LU87651A1 - ANTIBACTERIAL, ANTI-PLATE AND ANTI-SCALE COMPOSITION FOR ORAL USE AND METHOD OF USE - Google Patents

Description

The present invention relates to a composition for oral use antibacterial / anti-plaque and anti-tartar. More particularly / the invention relates to a composition for oral use containing a polyphosphate as an anti-scale agent and a compatible antibacterial agent effective for inhibiting dental plaque, the antiplaque activity being optimized by the presence of an antibacterial stimulating agent which improves the distribution and retaining said antibacterial agent on the surfaces of the oral cavity.

U.S. patents Nos. 4,627,977, 4,515,772 and 4,323,551 describe compositions for oral use which contain various polyphosphates. According to the aforementioned patent No. 4,627,977, a linear molecularly dehydrated salt polyphosphate is used in conjunction with a source of fluoride ions and a synthetic linear polymeric polycarboxylate to inhibit the formation of tartar. In the simultaneously pending European patent application No. 89 200 710.5, the anti-scale activity is optimized with a lower proportion of the linear molecularly dehydrated salt polyphosphate used jointly with the source of fluoride ions and a greater proportion of the synthetic linear polymeric polycarboxylate .

According to patents Nos. 4,515,772 and 4,323,551, use is made of a water-soluble di (alkali metal) pyrophosphate, alone or as a mixture with a tetra pyrophosphate (alkali metal).

The compositions for buccal use which inhibit the formation of tartar on the dental surfaces are very interesting, because tartar is one of the factors responsible for periodontal diseases. Therefore, its reduction promotes oral hygiene.

Plaque is a precursor to tartar. Unlike tartar, however, plaque can form anywhere on the surface of the tooth, including in particular at the gingival margin. As a result, in addition to its unsightly appearance, dental plaque is involved in the appearance of gingivitis.

Consequently, it would be very desirable to include antimicrobial agents, already known for reducing dental plaque, in compositions for oral use containing anti-scale agents. In fact, this has been described in the U.S. Patent. No. 4,022,550 in which a compound providing zinc ions is mixed as an anti-scale agent with an antibacterial agent effective in retarding the development of bacteria in dental plaque. A wide variety of antibacterial agents are described with zinc compounds, including cationic substances such as guanides and quaternary ammonium compounds, as well as non-cationic compounds such as halogenated salicylanilides and halogenated hydroxyphenyl ethers .

So far, cationic antibacterial substances such as chlorhexidine, benzethonium chloride and cetylpyridinium chloride have been the subject of the most important research on antibacterial anti-plaque agents. However / although used in conjunction with a zinc scale inhibitor / they are ineffective when used with anionic substances such as a polyphosphate type scale inhibitor. This ineffectiveness is considered to be entirely surprising, given that polyphosphates are chelating agents and that it has been previously recognized that the chelating effect increases 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 Cell, Hugo, 1971, page 215). In fact, a quaternary ammonium compound is present in the pyrophosphate antiplaque mouthwash of the U.S. Patent. No. 4,323,551, and a bis-biguanide is suggested as an antiplaque agent in the oral pyrophosphate scale composition of the U.S. Patent. No. 4,515,772.

Given the surprising incompatibility of cationic antibacterial agents with the polyphosphates present as anti-scale agents, it was completely unpredictable that other antibacterial agents would be effective.

An advantage of the present invention is that it offers certain antibacterial agents effective in inhibiting the formation of dental plaque in anti-scaling compositions for oral use containing a linear saline polyphosphate with molecular dehydration, a source providing fluoride ions and the agent. of the above-mentioned antibacterial stimulation.

Another advantage of the present invention is that it provides a composition which is effective in reducing the formation of dental calculus and optimizing the reduction of dental plaque.

Another advantage of the present invention is that it provides an anti-plaque anti-plaque composition for oral use which is effective in reducing the appearance of gingivitis.

Other advantages of the present invention will emerge from the description which follows.

In some of its aspects, the present invention relates to a composition for oral use comprising, in an acceptable vehicle for oral use, an effective amount against dental calculus of a material comprising approximately 0.1 to 3% by weight of at least a linear saline polyphosphate with molecular dehydration as an anti-scale agent, an amount effective against dental plaque of a non-cationic antibacterial agent substantially insoluble in water and, advantageously, up to about 4% by weight of an antibacterial stimulating agent which improves the distribution and retention of said antibacterial agent on the surfaces of the oral cavity, in which the weight ratio of polyphosphate ions to the antibacterial stimulating agent being 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 from about 1.7: 1 to about 2.3: 1 , and better still about 1.9: 1 about 2: 1. For example, when using tetrasodium pyrophosphate (PPTS) (providing about 1.3% pyrophosphate ions) with 2.5% of the antibacterial stimulating agent, a very advantageous weight ratio of about 1 is obtained. , 9: 1.

Representative examples of antibacterial agents which are particularly advantageous for considerations of efficacy against dental plaque, safety of use and formulation are as follows:

Halogenated diphenyl ethers 2 ', 4,4'-trichloro-2-hydroxy (diphenyl ether) (Triclosan) 2/21-dihydroxy-5,5'-dibromo (diphenyl ether) Halogenated salicylanilides 4', 5-dibromosalicylanilide 3/4 ', 5-trichlorosalicylanilide 3/4' / 5-tribromosalicylanilide 2 / 3.3 '/ 5-tetrachlorosalicylanilide 3.3,3', 5-tetrachlorosalicylanilide 3.5- dibromo-3'-trifluoromethyl-salicylanilide 5-n- octanoyl-3'-trifluoromethyl-salicylanilide 3.5- clibromo-4 '-trif luoromethyl-salicylanilide 375-dibromo-3'-trifluoromethyl-salicylanilide (Flurophene)

Benzo esters methyl p-hydroxybenzoate ethyl p-hydroxybenzoate propyl p-hydroxybenzoate butyl p-hydroxybenzoate

Halogenated carbanilides 3,4,4'-trichlorocarbanilide ^ 3-trifluoromethyl-4,4'-dichlorocarbanilide 3,3,4'-trichlorocarbanilide

Phenolic compounds (including phenol and its counterparts, halogenated mono- and polyalkyl- and aryl-phenols (e.g., F, Cl, Br, I), resorcinol, pyrocatechol and their derivatives, and bisphenolic compounds). These phenolic compounds include among others:

Phenol and its counterparts Phenol 2- methylphenol 3- methylphenol 4- methylphenol 4-ethylphenol 2/4-dimethylphenol 2/5-dimethylphenol 3/4-dimethylphenol 2I6-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-methylphenol (thymol)

Mono- and poly-alkyl- and aralkyl-halogenophenols Methyl-p-chlorophenol Ethyl-p-chlorophenol n-propyl-p-chlorophenol n-butyl-p-chlorophenol n-amyl-p-chlorophenol sec.-amyl-p-chlorophenol n-hexyl-p-chlorophenol Cyclohexyl-p-chlorophenol n-heptyl-p-chlorophenol n-octyl-p-chlorophenol o-chlorophenol Methyl-o-chlorophenol Ethyl-o-chlorophenol n-propyl-o-chlorophenol n-butyl- o-chlorophenol n-amyl-o-chlorophenol tert - amyl-o-chlorophenol n-hexyl-o-chlorophenol n-heptyl-o-chlorophenol p-chlorophenol o-benzyl-p-chlorophenol o-benzyl-m-methyl- p-chlorophenol o-benzyl-m, m-dimethyl-p-chlorophenol o-phenylethyl-p-chlorophenol o-phenylethyl-m-methyl-p-chlorophenol 3- raethyl-p-chlorophenol 3/5-diraethyl-p-chlorophenol 6-ethyl-3-raethyl-p-chlorophenol 6-n-propy1-3-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 l-3-methyl-p-chlorophenol 6-isopropyl-2-ethyl-3-methyl-p-chlorophenol 2-sec.-arayl-3/5-dimethyl-p-chlorophenol 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-propy1-m / m-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-hydroxydipheny line thane

