SK280834B6 - Oral composition - Google Patents

Abstract

An oral composition contains an orally acceptable vehicle, an effective anticalculus amount in the range of 0.1 to 3 wt.% of at least one linear molecularly dehydrated polyphosphoric salts as essential anticalculus agent, from 0.01 to 5 wt.% of non-cationic antibacterial agent, and up to 4 wt.% of an antibacterial activity enhancing agent. Said antibacterial activity enhancing agent-to-polyphosphoric ion weight ratio ranges between 1.6 : 1 to 2.7 : 1.

Description

Technical field

The invention relates to an oral composition, in particular a composition for oral administration having antibacterial action and against plaque and calculus formation. The oral composition comprises a pyrophosphate (or pyrophosphate) anti-tartar compound and a compatible antibacterial agent effective in inhibiting plaque, the antiplaque efficacy being optimized by the presence of an antibacterial efficacy enhancing agent promoting the release of the antibacterial agent and its retention on the oral cavity surface.

BACKGROUND OF THE INVENTION

U.S. Pat. Nos. 4,627,977 (Gaffar et al.), 4,515,772 (Parran et al.) And 4,323,551 (Parran) disclose oral compositions containing various polyphosphates. In Gaffar et al. Linear dehydrated polyphosphate salts are used in conjunction with a fluoride ion source and a synthetic linear polymeric polycarboxylate to prevent calculus formation. In European patent application no. 89 200 710.5 discloses an increase in anti-tartar efficacy with a small amount of a linear, molecularly dehydrated polyphosphate salt in conjunction with a fluoride ion source and an increased amount of a synthetic linear polymeric polycarboxylate.

U.S. Pat. 4,515,772 and 4,323,551 use a water-soluble alkali metal pyrophosphate (pyrophosphate) alone or in admixture with a tetraalkalic metal pyrophosphate.

Oral agents that prevent the formation of tartar on the surface of the teeth are highly desirable because tartar is one of the causes of disorders of function of the periondontal structures. Reducing tartar therefore improves oral hygiene.

Dental coatings are a prior stage of tartar formation. However, unlike tartar, plaque can form on any part of the tooth, especially at the tooth and gum line. Since the coating is virtually invisible, it remains adhering to the tooth surface and becomes the cause of gum inflammation.

Accordingly, it would be highly desirable to use antimicrobial agents which are known to reduce the formation of coatings in oral anti-tartar formulations. U.S. Pat. No. 4,022,550 (Vinson et al.) Discloses the use of a zinc ion-releasing compound as an anti-tartar agent as well as antibacterial agents to retard bacterial growth in dental plaques. Described herein is the use of a variety of antibacterial agents together with zinc compounds, for example, cationic agents such as guanides and quaternary ammonium compounds, as well as non-cationic agents, such as halogenated salicylamilides and halogenated hydroxydiphenyl ethers.

Until now, cationic antibacterial materials such as chlorhexidine and benzethonium chloride and acetylpyridinium chloride have been thoroughly investigated in which they have been tested as anti-dental agents. However, although they have been used with zinc-containing compounds that prevent the formation of tartar, they are not effective when used concurrently with anionic materials such as anti-tartar polyphosphates. This ineffectiveness is considered to be very surprising given that polyphosphates are chelating agents, and it is known that chelation usually increases the effectiveness of cationic antibacterials as described in the publication. Disinfection, Sterilization and Preservation, 2nd Edition, Black, 1977, p. 215. The quaternary ammonium compound is a mouthwash component for dental plaque suppression containing pyrophosphate (pyrophosphate) according to U.S. Pat. No. 4,323,551 (Parran) and the use of bisbiguanide as a dental plaque is suggested in the pyrophosphate-containing oral composition of U.S. Pat. No. 4,515,772 to Parran et al.

Given the unexpected incompatibility of antibacterial compounds of a cationic nature with polyphosphates used as anti-tartar agents, it was quite unexpected that other antibacterial agents not yet tested could be effective in this regard.

SUMMARY OF THE INVENTION

The present invention is based on the discovery that certain antibacterial compounds are effective in oral anti-tartar compositions comprising a linear, molecularly dehydrated pyrophosphate (pyrophosphate) salt, a fluoride ion source and said antibacterial agent to inhibit dental formation. coating (or plaque).

SUMMARY OF THE INVENTION It is an object of the present invention to provide a composition which effectively reduces the formation of tartar and, at the same time, optimally reduces the formation of dental plaque.

It is an object of the present invention to provide an oral composition which suppresses the formation of dental plaque and calculus, while at the same time effectively reducing the incidence of gum inflammation.

Other advantages of the oral composition of the invention will be described in more detail in the following description and example of the invention.

The essence of the oral composition of the present invention comprises:

- an orally acceptable vehicle,

% - 1 to 2.5 wt. % of a substance containing 0.1 to 3 wt. at least one linear molecular dehydrated polyphosphate salt as an anti-tartar agent,

0.01 to 5 wt. a non-cationic antibacterial agent; and

up to about 4% by weight of an antibacterial agent, wherein the weight ratio of said antibacterial agent to said polyphosphate ion is in the range of from 1.6: 1 to 2.7: 1.

Said antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated salicylanilides, benzoic acid esters, halogenated carbanilides and phenolic compounds. The halogenated diphenyl ether may be 2,4,4'-trichloro-2'-hydroxyphenyl ether. The phenolic compound may be a compound selected from phenol, thymol, eugenol and 2,2 ' -methylene-bis (4-chloro-6-bromophenol). The amount of antibacterial agent ranges from 0.25% to 0.5% by weight.

The linear molecular dehydrated polyphosphate salt may be an alkali metal pyrophosphate, for example tetrasodium pyrophosphate.

The weight ratio of polyphosphate ion to antibacterial enhancer ranges from 1.7: 1 to 2.3: 1.

As the vehicle, the oral composition may contain water, a humectant and a gelling agent, and further a dentally acceptable water-insoluble polishing agent.

In the form of a mouthwash, the composition may contain water and a non-toxic alcohol as a vehicle.

