DK176044B1 - Oral compsn. e.g. dentifrice, mouth-wash, lozenge, chewing gum - contg. water-insoluble non-cationic antibacterial anti-plaque agent, poly:phosphate anti-calculus agent, an antibacterial-enhancing agent, and vehicle - Google Patents

Abstract

An oral composition, e.g., a dentifrice, mouthwash, lozenge or chewing gum, consists of a vehicle with 0.1 wt.% polyphosphate salt (I) as anti-calculus agent, an anti-plaque amount of a substantially water-insoluble non-cationic antibacterial agent (II) and up to 4 wt.% antibacterial-enhancing agent (III) which enhances the delivery of (II) to, and retention on, oral surfaces. The wt. ratio of (I) ion : (III) is 1.6-2.7:1. Pref. (II) is a halogenated-diphenyl ether or -salicylanilides, benzoic esters, halogenated carbanilides and phenolic compounds, especially the ethers (specifically 2,4,4'-trichloro-2'-hydroxyphenyl ether (Trichlosan). (III) is an anionic polymer, especially a maleic acid-methyl vinyl ether copolymer or a polymer containing phosphonic groups. Also disclosed are compositions comprising (a) (II) and (III), (b) (I) and (II) and (c) (III) and (I) effective against any antibacterial agent.

Description

DK 176044 B1

The present invention relates to an antibacterial anti-plaque anti-tartar oral care agent. More particularly, it relates to an oral care agent comprising an orally acceptable carrier, an agent which is effective in enhancing the antibacterial effect of an antibacterial agent having an average molecular weight of about 10%. 1,000 to approx. 1,000,000, 5 contains at least one group which enhances the release of antibacterial activity, and at least one organic group which enhances retention of antibacterial activity, said agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium salt of synthetic , anionic, linear, polymeric polycarboxylic acid, having a molecular weight of approx. 1,000 to approx. 1,000,000, as well as polyphosphate 10 as anti-toothstone.

In U.S. Patents no; 4,627,977,4,515,772 and 4,323,551 disclose oral care products containing various polyphosphate compounds. In the former patent, a linear, molecularly dehydrated polyphosphate salt is used together with a source of fluoride ion and a synthetic, linear, polymeric polycarboxylate to prevent tartar formation. In the co-pending European patent application 89.200.710.5, anti-tartar efficiency is optimized with a reduced amount of the linear, molecularly dehydrated polyphosphate along with sources of fluoride ion and an increased amount of the synthetic linear polymeric polycarboxylate. In the other two US patents 20, water-soluble dialkali metal pyrophosphate is used alone or mixed with tetraalkali metal pyrophosphate.

Oral care agents that inhibit or prevent tartar formation on tooth surfaces are highly desirable, with tartar being one of the factors causing periodontal conditions. Reduction thereof therefore promotes oral hygiene.

Dental plaque is a precursor to tartar. Opposite tartar, however, plaque may form on any part of the tooth surface, especially including the gingival rim. In addition to being unattractive, it is therefore implicated in the occurrence of gingivitis.

30 DK 176044 B1 2

Therefore, it would be highly desirable to include antimicrobial agents known in reducing plaque in oral care agents containing anti-tartar agents. In fact, this is disclosed in U.S. Patent 4,022,550, wherein a compound which provides zinc ions as an anti-inflammatory agent is mixed with an anti-bacterial agent which is effective in inhibiting the growth of plaque bacteria. Many different antibacterial agents are described together with the zinc compounds, including cationic materials such as guanides and quaternary ammonium compounds as well as non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers.

To date, the cationic, antibacterial materials such as chlorhexidine, benzethonium chloride, and cetylpyridinium chloride have been the subject of major studies as antibacterial antiplaque agents. However, despite their use with zinc as an anti-tartar, they are not effective when used with anionic materials such as polyphosphate as an anti-tartar. This inefficiency is considered quite surprising as polyphosphates are chelating agents, and the chelating effect has been previously known to increase the effectiveness of cationic, antibacterial agents (see, for example: Disinfection, Sterilization and Preservation, 2nd Edition, Black, 1977, page 915, and Inhibition and Destruction of the Microbial Cell, Hugo, 1971, page 215). Quaternary ammonium compounds are actually found in the plaque-regulating mouthwash containing pyrophosphate according to U.S. Patent No. 4,323,551, and bis-biguanide antiplaque agent is proposed in the anti-dental pyrophosphate mouth care agent of U.S. Patent No. 4,515,772.

Given the surprising incompatibility of cationic antibacterial agents 25 with polyphosphates found as anti-tartar agents, it was quite unexpected that other antibacterial agents would be effective.

It is an advantage that certain antibacterial agents are effective in antitumor oral care agents containing a linear, molecularly dehydrated polyphosphate salt, a source of fluoride ion and the aforementioned antibacterial enhancer to prevent plaque formation.

DK 176044 B1 3

It is a further advantage of the invention that an agent is provided which is effective in reducing tartar formation and optimizing plaque reduction.

It is a further advantage of the invention that an anti-plaque anti-toothstone oral care agent is provided which is effective in reducing the incidence of gingivitis.

Further advantages of the invention will become apparent from the following description.

Preferred embodiments of the agent are set forth in the claims dependent on claim 1.

10

Typical examples of antibacterial agents that are particularly desirable for consideration of antiplaque efficacy, safety, and composition are:

Halogenated diphenyl ethers: 15 ------------------------------------ 2 ', 4,4'-trichloro 2-hydroxy-diphenyl ether (Triclosan), 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

Halogenated salicylanilides: 4 ', 5-dibromosalicylanilide, 3,4', 5-trichlorosalicylanilide, 3,4 ', 5-tribromosalicylanilide, 2,3,3', 5-tetrachlorosalicylanilide, 3,3,3 ', 5- tetrachlorosalicylanilide, 3.5-dibromo-3'-trifluonomethylsalicylanilide, 5-n-octanoyl-3'-trifluoromethylsalicylanilide, 3,5-dibromo-4'-trifluoromethylsalicylanilide, 3.5-dibromo-3'-trifluoromethyl

"--—— ι DK 176044 B1 4

benzoic acid:

Methyl-p-hydroxybenzoic acid ester, Ethyl p-hydroxybenzoic acid ester,

Propyl p-hydroxybenzoic acid ester,

Butyl-p-hydroxybenzoic acid ester.

