PT92733B - PROCESS FOR THE PREPARATION OF AN ANTI-PLASTIC ORAL ANTIBACTERIAL COMPOSITION, ANTICALCLE CONTAINING AN ANALALCLE AGENT BASED ON POLYPHOSPHATE - 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

This invention relates to a process for the preparation of an anti-calculus, anti-plaque, antibacterial oral composition. More specifically, it refers to an oral composition containing an anti-calculus agent (ie, anti-tartar based on poylphosphate and a compatible antibacterial agent effective to inhibit plaque where anti-plaque efficacy is optimized by the presence of a intensifying agent of anti-bacterial properties, which increases the release of said agent on the oral surfaces and their retention on them.

U.S. Patents 4,627,977 to Gaffar et al; 4,515,772 to Parran et al; and 4,323,551 to Parran, oral compositions are described that include various polyphosphate compounds. In the patent by Gaffar et al, a molecularly dehydrated linear polyphosphate salt is used in conjunction with a source that releases fluoride ions and a synthetic linear polymeric polycarboxylate to inhibit stone formation. In also pending European Patent Application, N2 89 200 700.5, the anti-calculus efficacy is optimized with a reduced amount of the molecularly dehydrated linear polyphosphate salt in conjunction with the source that releases fluoride ions and a greater amount of the synthetic linear polymeric polycarboxylate.

In the patents of Parran et al and Parran, water soluble alkaline dimethyl pyrophosphate is used alone or mixed with alkaline tetra metal pyrophosphate.

Oral compositions that inhibit «i» the formation of calculus on dental surfaces are highly desirable, since calculus is one of the factors that cause periodontal states. Thus, its reduction promotes oral hygiene.

Dental plaque is a precursor to calculus. However, contrary to the calculation, plaque can form anywhere on the tooth surface, especially including the gingival margin. For this reason, in addition to being invisible, it is implicated in the occurrence of gingivitis.

Accordingly, it would be highly desirable to include antimicrobial agents, which have been known to reduce plaque in oral compositions containing anti-calculating agents. In fact, this has been described in U.S. Patent 4,022,550 to Vinson et al, in which a compound that releases zinc ions as an anti-calculating agent is added, with mixing, to an antibacterial agent effective to retard the growth of plaque bacteria. A wide variety of anti-bacterial agents are described with the zinc compounds including catholic materials, namely guanides and quaternary ammonium compounds, as well as non-cationic compounds such as non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers.

Cationic antibacterial materials such as chlorhexidine, benzethonium chloride and cetyl-pyridinium chloride have, until now, been subject to further investigation as antibacterial antiplaque agents. However, despite being used in conjunction with the anti-zinc agent, they are not effective when used with anionic materials, namely polyphosphate anti-calculating agent. This ineffectiveness is considered to be quite surprising since polyphosphates are cheliferous agents and it is known in advance that the cheliferous effect increases the effectiveness of cationic antibacterial agents. (see, eg, Disinfection, sterilization and Preservation, Ed.2 Ed., Black, 1977, Pag. 915 and

Inhibition and Destruction of the Microbial Cell, Hugo, 1971 Page 215). In fact, the quaternary ammonium compound is present in the pyrophosphate-containing mouthwash solution of US Patent 4,332,551 to Pazran and the anti-plaque agent of biagunide is suggested in the oral pyrophosphate-based anti-calculation composition of the US Patent EU 4,515,772 to Parran et al.

in view of the surprising incompatibility of the cationic antibacterial agents with the polyphosphates present as anticoagulant agents, it was quite unexpected that other antibacterial agents were effective.

It is an advantage of this invention that certain antibacterial agents are effective in oral anti-calculus compositions containing a molecularly dehydrated linear polyphosphate salt, a source that releases fluoride ions and said antibacterial properties enhancing agent to inhibit plaque formation.

Another advantage of this invention is that it presents a composition that is effective in reducing calculus formation and optimizing the reduction of the plate.

It is another advantage of this invention that an anti-plaque, anti-calculating oral composition is present, which is effective in reducing the occurrence of gengi vite.

Other advantages of this invention will become apparent from the study of the following specification.

—Ir r 1

According to some of its aspects, this invention relates to an oral composition containing, in an orally acceptable vehicle, an effective amount of anti-calculation material consisting of about 0.1-37, by weight, of at least one molecularly linear polyphosphate salt dehydrated as an anti-calculating agent, an anti-plaque effective amount of a non-cstionic agent substantially insoluble in water and desirably up to about 47% by weight of an antibacterial-enhancing agent, which increases the release of said antibacterial agent .no on oral surfaces and their retention on them, where, typically, the weight ratio of antibacterial-enhancing agent 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, in particular from about 1.6: 1 to about 2.7: 1, preferably from about 1.7: 1 to about 2.3: 1 and most preferably about 1.9: 1 to about 2: 1. For example, when using 27 tetrasodium pyrophosphate (PFTS) (releasing about 1.37 pyrophosphate ion) with 2.57 of the anti-bacterial enhancing agent, a weight ratio of about 1.9 is highly desirable :1.

Typical examples of antibacterial agents, which are particularly desirable for reasons of anti-plaque effectiveness, safety and formulation are:

Halogenated Diphenyl Ethers

2 ', 4,4-trichloro-2-hydroxy-diphenyl ether (Triclosan) 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

Halogenated salicylanllides

4 ', 5-dibromo-sacilanilide

3,4 ', 5-trichloro-salicylanilide

3.4 ' _T 5-tribromo-sacilanilide

2,3,3 ', 5-tetrachloro-salicylanilide

3,3,3 ', 5-tetrachloro-salicylanilide

3.5- dibromo-3'-trifluoromethyl-salicylanilide

5-n-octanoyl-3'-trifluoromethyl-salicylanilide

3.5- dibromo-4'-trifluoromethyl-salicylanilide

3.5- dibromo-3'-trifluoro-methyl-salicylanilide (Fluorophene)

Benzoic esters

Methyl-p-Hydroxybenzoic ester Ethyl-p-Hydroxybenzoic ester Propyl-p-Hydroxybenzoic ester Butyl p-Hydroxybenzoic ester

Halogenated 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 bisphenolic compounds). Such phenolic compounds include, inter alia.

