DK175071B1 - Antibacterial Antiplaque Oral Care - Google Patents

Description

DK 175071 B1

The present invention relates to an antibacterial antiplaque oral care agent. More particularly, it relates to an oral care agent containing a substantially water-insoluble, non-cationic antibacterial agent which is effective in preventing plaque.

Dental plaque is a soft deposit formed on teeth to 5 unlike tartar, which is a hard, calcified deposit on teeth. Unlike tartar, plaque can be formed 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.

jq It is therefore highly desirable to include antimicrobial agents known to reduce plaque in oral care agents. Cationic antibacterial agents have been frequently proposed. According to U.S. Patent No. 4,022,880, a compound which provides zinc ions, as antitanking agent, is mixed with an antibacterial agent effective to retard 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. The non-cationic, antibacterial, antiplaque halogenated hydroxydiphenyl ether, Tri-closan, has also been described in combination with zinc citrate trihydrate in published European Patent Application No. 01661,899. Triclosan is also disclosed in published European Patent Application No. 0,271,332 as a toothpaste component containing a solubilizing agent such as propylene glycol.

The cationic antibacterial materials such as chlorhexidine, benzthonium chloride, and cetylpyridinium chloride have been the subject of the largest study as antibacterial antiplaque agents. However, they are generally not effective when they

* νν · V I

2 is used with anionic materials. Non-cationic antibacterial materials, on the other hand, may be compatible with anionic components of an oral care agent.

However, oral care agents are typically mixtures of numerous components, and even such typical neutral materials as moisture binding agents can affect the effect of such oral care agents.

Furthermore, even non-cationic antibacterial agents may have limited antiplaque efficacy along with commonly used materials such as polyphosphate antifouling agents described together in published British Patent Application No. 2200551 and in EP 0.251,591. In U.S. Patent Application No. 398,605, filed August 25, 1989, it is shown that the antiplaque efficiency is greatly increased by including an antibacterial enhancer (ΑΕΆ) which enhances the release of the antibacterial agent and its retention on oral surfaces and provides optimized amounts and proportions of polyphosphate and AEA.

It is an advantage of the present invention to provide an mouthwash agent wherein a substantially water-insoluble, non-cationic, antibacterial agent and an AEA are found to prevent plaque formation, and wherein the mouthwash agent contains an orally acceptable liquid carrier which is effective in enabling the antibacterial agent 25 to dissolve in saliva in an effective antiplaque amount.

It is a further advantage of the invention that the AEA enhances the delivery and retention of a small but effective antiplaque amount of the antibacterial agent on teeth and on soft oral tissue.

It is a further advantage of the invention that an antiplaque 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.

In certain embodiments, the invention relates to an oral antiplaque agent comprising an effective antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial agent, ca.

0/005 - 4% by weight of an antibacterial enhancer which enhances the delivery of the antibacterial agent to and retention thereof on mouth surfaces and an orally acceptable carrier effective to enable the antibacterial agent to dissolve in saliva in an effective antiplaque amount, which mouthwash is substantially free of polyphosphate anti-tartar agent1.

Typical examples of water-insoluble, non-cationic antibacterial agents which are particularly desirable for reasons of antiplaque efficacy, safety and composition are:

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

Halogenated salicylanilides: 4 ', 5-dibromo salicylanilide 3,4', 5-trichlorosalicylanilide 3,4 ', 5-tribromosalicylanilide 2,3,3', 5-tetrachlorosalicylanilide 3,3,3 ', 5-tetrachlorosalicylanilide 3.5 -dibromo-3'-trifluoromethylsalicylanilide 5-n-octanoyl-3'-trifluoromethylsalicylanilide 3.5-dibromo-4'-trifluoromethylsalicylanilide 3.5-dibromo-3'-trifluoromethylsalicylanilide (Flurophen) 4 DK 175071 B

benzoic acid:

Methyl p-hydroxybenzoic acid ester Ethyl p-hydroxybenzoic acid ester Propyl p-hydroxybenzoic acid ester Butyl p-hydroxybenzoic acid ester

Halogenated carbanilides: 3,4,4'-trichlorocarbanilide 3-trifluoromethyl-4,4'-dichlorocarbanilide 3,3,4'-trichlorocarbanilide 10 phenolic compounds (including phenol and its homologue, mono- and polyalkyl and aromatic halogen (e.g. F, Cl, Br, I) phenols, resorcin and pyrocatequin and their derivatives and bisphenolic compounds)

Phenol and its homologue: Phenol 2-methylphenol 3-methylphenol 4-methylphenol 4-ethylphenol 2,4-dimethylphenol 2,5-dimethylphenol 3,4-dimethylphenol 2,6-dimethylphenol 4-n-propylphenol 4-n-butylphenol 4-n -amylphenol 4-tert-amylphenol 4-n-hexylphenol 4-n-heptylphenol 2-methoxy-4- (2-propenyl) phenol (Eugenol) 2-isopropyl-5-methylphenol (Thymol) DK 175071 B1 5

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 10 n-heptyl-p-chlorophenol n-octyl-p-chlorophenol o-chlorophenol Methyl-o-chlorophenol Ethyl-o-chlorophenol n-propyl-o-chlorophenol n-butyl-o-chlorophenol n-amyl-o-chlorophenol chlorophenol tert-amyl-o-chlorophenol n-hexyl-o-chlorophenol n-heptyl-o-chlorophenol p-chlorophenol o-benzyl-p-chlorophenol o-benzyl-m-methyl-p-chlorophenol o-benzyl-m, m-dimethyl-p-chlorophenol o-phenylethyl-p-chlorophenol o-phenylethyl-m-methyl-p-chlorophenol 3-methyl-p-chlorophenol 3,5-dimethyl-p-chlorophenol 6-ethyl-3-methyl p-chlorophenol 6-n-propyl-3-methyl-p-chlorophenol 6-isopropyl-3-methyl-p-chlorophenol 2-ethyl-3,5-dimethyl-p-chlorophenol 6-sec-butyl-3-methyl -p-chlorophenol 2-isopropyl-3,5-dimethyl-p-chlorophenol 6-diethylmethyl-3-methyl-p-chlorophenol DK 175071 B1 6 6-isopropyl-2-ethyl-3-methyl-p-chlorophenol 2- sec-aryl-3,5-dimethyl-p-chlorophenol 2- diethylmethyl-3,5-dimethyl-β-chlorophenol 6-sec-octyl-3-methyl-β-chlorophenol 5β-bromophenol

Methyl p-bromophenol Ethyl p-bromophenol n-propyl-p-bromophenol n-butyl-p-bromophenol n-amyl-p-bromophenol sec-ainyl-p-bromophenol 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:

Resorcin Methylresorcin 30 Ethylresorcin n-propylresorcin n-butylresorcin n-amylresorcin DK 175071 B1 7 n-Hexylresorcin n-heptylresorcin n-octylresorcin n-nonylresorcin 5 Phenylresorcin

Benzylresorcin Phenylethylresorcin P henylpropylresorcin p-chlorobenzylresorcin 10. 5-Chloro-2,4-dihydroxydiphenylmethane 4'-chloro-2,4-dihydroxydiphenylmethane 5-bromo-2,4-dihydroxydiphenylmethane 4 ”-bromo-2,4-dihydroxydiphenylmethane

Bisphenolic Compounds:

Bisphenol A

2,2'-methylene bis (4-chlorophenol) 2,2'-methylene bis (3,4,6-trichlorophenol) (Hexachlorophen) 2,2 * -methylene bis (4-chloro-6-bromophenol) bis (2-hydroxy-3,5-dichlorophenyl) sulfide bis (2-hydroxy-5-chlorobenzyl) sulfide

The non-cationic antibacterial agent is present in the mouth care agent in an effective antiplaque amount of typically about 0.01 to 5% by weight, preferably approx. 0.03-1% and more preferably approx. 0.25 -0.5% or approx. 0.25% to less than 0.5% and most preferably about 25%. 0.25 - 0.35%, e.g. ca. 0.3%, in a dentifrice and preferably approx. 0.03 - 0.3% by weight, most preferably approx. 0.03 -0.1% in a mouthwash or liquid dentifrice.

The antibacterial agent is substantially water-insoluble, which means that its solubility is less than ca. 1 wt.% 30 in water at 25 ° C, and may be even less than ca. 0.1%.

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

DK 175071 B1 8

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. 3532860 in combination with a copper compound. In European Patent Application No. 0,278,744 it is described in combination with a tooth desensitizing agent containing a source of potassium ions. It is also described as an anti-plaque agent in a toothpaste composed to contain a lamellar, liquid, crystal surface-active phase having a lamella gap of less than 6.0 nm and which may optionally contain a zinc salt, in published European and U.S. Patent Application No. 0161,898, and in a dentifrice containing zinc citrate trihydrate in published European Patent Application No. 01661,899.

