CZ750989A3 - Mouth preparation - Google Patents

Abstract

An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such as tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncationic antibacterial agent such as 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Triclosan). Antiplaque effectiveness is optimized by the presence of an antibacterial-enhancing agent which enhances delivery of said antibacterial agent to, and retention thereof on, oral surfaces. Suitable enhancing agents are anionic polymers such as a maleic acid-methyl vinyl ether copolymer or a polymer containing phosphonic groups. Also disclosed are compositions comprising (1) the noncationic antibacterial agent and the enhancing agent, (2) the polyphosphate anticalculus agent and the noncationic antibacterial agent and (3) the enhancing agent and polyphosphate anticalculus agent effective against any antibacterial agent.

Description

Technical field i

Her

BACKGROUND OF THE INVENTION The present invention relates to an oral composition, and more particularly to an oral composition having an anabibacterial effect and to counteract plaque and calculus formation.

The oral composition comprises a pyrophosphate (or pyrophosphate) anti-tartar compound and a compatible antibacterial agent effective to inhibit plaque, wherein the anti-plaque activity is optimized by the presence of an antibacterial enhancing agent that promotes the release of the antibacterial agent and its retention on the oral cavity surface.

BACKGROUND OF THE INVENTION

In the United States patents. 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. is used linear dehydrated polyphosphate salts in conjunction with a fluoride ion source and a synthetic linear polymeric polycarboxylate to prevent calculus formation.

European Patent Application No. 89 200 710.5 describes increasing the anti-tartar efficacy by using a small amount of linear, molecularly dehydrated polyphosphate salt in conjunction with a fluoride ion source and an increased amount of synthetic linear polymeric polycarboxylate.

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

Oral formulations 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 the function of the periondontal structures. Reducing the formation of tartar thus improves oral hygiene.

Dental coatings are a prior stage of tartar formation. Unlike tartar, however, plaque can form on any part of the tooth surface, 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 gingivitis.

Accordingly, it would be highly desirable to use antimicrobial agents known to reduce the formation of coatings in oral anti-tartar compositions. U.S. Pat. No. 4,022,550 (Vinson et al.) Discloses the use of a zinc ion-releasing compound as an anti-tartar and antibacterial agent 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 salicylanilides and halogenated hydroxydiphenyl ethers.

Until now, cationic antibacterial materials such as chlorhexidine, benzethonium chloride and acetylpyridinine chloride have been subjected to thorough research in which they have been tested as anti-dental agents. However, although they have been used with zinc containing compounds to prevent calculus formation, they are not effective when used in conjunction with anionic materials such as anti-calculus polyphostates. This ineffectiveness is considered to be very surprising since polyphostates are chelating agents and it is known that chelation usually increases the effectiveness of cationic antibacterials as described in the publication; Disinfectton,

Sterilization and Preservation, 2nd Edition, Black, 1977, p. 215. Quaternary ammonium compound is a mouthwash component for dental plaque suppression of pyrophosphate (pyrophosphate) according to U.S. Patent No. 4,323,551 (Parran) and the use of bisbiguanide as The dental plaque is proposed in an oral pyrophosphate-containing oral composition of U.S. Pat. No. 4,515,772 to Parran et al.

Due to the unexpected incompatibility of antibacterial compounds of cationic nature with polyphostates used as anti-tartar agents, it has been completely unexpected that other antibacterial agents not yet tested could be effective in this regard.

SUMMARY OF THE INVENTION

The invention is based on the discovery that certain antibacterial compounds are effective in oral anti-tartar formulations comprising a linear, molecularly dehydrated pyrophosphate (pyrophosphate) salt, a fluoride ion source and the aforementioned antibacterial promoting agent, thereby inhibiting the formation of dental plaque (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 reduces the formation of dental plaques in an optimal manner.

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

Further advantages of the oral composition of the invention will be described in more detail in the following descriptive and exemplary parts of the invention.

The oral composition of the present invention comprises:

- an orally acceptable vehicle,

- an effective amount of anti-dental caries of at least one alkali metal pyrophosphate (or pyrophosphate) salt as an anticalculus agent in the range of 0.1% to 3% by weight.

an effective amount of an anti-dental plaque of a substantially water-insoluble non-cationic antibacterial agent in the range of from 0.01% to 5% by weight selected from the group consisting of halogenated diphenyl ethers, halogenated salicyclinides, benzoic esters such as e.g. hydroxybenzoic acid methyl ester, ethyl ester, propyl ester and butyl ester, halogenated carbanilides and phenolic compounds from the group consisting of phenol, hydroxyphenol, halophenol and substituted phenols, hydroxyphenols and halophenols, said substituents being alkyl, alkenyl, alkoxy, cycloalkyl, aryl and aralkyl groups containing 1 to 9 carbon atoms, hydroxydiphenylmethanes and sulfides and bisphenols - and up to 4% by weight of an antibacterial enhancing agent containing an acidic group promoting the release of said antibacterial agent into the oral cavity on the tooth surface The gum is selected from the group consisting of carboxylic acid, phosphonic acid, phosphinic acid and sulfonic acid residues and salts and mixtures thereof, and an organic group promoting the retention of said antibacterial agent in the oral cavity on the tooth surface. and gums, the retention promoting group having the general formula:

- (X) _n -R wherein:

X represents oxygen, nitrogen, sulfur, SO, S0 _2, P, PO or Si,

R has a molecular weight ranging from 19 to 60,000 and represents a hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, nitrogen-containing and / or oxygen-containing heterocyclic group, or inert non-hydrophilic substituted derivatives thereof, which do not substantially adversely affect the release and retention function of said antibacterial agent when n is 1 or zero,

- wherein the weight ratio of said antibacterial enhancer to said pyrophosphonate ion is in the range of from 1.6: 1 to 2.7: 1,

Preferably, the oral composition of the invention optionally comprises a fraction of a fluoride ion source providing sufficient to deliver 25-5000 ppm of fluoride ions.