Phenols and their counterparts

Phenol

Methyl

Methyl

Methyl 4 Ethyl

2,4-Dimethyl

2.5- Dimethyl 3,4-Dimethyl

2.6- Dimethyl 4-n Propyl 4-n Butyl 4-n Amyl 4-tert-Amyl 4-n-Hexyl 4-n-Heptyl

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

-Phenol

2-Methoxy-4- (2-Propenyl) -Fenol (Eugenol)

2-Isopropyl-5-Methyl-Phenol (Thymol)

Mono- and Poly-Alkyl and Aralkyl-Halofenóia

Methyl

Ethyl n-Propyl n-Butyl n-Amyl sec-Amyl n-Hexyl cyclohexyl n-Heptyn-Octyl

O-Chlorophenol

Methyl

Ethyl n-Propyl n-Butyl n-Amyl tert-Amyl n-Hexyl n-Heptil 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-iso-propyl-3-methyl

2-Ethyl-3,5-dimethyl

-p-chlorophenol

-p-chlorophenol

-p-Chlorophenol

-p-Chlorophenol

-p-chlorophenol

-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

-p-chlorophenol

-p-chlorophenol

6-sec-Butyl-3-methyl 2-iso-propyl-3,5-dimethyl 6-Diethylmethyl-3-methyl 6-iso-propyl-2-ethyl-3-met.il 2-sec-Amyl-3, 5-dimethyl 2-Diethylmethyl-3,5-dimethyl 6-sec-octyl-3-methyl p-Bromophenol

Methyl

Ethyl n-Propyl n-Butyl n-Amyl sec-Amyl n-Hexyl cyclohexyl o-Bromophenol tert-Amyl n-Hexyl n-Propyl-m, m-Dimethyl

2-Phenyl-Phenol

4-chloro-2-methyl-phenol

4-chloro-3-methyl-phenol

4-chloro-3,5-dimethylphenol

2,4-dichloro-3,5-dimethyl-phenol 3,4,5,6-tetrabromo-methylphenol

5- methyl-2-pentylphenol

4- isopropyl-3-methylphenol

5- chloro-2-hydroxydiphenyl-methane

-p-chlorophenol

-p-chlorophenol

-p-chlorophenol

-p-chlorophenol

-p-chlorophenol

-p-chlorophenol

-p-chlorophenol

-p-Bromophenol

-p-Bromophenol

-p-Bromophenol

-p-Bromophenol

-p-Bromophenol

-p-Bromophenol

-p-Bromophenol

-p-Bromophenol

-o-Bromophenol

-o-Bromophenol

-o-Bromophenol

Resorcinol and its derivatives

Resorcinol

Methyl -Resorcinol Ethyl -Resorcinol n-Propyl -Resorcinol n-Butyl -Resorcinol n-Amil -Resorcinol n-Hexil -Resorcinol n-Heptil -Resorcinol n-Octil -Resorcinol n-Nonil -Resorcinol Fenil -Resorcinol Benzyl -Resorcinol Phenyl-ethyl -Resorcinol Phenylpropyl -Resorcinol p-chlorobenzyl -Resorcinol 5-chlorine -2,4- -Dihydroxydiphenyl-methane 4'-chlorine -2,4- -Dihydroxydiphenyl-methane 5-Bromo -2,4- -Dihydroxydiphenyl-methane 4 ¹ -Bromine -2,4- -Dihydroxydiphenyl-methane

Bisphenolic Compounds

Bisphenol A

2,2 ¹ -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 antibacterial agent is present in the oral composition in an effective antiplaque amount, typically about 0.01-5% by weight, preferably about 0.03-1% and most preferably about 0.25-0.5% and most preferably about 0.25-0.35%.

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

Triclosan is the preferred halogenated diphenyl ether. Preferred phenolic compounds are phenol, 2,2 ^1- methylene bis (4-chloro-6-bromophenol), thymol and eugenol. The most preferred antibacterial anti-plaque compound is Triclosan. Triclosan is disclosed in US Patent 4,022,880 above, as an antibacterial agent in combination with an anti-calculating agent that releases zinc ions and in German Patent Specification 35 32 860 in combination with a copper compound. It is also revealed as an antiplaque agent in a toothpaste formulated to contain a phase of chrysanthemum surfactant.

such a lamellar liquid having a lamellar spacing of less than 6.0 nm and which may possibly contain a zinc salt in the published European Patent Application 0161898 by Lane et al and in a toothpaste containing zinc citrate trihydrate in the published patent application European 0161899 of Saxton.

Molecularly dehydrated linear polyphosphate salts suitable for this purpose as anti-calculating agents are well known and are generally used in the form of their alkali metal (eg potassium and preferably sodium) or water-soluble ammonium salts, fully or partially neutralized, and any mixtures thereof, representative examples include sodium heosametaphosphate, sodium tripolyphosphate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphates, the corresponding potassium salts and the like. Linear polyphosphates correspond to (NaPO ^) ^, where n is about 2 to about 125. In the present invention, they are used in oral compositions in approximate amounts, by weight, from 0.1 to 3%, typically 1 to 2.5% more typically 1.5 to 2%. When n is at least 3 in NaPO4), said polyphosphates are glassy in nature.

Particularly desirable anticalculation agents are alkaline tetra metal pyrophosphates, including mixtures thereof, such as tetrasodium pyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. Thus, the oral composition may contain polyphosphate binding agent, which is substantially free of tetrasodium pyrophosphate or substantially free of a combination of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in which the ratio of sodium pyrophosphate to potassium is 3: 1 or more than 3: 1. An anti-calculating agent consisting of about 2% by weight of oral compositions of pyrophosphate is especially effective14

to tetrasodium.

stimulating (or enhancing) agent of antibacterial properties (AEA), which increases “the release of said antibacterial agent on oral surfaces and its retention on them, is used in sufficient quantities to obtain such an increase within the range, in the oral composition, of about 0.057. to about 47, preferably about 0.17 to about 37, more preferably about 0.57 to about 2.57 by weight.

AEA may be a simple compound, preferably a polymerizable mariomer, more preferably a polymer, the latter being entirely generic, including, for example, oligomers, homopolymers, two or two copolymers.

more monomers, ionomers, blocked copolymers, implanted copolymers, polymers and cross-linked copolymers and the like. □ AEA can be natural or synthetic and insoluble in water or. preferably soluble in water (saliva) or swellable (hydratable, which forms hydrogel). Him? it has an average molecular weight of about 100 to about 1,000,000, preferably about 1,000 to about 1,000,000, more preferably about 2,000 or. 2,500 to about 25® «© 00 or 50®.00®.

