SK280567B6 - Antiplaque oral composition - Google Patents

Abstract

An oral anti-plaque composition in the form of a gel or paste dentifrice, liquid dentifrice, a liquid mouthwash, lozenge or chewing gum, which composition is substantially free of pyrophosphate agent against plaque formation, consists of a vehicle for oral application and a substantially water insoluble non-cationic antibacterial agent. The said vehicle contains an antibacterial efficacy supporting agent of a molecular weight in the range of about 100 to 1,000, 000. The said agent contains at least one acidic functional group with a deliver-enhanced activity for assisting the said antibacterial agent to be delivered to oral tooth and gum surfaces in the mouth cavity. It further contains at least one organic group with a retention-enhanced activity for assisting the said antibacterial agent to be attached upon oral tooth and gum surfaces in the mouth cavity, whilst the AEA agent contains various monomers, oligomers, homopolymers and copolymers.

Description

Technical field

The present invention relates to an anti-dental plaque composition for oral administration in the form of a gel-like or pasty dental cleanser, a liquid dental cleanser, a mouthwash, a lozenge or chewing gum that is substantially free of pyrophosphate anti-tartar. They are compositions based on an insoluble antibacterial substance of a non-cationic nature capable of effectively preventing the formation of dental plaques.

BACKGROUND OF THE INVENTION

Dental plaque is a soft deposit that forms on the teeth, as opposed to tartar, which is a hard calcified deposit. Unlike tartar, the dental plaque can be formed on any part of the tooth surface, especially at the boundary between the tooth and the gum. Although this deposit is not visible, it is likely to promote tooth inflammation.

Accordingly, it is highly desirable to use antimicrobials to reduce dental plaque formation in oral dentifrices. For this purpose, it is customary to use cardboard antibacterials in the prior art. U.S. Pat. No. 4,022,880 (Vinson et al.) Discloses the use of a mixture of a zinc ion-releasing compound as an antioxidant and an antibacterial agent effective in inhibiting the growth of bacteria in a dental plaque. A variety of antibacterial agents are known to be used in combination with these zinc compounds, including cationic agents such as guanides and quaternary ammonium compounds, as well as the use of non-cationic agents such as halogenated salicylanilides and halogenated compounds. hydroxydiphenylethers. These non-cationic antibacterial agents, such as halogenated hydroxydiphenyl ether or triclosan, in combination with zinc citrate trihydrate are described in published European patent application no. 161,899 (Saxton et al.). The use of this triclosan as a toothpaste component which additionally contained a solubilizing agent has also been described in published European patent application no. 0 271 332 by Davis.

Recently, cationic antibacterials such as chlorhexidine, benzotonium chloride and cetylpyridinium chloride have also been of great interest as anti-dental antibacterial agents. However, these substances are not usually effective when used together with anionic materials. On the other hand, non-cationic antibacterial agents are compatible with the anionic components in the oral compositions.

However, oral compositions usually comprise mixtures of many components and even typical neutral substances such as solvents and respiratory agents. humectants may affect the effectiveness of these compositions.

However, non-cationic antibacterial agents may have limited dental plaque effectiveness when used in combination with some commonly used materials, such as polyphosphates, which are disclosed in UK patent application Ser. 2,200,551 (Gaffar et al.) And European Patent 251,591 (Jackson et al.). It is also known in the art that anti-dental efficacy can be substantially increased by adding a substance which promotes the action of an antibacterial agent (hereinafter referred to as AEA) to the composition, which improves the delivery of the antibacterial agent to the dental plaque. and the retention of the substance on the surface of the oral cavity, and a solution is also known to optimize the amount of polyphosphate and AEA in the oral composition.

SUMMARY OF THE INVENTION

Unexpectedly, according to the invention, it has been found that by advantageously combining the various properties of the compounds, an oral formulation can be prepared in which substantially water-insoluble non-cationic antibacterial agents and compounds t) p AEA (antibacterial enhancing agent) are used to inhibit dental plaque formation. wherein the composition is a liquid vehicle for oral administration that allows effective dissolution of said antibacterial agent in saliva in an amount that can effectively prevent the formation of a dental plaque.

Accordingly, the present invention relates to an anti-dental plaque composition for oral administration in the form of a gel or psistic dental cleanser, a liquid dental cleanser, a mouthwash, a lozenge or a chewing gum substantially free of an anti-tartaric pyrophosphate (vehicle) containing vehicle for oral administration and 0.01 to 5% by weight of a substantially water-insoluble non-cationic antibacterial agent, dissolved in said daily vehicle in an effective amount against dental plaque formation, said composition also comprising from 0.005 to 5% 4% by weight of an antibacterial promoting agent having an average molecular weight of 100 to 1,000,000, comprising at least one acidic functional group with a release promoting effect to promote release and said antibacterial agent teeth and gums in the oral cavity and at least one organic group of the general formula:

-O (X) n-R, in which:

X is oxygen, nitrogen, sulfur, SO, SO 2, phosphorus, PO or silicon,

R is a hydrophobic alkyl group, an alkylene group, an alkyl group, an aryl group, an alkaryl group and an aralkyl group containing from 1 to 12 carbon atoms or their inert substituted derivatives, an el or zero, with a retention aid to promote retention an antibacterial agent on tooth and gum surfaces in the oral cavity, wherein the AEΛ agent comprises natural and synthetic polymerizable monomers, oligomers, homopolymers, copolymers formed of di or more monomers, ionomers, block copolymers, graft copolymers, or crosslinked polymers of polymers or crosslinked copolymers of polymers , phosphonated polymerized ethylenically unsaturated compounds, polymerized ethylenically unsaturated carboxylic acids, carboxyvinyl polymers, polysiloxanes, polyesters, polyurethanes, natural or synthetic polyamides.

Preferably, the composition for oral administration further optionally comprises solubilizing agents and / or polishing agents. Said solvent is present in an amount ranging from 0.5 to 50% by weight, being selected

EN 28056 ^'7 B6 from the group of propylene glycol, dipropylene glycol, hexvlénglykol, methyl cellosolve, ethyl cellosolve, vegetable oils and waxes containing at least 12 carbon atoms, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate. The dissolving agents may comprise propylene glycol, which is present in an amount of 0.5% by weight.

According to a preferred embodiment, the composition of the invention is in the form of a dentifrice and comprises 5 to 30% by weight of a polishing composition based on silica or aluminum silicate and said antibacterial agent is present in an amount ranging from 0.25 to 0.35% wherein a surfactant and a flavoring oil are further present.

According to a further preferred embodiment, the composition is in the form of a dentifrice and comprises 5 to 30% by weight of a polishing composition based on silica or aluminum silicate, said antibacterial agent being present in an amount of 0.01 to 5% by weight and the composition for oral the application comprising a dissolving agent for dissolving said antibacterial agent in the saliva.

Said antibacterial agent is preferably present in an amount of from 0.05 to 0.25% by weight, more preferably from 0.35% to 5% by weight, and most preferably from 0.35% to 0.5% weight.

This oral composition is preferably in the form of a creamy dentifrice containing 30 to 75% by weight of a water-insoluble dentally acceptable rinse aid.

According to a further preferred embodiment, the composition is in the form of a mouthwash or a liquid dentifrice, and said orally acceptable vehicle is an aqueous vehicle which comprises at least one surfactant, flavoring oil or non-toxic alcohol. The surfactant is preferably present in an amount ranging from 0.5 to 5% by weight and the flavoring oil in an amount ranging from 0.1 to 5% by weight.

Said composition is preferably in the form of a mouthwash and said aqueous vehicle comprises ethanol and the weight ratio of water to ethanol ranges from 1: 1 to 20: 1.

The composition of the invention is preferably in the form of a liquid dentifrice composition containing 0.3 to 2.0% by weight of a high molecular weight polysaccharide of greater than 1,000,000 containing 2: 1: 1 mannose, glucose, potassium glucuronate and acetyl groups. % As a suspending and thickening agent, and 10 to 20% by weight of a polishing agent.

Said antibacterial agent may be selected from the group consisting of halogenated diphenyl ethers, halogenated salicylanilides, benzoic acid esters, halogenated carbanilides and phenolic compounds. Preferably, said antibacterial agent is a halogenated diphenyl ether, most preferably said halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether.

The polishing agent used may be selected from the group consisting of sodium metaphosphate, dicalcium phosphate, dibasic calcium phosphate dihydrate, anhydrous dibasic calcium phosphate, pyrophosphate (pyrophosphate), magnesium orthophosphate, magnesium phosphate, aluminum phosphate, magnesium phosphate, mixtures of these substances, and the composition for oral administration is in the form of a cream dentifrice, preferably the polishing agent is calcium hydrogen phosphate dihydrate or hydrated alumina.

Said release-promoting group is preferably selected from the group consisting of carboxylic acids, phosphonic acids, phosphinic acids and sulfonic acids and their salts and mixtures thereof.

The antibacterial promoting agent is preferably an anionic polymer comprising a series of release-promoting and retention-promoting groups. The anionic polymer preferably comprises a chain comprising repeating units with at least one carbon atom. Each unit preferably comprises at least one release promoting group attached to the same atom, an adjacent atom or another atom in the chain.

Most preferably, said antibacterial enhancer is a copolymer of maleic acid or anhydride thereof with another inert, unsaturated, polymerizable monomer. Said second monomer of said copolymer is preferably methyl vinyl ether contained in a molar ratio ranging from 4: 1 to 1: 4 with respect to the amount of maleic acid or anhydride thereof. The copolymer preferably has a molecular weight ranging from 30,000 to 1,000,000, and is present in an amount ranging from 0.1 to 2% by weight, most preferably having an average molecular weight of 70,000.

In particular, the antibacterial enhancing agent may be a poly (β-styrene phosphonic acid) polymer or a poly (α-styrene phosphonic acid) polymer, or a copolymer of any of said styrene phosphonic acids with another ethylenically unsaturated monomer.

In a particular preferred embodiment, the composition for said antibacterial enhancing agent comprises an average molecular weight ranging from 1000 to 1,000,000 and substantially free of the water-soluble salt of an alkali metal or ammonia synthetic anionic linear polymerization polycarboxylate with a molecular weight ranging from 1000 to 1,000,000, wherein the antibacterial agent is present in an amount ranging from 0.25% to 0.5% by weight, most preferably in an amount ranging from 0.25% to 0.35% by weight. Further preferably, the composition comprises a polishing agent based on silicon dioxide or aluminum silicate.