The antibacterial enhancer (AEA), which enhances the delivery of the antibacterial agent and its retention on oral surfaces, is used in amounts effective to achieve this enhancement, in the range of the oral care agent from ca. 0.005 to approx. 4%, preferably approx. 0.1 - approx. 3% 20 and more preferably approx. 0.5% - approx. 2.5 weight *.

AEA may be a simple compound, preferably a polymerizable monomer and more preferably a polymer, which term is quite generic and includes e.g. oligomers, homopolymers, copolymers of two or more monomers, ionomers, block copolymers, graft copolymers, cross-linked polymers and copolymers, and the like. AEA can be natural or synthetic. It has an average molecular weight by weight of approx. 100 to approx. 1,000,000, preferably approx. 1,000 to approx. 1,000,000 and more preferably approx. 2,000 or 2,500 to approx. 250,000 or 500,000.

The AEA usually contains at least one release enhancer group which is preferably acidic, such as sulfonic acid, phosphonic acid or more preferably, phosphonic acid or carboxylic acid and at least one organic retention enhancer group, preferably more of both the release enhancer and the retaining 1 to 5 synthesizing group, the latter groups preferably having the formula - (X) n R, where X is O, N, s, SO, SO 2, P, PO or Si or the like, R is hydrophobic alkyl, alkenyl, acyl, aryl, alkaryl, aralkyl, heterocyclic or their inert substituted derivatives and n is 0, 1 or more. The aforementioned inert substituted derivatives should include substituents on R which are generally non-hydrophilic and do not significantly interfere with the desired functions of AEA as enhancing the delivery of the antibacterial agent and its retention to mouth surfaces such as halogen, eg. 15 Cl, Br, I and carbo and the like. Illustrations of such detention-enhancing groups are shown in the following table: L / r \ i f wvr i u i 10

η X - (X) R

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

1 o 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.

Butylsulphuric, allylsulphoxy, benzylsulphoxy, phenylsulphoxy etc.

SO2 butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.

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

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

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

DK 175071 B1 11

As used in the present specification, the delivery enhancer group refers to one which adheres or is substantially adhesive or cohesively or otherwise binds AEA (which carries the antibacterial agent) to oral surfaces (e.g. teeth and gums), thereby "delivering" the antibacterial agent to these surfaces. The organic retention enhancing group, in ordinary 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, whose structure by its nature provides an increased number of sites for such entrapment. The presence of a more high-molecular, more hydrophobic, cross-linking moiety in the cross-linked polymer further promotes the physical entrapment of the antibacterial agent to or of the cross-linked AEA polymer.

Preferably, the AEA is an anionic polymer comprising a chain or a base skeleton containing repeating units, each preferably containing at least one carbon atom and preferably at least one direct or indirect protruding monovalent release enhancing group and at least one direct or indirect protruding monovalent retention reinforcing group. 25, geminally, vicinally or, less preferably, otherwise bound 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 bonds in the polymeric chain instead of or in addition to carbon atoms or as cross-linking molecular moieties.

It will be appreciated that any examples or illustrations of AEA compounds described in the present specification which do not contain both delivery enhancer and retention enhancer groups may be and preferably are chemically modified in known manner. to obtain the preferred AEAs containing both such groups and preferably more of each of such groups. In the case of the preferred polymeric AEAs, it is desirable, in order to maximize the substantivity and delivery of the antibacterial agent to oral surfaces, that the repeating units in the polymeric chain or base skeleton containing the acidic release - reinforcing groups, constitute at least approx. 10%, preferably at least approx. 50% and more preferably at least approx. 80% up to 95% or 100% by weight of the polymer.

According to 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 (vinylphosphonic acid) containing units of formula I - [CH - CH] - Ηθ3Η2 20 which, however, does not contain a retention enhancing group. However, a group of the latter type will be found in poly (1-phosphonopropylene) having units of formula II - [CH - CH] - έθ3Η2

A preferred phosphonic acid-containing MA for use in the invention is poly (β-styrene phosphonic acid) containing units of formula III - [CH - CH] -

Ph PO3H2 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 β-styrene phosphonic acid with vinyl phosphonyl chloride having units of formula III, alternating with or in random connection with units of formula I above, or poly- (α-styrene phosphonic acid) containing units of formula IV -tCH 2 -yC -] -

Ph PO 3 H 2 in which the release enhancer and retention enhancer 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 approx. 2,000 to approx. 30,000, preferably from ca. 2,500 to approx. 10,000. Such "inert" monomers do not appreciably interfere with the desired function of a copolymer used as the AEA of the invention.

Other phosphonic acid-containing polymers include, e.g. phosphonated ethylene with units of formula V - [PH2) 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)) with units of formula VII - [CH 2 - CH ---] - CH 2 - N <(PO 3 H 2) 2

Other phosphonated polymers, e.g. poly (allyl phosphonoacetate>, DK 175071 B1 14 phosphonated polymethacrylate etc., and the geminal diphosphonate polymers described in published European Patent Application No. 0.321,233 can be used according to the invention as AEAs, provided they contain or are modified to contain the organic retention enhancing groups defined above.

In one embodiment of the invention, the oral agent comprises an orally acceptable carrier, an effective antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial agent, and an antibacterial enhancer, having an average molecular weight of about 10%. 1,000 to approx. 1,000,000 and contains at least one release-enhancing, functional group and at least one organic, retention-enhancing group, the agent containing said groups being free of or substantially free of water-soluble alkali metal salt or ammonium salt of synthetic anionic linear polymeric polycarboxylic acid having a molecular weight of approx. 1,000 to approx.

1,000,000.

In another preferred embodiment, the AEA may comprise a synthetic, anionic polymeric polycarboxylate. Although not used in the present invention to cooperate with polyphosphate antifouling agent, 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, has been used as an inhibitor of alkaline phosphatase enzyme to optimize the antitumor efficacy of linear, molecularly dehydrated polyphosphate salts, as disclosed in U.S. Patent No. 4,627,977. Indeed, in published British Patent Application No. 2200551, the polymeric polycarboxylate is described as an optional ingredient in mouth care agents containing linear, molecularly dehydrated polyphosphate salts and generally water-insoluble, non-cationic, antibacterial agent. It is further noted that in the context of the present invention, such a polycarboxylate is pronounced effective to promote the delivery and retention of the non-ionic, antibacterial anti-plaque anti-plaque agent on another surface (i.e., molecularly dehydrated polyphosphate). ) with which the polymeric polycarboxylate cooperates is absent, for example, when the component with which the polymeric polycarboxylate corresponds, in particular, is the non-cationic antibacterial agent.

Synthetic, anionic, polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnium 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. 4,138,477, and U.S. Patent No. 4,183,914.

10

The synthetic anionic polymeric polycarboxylates used in the invention are well known and are often used in the form of their free acids. 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, more preferably from approx. 30,000 to approx. 500,000.

These copolymers can be obtained e.g. such as "Gantrez", for example AN 139 (molecular weight 500,000), AN 119 (molecular weight 250,000), and preferably the pharmaceutical grade S-20 97 (molecular weight 70,000) from GAF Corporation.

Other AEA-active polymeric polycarboxylates containing e1 are modified to contain retention enhancing groups, including those described in U.S. Patent No. 3,956,480, such as the 1: 1 copolymers of maleic anhydride with

Ml \ I ff wv ff I w I

16 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, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, 5 methyl or ethyl acrylate, isobutyl, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

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

Suitable in general are retention-enhancing, group-containing, polymerized, olefinic or ethylenically unsaturated carboxylic acids containing an activated carbon-carbon olefinic double bond which readily functions in polymerization due to its presence in the monomeric molecule, either in the α-3 position. relative to a carboxyl group or part of a terminated methylene group. Examples of such acids are acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styrylacrylic acid, muconic acid, itaconic acid, glacial acid, citraconic acid, -phenylacrylic acid, 2-benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid and anhydrides. Other various olefinic monomers which are copolymerizable with these carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain a sufficient number of carboxylic acid salt groups to be water soluble.

Also useful for the invention are so-called carboxyvinyl polymers described as toothpaste components of U.S. Patents Nos. 3,980,767, 3,935,306, 3,919,409, 3,911,904 and 3,711,604.

DK 175071 B1 17

They are commercially available e.g. under the trademarks "Carbopol" 934, 940 and 941 by B.F.Goodrich, and these products consist essentially of a colloidal water-soluble polymer of polyacrylic acid, cross-linked with from ca. 0.75% to approx. 2.0% polyallyl-5 sucrose or polyallyl pentaerythrite as crosslinking agent, the crosslinked structure and crosslinking providing the desired retention enhancement by 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, but the lower amount, molecular weight and / or hydrophobicity of this crosslinking agent tends to give no or little retention enhancement. . 2,5-dimethyl-1,5-hexadiene exemplifies a more effective retention-enhancing crosslinking agent.