□ AEA normally contains at least one η o m and a d a intensifier group. m and n t e s u. 1 photon, single or. carboxylic, or a release, which is preferably acidic, phosphoryl or more preferably phosphose or. ammonium and at least one group —- to 1, by Kxemplu, organic metal that increases a.

a series of groups that increase action and groups that increase retention, these groups preferably having the formula ~ (X) -R, where X is 0, N SO2, P, Ρΰ or Si or . related, R is alkyl, alkenyl, acyl to loyal retention,

1ibertasequ.ndos

3, SD, aryl,

alkaryl, hydrophobic, heterocyclic aralkyl or its inert substituted derivatives, and n is zero or 1 or more. Said inert substituted derivatives are supposed to include substituents on R, which are generally non-hydrophilic and do not significantly interfere with the desired AEA functions, as they increase the release of the antibacterial agent on the oral surfaces and their retention on them, namely halo, e.g. eg, Cl, Br, I and carbo and the like. The following are illustrations of those groups that increase retention:

η X - < ^χ > _η Η 0 ---- methyl, ethyl, propyl, butyl, isobutyl, t- -butyl, cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl, acetyl benzoyl, butyryl, terephthaloyl, etc. 0 ethoxy, benzyloxy, thioacetoxy, phenoxy, carboethoxy, carbobenzyloxy, etc. Ν ethylamino, diethylamino, propylamido, benzylami- no, benzoyl starch, phenylacetamide, etc. s thiobutyl, thioisobutyl, thioalyl. thiobenzyl, thiophenyl, thiopropionyl, phenylthio acetyl, thiobenzoyl, etc. S0 butylsulfoxy, alylsulfoxy, benzylsulfoxy, phenyl- sulfoxy, etc. S0 ₂ butylsulfonyl, allylsulfonyl, benzylsulfonyl. phenylsulfonyl, etc. Ρ diethylphosphinyl, ethylvinylphosphinyl, ethylallylphos- finyl, ethylbenzylphosphinyl, ethylphenylphosphinyl, etc. ΡΟ diethylphosphinoxy, ethylvinylphosphinoxy, methylalkyl- phosphinoxy, methylbenzylphosphinoxy, methylphenylphosphinoxy, etc. Si trimethylsilyl, dimethylbutyl silyl, dimethyl- benzyl silyl, dimethyl vinyl silyl, dimethylalyl- silyl, etc.

As used herein, the release-enhancing group refers to a group that fixes or substantively, adhesive, cohesively or in any other way binds AEA (carrying the antibacterial agent) to oral surfaces (eg teeth and gums) thereby releasing the antibacterial agent on those surfaces.

The organic group that increases retention, usually hydrophobic, fixes or otherwise binds the antibacterial agent to the AEA, thus promoting the retention of the antibacterial agent in the AEA and indirectly on the oral surfaces. In some cases, the fixation of the antibacterial agent occurs through its physical arrest by the AEA, especially when the AEA is a cross-linked polymer, the structure of which inherently offers more sites for such a prison. The presence of one or higher molecular weight, plus hydrophobic crosslinked fraction to the crosslinking polymer further promotes the physical arrest of the antibacterial agent in or by the crosslinked AEA polymer.

Preferably, AEA is an anionic polymer consisting of a substantial chain or part containing repeating units, each preferably containing at least one carbon atom, and preferably at least one monovalent release enhancing group, directly or indirectly pendant and at least one monovalent retention enhancing group, directly or indirectly pendant, geminally and vicinally or, less preferably otherwise linked 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 links in the polymer chain, instead of, or in addition to, the carbon atoms, or as cross-linked fractions.

It is evident that any examples or illustrations of the AEAs disclosed herein, which do not contain as much release-enhancing groups as intensifying groups such as retention-enhancing groups, can and should preferably be chemically modified in the known manner to obtain the preferred AEA containing those groups and also, preferably, a series of each of those groups. In the case of preferred polymeric AEA, it is desirable, in order to maximize the fixation and release of the antibacterial agent on the oral surfaces, that the repeating units in the polymer chain or their substantial part containing the release-enhancing acidic groups constitute at least about 10% preferably about 50%, more preferably at least about 80% to 95% or 100%, by weight, of the polymer.

According to a preferred embodiment of this invention, the AEA consists of a polymer containing repeating units in which one or more phosphonic acid release enhancing groups are attached to one or more carbon atoms in the polymer chain. An example of such an AEA is poly (vinylphosphonic acid) containing units of formula I

- CH 7 / '

PO-.Hque, however, does not contain a retention-enhancing group.

A group of the latter type should however be present in poly (1 ~ phosphonoproperto) with units of the formula:

II - [CH - CH '1 / /

CI ~ U Ρ0_, Η _ο a preferred AEA containing phosphonic acid to be used for this purpose is poly (beta-styrenephosphonic acid> containing units of the formula:

III - [CH - CH 3 where Ph is 1 i be r t o o 3 o atoms acid beta units

Ph F'OH _r , phenyl, with the phosphonic intensifying group and the retention enhancing phenyl group being liquefied in the chain, or a styrene-phosphonic copolymer, having the vinyl-phosphonic chloride of formula III alternating or in random association with units of the previous formula I, or poly (phosphonic acid) containing units of the formula:

a 1 f a es t i r en o

IV - / 'CH - C ----- 77 /

Ph po ₃ h ₂ in which the release and retention enhancing groups are twinned in the chain.

These polymers of styrene-phosphonic acid and their copolymers with other inert ethylenically unsaturated monomers generally have molecular weights in the range of about 2000 to about 30,000, preferably about 2500 to about 10,000.

such inert monomers do not significantly interfere with the intended function of any copolymer used herein as an AEA.