Resorcinol and its derivatives Resorcinol Methylresorcinol Ethylresorcinol n-propylresorcinol n-butylresorcinol n-hexylresorcinol n-heptylresorcinol n-octylresorcinol-phenylresorin phenylresorin phenylresorinol phenylresorcinol phenylresorcinol 4'-chloro-2,4-dihydroxydiphenylmethane 5-bromo-2,4-dihydroxydiphenylmethane 4'-bromo-2,4-dihydroxydiphenylmethane Bisphenolic compounds Bisphenol A

2,2'-methylene-bis (4-chlorophenol) 2,2'-methylene-bis (3,4,6-trichlorophenol) (hexachlorophene) 2,2'-methylene-bis (4-chloro-6-bromophenol)

Bis (2-hydroxy-3,5-dichlorophenyl) sulfide

Bis (2-hydroxy-5-chlorobenzyl) sulfide The antibacterial agent is present in the composition for oral use in an amount effective against dental plaque, generally about 0.01 to 5% by weight, preferably of about 0.03 to 1%, most preferably about 0.25 to 0.5%, and at best about 0.25 to 0.35%. The antibacterial agent is substantially insoluble in water, 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 solubility is determined at a pH at which no ionization occurs.

The preferred halogenated diphenyl ether is Triclosan. The preferred phenolic compounds are phenol ·, thymol, eugenol, and 2,2'-methylene-bis (4-chloro-6-bromophenol). The most preferred anti-bacterial anti-bacterial compound is Triclosan. Triclosan is proposed in the U.S. patent. No. 4,022,880 mentioned above as an antibacterial agent in combination with an anti-scale agent which provides zinc ions and in R.F.A. patent No. 3,532,860 in combination with a copper compound. In European Patent No. 0 278 744, it is proposed in combination with a tooth desensitizing agent containing a source of potassium ions. It is also proposed in the published European patent application No. 0 161 898 as an antiplaque agent in a toothpaste formulated so as to contain a lamellar phase of a surface active agent of lamellar liquid crystal whose interlamellar spacing is less than 6 , 0 nm and which may optionally contain a zinc salt, as well as in the published European patent application No. 0 161 899 in a toothpaste containing zinc citrate trihydrate.

The linear saline polyphosphates with molecular dehydration which are effective here as anti-scale agents are well known compounds, generally employed in the form of water-soluble salts, totally or partially neutralized, of alkali metals (for example potassium, and preferably sodium) or ammonium, and any mixture of them. Representative examples include sodium hexametaphosphate, sodium tripoly-phosphate, disodium diacid pyrophosphates, trisodium and tetrasodium monoacids, corresponding potassium salts, etc. Linear polyphosphates have the formula (NaPO ^^ where n is from about 2 to about 125. In the present invention, they are used in compositions for oral use in weight proportions of · 0.1 to 3%, typically thence 2.5%, and more typically 1.5 to 2% When n is equal to or greater than 3 in (NaPOg) ^ these polyphosphates are vitreous in nature.

Particularly advantageous anti-scale agents are the tetra (alkali metal) pyrophosphates, including their mixtures, such as tetrasodium pyrophosphate, tetrapotassium pyrophosphate, and their mixtures. Thus, the composition for buccal use may contain a polyphosphate type anti-scale agent which is substantially free of tetrasodium pyrophosphate or substantially free of a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate where the ratio of potassium pyrophosphate to sodium pyrophosphate is equal to or greater than 3: 1. An anti-scale agent comprising approximately 2% by weight of tetrasodium pyrophosphate, relative to the weight of the compositions for oral use, is particularly effective.

The antibacterial stimulating agent (ASA) which improves the distribution and retention of said antibacterial agent on the oral surfaces, is used in effective amounts to achieve this improvement which are in the range of about 0/005% to about 4%, preferably from about 0.1% to about 3% and more preferably from about 0.5% to about 2.5% by weight in the composition for oral use.

ASA can be a simple compound, buccal rence a polymerizable monomer, better still a polymer, the latter term being taken in a completely generic sense and including for example oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, crosslinked polymers and copolymers, etc. ASA can be natural or synthetic, and insoluble in water or, preferably, soluble or swellable (hydra-table, forming a hydrogel) in water (saliva). It has an average molecular weight (by weight) of about 100 to about 1,000,000, preferably from about 1,000 to about 1,000,000 and more preferably from about 2,000 or 2,500 to about 250,000 or 500,000.

ASA ordinarily contains at least one distribution enhancing group, which is preferably acidic, for example of a sulfonic, phos-phonic, or more preferably phosphonic or carboxylic acid, or a salt thereof, for example of metal alkaline or ammonium, and at least one organic group improving the retention, preferably several of each of the groups improving the distribution and improving the retention, the latter groups preferably corresponding to the formula - (X) -R where X is 0 , N, S, SO, SO „, P, PO, n 2

If, etc., R is a hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic group or their derivatives with inert substituents, and n is zero or 1 or more. The above-mentioned "derivatives with inert substituents" have substituents on R which are generally non-hydrophilic and do not substantially disturb the functions which the ASA must fulfill to improve the distribution and the retention of the antibacterial agent on the oral surfaces, for example. halogen-gen substituents, in particular Cl, Br, I, and carbo, etc. Representative examples of such retention enhancing groups are presented in a table below.

η X - (X) n 0 --- methyl, ethyl, propyl, butyl, isobutyl, t-butyl, cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furannyl, acetyl, benzoyl, butyryl, terephthaloyl, etc. .

Ethoxy, benzyloxy, thioacetoxy, phenoxy, carbethoxy, carbobenzyloxy, etc.

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

S thiobutyl, thio-isobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenylthioacetyl, thiobenzoyl, etc.

50 butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc.

SO2 butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

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

PO diethylphophinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, methylbenzylphosphinoxy, methylphenylphosphinoxy, etc.

51 trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl, dimethylvinylsilyl, dimethylallylsilyl, etc.

As used herein, the term "distribution enhancing group" refers to a group which substantially or adhesively fixes or binds ASA (carrying the antibacterial agent) to surfaces from the oral cavity (eg teeth and gums), thereby "delivering" or "distributing" the antibacterial agent to these surfaces. The organic group improving retention, generally hydrophobic, fixes or otherwise binds the antibacterial agent to ASA, thereby improving the retention of the antibacterial agent to ASA and, indirectly, to the surfaces of the oral cavity. In some cases, the fixing of the antibacterial agent is carried out by its physical encroachment by ASA, in particular when the ASA is a crosslinked polymer, the structure of which offers by nature more sites suitable for such encroachment. The presence of a more hydrophobic crosslinking fragment, of higher molecular weight, in the crosslinked polymer further promotes the physical encroachment of the antibacterial agent by the crosslinked polymer forming the ASA.