The synthetic anionic polymeric polycarboxylate component is essentially a hydrocarbon with any halogen and O-containing substituents and bonds, e.g. in the ester, ether and OH groups, and are used in the present compositions in about 20% by weight of 0.05 to 4%, preferably from 0.05 to 3% and more preferably from 0.1 to 2%.

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

As illustrative AEA *, containing phosphinic acid and / or sulfonic acid delivery enhancing groups, there may be mentioned polymers 30 and copolymers containing units or moieties, obtained by polymerization of vinyl or allylphosphinic acid and / or sulfonic acid, substituted as needed in the first or second ( or third) carbon atom having an organic retention enhancing group, e.g. has the formula - (X) n-R, which is de 18

VI% I «VV« I I

veneered above. Mixtures of these monomers can be used as well as copolymers thereof with one or more inert, polymerizable, ethylenically unsaturated monomers such as those described above for active, synthetic, anionic polymeric polycarboxylates. In these and other polymeric AEAs effective for the invention, as a rule, only one acidic, release-enhancing 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 delivery and retention enhancing groups can also be used as AEAs for the invention. Also effective as AEAs are ionomers containing or modified to contain delivery enhancing and retention enhancing groups. Ionizers are described on pages 546-573 of the Kirk Othmer Encyclopedia of Chemical Technology, 3rd Edition, Supplementary Binding, John Wiley & Sons, Inc. copyright 1984. Also effective as AEAs for the invention, provided they contain or are modified to contain retention enhancing groups, are 20 polyesters, polyurethanes and synthetic and natural polyamides, including proteins and proteinaceous materials such as collagen, poly (arginine) and other polymerized amino acids.

In one embodiment of the invention, the AEA having an average molecular weight of approx. 1,000 to approx. 1,000,000, at least one release-enhancing functional group and at least one organic, retention-enhancing group, said agent containing said groups being free of or substantially free of water-soluble alkali metal salt or synthetic, anionic, linear, polymeric polycarboxylate ammonium salt, with a molecular weight of approx. 1,000 to approx. 1,000,000.

According to the invention, a preferred mouth care agent is a dentifrice containing about 0.3% by weight of the antibacterial agent (e.g., triclosan) and approx. 1.5 - 2% by weight of polycarboxylate t as AEA.

DK 175071 B1 19

Without being bound by any theory, it is believed that AEA, especially polymeric AEA, is generally an anionic film-forming material, which probably binds to tooth surfaces and forms a coherent film over the surfaces, thereby preventing bacterial attachment to tooth surfaces. It is possible that the non-cationic antibacterial agent forms a complex or other form of compound with AEA and thus forms a film of a complex or the like over tooth surfaces. The film-forming property of AEA and the enhanced release and retention of the antibacterial agent on tooth surfaces due to AEA appear to render tooth surfaces unfavorable for bacterial accumulation, especially since the direct bacteriostatic effect of the antibacterial agent inhibits bacterial growth. Through the combination of three modes of operation; 1) enhanced delivery, 2) long retention time on tooth surfaces, and 3) prevention of bacterial attachment on tooth surfaces, the mouthpiece is therefore effectively made to reduce plaque. Similar antiplaque efficacy is achieved on soft oral tissue at or near the gum line.

According to the invention, the orally acceptable carrier is effective in enabling the substantially water-insoluble, non-cationic antibacterial agent to dissolve in saliva in an effective antiplaque amount.

25 in the oral care agent, an orally acceptable carrier includes an aqueous phase together with a moisture-binding agent. In a gel dental care fidel, which typically contains approx. 5 to 30% by weight of a silicon polishing agent, water is typically present in an amount of at least about

3% by weight, generally approx. 3 to 35%, and moisture binding agent, preferably glycerine and / or sorbitol, typically in a total amount of about 3%. 6.5 - 75% or 80% by weight of the oral gel dentifrice. Mention in the present description of sorbitol refers to the material which is typically commercially available as a 70% aqueous solution.

When the amount of antibacterial agent is approx. 0.25 - 0.35% by weight, gel dentifrice does not require an additional component of the carrier to solubilize the antibacterial agent, although the presence of such a solubilizing agent is optional. When the amount of antibacterial agent is less than ca. 0.25% by weight, e.g. ca. 0.01 up to approx. 0.25 wt%, therefore, solubilizing agent must be present to ensure sufficient solubility in saliva to provide antiplaque efficacy. When the amount of antibacterial agent is above approx.

0.35% by weight, e.g. ca. 0.35 to approx. 0.5% or more, e.g.

5%, the solubilizing agent must therefore be present, since a significant portion of the antibacterial agent would otherwise remain insoluble.

When the mouthpiece medium is a toothpaste containing approx. 30-75% by weight of a dental acceptable polishing agent, the presence of such a solubilizing agent is also optional.

When the oral agent is a mouthwash or liquid dentifrice, the oral carrier comprises at least one of a surfactant, a flavoring oil or a non-toxic alcohol, each of which supports dissolution of the antibacterial agent and is again present in a such solubilizer optional.

When solubilizing agent is present in the mouth care compositions of the invention, it is typically in an amount of approx. 0.5 to 20% by weight, 25 having as little as approx. 0.5% by weight is sufficient when the amount of substantially water-insoluble, non-cationic antibacterial agent is low, e.g. up to approx. 0.3% by weight. When larger quantities such as at least approx. 0.5 wt.% Antibacterial agent is present, and especially when silicon-containing polishing agent is also present in an amount of approx.

30 to 30% by weight, it is desirable that at least approx. 5% by weight, typically up to approx. 20% or more of the solubilizing agent is present. It should be noted that there may be a tendency for the dentifrice to differ in a liquid and a solid portion when there are more than ca. 5% by weight of the solubilizing agent.

DK 175071 B1 21

The agent that is or may be present to solubilize the antibacterial agent in saliva may be incorporated into the carrier of water and moisture binding agent. Such solubilizing agents include moisture-binding polyols such as propylene glycol, dipropylene glycol and hexylene glycol, cellos solvents such as methylcellosolve and ethylcellosolve, vegetable oils, and 10 waxes containing at least about 100 wt. 12 carbon atoms in a straight chain such as olive oil, castor oil and petrolatum and esters such as amyl acetate, ethyl acetate and benzyl benzoate. As used in the present specification, "propylene glycol" includes 1,2-propylene glycol and 1,3-propylene glycol. Significant amounts of polyethylene glycol, especially with a molecular weight of 600 or more, should be avoided since polyethylene glycol effectively inhibits the antibacterial activity of the For example, when polyethylene glycol (PEG) 600 is present with Triclosan in a weight ratio of 25 Triclosan: 1 PEG 600, 20, the polyethylene glycol reduces the antibacterial effect of Triclosan by a factor of about 16 compared with the one having in the absence of polyethylene glycol.

In certain embodiments of the invention, an oral dentifrice may be substantially of gel character such as a gel dentifrice. Such a gel-like mouthpiece contains silicon-containing tooth polishing material. Preferred polishing materials include crystalline silica having a particle size of up to approx. 5 microns, an average particle size up to 2 to approx. 1.1 microns, and a surface area up to approx. 50,000 cm grams, silica gel or colloidal silica and complex amorphous alkali metal aluminum silicates.

When visually clear or unpaired gels are used, a colloidal silica polish such as those sold under the trademarks "Syloid" as "Syloid" 72 and "Syloid" 74

V% Iff VV I I ** I

22 or under the trademark "Santocel" as "Santocel" 100, or alkali metal aluminum silicate complexes (i.e. silica containing alumina in chemical composition in the matrix) are particularly useful as they are compatible with the gel-like texture and have refractive indices close to the refractive indices of the gelling indices. systems (including water and / or moisture-binding agent) commonly used in dentifrices.

The polishing material is generally found in the dentifrices such as toothpastes or gel abrasives at weight concentrations of about 10%. 5% to approx. 30%.

In the embodiment of the invention, wherein the oral care agent is a dentifrice, an orally acceptable carrier containing an aqueous phase is found together with a moisture-binding agent which is preferably glycerine and / or sorbitol, wherein water is typically present in an amount of 15 - 35% or 40% by weight, and glycerine and / or sorbitol typically total in 20 - 75% by weight of the dentifrice and more typically about 25 - 60%. The mention of sorbitol in turn refers to the material that is typically commercially available as a 70% aqueous solution.

