphonopropylene) having units of the formula: II - (CH - CH) - CH 3 o 3 H 2 A preferred phosphonic acid containing AEA for use herein is poly (beta styrene phosphonic acid) containing units of the formula: III - (CH -CH) - šh šb3H2 wherein Ph is phenyl, the emission-enhancing phosphone group and the retention-enhancing phenyl group are bonded to vicinal carbon atoms in the chain, or a copolymer of beta-512 333 '- 14 styrene phosphonic acid with vinylphosphonyl chloride unit according to form alternating or in random association with units of formula I above or poly (alpha-styrene phosphonic acid) containing units of the formula: Iv - (CH2;, c -----) - Ph o3H2 wherein the release and retention enhancing groups are geminally linked to the chain .

Its styrene phosphonic acid polymers and their copolymers with other internal ethylenically unsaturated monomers generally have molecular weights in the range of about 2,000 to about 30,000, preferably about 2,500 to about 10,000. These "inert" monomers do not substantially interfere with the intended function of any copolymer used herein as an AEA.

Other phosphone group-containing polymers include, for example, phosphonated ethylene having units of the formula: v - [§cø2) 14cHPo3H§1n- wherein in n may, for example, be a number or have a value which gives the polymer a molecular weight of about 3,000; and "sodium poly (butene-4,4-diphosphonate) having units of the formula: VI - (CH2 - cH ----) - cH2 - CH <(Po3Na2) 2 and poly (allyl bis (phosphonoethylamine)) having units of the formula: VII - (cH2: / cH ---) - CH2 - N <(PO3H2) 2 Other phosphonated polymers, for example poly (allylphosphonoacetate), phosphonated polymethyl acrylate etc. and the geminal diphosphonate polymers disclosed in EP-A- 0321233 can be used herein as AEA materials, provided, of course, that they contain or are modified to v? 512 333 i "- contain the organic retention enhancing groups defined above.

In one aspect of the present invention, the oral composition comprises an orally acceptable vehicle or carrier, an agent effective to enhance 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 a functional group which improves the release of antibacterial effect and at least one organic group which improves the retention of antibacterial effects, the agent containing these groups being free from or substantially free of water-soluble alkali metal or ammonium synthetic anionic linear polymeric polycarboxylate salt with a molecular weight of about 1,000 to 1,000,000, and polyphosphate as antitartar agent, such as a mixture of potassium and sodium salts, the ratio of potassium to sodium in the composition being in the range up to less than about 3: 1, for example. wise from about 0.37 to about 1.04: 1.

In another preferred embodiment, the AEA material 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 disclosed as anti-tartar agents per se, in e.g. 3,429,963 (Shedlovsky), U.S. Pat. No. 4,152,420 (Gaffar), U.S. Pat. No. 3,956,480 (Dichter et al), U.S. Pat. 4,138,477 (Gaffar) and U.S. Pat. 4, 1.83.94 (Gaffar et al). However, only a disclosure substantially equivalent to U.S. Pat. No. 4,627,977 (Gaffar et al.) Use of these polycarboxylates to inhibit the salivary hydrolysis effect of pyrophosphate comprising antitartar agents in combination with a compound which provides a source of fluoride ion.

It should be understood that the synthetic anionic polymeric polycaboxylates so disclosed in these mentioned patents n? 512 333 '' '16 writings, when containing or modified to contain the retention enhancing groups defined above, are operative as AEA materials in the compositions and methods of the invention and these disclosures are hereby incorporated herein by reference.

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

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

Additional operative polymeric polycarboxylates disclosed in the aforementioned U.S. Pat. 4,138,477 and U.S. Pat. 4,183,914, and containing or modified to contain retention enhancing groups, include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyidaconic and polymalic acids and sulfoacrylic oligomers with M.W. as low as 1,000, available as Uniroyal ND-2.