Halogenated Carbanilides: 10 ---------------------------------- 3,4,4'-Trichlorocarbanilide, 3-Trifluoromethyl -4,4'-dichlorocarbanilide, 3, 3, 4 '-trichlorocarbanilide.

15

Phenolic compounds (including phenol and its homologue, mono- and polyalkyl and aromatic halogen (e.g.

20 F, Cl, Br, I) -phenols, resorcin and pyrocatequin and their derivatives and bisphenolic compounds).

These phenolic compounds include, inter alia: 25 Phenol and its homologue:

Phenol, 2-methyl-phenol, 3-methyl-phenol, 4-methyl-phenol, DK-176044 B1 5 4-ethyl-phenol, 2,4-dimethyl-phenol, 2,5-dimethyl-phenol, 3,4-dimethyl-phenol , 2,6-dimethyl-phenol, 4-n-propyl-phenol, 4-n-butyl-phenol, 4-n-amyl-phenol, 4-tert-amyl-phenol, 4-n-hexyl-phenol , 4-n-heptyl-phenol, 2-methoxy-4- (2-propenyl) phenol (Eugenol), 2-isopropyl-5-methyl-phenol (Thymol).

Mono and polyalkyl and aralkyl halogen phenols:

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-octy-1-p-chlorophenol, o-chlorophenol,

Methyl-o-chlorophenol, Ethyl-o-chlorophenol, n-propyl-o-chlorophenol, DK-176044 B1 6 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, 10-phenylethyl-p-chlorophenol, o-phenylethyl-m-methyl-p-chlorophenol, 3-methyl-p-chlorophenol, 3,5-dimethyl-p-chlorophenol, 6-ethyl-3- methyl p-chlorophenol, 6-n-propyl-3-methyl-p-chlorophenol, 6-isopropyl-3-methyl-p-chlorophenol, 2-ethyl-3,5-dimethyl-p-chlorophenol, 6-sec -butyl-3-methyl-p-chlorophenol, 2-isopropyl-3,5-dimethyl-p-chlorophenol, 6-diethylmethyl-3-methyl-p-chlorophenol, 6-isopropyl-2-ethyl-3-methyl * p-chlorophenol} 2-sec-amyl-3,5-dimethyl-p-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, DK 176044 B1 7 n-hexyl-p-bromophenol .

Cyclohexyl-p-bromophenol, o-bromophenol, tert-amyl-o-bromophenol, n-hexyl-o-bromophenol, n-propyl-m, m-dimethyl-o-bromophenol, 2-phenylphenol, 4-chloro-2 -methylphenol, 4-chloro-3-methylphenol, 4-chloro-3,5-dimethylphenol, 2,4-dichloro-3,5-dimethylphenol, 3,4,5,6-tetrabromo-2-methylphenol, 5- methyl 2-pentylphenol, 4-isopropyl-3-methylphenol, 5-chloro-2-hydroxydiphenylmethane.

Resorcin and its derivatives: 20 Resorcin,

Methyl resorcinol,

Ethyl resorcin, n-propyl resorcin, n-butyl resorcin, n-amyl resorcin, n-hexyl resorcin, n-heptyl resorcin, n-octyl resorcin, n-nonyl resorcin, phenyl resorcin. resorcin, benzyl resorcin, DK 176044 B1 8 phenylethyl resorcin, phenylpropyl resorcin, p-chlorobenzyl resorcin, 5-chloro-2,4-dihydroxydiphenylmethane, 5 4'-chloro-2,4-dihydroxydiphenylmethane, 5-bromo 2,4-dihydroxydiphenylmethane, 4'-bromo-2,4-dihydroxydiphenylmethane.

Bisphenolic Compounds: 10 ---------------------------------

Bisphenol A, 2,2'-methylene-bis (4-chlorophenol), 2,2, -methylene-bis (3,4,6-trichlorophenol) (hexachlorophen), 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 oral care in an effective amount of antiplaque, typically from ca. 0.01 to 5% by weight, preferably from about 0.03 to 1% and very much preferred from approx. 0.25 to 0.5% and most preferably from about 0.25 to 0.35%. The antibacterial agent is substantially water-insoluble, which means that its solubility is less than ca.

1 wt.% In water at 25 ° C and may be even less than ca. 0.1%. If an ionizable group is present, solubility is determined at a pH at which no ionization occurs.

The preferred halogenated diphenyl ether is Triclosan. The preferred phenolic compounds are phenol, 2,2'-methylene-bis- (4-chloro-6-bromophenol), thymol and eugenol.

The most preferred antibacterial antiplaque compound is Triclosan. Triclosan is described in the aforementioned U.S. Patent No. 4,022,880 as an antibacterial agent in combination with an anti-tartaric agent which provides zinc ions and in German Patent No. 35 32,860 in combination with a copper compound. . It is also disclosed as an antiplaque agent in a dentifrice composition so as to contain a lamellar liquid crystal surfactant phase having a laminar gap of less than 6.0 nm and which may optionally contain a zinc salt, in published European patent application no. .

No. 5,161,898, and in a dentifrice containing zinc citrate trihydrate in published European Patent Application No. 0,161,899.

The linear, molecularly dehydrated polyphosphate salts which are effective in carrying out the invention as anti-tartar agents are well known and are generally used in the form of their partially or completely neutralized, water-soluble alkali metal salts (e.g., potassium and preferably sodium) or ammonium salts and mixtures thereof. Representative examples include sodium hexametaphosphate, sodium tripolyphosphate, di-sodium dihydrogen pyrophosphate, trisodium monohydrogen pyrophosphate and tetrasodium pyrophosphate, the corresponding potassium salts and the like. Linear polyphosphates correspond to (NaPO 3) n where n is approx. 2 - approx. 125. In the present invention, they are used in oral care products in weight amounts of ca. 0.1 to 3%, typically ffa 1 to 2.5% and more typically 1.5 to 2%. When n is at least 3 in (NaPO 3) n, the polyphosphates are glassy.