According to the invention, the dentifrice may be substantially paste-like in character, such as a toothpaste (toothpaste), although when using silicon-containing polishing material (which is generally not the case, since such a material is typically not used in an amount greater than about 10%. 30% by weight) may be of gel-25 character. The carrier in the dentifrice contains dental acceptable polishing material and examples of these are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate, anhydrous dicalcium phosphate, magnesium orthophosphate, calcium magnesium oxide, trimagnesium phosphate, calcium magnesium phosphate, trimagnesium phosphate, mixtures thereof with each other or with hard polishing materials such as calcined alumina and zirconium silicate, material containing the particulate thermosetting resins disclosed in DK 175071 B1 23

J

in U.S. Patent No. 3,070,510, such as melamine, phenolic and urea formaldehydes and cross-linked polyepoxides and polyesters. Preferred polishing materials include insoluble sodium metaphosphate, dicalcium phosphate and hydrated alumina.

5 Many of the so-called "water-insoluble" polishing materials are anionic in 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 Applied Chemistry, Volume 9, 4th Edition, pages 510 - 511. The 10 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 therein, usually a few percent such as 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.

20 pet 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.

Hydrated alumina is an example of a polishing material which is essentially non-ionic in nature. Typically, it has a small particle size, i.e. that at least approx. 85% of the particles are less than 20 microns, and are such as those classified as gibsite (α-alumina trihydrate), and are usually represented chemically as or Al (OH) The average particle size of gibsite is generally approx. 6-9 mi-30 kr. A typical quality has the following size distribution: 24 DK 175071 Bl

Micron% <30 94-99 <20 85-93 <10 56-67 5 <5 28-40

The polishing material is generally found in paste or gel preparations in weight amounts of approx. 30% to approx. 75%.

Toothpastes or toothpastes as well as gel dentifiers typically contain a natural or synthetic thickener or gelling agent in amounts of approx. 0.1 to 10%, preferably approx.

0.5 to approx. 5%. A suitable thickener is synthetic colloidal magnesium alkali metal silicate complex as a clay species obtainable e.g. such as "Laponite" (e.g., CP, SP 2002, D), negotiated by Laporte Industries Limited. Analysis of "Laponite" D 15 shows by weight approx. 58.00% SiO2, 25.40% MgO, 3.05% Na2O, 0.98% LijO 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 or gelling agents include Irish moss, iota carrageenan, tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose {e.g. can be obtained as "Natrosol"), sodium urocarboxymethyl cellulose and, especially when silicon-containing polishing agent is present, colloidal silica such as those available as finely divided "Syloid" 244 or "Sylodent" 15.

In the embodiment according to the invention, where the mouthwash is a mouthwash or liquid toothpaste, in particular in a mouthwash liquid t, the carrier is typically a mixture of water and alcohol. In general, the weight ratio of water to alcohol is in the range of about 1: 1 to 20: 1, preferably approx. 3: 1 - 10: 1 and more preferably approx. 4: 1 - approx. 6: 1. The total amount of water-alcohol mixture in this type of composition is typically in the range of from about. 70 to approx. 99.9% by weight. The alcohol is a non-toxic alcohol such as ethanol or isopropanol. Moisture-binding agents such as glycerine and sorbitol can be found in an amount of approx. 10 to 30% by weight. Liquid dentifrices typically contain approx. 50 - 85% water, may contain approx. 0.5 to 20% by weight of non-toxic alcohol and may also contain approx. 10 - 40 wt% of moisture binding agent such as glycerine and / or sorbitol. Reference to sorbitol refers to the commercially available material as a 70% aqueous solution. Ethanol is preferred as non-toxic alcohol. The alcohol is believed to support dissolution of the water-insoluble, non-cationic, antibacterial agent, and so is the aromatic oil.

As mentioned, the non-cationic antibacterial agent is substantially water-insoluble. However, in the present invention, along with AEA such as polycarboxylate found in the mouthwash or liquid dentifrice, organic, surfactant, aromatizing oil or non-toxic alcohol is believed to help dissolve the antibacterial agent and help it reach soft oral tissue at or near the gums as well as dental surfaces. Organic surfactants and / or flavoring oils can also help dissolve the antibacterial agents as optional ingredients in the oral care products.

Organic surfactants are also used in the compositions of the invention to achieve increased prophylactic effect, assist in obtaining thorough and complete dispersion of anti-bacterial antiplaque agent in the oral cavity and 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 monosulfates such as the sodium salt of the mono-sulfated monoglyceride of hydrogenated coconut oil fatty acid, higher alkyl sulfates such as sodium lauryl sulfone acetic acid sulfate, alkylaryl sulfate, alkylaryl sulfate of 1,2-dihydroxypropanesulfonate and the substantially saturated higher aliphatic acyl amides of lower aliphatic aminocarboxylic acid compounds such as those having 12-16 carbons 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 should be substantially free of soap or similar higher fatty acid material. The use of these sarcosinate compounds in the oral care compositions of the invention is particularly advantageous because these materials exhibit an extended and pronounced action to inhibit acid formation in the oral cavity due to carbohydrate degradation, in addition to exerting some reduction in the solubility of tooth enamel in acidic solutions. Examples of water-soluble, nonionic surfactants are condensation products of ethylene oxide having various reactive, 20 hydrogen-containing compounds r, which are reactive therewith and which have long hydrophobic chains (e.g., aliphatic chains having approx.

12. - 20 carbon atoms) which contain condensation products ("ethoxymers") containing hydrophilic polyoxyethylene molecules such as poly (ethylene oxide) condensation products with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate) and polypropylene oxide (for example, the materials called "Pluronic").

Surfactant is typically present in an amount of approx. 0.5 to 5% by weight, preferably approx. 1 - 2.5%.

When the mouth care agent is a liquid toothpaste, the natural or synthetic thickener or gelling agent is typically found in amounts of approx. 0.1 - approx. 10%, preferably from approx. 0.5 to approx. 5%.

In general, liquid dentifrices do not contain a polishing agent. As disclosed in U.S. Patent No. 3,506,757, ca. 0.3 - 2.0% by weight of a high molecular weight polysaccharide, in excess of 1,000,000, containing mannose, glucose, potassium-glucuronate and acetyl molecular moieties in a ratio of approx. However, 2: 1: 1: 1 is used as a suspending and thickening agent in a liquid dentifrice, which may then also contain approx.

10-20% of a polishing material such as hydrated alumina, dicalcium phosphate dihydrate, calcium pyrophosphate, insoluble sodium metaphosphate, anhydrous dicalcium phosphate, calcium carbonate, magnesium carbonate, magnesium oxide, silica, mixtures thereof and the like.

Without being bound by any theory of obtaining the advantages of the invention, it is believed that an aqueous, moisture-binding carrier is usually solubilized in surfactant micelles in the mobile phase (i.e., not containing gelling agent and polishing agent if present in a dentifrice ). During use, the mobile phase solution of dentifrice may be diluted with saliva which causes precipitation of Triclosan. It turns out that even in the absence of a particularly soluble material for Triclosan - when the amount of Triclosan is approx. 0.25% -0.35% by weight and AEA such as polycarboxylate is present - there is enough Triclosan to exert an excellent anti-plaque effect on the soft tissue at the gum line. Similar comments apply to other water-insoluble, non-cationic, antibacterial agents described herein.

The dentifrice may also contain a source of fluoride ions or a fluorine-releasing component as an anticary agent in an amount sufficient to provide approx. 25 ppm to 5,000 ppm fluoride ions. These compounds may be slightly soluble in water or may be completely water soluble. They are peculiar in their ability to release fluoride ions in water and by being essentially free of undesired reaction with other compounds in oral care in the downstream agent. Among these materials are inorganic fluoride salts such as soluble alkali metal salts, alkaline earth metal salts, e.g. sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprofluoride, zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorosulfonate, ammonium fluorosirconate, Alkali metal and tin fluorides such as sodium and stannofluorides, sodium monofluorophosphate (MFP) and mixtures thereof are preferred.

The amount of fluorine-providing compound depends to some extent on the type of the compound, its solubility and the type of mouthwash, but it should be a non-toxic amount, usually approx.

0.0005 to approx. 3.0%, in the composition. In a dentifrice, e.g. 15 a tooth gel, is an amount of such a compound which releases up to approx. 5,000 ppm F-ion by weight of the preparation, 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 ca. 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 approx. 0.05% to 1%. In the case of sodium monofluorophosphate, the compound ice can be found in an amount of approx. 0.1 to 3%, more typically approx.

0.76%.

It will be appreciated that the oral care products should be negotiated or otherwise distributed in suitable labeled packages in the usual manner. Thus, a toothpaste gel will usually be in a 30 s breast pressure tube, typically of aluminum, lined lead or plastic, or another dispensing container operated by squeezing, pumping or printing to measure the contents and having a mark which describes it as a dentifrice gel or the like.