Generally suitable are polymerized retention enhancing, group-containing, olefinically or ethylenically unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, i.e. an acid containing an olefinic double bond which acts rapidly upon polymerization due to its presence in the -beta position with respect to the carboxyl group or as part of a terminal with ethylene grouping. Illustrative of these acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, croton, beta-acryloxide oxide propion, sorbine, alpha-chlorosorbine, cinnamine, beta-styrylacrylic, mucon, itacone, citraconone -, mesacon, glutacone, aconite, alpha-phenylacryl, 2-benzylacrylic, 2-cyclohexylacrylic, angelin, umbellin, fumaric, maleic acids and anhydrides. Other various olefinic monomers that are copolymerizable with these carboxyl monomers include vinyl acetate, vinyl chloride, dimethyl, maleate and the like. Copolymers usually contain enough carboxyl salt groups for water solubility.

Also useful herein are so-called carboxyvinyl polymers disclosed as toothpaste components in U.S. Pat. No. 3,980,767 (Chown et al.), U.S. Pat. No. 3,935,306 (Roberts et al), U.S. Pat. 3,919,409 (Perla et al), U.S. Pat. 3,91l, 904 (Harrison) and U.S. Pat. 3.71l, 604 (Colodney et al). They are commercially available, for example, under the trademarks Carbopol 934, 940 and 941 (BV Goodrich), these products consist essentially of a colloidal water-soluble polymer of polyacrylic acid polymer crosslinked with from about 0.75 to about 2% polyallyl sucrose or polyallyl pentaerythritol as a crosslinking agent wherein the crosslinked structures and linkages provide the desired retention enhancement through hydrophobicity and / or physical retention of the antibacterial agent or the like. Polycarbophil is somewhat similar and is a polyacrylic acid crosslinked with less than 0.2% divinyl glycol with the lower proportion, molecular weight and / or hydrophobicity of this crosslinking agent tending to provide reduced or no retention improvement. 2,5-Dimethyl-1,5-hexadiene exemplifies a more effective retention enhancing crosslinking agent.

The synthetic anionic polymeric polycarboxylate component is usually a hydrocarbon with optionally halogen and O-containing substituents and linkages as present in, for example, ester, ether and OH groups and when present, is generally used in the present compositions in approximate amounts by weight of up to to about 4% (usually at least about 0.05%).

The AEA material may also comprise natural anionic polymeric polycarboxylates containing retention enhancing groups. Carboxymethyl, cullulose and other binders, gums and film formers that are free from the above-defined release enhancing and / or retention enhancing groups are ineffective as AEA materials.

As illustrative of AEA material-containing phosphinic acid and / or sulfonic acid as emission enhancing groups, there may be mentioned polymers and copolymers containing units or groups derived from the polymerization of vinyl or allyl phosphine and / or sulfonic acids substituted as needed on the 1 or 2 (or 3) carbon atom with a organic retention enhancing group having, for example, the formula defined above - (X) nR. Mixtures of these monomers can be utilized and copolymers thereof with one or more interpolymerizable ethylenically unsaturated monomers such as those described above with respect to the 512 333 "" 19 synthetic anionic polymeric carboxylates. As can be seen, in these and other operative polymeric AEA materials, usually only an acidic release enhancing group is attached to any given carbon atom or other atom in the polymer backbone or branch thereof. Polysiloxanes containing or modified to contain pendant release enhancing groups and retention enhancing groups may also be used as AEA materials herein.Also effective as AEA materials herein are ionomers containing or modified to contain release and retention enhancing groups. pp. 546-573 of the Kirk-Othmer Encyclopedia of Chemical Technology, Third Edition, Supplement Volume, John Wiley and Sons, Inc. copyright 1984, and this disclosure is hereby incorporated herein. Also effective as AEA materials herein, provided that they contain or are modified to contain retention enhancing groups, is polyester polyurethanes and synthetic and natural polyamides containing proteins and proteinaceous materials such as collagen, poly (argenin) and other polymerized amino acids.

When the oral preparation is prepared by initially dissolving the polyphosphate and the antibacterial agent in humectants and surfactants and adding thereto AEA, especially the polycarboxylate, in small steps, the solution becomes clear and can be characterized as a "microemulsion".

As the amount of polycarboxylate increases so that the finished oral preparation contains at least about 2.2% by weight thereof, the solution becomes milky and may be characterized as a "macroemulsion". In these "macroemulsion" type compositions, the anti-plaque action of the antibacterial agent appears to be optimized.