Preferably, the antibacterial agent in the present invention is halogenated diphenyl ether, most preferably the halogenated diphenyl ether is 2,4,4'-trichloro-2'-hydroxyphenyl ether. The antibacterial agent is preferably also said phenolic compound, wherein the phenolic compound is preferably a compound selected from phenol, thymol, eugenol and 2,2'-methylene-bis (4-chloro-6-bromophenol).

The amount of said antibacterial agent in the oral composition of the invention is preferably in the range of 0.25% to 0.5% by weight.

The alkali metal pyrophosphate is preferably tetrasodium pyrophosphate (or pyrophosphate).

The pyrophosphate salt may preferably be present in an amount ranging from 1% to 2.5% by weight.

The weight ratio of the antibacterial enhancer to the diforate ion is preferably from 1.7: 1 to 2.3; 1. most preferably in the range from 1.9: 1 to 2: 1.

In a preferred embodiment, in the oral composition, the vehicle comprises water, a humectant and a gelling agent, and the oral composition comprises a dentally acceptable water-insoluble polishing agent, the oral composition being in the form of a dentifrice, most preferably the vehicle comprises water and a nontoxic alcohol. wherein the oral composition is in the form of a mouthwash.

Said antibacterial enhancer preferably has an average molecular weight in the range of about 100 to about 1,000,000, most preferably in the range of about 2,000 to about 500,000.

The antibacterial enhancing agent is preferably an anionic polymer comprising at least two release promoting groups and organic retention promoting groups, most preferably said anionic polymer comprises a chain of repeating units, each containing at least one carbon aroma and each raro unit containing at least one promoting group releasing and at least one organic group promoting retention attached to the same atom, or an adjacent atom, or to another atom in the chain.

The release promoting group preferably comprises a carboxyl group or a salt thereof, and the antibacterial agent is preferably a copolymer of maleic acid or maleic anhydride with another ethylenically unsaturated polymerizable monomer or salt thereof.

Said further monomer is preferably methyl vinyl ether in a molar ratio with maleic acid or maleic anhydride in a ratio of from 4: 1 to 1: 4.

In this case, it preferably has said copolymer

- δ a molecular weight in the range from 30 000 to 1 000 000, preferably 70 000.

According to another preferred embodiment, said release promoting group comprises a phosphonic group or a salt thereof, said antibacterial enhancing agent is poly-β-styrene phosphonic acid, poly-α-styrene phosphonic acid, or a copolymer of styrene phosphonic acid or a salt thereof, and said antibacterial enhancing agent has a molecular weight in the range of 1,000 to 30,000, preferably in the range of 2,500 to 10,000.

According to another preferred embodiment, the oral composition according to the invention comprises:

- an orally acceptable vehicle,

- an effective amount of anti-dental caries of at least one alkali metal pyrophosphate (pyrophosphate) salt as an anti-tartar agent, ranging from 0.1 to 3% by weight,

- an effective amount of an anti-dental plaque substantially water-insoluble non-ionic antibacterial agent as an anti-dental plaque agent in the range of 0.01% to 5% by weight selected from halogenated diphenyl ethers, halogenated salicylanilides benzoic acid esters such as methyl, ethyl, propyl and butyl hydroxybenzoate, halogenated carbanilides and phenolic compounds from the group consisting of phenol, halophenol, hydroxyphenol and substituted phenols, wherein said substituents are alkyl, alkenyl, alkoxy, cycloalkyl, aryl and aralkyl groups containing 1 to 9 carbon atoms, hydroxydiphenylmethanes and sulfides and bisphenoids.

and up to 4% by weight of an antibacterial enhancer

- an effect comprising an acidic release promoting group of said antibacterial agent into the oral cavity on the surface of the teeth and gums, said release promoting group being selected from the group consisting of carboxylic acid, phosphonic acid, phosphinic acid and sulfonic acid residues and salts and mixtures thereof, with the proviso that when said release enhancing agent is a carboxyl compound, said antibacterial enhancing agent has a molecular weight of greater than 1,000,000,

- and an organic retention aid group which improves the retention of said antibacterial agent in the oral cavity on the surface of teeth and gums, said retention aid group having the general formula:

- (X) _n -R wherein:

X is oxygen, nitrogen, sulfur. SO, SO2. P, PO or Si,

R has a molecular weight ranging from 19 to 60,000 and represents a hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, nitrogen-containing and / or oxygen-containing heterocyclic group, or inert non-hydrophilic substituted derivatives thereof, which do not substantially adversely affect the release and retention function of said antibacterial agent, n being 1 or zero.

In one embodiment, the invention relates to an oral composition comprising a vehicle acceptable for oral administration, 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 antibacterial agent of a non-cationic nature, effective against dental plaque formation, and desirably present at most 4% by weight of an antibacterial agent to enhance the delivery and retention of the antibacterial agent to the oral cavity surface; 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 from 1: 1 to 3.5: 1, especially in the range of 1.6: 1 to 2.7: 1, preferably in the range of 1.7: 1 to 2.3: 1, and most preferably in the range of 1.9: 1 to 2: 1. when tetrasodium pyrophosphate (TSPP) is released, which releases about 1.3% by weight of the pyrophosphate ion, 2.5% by weight of an antibacterial agent is used simultaneously, thereby achieving a highly advantageous value of the above weight ratio

1.9: 1.

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

Halogenated di / phenyl ethers

2 ', 4,4'-trichloro-2-hydroxyd i phenylether (triclosan),

2,2'-d i hydroxy-5,5'-di bromdi phenylether,

Halogenated salicylanilides

4 ´, 5-dibromsalicylanilide,

3.4 ´, 5-trichlorosalicylanilide,

3,4 5, 5-tribromsalicylanilide,

2,3,3 ', 5-tetrachlorosalicylanilide.