DK 175071 B1 29

Various other materials can be incorporated into the mouth care agents of the invention, such as antifouling agents, preservatives, silicones, chlorophyll compounds and / or ammoniated materials such as urea, diammonium phosphate and mixtures thereof. When 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 10 zinc, magnesium and other generally soluble metal salts and materials which would complex with active components of the invention are to be avoided.

Any suitable flavoring or sweetening material may also be used. Examples of suitable flavoring ingredients 15 are flavoring oils, e.g. garden mint oil, peppermint, winter green, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange and methyl salicylate. Suitable sweeteners include sucrose, lactose, maltose, xylitol, sodium cyclamate, perillartin, AMP (aspartylphenylalanine methyl ester), saccharin and the like. Conveniently, aroma and sweeteners, each or together, may comprise from ca. 0.1% to 5% or more of the composition. Like the surfactant, aromatic oil is believed to help dissolve the antibacterial agent, along with or even in the absence of surfactant.

In the preferred practical application of the invention, an oral care agent according to the invention is preferably applied regularly to tooth enamel and soft oral tissue, especially at or near the gum line, e.g. every day or every other or every third day, 30 or preferably from 1 to 3 times a day, at a pH of approx. 4.5 to approx. 9 or 10, generally approx. 5.5 to approx.

8, preferably approx. 6 to 8 and most preferably from ca. 6.5 to approx. 7.5, for at least 2 weeks and up to 8 weeks or more, up to the rest of life. Even at a pH below 5, we do not descale or otherwise damage the enamel in 30 enamel. The pH can be adjusted with acid (eg citric or benzoic acid) or base (eg sodium hydroxide) or adjusted with buffer such as sodium citrate, benzoate, carbonate or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate etc. ).

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 outer surface of a rubber matrix, examples of which may be mentioned gelatin, rubber latex, vinyl resin etc., suitably red usual plasticizers or plasticizers, sugars or other sweetening sugars, sorbitol and the like.

The following examples further illustrate the nature of the invention.

All quantities here and in the claims are by weight, unless otherwise stated.

EXAMPLE 1.

The following dental care products are prepared:

Share

Ingredients A B

Glycerin 10.00

Propylene Glycol - 10.00

Sorbitol (70%) 25.00 25.00 Iotacarragenan 0.60 0.60 "Gantrez" S-97 2.00 2.00

Sodium saccharin 0.40 0.40

Sodium fluoride 0.243 0.243

Sodium hydroxide (50%) 1.00 1.00 (continued) DK 175071 B1 31

Share

Ingredients A B

Titanium oxide 0.50 0.50

Silicon dioxide polish ("Zeodent" 113) 20.00 20.00

Silica Thickener 5 ("Sylox" 15) 5.50 5.50

Sodium lauryl sulfate 2.00 2.00

Water 31,507 31,507

Triclosan 0.30 0.30

Aroma Oil 0.95 0.95 10 The above dentifrice A delivers Triclosan to the teeth and soft gum tissue, substantially as well as dentifrice B containing a special solubilizing agent for Triclosan. In other words, a particularly soluble agent is not required for the dentifrice of the invention to be effective. A similar dentifrice in which the "Gantrez" polycarboxylate is not present is substantially inferior to the delivery of Triclosan.

In the previous example, improved results can also be obtained by replacing Triclosan with other antibacterial agents described in the present disclosure, such as phenol, thymol, eugenol and 2,2'-methylene bis {4-chloro-6-bromophenol. ) and / or by replacing "Gantrez" with other AEAs such as a 1: 1 copolymer of maleic anhydride and ethyl acrylate, sulfoacrylic acid oligomer, "Carbopol" (e.g. 934) and polymers of α- or 25 (3 styrene phosphonic acid monomers and copolymers of these monomers with each other or with other ethylenically unsaturated polymerizable monomers such as vinyl phosphonic acid.

EXAMPLE 2.

The following liquid dentifrice solutions are tested for uptake and retention of Triclosan on saliva-coated HA slices, followed by the test methods described in Ex.3 below:

Ingredients A B C D

Sorbitol (70% solution) 30.0 30.0 30.0 30.0

Glycerin 9.5 9.5 9.5 9.5

Propylene glycol 0.5 0.5 0.5 0.5 SLS 20.0 20.0 20.0 20.0

NaF 0.243 0.243 0.243 0.243 Flavor oil 0.95 0.95 0.95 0.95

Triclosan 0.3 0.3 0.3 0.3

Water 56,507 54,507 54,507 54,507

Poly (β-styrene phosphonic acid) 2.0

Poly (α-styrene phosphonic acid) 2.0 Polyvinyl alcohol 2.0

Adjusted to pH 6.5 with NaOH,

Triclosan uptake in micrograms on saliva coated HA disc 31.0 174.0 86.0 36.0

Retention of Triclosan on saliva-coated HA disc: 20 Immediately 183.0

After 30 minutes 136.0 "1 hour 105.0" 3 hours 83.0

The above results show that solution D, containing non-AEA polyvinyl alcohol, gives an uptake of Triclo-25 san of only 36.0, as does the uptake of 31.0 of control solution A without additive. In contrast, solution C with poly (α-styrene phosphonic acid) gives an uptake of 86.0, more than twice the solutions A and D, and solution B

DK 175071 B1 33 with poly (β-styrene phosphonic acid) gives an uptake of approx.

5 times that of solutions A and D, which seems to show that vicinal substitution of the delivery enhancing groups yields better results. The above results also show the surprisingly good retention of Triclosan on the HA slices over time with solution B containing poly (O-styrene phosphonic acid) (molecular weight about 3,000 - 10,000).

EXAMPLE 3.

The effect of synthetic, anionic, linear polycarboxylate on the uptake, retention, and release from tooth surfaces of water-insoluble, non-cationic antibacterial agent is assessed in vitro on saliva-coated hydroxyapatite disc and on peeled buccal epithelial cells. The in vitro assays can be related to in vivo delivery and retention on 15 mouth surfaces.

For the sample delivering antibacterial agent to a saliva-coated hydroxyapatite slice, hydroxyapatite (HA) from Monsanto Co. washed extensively with distilled water, collected by vacuum filtration and allowed to dry overnight at 37 ° C. The dried HA is ground to a powder in a mortar. 150.00 mg of HA is placed in the chamber of a KBr pill matrix (Barnes Analytical, Stanford, CT) and compressed 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. Parafilm-25 stimulated full saliva is collected in an ice-cooled beaker. The saliva is cleared by centrifugation at 15,000 x g for 15 minutes at 4 ° C. Sterilization of the cleared saliva is performed at 4 ° C by stirring and irradiating the sample with UV light for 1.0 hour.

Each sintered disc is hydrated with sterile water in a polyethylene 30 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, the saliva is removed and the slices are treated with 1.00 ml of a solution containing antibacterial agent (Triclosan) in liquid toothpaste and incubated at 37 ° C while still shaking in the water bath. After 30 minutes transfer the disc to a new glass, add 5 and 5.00 ml of water, followed by shaking the disc gently with a Vortex. The disc is then transferred to a new glass and the washing process is repeated twice. Finally, the disc is gently transferred to a new glass to avoid fluid transfer along with the disc. Then add 1.00 ml of methanol 10 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. After this treatment, the methanol is transferred to HPLC (high performance liquid chromatography) bottles to determine antibacterial agent. Triple samples are used in all experiments.

For the sample of antibacterial retention on a saliva-coated HA disc, a saliva-coated HA disc is treated with 20 dentifrice slurries as described above. After incubation for 30 minutes at 37 ° C, the HA slice is taken out of the dentifrice slurry, washed twice with water and reincubated with parafilm-stimulated, fully human saliva, which has been cleared by centrifugation. After incubation at 37 ° C with constant shaking at various times, the HA slice is extracted from the saliva and the amount of antibacterial agent (Triclosan) retained on the slice and released into the saliva is determined by an analytical method using HPLC.

To measure the delivery of antibacterial agent to buccal 30 epithelial cells, the release is measured to determine the effect of PVM / MA on the delivery of antibacterial agent (Triclosan) to soft oral tissue from a dental pomegranate product. Buccal epithelial cells are collected with a wooden spatula by gently rubbing the mucous membrane of the mouth. Cells are suspended in Resting Saliva Salts DK 175071 B1 35 (Rss) buffer (50 nM NaCl, 1.1 nM CaCl 2 and 0.6 nM pH 7.0) to 5 - 6x10 cells / ml using a haemocytometer to count the cells and keep in ice until use.

0.5 ml of cell suspension, preincubated to 37 ° C in a water bath, is added together with 0.5 ml of the solution of the tested antibacterial agent and incubated at 37 ° C. The antibacterial solution in the incubation mixture is diluted at least 10 times to decrease the surfactant concentration and prevent destruction of cell membranes of the surfactant. After 30 minutes of incubation, the cells are harvested by centrifugation in Beckman Microfuge 11 at 5,000 revolutions per minute. minute for 5 minutes. The cells collected as a pill are washed three times with Rss buffer and treated with 1.5 ml of methanol. The sample is thoroughly mixed and analyzed for antibacterial agent by the HPLC method.