A desirable weight ratio of the substantially water-soluble noncationic antibacterial agent to the polyphosphate antitussive agent is in excess of about 0.72: 1 to less than about 4: 1, for example 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 antitartar effectiveness of the oral composition, there are advantageously inhibitors against enzymatic hydrolysis of the polyphosphate. These agents are an amount of a fluoride ion source sufficient to supply ppm to 5,000 ppm fluoride ions, and up to 3% or more of the synthetic anionic polymeric carboxylate having a molecular weight of about 1,000 to about 1,000,000, preferably about 30,000 to about 500,000.

The sources of fluoride ions or fluorine-providing component, such as acid phosphatase and pyrophosphatase enzyme inhibitor component, are well known in the art as anti-caries agents. These compounds may be poorly soluble in water or may be completely water soluble. They are characterized by their ability to release fluoride ions into water and by freedom from undesired reaction with other components of the oral preparation. These materials include inorganic fluoride salts such as soluble alkali metal, alkaline earth metal salt, for example sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprous fluoride, zinc fluoride, barium fluoride, sodium fluorosiliconate, ammonium fluorosiliconosilicate, ammonium fluorosiliconate and difluorophosphate and fluorinated sodium calcium pyrophosphate. Alkali metal and tin fluorides such as sodium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof are preferred.

The amount of fluorine-releasing 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 tooth 512 355 f? In the formulation of a pharmaceutical gel, for example a dental gel, toothpaste (including cream), tooth powder or dental tablet, an amount of this compound which releases up to about .000 ppm F ion on the basis of the weight of the preparation is considered to be satisfactory. Any suitable minimum amount of this compound can be used, but it is preferred to use a sufficient amount of compound to release about 300 to 2,000 ppm, more preferably about 800 to about 1,500 ppm fluoride ion.

Typically, in the case of alkali metal fluorides, this component is present in an amount of up to about 2% by weight, based on the weight of the formulation, preferably in the range of about 0-05% to 1%. In the case of sodium monofluorophosphate, the compound may be present in an amount of about 0.3%, more typically about 0.76%.

In oral formulations such as mouthwashes, tablets and chewing gum, the fluorine-providing compound is typically present in an amount sufficient to release up to about 500 ppm, preferably about 25 to 300 ppm by weight of fluoride ion. Typically, about 0.005 to about 1.0 weight percent of this compound is present.

In some highly preferred forms of the invention, the oral composition may be substantially liquid in nature, such as a mouthwash or mouthwash. In such a preparation, the vehicle is typically a water-alcohol mixture which suitably includes a humectant or humectant as described below. In general, the weight ratio of water to alcohol ranges from about 1: 1 to about 20: 1, preferably about 3: 1 to 10: 1, and preferably about 4: 1 to about 6: 1. The total amount of water-alcohol mixture in this type of preparation is typically in the range of from about 70 to about 99.9,512 ss to 22% by weight of the preparation. The alcohol is typically ethanol or isopropanol. Ethanol is preferred. The pH of this liquid and other formulations of the invention is generally in the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pH is preferably in the range of from about 6 to about 8.0. It is noteworthy that the compositions of the invention can be applied orally at a pH below 5 without substantially decalcifying or otherwise damaging dental enamel. The pH can be adjusted with an acid (eg citric acid or benzoic acid) or base (eg sodium hydroxide) or buffered (such as with sodium citrate, benzoate, carbonate or bicarbonate, disodium hydrogen phosphate, sodium dehydrogen phosphate, etc.).

In some other desirable form of the present invention, the oral composition may be substantially solid or pasty in nature, such as tooth powder, a dental tablet or dentifrice, i.e. a toothpaste (toothpaste) or a gel-like dentifrice. The vehicle for these solid or pasty oral preparations contains generally dentally acceptable polishing materials. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium dioxide, silica-carbonate, hydrated alumina, silicaate.

Other suitable polishing materials include the particulate thermosets described in U.S. Pat. 3,070,510, issued December 1962, such as melamine, phenol and urea formaldehydes and crosslinked polyepoxides and polyesters. Preferred polishing materials include crystalline silica having particle sizes 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 3 / g, silica gel or I * 512 333 "i" 23 collodial silica and complex amort alkali metal-aluminum silicate.