A great advantage of the composition according to the invention is that AEA favorably affects both the delivery and retention of a small but anti-dental coating of an effective amount of antibacterial agent, both on the teeth and on the soft tissues occurring in the oral cavity.

A further advantage of the present invention is that a composition is provided that reduces the incidence of gum inflammation.

The following are typical examples of non-cationic, water-insoluble antibacterial agents that are particularly useful in terms of dental plaque suppression, efficacy, safety in use and ease of formulation.

Halogenated diphenylethers 2 ', 4,4'-trichloro-2-hydroxydiphenyl ether (triclosan), 2,2'-dihydroxy-5,5'-dibromodiphenyl ether.

Halogenated Salicylanilides 4 ', 5-Tribromosalicylanilide, 3,4', 5-Trichlorosalicylanilide, 3,4 ', 5-Tribromosalicylanilide, 2,3,3', 5-Tetrachlorosalicylanilide, 3,3,3 ', 5-Tetrachlorosalicylanilide, 3,5-dibromo-3 'trifluórmetylsalicylanilid,

SK 280567. (.

5-n-octanoyl-3'-trifluórmetylsalicylanilid,

3,5-dibromo-4'-trifluoromethyl salicylanilide, 3,5-dibromo-3'-trifluoromethylsalicylanilide (fluorophene).

Benzoic acid esters methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate and butyl p-hydroxybenzoate.

Halogenated carbanilides 3,4,4 '-tri chlorocarbanilide,

3-Trifluoromethyl-4,4'-dichlorocarbanilide, 3,3,4'-trichlorocarbanilide.

Phenol compounds (including phenol and its homologues, mono- and polyalkylated and aromatic halogenated, i.e., fluorinated, chlorinated, brominated and iodinated phenols, resorcinol and catechol, and derivatives thereof, and bisphenolic compounds): 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).

Mono-, polyalkyl- and arylalkyl-halophenols methyl-p-chlorophenol, ethyl-p-chlorophenol, n-propyl-p-chlorophenol, n-butyl-p-chlorophenol, n-amyl-p-chlorophenol, sec-amyl-p-chlorophenol , n-hexyl-p-chlorophenol, cyclohexyl-p-chlorophenol, n-heptyl-p-chlorophenol, n-octyl-p-chlorophenol, o-chlorophenol, methyl-o-chlorophenol, ethyl-o-chlorophenol, n-propyl -o-chlorophenol, n-butyl-o-chlorophenol, n-amyl-o-chlorophenol, tert-amyl-o-chlorophenol, n-hexyl-o-chlorophenol, n-heptyl-o-chlorophenol, p-chlorophenol, o -benzyl-p-chlorophenol, o-benzyl-m-methyl-p-chlorophenol, o-benzyl-m, m-dimethyl-p-chlorophenol, o-phenylethyl-p-chlorophenol, o-phenylethyl-m-methyl-p -chlorophenol, 3-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-N-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-se-amyl-3,5-dimethyl-p-chlorophenol, 2-methyl-1,3,5-dimethyl-1-p-chlorophenol, 6-seA-octyl-3 -methyl-p-chlorophenol, p-bromophenol, m -yl-p-bromophenol, ethyl-p-bromophenol, n-iropyl-p-bromophenol, n-lutyl-p-bromophenol, n-imyl-p-bromophenol,. e-arnyl-p-bromophenol, n-texyl-p-bromophenol, cyclohexyl-p-bromophenol, o-bromophenol, te-c-amyl-o-bromophenol, n -exyl-o-bromophenol, n-iropyl- mm-dimethyl-o-bromophenol,

2-Phenylphenol

4-chloro-2-methylphenol, 4-chloro-3-methylphenol,

4-i: chloro-3,5-dimethylphenol, 2/1-chloro-3,5-dimethylphenol,

3,4,5,6-tetrabromo-2-methylphenol,

5-methyl-2-pentylphenol

4-Isopropyl-3-methylphenol

5- i: Chloro-2-hydroxydiphenylmethane.

Resorcinol and its derivatives methyl resorcinol, ethyl resorcinol, n-propyl resorcinol, n-butyl resorcinol, n-nmyl resorcinol, n-1-texresorcinol, n-heptylresorcinol, n-octylresorcinol, nilonylresorcinol, ferro-resorcinol, ferro-resorcinol, benzyl resorcinol, benzyl resorcinol, benzyl resorcinol , chlorobenzyresorcinol, 5-chloro-2,4-dihydroxydiphenylmethane, 4-chloro-2,4-dihydroxydiphenylmethane, 5-bromo-2,4-dihydroxydiphenylmethane, 4-bromo-2,4-dihydroxydiphenylmethane.

Birphenol compounds bis phenol A,

2,2'-methylenebis (4-chlorophenol), 2,2'-methylenebis (3,4,6-trichlorophenol) (hexachlorophene),

2,2-methylbis (4-chloro-6-bromophenol), bis 2-hydroxy-3,5-dichlorophenyl) sulfide, bis 2-hydroxy-5-chlorobenzyl) sulfide.

The antibacterial agent of a non-cationic nature is present in the oral composition according to the invention in an amount effective against dental plaque formation in an amount of from 0.01% to 5% by weight, in particular 0.03% to 1%. % by weight, preferably from 0.25% to 0.5%, and most preferably from 0.25%

Up to 0.5% by weight, most preferably from 0.25% to 0.35% by weight, for example 0.3% by weight in the dentifrice composition, or 0.03 to 0.3% by weight % by weight, in particular 0.03% to 0.1% by weight, of a composition used as a mouthwash or as a liquid dentifrice. The antibacterial agent should be substantially insoluble in water, meaning that its solubility in water should be less than about 1% by weight at 25 ° C, but may also be less than 0.1% by weight.

Of the halogenated diphenyl ethers, the preferred compound is triclosan. Among the phenolic compounds, the compounds are especially phenol, thymol, eugenol, hexylresorcinol and 2,2'-methylene-bis (4-chloro-6-bromophenol). However, the most preferred anti-tartaric antibacterial agent is triclosan. This triclosan is described in the aforementioned U.S. Pat. No. 4,022,880 as an antibacterial agent that can be used in combination with a tartaric agent that provides zinc ions. In addition, triclosan is also disclosed in DE 3,532,860 as a substance which can be combined with copper containing compounds. European patent 278,744 describes the use of triclosan in combination with substances that desensitize teeth and contain a source of potassium ions. Triclosan is also referred to as a dentifrice in a dentifrice composition comprising a lamellar liquid crystal surfactant in which the gaps between the individual lamellae are less than 6.0 nm, which composition may also contain a zinc salt, wherein this composition is described in European Patent 161 988 (Lane et al.). Triclosan has also been used in a dentifrice composition containing zinc citrate trihydrate, which composition is described in European patent no. 161,899 (Saxton et al.).

The antibacterial agent (AEA), which enhances the delivery and retention of the agent to the surface of the oral cavity, is used in an amount sufficient to achieve this effect, which is typically an amount ranging from 0.05% to 4% by weight. % by weight, preferably from 0.1% to 3% by weight, in particular from 0.5% to 2.5% by weight.

The AEA may be a single compound, preferably a polymerizable monomer, more preferably a polymer, and the term is quite general and includes, for example, oligomers, homopolymers, copolymers of two or more monomers, ionomers. block copolymers, graft copolymers, crosslinked polymers and copolymers and the like. The AEA may be of natural or synthetic origin, may be water insoluble or preferably water soluble (i.e., saliva), or may be swellable (hydratable, hydrogel-forming). The molecular weight of these substances can generally be in the range from 100 to 1 000 000, preferably from 1000 to 1 000 000, particularly preferably in the range from 2000 or 2 500 to 250 000 or 500 000.

These AEAs usually contain at least one group to promote the delivery of an active agent that is acidic in nature, such as a sulfonic acid, phosphonic acid residue, or preferably a phosphonic or carboxylic acid residue, or an acid salt such as an alkali metal salt or an ammonium salt. , and at least one organic group promoting the retention (or retention) of the active agent on the mucosal surface, wherein preferably the substance comprises a plurality of both kinds of said groups. The following retention-promoting groups can be represented by the general formula:

- (X) n-R, in which:

X represents oxygen, nitrogen, sulfur, SO, SO ₂ , phosphorus, PO or Si and the like,

R represents a hydrophobic alkyl group, an alkenyl group, an acyl group, an aryl group, an alkaryl group, a heterocyclic group, or an inertly substituted derivative thereof, and n is 0,1 or above.

By the term "inertly substituted derivatives" is meant substituents on the R group, which are generally non-hydrophilic and which do not substantially affect the desired functions of AEA in promoting the delivery of an antibacterial agent to the oral mucosal surface and retention thereof on the oral mucosal surface. the inertly substituted derivative may be a halogen substituted group such as chlorine, bromine, iodine or carboxy and the like. Examples of such groups promoting delivery of the antibacterial agent to the surface of the oral cavity and its retention on the surface of the oral cavity will be described below.

n x - (X) n R 0 - methyl, ethyl, propyl, butyl, isobutyl, tert-butyl; cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl, acetyl, benzoyl, butyryl, terephthaloyl and the like. 1 0 ethoxy, benzyloxy, thioacetoxy, phenoxy, carbethoxy, carbbenzyloxy and the like. N ethylamino, diethylamino, propylamido, benzylamino, benzoylamido, phenylacetamido and the like. WITH thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenythioacetyl, thiobenzyol and the like. SO butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy and the like. SO ₂ butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl and the like. P diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylphenylphosphinyl and the like. AFTER diethylphosphinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, methylbenzylphosphinoxy, methylphenylphosphinoxy and the like. Are u trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl, dimethylvinylsilyl, dimethylsilyl! etc.

When used in an oral formulation, the group promoting the delivery of the antibacterial agent to the oral cavity surface, i.e., the tooth and gum surfaces, is one that associates by adhesion, cohesion or otherwise with AEA (containing the antibacterial agent) to deliver the antibacterial agent to this surface. The organic moiety that promotes retention of the antibacterial agent on this surface is generally a hydrophobic moiety that binds or otherwise attaches the antibacterial agents to the AEA, thereby promoting the retention of the antibacterial agent to the AEA and thus indirectly on the oral cavity surface. In some cases, the capture of the antibacterial agent is achieved through the physical attachment of the agent by action

AEA, especially in cases where the AEA substance is a crosslinked polymer whose structure itself increases the number of sites to effect this binding, respectively. connection. The presence of a higher molecular weight moiety and the presence of a plurality of moieties with hydrophobic crosslinked moieties in the crosslinked polymer further enhance the possibility of physical attachment of the antibacterial agent to the crosslinked AEA polymer or the crosslinked polymer.