15 Dental care products are prepared having the following compositions:

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Ingredients A B

Propylene Glycol (1.2) 10.00 10.00 Lotacarrageenan 0.75 0.75 "Gantrez" S-97 - 2.00

Titanium dioxide 0.50 0.50

Sorbitol (70%) 30.00 30.00

Sodium fluoride 0.332 0.332

Sodium Saccharin 0.40 0.40 Silicon Dioxide Thickener ("Sylodent" 15) 3.00 3.00

Silicon dioxide polish ("Zeodent" 113) 20.00 20.00

Triclosan 0.20 0.20 Sodium lauryl sulfate 2.00 2.00

Flavor oil 0.95 0.95

Ethyl Alcohol 1.00 1.00

Water q.s. to 100.00 to 100.00 DK 175071 B1 36

The uptake of Triclosan on saliva-coated hydroxyapatite disk and on buccal epithelial cells, with and without the polymeric polycarboxylate, "Gantrez" S-97, is listed in Table 1 below.

TABLE 1.

5 Recording Triclosan 1 microgram into micrograms on saliva x 10 ° buccal

Dental Care Coated Disc Epithelial Cells A 25.0 38.0 B 54.0 96.0 These results show that the "Gantrez" material (found in Dental Care B) greatly increases the release and uptake of Triclosan into saliva-coated hydroxyapatite discs and to shelled, buccal epithelial cells.

Similar results are obtained when the dentifrices contain 15 0.30 parts of Triclosan.

EXAMPLE 4.

samples with saliva-coated hydroxyapatite slices and peeled buccal epithelial cells, different from those listed in Example 3, said toothpaste B containing 2.00% "Gantrez" 20 S-97 and 0.20% Triclosan, 10.00% propylene glycol and 2.00% sodium lauryl sulfate and an equivalent composite toothpaste (B ') f with the exception of the presence of 0.30% Triclosan, compared to a commercially available toothpaste (C) containing hydrated alumina as a polishing agent and (a) 0, 2% Triclosan, (b) no "Gantrez" material, (c) no propylene glycol, (d) 0.5% zinc citrate, (e) 2.5% surfactant and (f) sodium monofluorophosphate and hydrated alumina as a polishing agent, and DK 175071 B1 37 the toothpaste composition (C) below, which corresponds to the commercially available toothpaste C with the exception of the presence of 0.30% Triclosan:

Toothpaste C '.

Ingredients -------------% 5 Sorbitol (70%) 27.00

Sodium carboxymethyl cellulose 0.80

Sodium monofluorophosphate 0.85

Zinc citrate 0.50

Sodium Saccharin 0.18 10 Water 16.47

Hydrated alumina polishing agent 50.00

Ethanol 0.20

Sodium lauryl sulfate 1.875

Sodium dodecylbenzenesulfonate 0.625 Triclosan 0.30

Aroma 1.20

Since toothpastes C and C contain a total of 2.50% surfactant, there is more surfactant to dissolve Triclosan than in toothpastes B and B 'containing 2.00%.

However, propylene glycol found in the silicon-containing polishing agents in dentifrices B and B '(but not in the hydrated alumina found in dentifrices C and C') * ensures optimal dissolution of Triclosan.

The benefit of toothpastes B and B '(containing propylene glycol 25 and "Gantrez") compared to toothpastes C and C in terms of uptake of Triclosan on saliva-coated hydroxyapatite slices and on peeled buccal epithelial cells is shown in Table 2 below: TABLE 2.

DK 175071 B1 38

Delivery of Triclosan

For salivary epithelial cells hydroxyapatite slices g ^ (in micrograms) x 10 epithelial cells 5 Toothpaste B 41.1 101.6 "B '77.4 142.0" C 20.4 61.0 "C 42.6 100.0

Further experiments with toothpaste B '(0.3% Triclosan, "Gantrez", 10 propylene glycol) in a 50% slurry of the toothpaste, to determine the retention of Triclosan on the saliva-coated hydroxy-apatite disc over a period of time, show retention of excellent amounts of Triclosan as shown in Table 3 below: TABLE 3.

Retention of Triclosan adsorption from 15 toothpaste slurry

Retention of Triclosan Time (in minutes) (micrograms / disc) 0 70 30 60 60 70 20 120 65 180 57 240 59

These results show that toothpastes containing Triclosan, T3antrez material and propylene glycol can provide enhanced delivery of Triclosan to and retention on tooth surfaces and soft surfaces of the oral cavity, thereby providing enhanced anti-plaque and antibacterial effects.

EXAMPLE 5.

DK 175071 B1 39

For comparison purposes, the following compositions a and b are prepared:

Toothpaste:%

Ingredients a k 5 Glycerin 10.00

Propylene Glycol - 10.00

Iotacarragenan 0.60 0.60

Sorbitol (70%) 25.00 25.00

Sodium saccharin 0.40 0.40 Sodium fluoride 0.243 0.243

Titanium Dioxide 0.50 0.50 "Gantrez" S-97 2.00 2.00

Water 29,157 29,157

NaOH (50%) 2.00 2.00 15 "Zeodent" 113 (silica polish) 20.00 20.00 "Sylodent" 15 (silica thickening agent) 5.50 5.50

Aroma 1.10. 1.10

Triclosan 0.50 0.50

Sodium lauryl sulfate 2.00 2.00 Ethanol 1.00 1.00

Composition a is a toothpaste containing a "Gantrez" polycarboxylate together with 0.5% Triclosan as antibacterial anti-plaque agent and no solubilizing agent. Composition b contains propylene glycol as a solubilizing agent.

Composition a is poor for delivery of Triclosan on buccal epithelial cells, while composition b is pronounced effective.

40

l / l \ I f% / V f I V I

The previous results show excellent release of Triclosan. EXAMPLE 6.

A study was conducted on a group of volunteers to assess the effects of particular toothpastes on affecting gene-5 growth of plague by the method described by Addy, Wilis & Moran in J. Clin.Perio. 1983, Vol. 10, pages 89 - 99. The tested toothpastes included a placebo control containing no Triclosan (i) and a toothpaste of the invention containing 0.3% Triclosan, 10% propylene glycol (instead of 3% polyethylene glycol 600) and 2% "Gantrez" S-97 as well as propylene glycol and sorbitol moisturizing agent (ii). The compositions of the toothpastes are as follows:

Share (%)

Placebo Invention

Ingredients (i) (ii) Polyethylene Glycol 600 3.00

Glycerin 25.00

Propylene Glycol - 10.00

Sorbitol (70%) 41,617 25.00

Sodium carboxymethyl cellulose 0.35 Iotacarragenan - 0.60

Sodium benzoate 0.50

Sodium saccharin 0.20 0.20

Sodium fluoride 0.243 0.243

Silicon dioxide polish ("Zeodent" 113) 18.00 20.00 25 Silica thickener ("Sylox" 15) 5.50 5.50

Water 3.00 28.757 "Gantrez" S-97 - 2.00

Triclosan - 0.30 Titanium Dioxide 0.50 0.50

Sodium lauryl sulfate 1.20 2.50

Flavor 0.89 1.10

Ethyl alcohol 1.00

Sodium Hydroxide (50%) 2.00 DK 175071 B1 41

With regard to plaque reduction on the volunteers' teeth, the toothpaste of the invention (ii) provided a significant reduction of 20% compared to placebo (i).

Since smaller amounts of propylene glycol can dissolve the 0.3% Triclosan found in toothpaste (ii), similar results are expected when the amount of propylene glycol is reduced to 0.5 part and the amount of sorbitol is increased to 39.5 part. Likewise, the other solubilizing agents, dipropylene glycol, hexylene glycol, methyl cellosolve, ethyl celllosolve, olive oil, castor oil, petrolurethane, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate, instead of propylene glycol can effectively dispense tricyclic acid. Furthermore, similar results are expected when propylene glycol or other solubilizers are omitted by toothpaste (ii) containing 0.3% Triclosan.

EXAMPLE 7.