The antibacterial enhancing agent may have an average molecular weight in the range of about 100 to about 1,000,000, comprising at least one acidic functional group promoting delivery of the substance, selected from the group consisting of carboxylic, phosphonic, phosphinic, sulfonic, salts of these substances and mixtures of these substances and at least one organic retention promoting function of the general formula:

- (X) '- R, in which:

X is oxygen, nitrogen, sulfur, SO, SO ₂ , PO or Si,

R represents a hydrophobic alkyl group, an aryl group, an alkenyl group, an acyl group, an alkaryl group, an aralkyl group, a heterocyclic group or derivatives thereof with inert groups, and n is 1 or zero.

The antibacterial promoting agent may be an anionic polymer comprising a series of release promoting groups and organic retention groups containing a chain of repeating units each containing at least one carbon atom, each unit containing at least one release promoting group and at least one organic retention promoting group attached to the same atom or adjacent atom, or to another atom in the chain. The release promoting group may comprise a carboxyl group or a salt thereof.

Further, the antibacterial enhancing agent may be a copolymer of maltinic acid or maleic anhydride with another ethylenically unsaturated polymerizable monomer or a salt thereof. The other monomer may be methyl vinyl ether in a molar ratio with maleic acid or maleic anhydride in a ratio of from 4: 1 to 1: 4 and with an average molecular weight of about 30,000 to 1,000,000, preferably 70,000.

Further, the release promoting moiety may comprise a phosphonic group or a salt thereof and may be poly-β-styrene phosphonic acid, poly-α-styrene phosphonic acid or a copolymer of any styrene phosphonic acid with another styrene phosphonic acid or other inert polymerizable ethylenically unsaturated monomer or salts thereof. it has a molecular weight ranging from about 1,000 to about 30,000.

The oral composition of the invention may further comprise a fluoride ion source.

In one embodiment, the invention relates to an oral composition comprising a vehicle acceptable for oral administration of an effective amount of at least one linear molecular dehydrated pyrophosphate salt as an anti-tartar agent in an amount ranging from about 1% to 3% by weight of the effective amount. a substantially water-insoluble, non-cationic antibacterial agent effective against dental plaque formation and the presence of not more than 4% by weight of an agent promoting bacterial efficacy and improving the delivery and retention of the agent to the oral cavity surface is desired; the ratio of pyrophosphate ions to antibacterial agent enhancing agent ranges from greater than 0.72: 1 to less than 4: 1, for example in the range of 1: 1 to 3.5: 1, especially in the range of 1.7 : 1 to 2.3: 1 and most preferably in the range 1.9: 1 to 2: 1. For example, when tetrasodium pyrophosphate (TSPP) is used, which releases about 1.3% by weight of the pyrophosphate ion, it is used simultaneously with 2.5% by weight of an antibacterial agent to provide a highly advantageous value of said weight ratio of 1.9: 1.

The following are typical examples of non-cationic antibacterial agents that are particularly advantageous in terms of plaque formation, efficacy, safety in use and ease of formulation. Halogenated diphenyl ethers

2 ', 4,4'-trichloro-2-hydroxydithenyl ether (triclosan), 2,2'-dihydroxy-5,5'-dibromodiphenyl ether,

Halogenated salicylamides 4 ', 5-dibromosalicylanilide, 3,4', 5-trichlorosalicylanilide, 3,4 ', 5-tribromosalicylanilide, 2,3,3', 5-tetrachlorosalicylanilide, 3,3,3 ', 5-tetrachlorosalicylanilide,

3,5-dibromo-3'-trifluoromethylsalicylanilide, 5-n-octanoyl-3'-trifluoromethylsalicylanilide,

3,5-dibromo-4'-trifluoromethylsalicylanilide,

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'-trichlorocarbanilide,

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). These phenolic compounds include, but are not limited to: phenol,

2-Methylphenol

3-methylphenol,

4-Methylphenol

4-ethylphenol,

2,4- dimethylphenol,

2.5-dimethylphenol,

3,4-dimethylphenol,

2,6-dimethylphenol,

4-n-propyl phenol,

4-n-butylphenol, 4-n-amylphenol, 4-tert-amylphenol, 4-n-hexylphenol,

4-n-heptylphenol,

2-methoxy-4- (2-propenyl) phenol (eugenol), 2-isopropyl-5-methylphenol (thymol).

Mono- and polyalkyl- and arylalkyl halophenols methyl-p-chlorophenol, ethyl-p-chlorophenol, n-propyl 1-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, t-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-chlórfcnol,

methyl-p-chlorophenol,

3,5-dimethyl-p-chlorophenol,

6-ethyl-1-3-methyl-p-chlorophenol, 6-n-propyl-3-methyl-p-chlorophenol, 6-isopropyl-3-methyl-p-chlorophenol, 2-ethyl-3,5-dimethyl-p -chlorophenol, 6-sec-butyl-3-methyl-p-chlorophenol, 2-isopropyl-3,5-dimethyl-p-chlorophenol, 6-dimethyl-3-methyl-p-chlorophenol, 6-dimethyl-2-ethyl 3-methyl-p-chlorophenol, 2-sec-amyl-3,5-dimethyl-p-chlorophenol, 2-diethylmethyl-3,5-dimethyl-p-chlorophenol, 6-sec-octyl-3-methyl-p -chlorophenol, p-bromophenol, methyl-p-bromophenol, ethyl-p-bromophenol, n-propyl-p-bromophenol, n-butyl-p-bromophenol, n-amyl-p-bromophenol, sec-amyl-p-bromophenol , n-hexyl-p-bromophenol, cyclohexyl-p-bromophenol, o-bromophenol, tert-amyl-o-bromophenol, n-hexyl-o-bromophenol, n-propyl-m, m-dimethyl-o-bromophenol, 2 -fcnylfenol.

