GB2109686A - Anticalculus oral composition containing a dicarboxylic acid ester - Google Patents

Abstract

A substantially anhydrous oral composition is substantially devoid of normally staining antibacterial antiplaque agents and which contains an effective anticalculus amount of a bis(o-carboxyphenyl) ester of a C2-8 aliphatic dicarboxylic acid such as bis(o-carboxyphenyl) succinate.

Description

SPECIFICATION Anticalculus oral composition The present invention relates to oral compositions containing an anticalculus agent.

Calculus is a hard, mineralized formation which forms on the teeth. Regular brushing prevents a rapid build-up of these deposits, but even regular brushing is not sufficient to remove all of the calculus deposits which adhere to the teeth. Calculus is formed on the teeth when crystals of calcium phosphates begin to be deposited in the pellicle and extracellular matrix of the dental plaque and become sufficiently closely packed together for the aggregates to become resistant to deformation.

There is no complete agreement on the route by which calcium and orthophosphate ultimately become the crystalline material called hydroxyapatite (HAP). It is generally agreed, however, that at higher saturations, that is, above the critical saturation limit, the precursor to crystalline hydroxyapatite is an amorphous or microcrystailine calcium phosphate. "Amorphous calcium phosphate" although related to hydroxyapatite differs from it in atomic structure, particle morphology, and stoichiometry. The X-ray diffraction pattern of amorphous calcium phosphate shows broad peaks typical of amorphous materials, which lack the long-range atomic order characteristic of all crystalline materials, including hydroxyapatite.Whilst the invention is not dependent on its accuracy or otherwise a suggested mechanism by which the nontoxic anticalculus agents of this invention inhibit calculus formation probably involves such agents functioning to bind the amino groups in the matrix system in the oral cavity at physiological pH and temperatures and also cross-links the protein.

A substantial number of different types of compounds and compositions have been developed for use as antibacterial, and antiplaque and anticalculus agents in oral compositions, including for example such cationic materials as the bis-biguanide compounds and quaternary ammonium compounds, e.g.

benzethonium chloride and cetyl pyridinium chloride, disclosed in U.S. 4,080,441. These cationic materials however tend to stain the teeth with continued use.

The present invention aims to provide an improved anticalculus oral composition which will have relatively little or no tendency to stain the teeth.

The invention also aims to provide an oral composition which inhibits the transformation of amorphous calcium phosphate to the hydroxyapatite crystal structure normally associated with calculus.

The invention also aims to provide an improved method for inhibiting the formation of calculus.

In accordance with certain of its aspects, the present invention provides a substantially anhydrous oral composition substantially devoid of stain-inducing antibacterial antiplaque agents and comprising an orally acceptable vehicle and, in an amount effective as an anticalculus agent, at least one bis(o-carboxy phenyl) ester of a C28 aliphatic dicarboxylic acid. The invention also extends to the application of such composition to the teeth.

The anticalculus agents of the present invention may be represented, in their free acid form, by the tormula:

wherein preferably each R independently represents an H atom or C14 alkyl group, more preferably an H atom, and n is an integer from 0 to 6, preferably 2, the preferred anticalculus agent accordingly being bis(o-carboxyphenyl) succinate (BOCS). The CRRX group will be a single bond when n is O as in the bisesters of oxalic acid, or may be any C16 alkylene or alkenylene group, i.e. straight or branched, saturated or unsaturated, 0 or S chain interrupted, C14 alkoxy substituted, or the like. When the -CRR- group is part of an ethylenic group, one or both R's may be replaced by a valence bond.

Examples of anticalculus agents of the present invention include the bis(o-carboxyphenyl) esters of the following aliphatic dicarboxylic acids: oxalic (ethanedioic) malonic (propanedioic) succinic (butanedioic) glutaric (pentanedioic) adipic (hexanedioic) pimelic (heptanedioic) suberic (octanedioic) maleic (1 ,2-ethylenedicarboxylic HOOCCH :CH-COOH) itaconic (methylenesuccinic HOOCC(:CH2)CH2-COOH) isosuccinic (2-methylpropanedioic) muconic (2,4-hexadienedioic HOOCCH :CHCH :CH-COOH) dihydromuconic (HOOCCH2CH2CH:CHCOOH) dihydroitaconic (methylsuccinic) 3-ethylhexanedioic acid.