Particularly desirable anti-tartar agents are tetraalkali metal pyrophosphates, including mixtures thereof, such as tetrasodium pyrophosphate, tetras potassium pyrophosphate and mixtures thereof. Thus, the oral care agent may contain polyphosphate as an antifouling agent which is substantially free of tetrasodium pyrophosphate or substantially free of a combination of tetras potassium pyrophosphate and tetrasodium pyrophosphate, wherein the ratio of potassium to sodium pyrophosphate is 3: 1 or greater than 3: 1. An anti-toothstone agent comprising about 2% by weight of the tetrasodium pyrophosphate oral care agents is particularly effective.

The antibacterial enhancer (AEA) which enhances the delivery of the antibacterial agent (10) and its retention on oral surfaces is used in amounts effective to achieve this enhancement in the range of the oral care agent of approx.

DK 176044 B1 10 0.05% to approx. 4%, preferably from ca. 0.1% to approx. 3% and more preferably from ca. 0.5% to approx. 2.5% by weight.

AEA may be a simple compound, preferably a polymerizable monomer, more preferably a polymer, the latter term being completely generic and including e.g. oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, cross-linked polymers and copolymers, and the like.

The AEA may be natural or synthetic and water-insoluble or preferably water (saliva) -soluble or swellable (hydrable, hydrogel-forming). It has an average molecular weight by weight of approx. 100 to approx. 1,000,000, preferably from approx. 1,000 to approx.

1,000,000, more preferably from approx. 2,000 or 2,500 to approx. 250,000 or 500,000.

The AEA usually contains at least one release enhancing group which is preferably acidic, such as sulfonic acid, phosphinic acid, or more preferably phosphonic acid or carboxylic acid, or a salt thereof, e.g. alkali metal or ammonium, and at least one organic retention reinforcing group, preferably several of both the release reinforcing and retention reinforcing groups, the latter groups preferably having the formula - (X) + - R wherein X is O, N, S, SO , SO 2, P, PO or Si or the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or their independently substituted derivatives, and n is 0 or 1 or more. The aforementioned "inert substituted derivatives" are to be understood as including substituents on R which are generally not hydrophilic and do not significantly interfere with the desired functions of AEA as enhancing the delivery of the antibacterial agent and its retention on mouth surfaces, such as halogen. , eg. Cl, Br, I and carbo and the like. Illustrations of such detention-enhancing groups are shown in the table below:

η X - (X) n- R

0 - Methyl, ethyl, propyl, butyl, isobutyl, t-butyl, cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl, etc.

DK 176044 B1 11 1 0 Ethoxy, benzyloxy, thioacetoxy, phenoxy, carboethoxy, carbobenzyloxy etc.

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

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

SO butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc.

SO2 Butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

Diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylphenylphosphinyl, etc.

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

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

As used in the present specification, the delivery enhancer group refers to one which adheres or generally adhesively, cohesively or otherwise binds AEA (which carries the antibacterial agent) to mouth surfaces (e.g., gum or gum surfaces). thereby "delivering" the antibacterial agent to these surfaces. The organic retention enhancer group, generally hydrophobic, attaches or otherwise binds the antibacterial agent to the AEA, thereby promoting the retention of the antibacterial agent to the AEA and indirectly on the mouth surfaces. In some cases, the antibacterial agent is affixed through physical entrapment thereof by AEA, especially when AEA is a cross-linked polymer, the structure of which itself provides increased sites for such entrapment. The presence of a more high molecular weight, more hydrophobic, cross-linking moiety in the cross-linked polymer further promotes the physical entrapment of the antibacterial agent of the cross-linked AJEA polymer.

5

Preferably, the AEA is an anionic polymer comprising a chain or skeleton containing repeating units, each preferably containing at least one carbon atom and preferably at least one direct or indirect protruding, mono valent, release enhancing group and at least one direct or indirect protruding, monovalent, retaining member. sight-enhancing group, geminal, vicinal or, less preferably otherwise bonded to atoms, preferably carbon, in the chain. Less preferably, the polymer may contain delivery-enhancing groups and / or retention-enhancing groups and / or other divalent atoms or groups as the site of or adjacent to carbon atoms or as cross-linking molecular moieties.

15

It will be understood that examples or illustrations of AEAs described herein which do not contain both delivery enhancement and retention enhancer groups may or, preferably, be chemically modified in a known manner in order to obtain the preferred AEAs containing both of these groups, and preferably more of 20 each of such groups. In the case of the preferred polymers of AEAs, it is desirable, in order to maximize the substantivity and delivery of the antibacterial agent to mouth surfaces, that the repeating units in the polymeric chain or skeleton containing the acidic release enhancing groups constitute at least about 10%. 10%, preferably at least approx. 50% and more preferably at least approx. 80% and up to 95% or 100% by weight of the polymer.

In a preferred embodiment of the invention, the AEA comprises a polymer containing repeating units in which one or more phosphonic acid release enhancing groups are bonded to one or more carbon atoms in the polymeric chain. An example of such an AEA is poly (vinyl phosphonic acid) containing units of the formula DK 176044 B1 13 I. - [CH2 - CH> po3h2 5, however, which does not contain a retention enhancing group. However, a group of the latter type will be found in poly (1-phosphonopropene) containing units of formula II. - [CH - CH] -

10 I I

ch3 po3h2 in A preferred phosphonic acid-containing AEA for use in the invention is poly (/ 3-styrene phosphonic acid) containing units of formula 15 III. - [CH - CH] -

I I

Ph P03H2 wherein Ph is phenyl and the release-enhancing phosphonic acid group and the retention-enhancing phenyl group are bonded to vicinal carbon atoms in the chain, or a copolymer of / 3-styrene phosphonic acid with vinyl phosphonyl chloride having units of formula III alternately with or in random distribution with units of formula I above, or poly (α-styrene phosphonic acid) containing units of formula IV. - [CH2 -C --------] - / \

Ph PO2H2 30 wherein delivery-enhancing and retention-enhancing groups are geminally linked to the chain.