Preferably, the AEA is an antenna polymer comprising a chain or backbone containing repeating units, each containing at least one carbon atom and preferably at least one directly linked or indirectly attached, one linking group supporting the delivery of the active antibacterial agent. and at least one directly or indirectly coupled, monovalent attachment moiety promoting retention of the active antibacterial agent, geminally, vicmally, or less preferably by other means to the atoms in the chain, preferably to the carbon atoms. It is less preferred that the polymer contains antibacterial agent delivery support groups and / or antibacterial agent retention groups and / or other bivalent atoms or groups as linkers in the polymer chain instead of or in addition to the carbon atoms as crosslinking moieties.

It is contemplated that all examples of AEAs herein that do not contain both antibacterial agent delivery and retention groups may, and preferably are, chemically modifiable in such a way that they are obtained types of AEAs, which preferably comprise both of these types of groups and more preferably a plurality of these types of groups. In the case of preferred polymerizing AEAs, in order to maximize the effect and promote the delivery of the antibacterial agent to the oral cavity surface, it is desirable that repeating units in the polymerization chain or polymer backbone containing acidic groups promoting antibacterial agent delivery comprise at least about 10% by weight of the polymer; at least about 50% by weight, even more preferably at least about 80% by weight to about 95% by weight or even 100% by weight of the polymer.

Preferably, the AEA comprises a polymer comprising repeating units in which one or more phosphonic acid-based groups promoting the delivery of an antibacterial agent is bound to one or more carbon atoms in the polymerization molecule. An example of such AEAs is poly (vinylphosphonic acid) containing units of formula (I)

- [CH2-CH2- (I)]

I

PO ₃ H ₂

However, this group does not contain a group which promotes retention of the antibacterial on the surface of the oral cavity. However, a group of this type is present in poly (1-phosphonopropene) having the formula (II)

4CH2-CH] - (II)

II ch ₃ after ₃ h ₂

A preferred type of AEA containing phosphonic acid for use according to the invention is a poly (β-styrene phosphonic acid) of formula (III):

-JCH _r CH - (III),

I I

Ph PO ₃ H;

wherein Ph is a phenyl group, wherein the phosphonic group promoting the antibacterial agent and the phenyl group promoting the retention of the antibacterial agent are bonded to vicmal carbon atoms in the chain, or a copolymer of β-styrenephosphonic acid with vinylphosphonyl chloride having units of formula (III) (I) See in alternating or statistical order, or poly (α-styrenephosphonic acid) containing units of formula (IV):

ph

I

4ch ₂ -c -] - (iv)

Even after ₃ h ₂ in which both the feeder and retention groups of the antibacterial are bound to the same carbon atom in the chain.

These polymers of styrene phosphonic acid and their copolymers with other inert, ethylenically unsaturated monomers have, as already mentioned, a molecular weight per year. These inert monomers do not adversely affect the intended function of any polymer used in the AEA of the invention.

Other polymers containing phosphonic acid residues include, for example, phosphonated ethylene compounds having units of formula (V):

- [(CH 2 CH 3 CH 2 PO 3) 2, in which n may, for example, be an integer such that the polymer of formula (V) has a molecular weight of about 3000, and a sodium salt of poly (butene-4,4-diphosphonate) with units of formula (VI):

- [CH-CH-J- (VI)]

I

CH2-CH <(PO ₃ Na ₂ ) ₂ af oly (allyl-bis (phosphonomethylamine) with units of formula (VII):

- [CH 3 -CH -] - (VII)

I

CH ₂ -N <(PO ₃ Na ₂ ) ₂

Other phosphonated polymers such as poly (dylphosphonacetate), phosphonated polymethacrylate, etc., as well as the geminal diphosphonate polymers disclosed in European patent no. 321 233, may be used as AEAs, provided they contain or are modified to contain both types of said groups.

In one aspect, the oral composition comprises an orally acceptable vehicle, an effective amount of a substantially water-insoluble non-cationic antibacterial agent in an effective amount against dental plaque formation, and an antibacterial promoting agent having an average molecular weight ranging from about 1000 to about 1,000 No. 000, comprises at least one functional group promoting the delivery or release of an antibacterial agent and at least one organic group with a retention aid (retention promoting group), said agent not comprising or substantially free of a water-soluble synthetic anionic polycarboxylate salt of a linear alkali metal or ammonium polymer a salt having a molecular weight ranging from about 1000 to about 1,000,000.

SK 28056-6

According to another preferred embodiment, the AEA may comprise one of the synthetic anionic polymeric polycarboxylates. Although the following compounds are not used to interact with polyphosphate agents as anti-tartar agents according to the present invention, it should be noted that synthetic anionic polymeric polycarboxylates having a molecular weight of about 1000 to 1,000,000, preferably in the range of about 30,000 to 500,000 used as alkaline phosphatase enzyme inhibitors in optimizing the effectiveness of linear molecularly dysdrated polyphosphates against calculus formation, such as disclosed in U.S. Pat. No. 4,627,977 to Gaffar et al. In United Kingdom Patent Application Ser. No. 2,200,551 discloses polymeric polycarboxylates as an optional component of oral compositions comprising linear molecularly dehydrated polyphosphate salts and substantially water-insoluble non-cationic antibacterial agents. In addition, it has been found in connection with the present invention that the polycarboxylate is considerably more effective in delivering and retaining a nonionic antibacterial agent effective against the formation of a dental plaque on the tooth surface even when no other component is present with which by treatment with said polymerization polycarboxylate (i.e., molecular dehydrated polyphosphate), for example, when the component interacting with the polymerization polycarboxylate is mainly a non-cationic antibacterial agent.

Synthetic anionic polymerization polycarboxylates and their complexes with various cationic disinfectants, zinc and magnesium are known in the art as anti-tartar agents per se, for example, U.S. Pat. 3,429,963 (Shedlovsky), 4,152,420 (Gaffar), 3,956,480 (Dichter et al.), 4,138,477 (Gaffar), and 4,183,914 (Gaffar et al.). It should be noted, however, that the synthetic anionic polymeric polycarboxylates mentioned in these several patents, when they contain or are modified by retention-enhancing groups, are active agents that can thus be used in the oral compositions and processes of the invention. These publications are reference materials in the context of the present invention.

The synthetic anionic polymeric polycarboxylates used in the present invention are well known in the art, which are often used in the form of free acids or preferably in the form of partially neutralized salts, or even more preferably in the form of completely neutralized, water-soluble salts. or a water-swellable (hydratable form, gel-forming form), preferably being an alkali salt (such as a potassium salt or preferably a sodium salt) or ammonium salts. Preferred copolymers of maleic anhydride or maleic acid with another polymerizable ethylenically unsaturated monomer in a ratio of 1: 4 to 4: 1 are preferably methyl vinyl ether / maleic anhydride copolymers having a molecular weight ranging from about 30 to 30%. These copolymers are available under the designation Gantrez, such as AN 139 (molecular weight 500,000), AN 119 (molecular weight 250,000), and preferably S -97 with pharmaceutical grade (MW 70,000), manufactured by GAF Corporation.

Other AEA-efficient polymerization polycarboxylates containing or modified by retention-promoting groups include, for example, those disclosed in U.S. Pat. For example, copolymers of maleic anhydride with ethyl acrylate in a ratio of 1: 1, followed by hydroxyethylmethymylate, N-vinyl-2-pyrrolidone or ethylene, the latter being for example the commercially available product Monsanto EMA no. 1103 with a molecular weight of 10,000 and EMA Grad 61, and copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone in a 1: 1 ratio.

Other effective polymerization polycarboxylates include, for example, copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic acid, polyitaconic acid and polymaleic acid oligomers, and sulfoacrylic oligomers whose molecular weight is very low, about 1000, cited in the U.S. patents cited. Nos. 4,138,477 and 4,183,914, and commonly available under the trade name, for example, Uniroyal ND-2, which contain or are modified by antibacterial retention-promoting groups.

In general, retention-promoting groups which contain polymerizable olefinically or ethylenically unsaturated carboxylic acids containing an activated olefinic carbon-carbon double bond that are readily functional in polymerization due to their presence in the monomer molecule are suitable for the purposes of the present invention. at position a - β with respect to the position of the carboxyl group or as part of the terminal methylene group. Examples of such acids include acrylic acid, methacrylic acid, etacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styrylacrylic acid, β-styrylacrylic acid, , citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, α-phenylacrylic acid, 2-benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbelic acid, fumaric acid, maleic acid and anhydrides thereof. Other different olefinic monomers copolymerizable with said carboxyl monomers include vinyl acetate, vinyl chloride, dimethyl maleate and the like. The copolymers usually contain a sufficient number of carboxylic acid salt groups to achieve water solubility of these compounds.

The so-called &quot; carboxyvinyl polymers, referred to as toothpaste components in U.S. Pat. 3,980,767 (Chown et al.), 3,935,306 (Roberts et al.), 3,919,409 (Perla et al.), 3,911,904 (Harrison), and 3,711,604 (Colodney et al. ). These substances are commonly marketed, for example, under the trade names Carbopol 934, 940 and 941 by BF Goodrich, which products consist essentially of a colloidal, water-soluble polyacrylic acid polymer crosslinked by the addition of 0.75% to about 2.0% polyalylsaccharose or polyalylpentaerythritol as crosslinking agents, wherein the crosslinking structures and crosslinking bonds provide the desired retention enhancement due to the hydrophobic nature of these structures and / or due to the physical attachment of the antibacterial agent and the like. Polycarbophil is a similar substance, being a polyacrylic acid cross-linked with less than 0.2% divinyl glycol, with the lower proportion, molecular weight and / or hydrophobicity of the cross-linking agent providing little or no improvement in retention. In contrast, 2,5-dimethyl-1,5-hexadiene, for example, is a more effective crosslinking agent promoting retention of the antibacterial agent.

The synthetic anionic polymeric polycarboxylate component is most often a hydrocarbon-type component with optionally halogenated and substituents with an O-bond and with bonds present, for example, in the ester. ether and OH groups, wherein the component is present in the compositions of the present invention in an amount of from 0.05% to 4% by weight, preferably from 0.05% to 3% by weight, most preferably from 0.05% to 3% by weight. 0.1% to 2% by weight.

The AEA may also comprise natural anionic polymeric polycarboxylates containing retention groups of the antibacterial agent. Carboxymethylcellulose and other binders and film-forming agents which do not contain said antibacterial agent-promoting groups and / or retention-promoting groups of said antibacterial agent are ineffective as AEAs.

