GB2056857A - Oral composition - Google Patents

Abstract

An oral composition such as a mouthwash or a toothpaste is disclosed containing, as an anticalculus agent 0.01% to 10% by weight of a 2-phosphono-butane-1,2,4-tricarboxylic acid compound of formula: <IMAGE> where R = H, lower alkyl or carboxyl and R<1> = H or methyl. A normally staining antibacterial antiplaque agent may also be present.

Description

SPECIFICATION Oral composition This invention relates to oral compositions containing containing en anticalculus agent.

Calculus is a hard, mineralised formation which which brims on the teeth. Regular brushing prevents a rapid build-up of these deposits, but even regular brushing may not be 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 pscked together for the aggregates to become resistant to deformation.There is no complete agreement on the route by which calcium and orthophos- phate 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 hyadroxyapatite a an amorphous or microcryst-ailine 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 longrange atomic order characteristic of all crystalline materials, including hydroxyapatite. it is apparent therefore that agents which effectively interfere with crystalline growth of hydroxyapatite will be effective as anticalculus agents.

According to the present invention an oral composition such as a mouthwash or a toothpaste comprises an orally acceptable vehicle containing, as an anticalculus agent, approximately by weight 0.01% to 10% of a 2-phosphono-butane-1,2,4-tricarbolic acid compound of the formula

wherein R is hydrogen, lower alkyl or carboxyl, end R1 is hydrogen or mYeR gl, or an orally acceptable salt thereof.Preferred orally acceptable salts are water soluble salts such as with an alkali metal (e.g. sodium and potassiurY-i), ammonium, C1-C18 mono-, di- and tri-substituted ammonium (e.g. aikanol substitu"sd such as mono-, di- and tlri-stlhanolarrYmoniumY cation).

A suggested mechanism by which the compound of of Formula I (hereafter referred to as PBTA") inhibits calculus formation probably involves an increase of activation energy barrier thus inhibiting the transformation of precursor amorphous calcium phosphate to hydroxyapatite.

Studies have shown that there is a good correlation between the ability of a compound to prevent hydroxyapatite crystalline growth in vitro and its ability to prevent calcification in vivo.

PTBA compounds of the above formula, and methods for their production are disclosed in U.S. Patent Nos: 3886204 and 3886205 which disclosures are incorporated herein by reference. The preferred PETA compound for use in the present invention is the unsubstituted compound of the above formula I in which R and R1 are each hydrogen. When R is lower alkyl, it preferably contains 1 to 4 carbon atoms, especially waePhyB.

The concentration of the PBTA compound (or salt) in the oral compositions can range widely, typically upward from about 0.01% % by weight, the upper limit on the amount that can be utilized except also being dictated by cost or incompatibility with the vehicle. Generally concentrations of 0.01% to 10% and preferably 0.1% % to 6% by weight are utilized. Oral compositions which in the ordinary course of usage could be accidentally ingested preferably contain lower concentrations of the PBTA compound. Thus, a mouthwash in accordance with this invention preferably contains less than about 2 weight % of the PBTA compound, preferably 0.1 to 1.5 weight %.Other dentifrice compositions, topical solutions and prophylactic pastes, the latter to be administered professionally, can preferably contain 0.1 to 3 weight % of the PBTA compound.

The PBT compounds of this invention are antinucleating agents and oral compositions of this invention containing then, are effective in reducing formation of dental calculus without unduly decalcifying the dental enamel. Furthermore such PUB TEA compounds and compositions have little or no tendency to stain the teeth, in in addition to inhibiting gingivitis.

The inhibition on crystal growth of HAP by PBTA is demonstrated and evaluated by a pH Stat method. 1.0 ml of an aqueous solution of 1 x ec 10-4M to 1 x x 05M of the anticalculus agent being tested and 0.1 M sodium dihydrogen phosphate is placed in a reaction flask with 22 to 23 ml. of distilled water with continuous stirring in an atmosphere of nitrogen. To this is added 1 ml. of 0.1 M CaCI2 and the pH adjusted to 7.4 0.05 with NaOH (final conc. of Ca + + and P043 - = 4 x 10 - 3M). Consumption of 0.1 N NaOH is recorded automatically by a pH Stat (Radiometer). In this test, the formation of HAP occurs in 2 distinct phases.First rapid base consumption (1 -4min.) then diminishes until 15-20 minutes when second rapid uptake takes place. A delay in the time of second rapid consumption or a total absence of the second rapid consumption indicates an interference with the crystal growth of HAP. Agents which interfere with HAP crystal growth are effective anticalculus agents. When PBTA is tested by the foregoing procedure, the following results are obtained.