3,3,3 ', 5-tetrachlorosalicylanilide,

3,5-dibromo-3'-trifluoromethylsalicylaniide,

5-n-octanoyl-3'-trifluoromethylsalicylanilide,

3,5-dibromo-4'-trifluoromethylsalicylanide,

3,5-dibromo-3'-trifluoromethylsalicylanilide (fluorophene).

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

Halogenated carbane people

3,4,4’-trichlorocarbans,

3-Trifluoromethyl-4,4'-dichlorocarbanilide

3,3,4 * -trichlorocarbonate.

Phenol compounds (including phenol and its homologues, mono- and polyalkylated and aromatic halogenated, i.e., fluorinated, chlorinated, accumulated 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,

4, 2,4- dime thylphenol,

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- and 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, t-amyl-o-chlorophenol, n-hexyl-o-chlorophenol, n-heptyl-o-chlorophenol.

- 1'-p-chlorophenol, o-benzyl-p-chlorophenol, o-benzyl-m-methyl-p-chlorophenol, o-benzyl-m, m-dimethyl-p-chlorophenol, o-phenylethyl-p-chlorophenol, o-phenylethyl-m-methyl-p-chlorophenol,

3-methyl-p-chlorophenol,

3,5-dimethyl-p-chlorophenol, 6-ethyl-3-methyl-p-chlorophenol,

6-n-propyl-3-methyl-p-chlorophenol,

6-Isopropyl-3-methyl-p-chlorophenol

2-ethyl-3,5-dimethyl-p-chlorophenol,

6-sec-butyl-3-methyl-p-chlorophenol,

2-Isopropyl-3,5-dimethyl-p-chlorophenol.

6-diethylmethyl-3-methyl-p-chlorophenol,

6-Isopropyl-2-ethyl-3-methyl-p-chlorophenol 2-sec-amyl-3,5-dimethyl-p-chlorophenol

2-diethylmethyl-3,5-dimethyl-p-chlorophenol 6-sec-octyl-3-methyl-p-chlorophenol, p-bromophenol, methyl-p-bromophenol, ethyl-p-bromophenol, n-propyl-p-bromophenol .

n-butyl-p-bromophenol, n-amyl-p-bromophenol, sec-amyl-p-bromophenol, n-hexyl-p-bromophenol, cyclohexyl-p-bromophenol.

o-bromophenol, t-amyl-o-bromophenol, n-hexyl-o-bromophenol, n-propyl-m, m-dimethyl-o-bromophenol,

2-Phenylphenol

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

4-chloro-3,5-dimethylphenol,

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

5-Methyl-2-pentylphenol

4-Isopropyl-3-roethylphenol

5-chloro-2-hydroxydiphenylmethane.

Resorcinol and its derivatives resorcinol, methylresorcinol, ethylresorcinol, n-propylresorcinol, n-butylresorcinol, n-amylresorcinol, n-hexylresorcinol, n-heptylresorcinol, n-octylresorcinol, n-nonylresorcinol, phenylresorcinol, phenylresorcinol, phenylresorcinol, phenylresorcinol, phenylresorcinol, phenylresorcinol, phenylresorcinol, phenylresorcinol

5-chloro-2,4-dihydroxydiphenylmethane, 4 ' -chloro-2,4-dihydroxydiphenylmethane, 5-bromo-2,4-dihydroxydiphenylmethane.

4 ' -bromo-2,4-dihydroxydiphenylmethane.

Biphenol 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 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, which solubility may be less than 0.1% by weight. an ionizable group is determined, the solubility of such a substance is determined at a pH at which no ionization occurs.

Of the halogenated diphenyl ethers, triclosan is the preferred compound. Of 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. Patent No. 4,022,880 as an antibacterial agent which 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 compounds containing copper. Triclosan is also referred to as a dentifrice in a dentifrice composition comprising a lamellar liquid crystal surfactant in which:

16 gaps between individual slats are less than 6.0 nm and can also be used in the zinc salt composition described in European Patent 161 988 (Lané et al.) And in the dentifrice composition containing citrate trihydrate zinc, the composition of which is disclosed in European Patent No. 161,899 (Saxton et al.).

Linear molecularly dehydrated pyrophosphate (and generally polyphosphate or polyphosphate) salts for use as anti-tartar agents 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 salts or ammonium salts and mixtures thereof. An example of such materials is sodium hexametaphosphate.

disodium pyrophosphate, trisodium and tetrasodium, corresponding potassium salts and the like. Linear polyphosphates can be represented by the formula (NaPO4) _n wherein n is 2 to about 125. The oral compositions of the present invention can be used in an amount of from about 0.1% to about 3% by weight, usually from about 1% % to 2.5% by weight, preferably from 1.5% to 2% by weight. When n has a value of at least 3, said polyphosphates are vitreous in nature.

Particularly suitable anticalculus agents are tetraalkali metal pyrophosphates (pyrophosphates) and mixtures thereof, for example tetrasodium pyrophosphate (pyrophosphate), tetrapotassium pyrophosphate and mixtures thereof. Thus, the oral composition may comprise an anti-tartaric pyrophosphate (and common polyphosphate) antioxidant agent that is substantially free of tetrasodium pyrophosphate or substantially free of a mixture of potassium pyrophosphate and potassium pyrophosphate wherein the ratio of potassium pyrophosphate to sodium pyrophosphate is: higher.

Particularly effective is an anti-tartar agent comprising about 2% by weight of tetrasodium phosphate, based on the total weight of the oral composition.

The antibacterial agent (AEA), which improves 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. %, preferably from 0.1% to 3%, in particular from 0.5% to 2.5%.