When visually clear gels are used, a colloidal silica polish such as those sold under the trademark SYLOID such as Syloid 72 and Syloid 74 or under the trademark SANTOCEL such as Santocel 100, alkali metal-aluminum silicate complexes are particularly useful because they have refractive indices which are close refractive index for gelling agent-liquid (including water and / or humectants) systems 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. Thus, insoluble sodium metaphosphate can be formed in any suitable manner as illustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4th Edition, pages 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 show only a low solubility in water and are therefore commonly referred to as insoluble metaphosphates (IMP). There is a small amount of soluble phosphate material such as impurities, usually a few percent such as up to 4% by weight. The amount of soluble phosphate material assumed to include a soluble sodium trimetaphosphate in the case of insoluble metaphosphate can be reduced or eliminated by washing with water if desired.

The insoluble alkali metal metaphosphate is typically used in powder form with a particle size such that at most 1% of the material is greater than 37 microns.

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

In a toothpaste, the liquid carrier may comprise water and humectant, typically in an amount ranging from about 10% to about 80% by weight of the formulation. Glycerin, propylene glycol, sorbitol and polypropylene glycol provide examples of suitable humectants / carriers. Also advantageous are liquid mixtures of water and glycerin and sorbitol. In clear gels for which refractive index is an important aspect, about 2.5-30% by weight of water, 0 to about 70% by weight of glycerin and about 20-80% by weight of sorbitol are preferably used.

Toothpastes, creams and gels typically contain a natural or synthetic thickener or gelling agent in proportions of about 0.1 to about 10, preferably about 0.5 to about 5 weight percent. A suitable thickener is synthetic hectorite, a synthetic colloidal magnesium-alkali metal-silicate complex clay available for example such as Laponite (eg CP, SP 2002, D) marketed by Laporte Industries Limited.

Laponite D has an analysis which on a weight basis is approximately 58,002; sio2, 2s, 4o% Mgo, 3.05% Nazo, 0.98% Lizo and some water and trace metals. Its true specific gravity is 2.53 and it has an apparent bulk density (g / ml at 8% moisture) of 1.0.

Other suitable thickeners include Irish moss, iota carrageenan, gum tragacanth, polyvinylpyrrolidone starch, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose (e.g. available as Natrasol), such as sodium cellulose carboxyl In certain dentifrices prepared in accordance with the present invention, especially when more than 0.35% by weight of the water-insoluble antibacterial agent is used and a siliceous polish is present in an amount of less than 30% by weight, it may be desirable to include These solubilizers include humectants such as propylene glycol, dipropylene glycol and hexylene glycol, cell solvents such as methyl cellosolv and ethyl cellosolv, vegetable oils and waxes containing at least about 12 carbon chains in a straight chain such as ol. oil, castor oil and petrolatum and esters such as amyl acetate, ethyl acetate and benzyl benzoate.

It should be clear that, as is conventional, the oral preparations are intended to be sold or otherwise distributed in appropriately labeled packages. Thus, a can of mouthwash will have a label which substantially describes it as a mouthwash or mouthwash and has instructions for its use; and a toothpaste, cream or gel will usually be in a compressible type, typically of aluminum, lined lead or of plastic or any other squeezing dispenser, pump dispenser or pressurized dispenser for dosing the contents, provided with a label as in essentially describes the contents as a toothpaste, gel or toothpaste.

Organic surfactants are used in the compositions of the present invention to achieve increased prophylactic action, to assist in achieving thorough and complete dispersion of the anti-tartar agent and anti-plaque agent throughout the oral cavity, and to make the present compositions more cosmetically acceptable. The organic surfactant material is preferably anionic, nonionic or anphalytic in nature and it is preferred to use as a surfactant a detergent material which imparts detersive 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 monosulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkylaryl sulfonates such as sodium dodecyl sulfene benzene sulfate benzene sulfate benzenesulphene and the substantially saturated higher aliphatic acyl amides of lower aliphatic aminocarboxylic acid compounds such as those having 12 to 16 carbon atoms in the fatty acid, alkyl or acyl radicals and the like. Examples of the latter amides are N-lauroyl sarcosine and sodium, potassium and ethanolamine salts of N-lauroyl, N-myristoyl or N-palmitoyl sarcosine which should be substantially 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 prolonged marked effect in the inhibition of acid formation in the oral cavity due to carbohydrate degradation, in addition to exerting a certain reduction in the solubility of tooth enamel in acidic solutions.