Illustrative examples of AEAs containing groups derived from fostinic acid and / or sulphonic acid that promote the delivery of an antibacterial agent include polymers and copolymers containing units or moieties derived from the polymerization of vinyl tonicity or allylphosphonic acid and / or sulphonic acid substituted as necessary on one or two (or three) carbon atoms by retention-promoting organic groups, such as those of the formula - (X) n R. Mixtures of these monomers and copolymers of these may also be used with one or more inert polymerizable ethylenically unsaturated monomers, such as those disclosed in connection with effective synthetic anionic polymeric polycarboxylates. As will be noted, in these agents and in other polymeric AEAs suitable for the purpose of the present invention, usually only one acidic group promoting the antibacterial agent is bound to any carbon atom or other atom in the polymer backbone or to the branching of the backbone. Likewise, polysiloxanes containing pendant groups promoting or retention of the antibacterial agent or modified to contain these groups may be used as AEAs. As the AEAs, ionomers containing the abovementioned groups promoting the retention of the antibacterial agent and the retention of the antibacterial agent are also effective or modified to contain these groups. These ionomeric substances are described in Kirk Othmer Encyclopedia of Chemical Technology, 3rd ed., Supplement Volume, Jolrn Wiley &amp; Sons, Inc., copyright, 1984, p. 546-573, the disclosure of which is incorporated herein by reference. Also polyesters, polyurethanes and synthetic and natural polyamides, including proteins and protein materials such as collagen, poly (arginine) and other polymerizable amino acids, are also effective as AEAs when they contain or have been modified to contain retention-promoting groups.

According to one aspect of the present invention, an AEA having an average molecular weight of 1,000 to 1,000,000 comprises at least one functional group with a release-promoting effect and at least one organic group with a sustaining-promoting effect, wherein the substance is free of or substantially free of water. a synthetic anionic linear polymerization polycarboxylate alkali metal salt or ammonium salt having a molecular weight of 1000 to 1,000,000.

For oral use, a dentifrice composition containing about 0.3% by weight of an antibacterial (e.g., triclosan) and about 1.5 to 2% by weight of a pelycarboxylate such as AEA is suitable for oral use.

Without being bound to any theoretical explanation, it is likely that the AEA, especially the polymerization AEA, is generally an anionic film-forming material, and is believed to bind the film-forming material to the tooth surface and to produce a continuous pattern. film, preventing bacteria from accessing the surface of the teeth. It is possible that the non-cationic antibacterial agent forms a complex or other form of association with AEA, thereby forming a film of that complex or other form of association with AEA on the tooth surface. The film-forming property of the AEA and the anti-bacterial release effect and retention of the antibacterial on the tooth surface due to the effect of the AEA apparently cause the tooth surface to become an unfavorable surface for settling and accumulation of bacteria due to the direct bacteriostatic effect of the antibacterial. Therefore, three types of effect are combined:

1. a stimulating release effect;

2. prolonged retention time on the tooth surface; and

3. preventing the bacteria from adhering to the tooth surface, thereby effectively preventing the formation of a dental plaque. A similar effect can be achieved on the soft tissues of the oral cavity near and at the edge of the gums.

According to the invention, an orally acceptable vehicle permits efficient dissolution of a substantially water-insoluble non-cationic antibacterial in an effective amount to prevent plaque formation in the saliva.

In the composition for oral administration, the vehicle used comprises an aqueous phase with a solvent added. In a dentifrice composition, which typically contains from 5% to 30% by weight of the silica polishing composition, the water is usually present in an amount of 3% to 35% by weight and a solvent, preferably glycerol and / or sorbitol, which are usually present in total an amount of 6.5% to 75% by weight, or up to 80% by weight, based on the weight of the oral gel dentifrice. When sorbitol is mentioned, it is a material which is commercially available in the form of a 70% aqueous solution.

Gel dentifrices do not require an additional antibacterial solubilizing component when the antibacterial content is 0.25% to 0.35% by weight, but it is still possible to add such a component to the present invention. When the amount of antibacterial agent is less than 0.25% by weight, for example 0.01% to about 0.25% by weight, it is suitable to use a solubilizing agent to ensure sufficient saliva dissolution to achieve the necessary efficacy against dental plaque formation. In the case where the antibacterial agent is present in an amount greater than 0.35% by weight, for example 0.35% and 0.5% by weight or even more, it is also necessary to use a solubilizing agent since it will otherwise remain predominantly part of the antibacterial substance in the undissolved state.

When the composition for oral administration is a cleaning composition having a content of 30% to 75% by weight

If desired, it is also possible to add a solubilizing agent.

When the oral composition is a mouthwash or a liquid dentifrice, the oral vehicle comprises at least one surfactant, a flavoring oil or a non-toxic alcohol, each of which helps to dissolve the antibacterial so that the presence of the solubilizing agent is only possible and not necessary.

When the oral composition contains a solubilizing agent, the amount is usually in the range of 0.5% to 20% by weight. An amount of 0.5% by weight is usually sufficient when the amount of the substantially water-insoluble non-cationic antibacterial agent is low, for example up to 0.3% by weight. When a higher amount of antibacterial agent is used, for example at least 0.5% by weight, and especially when a silica polishing agent is present in an amount of 5% to 30%, it is desirable to use at least 5% by weight, usually up to 20% or more by weight of the solubilizing agent. If the amount of solubilizing agent is greater than 5% by weight, the composition may tend to separate into solid and liquid fractions.

The agent intended to aid in the dissolution of the antibacterial agent in the saliva may be contained in a vehicle containing water as a humectant. Such solubilizing or wetting agents (or also moisture stabilizers) are, for example, polyols such as propylene glycol, dipropylene glycol and hexylene glycol, methylcellosol, ethylcellosol, vegetable oils and waxes containing at least 12 carbon atoms in a straight chain, such as olive oil, castor oil, petrolatum, in addition, esters such as amyl acetate, ethyl acetate and benzyl benzoate may be used. Propylene glycol is understood to mean 1,2-propylene glycol and 1,3-propylene glycol. Larger amounts of polyethylene glycol should be avoided, especially with a molecular weight of 600 or more, because polyethylene glycol effectively reduces the antibacterial action of the non-cationic antibacterial agent. For example, when polyethylene glycol (PEG) 600 is included with triclosan in a triclosan: PEG ratio of 600 = 25: 1, the antibacterial activity of triclosan decreases sixteen times compared to that in the absence of PEG.

The dentifrice for oral administration may, according to one aspect of the present invention, be a gel, such as a goal dentifrice. The composition may comprise a silica polishing material, preferably a crystalline silica material having a particle size of up to 5 gm, an average particle size of up to 1.1 gm, and a specific surface area of up to about 50,000 cm ² / gram, which may be silica gel or colloidal silica. and a complex amorphous alkali metal aluminosilicate.

When a clear or opaque gel is used, it is particularly suitable to use colloidal silicon dioxide, such as those sold under the names Syloid 72 and Syloid 74 or Santocel. 100 or may be alkali metal aluminosilicates (i.e., silicon containing alumina incorporated in their matrix) as these meet the needs for achieving a gel structure and have a refractive index close to that of liquid gelling agent systems (including water and / or humectants) or solubilizers) generally used in dentifrices.

The polishing material is typically present in such compositions, such as toothpastes or gel formulations, in the range of from about 5% to about 30% by weight.

In one aspect of the present invention, when the oral composition is in the form of a dentifrice, it typically comprises an orally acceptable vehicle comprising an aqueous phase with a humectant (or solvent or moisture stabilizer), which is preferably glycerol and / or sorbitol, the water usually present. in an amount ranging from about 15 wt% to about 35 wt% or up to about 40 wt%, and glycerol and / or sorbitol is usually present in a total amount ranging from 20 wt% to about 75 wt%, preferably from about 25 wt% up to about 60% by weight. Again, sorbitol is a commercially available material in the form of a 70% aqueous solution.

The oral dentifrice composition of the present invention may be substantially pasty in nature, and thus may be a toothpaste, although in the presence of a silicone polishing agent (which is not customary since such material is generally not used in an amount greater than 30% by weight). the composition may be a gel. The vehicle for this oral dentifrice comprises a dentally acceptable polishing material, examples of which include water-insoluble sodium or potassium metaphosphate, calcium phosphate, calcium dihydrogen phosphate, anhydrous calcium hydrogen phosphate, calcium carbonate, aluminum silicate, hydrated aluminum oxide, hydrated silica , bentonite and mixtures thereof or mixtures thereof with harder polishing materials, for example, calcined alumina and zirconium silicate, which also include the resins described in U.S. Pat. No. 3,070,510 of December 15, 1962, such as melanin, phenol and urea-formaldehyde resins and crosslinked polyepoxides and polyesters. Insoluble aluminum metaphosphate is also a preferred polishing material.

Rad tzv. the water-insoluble polishing material is anionic in nature and, moreover, contains a small amount of soluble material. Insoluble sodium metaphosphate can be obtained by any suitable method, for example as described in the publication. Thorpe's Dictionary of Applied Chemistry, Vol. 9, 4 * Edition, p. Another example of suitable materials are some forms of insoluble sodium metaphosphate, known as Madrell's salt and Kurrol's salt. These salts have only a slight solubility in water, so they are usually referred to as insoluble metaphosphates (IMP). Small amounts of soluble phosphate material are usually present as impurities, usually up to 4% by weight. The amount of soluble phosphate, which may include soluble sodium trimetaphosphate, can be reduced or removed if necessary by washing with water. Insoluble alkali metal metaphosphates are generally used in the form of powders, the particle size of which is such that only a maximum of 1% of the material has particles larger than 37 gm.

An example of a non-ionic polishing agent is hydrated alumina. This substance is usually in the form of small particles, with at least 85% of the particles being less than 20 gm, this material is usually classified as α-alumina trihydrate (gibbsite) and is usually given its chemical formula as Al ₂ O ₃ . 3H ₂ O or Al (OH) ₃ . The average particle size of this material is usually 6 to 9 gmm. The particle size usually has the following distribution:

SK 280567-6

<10 56-67 <5 28-40

The polishing material is present in the composition in the form of a paste or gel, usually in an amount of 30% to 75% by weight.