The AEA may be a simple 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 a mixture of natural or synthetic origin, it may be a water-insoluble or preferably water-soluble (i.e. saliva) substance, or it may be a swellable (hydratable, hydrogel-forming) substance. The molecular weight of these materials can 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 2,000 or about 2,500 to about 250,000, or about 500,000.

These AEAs usually contain at least one group promoting the delivery of an active agent that is acidic in nature, such as a sulfonic, phosphonic or, preferably, phosphonic or carboxylic acid residue, or a salt thereof, such as an alkali metal or ammonium salt. and at least one organic group promoting retention (or retention) of the active agent on the mucosal surface, preferably comprising a plurality of both types of the above groups. These retention-promoting groups can be represented by the general formula;

- (J) n-R wherein;

X is oxygen, nitrogen, sulfur, SO. SO ₉ , 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 higher.

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 function of AEA in promoting the delivery of the antibacterial agent to the mucosal surface and retention of the agent on the mucosal surface. wherein the inertly substituted derivative may be a halogen substituted group such as chlorine, bromine, iodine, or a carbocycle and the like,

Examples of these 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 reviewed below.

X- (X) _nR

- methyl, ethyl, propyl, butyl, isobutyl, target, -butyl, cyclohexyl, allyl, benzyl, phenyl, chlorophenyl, xylyl, pyridyl, furanyl, acetyl, benzoyl .

butyryl, terephthaloyl, etc.

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

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

thiobutyl, thioisobutyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenylthioacetyl, thiobenzoyl, etc.

n X 1 Sat butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc. 1 Sat ₂ butylsulfonyl, allylsulfonyl a benzylsulfonyl group, phenylsulfonyl, etc. P diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylphenylphosphinyl, etc. AFTER diethylphosphinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, methylbenzylphosphinoxy, methylphenylphosphinoxy, etc. Si trimethylsilyl, dimethylbutylsilyl a benzylsilyl group, dimethylvinylsilyl group, a dimethylallylsilyl group, 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 a substance that associates by adhesion, cohesion or otherwise with AEA (containing the antibacterial agent) to achieve delivery of 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 agent to the AEA, thereby promoting the retention of the antibacterial agent to the AEA and thus indirectly to the oral cavity surface. In some cases, capture of the antibacterial agent is achieved by physically attaching the agent to AEA. especially in cases where the AEA is a cross-linked polymer, the structure of which itself increases the number of sites for carrying out this binding, respectively. connection. The presence of higher molecular weight moieties and the presence of multiple moieties with hydrophobic crosslinked moieties in the crosslinked polymer further enhance the possibility of physically entrapping the antibacterial agent onto or across the crosslinked AEA polymer.

Preferably, 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 linked or indirectly attached pendant monovalent moiety to promote delivery of the active antibacterial agent, and at least one directly or indirectly attached, monovalent, pendant moiety promoting retention of the active antibacterial agent, namely geminally, vicinally or less preferably by other means to atoms in the chain, preferably carbon atoms. It is less preferred that the polymer contains antibacterial agent delivery support groups and / or antibacterial retention group support groups and / or other divalent atoms or groups as linkers in the polymer chain instead of or in addition to the carbon atoms as crosslinkers

Li parts.

It is contemplated that any examples of AEAs herein that do not contain both antibacterial agent and retention groups may be, and preferably are chemically modified in such a way that such types of AEAs are obtained, which preferably contain both of these types of groups and more preferably a plurality of these types of groups. In the case of preferred polymeric AEAs, in order to maximize the effect and promote the delivery of the antibacterial agent to the oral surface, it is desirable that repeating units in the polymer chain or polymer backbone containing acidic antibacterial delivery promoting groups comprise at least about 10% by weight of the polymer, preferably 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 polymers.

Preferably, the AEA comprises a polymer comprising repeating units in which one or more phosphonic acid groups supporting the delivery of the antibacterial agent is bound to one or more carbon atoms in the polymer molecule. Examples of these AEAs are poly (tartaric phosphonic acid) containing units of formula I:

- [CH ₂ —CH] -

I (I) after ₃ h ₂

However, this group does not include a group which promotes retention of the antibacterial agent on the surface of the oral cavity. However, a group of this type is present in the poles (1-phosphonpropene) having the formula II:

- [CH — CH] -

II (Π) ch ₃ after ₃ h ₂

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

- [CH — CH] -

I f (ΙΠ)

Ph PO ₃ H ₂ wherein Ph is a phenyl group, wherein the antibacterial agent-promoting phosphonic acid group and the antibacterial agent-retention phenyl group are bonded to vicinal carbon atoms in the chain, or a β-styrene-phosphonic acid-vinylphosphonyl chloride copolymer having units of formula III with units of formula I, see above in alternating or statistical order, or poly (α-styrene phosphonic acid) containing units of formula IV:

Ph [CH (IV) after ₃ h ₂ in which both the feeder moieties and the anti-bacterial retention moieties 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, as mentioned above, a molecular weight in the range of about 2000 to about 30,000, preferably a molecular weight in the range of about 2500 to about 10,000. These inert monomers do not adversely affect the 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 ) ₁₄ CHPO ₃ H ₂ J _n - (V) wherein n can be, for example, an integer such that the polymer of formula (V) has a molecular weight of about 3000, and sodium salt poles (butene-4,4) -diphosphonate) with units of formula VI:

- (CH ₂ -CH ₂ ) - i (VI)

CH ₂ -CH <(PO ₃ Na ₂ ) ₂ and poles (allyl-bis (phosphonethylamine)) with units of formula VII - [CH ₂ -CH- ΙΙ (VII)

CH ₂ -N? (C ₂ H ₄ PO ₃ H ₂ ) ₂

Other phosphonated polymers, such as poles (allylphosphonacetate), phosphonated polymethacrylate, etc., as well as the geminal diphosphonate polymers disclosed in European Patent No. 321233, can be used as AEAs, provided they contain both types of the above groups or are modified in such a way as to include these two types.