Further, one or both phenyl moieties in the anticalculus agent may be nuclearly substituted with one or more C14 alkyl or alkoxy groups such as methyl or isobutoxy, or halo such as chloro, bromo, iodo orfluoro.

Suitable methods for preparing these anticalculus agents are disclosed in the aforementioned U.S. 4,080,441 which corresponds to G.B. 1 575699 the entire disclosure of which is incorporated herein by reference. Another improved method for such preparation is described in Example A below.

It will be understood that the free acid form of these anticalculus agents may be converted to and employed in their equivalent salt form by treatment with any base containing an orally acceptable cation such as alkali metal (e.g. sodium, potassium), alkaline earth metal (e.g. calcium, magnesium), metal, ammonium, mono-di-or tri- C,~,8 alkyl or alkanol- substituted ammonium or organic amine (e.g.

methyl, ethyl, hydroxyethyl substituents).

The anticalculus agents of this invention are antinucleating agents, oral compositions of this invention containing them are effective in reducing formation of dental calculus without unduly decalcifying the dental enamel, and in contrast to the above-mentioned cationic antibacterial, antiplaque and anticalculus agents, such agents and compositions have little or no tendency to stain the teeth, and can further be found to effectively reduce or inhibit gingivitis.

The concentration of these anticalculus agents in oral compositions can range widely, typically upward from about 0.01% by weight, with no upper limit on the amount that can be utilized except as dictated by cost or incompatibility with the vehicle. Generally, concentrations from about 0.01% to about 10%, preferably about 0.05% to about 8.0%, and more preferably about 0.1% to about 4% by weight are utilized. Oral compositions which in the ordinary course of usage could be accidentally ingested preferably contain concentrations in the lower portions of the foregoing ranges.

Although these anticalculus agents vary in water solubility depending upon their molecular weight, identity and proportions of salt-forming cations, etc, they are sufficiently soluble in aqueous media, e.g. in the oral cavity, in the low concentrations employed herein to be termed water soluble to that extent. It has however been found unexpectedly that oral compositions containing such agents in an aqueous medium undergo significant hydrolysis or other deterioration in storage. In accordance with a further aspect of this invention, it is preferred to provide oral compositions which are substantially anhydrous, e.g. containing 0 to less than about 0.2 moles of water per mole of the anticalculus agent.

When the oral compositions of this invention are in liquid, paste or cream form, as in mouthwashes and rinses, toothpastes and dental creams, a water-miscible (preferably water soluble) organic normally liquid orally acceptable vehicle is preferably employed. Typically, such vehicles include water soluble C24 monohydric and polyhydric alkanes and C14 alkyl ethers thereof such as ethanol, ethylene glycol, methyl, ethyl and butyl ethers thereof (methyl, ethyl and butyl Cellosolve), propylene glycol, tetramethylene glycol, and glycerin, and water soluble poly (ethylene glycols) such as diethylene glycol, methyl, ethyl, diethyl and butyl ethers thereof (methyl, ethyl, diethyl and butyl Carbitol), triethylene glycol, low molecular weight polyethylene glycols, e.g. 400, 600, and mixtures thereof.Polyhydric compounds in the aforementioned group, especially propylene glycol, glycerin, and the low molecular weight polyethylene glycols, generally function also as humectants which are desirable components of the oral compositions of this invention.

Other types of such water miscible liquid vehicles which may be employed are the polar aprotic solvents such as dimethyl formamide and sulphoxide, N-methyl pyrrolidone, sulpholane, tetramethyl sulphone, acetonitrile, and preferably ethylene and propylene carbonate.

Essentially water-immiscible organic liquid vehicles may also be employed representative of which are hydrocarbon, fatty acid and fatty acid ester oils such as mineral oil, tetradecane, pentane, caproic acid, oenanthylic acid, methyl caproate and laurate, and ethylene glycol dicaprylate.

Mixtures of the same types and/or of different types of liquid vehicles as described above may of course be employed.