Toothpastes or creams or gel dentifrices generally comprise a natural or synthetic thickener or gel-forming agent in an amount of 0.1% to 10% by weight, preferably 0.5% to 5% by weight. A suitable thickener is, for example, an alkali metal complex magnesium silicate based on, for example, Laponite (e.g., CP, SP 2002 or D, Laporte Industries Limited). Laponite D analysis gave a composition (in weight) of 58.00% SiO ₂ , 25.40% MgO, 3.05% Na ₂ O, 0.98% Li ₂ O and a small amount of water and a trace of metal. The density of this material is 2.53 g / cm ³ and the bulk density at a moisture content of 8% by weight is 1.0 g / ml.

Another suitable thickener or gel former is Irish moss, carrageenan, iota-carrageenan, tragacanth gum, starch, polyvinylpyrrolidone, hydroxyelylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose (for example, the product under the name Natrosol), sodium carboxylate, sodium carboxylate is also a colloidal silica, for example, a product currently marketed as Syloid 244 or Sylodent 15.

In another aspect of the present invention, the oral composition is a mouthwash or a liquid dentifrice having a substantially liquid nature, in which case the vehicle used is typically a mixture of water and alcohol. The weight ratio of water to alcohol is usually in the range from 1: 1 to 20: 1, preferably in the range from 3: 1 to 10: 1, and in particular in the range from 4: 1 to 6: 1. such compositions range from 70% to 99.9% by weight. The alcohols used are non-toxic alcohol, for example ethanol or isopropanol. Glycerol or sorbitol can be used as wetting agents (or moisture stabilizers or solvents), and these are used in an amount of from 10% to 30% by weight. Liquid dentifrices typically contain 50% to 85% by weight of water, and may contain 0.5% to 20% by weight of a non-toxic alcohol, as well as 10 to 40% by weight of a wetting agent (moisture stabilizer or solvent) such as glycerol and / or or sorbitol. Sorbitol is a commercially available material in the form of a 70% aqueous solution. The preferred non-toxic alcohol is ethanol. Alcohol is likely to help dissolve the water-insoluble non-cationic antibacterial, and it is believed that aromatic oil is also likely to have the same effect.

As mentioned above, the non-cationic antibacterial is a substance that is substantially insoluble in water. However, in an oral composition of the invention containing AEA, such as a polycarboxylate that is in the form of an oral rinse or a liquid dentifrice, it is believed that the organic surfactant, flavoring oil or nontoxic alcohol helps to dissolve the antibacterial agent and thereby contribute to the fact that this substance is also easier to reach the soft tissues of the oral cavity, especially near or at the edge of the gums and also to the surface of the teeth. The organic surfactants and / or flavoring oils may also be co-solvents for dissolving the antibacterial agent as well as any other ingredients present in the oral dentifrices.

To enhance the prophylactic effect, organic surfactants are also used in the compositions of the invention to aid in the complete dispersion of the antibiotic; at the same time, these substances help to make the composition more cosmetically acceptable. The organic surfactant material preferably has an anionic, nonionic or ampholytic nature, in which case it is preferable to use a wetting agent which simultaneously has a cleaning and foaming effect. Suitable examples of arionic surfactants are the water-soluble salts of higher aliphatic acids with monoglyceride monosulfates, e.g. sodium salts of monoglyceride monosulfates such as coconut oil fatty acids; esters of higher fatty acids with

1,2-dihydroxypropanesulfonate and substantially saturated higher aliphatic acylamides derived from lower aliphatic aninocarboxylic acids, e.g. containing 12 to 1 (carbon atoms in the fatty acid, alkyl or acyl residue, and the like). Examples of said amides are N- lauroyl sarcosine and the sodium or potassium salt of la-lauroyl-, N-myristoyl- or N-palmitoyl sarcosine, or a salt of these with ethanolamine, which should be substantially free of soaps or similar materials containing higher saturated aliphatic acids. it is particularly advantageous since these materials have a long-lasting and significant effect in inhibiting oral acid formation in carbohydrate disintegration and furthermore reduce the enamel solubility in acidic solutions somewhat. ethylene oxide condensation products with various reactive hydrogen-containing compounds with a long, hydrophobic chain, for example an aliphatic chain containing 12 to 20 carbon atoms, the condensation products (etoxamers) containing hydrophilic polyoxyethylene moieties, for example polyethylene oxide condensation products with fatty acids, fatty acids alcohols, fatty amides, polyhydric alcohols such as sorbitan mono stearate and polypropylene oxides (such as the product available under the name Pluronic).

The surfactant is usually present in an amount of from about 0.5% to about 5% by weight, preferably from 1% to 25% by weight.

When the oral composition is in the form of a liquid dentifrice, it typically contains a natural or synthetic thickener or gel former as defined herein in an amount ranging from about 0.1% by weight. % to about 10% by weight, preferably from 0.5% to 5% by weight.

Liquid dentifrices usually do not contain a buffing agent. Well, as described in U.S. Pat. No. 3,506,757 (Salzmann), said composition may comprise a polishing agent, said composition comprising from 0.5% to 2.0% by weight of a polysaccharide having a molecular weight greater than 1,000,000 and containing knife groups , glucose groups, potassium glucuronate groups and acetyl groups in an approximate ratio of 2: 1: 1: 1 as a suspending and thickening agent, and optionally contains 10% to 20% by weight of the composition.

These materials include hydrated alumina, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, insoluble sodium metaphosphate, anhydrous calcium phosphate, calcium carbonate, magnesium carbonate, magnesium carbonate, silica, or mixtures thereof.

Without being bound by theory, it is likely that the aqueous vehicle (humectant or humectant) will normally dissolve in micelles of the surfactant material in the mobile phase (i.e., the non-gelling and polishing phase). (if present in a dentifrice). This mobile solution-forming phase can be diluted with saliva in use to precipitate triclosan. That is, even in the absence of a particular solubilizing material for triclosan, at a total triclosan content of between 0.25% and 0.35% by weight and an AEA such as polycarboxylate, sufficient triclosan is present to provide an excellent anti-soft coating effect. tissues and the edge of the gum. The same applies to the other water-insoluble non-cationic antibacterial agents mentioned.

The oral composition may also contain a fluoride ion source or fluorine releasing component as an anti-caries agent in an amount sufficient to deliver about 25 ppm to 5000 ppm of fluoride ions. These substances are characterized by their ability to release fluoride ions into water and are not intended to have a substantial adverse effect on the action of the other components of the formulation. These include, for example, inorganic fluorides, for example soluble alkali metal and alkaline earth metal salts such as sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, copper fluoride such as copper (I) fluoride, zinc fluoride, barium fluoride, and sodium fluorosilicate or ammonium fluorosilicate, sodium fluorosilicate or ammonium fluorosilicate, sodium monofluorophosphate, aluminum mono- and difluorophosphate and calcium pyrophosphate. Alkali metal tin fluorides such as sodium and stannous fluoride, sodium monofluorophosphate (MFP) and mixtures thereof are most preferred.

The amount of the fluorine-providing compound depends to some extent on the type of compound, its solubility, and the type of final oral composition, but it must be a nontoxic amount, typically in the range of about 0.0005% by weight to about 3.0 % by weight. In a dentifrice composition, such as a dental gel, an amount of said substance that releases about 5000 ppm of fluoride ion based on the weight of the composition is acceptable. In the present case, any minimum amount of this substance may be used, but it is preferred to use an amount that releases about 300 to about 2000 ppm, preferably 800 ppm to 1500 ppm of the fluoride ion.

In the case of alkali metal fluorides, this component is usually present in an amount of up to about 2% by weight based on the total composition, preferably in an amount ranging from about 0.05% to about 1% by weight. In the case of sodium monofluorophosphate, it may be present in an amount ranging from about 0.1% to about 3% by weight, preferably 0.76% by weight.

It will be appreciated that the oral composition will be sold or otherwise distributed, as is conventional, in a suitably labeled package. For example, a dentifrice gel will usually be placed in a compressible tube, usually of aluminum, coated or plastic, or another container may be used to compress, exhaust or measure its contents, the container being always marked with an indication of what means goes.

Other materials may be incorporated into the oral compositions, for example, bleaching agents, preservatives, silicones, chlorophyll compounds and / or ammonia-derived materials such as urea, ammonium hydrogen phosphate, and mixtures thereof. These auxiliary components, when used, are incorporated into the composition in an amount that does not substantially adversely affect the desired properties and effects of the composition. Larger amounts of zinc, magnesium and other metal salts, which are usually soluble and could complex with the active ingredient of the composition, should not be used.

It is also possible to use suitable flavorings or sweeteners. Examples of such flavoring or flavoring agents include some essential oils, such as spearmint, peppermint, menthol, sasafras, clove, sage, eucalypt, marjoram, cinnamon, lemon or orange, or methyl salicylate. A suitable sweetener is, for example, sucrose, lactose, maltose, xvlitol, sodium cyclamate, perilartin, AMP (asparylalanine methyl ester), saccharin and the like. Flavoring or flavoring agents and sweeteners may individually or together comprise from about 0.1% to about 5% by weight of the composition. As with surfactants, essential oils are likely to aid in the dissolution of the antibacterial agent with or in the absence of the surfactant.

The preferred composition of the invention for oral administration is preferably applied periodically to enamel and soft tissue of the oral cavity, particularly at and around the gum edge, for example every day or every other day, or every third day, preferably 1 to 3 times a day at about pH. 4.5 to about 9 or 10, usually about 5.5 to about 8, preferably about 6 to about 8, and especially about 6.5 to about 7.5, for at least two weeks to 8 weeks or longer for life. Even with a low saw of about 5 or even lower, there is no decalcification or other breakdown of the enamel. The pH can be controlled with an acid such as citric or benzoic or a base (such as sodium hydroxide) or a buffer containing sodium citrate, benzoate, sodium carbonate or bicarbonate, sodium hydrogen phosphate, sodium dihydrogen phosphate and the like.

The composition according to the invention may be incorporated in the form of lozenges for sublingual use in chewing gum or other similar products by, for example, mixing into a warm base of the gum or applying to the exterior surface of chewing gum, for which purpose jelutong may be used. gum latex, vinyl resin and the like, preferably these are used together with conventional plasticizers or plasticizers, sugar or other sweeteners or carbohydrates such as glucose, sorbitol and the like.

DETAILED DESCRIPTION OF THE INVENTION

The dental plaque composition for oral administration will be described in more detail by way of the following specific embodiments given in the examples, which are illustrative only and are not intended to limit the scope of the invention in any way. All proportions and amounts indicated in the Examples are by weight unless otherwise indicated.