TABLE I Anticalculus Time for Delay in Agent (conc) HAP Formation HAP Formation Water (control) 1 5 min PBTA (4 ppm) 25 min 10 min PBTA (8 ppm) 75 min 60 min PBTA (10 ppm) 129 min 114 min PBTA (20 ppm) 33.8 hrs 33.55 hrs The above results show that PBTA effectively inhibits crystal growth of HAP in vitro and that the inhibition is not due to complexation or chelation of calcium since sub-stoichiometric ratios of PBTA: calcium are employed.

Cationic nitrogen-containing antibacterial materials are well known in the art. See, for instance the section on "Quaternary Ammonium and Related Compounds" in the article on "Antiseptics and Disinfectants" in Kirk-Othmer Encyclopedia of Chemical Technology, second edition (Vol 2, pp. 632-635), incorporated herein by reference. Cationic materials which possess antibacterial activity (i.e. are germicides) are used against bacteria and have been used in oral compositions to counter plaque formation caused by bacteria in the oral cavity.

Among the most common of these antibacterial antiplaque quaternary ammonium compounds in benzethonium chloride, also known as Hyamine 1 622 or di-isobutylphenoxyethoxyethyl dimethyl benzyl ammonium chloride. In an oral preparation this material is highly effective in promoting oral hygiene by reducing formation of dental plaque and calculus, which is generally accompanied by a reduction in caries formation and periodontal diseases. Other cationic antibacterial agents of this type are those mentioned. For instance, in U.S. Patent Nos: 2984639, 3325402, 3431208 and 3703583 and British Patent No: 1319396.

Other antibacterial anti-plaque quaternary ammonium compounds include those in which one or two of the substituents on the quaternary nitrogen has a carbon chain length (typically alkyl group) of some 8 to 20, typically 10 to 18, carbon atoms while the remaining substituents have a lower number of carbon atoms (typically alkyl or benzyl group), such as 1 to 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethyl ammonium bromide, dodecyl dimethyl (2phenoxyethyl) ammonium bromide, benzyl dimethyl stearyl ammonium chloride, cetyl pyridinium chloride and quaternized 5-amino-1,3,-bis (2-ethyl-hexyl)-5-methyl hexa hydropyrimidine are exemplary of other typical quaternary ammonium antibacterial agents.

Other types of cationic antibacterial agents which are desirably incorporated in oral compost tions to promote oral hygiene by reducing plaque formation are the amidines such as the substituted guanidines e.g. chlorhexidine and the corresponding compound, alexidine, having 2ethylhexyl groups instead of chlorophenyl groups and other bis-biguanides such as those described in German Patent application No:P2332383 published January 10, 1974, which sets forth the following formula:

in which A and A' signify as the case may be either (1) a phenyl radical, which as substituent can contain up to 2 alkyl or alkoxy groups with 1 up to about 4C-atoms, a nitro group or a halogen atom, (2) an alkyl group which contains 1 to about 12C-atoms, or (3) alicyclic groups with 4 to about 12C-atoms, X and X' as the case may be may represent an alkylene radical with 1-3C atoms, z and z' are as the case may be either zero or 1, R and R' as the case may be may represent either hydrogen, an alkyl radical with 1 to about 1 2C-atoms or an aralkyl radical with 7 to about 12atoms, n is a whole number of 2 to inclusively 1 2 and the polymethylene chain (CH2) can be interrupted by up to 5 ether, thioether, phenyl- or naphthyl groups; these are available as pharmaceutically suitable salts. Additional substituted guanidines are: N'-4(4chlorobenzyl-N5-(2,4-dichlorobenzyl) biguanide; p-chlorobenzyl biguanide; 4-chlorobenzhydryl guanylurea; N-3-lauroxypropyl-N5-p-chlorobenzyl biguanide; 5,6-dichloro-2-guanidobenzimida- zole; and N-p-chlorophenyl-N5-iaurylbiguanide.

The long chain tertiary amines also possess antibacterial and antiplaque activity. Such antibacterial agents include tertiary amines having one fatty alkyl group (typically 1 2 to 1 8 carbon atoms) and 2-poly(oxyethylene) groups attached to the nitrogen (typically containing a total of from 2 to 50 ethenoxy groups per molecule) and salts thereof with acids and compounds of the structure:

where R is a fatty alkyl group containing 1 2 to 1 8 carbon atoms and x, y and z total 3 or higher, as well as salts thereof. Generally, cationic egents are preferred for their antiplaque effectiveness.