Preferably, ASA is an anionic polymer comprising a chain or skeleton having repeating units which each preferably contain at least one carbon atom and, preferably, at least one monovalent group improving the distribution attached laterally directly or indirectly and at least one monovalent retention improving group laterally attached directly or indirectly, which are linked in twin, vicinal or, less preferably, in another way to atoms of the chain, preferably carbon atoms. Less preferably, the polymer may contain distribution improving groups and / or retention improving groups and / or other divalent atoms or groups such as mail-

Ions of the polymer chain in place of or in addition to carbon atoms, or as crosslinking fragments.

It will be understood that all of the examples or illustrations of ASAs presented herein which do not contain both distribution improving groups and retention improving groups can, and preferably must, be chemically modified in a known manner to form ASAs preferred containing these two types of groups, and preferably more than one of each type of these groups. In the case of preferred polymeric ASAs, it is advantageous, in order to maximize the substantivity and the distribution of the antibacterial agent to the surfaces of the oral cavity, that the recurring units of the polymer chain or skeleton comprising the acid groups improving the distribution constitute at least 10%, preferably at least about 50%, and more preferably at least about 80% to 95% or 100% by weight of the polymer.

According to a preferred embodiment of the present invention, the ASA consists of a polymer containing repeating units in which one or more distribution improving phosphonic acid groups are linked to one or more carbon atoms of the polymer chain. An example of such an ASA is a poly (vinylphosphonic acid) having units of formula:

which, however, does not contain a retention enhancing group. A group of the latter type is however present in a poly (1-phosphonopropene) having units of formula:

An ASA containing phosphonic acid which it is preferred to use here is a poly (beta-styrene-phosphonic acid) having units of formula:

where Ph is the phenyl group / the phosphonic group improving the distribution and the phenyl group improving the retention being linked to vicinal carbon atoms of the chain / or a copolymer of beta-styrene-phosphonic acid with vinylphos-phonyl chloride containing the units of formula III alternately or in statistical association with units of formula I above / or also a poly (alpha-styrene-phosphonic acid) having units of formula:

where the groups improving the distribution and the groups improving the retention are linked in female relation to the chain.

These styrene-phosphonic acid polymers and their copolymers formed with other inert ethylenically unsaturated monomers generally have molecular weights in the range of from about 2000 to about 30,000 / preferably from about 2,500 to about 10,000. These "inert" monomers do not significantly disturb the function assigned to any copolymer used here as ASA.

Other polymers containing phosphonic groups include / for example, a phosphonated ethylene polymer having units of formula:

where n can, for example, be an integer or have a value giving the polymer a molecular weight of approximately 3000 ‘and a poly (butene-4/4-sodium diphosphonate) having units of formula:

and a poly (allyl-bis (phosphonoethyl) amine) having units of formula:

Other phosphonated polymers, for example a poly- (allyl-phosphono-acetate), a phos-phoné polymethacrylate, etc./ and the polymers with two twin phosphonate groups described in European patent No. 0 321 233 can be used here as ASA / provided of course that they contain or are modified to contain the organic groups improving the retention defined above.

In one aspect of the present invention, the composition for oral use comprises an acceptable vehicle for oral use, an ageni: which is effective in stimulating the antibacterial effect of an antibacterial agent, which has an average molecular weight of about 1000 to about 1,000,000, contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group improving the retention of the antibacterial effect, said agent containing said groups being free or substantially free of synthetic anionic linear polymer polycarboxylate water-soluble alkali metal or ammonium, having a molecular weight of about 1000 to 1,000,000, and a polyphosphate type anti-scale agent, for example a mixture of potassium and sodium salts, the ratio of potassium to sodium in the said composition being in the range of up to less than about 3: 1 / for example from about 0.37 to about 1.04: 1.

In another preferred embodiment, the ASA comprises a synthetic anionic polymeric polycarboxylate which is also an alkaline phosphatase inhibitor. Synthetic anionic polymeric polycarboxylates and their complexes formed with various cationic germicides, zinc and magnesium have been previously proposed as scale inhibitors by themselves, for example in U.S. patents. Nos. 3,429,963, 4,152,420, 3,956,480, 4,138,477 and 4,183,914. However, it is only in a disclosure essentially corresponding to the U.S. patent. No. 4,627,977, the use of these polycarboxylates to inhibit the hydrolysis by saliva of an anti-scale agent of the pyrophosphate type in association with a compound providing fluoride ions is described. It will be understood that the synthetic anionic polymeric polycarboxylates thus proposed in these various patents, when they contain or are modified to contain retention-improving groups, can be used in the compositions and methods of the present invention and, to this extent, the relevant presentations of these patents are incorporated herein by reference to them.

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

Other polymeric polycarboxylates usable as ASA, containing or modified to contain retention improving groups include those proposed in the U.S. Patent. No. 3,956,480 cited above, such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone -or ethylene, the latter type of copolymer being available, for example, under the designations EMA No. 1103, PM 10,000, and EMA Grade 61 from Monsanto, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, 1 ' methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrro-lidone.

Other usable polymeric polycarboxylates proposed in US patents. Nos. 4,138,477 and 4,183,914 cited above, containing or modified to contain retention enhancing groups, include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic acids , polyitaconic and polymaleic, and sulfoacrylic oligomers of PM as low as 1000, available under the designation ND-2 from Uniroyal.

Suitable monomers in general are the olefinically or ethylenically unsaturated carboxylic acids containing a retention-improving group, which have an activated carbon-carbon olefin double bond which easily polymerizes because it is present in the molecule of monomer either in the alpha-beta position relative to a carboxyl group, or as part of a terminal methylene group. Representative examples of such acids are acrylic, methacrylic, ethacrylic, alpha-chloracrylic, crotonic, beta-acryl-oxypropionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic acids. , glutaconic, aconitic, alpha-phenylacrylic, 2-benzylacrylic, 2-cyclohexyl-acrylic, ang.elic, umbellic, fumaric, maleic and their anhydrides. Other different olefinic monomers copolymerizable with these carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymers contain enough salified carboxylic groups to ensure their solubility in water.

Substances also useful here are so-called carboxyvinyl polymers proposed as components of toothpaste in U.S. patents. No. 3,980,767, 3,935,306, 3,919,409, 3,911,904 and 3,711,604. These polymers are commercially available, for example under the trademarks Carbopol 934, 940 and 941 from BF Goodrich, these products being essentially consisting of a colloidally water-soluble polymer of polyacrylic acid crosslinked with approximately 0.75% to approximately 2.0% of polyallyl-saccha-rose or of polyallyl-pentaerythritol as crosslinking agent, the crosslinked structure and the bonds of crosslinking ensuring the desired retention improvement by hydrophobia and / or physical overlapping of the antibacterial agent, or the like. A carbophilic polymer is quite similar, being a polyacrylic acid crosslinked with less than 0/2% of divinylglycol, the lower proportion / molecular weight and / or hydrophobicity of this crosslinking agent tending to offer little or no improvement in retention. 2; 5-dimethyl-1/5-hexadiene is an example of a more effective cross-linking agent which improves retention.

The synthetic anionic polymer polycarboxylate component is most often a hydrocarbon bearing optional halogenated and oxygenated substituents and bonds / as it exists for example in ester / ether and OH groups / and / when it is present / it is generally used in the present compositions in approximate weight proportions of up to about 4% (generally at least about 0/05%).

The ASA can also include natural anionic polymeric polycarboxylates containing retention enhancing groups. Carboxymethylcel-lulose and other binding agents / gums and film-forming agents lacking the distribution improving and / or retention improving groups defined above are ineffective as ASAs.