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

4-chloro-3,5-dimethylphenol, 2,4-chloro-3,5-dimethylphenol,

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

5-Methyl-2-pentylphenol

4-Isopropyl-3-methylphenol

5-chloro-2-hydroxydiphenylmethane. Resorcinol and its derivatives resorcinol, methyl resorcinol, ethyl resorcinol, n-propylcresorcinol, n-butyl resorcinol, n-amylresorcinol, n-hexylresorcinol, n-heptylresorcinol, n-octylresorcinol, n-nonylresorcinol, phenylresorcinol, fresorresorcinol, fresorresorcinol, benzylresorcinol, benzenesorcinol, benzylresorcinol, benzylresorcinol -chloro-2,4-dihydroxydiphenylmethane, 4'-chloro-2,4-dihydroxydiphenylmethane, 5-bromo-2,4-dihydroxydiphenylmethane, 4'-bromo-2,4-dihydroxydiphenylmethane.

Bisphenyl compounds

Bisphenol A, 2,2'-methylenebis (4-chlorophenol), 2,2'-methylenebis (3,4,6-trichlorophenol) (hexachlorophene), 2,2'-methylenebis (4-chloro-6-bromophenol), bis (2-hydroxy-3,5-dichlorophenyl) sulfide; bis (2-hydroxy-5-chlorobenzyl) sulfide.

The antibacterial agent is present in the oral composition in an amount effective against dental plaque formation, usually in the range of from 0.01% to 5% by weight, in particular in the range of 0.03% to 1% by weight, preferably in the range of 0, 25% to 0.5% by weight, and most preferably in the range of 0.25% to 0.35% by weight. The antibacterial agent should be substantially insoluble in water, which means that its solubility in water is less than about 1% by weight at 25 ° C, and may also be less than 0.1% by weight. If an ionizable group is present, the solubility of such a substance is determined at a pH at which no ionization occurs.

Of the halogenated diphenyl ethers, the preferred compound is triclosan. Among the phenolic compounds, phenol, 2,2'-methylenebis (4-chloro-6-bromophenol), thymol and eugenol are particularly preferred. However, the most preferred antibacterial agent effective against plaque formation 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 mentioned in DE 3,532,860 as a substance which can be combined with compounds containing copper. 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 and can also be used in a zinc containing composition a salt as described in European Patent 161,988 (Lane et al), and a dentifrice composition containing zinc citrate trihydrate, which composition is described in European Patent No. 5,950,549. 161,899 (Saxton et al.).

Linear molecular dehydrated pyrophosphate (and generally polyphosphate or polyphosphate) salts for use as an anti-tartar agent are known substances which are generally used in the form of their wholly or partially neutralized water-soluble alkali metal salts, for example potassium, preferably sodium, or also ammonium salts and mixtures thereof. Examples of such materials are sodium hexametaphosphate, disodium pyrophosphate, trisodium and tetrasodium, corresponding to the potassium salt and the like. Linear polyphosphates can be represented by the general formula (NaPO ₃ ) _n , wherein n is 2 to about 125. The oral compositions of the present invention may be used in an amount of from about 0.1% to about 3% by weight, usually from about 1% to about 1%. % to 2.5% by weight, preferably in the range from 1.5% to 2% by weight. When n has a value of at least 3, said polyphosphates are of glassy nature.

Particularly suitable anticalculus agents are tetraalkali metal pyrophosphates (or pyrophosphates) and mixtures thereof, for example tetrasodium pyrophosphate (or pyrophosphate), tetrapotassium pyrophosphate and mixtures thereof. Thus, the oral composition may comprise an anti-tartaric agent of the pyrophosphate (and generally polyphosphate) type, which is substantially free of dipotassium pyrophosphate or substantially free of a mixture of dipotassium pyrophosphate and potassium pyrophosphate wherein the ratio of potassium or sodium pyrophosphate to pyrophosphate is 3: higher. Particularly effective is an anti-tartar agent comprising about 2% by weight of tetrasodium pyrophosphate based on the total weight of the oral composition.

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, even 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, hydrogen-forming). The molecular weight of these compounds may generally be in the range of about 100 to about 1,000,000, preferably about 1,000 to about 1,000,000, particularly preferably in the range of about 2000 or about 2,500 to about 250,000 or about 500,000 .

These AEAs usually contain at least one group to aid in the delivery of an active agent that is acidic in nature, such as a sulfonic, phosphonic or, preferably, 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 expressed with the general formula:

- (X) '- 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 represents 0, 1 or a number 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 AEA function in promoting the delivery of the antibacterial agent to the oral mucosal surface and retention of the agent on the oral mucosal surface. wherein the "inertly substituted derivatives" can be groups substituted by a halogen atom such as chlorine, bromine, iodine or carbocycle 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) nR _____________________________________________________________________________ Methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl , acetyl, benzoyl, butyryl, terephthaloyl, etc.,

O ethoxy, benzyloxy, thioacetoxy, phenoxy, carbethoxy, carbobenzyloxy, etc.,

N ethylamino, diethylamino, propylamido, benzylamino, benzoylamino, phenylacetamide, etc.,

S thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenythioacetyl, thiobenzoyl, etc., butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, thioisobutyl, thiobenzyl, thiophenyl, thiophenyl, thiophenyl, thiophenyl;

SO ₂ butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonyl, etc.,

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

PO diethylphosphinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, methylbenzylphosphinoxy, methylphenylphosphinoxy, etc., trimethylsilyl, dimethylbutylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl, dimethylsilyl.

When used in an oral formulation, the group promoting the delivery of an antibacterial agent to the oral cavity surface, i.e., the tooth and gum surfaces, is a substance that associates with adhesion, cohesion or otherwise with AEA (containing the antibacterial agent) to achieve "delivery" an antibacterial agent to this surface. The organic group that promotes retention of the antibacterial agent on this surface is generally a hydrophobic group that binds or otherwise attaches 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 by physically attaching the agent to the AEA, particularly when the AEA is a crosslinked polymer, the structure of which itself increases the number of sites to effect this binding, respectively. connection. The presence of higher molecular weight moieties and the presence of several 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.