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 in the range of about 1,000 to about 1,000,000, comprises at least one functional group that promotes the release and delivery of an antibacterial effect and at least one organic group which promotes retention of antibacterial effects, said agent containing said groups being free or substantially free of a synthetic anionic linear polymeric polycarboxylate with an alkali metal or ammonium salt of said polycarboxylate of molecular weight about 1,000 to 1,000,000, and a pyrophosphate (or pyrophosphate) anti-tartar agent, such as a mixture of potassium and sodium salts. wherein the ratio of potassium to 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 a further preferred embodiment, said substance may

AEAs contain a synthetic anionic polymeric polycarboxylate which is also an inhibitor of the alkaline phosphatase enzyme. Synthetic anionic polymeric 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. Patent 3,429,963 (Shedlovsky), 4 152,420 (Gaffar), 3,956,480 (Dichter et al.). 4,138,477 (Gaffar et al.) And 4,183,914 (Gaffar et al.). However, only 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 combination with a fluoride ion source compound. It should be noted, however, that the synthetic anionic polymeric polycarboxylates disclosed in these several patents, when containing or modified by the above-mentioned retention aid groups, are active AEAs that can be used in the oral compositions and preparation processes of the invention. These publications are reference materials in the context of the present invention.

The synthetic anionic polymeric polycarboxylates are often used in the form of the free acids or preferably in the form of partially neutralized salts or even more preferably in the form of completely neutralized salts which are water-soluble or water-swellable (hydratable form, gel-forming form). an alkaline salt (such as a potassium salt or preferably a sodium salt) or ammonium salts. Preferably

£. copolymers of maleic anhydride or maleic acid with another polymerizable ethylenically unsaturated monomer in a ratio of 1: 4 to 4 are used; 1, preferably a methyl vinyl ether / maleic anhydride copolymer having a molecular weight ranging from about 30,000 to about 1,000,000. 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 of pharmaceutical grade (molecular weight 70,000), manufactured by GAF Corporation.

Other AEA active polymeric polycarboxylates which contain or are modified by retention-promoting groups include, for example, those disclosed in U.S. Pat.

956,480 mentioned above, in particular copolymers of maleic anhydride with ethyl acrylate in a ratio of 1: 1, followed by 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 Grade 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 disclosed in U.S. Patent Nos. 4,138,477 and 4,183,914, which contain or are modified to contain antibacterial retention groups are copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether. polyacrylic acid

- 28 acid and polymaleic acid and sulfoacrylic oligomers, the molecular weight of which is very low, about 1000, 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 during polymerization due to its presence in the monomer molecule either in 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, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styrylacrylic acid, muconic 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 carboxylic 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 the compounds.

The so-called carboxyvinyl polymers cited as toothpaste components in U.S. Patent Nos. 3,980,767 (Chown et al.), 3,935,306 (Roberts et al.), Are also useful for the above purposes.

919,409 (Perla et al.), 3,911,904 (Harrison) and 3,711,604 (Colodney et al.). These materials are commonly marketed under the tradenames Carbopol 934, 940 and 941 by B.F. Goodrich, wherein the products consist essentially of a colloidal water-soluble polyacrylic acid polymer crosslinked by the addition of 0.75% to about 2.0% polyallylsaccharose or polyallylpentaerythritol as crosslinking agent, wherein the crosslinked structures and crosslinking bonds provide the desired retention enhancement due to the hydrophobic nature of the structures and / or due to physical entrapment 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, 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 cross-linking agent that promotes retention of the antibacterial agent.

Synthetic anionic polymeric polycarboxylates as a component of the compositions of the invention are most often of the hydrocarbon type optionally containing halogen and O-containing moieties and linkages, 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).

S> .t

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 the above-mentioned antibacterial agent-promoting groups and / or retention-promoting groups of the antibacterial agent are ineffective as AEAs.

Illustrative examples of AEAs containing phosphinic acid and / or sulfonic acid groups that promote the delivery of an antibacterial agent include polymers and copolymers containing units or moieties derived from the polymerization of vinylphosphonic or allylphosphonic acid and / or sulfonic acid substituted as needed on one or two (or three) carbon atoms by organic retention promoting groups, such as the groups of the above formula - (X) _n -R as defined above. Mixtures of these monomers and copolymers of these with one or more inert polymerizable ethylenically unsaturated monomers, such as those mentioned above in connection with active synthetic anionic polymeric polycarboxylates, may also be used. As will be noted, in these agents and in other polymeric AEAs suitable for the purpose of the present invention, usually only one acid group promoting the delivery of the antibacterial agent is bound to any carbon atom or other atom in the polymer backbone or to the branching of the 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. Also ionomers containing said groups are effective as AEAs

J1 promoting the retention of the antibacterial agent and retention of the antibacterial agent, or modified to contain these groups. These ionomeric materials are described in Kirk Othmer Encyclopedia of Chemical Technology, Third Edition, Supplement Volume, John Wiley & Sons, Inc. copyright, 1984, pp. 546-573, the disclosure of which is incorporated herein by reference. Also useful as AEAs are polyesters, polyurethanes, and synthetic and natural polyamides, including proteins and protein materials such as collagen, poles (arginine) and other polymerizable amino acids when they contain or have been modified to contain retention-promoting groups.

When the oral composition is prepared 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 polycarbaxylate so that the finished oral composition contains at least 2.2% by weight of the substance, 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 desirable 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 to about 3.5: 1, with preferably about 1.6: 1 to about 2.7: 1.