Examples of water-soluble nonionic surfactants are ethylene oxide condensation products with various reactive hydrogen-containing compounds which are reactive therewith and have long hydrophobic chains (for example aliphatic chains having about 12 to 20 carbon atoms) which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene groups such as condensation ethylene oxide) with fatty acids, polyhydric alcohols (eg sorbitan monostearate) and polypropylene oxide (eg Pluronic material). 0.1-5% by weight, preferably about 1-2.5%. It is noteworthy that the surfactant can help to dissolve the non-cationic antibacterial agent and thereby reduce the required amount of solubilizing humectant.

Various other materials may be incorporated into the oral formulations of the present invention, such as whitening agents, preservatives, silicones, chlorophyll compounds and / or ammoniated materials such as urea, diamonium phosphate and mixtures thereof. If these adjuvants or excipients are present, they are incorporated into the formulations in amounts which do not have a significant adverse effect on desired properties and characteristics. Significant amounts of zinc, magnesium and other metal salts and materials, generally soluble, which would form complexes with the active components of the present invention should be avoided.

Any suitable seasoning or sweetening material can also be used. Examples of suitable flavoring ingredients are flavoring oils, for example spearmint, peppermint, evergreens, sassafras, clover, sage, eucalyptus, marjoram, cinnamon, lemon and orange and methyl salocylate. Suitable sweeteners include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartine, AMP (aspartylphenylalanine, methyl ester), saccharin and the like. The flavoring and sweetening agents may suitably each or together comprise from about 0.1% to 5% or more of the formulation. Furthermore, flavoring oils appear to contribute to the dissolution of the antibacterial agent.

In the preferred practice of the present invention, an oral preparation according to the invention, such as an oral rinse or a dentifrice containing the composition of the present invention, is preferably applied regularly to dental enamel, such as every day or every other or every third day or preferably from 1 to 3 times daily, at a pH of about 4.5 to about 9, generally about 5.5 to about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more up to life.

The compositions of the present invention may be incorporated into lozenges or chewing gum or other products, for example by stirring in a hot gum base, or coating the outer surface of a gum base of which, by way of illustration, may be mentioned gelutone, gum latex, vinylite resins, etc., preferably with conventional plasticizers or plasticizers, sugars or other sweeteners or the like, such as glucose, sorbitol and the like.

The following examples are further illustrative of the nature of the present invention, but it should be understood that the invention is not limited thereto. All amounts and proportions set forth herein and in the appended claims are by weight unless otherwise indicated.

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

Example 1 The adsorption to and release from dental minerals with respect to antiplack / antifungal efficacy is evaluated by the adsorption of antibacterial agent on saliva-coated dental mineral disc of hydroxyapatite, in the presence of pyrophosphate and various amounts of polycarboxylate.

The prescriptions for the evaluated toothpastes are: Weight parts è ä 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 (deionized577) 9.95 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 0.3000 G in an amount of 2.5 parts in toothpaste A and 2.0 parts in toothpaste B.

For the test of the delivery of antibacterial agent to a saliva-coated hydroxyapatite wafer, hydroxyapatite (HA) obtained from Monsanto Co. is washed. vigorously with distilled water, collected by vacuum filtration and allowed to dry overnight at 37 ° C. This dried HA is ground to a powder with a mortar and pestle. 150.00 mg of HA is placed in the cavity of a KBr pelletizing pad (Barnes Analytical, 512 333 1 "'Stanford, CT) and compressed for 6 minutes at 4,536 kg in a Carver Laboratory press. The resulting 13 mm discs are sintered under 4 hours at 800 ° C in a Thermolyne oven. Parafilmimulated whole saliva is collected in an ice-cold glass beaker. The saliva is clarified by centrifugation at 15,000 g for 15 minutes at 4 ° C. Sterilization of the clarified saliva is carried out at 4 ° C with stirring by irradiation of the sample with UV light for 1.0 hour.