In a preferred embodiment, the AEA is an anionic polymer consisting of a chain or backbone containing repeating units, each containing at least one carbon atom and preferably at least one directly bonded or indirectly bonded attachment monovalent group to promote the delivery of the active antibacterial agent, and at least one directly or indirectly attached, monovalent attachment group promoting retention of the active antibacterial agent, i.e. geminally, vicinally 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 and / or antibacterial retention aid groups and / or other divalent atoms or groups as linkers in the polymer chain instead of, or in addition to, carbon atoms as crosslinking moieties.

It is contemplated that all of the AEA ingredients mentioned herein that do not contain both antibacterial agent delivery groups and retention groups of the antibacterial agent may, and preferably are, chemically modified in such a way that such types of agents are obtained. AEAs, which preferably comprise both of these types of groups and more preferably a full range of these types of groups. In the case of preferred polymeric AEAs, it is desirable, in order to maximize the effect and promote the delivery of the antibacterial agent to the oral cavity surface, that the repeating units in the polymer chain or polymer backbone containing acidic groups promoting antibacterial agent delivery are at least about 10% by weight of the polymer. at least about 50% by weight, even more preferably at least about 80% by weight, up 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 polymer molecule. An example of these AEAs are poly (vinylphosphonic acid) containing units of formula (I):

- [CH ₂ -CH] I (I).

PO3H2

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):

- [CH-CH 3 I (II).

ch ₃ after ₃ h ₂

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

- [CH-CHI I (III)],

Ph PO ₃ H wherein pH is a phenyl group, wherein the antibacterial agent-promoting phospho group and the antibacterial agent-retention phenyl group are bonded to vicinal carbon atoms in the chain, or a β-styrenephosphonic acid copolymer with vinylphosphonyl chloride having units of formula (III) ) with units of formula (I), see above in alternating or statistical order, or poly (α-styrenephosphonic acid) containing units of formula (IV):

ph

I - [CH ₂ -C -I (IV),

PO ₃ H ₂ in which both the feeder and retention groups of the antibacterial are bonded to the same carbon atom in the chain.

These styrene-phosphonic acid polymers and copolymers thereof with other inert, ethylenically unsaturated monomers have a molecular weight in the range of about 2000 to about 30,000, preferably in the range of about 2500 to about 10,000. These "inert" monomers do not adversely affect the intended function of any polymer used in the AEA of the invention.

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

- [(CH ₂ ) ₁₄ CHPO ₃ H ₂ ] _n - (V), in which n can be, for example, an integer with a value such that the polymer of formula (V) has a molecular weight of about 3000, and sodium (poly (butene) -4,4-diolosonate) with units of formula (VI):

- [CH ₂ -CH] I (VI),

CH ₂ -CH <(PO ₃ Na ₂ ) ₂ and poly (allyl-bis (losolylethylamine)) with units of formula (VII):

- [CH ₂ -CH] I (VII).

CH ₂ -N? (C ₂ H ₄ PO ₃ H ₂ ) ₂

Other polycloned polymers such as poly (allylolyl acetate), polycloned polymethacrylate, etc. as well as the geminal diacidate polymers disclosed in European patent no. 321233, can be used as AEAs, provided they contain or are modified to contain both types of said groups.

According to one aspect of the present invention, the oral composition comprises an orally acceptable vehicle, an agent effective to promote the antibacterial effect of the antibacterial agent used, having an average molecular weight ranging from about 1000 to about 1,000,000, comprises at least one functional group that promotes releasing and delivering an antibacterial effect and at least one organic group that promotes retention of antibacterial effects, said agent comprising said groups being free or substantially free of a synthetic anionic linear polymeric polycarboxylate with an alkali metal or an ammonium salt of said polycarboxylate having a molecular weight ranging from about 1000 to about 1,000,000, and a pyrophosphate (or dicalcium) anti-tartar agent, such as a mixture of potassium and sodium salts, wherein the ratio of potassium to sodium the sodium in said composition is in the range of up to about 3: 1 or less, such as in the range of about 0.37 to about 1.04: 1.

According to another preferred embodiment, said AEA may comprise a synthetic anionic polycarboxylate polymer which is also an inhibitor of the alkaline phosphatase enzyme. Synthetic anionic 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.). But only in U.S. Pat. No. 4,627,977 to Gaffar et al. Discloses the use of these polycarboxylates to inhibit the hydrolysis of pyrophosphate (or pyrophosphate) anti-tartar agents by the combination of a fluoride ion source compound. It should be noted, however, that the synthetic anionic polymeric polycarboxylates cited in several patents when they contain defined retention-enhancing groups or are not modified by these groups are effective AEAs that can thus be used in the oral compositions and preparation processes of the invention. These publications are reference materials in the context of the present invention.

Said synthetic anionic polycarboxylates are used many times in the form of free acids or preferably in the form of partially neutralized salts or even preferably in the form of completely neutralized salts which are water-soluble or water-swellable (hydratable form, gel-forming form), preferably alkaline salts (such as potassium salt or preferably sodium salt) or ammonium salts. Preferred are copolymers of maleic anhydride or maleic acid with another polymerizable ethylenically unsaturated monomer in a ratio of 1: 4 to 4: 1, preferably a methyl vinyl ether / maleic anhydride copolymer having a molecular weight ranging from about These copolymers are available under the designation Gantrez, such as AN 139 (500,000 molecular weight), AN 119 (250,000 molecular weight), and preferably S-97 with pharmaceutical grade (70,000 molecular weight) , manufacturer GAF Corporation.

Other AEA-active polymeric polycarboxylates which contain or are modified by retention-enhancing groups include, for example, those disclosed in U.S. Pat. No. 3,956,480 mentioned above, in particular copolymers of maleic anhydride with ethyl acrylate in a ratio of 1: 1, further with hydroxyethyl methacrylate, 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 useful polymeric polycarboxylates are disclosed in U.S. Pat. Nos. 4,138,477 and 4,183,914 and containing or modified to contain antibacterial agent retention groups which are modified to include these groups are copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic acid, polyitaconic acid and polymaleic acid, and sulfoacrylic oligomer whose molecular weight is very low, about 1000, and these products are available under the name Uniroyal ND-2.