These nitrogen-containing cationic antibacterial agents and long chain tertiary amine antibacterial agents effectively promote oral hygiene, particularly by removing plaque. However, their use has been observed to lead to staining of dental surfaces or discolouration.

The reason for the formation of such dental stain has not been clearly established. However, human dental enamel contains a high proportion 6about 95%) of hydroxyapatite (HAP) which includes Ca+2 and P04-3 ions. In the absence of dental plaque additional Ca+2 and P04-3, particularly from saliva, can be deposited on the enamel and such deposits can include colour bodies which ultimately stain the tooth enamel as a calcified deposit thereon. It can be that as the cationic or long chain tertiary amine antibacterial agents remove plaque they also denature protein from saliva in the oral environment and the denatured protein can then act as a nucleating agent which is deposited on and stains or discolours tooth enamel.

Previously employed additives which reduced dental staining by cationic antibacterial antiplaque agents also generally reduced the activity of antibacterial antiplaque agents such as bisbiguanido compounds, as by forming a precipitate with such agents.

It has however now been found that the anti-nucleating anticalculus PBTA compounds of the present invention unexpectedly inhibit, i.e. prevent, reduce or remove, the staining of dental enamel caused by the above-described nitrogen-containing antiplaque, antibacterial agents without precipitating or substantially adversely affecting their antibacterial and antiplaque activity. Not all anti-nucleating agents are effective to prevent staining by such antibacterial agents. Victamide (also known as Victamine C) which is a condensation product of ammonia with phosphoruspentoxide, actually increases staining even in the absence of such antibacterial agents.

When present, these normally staining antibacterial antiplaque agents are typically employed in normally effective amounts, e.g. such that the oral product contains between 0.001 and 15% by weight thereof. Preferably for desired levels of antiplaque effect, the finished oral product contains from 0.01 to 5%, and most preferably from 0.25 to 1.0% by weight of the antibacterial antiplaque agent, referring to its free base form. Most desirably the PBTA compound is present in a molar excess relative to the amount of antibacterial antiplaque agent (based on its free base form) in order to best minimize, inhibit or prevent staining.

The antibacterial antiplaque agents normally preferred have an antibacterial activity such that its phenol co-efficient is well over 50, more preferably well above 1 duo, such as above about 200 or more for S. aureus; for instance the phenol coefficient (A.O.A.C.) of benzethonium chloride is given by the manufacturer as 410 for S. aureus. The cationic antibacterial agent will generally be a monomeric (or possibly dimeric) material of molecular weight well below 2,000, such as less than about 1 ,000. It is, however, possible to employ a polymeric cationic antibacterial agent.The cationic antibacterial is preferably supplied in the form of an orally acceptable salt thereof, such as the chloride, bromide, sulphate, alkyl sulphonate, such as methyl sulphonate and ethyl sulphonate, phenylsulphonate, such as p-methylphenyl sulphonate, nitrate, acetate and gluconate.

In certain highly preferred forms of the invention the oral composition may be substantially liquid in character, such as a mouthwash or rinse. In such a preparation the vehicle is typically a water-alcohol mixture desirably including a humectant as described below. Generally the ratio of water to alcohol is in the range of from 1:1 to 20: 1, preferably 3:1 to 1 0:1 and most preferably 4:1 to 5: 1, by weight. The total amount of water-alcohol mixture in this type of preparation is typically in the range of from 70% to 99.9% by weight of the preparation. The pH of such liquid and other preparations of the invention is generally in the range of from 4.5 to 9 and typically from 5.5 to 8. The pH is preferably in the range of from 6 to 8.0.It is noteworthy that the compositions of the invention may be applied orally at a pl I below 5 without substantially decalcifying dental enamel. The pH can be controlled with acid (e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) or buffered (as with phosphate buffers). Such liquid oral preparations may also contain a surface active agent and/or a fluorine-providing compound.

In certain other desirable forms of this invention, the oral composition may be substantially solid or pasty in character, such as toothpaste, a dental tablet, a toothpaste or dental cream. The vehicle of such solid or pasty oral preparations generally contains polishing material. Examples of polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate. calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, alumina, hydrated alumina, aluminium silicate, zirconium silicate, silica, bentonite, and mixtures thereof. Preferred polishing materials include silica gel or colloidal silica, complex amorphous alkali metal aluminosilicate and hydrated alumina.