The proportion of the aforementioned liquid vehicle employed in these oral compositions will obviously depend for the most part upon the desired degree of fluidity or viscosity and will be readily determinable in routine manner in any particular instance. Typically, liquid compositions such as mouthwashes and rinses contain about 70% to about 99.9%, and toothpastes and dental creams contain about 10% to about 80%, by weight of such liquid vehicle, about 10% to about 100% of which may be a humectant. Normally solid humectants such as sorbitol may also be included.

The oral compositions of this invention typically have, in aqueous medium, e.g. in the oral cavity or in the form of a 20% aqueous slurry or solution, a pH of about 3.5 to about 8, preferably about 4 to about 7, more preferably about 4 to 6. Such pH can be controlled by inclusion of the required amounts of acidic substances such as citric or benzoic acid, basic substances such as sodium hydroxide, and/or buffering agents such as sodium citrate, benzoate, bicarbonate or carbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, or mixtures thereof.

The vehicle in solid or pasty compositions such as toothpowders, tablets, toothpastes and dental creams generally contains polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate (IMP), potassium metaphosphate, tricalcium phosphate, anhydrous, monohydrated and dihydrated calcium and dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, magnesium and calcium carbonate and sulphate, alumina, hydrated alumina, aluminium silicate, alkali metal and alkaline earth metal aluminosilicates, zirconium silicate, silica, bentonite, and mixtures thereof. Preferred polishing materials include crystalline and colloidal silica, silica gel, complex amorphous alkali metal and aluminosilicate, hydrated alumina and IMP.

Alumina, particularly the hydrated alumina sold by Alcoa as C333, which has an alumina content of 64.9% by weight, a silica content of 0.008%, a ferric oxide content of 0.003%; and a moisture content of 0.37%, at 1 1 OOC, and which has a specific gravity of 2.42 and particle size such that 100% of the particles are less than 50 microns and 84% of the particles are less than 20 microns, is very effective.

When visually clear gels are employed, a polishing agent of colloidal silica, such as those sold under the trademark SYLOID (Registered Trade Mark) as Syloid 72, 74 or 244 or under the trade mark SANTOCEL (Registered Trade Mark) as Santocel 100 and alkali metal aluminosilicate complexes are particularly useful, since they have refractive indices close to the refractive indices of gelling agentliquid systems commonly used in dentifrices.

Many of the so-called "water-insoluble" polishing materials are anionic in character and also include small amounts of soluble material. Thus, insoluble sodium metaphosphate may be formed in any suitable manner, as illustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9,4th Edition, pp. 510-511. The forms of insoluble sodium metaphosphate known as Madrell's salt and Kurrol's salt are further examples of suitable materials. These metaphosphate salts exhibit a minute solubility in water, and therefore are commonly referred to as insoluble metaphosphate. There is present therein a minor amount of soluble phosphate material as impurities, usually a few percent such as up to 4% by weight.The amount of soluble phosphate material, which is believed to include a soluble sodium trimetaphosphate in the case of insoluble metaphosphate, may be reduced by washing with water if desired. The insoluble alkali metal metaphosphate is typically employed in powder form of a particle size such that no more than about 1% of the material is larger than about 37 microns.

The polishing material is generally present in amounts ranging from about 20% to about 99% by weight of the oral preparation. Preferably, it is present in amounts ranging from 20% to about 75% in toothpaste, and from about 70% to about 99% in toothpowder.

In the preparation of toothpowders, it is usually sufficient to admix mechanically, e.g. by milling, the various solid ingredients in appropriate quantities and particle sizes.

In a toothpaste, cream or gel, the liquids and solids typically are suitably proportioned to form a creamy or gelled mass which is extrudable from a pressurized container or from a collapsible tube.

Thickening to the proper desired viscosity or flowability is typically facilitated or achieved by inclusion of a binding, thickening or gelling agent such as natural or synthetic gums or gum-like materials, typically such as Irish moss, Pluronics (Registered Trade Mark), sodium carboxymethylcellulose and carboxyethylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, Laponite (Registered Trade Mark) CP or SP (synthetic hectorite clay of Laporte Industries (Ltd.), viscarin, gelatin, glucose, sucrose, Carbopols (e.g.