These styrene phosphonic acid polymers and their copolymers with other inert ethylenically unsaturated monomers generally have molecular weights in the range of about

2,000 to approx. 30,000, preferably from ca. 2,500 to approx. 10,000. Such "inert" monomers do not substantially interfere with the desired function of any copolymer used as the AEA of the invention.

Other phosphonic acid-containing polymers include, e.g. phosphonated ethyl one having 5 units of formula V. - [(CH2) 14CHPO3H2] n- wherein n e.g. may be an integer or have a value giving the polymer a molecular weight of approx. 3,000, and sodium poly (butene-4,4-diphosphonate) having units of formula VI. - [CH 2 - CH -------] - CH 2 - CH <(PO 3 Na 2) 2 and poly (allyl-bis-phosphonoethylamine) having units of the formula VIL - [CH 2 - CH -]

20 I

CH2-N <(P03H2) 2

Other phosphonated polymers, e.g. poly (allyl phosphonoacetate), phosphonated polymethacrylate etc., and the geminal diphosphonate polymers described in EP 25 Publication No. 0.321.233 can be used according to the invention as AEA, provided, of course, that they contain or are modified to contain the organic retention enhancing groups defined above.

In one embodiment of the invention, the oral care agent comprises an orally acceptable carrier, an agent effective in enhancing the antibacterial effect of an antibacterial agent having an average molecular weight of approx. 1,000 to approx.

1,000,000, contains at least one functional group which enhances the delivery of antibacterial activity, and at least one organic group which enhances retention of anti-bacterial effects, the agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium salt of synthetic, anionic, linear polymeric polycarboxylic acid having a molecular weight of approx. 1,000 to 1,000,000, and polyphosphate antifouling agent, such as a mixture of potassium and sodium salts, the ratio of potassium to sodium in the agent being in the range of up to less than about 100%. 3: 1, e.g. from approx. 0.37 to approx. 1.04: 1st

In another preferred embodiment, the AEA comprises a synthetic anionic polymeric polycarboxylate which is also an inhibitor of alkaline phosphatase enzyme. Synthetic, 10 anionic, polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnesium have been previously described as anti-tartar agents as such in e.g. U.S. Patent No. 3,429,963, U.S. Patent No. 4,152,420, U.S. Patent No. 3,956,480, U.S. Patent No. 14,138,477, and U.S. Patent No. 4,183,914. However, in descriptions substantially similar to U.S. Patent No. 4,627,977, use of such polycarboxylates has been disclosed to inhibit salivary hydrolysis of pyrophosphate antitanking agents in combination with a source of fluoride ion. It is understood that when the synthetic anionic polymeric polycarboxylates thus disclosed in several patents contain or are modified to contain the retention enhancing groups mentioned above, they act as AEAs in the agents and 20 to the methods of the present invention, and to this extent reference may be made to the aforementioned patents.

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

DK 176044 B1 16

Other AEA-active polymeric polycarboxylates containing or modified to contain retention enhancing groups include those described in U.S. Patent No. 3,956,480, such as 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl 2-pyrrolidone or ethylene, the latter of which can be obtained e.g. as "Monsanto" EMA No. 1103 (molecular weight 10,000) and EMA grade 61, as well as 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Other active polymeric polycarboxylates disclosed in the aforementioned U.S. Patents Nos. 4,138,477 and 4,183,914, which contain or are modified to contain retention enhancing groups, include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether. , polyacrylic acid, polyitaconic acid and polymaleic acid and sulfoacrylic acid oligomers with molecular weights as low as 1,000, available as "Uniroyal" ND-2.

15

Suitable generally are polymerized retention-enhancing, group-containing, olefinic or ethylenically unsaturated carboxylic acids containing an activated carbon-carbon olefinic double bond and at least one carboxyl group, i.e. an acid containing an olefinic double bond which readily acts by polymerization due to its presence in the monomeric molecule, either in α-β position relative to a carboxyl group or as part of a terminated methylene group. Illustrative of such acids are acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, crotonic acid, / 5-acyloxy propionic acid, sorbic acid, ct-chlorosorbic acid, cinnamonic acid, , α-phenylacrylic acid, 2-25 benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid and anhydrides. Other various olefinic monomers which are copolymerizable with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate and the like. Copolymers usually contain enough carboxylic acid salt groups to be water soluble.

30 DK 176044 B1 17

Also useful in the invention are so-called carboxyvinyl polymers described as toothpaste components of U.S. Patent No. 3,980,767, U.S. Patent No. 3,935,306, U.S. Patent No. 3,919,409, U.S. Patent No. 3,911,904, and U.S. Patent No. 3,711,604. They are commercially available, e.g. under the trademarks "Carbopol" 934, 940 and 941 from B.V. Goodrich, and these 5 products consist essentially of a colloidal water-soluble polymer of polyacrylic acid crosslinked with from ca. 0.75% to approx. 2.0% polyallyl sucrose or polyallyl penta-erythrite as crosslinking agent, the crosslinked structures and bonds providing the desired retention enhancement by virtue of hydrophobicity and / or physical entrapment of the antibacterial agent or the like. "Polycarbophil" is somewhat similar in that it is polyacrylic acid crosslinked with less than 0.2% divinyl glycol in that the lower amount, molecular weight and / or hydrophobicity of this crosslinking agent tends to provide reduced or no retention reinforcement. 2,5-dimethyl-1,5-hexadiene is an example of a more effective retention-enhancing crosslinking agent.

15

The synthetic anionic polymeric polycarboxylate component is most often a hydrocarbon with any halogen and O-containing substituents and bonds found e.g. in ester, ether and OH groups, and, when found, are generally used in the present compositions in amounts of weight up to approx. 4% (generally at least about 0.05%).