In general, retention-promoting groups which contain polymerizable olefinically or ethylenically unsaturated carboxylic acids containing an activated olefinic carbon-carbon double bond and at least one carboxyl group, i.e. an olefinic double bond, which is easily functional in polymerization due to its presence in the monomeric molecule either at the α-β position relative to the position of the carboxyl group or as part of the terminal methylene group. Illustrative 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, mucylic acid, mucylic acid itaconic 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 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% polyallyl sucrose or polyallylpentaerythritol as crosslinker. The crosslinked structures and crosslinks 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 crosslinked with less than 0.2% divinyl glycol, with the lower proportion, molecular weight and / or hydrophobicity of the crosslinking 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 an antibacterial agent.

Synthetic anionic polymeric polycarboxylates as a constituent of the compositions of the invention are most commonly of the hydrocarbon type optionally containing halogen and O-containing moieties and bonds, such as ester, ether and hydroxyl groups, as substituents, usually present in these compositions in an approximate amount up to 4% by weight (usually at least about 0.05% by weight).

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

Illustrative examples of AEAs containing phosphinic acid and / or sulfonic acid groups that promote antibacterial agent delivery include polymers and copolymers containing units or moieties derived from the polymerization of vinylphosphonic or allylphosphonic acid and / or sulfonic acid, optionally substituted on one or two (or three) carbon atoms by organic retention groups, such as those of the formula - (X) _n -R as defined above. 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 with respect to active synthetic anionic polymeric polycarboxylates. As will be noted, in these agents and other polymeric AEA agents suitable for the purposes of the present invention, usually only one acid group promoting the introduction of the antibacterial agent is bound to any carbon atom or to another atom in the polymer backbone or to branching this backbone. It is also possible to use polysiloxanes containing pendant groups to promote the delivery of the antibacterial agent and the retention of the agent or modified to contain these groups as AEAs. The ionomers containing the abovementioned groups promoting the retention of the antibacterial agent and the retention of the antibacterial agent or modified to contain these groups are equally effective as AEAs. These ionomeric substances are described in Kirk Orhmer Encyclopedia of Chemical Technology, Third Edition, Supplement Volume, John Wiley & 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 if they contain or have been modified to contain retention-promoting groups.

When the oral composition is produced by first dissolving the pyrophosphate (generally polyphosphate) and the antibacterial in a solvent with a wetting agent and then gradually adding AEA, especially polycarboxylate, the solution becomes clear and can be characterized as a "microemulsion" . By increasing the amount of polycarboxylate so that the finished oral composition contains at least 2.2% by weight of the latter, the solution becomes cloudy and can be characterized as a "macroemulsion". In compositions of this type, the anti-bacterial effect of anti-coatings achieves an optimum degree.

The desired weight ratio of the substantially water-insoluble non-cationic antibacterial agent to the anti-tartar polyphosphate agent is greater than 0.72: 1 to less than 4: 1, for example about 1: 1 to about 3.5: 1 preferably about 1.6: 1 to about 2.7: 1.

In order to optimize the anti-calculus effect of the oral composition, it is desirable to include inhibitors against the enzymatic hydrolysis of pyrophosphate (generally polyphosphate). These agents are typically a source of fluoride ions, the amount of which is sufficient to provide between 25 ppm and 5000 ppm of fluoride ions, and about 3% or more of the synthetic anionic polymeric polycarboxylate having a molecular weight ranging from about 1000 to about

000,000, preferably about 30,000 to about 500,000.

The fluoride ion source or fluorine-providing component, such as the acid phosphatase and pyrophosphatase inhibitor component, are generally known anti-tartar agents. These compounds may be sparingly soluble in water or may be completely soluble in water. These substances are characterized by their ability to release fluoride ions into water and are not intended to have a substantially undesirable effect on the action of the other components of the formulation. These include, for example, inorganic fluorides such as 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 more 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 non-toxic amount, typically in the range of about 0.0005% to about 3.0% weight. In a dentifrice composition, such as tooth gel, toothpaste (including creams), tooth powder or dental tablets, an amount of said substance that releases about 5,000 ppm of fluoride ion based on the weight of the composition is acceptable. Any minimum amount of this material may be used in the present case, but it is preferred to use an amount that releases about 300 to about 2000 ppm, preferably 800 ppm to 1500 ppm of 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.

In oral compositions such as mouthwashes, sublingual lozenges and chewing gums, the fluorine-releasing compound is usually present in an amount sufficient to release up to about 500 ppm of fluoride ions, preferably 25 to 300 ppm of fluoride ions. Typically, the compound is used in an amount ranging from about 0.005% to about 1.0% by weight.

In certain highly preferred embodiments of the oral composition of the invention, the composition is of a substantially liquid nature, for example, a mouthwash or a composition used to rinse the oral cavity. In such compositions, the vehicle is typically a mixture of water and an alcohol, optionally preferably containing a humectant as described above. The weight ratio of water and alcohol is generally in the range of 1: 1 to 20: 1, preferably in the range of 3: 1 to 10: 1, and in particular in the range of 4: 1 to 6: 1. preparations of this type range from 70% by weight to about 99.9% by weight. A typical alcohol is ethanol or isopropanol, ethanol is preferred.

A liquid composition of this type or other composition of the invention typically has a pH in the range of about 4.5 to about 9, typically in the range of about 5.5 to about 8. Preferred

The pH range is from 6 to 8.0. It should be noted that the composition of the invention can also be used orally at a pH of less than 5 without substantial decalcification or other damage to the enamel. The pH can be controlled with an acid (such as citric or benzoic acid), bases (such as sodium hydroxide) or buffers (such as sodium citrate, sodium benzoate, sodium carbonate or sodium bicarbonate, sodium hydrogen phosphate, dihydrogen phosphate sodium and the like).