934,940,941) (Registered Trade Mark), gum karaya, gum arabic, gum tragacanth, polyvinylpyrrolidone, polyvinyl alcohol and starch. They are usually present, singly or plurally, in an amount up to about 10% by weight, preferably in the range of from about 0.5% to about 5%. The preferred gelling agents are Pluronics and hydroxypropyl cellulose. Pluronics such as F108 and F127 are polyoxypropylene polyoxyethylene block polymers which simultaneously function as nonionic surfactants.

The oral compositions of this invention may contain a non-soap synthetic sufficiently water soluble organic anionic or nonionic surfactant in concentrations generally ranging from about 0.05 to about 10, preferably about 0.5 to about 5, weight percent, to promote wetting, detersive and foaming properties. U.S. Patent No. 4,041,149 discloses such suitable anionic surfactants in column 4, lines 31-38 and such suitable nonionic surfactants in column 8, lines 30-68 and column 9, lines 112, which passages are incorporated herein by reference thereto.

Thus, suitable anionic surfactants include, for example, the water-soluble salts of higher fatty acid monoglyceride monosulphate detergents (e.g. sodium coconut fatty acid monoglycedde monosulphate), higher alkyl sulphates (e.g. sodium lauryl sulphate), alkyl aryl sulphonates (e.g. sodium dodecyl benzene sulphonate), higher fatty acid esters of 1 ,2-dihydroxypropanesulphonate and the like.

Suitable non-ionic organic surface active compounds include water-soluble products which are derived from the condensation of an alkylene oxide or equivalent reactant and a reactive-hydrogen hydrophobe. The hydrophobic organic compounds may be aliphatic, aromatic or heterocyclic, although the first two classes are preferred. The preferred types of hydrophobes are higher aliphatic alcohols and alkyl phenols, although others may be used such as carboxylic acids, carboxamides, sulphoamides, etc.

The ethylene oxide condensates with higher-alkyl phenols represent a preferred class of non-ionic compounds. Usually the hydrophobic moiety should contain at least about 8 carbon atoms, and may contain as many as about 50 carbon atoms or more. The amount of alkylene oxide will vary considerably, depending upon the hydrophobe, but as a general guide and rule, at least about 5 moles of alkylene oxide per mole of hydrophobe should be used. The upper limit of alkylene oxide will vary also, but no particular criticality can be ascribed thereto. As much as 200 or more moles of alkylene oxide per mole of hydrophobe may be employed. While ethylene oxide is the preferred and predominating oxyalkylating reagent, other lower alkylene oxides such as propylene oxide, butylene oxide, and the like, may also be used or substituted in part for the ethylene oxide.Other non-ionic compounds which are suitable are the polyoxyalkylene esters of the organic acids such as the higher fatty acids, the rosin acids, tall oil acids, acids from petroleum oxidation products, etc. These esters will usually contain from about 10 to about 22 carbon atoms in the acid moiety and from about 12 to about 30 moles of ethylene oxide or its equivalent.

Still other non-ionic surfactants are the alkylene oxide condensates with the higher fatty acid amides. The fatty acid group will generally contain from about 8 to about 22 carbon atoms and this will be condensed with about 10 to about 50 moles of ethylene oxide as the preferred illustration. The corresponding carboxamides and sulphonamides may also be used as substantial equivalents.

Still another class of non-ionic products are the oxyalkylated higher aliphatic alcohols. The fatty alcohols should contain at least 6 carbon atoms, and preferably at least about 8 carbon atoms. The most preferred alcohols are lauryl, myristyl, cetyl, stearyl and oleyl alcohols and the said alcohols should be condensed with at least about 6 moles of ethylene oxide, and preferably about 10 to 30 moles of ethylene oxide. A typical non-ionic product is oleyl alcohol condensed with 1 5 moles of ethylene oxide.

In certain forms of this invention a fluorine-providing compound is present in the oral preparation.

These compounds may be slightly soluble in water or may be fully water-soluble. They are characterised by their ability to release fluoride ions in water and by substantial freedom from reaction with other compounds of the oral preparation. Among these materials are inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal and heavy metal salts, for example, sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, a copper fluoride such as cuprous fluoride, zinc fluoride, a tin fluoride such as stannic fluoride or stannous chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium fiuorosilicate, sodium fluorozirconate, sodium monofluorophosphate, aluminium mono- and di-fluorophosphate, and fluorinated sodium calcium pyrophosphate.Alkali metal and tin fluorides, such as sodium and stannous fluorides, sodium monofluorophosphate and mixtures thereof are preferred.