In order to optimize the effect of the oral composition against tartar formation, it is appropriate to add to this

ΛΖ composition inhibitors acting against enzymatic hydrolysis of pyrophosphate (generally polyphosphate). Typically, such agents are a source of fluoride ions, the amount of which is sufficient to provide 25 ppm to 5,000 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 1,000,000, 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 well 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 adverse effect on the action of the other components of the composition. 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 fluoride, zinc fluoride, barium fluoride, sodium fluorosilicate or ammonium fluorosilicate, sodium fluorosilicate or ammonium fluorosilicate, sodium monofluorophosphate, aluminum monofluorophosphate 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 non-toxic amount, typically in the range of about 0.0005% to about 3.0% % by weight. In a dentifrice composition, such as a dental gel, toothpaste (including creams), toothpaste 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 minimal amount 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 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 wt% to about 3 wt%, preferably 0.76 wt%.

In oral compositions such as mouthwashes, sublingual lozenges, and chewing gum, the fluorine releasing compound is usually present in an amount sufficient to release up to about 500 ppm of fluoride ions, preferably up 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, such as a mouthwash or a composition used to rinse the oral cavity. In such compositions, the vehicle is usually a mixture of water and an alcohol, optionally containing a humectant, as described above. The water to alcohol weight ratio generally ranges from 1; 1 to 20: 1, preferably in the range of 3; The total amount of water / alcohol mixture in formulations of this type is in the range of 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, usually in the range of about 5.5 to about 8. The preferred pH range is from 6 to 8.0. It should be noted that the composition of the invention may be orally used at a pH of less than 5 without substantial decalcification or other dental enamel damage. 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 gel dentifrice. The vehicle for such solid or pasty oral dentifrices comprises a dental acceptable polishing material, such as 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. Such suitable polishing materials also include the thermosetting resins described in U.S. Patent 3,070,510 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 µmη, a mean particle size of up to about 1.1 µmη, and a surface area of up to about 50,000 cm / g, which may be silica gel or colloidal silica gel and complex amorphous aluminosilicate aluminosilicon ,

When using clear gels, it is particularly useful to use colloidal silicon dioxide as a polishing material, such as those sold 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 because these substances have a refractive index close to that of liquid gelling agent systems (including water and / or wetting or dissolving agents) 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 as described in Thorpe &apos; s Dictionary of Applied Chemistry, Vol. 9, 4th Edition, pp. 510-511. 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 a low 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, the particle size of which is such that only a maximum of 1% of the material has particles larger than 37 μτπ.

The polishing material is usually present in the solid or pasty compositions of the present invention in an amount of 10% to 99% by weight, preferably 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, the toothpaste is usually present in an amount ranging from 10% to 30% by weight. Other polishing materials are typically included 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. Liquid mixtures of water, glycerol and sorbitol are also preferred.

In clear gels where the refractive index is an important value, about 2.5% to 30% by weight of water, up to 70% by weight of glycerol and 20% to 80% by weight are preferably used.

J / sorbol tolu.

Toothpastes, creams or gel cleaning compositions generally comprise 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 suitable thickener is, for example, synthetic hectorite, a synthetic colloidal magnesium alkali metal silicate complex that is available, for example, as Laponite (e.g., CP, SP 2002 or D, Laporte Industries Limited). Laponite D analysis gives 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 metal trace. The density of this material is 2.53 g / cm @ 2 and bulk density at. a moisture content of 8% by weight is 1.0 g / ml.

Another suitable thickener is Irish moss. carrageenan, iota-carageenan, tragacanth rubber, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose. hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose (such as the product under the name Natrosol), sodium carboxymethylcellulose and colloidal silica such as the finely divided Syloid (e.g. the product under the name 244). In some dentifrice compositions of the invention, particularly when more than 0.35% by weight of a water insoluble antibacterial agent and a silica polishing agent are used in an amount of less than 30% by weight, it may be appropriate to add an antibacterial dissolving agent . These solubilizers, including humectants, may be certain polyols such as propylene glycol, dipropylene glycol and hexylene glycol, whole oils such as methyl cellulose and ethyl cellulose, vegetable oils and waxes containing at least 12 carbon atoms, in a straight chain such as olive oil, castor oil and petrolatum, and esters such as amyl acetate. ethyl acetate and benzyl benzoate,

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 instructions for use and instructions for use, the toothpaste, cream or gel will usually be contained in a tube, usually of aluminum, coated lead or plastic or other material from which the paste can be extruded and wherein the paste may also be supplemented by a pump or dispensing device under pressure to dispense the contents, the tube will also bear an indication 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 is preferably anionic, nonionic or ampholytic in nature, and in this context it is preferred to use a surfactant as a surfactant which simultaneously has a cleansing and foaming effect. Suitable examples of anionic surfactants are the water-soluble salts of higher fatty acids with monoglyceride monosulfates, for example sodium salts of monoglyceride monosulfates of hydrogenated coconut oil, higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecylbenzenesulfonate esters, higher sodium alkyl esters sulfonates with 1,2-dihydroxypropanesulfonate and substantially saturated higher aliphatic acylamides derived from lower aliphatic aminocarboxylic acids, for example 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 la-lauroyl-, N-myristoyl- or N-palmitoyl sarcosine, or a salt of these with ethanolamine, which should be substantially free of soaps or similar higher-content materials. saturated aliphatic acids. The use of these sarcosinate compounds is particularly advantageous as they have a long-lasting and prominent effect in inhibiting oral acid formation in carbohydrate disintegration and further 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, for example an aliphatic chain containing 12 to 20 carbon atoms, which condensation products (ethoxamers) contain hydrophilic polyoxyethylene moieties, e.g. polyethylene oxide condensation products with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols such as sorbitan monostearate and polypropylene oxides (such as the product available under the Pluronic brand name).

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 context, it should be noted that the surfactant may assist in dissolving the non-ionic antibacterial agent and thereby reducing 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.