As representative examples of ASA containing phosphinic acid and / or sulfonic acid groups improving the distribution / mention may be made of polymers and copolymers containing units or fragments originating from the polymerization of vinyl- or allyl-phosphinic acids and / or sulfonic substituted / as necessary / on the carbon atom in 1 or 2 (or 3) by an organic group improving retention / corresponding for example to the formula - (X) -R defined above. It is possible to use mixtures of these monomers and their copolymers formed with one or more inert polymerizable ethylenically unsaturated monomers such as those described above with regard to the synthetic anionic polycarboxylates which can be used. As will be noted / in these polymeric ASAs as well as others usable here, there is generally only one acid group improving the distribution linked to any given atom of carbon or other of the backbone of the polymer or a branching thereof. Polysiloxanes containing or modified to contain side groups improving the distribution and side groups improving the retention can also be used here as ASA. Ionomers containing or modified to contain distribution and retention enhancing groups are also effective here as ASA. These ionomers are described on pages 546-573 of the supplemental volume of "Kirk Othmer Encyclopedia of Chemical Technology", third edition, John Wiley & Sons, Inc., copyright 1984, the description of which is incorporated herein by reference. Substances also effective here like ASA are synthetic and natural polyesters, polyurethanes and polyamides, including proteins and proteinaceous materials such as collagen, poly (arginine) and other polymerized amino acids, provided that they contain or be modified to contain groups improving retention.

When the composition for oral use is prepared by first dissolving the polyphosphate and the antibacterial agent in a humectant and a surfactant and adding ASA, in particular the polycarboxylate, in successive portions, the solution becomes clear and can be characterized as a "microemulsion". As the proportion of polycarboxylate increases so that the finished preparation contains at least about 2.2% by weight, the solution becomes cloudy and can be characterized as a "macroemulsion". In these "macroemulsion" type compositions / the antiplaque effect of the antibacterial agent turns out to be optimized.

An advantageous weight ratio of the non-cationic antibacterial agent substantially insoluble in water to the anti-scale agent of the polyphosphate type is between more than about 0.72: 1 and less than about 4: 1, for example d '' about 1: 1 to about 3.5: 1, especially about 1.6: 1 to about 2.7: 1.

In order to optimize the anti-tartar efficacy of the composition for oral use, it is desirable that inhibitors are present which prevent the enzymatic hydrolysis of polyphosphate. These agents consist of a proportion of a source of fluoride ions sufficient to provide 25 to 5000 x 10-4% of fluoride ions, and up to 3% or more of the synthetic anionic polymer polycarboxylate having a molecular weight of about 1000 to about 1,000,000, preferably from about 30,000 to about 500,000.

Sources of fluoride ions, or fluorine-providing compounds, used as a pyrophosphatase and acid phosphatase inhibitor component, are well known in the art as anti-caries agents. These compounds may be slightly soluble in water or may be completely soluble in water. They are characterized by the ability to release fluoride ions into water and by their absence of undesirable reaction with the other compounds contained in the composition for oral use. Among these substances are mineral salt fluorides, such as soluble salts of alkali metals and alkaline earth metals such as, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride , a copper fluoride such as cuprous fluoride, zinc fluoride, barium fluoride / sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, ammonium fluorozir-conate, sodium monofluorophosphate, aluminum mono- and difluorophosphates, and fluorinated sodium and calcium pyrophosphate. Preferred are alkali metal and tin fluorides, such as sodium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof.

The proportion of fluorine-providing compound depends to some extent on the type of compound, its solubility and the type of oral preparation, but this should be a non-toxic proportion, generally from about 0.005 to about 3.0% in the preparation. In a preparation of toothpaste, for example a toothpaste gel, a toothpaste (including a cream), a toothpaste or a dental tablet, it is considered satisfactory a proportion of such a compound which releases a maximum of about 5000 x 10% by weight of F ions, relative to the weight of the preparation. Any lower proportion of this compound can be used, but it is preferable to use -4 sufficient to liberate about 300 to 2000 x 10%, -4 and more preferably about 800 to about 1500 x 10%, of fluoride ions.

In the case of alkali metal fluorides, this component is typically present in an amount limited to about 2% by weight, based on the weight of the preparation, and preferably in the range of about 0.05 to 1%. In the case of sodium phate monofluorophos, this compound may be present in an amount of about 0.1 to 3%, more specifically about 0.76%.

In preparations for oral use such as mouthwashes, lozenges and chewing gum, the fluorine-providing compound is typically present in an amount sufficient to release maxi -4. -4 mum. about 500 x 10%, preferably 25 to 300 x 10% by weight of fluoride ions. In general, this compound is present in an amount of 0.005 to 1.0% by weight.

In certain embodiments of the invention which are very particularly preferred, the composition for oral use may be of a substantially liquid nature, being for example a bath for washing or rinsing the mouth. In such a preparation, the vehicle is typically a water-alcohol mixture advantageously containing a humectant as described below. In general, the weight ratio of water to alcohol is in the range of from about 1: 1 to about 20: 1, preferably from about 3: 1 to 10: 1, and more preferably, from 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 about 70 to about 99.9% by weight of the preparation. The alcohol is typically ethanol. or isopropanol. Ethanol is preferred.

The pH of these liquid preparations and the other preparations of the invention is generally in the range of about 4.5 to about 9, and typically about 5.5 to 8. The pH is preferably in the range range from about 6 to about 8.0. It is interesting to note that the compositions of the invention can be applied to the oral cavity at a pH below 5 without significantly decalcifying or otherwise damaging the dental enamel. The pH can be adjusted by an acid (for example citric acid or benzoic acid) or by a base (for example sodium hydroxide), or can be buffered (as by citrate, benzoate, carbonate or sodium bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In certain other advantageous embodiments of the present invention, the composition for oral use can be of a substantially solid or pasty nature, being for example a toothpaste, a dental tablet or a toothpaste, it i.e. toothpaste (dental cream) or toothpaste gel. The vehicle for these solid or pasty oral preparations generally contains an acceptable polishing material for the teeth. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, calcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate and trimagnesium phosphate , calcium carbonate, hydrated alumina, calcined alumina, aluminum silicate, zirconium silicate, silica, bentonite, and mixtures thereof. Other suitable polishing materials include the particulate thermosetting resins described in the U.S. Patent. No. 3,070,510, such as melamine, phenolic and urea formaldehyde resins, and crosslinked polyesters and polyepoxides. Preferred polishing materials include crystalline silica having a particle size of about 5 micrometers maximum, an average particle size of about 1.1 micrometers maximum and a specific surface of about 50,000 cm / g at most, a silica gel or a colloidal silica, and an amorphous alkali metal aluminosilicate.

When using gels with a transparent appearance, particularly useful polishing agents are colloidal silicas, such as the products sold under the trademark SYLOID such as Syloid

72 and Syloid 74 or under the trademark SANTOCEL

such as Santocel 100, or complex aluminosilicates of alkali metals, because their refractive index is close to the refractive index of gelling agent-liquid systems (comprising water and / or a humate) commonly used in toothpaste.