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

V - / - CH ₂ ) ₁₄ CHPO ₃ H ₂ _7 _n where n can, for example, be an integer or have a value giving the polymer a molecular weight of about 3000; and sodium poly (butene-4,4-diphosphonate) having units of the formula:

-21VI

-Γ CH ₂ - CH —_7 CH - CH <

( ^p O3 ^H 2) ₂ poly (allyl-bis- (phosphonoethyl-amine) having units of the formula:

VII - / ”ch ₂ -CH ----_ 7ch ₂ - n <(po ₃ h ₂ ) ₂

Other phosphonated polymers for example poly (allyl-phosphono-acetate), phosphonated polymethacrylate, etc. and the twin diphosphonate polymers disclosed in European Patent Application 0321233 can be used as an AEA here, provided that, of course, they contain or are modified to contain the organic retention enhancing groups mentioned above

According to one aspect of this invention, the oral composition consists of an orally acceptable carrier, an agent that is effective in enhancing the anti-bacterial effect of an antibacterial agent that has an average molecular weight of about 1000 to about 1,000 000, contains at least one functional group that increases the release of the antibacterial effect and at least one organic group that increases the retention of the antibacterial effects, said groups containing said agent being free or substantially free of synthetic anionic linear polymeric polycarboxylate metal salt alkaline or

water-soluble ammonium having a molecular weight of about 1000 to 1 000 000 and polyphosphate anti-calculating agent, such as a mixture of potassium and sodium salts, the potassium to sodium ratio in that composition being in the range up to less than about 3: 1, e.g., about 0.37 to about 1.04: 1.

According to another preferred embodiment of the invention the AEA consists of a synthetic anionic polymeric polycarboxylate, which is also an alkaline phosphatase enzyme inhibitor. Synthetic anionic polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnesium have previously been disclosed as anti-calculating agents per se, for example in U.S. Patent Νδ 3,429,963 to Shedlovsky; U.S. patent NS 4,152,420 to Gaffar; U.S. Patent

Νδ 3,956,480 to Dichter et al; U.S. Patent Νδ 4,138,477 to Gaffar; and U.S. Patent Νδ 4,183,914 to Gaffar et al. However, only in disclosure essentially corresponding to U.S. Patent 4,627,977 to Gaffar et al does the use of such polycarboxylates for inhibiting the salivary hydrolysis of anti-pyrophosphate agents in combination with a compound providing a fluoride ion source be described.

It should be understood that the synthetic anionic polymeric polycarboxylates required in these various patents, when containing or modified to contain the retention enhancing groups described above, are useful as AEA in the compositions and methods of this invention and these disclosures are included herein by reference.

These synthetic anionic polymeric polycarboxylates are often used in the form

of its free acids or preferably alkali metal salts (eg potassium and preferably sodium) or partially ammonium, or more preferably completely neutralized, soluble in water or swellable in water (hydratable, which form a gel). Copolymers of 1: 4 to 4: 1 of maleic acid or anhydride with another ethylenically unsaturated polymerizable monomer, preferably methyl vinyl ether maleic anhydride having a molecular weight (MW) of about 30,000 to about 2,000,000 are preferred. copolymers are sold, for example, as Gantrez eg AN 139 (pM 500 000), AN 119 (PM 250 000); and preferably in Pharmaceutical Grade S-97 (P.M. 70,000), by GAF Corporation.

Other useful AEA polymeric polycarboxylates, containing or modified to contain groups that increase retention include those disclosed in US Patent NS 3,956,480 referred to above, namely 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N -vinyl-2-pyrrolidone, or ethylene, the latter being sold, for example, as Monsanto EMA NS 1103, PM 10 000 and EMA Grade 61 and copolymers of 1: 1 acrylic acid with methyl methacrylate or hydroxyethyl, methyl acrylate or ethyl and isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Other useful polymeric polycarboxylates disclosed in said US Patent Nos. 4,138,477 and 4,183,914, containing or modified to contain retention enhancing groups include maleic anhydride copolymers with ethyl vinyl ether, isobutylene or styrene, polyacrylic acids, poly-itaconic and polyfoam and sulfoacrylic PM oligomers as low as 1000, marketed as Uniroval ND-2.

Olefinically or ethylenically unsaturated carboxylic acids containing a polymerized retention enhancing group, containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, that is, an acid containing an olefinic double bond that works readily in polymerization, are generally suitable. due to its presence in the monomer molecule, either in the alpha-beta position relative to a carboxyl group or as part of a terminal methylene group. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy-propionic, sorbic, chloro-sorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, glacial, citronic, itaconic, mesaconic, citraconic, mesacutic, glaconic, mesaconic, citronic, glaconic, mesaconic, glazed, and acetic acids. , aconitic, alpha-phenylacrylic, 2-benzyl-acrylic, 2-cyclohexylacrylic, angelic, umbilic, fumaric, maleic. Other different olefinic monomers copolymerizable with those carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate and the like.

Copolymers usually contain groups of sufficient carboxylic salts for solubility in water.

Also useful for this purpose are the polymers called carboxyvinyls disclosed as components of toothpaste in U.S. Patents 3,980,767 to Chown et al; 3,935,306 to Roberts et al; 3,919,409 to perla et al; 3,911,904 by Harrison and 3,711,604 by Colodney et al. They are marketed, for example with the registered trademarks of Carbopol 934,940 and 941 by BV Goodrich, these products being essentially constituted by a colloidally water-soluble polymer of cross-linked polyacrylic acid with about 0.75% to about 2.0 % polyalkyl sucrose or polyolyl pentaerythritol, as a crosslinking agent, provides the crosslinked bonds and structures and desired increase in

retention by hydrophobicity and / or physical arrest of the antibacterial agent or the like. The polycarbophil is somewhat similar, being cross-linked polyacrylic acid with less than 0.2% divinyl glycol, the lower proportion, molecular weight and / or hideophobicity of this cross-linking agent tending to provide little or no increase in retention . The 2,5-dimethyl-1,5-hexadiene exemplifies a more effective cross-linking agent that increases retention.

synthetic anionic polymeric polycarboxylate component is very often a hydrocarbon possibly with a halogen and bonds and substituents containing 0, present for example in ester, ether and OH groups and, when present, is generally used in the present compositions in approximate amounts, by weight, of up to about 4% (usually at least about 0.05%).

AEA can also comprise natural anionic polymeric polycarboxylates containing groups that increase retention. Carboxymethylcellulose and other binding agents, gums and film-forming agents free of the previously defined release enhancing groups and / or retention enhancing groups are ineffective as AEA.