Example 1

According to this example, a dentifrice having the following composition was prepared:

component Parts by weight A B glycerol 10.00 - propylene glycol - 10.00 Sorbitol (70%) 25.00 25.00 jota carrageenan 0.60 0.60 Gantrez S-97 2.00 2.00 saccharin sodium 0.40 0.40 sodium fluoride 0,243 0,243 sodium hydroxide (50% -nv) 1.00 1.00 titanium dioxide 0.50 0.50 silica polishing agent (Zeodent 113) 20.00 20.00 silicate thickener (Svlox 15) 5.50 5.50 sodium laurylsiran 2.00 2.00 Water 31,507 31,507 Triclosan 0.30 0.30 flavoring oil (silica) 0.95 0.95

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

Said dentifrice A releases triclosan by the teeth and on the soft gum tissue substantially as well as dentifrice B containing a particular solubilizing agent for triclosan. Accordingly, it is not necessary to use a particular solubilizing agent to achieve adequate performance of the composition of the invention. The corresponding formulation, in which the polycarboxylate (Gantrez) was omitted, released triclosan much worse.

According to this example, very good results can be obtained even if triclosan is replaced by another antibacterial mentioned in the description, such as phenol, thymol, eugenol and 2,2-methylenebis (4-chloro-6-bromophenol) and / or or by adding a methyl vinyl ether / maleic anhydride copolymer (Gantrez product) ualu with another AEA type, such as a 1: 1 maleic anhydride / ethyl acrylate polymer, a sulfoacrylate oligomer, some of Carbopol's, which are essentially carboxyvinyl polymers, polyacrylic acid polymers cross-linked with polyalylsaccharose or polyalylpentaerythritol (for example, product number 934), and polymers of α- or β-styrene-phosphonic acid monomers and copolymers thereof or copolymers with other ethylenically unsaturated polymers such as polymers which are polymerizable as polymers.

Example 2

According to this example, the following test solutions for dentifrices in the form of a liquid phase for triclosan feed and retention on HA-coated discs were tested in a similar manner to Example 1. The composition of the composition is shown in the following table, in the following table the test result is shown.

component Parts by weight A B C D Sorbitol (70%) 30.0 30.0 30.0 30.0 glycerol 9.5 9.5 9.5 9.5 propylene glycol 0.5 0.5 0.5 0.5

SL5 20.0 20.0 20.0 20.0 NaF 0,243 0,243 0,243 0,243 triclosan 0.3 0.3 0.3 0.3 silica 0.95 0.95 0.95 0.95 Water 56,507 56,507 56,507 56,507 poly / N-stenephosphonic acid) 2.0 poly (α-stenephosphonic acid) 2.0 polyvinyl alcohol 2.0

All formulations were adjusted to pH 6.5 by addition of sodium hydroxide.

A B C D triclosan feed in pg on saliva coated discs 31.0 174.0 86.0 36.0 Triclosan titanium on saliva coated HA discs at the start of the test 183.0 after 30 minutes 136.0 after 1 hour 105.0 after 3 hours 83.0

These results show that solution D, which contained polyvinyl alcohol not covered by the term AEA, provided a triclosan feed of only 36.0 µm, similar to control solution A, totally without additive for which the value was 31.0 µm. In contrast, solution C, which contains poly (α-styrene phosphonic acid), provides a feed of 86.0 μη.m, which is more than twice that of both solutions A and D, and solution B containing poly (β-styrenic acid). ej) provides approximately five times the feed rate compared to solutions A and D, thus it is clear that vicinal substitution of the antibacterial infiltrating group provides very good results in this regard. The results also show surprisingly good retention of triclosan on HA discs of solution B which contained poly (i-styrenephosphonic acid) having a molecular weight ranging from 3000 to 10,000.

Example 3

The effect of synthetic anionic linear polycarboxylates on the delivery, retention and release of the water insoluble non-cationic antibacterial from the tooth surface was tested in vitro on saliva-coated hydroxyapatitic discs and isolated facial mucosal epithelial cells according to this example. The results obtained in vitro are comparable to similar values in vivo.

Hydroxyipatite (HA), obtained from Monsato Co., was thoroughly washed with distilled water, filtered in vacuo and dried overnight at 37 ° C to test the delivery of antibacterial agent to saliva-coated hydroxyapatite disks. The dried hydroxyapatite was ground in a mortar. Then 150 mg of HA was placed in a chamber for production of potassium bromide pellets (Bames Analytical, Stanford, CT) and the material was pressed for 6 minutes at a pressure of approximately 5000 kg in a laboratory press (Carver Laboratory). The resulting discs of 13 mm diameter were sintered for 4 hours at 800 ° C in an oven (Thermolyne). The saliva was collected in ice-cooled glass vials and clarified by centrifugation for 15 minutes at 15,000 x g at 4 ° C. then

SK 28056´ pri6 were sterilized at the same temperature of 4 ° C and stirred by irradiating the sample with ultraviolet light for 1 hour.

Each sintered disc was hydrated with sterile water in a polyethylene test tube. The water was then removed and replaced with 2.0 ml saliva. Incubation of the disc overnight at 37 ° C and continuous shaking in a water bath created a saliva coating. The saliva was then removed and the discs were placed in a 1.0 ml solution containing antibacterial (Triclosan) for a liquid phase dental cleaner, and then the discs were incubated at 37 ° C with stirring in a water bath. After 30 minutes, the discs were transferred to a new tube, 5 ml of water was added and the disc was gently shaken (Vortex). The disc was then transferred to a new tube and the wash was repeated two more times. Finally, the disc was carefully transferred to a new tube so that no liquid was transferred. 1 ml of methanol was then added to the disc and the disc was vigorously shaken (Vortex). The sample was then left at room temperature for 30 minutes to extract the absorbed triclosan into methanol. The methanol was then aspirated and clarified by centrifugation for 5 minutes in a microcentrifuge (Backman Microfuge 11) at 10,000 rpm. Methanol was then transferred to high performance liquid chromatography vials to determine the antibacterial content. Each assay in all experiments was performed in triplicate.

In an antibacterial retention test on saliva-coated HA discs, the discs were contacted with a dentifrice suspension as described above. After incubation for 30 minutes at 37 ° C, the disks were removed, washed twice with water and then incubated again using paraffil-stimulated saliva stimulated after centrifugation. After incubation at 37 ° C with shaking, the disks were removed, and the amount of antibacterial (triclosan) retained on the disks and then released into the saliva was determined using high performance liquid chromatography.

In the test for release and delivery of the antibacterial to the epithelial cells of the mucous membrane of the face, the effect of PVM / MA on the delivery of the antibacterial (triclosan) to the soft tissues of the oral cavity from the dentifrice was measured. Cells from the facial mucosa were separated by a wooden stick which was carefully wiped off the oral mucosa. The cells were suspended in a buffer containing salts usually present in saliva (RSS buffer) containing 50 nM NaCl, 1.1 nM C.aCl ₂ and 0.6 nM KH ₂ PO ₄ (pH 7.0), 5 to 6 x 10 ⁵ cells / ml were used for each assay using a hemocytometer to count cells that were kept on ice until use. Then, 0.5 ml of the cell suspension previously incubated at 37 ° C in a water bath was added, along with 0.5 ml of the antibacterial test solution, and the mixture was incubated at 37 ° C. The antibacterial solution (triclosan) was diluted 10-fold in the incubation mixture to reduce the surfactant concentration and prevent cell membrane destruction by the agent. After 30 minutes of incubation, the cells were separated by centrifugation for 5 minutes at 5000 rpm in a microfuge of the same type as above. The cells, selected as pellet, were washed three times with RSS buffer, and then 1.5 ml of methanol was added. The sample was mixed thoroughly and then analyzed for antibacterial content by high performance liquid chromatography.

In addition, dentifrice compositions containing the individual ingredients listed in the following table were prepared.

component Parts by weight A B propylene glycol (1,2) 10.00 10.00 jota carrageenan 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 saccharin sodium 0.40 0.40 silicate thickener (Sylodent15) 3.00 3.00 silicate polishing agent (Zeodent113) 20.00 20.00 Triclosan 0.20 0.20 sodium lauryl sulfate 2.00 2.00 silica 0.95 0.95 ethanol 1.00 1.00 water to 100.00 100.00

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

The supply of triclosan to the hydroxyapatite disc, coated with saliva and facial mucosal epithelial cells in the presence and absence of Gantrez S-97 polymerization polycarboxylate, is summarized in Table 1 below.

Table 1

means Triclosan intake in gmg for discs coated with marl x 10 ³ cells of mucosa shape A 25.0 38.0 B 54.0 96.0

From the above results, it is evident that the Gantrez formulation contained in the formulation B greatly supports the supply of triclosan to both the hydroxyapatite disks and the facial mucosal cells.

Similar results were obtained with 0.30 parts by weight of triclosan.

Example 4

Saliva-coated hydroxyapatite discs and detached facial mucosal cells other than those of Example 1 were run using formulation B containing 2.00% by weight of Gantrez S-97 (which is a copolymer of methyl vinyl ether and maleic anhydride with a molecular weight of 70,000), 0.20% by weight of triclosan, 10.00% by weight of propylene glycol and 2.00% by weight of sodium lauryl sulphate and an equivalent composition B 'of the same composition except triclosan content of 0 30% by weight, these compositions being compared to a commercially available composition C containing hydrated alumina as a polishing agent, and

(a) 0,2% by weight of triclosan,

(b) no Gantrez means;

(c) no propylene glycol;

(d) 0,5% by weight of zinc citrate;

(e) 2,5% surfactant,

f) sodium monofluorophosphate and hydrated alumina as a polishing agent and further used to compare composition C 'to composition C except for the triclosan content, which in this case was 0.30% by weight. The composition of composition C 'is shown in the table.

Formulation C '

component % by weight Sorbitol (70%) 27.00 sodium carboxymethylcellulose 0.80 sodium monotluorophosphate 0.85 zinc citrate 0.50 saccharin sodium 0.18 Water 16.47 hydrated alumina polishing agent 50.00 ethanol 0.20 sodium lauryl sulphate 1,875 sodium dodecylbenzenesulfonate 0,625 triclosan 0.30 flavorings 1.20

Since compositions C and C 'contain a total of 2.50% by weight of surfactant, a larger amount of this agent is available to dissolve triclosan than in compositions B and B' which contain 2.00% by weight of the surfactant. However, propylene glycol, which is contained in the silica polishing agent (but not contained in the hydrated alumina polishing agent in compositions C and C '), ensures optimal dissolution of the triclosan.

Thus, the advantage of compositions B and B 'containing propylene glycol and Gantrez compared to compositions C and C' consists in an improved supply of triclosan to both the saliva-coated hydroxyapatite disks and the isolated facial mucosal cells, as shown in Table 2.