The following toothpastes according to the invention are prepared:

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Ingredients A B

Glycerin - 20.00 20 Propylene Glycol 10.00 0.50

Sorbitol (70%) 25.00 19.50

Sodium Carboxymethyl Cellulose - 1.10

Iotacarragenan 0.600

Sodium saccharin 0.40 0.30 Sodium fluoride 0.243 0.243

Silicon dioxide polish ("Zeodent" 113) 20.00 20.00

Silicon dioxide thickener ("Sylox" 15) 5.50 3.00 30 water 28.757 15.307 "Gantrez" S-97 2.00 2.00

Triclosan 0.50 0.30

tforts. L

42

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Ingredients A B

Titanium dioxide 0.50 0.50

Sodium lauryl sulfate 2.50 2.00

Aroma 1.10 0.95

Ethanol 1.00 Sodium Hydroxide (50%) 2.00 1.60 In the previous examples, improved results can also be obtained by replacing Triclosan with other antibacterial agents described in the present specification, such as phenol, thymol, eugenol and 2.2 -methylene bis (4-chloro-6-bromophenol) and / or 10 by replacing "Gantrez" with other AEAs, such as a 1: 1 copolymer of maleic anhydride and ethyl acrylate, sulfoacrylic acid oligomers, "Carbopol" (e.g. 934), polymers of α- or β-styrene phosphonic acid and copolymers of these styrene phosphonic acid monomers with each other or with other ethylenically unsaturated polymerizable monomers such as vinyl phosphonic acid.

EXAMPLE 8.

The following toothpastes are prepared:

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Ingredients AB C

Α-alumina trihydrate 48.00 48.00 48.00

Propylene glycol - 0.50 0.50

Sorbitol (70%) 21.70 21.70 21.70 "Gantrez" S-97 (13% solution) 15.00 15.00 "Gantrez" S-97 (powder) - - 2.00 Sodium lauryl sulfate 2.00 2.13 2.13

Sodium saccharin 0.30 0.30 0.30

Sodium hydroxide (50%) 1.20 1.20 1.20

Aroma 0.95 0.95 0.95 (continued) DK 175071 B1 43

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Ingredients ABC

Irish moss' 1.00

Sodium Carboxymethyl Cellulose - 1.00 1.00

Sodium monofluorophosphate 0.76 0.76 0.76 Titanium dioxide - 0.50 0.50

Triclosan 0.30 0.30 0.30

Water q.s. to 100.00 100.00 100.00

The preceding toothpastes deliver Triclosan to the teeth and soft tissue areas substantially more effectively than similar 10 toothpastes in which there is no "Gantrez" polycarboxylate.

EXAMPLE 9.

The following toothpastes are prepared:

Ingredients Parts

Glycerin 22.00 10.00

Sorbitol (70%) 17.00 Sodium Carboxymethyl Cellulose 1.00 1.00 "Gantrez" S-97 2.00 2.00

Sodium saccharin 0.20 0.20

Sodium benzoate 0.50 0.50

Sodium monofluorophosphate 0.76 0.76 Dicalcium phosphate dihydrate 48.76 48.76

Triclosan 0.30 0.30

Sodium lauryl sulfate 1.20 1.20

Flavor 0.89 0.89

Water q.s. to 100.00 100.00 The foregoing toothpastes deliver Triclosan to saliva-coated hydroxyapatite disc more effectively than similar toothpastes in which "Gantrez" polycarboxylate is not present.

Example 17.

The following antiplague dentifrice is prepared:

Ingredients Parts

Glycerin 15.00 5 Propylene Glycol 2.00

Sodium carboxymethyl cellulose 1.50

Water 24.93

Vinyl methyl ether / maleic anhydride copolymer (42% solution) 4.76

Sodium monofluorophosphate 0.76 Sodium saccharin 0.30

Insoluble sodium metaphosphate 47.00

Titanium dioxide 0.50

Sodium lauryl sulfate 2.00

Triclosan 0.30 15 Flavor 0.95 In the previous examples, improved results are also obtained when

Triclosan is replaced with each of phenol, 2,2'-methylene bis (4-chloro-6-bromophenol), eugenol and thymol, and / or when "Gantrez" is replaced by other AEAs such as "Carbopol" (e.g. (934) or 20 molecular weight styrene phosphonic acid polymers 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.

EXAMPLE 11.

DK 175071 B1 45

Mobile toothpaste phases containing Triclosan:

Composition,% w / w

Components A B

Sorbitol (70%) 53.33 40.00 Water 40.48 39.15 "Gantrez" S (15%) 13.33

NaOH (50%) 1.33

Saccharin 0.40 0.40

Sodium Fluoride 0.32 0.32 10 Aroma Oil 1/47 1.47

Sodium lauryl sulfate 3.33 3.33

Triclosan 0.67 0.67

The concentration of the above components is 1.33% of the amount of toothpaste to reflect 25% of abrasive which may be necessary to make the complete toothpaste.

The aforementioned mobile phases of the toothpaste composition compositions shown are tested for Triclosan uptake on saliva-coated HA slices. The results are shown in the following table: TABLE.

20 Uptake of Triclosan on saliva-coated hydroxyapatite slices from diluted and undiluted mobile toothpaste phases:

A B

% Triclosan 0.67 0.67

Ion strength (M / L) (calculated) 0.375 pH 8.7 7.6

Triclosan uptake (jug / disc) (undiluted) 55 122

The above results show a more than twice the size

Triclosan uptake obtained with composition B containing "Gantrez" compared to composition A without "Gantrez".

Example 17.

5 Concentration and uptake of Triclosan on HA from the remaining liquid of 1: 1 slurries of toothpaste in water:

Toothpaste containing Triclosan Oug / ml) in Triclosan - 0.5% Triclosan and supernatant fluid uptake.

2.5% sodium lauryl sulfate of 1: 1 slurry / µg slice 25% hydrated silica + 10 1.5% "Gantrez" S-97 1.650 52 50% alumina + 1.5% "Gantrez" S-97 1,905 74

Overlying liquids of 1: 1 toothpaste / water slurries of the above toothpastes are tested for concentration of Triclosan 15 in the overlying fluid and for Triclosan uptake on saliva-coated HA slices. The results show that by using 50% alumina as abrasive, Triclosan is significantly increased under low (1: 1) dilution conditions (from 1,650 to 1,905), resulting in a significant increase in Triclosan uptake 20 (from 52 to 74).

EXAMPLE 13.

The mouthwashes below are effective in reducing plaque by increasing the uptake and retention of Triclosan on mouth surfaces: DK 175071 B1 47

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Ingredients A B C D E

"Gantrez" S-97 0.24 0.25 0.25 0.25 0.25

Glycerin 15.00 10.00 15.00 10.00 15.00

Ethanol - - 12.50 12.50 -

Propylene Glycol - 5.00 - 5.00 - 5 "Pluronic" F108 (polyoxyethylene / polyoxypropylene copolymer) 2.00

Sodium lauryl sulfate - 0.20 0.20 0.20 Triclosan 0.10 0.10 0.06 0.06 0.03

Flavor oil 0.40 0.40 0.40 0.40 0.40

Water q.s. to 100.00 100.00 100.00 100.00 EXAMPLE 14.

The following liquid dentifrices are also effective in reducing plaque by increasing the uptake and retention of Triclosan on oral surfaces:

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Ingredients ABC

Glycerin 20.0 20.0 20 "Gantrez" S-97 0.3 0.3 0.3

High molecular weight polysaccharide, wherein the molecule contains mannose, glucose, potassium glucuronate and acetyl molecules 25 in molar ratio 2: 1: 1: 1 (approx.) 0.8 - 1 »0

Sodium benzoate 0.5 0.5 0.5

Saccharin sodium 0.5 0.5 0.5

Water 61.3 73.1 71.6

Sodium lauryl sulfate 3.0 3.0 3.0 30 Insoluble sodium metaphosphate 10.0 - 10.0 (continued) DK 175071 B1 48

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Ingredients ^ B C

Anhydrous dicalcium phosphate 1.0 - 2.5

Aroma oil 2.5 2.5 2.5

Ethyl alcohol - - 10.0

Triclosan 0.1 0.1 0.1 In the previous examples, improved results can also be obtained when replacing Triclosan with each of phenol, 2,2'-methylene-bis- (4-chloro-6-bromophenol), eugenol and Thymol, and / or when "Gantrez" is replaced by other AEAs such as "Carbopol" (e.g., 934) or styrene-phosphonic acid polymers having a molecular weight in the range of about 10 3,000 to 10,000, such as poly (fl-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.