The AEA may also comprise natural, anionic polymeric polycarboxylates containing in retention enhancing groups. Carboxymethyl cellulose and other binders, rubbers and film formers which lack the aforementioned release enhancer and / or retention enhancer groups are ineffective as AEA.

25

Illustrative of AEAs containing phosphinic acid and / or sulfonic acid release enhancing groups may be mentioned polymers and copolymers containing units or moieties derived from the polymerization of vinyl or allyl phosphinic acid and / or sulfonic acid, substituted as necessary in 1 or the 2 (or 3) carbon atom having an organic retention enhancing group, e.g. of the formula - (X) + - R as defined above. Mixtures of these monomers may be used, as well as copolymers thereof, with one or more inert, polymerizable, ethylenically unsaturated monomers such as those described above during the discussion of the active, synthetic, anionic, polymeric polycarboxylates. In these and other polymeric AEAs effective in the invention, as will be noted, as a rule, only an acidic, release-reinforcing group is attached to a given carbon atom or other atom in the polymeric backbone or branch thereof. . Polysiloxanes containing or modified to contain protruding, release enhancing and retention enhancing groups can also be used as AEAs of the invention. Also effective as AEAs for the invention are ionomers containing or modified to contain delivery enhancer and retention enhancer groups. Ionomers are described on pages 546 - 573 of the Kirk-Othmer Encyclopedia of Chemical Technology, 3rd Edition, Supplementary Binding, John Wiley and Sons, Inc., copyright 1984, to which reference is made. Effective as AEAs of the invention, provided they contain or are modified to contain retention enhancing groups, are also polyesters, polyurethanes and synthetic and natural polyamides containing proteins and proteinaceous materials such as collagen, poly (arginine) and other polymerized amino acids .

When the oral care agent is prepared by first dissolving the polyphosphate and antibacterial agent in moisture-binding agent and surfactant and adding AEA, in particular the polycarboxylate, portionwise, the solution becomes clear and can be characterized as a "microemulsion". As the amount of the polycarboxylate grows so that the complete oral care agent contains at least approx. 2.2% by weight thereof, the solution becomes cloudy and can be characterized as a "macro emulsion". In such macromulsion type agents, the antiplaque action of the antibacterial agent appears to be optimized.

A desirable weight ratio of the substantially water-insoluble, non-cationic, antibacterial agent to the polyposphate antitanking agent is from ca. 1.6: 1 to approx. 2.7: 1st

To optimize the antitumor effectiveness of the oral care agent, enzymatic hydrolysis inhibitors of the polyphosphate are conveniently present. Such agents are an amount of a fluoride ion source sufficient to yield from 25 ppm to 5,000 ppm of fluoride ions, and up to 3% or more of the synthetic, anionic polymeric polycarboxylate having a molecular weight of approx. 1,000 to approx. 1,000,000, preferably from approx. 30,000 to approx. 500,000.

5

The sources of fluoride ions or fluorine-providing component as inhibitor component of acid phosphatase and pyrophosphatase enzyme are well known as anticaries. These compounds may be slightly soluble in water or may be completely water soluble. They are characterized by their ability to release fluoride ions in water and by the freedom of undesired reaction with other compounds in the oral care agent. Among these materials are inorganic fluoride salts such as soluble alkali metal and alkaline earth metal salts, e.g. sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprofluoride, zinc fluoride, sodium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorosulfonate, ammonium fluorosulfonate, Alkali metal and tin fluorides such as sodium and stannofluoride, sodium monofluorophosphate (MFP) and mixtures thereof are preferred.

The amount of fluorine-releasing compound depends to some extent on the type of the compound, its solubility and the type of oral care agent, but it should be a non-toxic amount, generally from about 1 to about 5. 0.005 to approx. 3.0% in the composition. In a dentifrice, e.g. a tooth gel, toothpaste (including cream), tooth powder, or tooth tablet, an amount of such a compound which releases up to approx. 5,000 ppm F-ion by weight, too satisfactory. Any suitable minimum amount of such a compound can be used, but it is preferred to use sufficient compound to release approx.

300 to 2,000 ppm, more preferably from about 800 to approx. 1,500 ppm fluoride ion.

Typically, in the case of alkali metal fluorides, this component is present in an amount of up to approx. 2% by weight, based on the weight of the composition, and preferably in the range of about 30%. 0.05% to 1%. In the case of sodium monofluorophosphate, the compound can be found in an amount of approx. 0.1 to 3%, more typically approx. 0.76%.

In oral care products such as mouthwashes, lozenges, and chewing gum, the fluorine-providing compound is typically present in an amount sufficient to release up to approx.

. 500 ppm, preferably approx. 25 - 300 ppm by weight, fluoride ion. Generally, there are from ca. 0.005 to approx. 1.0% by weight of such a compound.

In certain very preferred embodiments of the invention, the oral care agent may be substantially liquid, e.g. a mouthwash or rinse liquid. In such a composition, the carrier is typically a water-alcohol mixture suitably containing a moisture-binding agent as described below. Generally, the weight ratio of water to alcohol is in the range of about 1: 1 to approx. 20: 1, preferably from ca. 3: 1 to 10: 1 and more preferably from ca. 4: 1 to approx. 6: 1. The total amount of water-alcohol mixture in this type of preparation is typically in the range of about 70 to approx. 99.9% by weight of the composition. The alcohol is typically ethanol or isopropanol. Ethanol is preferred.

The pH of such a liquid composition or other compositions of the invention is generally in the range of from 4.5 to approx. 9 and typically from ca. The pH is preferably in the range of from about 5 to about 8. 6 to approx. 8.0. It is worth noting that the compositions of the invention can be used 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 buffer (such as with sodium citrate, benzoate, carbonate or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate etc. ).

In certain other desirable embodiments of the invention, the oral care agent may be substantially solid or paste-like in character, such as dental powder, a dental tablet or a dental care agent, i.e. a toothpaste (toothpaste) or a gel dentifrice. The carrier in such solid or paste-like oral care composition generally contains dental acceptable polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dehydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, tri-magnesium phosphate, calcium carbonate, hydrated alumina, hydrated alumina. bentonite and mixtures thereof.