The amount of the fluorine-providing compound is dependent to some extent upon the type of compound, its solubility, and the type of oral preparation, but it must be a nontoxic amount. In a thickened or solid oral preparation, such as toothpaste or toothpowder, an amount of such compound which releases a maximum of about 1% by weight of the preparation is considered satisfactory. Any suitable minimum amount of such compound may be used, but it is preferable to employ sufficient compound to release about 0.005% to 1 9/0, and preferably about 0.19/0 of fluoride ion.Typically, in the cases of alkali metal fluorides and stannous fluoride, this component is present in an amount up to about 2% by weight, based on the weight of the preparation, and preferably in the range of about 0.05% to 1%. In the case of sodium monofluorophosphate, the compound may be present in an amount up to 7.6% by weight, more typically about 0.5 to about 1% by weight.

In a liquid oral preparation such as a mouthwash, the fluorine-providing compound is typically present in an amount sufficient to release up to about 0.0005 to about 0.2%, preferably about 0.001 to about 0.1% and more preferably about 0.0013% by weight of fluoride ion.

Various other materials may be incorporated in the oral preparations of this invention such as whitening agents, preservatives, silicones, chlorophyli compounds, other anticalculus agents, antibacterial antiplaque agents, and/or ammoniated material such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, where present, are incorporated in the preparations in amounts which do not substantially adversely affect the properties and characteristics desired.

Any suitable flavouring or sweetening material may also be employed.

Examples of suitable flavouring constituents are flavouring oils, e.g. oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange, menthol, eugenol, cineol, and methyl salicylate. Suitable sweetening agents include sucrose, fructose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartine, APM (aspartyl phenyl alanine, methyl ester) and saccharine. Suitably, flavour and sweetening agents may together comprise from about 0.019/0 to 5% or more of the preparation.

In preparing the oral compositions of this invention, it is preferred but not essential to add the anticalculus agent after the other ingredients (except perhaps some of the water) are mixed or contacted with each other to avoid a tendency for such agent to be precipitated.

It will be understood that, as is conventionai, the oral preparations are to be sold or otherwise distributed in suitable labelled packages. Thus a jar of mouthrinse will have a label describing it, in substance, as a mouthrinse or mouthwash and having directions for its use; and a toothpaste will usually be in a collapsible tube, typically aluminium, lined lead or plastic, or other squeeze dispenser for metering out the contents, having a label describing it, in substance, as a toothpaste or dental cream.

In the practice of this invention an oral composition according to this invention such as a mouthwash or toothpaste containing the described anticalculus agent in an amount effective to inhibit calculus on dental surfaces is applied regularly to the oral cavity, especially dental enamel, preferably from about 1 to 3 times daily.

The invention may be put into practice in various ways and a number of specific embodiments will be described to illustrate the invention with reference to the accompanying examples.

All amounts and proportions referred to herein and in the appended claims are by weight and temperatures are in OC, unless otherwise indicated.

Example A Preparation of Bis(o-carboxyphenyl)succinate 55.2 grams (0.4 moles) of salicylic acid and 31.2 ml (0.4 moles) of pyridine were dissolved in 90 ml of acetone. To the resulting clear solution 31.0 grams (0.2 moles) of succinyl chloride in 90 ml of acetone were added, with stirring, at a rate to keep the acetone refluxing for half an hour. During this addition, the desired BOCS product began to separate and the mixture turned dark purple. The reaction slurry was stirred for half an hour after all the succinyl chloride had been added. Then 200 ml of water was added, the acetone evaporated off from the slurry in a rotary evaporator at 350C and the desired BOCS product collected on a suction filter, washed with water and dried in vacuum at 600 C.

Yield-66.5 grams (93%) M.P. 1770--177.50C Neutral Equivalent 179.9* Saponification Eq. 1 86.8* *Calculated for C,8H,408 Example 1 The following formulation is illustrative of a toothpaste in accordance with the present invention which is effective to inhibit calculus.