As examples of groups that increase the release based on phenolic acid and / or sulfonic acid containing AEA, reference can be made to polymers and copolymers containing units or fractions derived from the polymerization of substituted vinyl or allyl phosphonic and / or sulfonic acids, when necessary, on carbon atom 1 or 2 (or 3) by an organic group, which increases retention, for example having the formula - (X) -R previous26

referred to. Mixtures of these manomers and their copolymers can be used with one or more inert ethylenically unsaturated polymerizable manomers such as those described above for useful ionic polymeric polycarboxylates. As will be seen, in these and other polymeric AEA useful for this purpose, normally only one acidic release-enhancing group is attached to any given carbon or other atom in the polymer backbone or branch. Polysilos xanes containing or modified to contain pending release enhancing groups and retention enhancing groups can also be used for this purpose as AEA. The ionomers containing or modified to contain groups that increase release and retention are also effective here as AEA »The ionomers are described on pages 54Ó-573 of the Kirk-Othmer Chemical Technology Encyclopedia, 3rd edition, Supplementary volume, John Wiley and Sons, Inc. copy-right Γ794, the description of which is incorporated herein by reference. Equally effective as AEA for this purpose, as long as they contain or are modified to contain groups that increase retention are synthetic and natural polyesters, polyurethanes and polyamides including proteins and proteinaceous materials such as glue.gene, poly (argenine) and other polymerized amino acids .

When the oral preparation is done by initially dissolving the polyphosphate and the antibacterial agent in a humectant and surfactant when adding the AEA, especially the polycarboxylate in an increasing way, the solution becomes clear and can be characterized as a microemulsion ”. As the amount of the polycarboxylate increases, so that the complete oral preparation contains at least about 2.27 'of it by weight, the solution becomes cloudy and can be characterized as a healthy macroemu.-t 1. In these macroemulsion type compositions, the

antiplaque effect of the antibacterial agent appears to be optimized.

A desirable weight ratio of the substantially water-insoluble non-cationic antibacterial agent to the polyphosphate anti-calculating agent is greater than about 0.72: 1 to less than about 4: 1, for example from about 1: 1 to about from 3.5: 1, especially from about 1.6: 1 to about 2.7: 1.

In order to optimize the anti-calculation efficacy of the oral composition, inhibitors against polyphosphate enzymatic hydrolysis are desirably present. Such agents constitute an amount of a fluoride ion source sufficient to provide 25 ppm to 5000 ppm of fluoride ions and up to 3% or more of the synthetic anionic polymeric polycarboxylate having a molecular weight of about 1000 to about 1,000,000, preferably about 30,000 to about 500,000. Sources of fluoride ions, or fluorine releasing components, as enzyme phosphatase and acid pyrophosphatase inhibiting components, are well known in the art as anti-caries agents. These compounds are slightly soluble in water or can be completely soluble in water. They are characterized by their ability to release fluoride ions in water and by the absence of undesirable reaction with other compounds of the oral preparation. Among these materials are inorganic fluoride salts, namely soluble alkali metal, alkaline earth metal salts, for example sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprous fluoride , zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, ammonium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate, epirophosphate

sodium and fluorinated calcium. Tin and alkali metal fluorides, namely sodium and stannous fluorides, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred.

The amount of fluoride-releasing compound is somewhat dependent on the type of compound, its solubility, and the type of the oral preparation, although it should be a non-toxic amount, generally about 0.005 to about 3.0% in the preparation. In a toothpaste preparation, for example tooth gel, toothpaste (including cream), toothpaste powder or dental lozenges, an amount of that compound which releases up to about 5000 ppm F ion, by weight, from the preparation is considered satisfactory. Any suitable minimum amount of that compound can be used, although it is preferable to use enough compound to release about 300 to 2000 ppm more preferably about 800 to about 1500 ppm of 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 preparation and, preferably, in the range of about 0.05% to 1%. In the case of sodium monofluorophosphate, the compound can be present in an amount of about 0.1-3%, more typically about 0.76%.

In oral preparations, namely mouthwashing solutions, lozenges and chewing gum, the fluorine-releasing compound is typically present in an amount sufficient to release up to about 500 ppm, preferably about 25 to 300 ppm, by weight, from fluoride ion. An amount of about 0.005 to about 1.0% by weight of that compound is generally present.

In certain highly preferred forms of the invention, the oral composition can be of a substantially liquid nature, namely in the form of a solution for washing or rinsing the mouth. In such a preparation, the vehicle is typically a water-alcohol mixture preferably including a humectant, as described below. Generally, the weight ratio of water to alcohol is in the range of about 1: 1 to about 20: 1, preferably about 3: 1 to 10: 1 and more preferably about 4: 1 to about 6: 1. The total amount of the 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 that liquid preparation and the others 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 of 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 descaling or otherwise damaging tooth enamel. The pH can be controlled with acid (eg, citric acid or benzoic acid) or base (eg sodium hydroxide) or with a buffer solution (namely with benzoate, carbonate, sodium bicarbonate or citrate, disodium hydrogen phosphate , sodium dihydrogen phosphate, etc.

In another particular preferred form of this invention, the oral composition may be of a substantially solid or pasty nature, such as compressed dental powder or a toothpaste, which is a toothpaste (toothpaste) or emapl dentifrice. The carrier of those solid or pasty oral preparations generally contains dentally acceptable polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, fos-30-

fact of dehydrated calcium, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnium phosphate, calcium carbonate, hydrated alumina, calcined alumina, aluminum silicate, zirconium silicate, silica, bentonite, and mixtures thereof. Other suitable polishing materials include the particle-shaped, hot-hardening resins described in the E.LJ. NS 3.0 70.510, published on December 15, 1962, such as melamine, phenolic and urea formaldehydes, and cross-linked polyesters and polyepoxides. Preferred polishing materials include crystalline silica having particles up to about 5 microns in size, an average particle size up to about 1.1 microns and a surface area of up to about 50,000 cm / g silica gel or colloidal silica and complex amorphous alkali metal aluminosilicate.

When visibly transparent gels are used, colloidal silica polishing agents, such as salespeople, with the registered trademark of SYLOID, such as Syloid 72 and Syloid 74 or with the registered trademark of SANTOCEL, such as Santocel 100, are particularly useful. alkali metal aluminosilicate complexes, since they have refractive indexes close to refractive indexes close to the refractive indexes of liquid systems (including water and / or humectant) - gelling agent normally used in toothpaste.

Many of the polishing materials called water insoluble 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 in Thorpe's Dictionary of Applied Chemistry, volume 9, 4th edition, p. 510-511. The forms of insoluble sodium metaphosphate know-31-

Madrell salt and Kurrol salt are other examples of suitable materials. These metaphosphate salts have only a very small solubility in water and, therefore, are commonly called insoluble metaphosphates (IMP). There is a smaller amount of soluble phosphate material present in the form of impurities, usually a small percentage, such as up to 4%, by weight. The amount of soluble phosphate material believed to include 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 no more than 1% of the material is greater than 37 microns.

polishing material is generally present in solid or pasty compositions, in concentrations, by weight, 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 the toothpaste powder. In toothpaste, when the polishing material is siliceous in nature, it is generally present in an amount of about 10-30% by weight. Other polishing materials are typically present in an amount of about 30-75% by weight.