In other preferred embodiments, the oral form of the present invention may be a substantially solid or pasty substance, such as a toothpaste, a dental tablet or a dentifrice, i.e. a toothpaste (dental cream) or a goal dentifrice. The vehicle for these solid or pasty oral dentifrices comprises a dentally acceptable polishing material, examples of which include water-insoluble sodium or potassium metaphosphate, calcium phosphate, anhydrous calcium phosphate, calcium pyrophosphate, magnesium orthophosphate, magnesium phosphate, calcium carbonate, alumina, calcined alumina, aluminum silicate, zirconium silicate, silica, bentonite and mixtures thereof. These suitable polishing materials also include the thermosetting resins described in U.S. Pat. No. 3,070,510 of December 15, 1962, such as melamine-, phenol- and urea-formaldehyde resins and cross-linked polyepoxides and polyesters. A preferred polishing material is crystalline silica having a particle size of up to about 5 µm, an average particle size of up to about 1.1 µm, and a surface area of up to about 50,000 cm ² / g, which may be silica gel or colloidal silica and complex amorphous alkali metal aluminosilicates. .

In the case where clear gels are used, it is particularly suitable to use colloidal silicon dioxide as a polishing material, such as those supplied under the Syloid designation, such as Syloid 72 and Syloid 74 or under the designation Santocel, such as Santocel 100, or o alkali metal aluminosilicate complexes which are particularly suitable or have a refractive index close to that of liquid gelling agent systems (including water and / or humectants or solubilizers) generally used in dentifrices.

Many of the so-called "water-insoluble" polishing materials are anionic in nature and, moreover, contain a small amount of soluble material. Insoluble sodium metaphosphate can be obtained by any suitable method, for example according to: Thorpes Dictionary of Applied Chemistry, Vol. 9, ^4'h Edition, p. Another example of suitable materials are some forms of insoluble sodium metaphosphate, known as Madrell's salt and Kurrol's salt. These metaphosphate salts have only 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 includes probably soluble sodium trimetaphosphate, can be reduced or removed if necessary by washing with water. Insoluble alkali metal metaphosphates are usually used in the form of powders, their particle size being such that only a maximum of 1% of the material has a particle size greater than 37 µm.

The polishing material is usually present in the solid or pasty compositions of the invention in an amount of 10% to 99% by weight, preferably in an amount of 10% to 75% by weight in the toothpaste and 70% to 99% by weight in the tooth powder. In the case of a silicon-based polishing material, it is usually present in the toothpaste in an amount ranging from 10% to 30% by weight. Other polishing materials are typically comprised in the toothpastes in the range of 30% to 70% by weight.

In a toothpaste, the liquid vehicle may contain water and an additional humectant, usually in an amount ranging from 10% to 80% by weight of the composition. Examples of humectants / carriers are preferably glycerol, propylene glycol, sorbitol and polypropylene glycol. Also preferred are liquid mixtures of water, glycerol and sorbitol. In clear gels, where the refractive index is an important value, about 2.5% to 30% by weight of water, 0 to 70% by weight of glycerol and 20 to 80% by weight of sorbitol are preferably used.

Toothpastes, creams or gel cleansers generally contain a natural or synthetic thickener or gel-forming agent in an amount of about 0.1% to about 10% by weight, preferably about 0.5% to about 5% by weight. A preferred thickener is, for example, synthetic hectorite, a synthetic colloidal magnesium alkali metal silicate complex, which is available, for example, as Laponite (e.g., CP, SP 2002 or D, Laportc Industries Limited). Laponite D analysis gave a composition (in% by 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.

Other suitable thickeners are Irish moss, carrageenan, iota-carageenan, tragacanth yarn, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, sodium carboxymethylcellulose, such as carboxymethylcellulose, such as carboxymethylcellulose; for example, finely crushed Syloid (e.g., product under the designation 244). In some dentifrice compositions of the invention, particularly when more than 0.35% by weight of the water-insoluble antibacterial agent and silica polishing agent are used in an amount of less than 30% by weight, it may be appropriate to add a substance to dissolve the antibacterial agent . Such dissolving agents, including humectants, may be some polyols such as propylene glycol, dipropylene glycol and hexylene glycol, whole-cell oils such as methylcellulose and ethylcellulose, straight-chain vegetable oils and waxes such as olive oil and castor oil, castor oil and esters such as amyl acetate ethyl acetate and benzyl benzoate.

It is understood that the oral compositions of the invention will be sold or otherwise delivered in a suitably labeled package. For example, a mouthwash bottle will be labeled with a description of the use and instructions for use, the toothpaste, cream or gel will usually be stored in a tube, usually aluminum, coated in lead or plastic or other material from which the paste can be made If the paste can also be supplemented with a pump or dispensing device under pressure to dispense the contents, the tube will also bear a mark that it is a toothpaste, cream or gel.

To enhance the prophylactic effect, organic surfactants are also used in the compositions of the invention to aid in the complete dispersion of the antibacterial anti-plaque and tartar throughout the oral cavity, while also making the composition more cosmetically acceptable . The organic surfactant material preferably has an anionic, nonionic or amololytic nature, and in this context it is preferred to use a surfactant as a surfactant which simultaneously has a cleaning and foaming effect. Suitable examples of anionic surfactants are the water-soluble salts of higher fatty acids with monoglyceride monosulfates, e.g. with 1,2-dihydroxypropanesulfonate and substantially saturated higher aliphatic acylamides derived from lower aliphatic aminocarboxylic acids, e.g. containing 12 to 16 carbon atoms in the fatty acid, alkyl or acyl residue, and the like. Examples of such amides are N-lauroyl-sarcosine and the sodium or potassium salt of Ν-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 levels. saturated aliphatic acids. The use of these sarcosinate compounds is particularly advantageous since these materials have a long-lasting and significant effect in inhibiting the formation of acids in the oral cavity in the breakdown of carbohydrates, and furthermore reduce the solubility of enamel in acidic solutions. Examples of water-soluble nonionic surfactants are the condensation products of ethylene oxide with various reactive compounds containing hydrogen with a long hydrophobic chain, such as 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 alcohols, fatty amides, polyhydric alcohols such as sorbitan monostearate and polypropylene oxides (e.g., the product available under the name Pluronic).