Parts by weight Propylene 42.0 Hydroxypropyl cellulose 1.0 Polyethylene glycol 600 10.0 Sodium saccharin 0.2 TiO2 0.4 IMP 28.0 Syloid 244 12.0 Sodium lauryl sulphate 1.5 Flavour 1.0 BOCS 3.0 Examples 2,3 and 4 The following formulations, given in parts by weight in Table 1, are illustrative of mouthwashes in accordance with the present invention which are effective to inhibit calculus.

Table 1 Example 2 3 4 Flavour 0.22 0.22 0.22 Ethanol 15.0 15.0 15.0 Pluronic F108 3.0 3.0 3.0 Glycerine 10.0 10.0 10.0 Sodium saccharin 0.03 0.03 0.03 BOCS 0.05 0.50 1.0 The mouthwash formulations of Examples 2-4 above may be applied to the oral cavity as is or after dilution with about 2 to 4 times their volumes of water, i.e. volume ratios of formulation: water of about 1:2 to about 1:4.

Examples 5 to 13 Substitution of equivalent amounts of the following bis ester-containing compounds for the BOCS employed in the formulations of Examples 1 -4 yield formulations also effective for inhibiting dental calculus.

Example Bis ester-containing compound 5 bis(2-carboxy-4-butoxyphenyl)oxa late 6 bis(2-carboxy-4-propyl-6-chlorophenyl)glutarate 7 bis(2-carboxy-4-methyl-6-bromophenyl)adipate 8 bis(2-carboxy-4-iodo-6-ethoxyphenyl)suberate 9 bis(2-carboxyphenyl)pimelate 10 bis(2-ca rboxy-5-methoxyphenyl)ma Ion ate 11 bis(2-carboxy-6-butylphenyl)maleate 12 bis(2-carboxyphenyl)itaconate 1 3 bis(2-carboxy-4-fluorophenyl)muconate Example 14 In this study on 24 rats, a placebo of water and as the test anticalculus mouthrinse a 0.1% solution of BOCS in dimethyl sulphoxide, pH 7.10, were evaluated for effectiveness against formation of calculus for a 30 day period. Litter matured Osborne-Mendel rats were used.On days 21 and 22 they were inoculated intraorally with Strep-mutans and Actinoymyces viscsous and feces from cariesactive Osborne-Mendel rats, placed on calculogenic diet 580F supplemented with 0.2% P as Na2PO4, and the placebo and the test mouthrinse each applied to molars of a group of 1 2 such rats twice daily on Monday to Friday and once daily on Saturday and Sunday for a period of 30 days. The animals were weighed at the beginning and at the end of the study to assure that the rats remained in otherwise normal condition. At the end of the period, calculus formulation was assessed according to routine procedures and the results given in Table 2 were found: Table 2 Mean No. Mean terminal calculus Signifi animals weight gain units* cance Placebo (Water) 12 128 grams 17.9 Mounthrinse 12 135 grams 14.8 (z < 0.01 (0.1% BOCS) *20 units at risk The above results establish that BOCS at 0.1% level when applied topically is significantly effective (at the +99% level) in reducing calculus formation.

Claims (8)

Claims

1. A substantially an hydros oral composition substantially devoid of stain inducing antibacterial antiplaque agents and comprising an orally acceptable vehicle and in an effective amount as an anticalculus agent at least one bis(o-carboxyphenyl) ester of a C28 aliphatic dicarboxylic acid.

2. An oral composition as claimed in Claim 1 in which the said anticalculus agent is bis(ocarboxyphenyl) succinate.

3. An oral composition as claimed in Claim 1 or Claim 2 containing approximately 0.01% to 10% by weight of the said anticalculus agent.

4. An oral composition as claimed in Claim 3 containing approximately 0.05% to 5% by weight of the said anticalculus agent.

5. An oral composition as claimed in any one of Claims 1 to 4 which is a mouthwash containing a liquid vehicle and having, in aqueous medium, a pH of about 3.5 to about 8.

6. An oral composition as claimed in any one of Claims 1 to 4 which is a toothpaste containing a liquid vehicle, a gelling agent and a dentally acceptable polishing agent and having, in aqueous medium, a pH of about 3.5 to about 8.

7. An oral composition as claimed in Claim 1 substantially as specifically described herein with reference to any one of Examples 1 to 13.

8. A method comprising applying to the oral cavity a calculus-inhibiting amount of a composition as claimed in any one of Claims 1 to 7.