Many of the so-called "water-insoluble" polishes are anionic in character and also contain small amounts of soluble material. Thus, an insoluble sodium metaphosphate can be prepared by any suitable method as explained, for example, in the book "Dictionary of Applied Chemistry" by Thorpe, Volume 9, 4th edition, pages 510-511. Other examples of suitable materials are the forms of insoluble sodium metaphosphate known as Madrell salt and Kurrol salt. These saline metaphosphates show only a minute solubility in water and are therefore commonly called insoluble metaphosphates (MPI). There are found, as impurities, a minor proportion of soluble phosphates, usually a few percent, for example 4% by weight at most. The amount of soluble phosphate material, which is assumed to include a soluble sodium trimetaphos-phate in the case of an insoluble metaphosphate, can optionally be reduced or removed by washing with water. The insoluble alkali metal metaphosphate is typically used in the form of a powder whose particle size is such that a maximum of 1% of the material is larger than 37 micrometers.

The polishing material is generally present in solid or pasty compositions in weight concentrations of about 10 to about 99%. Preferably, this material is present in pro portions ranging from about 10% to about 75% in a toothpaste, and from about 70% to about 99% in a tooth powder. In toothpaste, when the polishing material is of a siliceous nature, it is generally present in a proportion of about 10 to 30% by weight. The other polishing materials are typically present in an amount of about 30 to 75% by weight.

In a toothpaste, the liquid vehicle may include water and a humectant, typically in an amount of from about 10% to about 80% of the weight of the preparation. Representative examples of suitable vehicles / humectants are glycerol, propylene glycol, sorbitol and polypropylene glycol. Liquid mixtures of water, glycerol and sorbitol are also advantageous. In transparent gels where the refractive index is an important criterion, preferably between about 3 and 30% by weight of water, 0 to about 70% by weight of glycerol and about 20 to 80% by weight of sorbitol are used. .

Toothpastes, creams and gels typically contain a natural or synthetic gelling or thickening agent in proportions of about 0.1 to about 10%, preferably about 0.5 to about 5%, by weight. A suitable thickener is synthetic hectorite, a synthetic colloidal clay consisting of a silicate complex of alkali metals and magnesium, commercially available under the designation Laponite (for example CP, SP, 2002, D), these products being marketed by Laporte Industries Limited. Analysis of Laponite D indicates, by weight, approximately 58.00% SiO2 /% M9 ° 3.05% Na2O, 0.98% LI2O and traces of metals. Its real density is 2.53 and its apparent density (at 8% humidity) of 1.0.

Other suitable thickeners include Irish moss, iota-carrageenan, tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose (available for example under the designation Natrosol, sodium carboxymethylcellulose and a finely ground colloidal silica such as Syloid (eg 244). In certain toothpastes prepared according to the present invention, in particular when more than about 0.35% by weight of the antibacterial agent insoluble in water and a siliceous polishing agent is present in an amount less than about 30% by weight, it may be advantageous to include an agent which dissolves the antibacterial agent. Such solubilizing agents include humectant polyols such as propylene glycol, dipropylene glycol and hexylene glycol, products of the Cellosolve type such as methylcellos olve and Ethylcellosolve, vegetable oils and waxes containing at least about 12 carbon atoms in a straight chain configuration, such as olive oil, castor oil and petrolatum and esters such as l amyl acetate, ethyl acetate and benzyl benzoate.

It will be understood that, as is usual, preparations for oral use must be sold or otherwise distributed in suitably labeled packages. Thus, a mouthwash bottle must bear a label which essentially describes it as such and gives indications for its use; and a toothpaste, gel or dental cream is usually packaged in a compressible tube, typically aluminum, coated lead or plastic, or in another compressible dispenser, pump or pressure, intended to deliver its contents. dosed and labeled, describing it primarily as a toothpaste / gel or dental cream.

Organic surfactants are used in the compositions of the present invention to exert an increased prophylactic action / help to achieve a complete and uniform dispersion of the anti-scale agent and the anti-plaque agent throughout the oral cavity / and make the present compositions more acceptable from the cosmetic point of view. The organic surface-active substance is preferably of anionic, nonionic or ampholytic character, and it is preferred to use as a surface-active agent a detersive substance which gives the composition detergent and foaming properties. Examples of suitable anionic surfactants are the water-soluble salts of higher fatty acid monoglyceride monosulphates, such as the sodium salt of the monoglyceride monosulphate of hydrogenated coconut oil fatty acids, higher alkyl sulphates such as lauryl sulphate sodium, alkylarylsulfonates such as sodium dodecylbenzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2-dihydroxypropane sulfonates, and substantially saturated higher aliphatic acylamides formed with lower aliphatic aminocarboxylic acids, such than those whose fatty acid, alkyl or acyl radicals have 12 to 16 carbon atoms, etc. Examples of the last mentioned amides are N-lauroylsarcosine, and the sodium, potassium and ethanolamine salts of N-lauroyl-, N-myristoyl- or N-palmitoyl-sarcosine which must be substantially free from soap or similar derivatives of higher fatty acids. The use of these sarcosinates in the compositions for buccal use of the present invention is particularly advantageous because these substances exert a marked and prolonged effect of inhibition of the formation of acids by decomposition of carbohydrates in the buccal cavity, and additionally exert some reduction in the solubility of dental enamel in acid solutions. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various labile hydrogen compounds reactive with ethylene oxide which have long hydrophobic chains (e.g., aliphatic chains of about 12 to 20 carbon atoms), these condensation products ("ethoxamers") containing hydrophilic polyoxyethylene fragments, for example the condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyalcohols (for example sorbitan monostearate) and poly (propylene oxide) (for example the products of the Pluronic series).

The surfactant is generally present in an amount of about 0.1 to 5% by weight, preferably about 1 to 2.5%. It is interesting to note that the surfactant can promote the dissolution of the non-cationic antibacterial agent and thus reduce the amount of solubilizing humectant required.

Various other substances can be incorporated into the oral preparations of the present invention, such as bleaches, preservatives, silicones, chlorophyll compounds and / or ammoniated substances such as urea and diammonium phosphate , and mixtures thereof. These adjuvants, if present, are incorporated into the preparations in amounts which do not substantially affect the desired properties and characteristics. Large portions of generally soluble salts and substances, containing zinc, magnesium and other metals, which would form complexes with the active components of the preparations of the present invention, should be avoided.

Any suitable flavoring or sweetening substance may also be used. Examples of suitable flavoring constituents are flavoring essential oils, for example, spearmint, peppermint, wintergreen, sassafras, cloves, sage, eucalyptus, marjoram, cinnamon, lemon and orange, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, xylitol, sodium cyclamate, perillartine, AMP (aspartylphenyl-alanine methyl ester), saccharin, etc. The flavoring and sweetening agents may suitably constitute together about 0.1% to 5% or more of the preparation. In addition, the flavoring essence is found to facilitate the dissolution of the antibacterial agent.

In the preferred practical application of the present invention, a composition for buccal use according to the invention, for example a mouthwash or a toothpaste containing the composition of the present invention, is preferably applied at regular intervals to the dental enamel. , for example every day or every two or three days, or preferably 1 to 3 times a day, at a pH of about 4.5 to about 9, generally from about 5.5 to about 8 and of preferably about 6 to 8, for at least 2 to 8 weeks or more, or even for life.

The compositions of the present invention can be incorporated into lozenges or into chewing gum or other products, for example by stirring them in a hot gum base or by applying them to the exterior surface of a gum base of which representative examples which may be mentioned are jelutong, rubber latex, vinylite resins, etc., advantageously combined with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates, such as glucose, sorbitol, etc.

The following examples further illustrate the present invention without, however, limiting it. All the quantities and proportions mentioned therein are expressed by weight.