Table 2

means Triclosan supply in the leagues for HA-coated wheels x 10 ⁴ cells of mucosa shape B 41.1 101.6 B ' 77.4 142.0 C 20.4 61.0 C ' 42.6 100.0

Further experiments with the composition B ¹ (containing 0.3 wt% triclosan, Gantrez, eg a copolymer of methyl vinyl ether and maleic anhydride and propylene glycol) in a 50% slurry of the dentifrice are performed to determine the retention of triclosan on the hydroxyapatite discs coated with saliva during the time. In these experiments, very advantageous values for triclosan, as shown in Table 3, were shown.

Table 3 - Retention of adsorbed triclosan from a dentifrice suspension

Time (minutes) Triclosan retention (pg / disc) 0 70 30 60 60 70 120 65 180 57 240 59

These results demonstrate that dentifrices containing triclosan, Gantrez-type material and propylene glycol provide improved triclosan delivery and retention on the tooth surface and on the soft cavity surface

They thus provide an improved anti-coating effect and an improved antibacterial effect of the compositions.

Example 5

According to this example, two formulations A and T were prepared to compare them with each other.

component Content in% by weight and b gbcerol 10.00 - propylene glycol - 10.00 jota carrageenan 0.60 0.60 Sorbitol (70%) 25.00 25.00 saccharin sodium 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 sodium hydroxide (50%) 2.00 2.00 silicate polishing agent (Zeodent 113) 20.00 20.00 silicate thickened butter (Sylodent 15) 5.50 5.50 flavoring substance 1.10 1.10 triclosan 0.50 0.50 sodium laurosulphate 2.00 2.00 ethanol 1.00 1.00

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

Composition A is a dentifrice composition comprising a polycarbovylate-based Gantrez composition, 0.5% by weight triclosan as an antibacterial, and no solubilizing agent. Composition b, which m; otherwise the same composition contains propylene glycol as a solubilizing agent.

In testing these formulations, it was found that formulation a did not provide sufficient triclosan delivery, while formulation b provided good triclosan delivery to the oral mucosa cells.

It is therefore clear that all of the above results confirm the influx of triclosan from dentifrices

Example 6

In this example, experiments were conducted with a group of volunteers to determine the effect of certain dentifrices on the effect of repeated dental plaque formation using the method described by Addy, Wilis and Moran, J. Clin. Peio, 1983, Vol. 10, p. The compositions tested included a control placebo (i) free of triclosan and a dentifrice of the invention (ii) containing 0.3% by weight of triclosan, 10% propylene glycol (instead of 3% polyethylene glycol 600) and &lt; tb &gt; . % by weight of Gantrez S-97, wherein the enhancer (or solubilizer) contained propylene glycol and sorbitol. The composition is given in the following table.

component Component content in% by weight (I) (H) polyethylene glycol 600 3.00 - gl) cerol 25.00 - propylene glycol - 10.00 Sorbitol (70%) 41,617 25.00 sodium carboxy- 0.35 -

SK 28056 '' B6

methylcellulose jota carrageenan - 0.60 sodium benzoate 0.50 - saccharin sodium 0.20 0.40 sodium fluoride 0,243 0,243 silica polishing agent (Zeodent113) 18,00 20.00 silicate 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 sulphate 1.20 2.50 flavoring substance 0.89 1.10 ethanol - 1.00 sodium hydroxide (50%) - 2.00

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

Regarding the reduction of dental plaque formation on volunteer teeth, a statistically significant 20% reduction in plaque formation compared to the effect of composition (i) could be demonstrated for composition (ii) of the invention.

Since the content of 0.3% by weight of triclosan in toothpaste (ii) may be dissolved by a smaller amount of propylene glycol, similar results are expected if the propylene glycol content is reduced to 0.5% by weight and the amount of sorbitol is increased to 39.5% by weight. In the same way, other solubilizing agents may be used instead of propylene glycol, such as dipropylene glycol, hexylene glycol, methylcellosol, ethylcellosol, olive oil, castor oil, petrolatum amyl acetate, ethyl acetate, glyceryl tristearate, and the active substance benzyl benzoate to be effective. Similar results can also be expected when the toothpaste composition (ii) is present; which contains 0.3% by weight of triclosan does not use propylene glycol or other solubilizing agent.

Example 7

According to this example, further dentifrice compositions of the present invention have been prepared, the composition of which is shown in the following table:

component Parts by weight A B glycerol - 20.00 propylene glycol 10.00 0.50 Sorbitol (70%) 25.00 19.50 carboxymethylcellulose sodium - 1.10 jota carrageenan 0.60 - saccharin sodium 0.40 0.30 sodium fluoride 0,243 0,243 silica polishing agent (Zeodent 113) 20.00 20.00 silicate thickener (Sylox) 5.50 3.00 Water 28,757 28,757 Gantrez S-97 2.00 2.00 triclosan 0.50 0.30 titanium dioxide 0.50 0.50 sodium lauryl sulphate 2.50 2.00 flavoring 1.10 0.95 ethanol 1.00 - sodium hydroxide (50%) 2.00 1.60

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

In the previous examples, similar results can also be obtained if triclosan is replaced by another antibacterial agent such as phenol, thymol, eugenol and 2,2-methylenebis- (4-chloro-6-bromophenol) and / or by replacing Gantrez with another type of AEA, such as a 1: 1 ratio of maleic anhydride / ethyl acrylate copolymer, sulfoacrylic acid oligomers, some of Carbopol (which are essentially colloidal, water-soluble polyacrylic acid polymers crosslinked with 0, 75% to about 2.0% of polyalylsaccharose or polyalylpentaerythritol), for example Carbopol 934, polymers of monomers α- or β-styrenephosphonic acids and copolymers of these styrenephosphonic acid monomers or copolymers with another ethylenically unsaturated polymerizable monomer, for example vinyl acid.

Example 8

According to this example, dentifrices having the following composition were prepared:

component Parts by weight A B 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 saccharin sodium 0.30 0.30 0.30 sodium hydroxide (50%) 1.20 1.20 1.20 flavoring substance 0.95 0.95 0.95 carrageenan 1.00 - - sodium salt - 1.00 1.00 carboxymethylcellulose sodium monofluorophosphate 0.76 0.76 0.76 titanium dioxide - 0.50 0.50 triclosan 0.30 0.30 0.30 water to 100.00 100.00 100.00

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

All said dentifrices provide substantially better delivery of triclosan to the tooth and soft tissue surfaces of the oral cavity than the corresponding dentifrices which do not contain polycarboxylate-based Gantrez.

Example 9

According to this example, dentifrices having the following composition were prepared:

component Parts by weight glycerol 22,00 10.00 Sorbitol (70%) - 17,00 sodium carboxymethylcellulose 1.00 1.00 Gantrez S-97 2.00 2.00 saccharin sodium 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 sulphate 1.20 1.20 flavoring substance 0.89 0.89 water to 100.00 100.00

Bf * copolymer of methyl vinyl ether and maleic anhydride with a molecular weight of 70 000.

The two dentifrices mentioned provide a much better supply of triclosan to the saliva-coated hydroxyapatite discs than the corresponding dentifrices which do not contain a polycarboxylate-type Gantrez.

Example 10

A dentifrice having anti-tartar activity can be prepared from the following ingredients:

component Parts by weight glycerol 15,00 propylene glycol 2.00 carboxymethylcellulose sodium 1.50 Water 24.93 copolymer of vinyl methyl ether and maleic anhydride (42% solution) 4.76 sodium monotluorophosphate 0.76 carbohydrate sodium 0.30 insoluble sodium metaphosphate 47.00 titanium dioxide 0.50 sodium laurylsiran 2.00 triclosan 0.30 flavoring substance 0.95

In the previous examples, improved results can be obtained even when triclosan is replaced by phenol, 2,2'-methylene-bis (4-chloro-6-bromophenol), eugenol or thymol and / or Gantrez is replaced by another type of AEA, such as is, for example, Carbopol (which is substantially colloidal, water-soluble polyacrylic acid polymers crosslinked by the addition of 0.75% to about 2.0% polyalylsaccharose or polyalylpentaerythritol), for example the product designated 934, or polymers of styrene phosphonic acid having a molecular weight ranging from about 3000 up to 10,000 such as β-styrenephosphonic acid polymer, copolymers of vinylphosphonic acid with β-styrenephosphonic acid and polymers of α-styrenephosphonic acid, sulfoacrylic acid oligomers or copolymers of maleic anhydride with ethyl acrylate in a ratio of 1: 1.

Príkladll

According to this example, the mobile phases of the dentifrice containing triclosan were prepared, the total composition of which is given in the following table:

component Content in% by weight A B Sorbitol (70%) 53,33 40.00 Water 40.48 39.15 Ganúez S * (14%) - 13.33 sodium hydroxide (50%) - 1.33 saccharin 0.40 0.40 sodium fluoride 0.32 0.32 flavoring substance 1.47 1.47 sodium laurylsiran 3, 33 3.33 triclosan 0.67 0.67

* synthetic anionic polycarboxylate-based product

The concentration of said ingredients in the dentifrice was 1.33% by weight, in addition, the dentifrice composition contained up to 25% by weight of the abrasive material required to replenish the detergent composition.

The mobile phases were tested for triclosan feed and retention on saliva-coated IIA discs. The results are shown in the following table.

Table - Triclosan feed to saliva-coated HA disc from diluted and undiluted mobile phase detergent

A B hi: triclosan weight 0.67 0.67 calculated ionic strength (M / L) 0,375 - pH 8.7 7.6 intake of undiluted triclosan (pg / disc) 55 122

The above results show a more than two-fold increase in the triclosan intake of formulation B containing Gantrez compared to the effect of formulation A without Gantrez.

Example 12

The supply of triclosan to HA disks from a 1: 1 dentifrice suspension supernatant was investigated, the dentifrice containing 0.5% by weight triclosan and 2.5% by weight sodium lauryl sulphate. The other ingredients are listed in the table as well as the results obtained.

Another component of a dentifrice Triclosan content in supernatant suspension 1: 1 (pg / ml) Triclosan intake (pg / disc) 25% by weight of hydrated SiO ₂ + 1.5 wt% Gantrez * 1,650 52 50% Alumina + 1.5% Gantrez * 1,905 74

A polycarboxylate-based anionic product

Supernatants of said detergent suspension and odor in a 1: 1 ratio were investigated for triclosan concentration and its delivery to saliva coated HA disks. The results show that using 50% alumina as the abrasive, the triclosan concentration is greatly increased at a large dilution, i.e., from 1.650 to 105, and thus the triclosan feed is also increased from 52 to 74.