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 110"C, and which has a specific gravity of 2.42 and a 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 anticalculus gels are employed, a polishing agent of colloidal silica, such as those sold under the trade mark SYLOID as Syloid 72 and Syloid 74 or under the trade mark SANTOCEL as Santocel 100 and alkali metal aluminosilicate complexes are particularly useful, since they have refractive indices close to the refractive indices of gelling agent-liquid (including water and/or humectant) systems commonly used in dentifrices. For similar reasons, alkali metal aluminosilicate complexes are particularly useful as polishing agents in visually clear gels containing PBTA compound in combination with the described nitrogen-containing antibacterial antiplaque agents.

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 metaphosphates. 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 10% to 99% by weight of the oral preparation. Preferably, it is present in amounts ranging from 10% to 75% in toothpaste, and from 70% to 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 pasty oral preparations the PBTA compound should be compatible with the other components of the preparation. Thus, in a toothpaste, the liquid vehicle may comprise water and humectant typically in an amount ranging from 10% to 90% by weight of the preparation.

Glycerine, propylene glycol, sorbitol, or polyethylene glycol 400 may also be present as humectants or binders. Particularly advantageous liquid ingredients comprise mixtures of water, glycerine and sorbitol. In clear gels where the refractive index is an important consideration from 3 to 30% by weight of water, 0 to 80% by weight of glycerine, and 20 to 80% by weight of sorbitol is preferably employed. A gelling agent, such as natural or synthetic gums or gum-like materials, typically Irish moss, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, the Carbopols (e.g. 934, 940 and 941), gum tragacanth, polyvinylpyrrolidone or starch or mixtures thereof or the like is usually present in toothpaste in an amount up to about 10% by weight, preferably in the range of from 0.5% to 5%.In a toothpaste or gel, the liquids and solids are proportioned to form a creamy or gelled mass which is extrudable from a pressurized container or from a collapsible, e.g. aluminium or lead, tube.

The solid or pasty oral preparation which typically has a pH measured on a 20% slurry of 4.5 to 9, generally 5.5 to 8 and preferably 6 to 8.0, may also contain a surface active agent and/or a fluorine-providing compound.

It will be understood that, as is conventional, 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 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.

Organic surface-active agents are used in the compositions of the present invention to achieve increased prophylactic action, assist in achieving thorough and complete dispersion of the PBTA agent throughout the oral cavity, and render the instant compositions more cosmetically acceptable. The organic surface-active material is preferabl > , anionic, nonionc or ampholytic in nature, and it is preferred to employ as the surface-active agent a detersve material which imparts to the composition detersive and foaming properties.Suitable e:amples of anionic surfactants are water-soluble salts of higher fatty acid monoglycende monosulphates, such as the sodium salt of the monosulphated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulphates, such as sodium lauryl sulphate, alkyl aryl sulphonates such as sodium dodecyl benzene sulphonate, higher alkyl sulphoacetates, higher fstW acid esters of 1,2 dihydrnxy propane sulphonate and the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds, such as those having 1 2 to 16 carbons in the fatty acid, alkyl or acyl radicals, and the like. Examples of the last mentioned amides are N lauroyl sarcosine, and the sodium potassium and ethanolamine salts of N-lauroyl, N-myristoys, or N-palmitoyl sarcosine which should be substantially free from soap or sirnílar higher fatty acid material.The use of these sarcosinate compounds in dentifrice compositions of the present invention is particularly advantageous since these materials exhibit a prolonged and marked effect in the inhibition of acid formation in the oral cavity due to carbohydrate breakdown in addition to exerting some reduction in the solubility of tooth enamel in acid solutions.

Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydropho bic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain hydrophilic polyoxyathelene moities, such as condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g.

sorbitan monostearate) and polypropylene oxide (i.e. Pluronic materials).

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, a copper fluoride such as cuprous fluoride, zinc fluoride, a tin fluoride such as stannic fluoride or stannous chlorofluoride, barium fluoride, sodium fluorsilicate, ammonium fluorosilica < e, sodium fluorozirconate, sodium monofluorophosphate, aluminium mono- and di-fEuoroplaosphaie, and fluorinated sodium cal cium 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 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, bu: it is preferably to employ sufficient compound to release 0.005% to 1%, and preferably about 0.1% 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 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 0.75%.

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 0.13% preferably 0.0013% to 0.1% and most preferably 0.0013% to 0.5% by weight, of fluoride ion.

Various other materials may be incorporated in the oral preparations of this invention such as whitening agents, preservatives, silicones, chlorophyll 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. oil of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, rnarjoram, cinnamon, lemon and orange, and methylsalicy late. Suitable sweetening agents include sucrose, lactose, maltase, sorbitol, xylitol, sodium cyclamate, perillartine, APM (aspartyl phenyl alanine, methyl ester) and saccharine. Suitably flavour and sweetening agents may together comprise from 0.01 % to 5% or more of the preparation.