Other suitable polishing materials include the particulate, thermosetting resins disclosed in U.S. Patent No. 3,070,510, such as melamine, phenol and urea formaldehydes and cross-linked polyepoxides and polyesters. Preferred polishing materials 5 include crystalline silica having a particle size up to approx. 5 microns, an average particle size up to approx. 1.1 microns and a surface area up to approx. 50,000 cm 2 per grams, silica gel or colloidal silica and complex amorphous alkali metal-aluminum silicates.

When visually clear gels are used, a colloidal silica polishing agent such as those sold under the trademark "Syloid" as "Syloid" 72 and "Syloid" 74, or under the trademark "Santocel" as "Santocel" 100, alkali metal aluminum silicate grains -plexes, particularly useful as they have refractive indices close to the refractive indices of the gelling and liquid systems (including water and / or moisture-binding agents) commonly used in dentifrices.

Many of the so-called "water-insoluble" polishing materials are of anionic nature and also contain small amounts of soluble material, thus insoluble sodium metaphosphate can be formed in any suitable manner, as illustrated in Thorpe's Dictionary of 20 Applied Chemistry, Volume 9, 4th Edition, page 510 - 511. The forms of insoluble sodium metaphosphate known as Madrell's salt and Kurrol's salt are other examples of suitable materials. These metaphosphate salts exhibit only very little solubility in water and are therefore generally referred to as insoluble metaphosphates (IMPs). There is a lesser amount of soluble phosphate material as impurities, usually a few percent, e.g. up to 4% by weight. The amount of soluble phosphate material, which is believed to include a soluble sodium trimetaphosphate, in the case of insoluble metaphosphate, can be reduced or removed by washing with water if desired.

The insoluble alkali metal metaphosphate is typically used in powder form with a particle size such that no more than 1% of the material is greater than 37 microns.

30 DK 176044 B1 22

The polishing material is generally found in solid or paste-like agents in weight concentrations of approx. 10% to approx. 99%. Preferably, it is present in amounts ranging from approx. 10% to approx. 75% in toothpaste, and from approx. 70% to approx. 99% in tooth powder. When the polishing material is silicon-containing in the form of toothpastes, it is generally found in amounts of approx.

10-30% by weight. Other polishing materials are typically found in an amount of approx. 30 - 75% by weight.

In a toothpaste, the liquid carrier may comprise water and moisture-binding agent, typically in an amount ranging from approx. 10% to approx. 60% by weight of the composition. Glycerin, propylene glycol, sorbitol and polypropylene glycol are examples of suitable moisture binding agents / carriers. Also advantageous are liquid mixtures of water, glycerine and sorbitol. In clear gels where the refractive index is of importance, preferably approx. 2.5 to 30% by weight of water, from 0 to about 70% by weight glycerine and approx. 20 - 80% by weight sorbitol. Typically, toothpastes, creams and gels contain a natural or synthetic thickener or gelling agent in amounts of approx. 0.1 to approx. 10, preferably from ca. 0.5 to approx.

5% by weight. A suitable thickener is synthetic hectorite, a synthetic, colloidal magnesium alkali metal silicate complex obtainable e.g. such as "Laponite" (e.g., CP, SP 2002, D), negotiated by Laporte Industries Limited. "Laponite" D analysis shows by weight approx.

20, 58.00% SiO 2, 25.40% MgO, 3.05% Na 2 O, 0.98% Li 2 O and some water and trace metals.

Its true density is 2.53 and it has an apparent bulk density (g / ml at 8% humidity) of 1.0.

Other suitable thickeners include Irish moss, iotacarrageenan, tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose (e.g. (e.g., 244). In some of the dental preparations according to the invention, especially when more than approx. 0.35% by weight of the water-insoluble antibacterial agent, and a silicon-containing polishing agent is present in an amount of less than about 100%. 30 weight percent, it may be desirable to include an agent which dissolves the antibacterial agent. Such solubilizing agents include moisture-binding polyols such as propylene glycol, dipropylene glycol and hexylene glycol, cellos solvents such as methylcellosolve and ethyl cellosolve, vegetable oils and waxes containing at least about 100%. 12 carbon atoms in a straight chain such as olive oil, castor oil and petrolatum, and esters such as amyl acetate, 5 ethyl acetate and benzyl benzoate.

It will be understood that the oral care products must be negotiated or otherwise distributed in suitable labeled packages in the usual manner. Thus, a glass with mouthwash will have a label describing it as a mouthwash or mouthwash, as well as a user manual, and a toothpaste, cream or gel will usually be in a compressible tube, typically of aluminum, lined lead or plastic. , or other clamp dispensing apparatus, pump or pressure apparatus for measuring the contents, and having a label describing it as a toothpaste, gel or toothpaste.

Organic surfactants are used in the compositions of the invention to achieve increased prophylactic effect, help to achieve thorough and complete distribution of the antitumor and antiplaque agent in the oral cavity, and to make the present agents cosmetically more acceptable. The organic surfactant is preferably anionic, nonionic or ampholytic in nature, and it is preferred to use as a surfactant a purifying material which imparts the scavenging and foaming properties of the agent. Suitable examples of anionic surfactants are water-soluble salts of higher fatty acid monoglyceride monosulphates, e.g. the sodium salt of monosulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkylarylsulfonates such as sodium dodecylbenzenesulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2-dihydroxypropane sulfonate, and higher fatty acid esters of 1,2-dihydroxypropanesulfonate and .g. those having 12-16 carbon atoms in the fatty acid, alkyl or acyl radical, and the like. Examples of the latter amides are N-lauroylsarcosine and the sodium, potassium and ethanolamine salts of N-lauroyl, N-myristoyl or N-palmitoylsarcosine, which must be substantially free of soap or similar higher fatty acid material. The use of these sarcosinate compounds in the oral care agents of the invention is particularly advantageous, as these materials exhibit an extended and pronounced effect for inhibiting acid formation in the oral cavity due to carbohydrate degradation, in addition to exerting some reduction in the solubility of the tooth enamel. in acidic solutions. Examples of water-soluble, nonionic surfactants are ethylene oxide condensation products with various reactive hydrogen containing compounds, which are reactive therewith and have long hydrophobic chains (e.g., aliphatic chains of about 12-20 carbon atoms). ), which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene molecule moieties, such as poly (ethylene oxide) condensation products 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 approx. 0.1-5% by weight, preferably approx. 1 - 2.5%. It is worth noting that surfactant can help dissolve the non-cationic antibacterial agent, thereby reducing the amount of necessary solubilizing, moisture-binding agent.