In the examples which follow, the antibacterial agent Triclosan, that is to say 2,4,4'-trichloro-2'-hydroxy (diphenyl ether) is designated by "TCHE": sodium lauryl sulfate is designated by "LSS"; the copolymer of maleic anhydride and methyl vinyl ether available from GAF Corporation under the designation "Gantrez S-97" is identified by "Gantrez"; tetrasodium pyrophosphate is identified by "pyrophosphate"; and sodium fluoride is identified by "NaF".

Example 1

The adsorption and the release by the mineral constituents of the teeth are evaluated in order to determine the anti-plaque / anti-scale effectiveness of the agents by proceeding by adsorption of the antibacterial agent on a dental mineral hydroxyapatite disc, coated with saliva, in the presence of pyrophosphate. and various amounts of polycarboxylate.

The formulations of the toothpastes evaluated are as follows:

Parts by weight A B

Glycerol 10/000 10/000 lota-carrageenan 0/750 0.750

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

Propylene glycol 0/500 0/500

Gantrez (13/02% solution) 19/000 15/500

Titanium dioxide 0/500 0/500

Water (deionized) 9.957 13/457

NaF 0/243 0/243

Sodium saccharinate 0/300 0/300

Pyrophosphate 2/000 2/000

Sodium hydroxide (50% 1/000 1/000

Polishing agent (silica) (Zeodent 113) 20/000 20/000

Thickener (silica) (Sylodent 15) 2,500 2,500

Flavoring essence 0.950 0.950 TCHE 0/300 0.300 LSS 2,000 2/000

The Gantrez product is present as an active ingredient in an amount of 2.5 parts in toothpaste A and 2.0 parts in toothpaste B.

To test the distribution of the antibacterial agent on a hydroxyapatite disc coated with saliva, hydroxyapatite (HA) supplied by Monsanto Co. is abundantly washed with distilled water, collected by vacuum filtration and dry overnight at 37 ° C. The dried HA is ground to a powder using a mortar and pestle. 150.00 mg of HA are placed in the cavity of a KBr pellet matrix (Barnes Analytical, Stanford, CT.) And compressed for 5 minutes under a pressure of 4540 kg in a Carver laboratory press. The resulting 13 mm discs are sintered for 4 hours at 800 ° C in a Thermolyne oven. Whole saliva produced by parafilm stimulation is collected in an ice-cold glass beaker. The saliva is clarified by centrifugation at 15,000 x g for 15 minutes at 4 ° C. Sterilization of the clarified saliva is carried out, with stirring at 4 ° C., by irradiation of the sample with a UV lamp for 1.0 hour.

Each sintered disc is hydrated with sterile water in a polyethylene test tube. The eastern water is then removed and replaced with 2.00 ml of saliva. A saliva film is formed by incubating the disc overnight at 37 ° C in a water bath with continuous shaking. After this treatment, the saliva is removed and the discs are treated with 1.00 ml of a solution containing the antibacterial agent (Triclosan) in a liquid phase solution of toothpaste and incubated at 37 ° C in the bath -marie with continuous shaking by shaking. After 30 minutes, transfer the disc to a new tube and add 5.00 ml of water, then gently shake the disc with a Vortex machine. The disc is then transferred to a new tiibe and the washing operation is repeated twice. Finally, the disc is transferred to a new tube carefully to avoid simultaneous transfer of any liquid with the disc. Then add 1.00 ml of methanol to the disc and shake vigorously with a Vortex machine. The sample is left at room temperature for 30 minutes to extract the adsorbed Triclosan by passing it through methanol. The methanol is then removed by aspiration and clarified by centrifugation in a Beckman Microfuge 11 apparatus at 10,000 rpm for -5 minutes. After this treatment, the methanol is transferred into flasks of HPLC (high performance liquid chromatography) for the determination of the antibacterial agent. Triplicate samples are used in all experiments.

The table below summarizes the results: Table

Distribution of TCHE on a hydroxyapatite disc coated with saliva Toothpaste _ (micrograms) _ A 130 B 30

The results show that with the increase in the amount of Gantrez (Toothpaste A) / there is a very large increase in the distribution of TCHE on dental minerals coated with saliva.

Example 2

The following toothpaste is effective as an anti-plaque and anti-scale composition:

Parts by weight

Sorbitol (70%) 22/00

Irish Moss 1/00

Sodium hydroxide (50%) 1/00

Gantrez (13/02% solution) 19/00

Water (deionized) 2/69

Sodium monofluorophosphate 0/76

Sodium saccharin 0/30

Pyrophosphate 2/00

Hydrated alumina 48/00

Flavoring Essence 0/95 TCHE 0.30 LSS 2/00

Example 3

Mouthwash Parts

Tetrasodium pyrophosphate 2.00

Gantrez S-97 2.50

Glycerol 10.00

Sodium fluoride 0.05

Sodium lauryl sulfate 0.20 TCHE 0.06

Flavoring essence 0.40

Water, q.s. for 100.00

Example 4

Percent pastilles

Sugar 75-80

Glucose syrup 1-20

Flavoring essence 0.1-1.0

Tetrasodium pyrophosphate 2

Gantrez S-97 2.50

NaF 0.01-0.05 TCHE 0.01-0.1

Magnesium stearate (lubricant) 1-5

Water 0.01—0.2

Example 5

Chewing gum Parties

Gum base 25.00

Sorbitol (70%) 17.00 TCHE 0.50-0.10

Tetrasodium pyrophosphate 2.00

Gantrez S-97 2.50

In a variant of the Example above, we can omit Gantrez S-97.

Example 6

Chewing gum Parties

Gum base 30/00 TCHE 0.50

Gaunt 2.00

0.05 NaF

Glycerol 0.50

Sorbitol crystalline 53.00

Tetrasodium pyrophosphate 2.00

Flavoring essence and water, q.s. for 100.00

In the above examples, the best results can also be achieved when TCHE is replaced by either phenol, 2,2'-methylene-bis (4-chloro-6-bromophenol), l eugenol and thymol, and / or when Gantrez is replaced by other ASAs such as Carbopol products (for example 934), or polymers of styrene-phosphonic acid having molecular weights falling within the range d '' about 3000 to 10 000, such as a poly (beta-styrene-phosphonic acid), copolymers of vinylphosphonic acid and beta-styrene-phosphonic acid and a poly (alpha-styrene-phospbonic acid ), or sulfoacrylic oligomers, or a 1: 1 copolymer of maleic anhydride and ethyl acrylate.

Similar results are also obtained by replacing pyrophosphate (tetrasodium pyrophosphate) with tetrasodium pyrophosphate and tetrapotassium pyrophosphate, the weight ratio of potassium to sodium being a) 0.37: 1, b) 1.04: 1, c ) 3: 1, and d) 3.5: 1.

It goes without saying that the invention is not limited to the embodiments described and that various variants and modifications can be made thereto without departing from its scope.