Each sintered disk is hydrogenated with sterile water in a polyethylene test tube. The water is then removed and replaced with 2.00 ml of saliva. A salivary membrane 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 liquid phase dentifrice solution, and incubated at 37 ° C with continuous shaking in the water bath. After 30 minutes, transfer the disc to a new tube and add 5.00 ml of water, followed by gently shaking the disc with a Vortex. The disc is then transferred to a new tube and the washing procedure is repeated twice. Finally, the disc is carefully transferred into a new tube to avoid co-transfer of any liquid along with the disc. Then add 1.00 ml of methanol to the disc and shake it vigorously with a Vortex. The sample is left at room temperature for 30 minutes to extract the adsorbed triclosan in the methanol. The methanol is then aspirated and clarified by centrifugation in a Beckman Microfuge 11 at 10,000 rpm for 5 minutes. After this treatment, the methanol is transferred into HPLC (high performance liquid chromatography) vials to determine the concentration of antibacterial agent. Triple samples were used in all experiments. 512 533 31 The table below summarizes the data: Table Delivery of TCHE to saliva transfer- Toothpaste coated hydroxyapatite disc in micrograms A 130 B 30 Data given indicate that with increasing amount of Gantrez (toothpaste A) there is a very sharp increase in the delivery of TCHE to saliva coated tooth mines .

Example_2 The following toothpaste is effective as an anti-plaque and anti-tartar composition: Parts by weight Sorbitol (70%) 22.00 Irish Moss 1.00 Sodium hydroxide (50%) 1.00 Gentrex (13.02% solution) 19.00 Water (deionized) 2 , 69 Sodium monofluorophosphate 0.76 Sodium saccharin 0.30 Pyrophosphate 2.00 Hydrogenated alumina 48.00 Flavor oil 0.95 TCHE 0.30 SLS 2.00 512 333 32 Exemgel 3 Mouthwash Tetranodium pyrophosphate Gantrez S-97 Glyceride Atomic acid Exemgel 4 Tablet 75-80% sugar 1-20% corn syrup 0.1-1.0 Flavor oil oil tetrasodium pyrophosphate 2.50% Gantrez S-97 0.01 to 0.05% NaF 0.01 to 0.1% TCHE 1 to 5% magnesium stearate, lubricant 0.01 to 0.2% water Exemgel 5 Chewing gum Gum base Sorbitol (70%) TCHE tetrasodium pyrophosphate Gantrex S-97 Parts 2.00 2.50 .00 * 0.05 0.20 0.06 0.40 100.00 Parts .00 17.00 0.50 2.00 2.50 to 0.10 512 ass 33 In the previous examples, improved results are obtainable even when TCHE is replaced with each o and one of phenol, 2,2'-methylene bis (4-chloro-6-bromophenol), eugenol and thymol and / or when Gantrez is replaced by other AEA materials such as carbopoles (eg 934) or styrene phosphonic acid polymers having molecular weights within the range about 3,000 to 10,000, such as poly (beta-styrene phosphonic acid), copolymers of vinylphosphonic acid with beta-styrene phosphonic acid, and poly (alpha-styrene phosphonic acid), or sulfoacrylic oligomers, or a 1: 1 copolymer of maline anhydride with ethyl acrylate.

Similar results are obtained when pyrophosphate (tetra4 sodium pyrophosphate) is replaced by tetrasodium pyrophosphate and tetrachotassium pyrophosphate, the weight ratio of potassium to sodium being a) 0.37: 1, b) 1.4: 1, c) 3: 1 and 3.5: 1.

This invention has been described with respect to certain preferred embodiments, and it is to be understood that modifications and variations thereof which will be apparent to those skilled in the art are included within the scope of the present application and the scope of the appended claims.