Suitable flavoring or flavoring or sweetening agents may also be used. Examples of such flavoring or flavoring agents are some essential oils (flavoring oils) such as peppermint, peppermint, menthol, sassafras. cloves, 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 flavorings (not essential oils) are likely to aid in the dissolution of the antibacterial together with the surfactant or even in the absence thereof.

In a preferred embodiment of the compositions of the invention, these oral preparations, such as mouthwash or dentifrice containing the composition of the invention, are applied regularly to the dental enamel, such as every day or every second or third day, or preferably once to three times a day. 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 to be placed under the tongue, in chewing gum or other similar cak products. For example, jelutong may be used to mix it into a warm rubber base or to apply it to the outer surface of a chewing gum. rubber latex, vinyl resin and the like, preferably 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 present invention and its use will now be described in more detail by way of specific examples, which are, however, merely illustrative and not limiting of the scope of the invention. All parts and amounts referred to herein, as in the foregoing description and claims, are by weight unless otherwise indicated or indicated.

In the following examples, triclosan, which is

2,4,4-trichloro-2-hydroxy-diphenyl ether, referred to as (TCHE), sodium lauryl sulphate will be referred to as SLS, maleic anhydride copolymer and methyl vinyl ether, marketed under the name Gantrez S-97 (GAF Corporarion) will be referred to as Gantrez, pyrophosphate ) tetrasodium will only be referred to as pyrophosphate (or pyrophosphate) and sodium fluoride will be referred to under its chemical name 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 by adsorption of antibacterial agents to a mineral-coated hydroxyapatite disc in the presence of pyrophosphate and varying amounts of polycarboxylates.

The evaluated toothpastes had the following composition ^-

component weight parts A B

glycerol 10.00 10.00 Iota Carragenan 0.750 0.750 sorbitol (70% solution) 30,000 30,000 propylene glycol 0.500 0.500 Gantrez (13.02% solution) 19,000 15,500 titanium dioxide 0.500 0.500 water (deionized) 9,957 13,457 NaF 0.243 0.243 saccharin sodium 0.300 0.300 pyrophosphate 2,000 2,000 sodium hydroxide (50%) 1,000 1,000 polishing agent for silica based (Zeodent 113) 20,000 20,000 an oxide-based thickener Silica (Sylodent 15) 2,500 2,500 aromatic essential oil 0,950 0,950 TCHE 0.300 0.300 SLS 2,000 2,000

Gantrez is present as an active ingredient in an amount

2.5 parts by weight in toothpaste A and 2.0 parts by weight in toothpaste B.

Hydroxyapatite (HA) obtained from Monsato Co. was used to test the delivery of antibacterial agent to saliva-coated hydroxyapatite disks, which was thoroughly washed with distilled water, filtered in vacuo, and then dried overnight at 37 ° C. The dried hydroxyapatite was ground to a powder in a mortar. Then, 150 milligrams of HA was placed in a chamber for production of potassium bromide pellets (Barnes Analytical, Stanford, CT) and the material was compressed for 6 minutes at a pressure of approximately 5,000 kg in a laboratory press (Carver Laboratory). The resulting 13 mm diameter discs were sintered at 800 ° C in a furnace (Thermolyne) for 4 hours. The saliva was collected in an ice-cooled glass vial and clarified by centrifugation for 15 minutes at 15,000 xg at 4 ^and C. They were then sterilized at the same temperature of 4 ° C and irradiated with ultraviolet light for 1 hour with stirring.

Each sintered disc was hydrated with sterile water in a polyethylene test tube. The water was then removed and replaced with 2.00 ml of 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 1.0 ml of a 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. Then 1 ml of methanol was added to the plate and the plate 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. Then, methanol was 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

Toothpaste Supply of TCHE to hydroxyapatite saliva-coated discs in gg AND 130 (B) 30

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

Example 2

In this example, a toothpaste having the following compositions was prepared, which is effective as an anti-tartar and tartar agent.

component weight parts Sorbitol (70%) 22,00 karagen 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 essential oil 0.95 TCHE 0.30 SLS 2.00

Example 3

In this example, an oral rinse solution was prepared consisting of the following components:

component weight parts tetrasodium pyrophosphate 2.00 Gantrez S-97 2.50 glycerol 10.00 sodium fluoride 0.05 sodium lauryl sulphate 0.20 TCHE 0.06 aromatic essential oil 0.40 water supplement to 100.00

Example 4 In this example, pills were prepared for dissolution under the tongue o the following composition: component % by weight sugar 75 - 80 corn syrup 1 - 20 aromatic essential oil 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 - 0.10 tetrasodium pyrophosphate 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 pyrophosphate 2.00 aromatic essential oil and water: Supplement up to 100.00

In the previous examples, improved results can also be obtained if the TCHE component is replaced by phenol, 2,2-methylenebis (4-chloro-6-bromophenol), eugenol or thymol and / or Gantrez is replaced by another an AEA type, such as one of Carbopol, such as 934 (which is a cross-linking polycarboxylate of 3,000,000 molecular weight), or styrene-phosphonic acid polymers of 3,000 to 10,000 molecular weight, such as poly (β-styrene phosphonic acid) , copolymers of vinylphosphonic acid with β-styrenephosphonic acid or poly (alpha-styrenephosphonic acid) or sulfoacrylic acid oligomers or copolymers of maleic anhydride with ethyl acrylate in a 1: 1 part 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.