Claims (58)

1. Composition for oral use / characterized in that it comprises, in a vehicle acceptable for oral use, an effective amount against dental tartar of a material comprising approximately 0.1 to 3% by weight of at least one polyphosphate linear salt with molecular dehydration as an anti-scale agent, an amount effective against dental plaque of a non-cationic antibacterial agent substantially insoluble in water and up to about 4% by weight of an antibacterial stimulating agent which improves the distribution and retaining said antibacterial agent on the surfaces of the oral cavity, the weight ratio of polyphosphate ions to the antibacterial stimulating agent ranging from about 1.6: 1 to about 2.7: 1. 2. Composition for oral use according to claim 1, characterized in that said antibacterial agent is chosen from the group formed by halogenated diphenyl ethers, halogenated salicylanilides, benzoic esters, halogenated carbanilides and phenolic compounds. 3. Composition for oral use according to claim 1, characterized in that said antibacterial agent is a halogenated diphenyl ether. 4. Composition for oral use according to claim 3, characterized in that said halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxy- (diphenyl ether). 5. Composition for oral use according to claim 1, characterized in that said antibacterial agent is a phenolic compound. 6. Composition for oral use according to claim 5, characterized in that said phenolic compound is chosen from phenol, thymol, eugenol and 2,2'-methylene-bis (4-chloro-6-bromophenol). 7. Composition for oral use according to claim 2 / characterized in that said antibacterial agent is present, in an amount of about 0.01 to 5% by weight. 8. Composition for oral use according to claim 7, characterized in that the amount of the antibacterial agent is approximately 0.25 to 0.5%. 9. Composition for buccal use according to claim 1, characterized in that said linear saline polyphosphate with molecular dehydration is an alkali metal pyrophosphate present in an amount of about 1 to 2.5% by weight. 10. Composition for oral use according to claim 9, characterized in that said alkali metal pyrophosphate is tetra-sodium pyrophosphate. 11. Composition for oral use according to any one of claims 1 to 10, characterized in that the weight ratio of polyphosphate ions to the antibacterial stimulating agent is from about 1.7: 1 to about 2.3: 1 . 12. Composition for oral use according to any one of claims 1 to 11, characterized in that said vehicle comprises water, a humectant and a gelling agent, and said composition is a toothpaste and contains a polishing agent insoluble in water acceptable for teeth. 13. Composition for oral use according to any one of claims 1 to 11, characterized in that said vehicle comprises water and a non-toxic alcohol and said composition is a mouthwash. 14. Composition for oral use according to any one of claims 1 to 15, characterized in that said antibacterial stimulating agent has an average molecular weight of approximately 1000 to approximately 1,000,000. 15. Composition for oral use according to claim 14 / characterized in that said antibacterial stimulation agent contains at least one functional group improving the distribution and at least one organic group improving the retention. 16. Composition for oral use according to claim 15 / characterized in that said group improving the distribution is an acid group. 17. Composition for oral use according to claim 16 / characterized in that said group improving the distribution is chosen from carboxylic, phosphonic, phosphinic and sulfonic acids / their salts / and their mixtures. 18. Composition for buccal use according to claim 17 / characterized in that the organic group improving the retention corresponds to the formula - (X) n ~ R where X is 0 / N / S, SO / SC ^ / PO or Si / R is an alkyl / aryl / alkenyl / acyl group; alkaryl / aral-kyle or heterocyclic hydrophobic / or one of their derivatives with inert substituents, and n is 1 or zero. 19. Composition for oral use according to claim 17, characterized in that said antibacterial stimulating agent is an anionic polymer containing several of said distribution improving groups and organic groups improving retention. 20. Composition for oral use according to claim 19 / characterized in that said anionic polymer comprises a chain containing recurring units each having at least one carbon atom. 21. Composition for buccal use according to claim 20, characterized in that each unit contains at least one group improving the distribution and at least one organic group improving the retention linked to the same atom or to vicinal atoms or to other atoms of chain. 22. Composition for oral use according to claim 17 / characterized in that the group improving the distribution comprises a carboxyl group or a salt thereof. 23. Composition for oral use according to claim 22 / characterized in that the antibacterial stimulating agent is a copolymer of maleic acid or anhydride and of another ethylenically unsaturated polymer-sand monomer / or a salt thereof. 24. Composition for oral use according to claim 23 / characterized in that said other monomer is methyl ether of vinyl in a molar ratio of 4: 1 to 1: 4 with maleic acid or anhydride. 25. Composition for oral use according to claim 24 / characterized in that said copolymer has a molecular weight of approximately 30,000 to 1,000,000. 26. Composition for oral use according to claim 25 / characterized in that the copolymer has an average molecular weight of approximately 70,000. 27. Composition for buccal use according to claim 17 / characterized in that the group improving the distribution comprises a phosphonic group or a salt thereof. 28. Composition for buccal use according to claim 27 / characterized in that the antibacterial stimulating agent is a poly (beta-styrene-phosphonic acid) / a poly (alpha-styrene-phosphonic acid) or a copolymer formed between these two acids or with another inert polymerizable ethylenically unsaturated monomer / or a salt thereof. 29. Composition for oral use according to claim 28, characterized in that said antibacterial stimulating agent has a molecular weight of approximately 1000 to approximately 30,000. 30. Composition for oral use according to one of claims 1 to 29, characterized in that it contains a source of fluoride ions. 31. A method for fighting against dental plaque, characterized in that it consists in applying to the buccal surfaces an amount capable of fighting plaque of a composition as defined in any one of claims 1 to 30. 32. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, an agent which is effective in stimulating the antibacterial effect of an antibacterial agent, the average molecular weight of which is approximately 1000 to approximately 1,000,000, and which contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group promoting the retention of the antibacterial effect, said agent containing said groups being free or substantially free of linear polymeric saline polycarboxylate alkali metal or ammonium hydrosoluble synthetic anionic having a molecular weight of approximately 1000 to approximately 1,000,000, and a polyphosphate type anti-scale agent, said polyphosphate type anti-scale agent being a mixture of potassium and sodium salts, potassium to sodium ratio in said composition being in the range of less than about 3: 1. 33. Composition for oral use according to claim 32, characterized in that the ratio of potassium to sodium is from about 0.37: 1 to about 1.04: 1. 34. Composition for oral use according to claim 32, characterized in that the said group improving the distribution is chosen from phosphonic, phosphinic and sulfonic acids, their salts, and their mixtures. 35. Composition for buccal use according to claim 33, characterized in that said organic group promoting retention corresponds to the formula - (x) -R, where X is 0, N, S, SO, S0 „, PO or Si, R is a nb alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl or heterocyclic hydrophobic group, or one of their derivatives with inert substituents, and n is 1 or zero. 36. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, an agent which is effective in stimulating the antibacterial effect of an antibacterial agent, the average molecular weight of which is approximately 1000 to approximately 1000000 and which contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group improving the retention of the antibacterial effect, said agent containing said groups being free or substantially free of anionic linear polymeric polycarboxylate salt alkali metal or ammonium water-soluble synthetic having a molecular weight of about 1000 to about 1,000,000, and a scale inhibitor of the polyphosphate type. 37. Composition for oral use according to claim 36, characterized in that the said agent improving the distribution is chosen from phosphonic, phosphinic and sulfonic acids, their salts and their mixtures. 38. Composition for oral use according to claim 37, characterized in that said organic retention-improving group corresponds to the formula - (X) -R, where X is O, N, S, SO, SO „, PO or Si, R is an alkyl group, aryl, alkenyl, acyl, alkaryl, aralkyl or hydrophobic heterocyclic or one of their derivatives with inert substituents / and n is 1 or zero. 39. Composition for oral use / characterized in that it comprises an acceptable vehicle for oral use / an effective amount against dental plaque of a non-cationic antibacterial agent substantially insoluble in water, an antibacterial stimulating agent which has a average molecular weight of approximately 1000 to approximately 1,000,000 and contains at least one functional group improving the distribution and at least one organic group improving the retention, said agent containing said groups being free or substantially free of water-soluble synthetic anionic linear polymeric saline polycarboxylate of alkali metal or ammonium having a molecular weight of about 1000 to about 1,000,000, and a scale inhibitor of the polyphosphate type. 40. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, an agent which is effective in stimulating the antibacterial effect of an antibacterial agent, the average molecular weight of which is approximately 1000 to approximately 1000000 and which contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group improving the retention of the antibacterial effect, said agent containing said groups being free or substantially free of water-soluble synthetic anionic linear polymer polycarboxylate alkali or ammonium metal having a molecular weight of about 1000 to about 1,000,000, and a polyphosphate-type anti-scale agent, the weight ratio of said polyphosphate anti-scale agent to the antibacterial agent being greater than 0.72: 1 and less than 4: 1. 41. Composition for oral use according to claim 40 / characterized in that said weight ratio is from about 1: 1 to about 3.5: 1. 42. Composition for oral use according to claim 40, characterized in that said weight ratio is from 1.6: 1 to approximately 2.7: 1. 43. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, an agent which is effective in stimulating the antibacterial effect of an antibacterial agent, the average molecular weight of which is approximately 1000 to approximately 1000000 and which contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group improving the retention of the antibacterial effect, and a scale inhibitor of the polyphosphate type, provided that the composition is free or substantially free of tetrasodium pyrophosphate. 44. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, an agent which is effective in stimulating the antibacterial effect of an antibacterial agent, the average molecular weight of which is approximately 1000 to approximately 1,000,000 and which contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group improving the retention of the antibacterial effect, and an anti-scale agent of the polyphosphate type, provided that the composition is free or substantially free from a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium pyrophosphate to sodium pyrophosphate is 3: 1 or more. 45. Composition for buccal use, characterized in that it comprises an acceptable vehicle for buccal use, an effective amount against the plaque of a non-cationic antibacterial agent substantially insoluble in water and an antitartar agent of the polyphosphate type / with the proviso that the composition is free or substantially free of tetrasodium pyrophosphate. 46. Composition for oral use / characterized in that it comprises an acceptable vehicle for oral use / an effective amount against dental plaque of a non-cationic antibacterial agent substantially insoluble in water and an anti-scale agent of the polyphosphate type / under provided that the composition is free or substantially free from a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium pyrophosphate to sodium pyrophosphate is equal to or greater than 3: 1. 47. Composition for oral use / characterized in that it comprises an acceptable vehicle for oral use / an effective amount against dental plaque of a non-cationic antibacterial agent substantially insoluble in water / an antibacterial stimulating agent whose weight average molecular is from about 1000 to about 1,000,000 and which contains at least one functional group improving the distribution and at least one organic group improving the retention, said agent containing said groups being free or substantially free of synthetic anionic linear polymeric saline polycarboxylate water-soluble alkali metal or ammonium having a molecular weight of about 1000 to about 1,000,000, and a scale inhibitor of the polyphosphate type, provided that the composition is free or substantially free of tetrasodium pyrophosphate. 48. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, an effective amount against dental plaque of a non-cationic antibacterial agent substantially insoluble in water, an antibacterial stimulating agent whose weight average molecular is from about 1000 to about 1,000,000 and which contains at least one functional group improving the distribution and at least one organic group improving the retention, said agent containing said groups being free or substantially free of synthetic anionic linear polymeric saline polycarboxylate water-soluble alkali metal or ammonium having a molecular weight of about 1000 to about 1,000,000, and a scale inhibitor of the polyphosphate type, provided that the composition is free or substantially free from a combination of potassium pyrophosphate and pyrophosphate tetra-sodium in which the ratio of potassium pyrophosphate to pyropho sodium sphate is equal to or greater than 3: 1. 49. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use and an agent which is effective in stimulating the antibacterial effect of an antibacterial agent, the average molecular weight of which is approximately 1000 to approximately 1,000,000 and which contains at least one functional group improving the distribution of the antibacterial effect and at least one organic group improving the retention of the antibacterial effect, said agent containing said groups being free or substantially free of anionic linear polymeric polycarboxylate salt water-soluble synthetic of alkali metal or ammonium having a molecular weight of approximately 1000 to approximately 1,000,000, and an anti-scale agent of the polyphosphate type, said composition containing potassium or sodium salts or ions, the ratio of potassium to sodium in said composition being in the range less than 3: 1. 50. Composition for oral use according to claim 48 / characterized in that said ratio of potassium to sodium is from approximately 0.37: 1 to approximately 1.04: 1. 51. Composition for buccal use, characterized in that it comprises a vehicle acceptable for buccal use, a non-cationic antibacterial agent substantially insoluble in water in an amount of 0.25% to 0.35% and an anti-scaling agent of polyphosphate type. 52. Composition for oral use, characterized in that it comprises an acceptable vehicle for oral use, a non-cationic antibacterial agent substantially insoluble in water in an amount of 0.25 to 0.35% and an anti-scale agent of the type polyphosphate, the anti-scale agent of the polyphosphate type being a mixture of potassium and sodium salts, the ratio of potassium to sodium in said composition being in the range of less than about 3: 1. 53. Composition for oral use according to claim 52, characterized in that said ratio is from approximately 0.35: 1 to approximately 1.04: 1. 54. Composition for buccal use, characterized in that it comprises an acceptable vehicle for buccal use, a non-cationic antibacterial agent substantially insoluble in water in an amount of 0.25 to 0.35% and an antitartar agent of the type polyphosphate, provided that the composition is free or substantially free of tetrasodium pyrophosphate. 55. Composition for buccal use, characterized in that it comprises a vehicle acceptable for buccal use, a non-cationic antibacterial agent substantially insoluble in water in an amount of 0.25 to 0.35% and an antitartar agent of the type polyphosphate, provided that the composition is free or substantially free from a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of potassium pyrophosphate to sodium pyrophosphate is equal to or greater than 3: 1. 56. Composition for oral use / characterized in that it comprises an acceptable vehicle for oral use / an effective amount against dental plaque of a non-cationic antibacterial agent substantially insoluble in water / an antibacterial stimulating agent whose weight average molecular is from about 1,000 to about 1,000,000 and which contains at least one functional group improving the distribution and at least one organic group improving the retention / said agent containing said groups being free or substantially free of synthetic anionic linear polymeric saline polycarboxylate water-soluble alkali metal or ammonium having a molecular weight of about 1000 to about 1,000,000 / and an anti-scale agent of the polyphosphate type / said anti-scale agent of the polyphosphate type being a mixture of potassium and sodium salts / the ratio of potassium to sodium in said composition being in the range of less than about 3: 1. 57. Composition for oral use according to claim 55 / characterized in that said ratio is from about 0/37: 1 to about 1/04: 1. 58. Composition for buccal use / characterized in that it comprises an acceptable vehicle for the buccal route / an effective amount against dental plaque of a non-cationic antibacterial agent substantially insoluble in water and an antibacterial stimulating agent, the weight average molecular weight is from about 1,000 to about 1,000,000 and which contains at least one functional group improving distribution and at least one organic group improving retention / said agent containing said groups being free or substantially free of polymeric salt polycarboxylate alkali metal or ammonium water-soluble synthetic anionic linear having a molecular weight of approximately 1000 to approximately 1,000,000, said composition containing potassium or sodium salts or ions, the ratio of potassium to sodium in said composition being included in the range from 0.37: 1 to 1/04: 1.