Various other materials may be incorporated into the oral care compositions of the invention, such as whitening agents, preservatives, silicones, chlorophyll compounds and / or ammoniated materials such as urea, diammonium phosphate and mixtures thereof.

Where these additives are present, they are incorporated into the compositions in amounts which have no significant detrimental effect on the desired properties. Significant amounts of zinc, magnesium and other metal salts and materials, generally soluble which could form complex with active components of the invention, are to be avoided.

25

Any suitable flavored or sweetening material may also be used. Examples of suitable flavoring ingredients are essential oils, e.g. garden mint oil, peppermint, winter green, sassafras, spice, sage, eucalyptus, marjoram, cinnamon, lemon and orange, and methyl salicylate. Suitable sweeteners include sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartin, AMP (aspartylphenylalanine, methyl ester), saccharin and the like. Conveniently, aroma and sweetener, each individually or together, may amount to approx. 0.1% to 5% or more of the composition. In addition, essential oil seems to help dissolve the antibacterial agent.

In the preferred practical application of the invention, a mouth care agent according to the invention, such as a mouthwash liquid or dentifrice containing the composition of the invention, is preferably applied regularly to tooth enamel, such as every day or every other or every three days, or preferably from 1 to 3 times a day. , at a pH of approx. 4.5 to approx. 9, generally approx. 5.5 - 8, preferably from ca. 6 to 8, for at least 2 weeks and up to 8 weeks or more or throughout life.

10

The compositions of the invention may be incorporated into lozenges or in chewing gum or other products, e.g. by stirring in a hot rubber matrix or by coating the outside of a rubber matrix, examples of which may be mentioned gelatin, rubber latex, vinylith resins, etc., conveniently with conventional plasticizers or plasticizers, sugars or other sweetening agents such as .

The following examples further illustrate the nature of the invention, but it will be understood that the invention is not limited thereto. All quantities in the specification and claims are after 20 weight unless otherwise stated.

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

EXAMPLE 1.

The adsorption to and release from tooth minerals for antiplaque / antitumor effectiveness of agents is assessed by adsorption of antibacterial agent to saliva coated slices of the dental mineral hydroxyapatite in the presence of pyrophosphate and various amounts of polycarboxylate.

The compositions of the assessed toothpastes are: 10

Weight parts A B

Glycerin 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 19,000 20 Titanium Dioxide 0.500 0.500

Water (deionized) 9,957 13,457

NaF 0.243 0.243

Sodium saccharin 0.300 0.300

Pyrophosphate 2,000 2,000 25 Sodium hydroxide (50%) 1,000 1,000

Silicon dioxide polish ("Zeodent" 113) 20,000 20,000

Silicon dioxide thickener ("Sylodent" 15) 2,500 2,500 30 Aroma oil 0.950 0.950 TCHE, 0.300 0.300 DK 176044 B1 27 SLS 2,000 2,000 "Gantrez" is available as an active ingredient in 2.5 parts in toothpaste A and 2.0 parts in toothpaste B.

5

To test the delivery of antibacterial agent to a saliva-coated hydroxyapatite slice, hydroxyapatite (HA) from Monsanto Co. washed thoroughly with distilled water, collected by vacuum filtration and allowed to dry overnight at 37 ° C. The dried HA is ground to a powder with a mortar. 150.00 mg of HA is placed in a chamber in a KBr 10 pill matrix (Bames Analytical, Stanford, CT) and pressed together for 6 minutes at 10,000 pounds in a Carver laboratory press. The resulting 13 mm slices are sintered for 4 hours at 800 ° C in a Thermolyne oven. Whole saliva stimulated with parafilm is collected in an ice-cooled beaker. The saliva is prepared by centrifugation at 15,000 x g for 15 minutes at 4 ° C. Sterilization of the cleared saliva is performed at 4 ° C with stirring and irradiation of the sample with UV light for 1.0 hour.

Each sintered disk is hydrated with sterile water in a polyethylene test tube. The water is then removed and replaced with 2.00 ml of saliva. A saliva is formed by incubating the disc overnight at 37 ° C while still shaking in a water bath. After this treatment, 20 saliva is removed and the slices are treated with 1.00 ml of a solution containing antibacterial agent (Triclosan) in a liquid dentifrice phase and incubated at 37 ° C while still shaking in the water bath. After 30 minutes, transfer the slice to a new glass and add 5.00 ml of water, followed by shaking the slice gently with a vortex. The disc is then transferred to a new glass and the washing procedure repeated twice. Finally, the disc is gently transferred to a new glass to avoid co-transfer of any fluid along with the disc. Then add 1.00 ml of methanol to the disc and shake vigorously with a vortex. The sample is left at room temperature for 30 minutes to extract the Triclosan adsorbed in the methanol. The methanol is then extracted and cleared by centrifugation in a Beckman Microfuge 11 at 10,000 rpm. minute for 5 minutes. Following this treatment, the methanol is transferred to HPLC (high performance liquid chromatography) vials for DK 176044 B1 28 to determine the concentration of antibacterial agent. Three tests are taken for all experiments.

The table below summarizes these data: 5 TABLE.

Toothpaste Delivery of TCHE to saliva-coated 10 hydroxyapatite discs (micrograms) A 130 B 30 15

The data shows that with the increasing amount of "Gantrez" (toothpaste A) there is a very large increase in the delivery of TCHE to saliva coated tooth minerals.