In a toothpaste, the liquid carrier can consist of water and humectant, typically in an amount ranging from about 10% to about 80%, by weight, of the preparation. Glycerin, propylene glycol, sorbitol and propylene glycol exemplify suitable humectants / vehicles. Liquid mixtures of water, glycerin and sorbitol are also advantageous. In transparent gels, where the refractive index is an important factor, approximately 2.5-30% by weight of water is used, 0 to

about 70% by weight of glycerin and about 20-80% by weight of sorbitol.

Toothpastes, creams and gels typically contain a natural or synthetic thickening or gelling 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 complex clay of alkali metal silicate and synthetic colloidal magnesium marketed, for example, as Laponite (eg, CP, SP 2002, D) marketed by Laporte Industries Limited. The analysis of Laponite D reveals, in approximate values, by weight, 58.00% SiC ^, 25.40% Mg O, 3.05% Na ₂ O, 0.98% Li ₂ O and some trace metals and water. Its actual specific weight is 2.53 and has an apparent density (g / ml at 8% humidity) of 1.0.

Other suitable thickeners include Irish moss, iota-carrageenan, tragacanth gum, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose (e.g., sold as Natrosol) sodium carboxymethyl cellulose and sodium colloidal silica such as finely crushed Syloid (eg 244). In some dentifrices prepared in accordance with the present invention, in particular when more than about 0.35% by weight of the water-insoluble antibacterial agent is used and a siliceous polishing agent is present in an amount of less than about 30% by weight, it may be desirable to include an agent that dissolves the antibacterial agent. Such solubilizing agents include humectant polyols such as propylene glycol, dipropylene glycol and hexylene glycol, celosolves such as methylcelosolve and ethylcelosolve, vegetable oils and waxes containing at least about 12 carbons in a linear chain such as olive oil, castor oil and petrolatum and esters such as amyl acetate, ethyl acetate and benzoate

benzyl.

It is evident that, as stipulated, oral preparations are intended to be sold or otherwise distributed in suitable labeled packaging.

Thus, a mouth rinse solution bottle will have a label describing it briefly, as a rinse or mouth rinse solution and with instructions for its use; and a toothpaste, cream or gel will normally be presented in a flexible tube, typically aluminum, coated lead or plastic, or other compressible pump delivery device or pressurized to dose the contents, having a label describing them in resu such as a toothpaste, gel or toothpaste.

Organic surfactants are used in the compositions of the present invention to obtain a greater prophylactic action, to contribute to obtain a uniform and complete dispersion of the anti-calculus and anti-plaque agent throughout the oral cavity and to make the present compositions more acceptable from the cosmetic point of view.

The organic surfactant material is preferably of anionic, non-ionic or ampholytic nature, and it is preferable to use a detergent material as surfactant that gives the composition detersive and foaming properties. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride-monosulfates such as the sodium monoglyceride sodium salt of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate , alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxypropane sulfonate and acyl aliphatic ones

upper-substantially saturated amides of lower aminocarboxylic acid aliphatic compounds, such as those having 12 to 16 carbons in the acyl, alkyl or fatty acid radicals and the like. Examples of the amides referred to lastly are N-lauroylsarcosine and the sodium, potassium and eta nolamine salts of N-lauroyl, N-myristoil or N-palmitoyl-sarcosine, which must be substantially free of soap or other higher fatty acid material. similar.

The use of these sarcosinate compounds in the oral compositions of the present invention is particularly advantageous since these materials have a prolonged and marked effect on the inhibition of acid formation in the oral cavity due to the decomposition of carbohydrates in addition to exerting some reduction in the enamel solubility in acidic solutions.

Examples of non-ionic water-soluble surfactants are condensation products of ethylene oxide with various reactive compounds containing hydrogen having long hydrophobic chains (eg aliphatic chains of about 12 to 20 carbon atoms), condensation products those (ethoxamers) containing hydrophilic polyoxyethylene fractions, namely condensation products of polyethylene oxide with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g., sorbitan monostearate) and polypropylene oxide (e.g. , Pluronic materials).

The surfactant is typically present in an amount of about 0.1-5%, by weight, preferably about 1-2.5%.

It is noteworthy that the surfactant can contribute to the dissolution of the non-cationic antibacterial agent and thereby decrease the amount of solubilizing humectant required.

Various other materials can be incorporated into the oral preparations of this invention namely bleaching agents, preservatives, silicones, chlorophyll compounds and / or ammonia material such as urea, diamonium phosphate and mixtures thereof. These adjuvants, when present, are incorporated into the preparations in amounts that do not substantially adversely affect the desired properties and characteristics. Significant amounts of zinc, magnesium, and other salts and metal materials, generally soluble, which would form complex with the active components of the present invention are to be avoided. Any suitable flavoring or sweetening material can also be used. Examples of suitable flavoring constituents are flavoring oils, eg, mint oil, peppermint, gaulteria, sassafras, cloves, eucalyptus, hydrangea-majorana (marjoram), cinnamon, lemon and orange, and methyl-salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perylartine, AMP (aspartyl-phenylalaline, methyl ester), saccharin and the like. Accordingly, flavoring and sweetening agents can each or together make up about 0.1% to 5% of the preparation. In addition, the flavoring oil appears to contribute to the dissolution of the antibacterial agent.

In the preferred practice of this invention, an oral composition according to this invention, namely a mouthwash or dentifrice solution containing the composition of the present invention is preferably applied regularly to the date enamel, namely

every day or every other day or every three days, or preferably 1 to 3 times a day, at a pH of about 4.5 to about 9, usually from about 5.5 to about from 8, preferably about 6 to 8, for at least 2 weeks to 8 weeks or more or for life.

The compositions of this invention can be incorporated into lozenges, or chewing gum or other products, for example, by introducing them into a hot base gum or by coating the outer surface of a base gum. jelutong, rubber latex, vinyl resins, etc., preferably with conventional plasticizers or softeners, sugar or other sweeteners, or glucose, sorbitol and the like.