Example 13

Mouthwashes of this composition were prepared that effectively reduced dental plaque formation by effectively increasing the uptake and retention of triclosan on the oral cavity surface.

component Parts by weight A B C D E Gantrez S-97 0.24 0.25 0.25 0.25 0.25 glycerol 15,00 10.00 15,00 10.00 15,00 ethanol 12.50 12.50 prepylénglykol 5.00 5.00 polyoxyethylene polyoxyethylene block copolymer; polyoxypropylene (Pluronic F108) 2.00 - sodium laurylsiran 0.20 0.20 0.20 triclosan 0.10 0.10 0.06 0.06 0.03 flavoring substance 0.40 0.40 0.40 0.40 0.40 water to 100.00 10.00 100.00 100.00 100.00

A copolymer of methyl vinyl ether and maleic anhydride having a molecular weight of 70,000.

Example 14

According to this example, the following liquid dentifrice compositions were prepared which also effectively reduced dental plaque formation by increasing the uptake and retention of triclosan on the oral cavity surface.

component Parts by weight A B C glycerol 20.00 20.00 - Gantrez S-97 0.3 0.3 0.3 high molecular weight polysaccharide containing mannose, glucose, potassium glucuronate and acetyl groups in an approximate molar ratio of 2: 1: 1: 1 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 laurosulphate 3.0 3.0 3.0 insoluble sodium metaphosphate 10.0 - 10.0 anhydrous dibasic calcium phosphate 1.0 - 2.5 flavoring substance 2.5 2.5 2.5 ethanol - - 10.0 triclosan 0.1 0.1 0.1

* methyl vinyl ether / maleic anhydride copolymer with a molecular weight of 70,000.

In the embodiments of the previous examples, improved results can also be obtained when triclosan is replaced by phenol, 2,2'-methylenebis (4-chloro-6-bromophenol), eugenol or thymol, and / or when Gantrez is replaced by another type of AEA such as Carbopol product designation 934 (which is essentially a product consisting of a colloidal, water-soluble polyacrylic acid polymer crosslinked by the addition of 0.75% to about 2.0% polyalylsaccharose or polyalylpentaerythritol as crosslinking agent) or styrene phosphonic acid polymers of molecular weight in the range of 3,000 to 10,000, such as polymers of β-styrenephosphonic acid, copolymers of vinylphosphonic acid and β-styrenephosphonic acid, polymers of α-styrenephosphonic acid or sulfomers of sulfoacrylic acid or also copolymers of maleic anhydride with ethyl acrylate in a ratio of 1: 1.

The invention has been described in connection with several preferred embodiments, but it will be apparent that many modifications may be envisaged which are obviously intended to be encompassed within the scope of the invention and will therefore form part thereof. Thus, the invention is not limited to the above embodiments.

Claims (35)

PATENT CLAIMS An anti-dental plaque composition for oral administration in the form of a gel-like or pasty dentifrice, liquid dentifrice, mouthwash, lozenge or chewing gum substantially free of a pyrophosphate anti-tartar composition comprising an oral delivery vehicle and an O; 0.015 to 5% by weight of a substantially water-insoluble non-cationic antibacterial agent dissolved in said vehicle in an effective amount against dental plaque formation, wherein the vehicle also comprises from about 0.005% to about 4% by weight of the average molecular weight promoting agent a weight of from 100 to 1,000,000, which comprises at least one acidic functional group with a sustaining release effect to promote the release of said antibacterial agent on the surfaces of teeth and gums in the oral cavity and at least one or ganic group of general formula: - O (X) n - R, in which: X is oxygen, nitrogen, sulfur, SO, SO ₂ , phosphorus, PO or silicon, R is a hydrophobic alkyl group, an alkylene group, an acyl group, an aryl group, an alkaryl group, and an aralkyl group containing from 1 to 12 carbon atoms or their inert substituted derivatives and n is 1 or zero, with a retarding effect to promote retention of said antibacterial agent tooth and gum surfaces in the oral cavity, wherein the AEA comprises natural and synthetic polymerizable monoiners, oligomers, homopolymers, copolymers consisting of two or more monomers, ionomers, block copolymers, cleaved copolymers or crosslinked copolymers, polymers containing polymers, polymers containing polymers, polymers containing polymers, polymers containing polymers, compounds, polymerized ethylenically unsaturated carboxylic acids, carboxyvinyl polymers, polysiloxanes, polyesters, polyurethanes, natural or synthetic polyamides. Oral administration composition according to claim 1, characterized in that it further optionally contains dissolving agents and / or polishing agents. Oral composition according to claim 1, characterized in that the composition is in the form of a dentifrice and contains 5 to 30% by weight of a silica or aluminum silicate polishing agent, and said antibacterial agent is present in an amount ranging from 0.25 to 0.35% by weight, further comprising a surfactant and a flavoring oil. The oral composition according to claim 1, wherein the composition is in the form of a dentifrice and contains 5 to 30% by weight of a silica or aluminate silicate polishing agent, said antibacterial agent being present in an amount of from 0, The composition for oral administration comprises a solubilizing agent for dissolving said antibacterial agent in saliva. The composition for oral administration of claim 4, wherein said antibacterial agent is present in an amount of from 0.05% to 0.25% by weight. The composition for oral administration of claim 4, wherein said antibacterial agent is present in an amount of from 0.35% to 5% by weight. The composition for oral administration of claim 6, wherein said antibacterial agent is present in an amount of from 0.35% to 0.5% by weight. The oral composition according to claim 1, wherein the oral composition is in the form of a creamy dentifrice containing 30 to 75% by weight of a water-insoluble dentally acceptable rinse aid. SK 280567 Br The composition for oral administration of claim 1, wherein the composition is in the form of a mouthwash or a liquid dentifrice, and said orally acceptable vehicle is an aqueous vehicle comprising at least one surfactant, a flavoring oil, or a nontoxic alcohol. The oral dentifrice composition of claim 1, wherein the dentifrice composition is present in an amount ranging from 0.5 to 5% by weight. A composition for oral administration in the form of a dentifrice composition according to claim 1 or 10, characterized in that it contains flavoring oil in an amount ranging from 0.1 to 5% by weight. The composition for oral administration of claim 9, wherein the composition is in the form of a mouthwash and said aqueous vehicle comprises ethanol and the weight ratio of water to ethanol is in the range of 1: 1 to 20: 1. A composition for oral administration according to claim 9, wherein the composition is in the form of a liquid dentifrice containing from 0.3 to 2.0% by weight of a high molecular weight polysaccharide of greater than 1,000,000 containing mannose. glucose, potassium glucuronate and acetyl groups in a ratio of 2: 1: 1: 1 as a suspending and thickening agent, and further 10 to 20% by weight of the polishing agent. The composition for oral administration of claim 1, wherein said antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated sahcylanilides, benzoic acid esters, halogenated carbanilides, and phenolic compounds. The composition for oral administration of claim 14, wherein said antibacterial agent is a halogenated diphenyl ether. The composition for oral administration of claim 15, wherein said halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. The composition for oral administration of claim 2, wherein said solvent is present in an amount ranging from 0.5 to 50% by weight, selected from the group consisting of propylene glycol, dipropylene glycol, hexylene glycol, methyl cellosol, ethyl cellosol, vegetable oils and waxes containing at least 12 carbon atoms, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate. The oral composition of claim 17 in the form of a dentifrice composition, wherein said solvent comprises propylene glycol present in an amount of 0.5% by weight. The composition for oral administration of claim 1 or 17, comprising a polishing agent selected from the group consisting of sodium metaphostat, calcium phosphate, dibasic calcium phosphate dihydrate, anhydrous dibasic calcium phosphate, magnesium pyrophosphate, magnesium phosphate, phosphate calcium carbonate, aluminum silicate, hydrated alumina, silica, bentonite, and mixtures thereof, and this oral composition is in the form of a cream dentifrice. The oral dentifrice composition of claim 19, wherein said polishing agent is a calcium hydrogen phosphate wire or hydrated alumina. 21. A composition for oral administration according to claim 1, wherein said sustained release group is selected from the group consisting of carboxylic acids, phosphonic acids, folinic acids and sulfonic acids and salts thereof, and mixtures thereof. . The composition for oral administration of claim 1, wherein said antibacterial enhancing agent is an anionic polymer comprising a series of release-enhancing and retention-enhancing groups. A composition for oral administration according to claim 22, wherein said anionic polymer comprises a chain comprising repeating units with at least one carbon atom. The composition for oral administration of claim 23, wherein each unit comprises at least one release promoting group attached to the same atom, adjacent atom, or other atom in the chain. The composition for oral administration of claim 21, wherein the release promoting group is a carboxyl group or a salt derived therefrom. The composition for oral administration of claim 25, wherein the antibacterial enhancing agent is a maleic acid or anhydride copolymer with another inert, ethylenically unsaturated polymerizable monomer. The composition for oral administration of claim 26, wherein said second n monomer of said copolymer is methyl vinyl ether contained in a molar ratio ranging from 4: 1 to 1: 4 based on the amount of maleic acid or anhydride thereof. The composition for oral administration of claim 27, wherein said copolymer has a molecular weight ranging from 30,000 to 1,000,000 and is present in an amount ranging from 0.1 to 2% by weight. The composition of claim 28, wherein said polymer has an average molecular weight of 70,000. 30. The composition of claim 21, wherein said release enhancing group is a group derived from phosphonic acid or a salt thereof. 31. The composition of claim 30, wherein the antibacterial enhancing agent is a poly (p-styrene phosphonic acid) polymer or a poly (.alpha.-styrene phosphonic acid) or a copolymer of any of said styrene phosphonic acids with another ethylenically unsaturated monomer. The oral composition of claim 21, wherein said antibacterial promoting agent has an average molecular weight in the range of from 1,000 to 1,000,000 and is substantially free of the water-soluble salt of synthetic anionic linear alkali metal polycarboxylates. or ammonia with a molecular weight ranging from 1000 to 1,000,000. SK 280567-6 The composition for oral administration of claim 32, wherein said antibacterial agent is present in an amount ranging from 0.25% to 0.5% by weight. 34. The composition for oral administration of claim 32, wherein said antibacterial agent is present in an amount ranging from 0.25% to 0.35% by weight. The composition for oral administration of claim 33 or 34, wherein said composition comprises a polishing agent based on silicon dioxide or aluminum silicate.