EXAMPLE 2.

20 ------------------ The following toothpaste is effective as an antiplaque and anti-toothpaste: Weight Parts 25 ------------

Sorbitol (70%) 22.00

Irish moss 1.00

Sodium hydroxide (50%) 1.00 "Gantrez" (13.02% solution) 19.00

Water (deionized) 2.69 DK 176044 B1 29

Sodium monofluorophosphate 0.76

Sodium saccharin 0.30

Pyrophosphate 2.00

Hydrated Alumina 48.00 5 Flavor Oil 0.95 TCHE 0.30 SLS 2.00 EXAMPLE 3.

10 -------------------

Mouthwash: Parts

Tetrasodium pyrophosphate 2.00 15 "Gantrez" S-97 2.50

Glycerin 10.00

Sodium fluoride 0.05

Sodium lauryl sulfate 0.20 TCHE 0.06 Aroma oil 0.40

Water q.s. to 100.00 EXAMPLE 4.

25

Suction tablet: 75-80% sugar 1-20% corn syrup 30 0.1-1.0% flavor oil 2% tetrasodium pyrophosphate DK 176044 B1 30 2.50% "Gantrez" S-97

0.01-0.05% NaF 0.01-0.1% TCHE

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

10 Chewing Gum: Parts

Rubber matrix 25.00

Sorbitol (70%) 17.00 TCHE 0.50 - 0.10 15 Tetrasodium pyrophosphate 2.00 "Gantrez" S-97 2.50 In a variant example of the preceding example, "Gantrez" S-97 can be omitted.

EXAMPLE 6.

Chewing gum: Parts 25 Rubber matrix 30.00 TCHE 0.50 "Gantrez" 2.00

NaF 0.05

Glycerin 0.50 Crystalline sorbitol 53.00

Tetrasodium pyrophosphate 2.00 DK 176044 B1 31

Aroma oil and water q.s. In the previous examples, improved results can also be obtained when TCHE is replaced with each of phenol, 2,2'-methylene bis (4-chloro-6-bromophenol), Eugenol and Thymol, 5 and / or when " Gantrez "is replaced by other AEAs such as" Carbopol "(e.g., 934) or styrene phosphonic acid polymers having molecular weights in the range of about 3,000 to 10,000, such as poly (/ 3-styrene phosphonic acid), copolymers of vinyl phosphonic acid with β styrene phosphonic acid and poly (α-styrene phosphonic acid) or sulfoacrylic acid oligomers, or a 1: 1 copolymer of maleic anhydride with ethyl acrylate.

10

Similarly, similar results can be obtained when pyrophosphate (tetrasodium pyrophosphate) is replaced by tetrasodium pyrophosphate and tetracassium pyrophosphate, the weight ratio of potassium to sodium being a) 0.37: 1, b) 1.04: 1, c) 3: 1 and 3.5: first

The invention is thus described with reference to certain preferred embodiments, and it will be understood that modifications and variations thereof obvious to those skilled in the art will be included and are within the scope of the following claims.

Claims (17)

An oral care agent comprising an orally acceptable carrier, an agent which is effective to enhance the antibacterial effect of an antibacterial agent having an average molecular weight of approx. 1,000 to approx. 1,000,000 contains at least one group which enhances the release of antibacterial action and at least one organic group which enhances retention of antibacterial action, the agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium salt. of synthetic, anionic, linear, polymeric polycarboxylic acid, having a molecular weight of approx. 1,000 to approx. 1,000,000, as well as polyphosphate as an anti-toothstone. Oral care agent according to claim 1, characterized in that the polyphosphate is a mixture of potassium and sodium salts, the ratio of potassium to sodium in the agent being in the range of up to less than approx. 3: 1. Oral care product according to claim 2, characterized in that the ratio of potassium to sodium is from approx. 0.37: 1 to approx. 1.04: 1st Oral care composition according to claim 2, characterized in that the group which enhances the release is selected from the group consisting of phosphonic acid, phosphinic acid and sulfonic acid and their salts and mixtures thereof. Oral care agent according to claim 3, characterized in that the organic group which enhances retention comprises the formula - (X) n R, wherein X is O, N, S, SO, SO 2, PO or Si, R is hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic or their inert substituted derivatives, and n is 1 or 0. Oral care agent according to claim 1, characterized in that the release enhancing group is selected from the group consisting of phosphonic acid, phosphinic acid and sulfonic acid and their salts and mixtures thereof. DK 176044 B1 Oral care agent according to claim 6, characterized in that the organic retention-enhancing group comprises the formula - (X) + - R wherein X is O, N, S, SO, SO2, PO or Si, R is hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, heterocyclic or their inert substituted derivatives, and n is 1 or 0. 5 The oral care agent of claim 1, further comprising an effective amount of antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial agent. Oral care agent according to claim 1, characterized in that the weight ratio of the polyphosphate of the anti-tartar agent to the antibacterial agent is from more than 0.72: 1 to less than 4: 1. Oral care composition according to claim 9, characterized in that the weight ratio is from approx. 1: 1 15 to approx. 3.5: 1st Oral care composition according to claim 9, characterized in that the weight ratio is from 1.6: 1 to approx. 2.7: 1st Oral care agent according to claim 1, characterized in that the agent is free of or substantially free of tetrasodium pyrophosphate. Oral care agent according to claim 12, characterized in that it further comprises an effective antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial agent. Oral care agent according to claim 1, characterized in that the agent is free of or substantially free of combination of tetras potassium pyrophosphate and tetrasodium pyrophosphate, wherein the ratio of potassium to sodium pyrophosphate is 3: 1 or more than 3: 1. 30 DK 176044 B1 Oral care agent according to claim 14, characterized in that it further comprises an effective antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial agent. Oral care product according to claim 15, characterized in that the ratio of potassium to sodium is from approx. 0.37: 1 to approx. 1.04: 1st Oral care agent according to claim 1, characterized in that it contains potassium and sodium salts or ions, the ratio of potassium to sodium in the agent being in the range of up to less than 3: 1.