The following examples are more illustrative of the nature of the present invention, but it is clear that the invention is not limited to them. All quantities and proportions referred to therein and in the appended claims are by weight, unless otherwise stated.

In the following examples, the agent Triclosan, 2,4,4'-trichloro-2'-hydroxydiphenyl ether is called TCHE, sodium lauryl sulfate is called SLS, the maleic anhydride and methyl vinyl ether eopolymer sold by GAF Corporation, as Gantrez S-97 is identified as Gantrez; tetrasodium pyrophosphate is identified as pyrophosphate; and sodium fluoride is identified as NaF.

EXAMPLE 1

The adsorption and release of minerals from the teeth for anti-plaque / anti-tartar efficacy is assessed by the attachment of the antibacterial agent to the hydroxyapatite disk of the minerals in the saline-coated teeth in the presence of pyrophosphate and different amounts of polycarboxylate.

The toothpaste formulations subject to evaluation are:

Parts by weight

A B

Glycerin

Iota-carrageenan

Sorbitol (70% solution) Propylene glycol Gantrez (13.02% solution) Titanium dioxide Water (deionized)

In F

Sodium saccharin

Pyrophosphate

Sodium hydroxide (50%)

Polishing agent based on silica (Zeodent 113)

Thickener based on silica (Sylodent 15) flavoring oil

TCHE

SLS

0.000 10,000 0. 750 0. 750 ! 000 30,000 0.500 0.500 19,000 15,500 0.500 0.500 9,957 13,457 0.243 0.243 0. 300 0.300 2,000 2,000 1,000 1,000

20,000 20,000 2,500 2,500 0.950 0.950 0. 300 0. 300 2,000 2,000

Gantrez is present as I.A. in an amount of 2.5 parts in toothpaste A and 2.0 parts in toothpaste B.

For the release test of antibacterial agent on a saliva-coated hydroxyapatite disc, the hydroxyapatite (HA) obtained from Monsanto Co. is extensively removed with distilled water, recovered by vacuum filtration and allowed to dry overnight at 37 ° C. The dry HA is crushed to a powder with a mortar and hand. 150,000 mg of HA are placed in the chamber of a KBr pellet mold (Barnes Analytical, Stanford, CT), which are compressed for 6 minutes at 10,000 pounds (20,205 kg) in a Carver Laboratory press. The resulting 13 nm disks are sintered for 4 hours at 800 ° C in a Thermolyne oven. All the saliva stimulated by the parapelicula is introduced into an ice-cooled glass beaker. The saliva is clarified by centrifugation at 15,000 Xg (gravity times) for 15 minutes at 42 ° C. Sterilization of the clarified saliva is done at 4 ° C with agitation by irradiating the sample with UV light for 1.0 hour.

Each sintered disc is hydrated with sterile water in a polyethylene test tube.

The water is then removed and replaced with 2.00 ml of saliva. A salivary film is formed by incubating the disc overnight at 37 ° C with continuous agitation in a water bath. After this treatment, the saliva is removed and the discs are treated with 1.00 ml of a solution containing antibacterial agent (Triclosan) in a liquid phase dentifrice solution and incubated at 372C with continuous agitation in the water bath. After 30 minutes, the disc is transferred to a new tube and 5.00 ml of water are added, followed by a gentle agitation of the disc with a Vortex.

The disc is then transferred to a new tube and repeats 40-

wash the procedure twice. Finally, the disc is carefully transferred to a new tube to avoid co-transferring any liquid along the dynamic. Then add 1.00 ml of methanol to the disk and shake vigorously with a Vortex. The sample is left at room temperature for 30 minutes to extract the Triclosan adsorbed on methanol. The methanol is then aspirated and clarified by centrifugation in a Beckman Microfuge 11 at 10,000 rpm for 5 minutes. After this treatment, the methanol is transferred to HPLC vials (liquid chromatography of due yield) to determine the concentration of the antibacterial action. Triplicate samples are used in all experiments.

The following table summarizes the values:

Painting

Toothpaste

Release of TCHE on the microgram saliva-coated Hidp ^ xiapatite

130

The values indicate that, with the increasing amount of Gantrez (Toothpaste A) there is a huge increase in the release of TCHE in the minerals of saliva-coated teeth.

EXAMPLE 2

The following toothpaste is effective as an anti-plaque and anti-calculus 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 oil 0.95 TCHE 0.30 SLS 2.00

EXAMPLE 3

Rinsing solution Parties mouth Tetrasodium pyrophosphate 2.00 Gantrez S-97 2.50 Glycerin 10.00 Sodium fluoride 0.05 Sodium lauryl sulfate 0, 20 TCHE 0, 06 Flavoring oil 0.40 Water to make up 100.00

EXAMPLE 4

Tablet

75-80% Sugar

1-20% Corn syrup

0.1-1.0% flavoring oil 2% tetrasodium pyrophosphate 2.50% Gantrez S-97 0.01 to 0.05% NaF, 01 to 0.1% TCHE to 5% Magnesium Stearate-based Lubricant 0.01 to 0.2% Water

EXAMPLE 5

Bubble gum

Base gum

Sorbitol (70%)

TCHE

Tetrasodium pyrophosphate

Gantrez S.97 parts, 00, 00, 50 to 0, 10 2, 00

2.50

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

EXAMPLE 6

Bubble gum

Base gum

TCHE

Gantrez

In F

Glycerin

Crystalline sorbitol

Tetrasodium pyrophosphate Flavoring oil and water

Parts, 00, 50, 00, 05, 50 53, 00, 00 to make 100, 00

In the previous Examples, better results are also obtained when TCHE is replaced by phenol, 2,2 ^1- methylene bis (4-chloro-6-bromophenol), eugenol or thymol and / or when Gantrez is replaced by other AEA, namely Carbopols (eg 934) or polymers of styrene-phosphonic acid having molecular weights within the range of about 3000 to 10,000, such as poly (beta-styrene-phosphonic acid), copolymers of vinyl-phosphonic acid with beta acid -styrenephosphonic, and poly (alpha-styrenephosphonic acid), or sulfoacrylic oligomers, or a 1: 1 copolymer of maleic anhydride with ethyl acrylate.

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

This invention has been described with respect to certain embodiments and it is evident that modifications and obvious variations to those skilled in the art can be made within the scope of this application and the appended claims.