'i.?;* Λ alcohol 6 A 5 0

Claims (27)

PATENT CLAIMS, I ‘j I 't' X, An oral composition comprising ¹ : ^x '··' an orally acceptable vehicle,! _-f . - an effective amount of anti-dental caries for at least one alkali metal pyrophosphate salt as an anti-tartar agent, ranging from 0.1% to% by weight, an effective amount of a dental plaque of a substantially water-insoluble non-cationic antibacterial agent in the range of from 0.01% to 5% by weight selected from the group consisting of halogenated diphenyl ethers, halogenated salicylanilides, benzoic acid esters such as e.g. hydroxybenzoic acid methyl ester, ethyl ester, propyl ester and butyl ester, halogenated carbanilides and phenolic compounds selected from phenol, hydroxyphenol, halophenol and substituted phenols, hydroxyphenols and halophenols, wherein said substituents are alkyl, alkenyl, alkoxy, cycloalkyl, aryl and aralkyl groups containing 1 to carbon atoms, hydroxydiphenylmethanes and sulfides and bisphenols, and up to 4% by weight of an antibacterial agent comprising an acidic group promoting release of said antibacterial agent into the oral cavity on the tooth and gum surfaces, said group promoting release being selected from the group consisting of carboxylic acid, phosphonic acid, phosphinic acid and sulfonic acid residues acids and salts and mixtures thereof, and an organic retention aid group for said antibacterial agent in the oral cavity on the surface of teeth and gums, said retention aid group having the general formula: - (X) _n -R wherein: X represents oxygen, nitrogen, sulfur, SO, S0 _2, P, PO or Si, R has a molecular weight ranging from 19 to 60,000 and represents a hydrophobic alkyl, aryl, alkenyl, acyl, alkaryl, aralkyl, nitrogen-containing and / or oxygen-containing heterocyclic group, or inert non-hydrophilic substituted derivatives thereof, which do not substantially adversely affect the release and retention function of said antibacterial agent when n is 1 or zero, - wherein the weight ratio of said antibacterial enhancer to said pyrophosphate ion is in the range of from 1.6: 1 to 2.7: 1, Oral composition according to claim 1, characterized in that it optionally contains a fraction of a fluoride ion providing source sufficient to deliver 25 to 5,000 ppm of fluoride ions. The oral composition of claim 1 or 2, wherein said 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 or 2, wherein said antibacterial agent is a phenolic compound as specified in claim 1. 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 &apos; -nethylene-bis (4-chloro-6-bromophenol). The oral composition of claim 1 or 2, wherein the amount of said antibacterial agent is in the range of 0.25% to 0.5% by weight. The oral composition of claim 1 or 2, wherein said alkali metal pyrophosphate is tetrasodium pyrophosphate. , _t ; , Μ The oral composition of any one of claims 1-8, wherein said pyrophosphate salt is present in an amount ranging from 1% to 2.5% by weight. The oral composition of any one of claims 1-8, wherein the weight ratio of antibacterial enhancer to pyrophosphate ion is in the range of 1.7: 1 to 2.3: 1. The oral composition of claim 10, wherein said weight ratio is in the range of from 1.9: 1 to 2: 1. The oral composition of any one of claims 1 + 8, wherein said vehicle comprises water, a humectant and a gelling agent, and the oral composition comprises a dentally acceptable water-insoluble polishing agent, wherein the oral composition is in the form of a dentifrice. Oral composition according to any one of claims 1 to 8, characterized in that said vehicle comprises water and a non-toxic alcohol, said oral composition being in the form of a mouthwash. The oral composition of any one of claims 1-8, wherein said antibacterial enhancing agent has an average molecular weight ranging from 100 to 1,000,000. The oral composition of any one of claims 1-8, wherein said antibacterial enhancing agent has an average molecular weight in the range of 2,000 to 500,000. The oral composition of any one of claims 1-8, wherein said antibacterial enhancing agent is an anionic polymer comprising at least two release promoting groups and organic retention promoting groups. The oral composition of claim 16, wherein said anionic polymer comprises a chain of repeating units, each containing at least one carbon atom and each unit comprising at least one release promoting group and at least one retention promoting organic group attached to the same atom. , or an adjacent atom or 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 18, wherein the antibacterial enhancer is a maleic acid or maleic anhydride copolymer with another ethylenically unsaturated polymerizable monomer or salt thereof. The oral composition of claim 19, wherein said additional monomer is methyl vinyl ether in a molar ratio with maleic acid or maleic anhydride in a ratio of 4; 1 to 1: 4. The oral composition of claim 19, wherein said copolymer has a molecular weight of 30,000 to 1,000,000. The oral composition of claim 21, wherein said copolymer has an average molecular weight of 70,000. 23. An oral formulation according to claim 16 wherein said release promoting group comprises a phosphone group or a salt thereof. The oral composition of claim 23, wherein said antibacterial enhancing agent is poly-β-styrene phosphonic acid, poly-α-stenephosphonic acid, or a copolymer of styrene phosphonic acid or a salt thereof. The oral composition of claim 23, wherein said antibacterial enhancer has a molecular weight ranging from 1,000 to 30,000. The oral composition of claim 25, wherein said antibacterial enhancer has a molecular weight in the range of 2,500 to 10,000. 27. An oral composition according to claim 1 or 2 comprising - an orally acceptable vehicle, - an effective amount of anti-caries for at least one alkali metal pyrophosphate salt as an anti-tartar agent in the range of 0.1 to% by weight, - an effective amount of an anti-dental coating of a substantially water-insoluble non-cationic antibacterial agent as an anti-dental coating in the range of 0.01% to 5% by weight selected from halogenated diphenyl ethers, halogenated salicylanilides, benzoic esters such as methyl, ethyl, propyl and butyl hydroxybenzoate, halogenated carbanilides and phenolic compounds from the group consisting of phenol, halophenol, hydroxyphenol and substituted phenols, wherein said substituents are alkyl, alkenyl, alkoxy, cycloalkyl, aryl and aralkyl groups containing 1 to 9 carbon atoms, hydroxydiphenylmethanes and sulfides and bisphenoids, and up to 4% by weight of an antibacterial enhancer comprising an acidic group promoting the release of said antibacterial agent into the oral cavity on the surface of the teeth and gums, said group