Claims (31)

512 333 34 P a t e n t k r a v An oral composition characterized in that it comprises an orally acceptable vehicle, an effective amount of anti-tartar material amounting to about 0.1-3% by weight of at least one linear molecularly dehydrated polyphosphate salt as anti-tartar agent, an effective anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent and up to about 4% by weight of an antibacterial action enhancing agent, which improves the delivery of the antibacterial agent to and the retention thereof on oral surfaces, the weight ratio of antibacterial action enhancing agent to polyphosphate ion being in the range of from about 1, 6: 1 to about 2.7: 1. Oral composition according to claim 1, characterized in that the antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated salicyl anilides, benzoesters, halogenated carbanilides and phenolic compounds. An oral composition according to claim 1, wherein the antibacterial agent is a halogenated diphenyl ether. Oral composition according to Claim 3, characterized in that the halogenated definyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. Oral composition according to claim 1, wherein the antibacterial agent is a phenolic compound. Oral composition according to claim 5, characterized in that the phenol compound is selected from the group consisting of phenol, thymol, eugenol and 2,2'-methylene bis (4-chloro-6-bromophenol). Oral composition according to claim 2, characterized in that the antibacterial agent is present in an amount of about 0.01-5% by weight. Oral composition according to claim 7, characterized in that the amount of antibacterial agent is about 0.25-0.5%. Oral composition according to claim 1, characterized in that the linear molecularly dehydrated polyphosphate salt is an alkali metal pyrophosphate present in an amount of 1-2.5% by weight. An oral composition according to claim 9, characterized in that the alkali metal pyrophosphate is tetrasodium pyrophosphate. 11. ll. Oral composition according to any one of claims 1-10, characterized in that the weight ratio of antibacterial effect enhancing agent to polyphosphate ion is about 1.7: 1 to about 2.3: 1. An oral composition according to any one of claims 1 to 11, characterized in that the vehicle comprises water, humectant and a gelling agent and that the oral composition contains a dentally acceptable water-insoluble polish and is a dentifrice. An oral composition according to any one of claims 1 to 11, characterized in that the vehicle comprises water and a non-toxic alcohol and that the oral composition is a mouthwash. _ 512 533 36 An oral composition according to any one of claims 1 to 15, characterized in that the antibacterial action enhancing agent has an average molecular weight of about 1,000 to about 1,000,000. Oral composition according to claim 14, characterized in that the antibacterial action enhancing agent contains at least one release-improving functional group and at least one organic retention-improving group. Oral composition according to claim 15, characterized in that the release-enhancing group is acidic. An oral composition according to claim 16 characterized in that the release enhancing group is selected from the group consisting of carboxyl, phosphonic, phosphine and sulfonic acids and their salts and mixtures thereof. Oral composition according to claim 17, characterized in that the organic retention enhancing group has the formula - (X) n R wherein X is O, N, S, SO, SO 2, PO or Si, R is hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic, or their inert-substituted derivatives, and n is 1 or zero. An oral composition according to any one of claims 1 to 18, characterized in that the antibacterial action enhancing agent is an anionic polymer containing a plurality of release enhancing groups and organic retention enhancing groups. Oral composition according to claim 19, characterized in that said anionic polymer comprises a chain containing repetitive units each containing at least one carbon atom. 512 333 37 The oral composition of claim 20 wherein each moiety contains at least one release enhancing group and at least one organic retention enhancing group attached to the same atom or to vicinal atoms or other atoms in the chain. Oral composition according to claim 17, characterized in that the release enhancing group comprises a carboxyl group or a salt thereof. An oral composition according to any one of the preceding claims, characterized in that the antibacterial action enhancing agent is a copolymer of maleic acid or anhydride with an ethylenically unsaturated polymerizable monomer or a salt thereof. 24. I24. Oral composition according to claim 23, characterized in that the second monomer is methyl vinyl ether in a 4: 1 to 1: 4 molar ratio to the maleic acid or anhydride. Oral composition according to any one of claims 1-24, characterized in that the copolymer has a molecular weight of about 30,000-1,000,000. A composition according to claim 25, characterized in that the copolymer has an average molecular weight of about 70,000. 27. A composition according to claim 17 characterized in that the release enhancing group comprises a phosphone group or a salt thereof. Composition according to claim 27, characterized in that the antibacterial action 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 ethylene unsaturated monomer or its salts. 29. A composition according to claim 28 characterized in that the antibacterial action enhancing agent has a molecular weight of about 1,000 to about 30,000. An oral composition according to any one of claims 1-29 characterized in that it contains a fluoride-ion donating source. An oral composition according to any one of claims 1-30 for the manufacture of plaque inhibiting agents for the treatment of oral surfaces.