The surfactant is usually present in an amount of from about 0.1% to about 5% by weight, preferably from 1% to 2.5% by weight. In this regard, it should be noted that the surfactant may assist in dissolving the non-cationic antibacterial agent and thereby reduce the amount of dissolving humectant required.

Other materials may be incorporated into the oral compositions of the present invention, 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 form a 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 (flavoring oils) such as peppermint, peppermint, peppermint, mint, clove, sage, eucalyptus, marjoram, cinnamon, lemon or orange or methyl salicylate. Suitable sweeteners are, for example, sucrose, lactose, maltose, xylitol, sodium cyclamate, perillartin, 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. In addition, these flavoring agents (or essential oils) are likely to aid in the dissolution of the antibacterial agent with or in the absence of the surfactant.

In a preferred embodiment of the composition of the invention, these oral preparations, such as mouthwash or dentifrice containing the composition of the invention, are applied regularly to the enamel, such as every day, or every second or third day, or preferably one to three times. daily at a pH of about 4.5 to about 9, usually about 5.5 to about 8, preferably about 6 to about 8, for example at least two weeks to 8 weeks or more, until the end of life.

The composition of the invention may be incorporated in the form of lozenges for sublingual use in chewing gum or other similar products by, for example, being mixed into a warm gum base or applied to the exterior surface of chewing gum, for which purpose jelutong may be used. , rubber 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 oral composition of the invention and its use will now be described in more detail by way of specific examples, which are, however, illustrative only and not limiting of the scope of the invention. All parts and amounts referred to herein as in the foregoing description and claims are intended to be by weight unless otherwise indicated or indicated.

In the following examples, triclosan, which is 2,4,4-trichloro-2-hydroxydiphenyl ether, will be referred to as (TCHE), sodium lauryl sulfate will be referred to as SLS, maleic anhydride copolymer and methyl vinyl ether, sold under the name Gantrez S-97 (GAF Corporation). referred to as Gantrez, tetrasodium pyrophosphate (or pyrophosphate) will only be referred to as pyrophosphate (or pyrophosphate) and sodium fluoride will be referred to under its chemical brand NaF.

Example 1

Adsorption to the tooth surface and the release of minerals to determine the effectiveness of certain anti-tartar and plaque agents have been investigated for adsorption of antibacterial agents to a hydroxyapatite disc containing minerals coated with saliva in the presence of pyrophosphate and varying amounts of polycarboxylates.

SK 280834 Β6

The toothpaste to be evaluated had the following composition:

component Weight parts A B glycerol 10.00 10.00 Iota-carrageenan 0,750 0,750 Sorbitol (70% solution) 30,000 30,000 propylene 0,500 0,500 Gantrez (13.02% solution) 19,000 19,000 Titanium dioxide 0,500 0,500 Water (deionized) 9,957 9,957 NaF 0,243 0,243 Saccharin sodium 0,300 0,300 pyrophosphate 2,000 2,000 Sodium hydroxide (50%) 1,000 1,000 Silica based polishing agent (Zeodent113) 20,000 20,000 Silica-based thickener 2,500 2,500 Sylodent 15 Aromatic silica 0,950 0,950 TCHE 0,300 0,300 SLS 2,000 2,000

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

Hydroxyapatite (HA), obtained from Monsato Co., was thoroughly washed with distilled water, filtered in vacuo and then 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 milligrams 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 13 mm diameter discs were sintered for 4 hours at 800 ° C in an oven (Thermolyne). Saliva was collected in an ice-cooled glass vial, clarified by centrifugation for 15 minutes at 15,000 x g at 4 ° C. They were then sterilized at the same temperature of 4 ° C and with stirring 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 2.00 ml saliva. Incubation of the disc overnight at 37 ° C and continuous shaking in a water bath created a saliva coating. Thereafter, the saliva was removed and the discs were placed in a 1.0 ml solution containing antibacterial (Triclosan) for a dental liquid 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 aspirated and clarified by centrifugation for 5 minutes in a microcentrifuge (Backman Microfuge 11) at 10,000 rpm. The methanol was then transferred to high pressure liquid chromatography vials to determine the antibacterial content. Each assay in all experiments was performed in triplicate.

The results are summarized in the following table:

table

Dental Supply of TCHE to hydroxyapatite disc with saliva-coated paste in pg

A 130

B 30

The data show that as the amount of Gantrez (toothpaste A) increases, the TCHE feed to the saliva-coated minerals increases.

Example 2 According to this example, a toothpaste having the following composition was prepared, which is effective as an anti-plaque and tartar agent. component Weight parts Sorbitol (70%) 22,00 carrageenan 1.00 Sodium hydroxide (50%) 1.00 Gantrez (13.02% solution) 19,00 Water (deionized) 2.69 Sodium monofluorophosphate 0.76 Saccharin sodium 0.30 diphosphate 2.00 Hydrated alumina 48,00 Aromatic silica 0.95 TCHE 0.30 SLS 2.00

Example 3

An oral rinse solution was prepared according to this example, consisting of the following components:

component Weight parts Tetrasodium diphosphate 2.00 Gantrez S-97 2.50 glycerol 10.00 Sodium fluoride 0.05 Sodium lauryl sulphate 0.20 TCHE 0.06 Aromatic silica 0.40 Water supplement to 100.00

Example 4 According to this example, pill dissolution pills were prepared having the following composition: component % by weight sugar 75-80 Corn syrup 1-20 Aromatic silica 0.1-1.0 Tetrasodium diphosphate 2.0 Gantrez S-97 2.50 Sodium fluoride 0.01-0.05 TCHE 0.01-0.1 Magnesium stearate 1.0-5.0 Water 0.01-0.2 Example 5 Chewing gum parts basis 25.00 Sorbitol (70%) 17,00 TCHE 0.50 to 0.10 Tetrasodium diphosphate 2.00 Gantrez S-97 2.50

Alternatively, the Gantrez component may be omitted.