Claims (34)

I ^a . - Process for the preparation of an oral composition, characterized in that, in an orally acceptable vehicle, an effective anti-calculation amount of material comprising about 0.1-3% by weight of at least one linearly dehydrated linear polyphosphate salt, such as anti-calculating agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial agent and up to about 4% by weight of an antibacterial-enhancing agent, which increases the release of said antibacterial agent on oral surfaces and retention in them, the weight ratio of the antibacterial enhancing agent for polyphosphate ion is in the range of about 1.6: 1 to about 2.7: 1. 2 ^a . Process according to claim 1, characterized in that said antibacterial agent is selected from the group formed by halogenated diphenyl ethers, halogenated salicylanilides, benzoic esters, halogenated carbanilides and phenolic compounds. 3 ^a . Process according to claim 1, characterized in that said antibacterial agent is halogenated diphenyl ether. 4 ^a . Process according to claim 3, characterized in that said halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. 5 ^a . Process according to claim 1, characterized in that said antibacterial agent is a phenolic compound. 6 ^a . Process according to claim 5, characterized in that said phenolic compound is selected from the group formed by phenol, thymol, eugenol and 2,2'-methylene bis (4-chloro-6-bromophenol). 7 ^a . Process according to claim 2, characterized in that said antibacterial agent is present in an amount of about 0.01-5% by weight. 8 ^a . Process according to claim 7, characterized in that said amount of antibacterial agent is about 0.25-0.5%. 9 ^a . Process according to claim 1, characterized in that said molecularly dehydrated linear polyphosphate salt is an alkali metal pyrophosphate in an amount of about 1-25% by weight. 10 ^a . Process according to claim 9, characterized in that said alkali metal pyrophosphate is tetrasodium polyphosphate. 1 Γ. - Process according to any of the claims 1-10, characterized in that the weight ratio of the antibacterial properties enhancing agent to the polyphosphate ion is from about 1.7: 1 to about 2.3: 1. 12 ^a . - Process according to any of the claims 1-11, characterized in that said vehicle consists of water, humectant and a gelling agent, in that said oral composition includes an ondotologically acceptable water-insoluble polishing agent and because it is a toothpaste. 13 ^a . - Process according to any of the claims 1-11, characterized in that said vehicle consists of water and a non-toxic alcohol and that said composition is a mouthwash. 14 ^a . - Process according to any of the claims 1-15, characterized in that said antibacterial-enhancing agent has an average molecular weight of about 1,000 to about 1,000,000. 15 ^a . Process according to claim 14, characterized in that said antibacterial properties enhancing agent contains at least one release enhancing functional group and at least one retention enhancing organic group. 16 ^a . Process according to claim 15, characterized in that said release enhancing group is acidic. 17 ^a . Process according to claim 16, characterized in that said release enhancing group is selected from the group formed by carboxylic, phosphonic, phosphonic and sulfonic acids and their salts and mixtures. 18 ^a . Process according to claim 17, characterized in that said retention enhancing organic group has the formula - (X) _n -R, where X is O, N, S, SO, SO2, PO or Si, R is alkyl hydrophobic, or aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic, or their inert substituted derivatives, and n is 1 or zero. -419 ^a . Process according to claim 17, characterized in that said antibacterial properties enhancing agent is an anionic polymer containing a series of release enhancing groups and retention enhancing organic groups. 20 ^a . Process according to claim 19, characterized in that said anionic polymer consists of a chain containing repeating units, each containing at least one carbon atom. 21 ^a . Process according to claim 20, characterized in that each unit contains at least one release enhancing group and at least one retention enhancing organic group attached to them or to vicinal atoms or other atoms in the chain. 22 ^a . Process according to claim 17, characterized in that the release enhancing group is a carboxylic group or a salt thereof. 23 ^a . Process according to claim 22, characterized in that the antibacterial-enhancing agent is a maleic acid or anhydride copolymer with another ethylenically unsaturated polymerizable monomer or a salt thereof. 24 ^a . Process according to claim 23, characterized in that said other monomer is methyl vinyl ether in a molar ratio of 4: 1 to 1: 4 with the maleic anhydride acid or anhydride. 25 ^a . Process according to claim 24, characterized in that said copolymer has a molecular weight of about 30,000 to 1,000,000. 26 ^a . Process according to claim 25, characterized in that the eopolymer has an average molecular weight of about 70,000. 27 ^a . Process according to claim 17, characterized in that the release enhancing group is a phosphonic group or a salt thereof. 28 ^a . Process according to claim 27, characterized in that the antibacterial properties-enhancing agent is poly (beta-styrenephosphonic acid), poly (alpha-styrene-phosphonic acid), or a styrene-phosphonic acid eopolymer with another styrene-phosphonic acid or with another monomer polymerizable inert ethylenically unsaturated or its salts. 29 ^a . Process according to claim 28, characterized in that said anti-bacterial enhancing agent has a molecular weight of about 1,000 to about 30,000. 30 ^a . Process according to any one of claims 1-29, characterized in that a source providing fluoride ions is included in said composition. 31 ^a . - Process for the preparation of an oral composition, characterized in that said composition includes an orally acceptable carrier, an effective antiplaque amount of a substantially water insoluble non-cationic antibacterial agent, an agent that increases the antibacterial property, which has a molecular weight average of about 1,000 to about 1,000,000, and contains at least one functional group that enhances release and at least the organic retention-identifying group, said groups containing said agent being free or substantially free of polymeric polycarboxylate salt linear anionic ammonium or -6 water-soluble alkali metal, having a molecular weight of about 1,000 to about 1,000,000, and a polyphosphate-based anticalculation agent. 32 ^a . Process according to claim 31, characterized in that a composition free or substantially free of tetrasodium pyrophosphate is obtained. 33 ^a . Process according to claim 31, characterized in that a composition free or substantially free of tetrasodium pyrophosphate and tetrasodium pyrophosphate is obtained, wherein the ratio of potassium pyrophosphate to sodium is 3: 1 or more than 3: 1. 34 ^a . Process according to claim 31, characterized in that a composition is obtained in which said polyphosphate-based anticalculation agent is a mixture of potassium and sodium salts, the potassium to sodium ratio being in the said composition in the range of to less than 3: 1, approximately. 35 ^a . Process according to claim 34, characterized in that said ratio is from about 0.37: 1 to about 1.04: 1. 36 ^a . Process according to claim 31, characterized in that a composition is obtained which contains a mixture of potassium and sodium salts, the potassium to sodium ratio in the said composition being in the range of 0.37: 1 to 1.04 :1.