Claims (49)

An oral care agent comprising an effective antiplaque amount of a substantially water-insoluble, non-cationic, antibacterial agent, ca. 0.005 - 4% by weight antibacterial enhancer which enhances delivery of the antibacterial agent to and retention on oral surfaces, and an orally acceptable carrier which. is effective in that. enable the antibacterial agent to dissolve in saliva in an effective amount of antiplaque, which oral care agent is substantially free of polyphosphate anti-tooth detergent. Oral care composition according to claim 1, characterized in that it is a dental care composition comprising approx. 5-30% by weight of a silicon-containing polishing agent, wherein the antibacterial agent is present in an amount of approx. 0.25 - 0.35% by weight and there is * at least one surfactant and an aromatizer. Oral care composition according to claim 1, characterized in that it is a dental care composition comprising approx. 5 to 30% by weight of a silicon-containing polishing agent, wherein the antibacterial agent is present in an amount of approx. 0.01 to 5% by weight, and the oral care agent comprises a solubilizing material in an amount sufficient to dissolve the antibacterial agent in saliva. An oral care agent according to claim 3, characterized in that the antibacterial agent is present in an amount of approx. 0.05% up to less than approx. 0.25% by weight. 5. Oral care agent according to claim 3, characterized in that the antibacterial agent is present in an amount above ca. 0.35% up to approx. 5% by weight. Vl% I f vvi> v I Oral care agent according to claim 5, characterized in that the antibacterial agent is present in an amount above 0.35% up to approx. 0.5% by weight. Oral care composition according to claim 1, characterized in that it is a dental care composition comprising approx. 30-75% by weight of a dental acceptable water-insoluble polish. An oral care agent according to claim 1, characterized in that it is a mouthwash liquid or a liquid toothpaste and that the orally acceptable carrier is an aqueous carrier containing at least one surfactant, a flavoring oil or a non-toxic alcohol. Oral care agent according to one of the preceding claims, characterized in that it contains surfactant in an amount of approx. 0.5 to 5% by weight. An oral care agent according to any one of the preceding claims, characterized in that it contains flavoring oil in an amount of approx. 0.1 - 5% by weight. Oral care composition according to claim 8, characterized in that it is a mouthwash liquid and the aqueous carrier contains 20 ethanol, and the weight ratio of water to ethanol is from approx. 1: 1 to approx. 20: 1. Oral care composition according to claim 8, characterized in that it is a liquid toothpaste containing approx. 0.3 - 2.0% by weight of a high molecular weight polysaccharide, over 1,000,000, containing mannose, glucose, potassium glucuronate and acetyl molecule in a ratio of about 2: 1: 1: 1 as suspending and thickening agent, and approx. 10-20% by weight of a polishing material. Oral care agent according to claims 1-8, characterized in that the antibacterial agent is selected from the group consisting of DK 175071 B1 of halogenated diphenyl ethers, halogenated salicylic anilides, benzoic acid esters, halogenated carbanilides and phenolic compounds. Oral care agent according to claim 13, characterized in that the antibacterial agent is a halogenated diphenyl ether. Oral care agent according to claim 14, characterized in that the halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. Mouthpiece according to claims 1 and 3-6, characterized in that the solubilizing agent is present in an amount of approx. 0.5 to 50% by weight and is selected from the group consisting of propylene glycol, dipropylene glycol, hexylene glycol, methyl cellulose, ethylcellosolve, vegetable oil and wax containing at least approx. 12 carbon atoms, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate. Oral care agent according to claim 16, characterized in that the solubilizing agent is propylene glycol and is present in an amount of approx. 0.5% by weight. Oral care composition according to claim 1 or 16, characterized in that it contains a polishing agent selected by the group consisting of sodium metaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, calcium carbonate, trimagnium phosphate, calcium , Silicon dioxide, bentonite and mixtures thereof, of which oral care agent is a toothpaste. Oral care agent according to claim 18, characterized in that the polishing agent is dicalcium phosphate dihydrate or hydrated alumina. DK 175071 B1 20. Oral Care. according to claims 1-8, characterized in that the antibacterial enhancer has an average molecular weight of approx. 100 to approx. 1,000,000. Oral care agent according to claim 20, characterized in that the antibacterial-enhancing agent contains at least one release-enhancing, functional group and at least one organic retention-enhancing group, Oral care agent according to claim 21, characterized in that the delivery enhancing group is acidic. The mouth care agent according to claim 22, characterized in that the release enhancing group is selected from the group consisting of carboxylic acid, phosphonic acid, phosphinic acid and sulfonic acid and their salts and mixtures thereof. Oral care agent according to claim 23, characterized in that the organic retention enhancing group comprises the formula 0 (X) n ~ R, wherein X is O, N, S, SO, SO2, P, PO or Si, R is hydrophobic alkyl, alkylene, acyl, aryl, alkaryl, aralkyl, heterocyclic or their inert substituted derivatives, and n is 1 or 0. 20, Oral pesticide according to claims 20-24, characterized in that anionic polymer containing several of the release enhancer and backbone e s-for s-labeling group r. The mouth care agent according to claim 25, characterized in that the anionic polymer comprises a chain containing repeating units, each containing at least one carbon atom. Mouth care agent according to claim 26, characterized in that each unit contains at least one release enhancing group linked to the same vicinal or other atoms in the chain. DK 175071 B1 The oral care product according to claim 23, characterized in that. the release enhancing group is a carboxylic acid group or a salt thereof. Oral care agent according to claim 28, characterized in that the antibacterial enhancer is a copolymer of maleic or maleic anhydride with another inert, ethylenically unsaturated polymerizable monomer. An oral pie agent according to claim 2.9, characterized in that the second monomer in the polymer is methyl vinyl ether in a molar ratio of 4: 1 to 1: 4 with the maleic acid or maleic anhydride. Mouthpiece according to claim 30, characterized in that the copolymer has a molecular weight of approx. 30,000 - 1,000,000 and is available in an amount of approx. 0.1 - 2% by weight. An agent according to claim 31, characterized in that the co-polymer has an average molecular weight of approx. 70,000. An agent according to claim 23, characterized in that the release enhancing group is a phosphonic acid group or its salt. Agent according to claim 33, characterized in that the antibacterial-enhancing agent is poly (β-styrene phosphonic acid) or poly (α-styrene phosphonic acid) polymer or a copolymer of a styrene phosphonic acid with another ethylenically unsaturated monomer. A method of controlling oral plaque, characterized in that an effective plaque-regulating amount of an agent according to any one of the preceding claims is applied to mouth surfaces. DK 175071 B1 An oral care agent according to claim 1, wherein the antibacterial enhancer having an average molecular weight of approx. 1,000 to approx. 1,000,000, contains at least one release enhancing, functional group and at least one organic, retention enhancing group, said agent containing said groups being free of or substantially free of water-soluble alkali metal or ammonium salt of synthetic, anionic, linear, polymeric polycarboxylate having a molecular weight of approx. 1,000 to approx. 1,000,000. Oral care agent according to claim 36, characterized in that the antibacterial agent is present in an amount of from approx. 0.25% to less than 0.5% by weight. An oral care agent according to claim 36, characterized in that the antibacterial agent is present in an amount of from 0.25% to approx. 0.35% by weight. An oral care agent according to claim 37, characterized in that it contains a silicon-containing polishing agent. Oral care agent according to claim 38, characterized in that it contains a silicon-containing polishing agent. 20 An oral care agent according to claim 1 comprising approx. 0.005-4% by weight polyvinylphosphonate with repeating groups -CHrCH- In HO-P = 0 OH 30 and an average molecular weight of at least approx. 1,000 to approx. 1,000,000, as well as an orally acceptable carrier which is effective in enabling the antibacterial agent to dissolve in saliva in an effective amount of antiplaque, which oral care agent has a pH of approx. 4.5 to approx. 10. DK 175071 B1 5 5 The oral care agent according to claim 41, characterized in that the oral care agent is a dental care agent comprising approx. 5-30% by weight of a silicon-containing polishing agent and that the anti-bacterial agent is present in an amount of approx. 0.25-0.35% by weight. 10 43. Oral agent according to claim 41, characterized in that the oral care agent is a dentifrice comprising about 5-30% by weight of a silicon-containing polishing agent, the antibacterial agent being present in an amount of approx. 0.01-5% by weight, and the oral care agent comprises a solubilizing material in an amount to support dissolution of the antibacterial agent in saliva. An oral care agent according to any one of claims 41 20 to 43, characterized in that the oral care agent is a dental care agent comprising approx. 30-75% by weight of a dental acceptable water-insoluble polishing agent. An oral care agent according to any one of claims 41 to 43, characterized in that the oral care agent is a mouthwash or liquid dentifrice and the orally acceptable carrier is an aqueous carrier in which there is a non-toxic alcohol. present. An oral care agent according to any one of claims 41 to 45, characterized in that the antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated silicanyl esters, benzoic acid esters, halogenated carbanilides and phenolic compounds. 35 47. An oral pie agent according to claim 46, characterized in that the antibacterial agent is a halogenated diphenyl ether. DK 175071 B1 The mouth care agent according to claim 47, characterized in that the halogenated diphenyl ether is 2,4,4 '-trichloro-2' '* hydroxyphenyl ether. The mouth care agent according to any one of claims 41 to 48, characterized in that the phosphonate is present in an amount of approx. 0.5-2.5% by weight. 10 15 20 25 30 35