Example 6

chewing gum Weight parts basis 30.00 TCHE 0.50 Gantrez 2.50 NaF 0.05 glycerol 0.50 Crystalline sorbitol 53.00 Tetrasodium diphosphate 2.00 Aromatic silica and water: Supplement up to 100,00

In the previous examples, improved results can also be obtained by replacing TCHE with phenol, 2,2-methylene-bis (4-chloro-6-bromophenol), eugenol or thymol, and / or with Gantrez. type AEA, for example by means of a Carbopol, for example 934 (which is a cross-linking polycarboxylate having a molecular weight of 3,000,000), or polymers of styrene and phosphonic acid having a molecular weight of 3,000 to 10,000, such as poly (β-styrenephostonic acid); vinylphosphonic acid with acid, β-styrenephosphonic acid or poly (alpha-styrenephosphonic acid) or sulfoacrylic acid oligomers, or copolymers of maleic anhydride with ethyl acrylate in a 1: 1 ratio by weight.

Similar results can be obtained if the pyrophosphate (or pyrophosphate) used, in this case tetrasodium, is replaced by a mixture of tetrasodium and tetrasodium pyrophosphate at a potassium to sodium weight ratio of (a) 0.37: 1, (b) 1.04: 1, (c) 3: 1: 3.5: 1.

The invention has been described in connection with various preferred embodiments, it being understood that various other simple modifications and variations may be made by those skilled in the art and are within the scope of the invention.

Claims (29)

PATENT CLAIMS Oral anti-dental plaque and tartar in the form of a gel or paste dentifrice, liquid dentifrice, mouthwash, lozenge or chewing gum, characterized in that it contains an orally acceptable vehicle, 1 to 2.5% by weight a substance containing from 0.1 to 3% by weight of at least one linear molecular dehydrated polyphosphate salt as an anti-tartar, 0.01 to 5% by weight of a non-cationic antibacterial agent, and up to about 4% by weight of an antibacterial enhancer, improving the antibacterial effect to said polyphosphate ion is in the range of from 1.6: 1 to 2.7: 1. The oral composition of claim 1, wherein said antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated salicylanilides, benzoic acid esters, halogenated carbanilides, and phenolic compounds. Oral composition according to claim 1, characterized in that the antibacterial agent is a halogenated diphenyl ether. The oral composition of claim 3, wherein said halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. The oral composition of claim 1, wherein said antibacterial agent is a phenolic compound. The oral composition of claim 5, wherein said phenolic compound is a compound selected from the group consisting of phenol, thymol, eugenol, and 2,2'-methylene-bis (4-chloro-6-bromophenol). The oral composition of claim 2, wherein the amount of antibacterial agent is in the range of 0.25% to 0.5% by weight. The oral composition of claim 1, wherein said linear molecular dehydrated polyphosphate salt is an alkali metal pyrophosphate. The oral composition of claim 8, wherein said alkali metal pyrophosphate is tetrasodium pyrophosphate. The oral composition of any one of claims 1 to 7, wherein the weight ratio of polyphosphate ion to antibacterial enhancer is in the range of from about 1.7: 1 to about 2.3: 1. The oral composition of any one of claims 1 to 11 10, characterized in that it comprises as a vehicle water, a humectant and a gelling agent, and the oral composition comprises a dentally acceptable water-insoluble polishing agent. The oral composition of any one of claims 1 to 12 11, characterized in that it comprises water and a non-toxic alcohol as the vehicle and the composition is a mouthwash. The oral composition of any one of claims 1 to 13 12, wherein said antibacterial enhancing agent has an average molecular weight ranging from about 100 to about 1,000,000. 14. An oral formulation according to claim 13 wherein said antibacterial agent comprises at least one functional group promoting delivery of said substance and at least one organic functional group promoting retention. SK 280834 Β6 The oral composition of claim 14, wherein said delivery promoting group is of an acidic nature. The oral composition of claim 15, wherein the antibacterial delivery promoting group is selected from the group consisting of residues derived from carboxylic, phosphonic, phosphinic, sulfonic acid, salts thereof, and mixtures thereof. The oral composition of claim 16, wherein said organic retention aid group has the general formula: - (X) n-R, in which: X is oxygen, nitrogen, sulfur, SO, SO ₂ , PO or Si, R represents a hydrophobic alkyl group, an aryl group, an alkenyl group, an acyl group, an alkaryl group, an aralkyl group, a heterocyclic group or derivatives thereof with inert groups, and n is 1 or zero. The oral composition of claim 16, wherein said antibacterial enhancing agent is an anionic polymer comprising a series of release promoting groups and organic retention promoting groups. The oral composition of claim 18, wherein the anionic polymer comprises a chain of repeating units each containing at least one carbon atom. The oral composition of claim 19, wherein each unit comprises at least one release promoting group and at least one retention promoting organic group attached to the same atom or adjacent atom, or to another atom in the chain. The oral composition of claim 16, wherein the release promoting group comprises a carboxyl group or a salt thereof. The oral composition of claim 21, wherein the antibacterial enhancer is a maleic acid or maleic anhydride copolymer with another ethylenically unsaturated polymerizable monomer or salt thereof. 23. The oral composition of claim 22 wherein said additional monomer is methyl vinyl ether in a molar ratio with maleic acid or maleic anhydride in a ratio of from 4: 1 to 1: 4. The oral composition of claim 23, wherein said copolymer has a molecular weight of about 30,000 to 1,000,000. The oral composition of claim 24, wherein said copolymer has an average molecular weight of about 70,000. The oral composition of claim 16, wherein said release promoting group comprises a phosphone group or a salt thereof. The oral composition of claim 26, wherein said antibacterial enhancing agent is poly-β-styrene phosphonic acid, poly-α-styrene phosphonic acid or a copolymer of any styrene phosphonic acid with another styrene phosphonic acid or other inert polymerizable non-ethylenically polymerizable monomer. or a salt thereof. The oral composition of claim 27, wherein said antibacterial enhancing agent has a molecular weight ranging from about 1,000 to about 30,000. Oral composition according to any one of claims 1 to 28, characterized in that it comprises a fluoride ion source.