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

For instance a mouthrinse or mouthwash may be prepared by mixing ethanol and water with flavouring oil, surfactant, humectant, optional antibacterial antiplaque agent, such as cetyl pyridinium chloride, benzethonium chloride or chlorohexidine, sweetener, colour and then the above-defined PBTA compound followed by additional water as desired.

A toothpaste may be prepared by forming a gel with humectant, gum, thickener or gelling agent such as hydroxyethyl cellulose, sweetener and adding thereto polishing agent flavour, optional antibacterial antiplaque agent, additional water, and then the above-defined PBTA compound. If sodium carboxymethylcellulose is employed as the gelling agen; vogelher with a bis-biguanide type antibacterial antiplaque agent, the procedure of either U.S. Za-er,t No: 3842168 or U.S. Patent No: 3843779 modified by the inclusion of the PBTA compound is followed.

In the practice of this invention an oral composition according to this invention such as a mouthwash or toothpaste is applied regularly to dental enamel, preferably from 1 to 3 times daily, at a pH of 4.5 to 9, generally 5.5 to 8, preferably 6 to 8.

The following Examples are illustrative of the present invention. All amounts and proportions are by weight unless otherwise indicated.

Mouthwash formulations according to the invention were made up as follows, Pluronic Fl 08 being a polyalkylene oxide block polymer. (PLURONIC is a trade mark).

EXAMPLES 2 2 3 4 Flavour 0.22 0.22 0.22 0.22 Ethanol 15.0 15.0 15.0 15.0 Pluronic F108 3.0 3.0 3.0 3.0 Glycerine 10.0 10.0 10.0 10.0 Sodium Saccharin 0.03 0.03 0.03 0.03 PBTA 0.1 0.2 0.5 1.0 Waterq.s.to 100 400 100 100 ph (with NaOH) 7.4 7.4 7., 7.4 Appearance Clear Clear Clear Clear The following Example is illustrative or anticalculus toothpaste made u9 in accordance with the invention.

EXAMPLE 5 Silica 30 Glycerine 1 6 Sorbitol (70%) 6 Pluronic F-108 3 Hydroxyethyl cellulose 1.2 PBTA 2 Sodium Saccharin 0.17 Flavour 0.8 Water q.s. to 100 Table il below is illustrative of further mouthwash formulations according to the invention and the antistaining activity of the preferred PBTA additive therein. The tooth staining characteristics of the formulations are evaluated by slurrying hydroxyapatite (Biogel), a specific salivary protein, a carbonyl source (e.g. acetaldehyde), and a pH 7 phosphate buffer, with and without the mouthwash formulations being tested. The mixture is shaken at 37"C. for 18 hours. The coloured HAP powder is separated by filtration dried and the colour levels (in reflectance units) determined on a Gardner colour difference meter.

TABLE 11 CLEAR MOUTHWASH FORMULATIONS CONTROLS EXAMPLES 1 2 6 7 8 9 10 Ethanol 10% 10% 10% 10% 10% 10% 10% Glycerine 10 10 10 10 10 10 10 Pluronic F108 3.0 3.0 3.0 3.0 3.0 3.0 3.0 Flavour 0.146 0.146 0.146 0.146 0.146 0.146 0.146 Sodium Saccharin 0.03 0.03 0.03 0.03 0.03 0.03 0.03 Cetyl Pyridinium Chloride (CPC) 0.1 0.1 0.1 0.1 0.1 0.1 PBTA - - 0.1 0.2 0.3 0.5 1.0 Water q.s. to 100% 100% 100% 100% 100% 100% 100% Ph (with 1N NaOH) 7.0 7.0 7.0 7.0 7.0 7.0 7.0 Reflectance 56.8 39.6 42.1 43.6 46.2 47.8 55.9 Difference RD - + 17.2 - 2.5 - 4.0 - 6.6 - 8.2 - 16.3 COMPARED TO CONTROL 2 The above results plainly establish that the additives of the present invention, as exemplified by PBTA, substantially reduce dental staining ordinarily produced by antibacterial antiplaque agents as exemplified by CPC. A PBTA concentration of about 1.0% appears to yield excellent results. Such additives also reduce or inhibit calculus gingivitis and do not significantly reduce the antiplaque activity of the indicated antiplaque agents.

Substitution of equivalent amounts of the following antibacterial antiplaque agents for the CPC employed in Examples 6-10 yield formulations also producing an unexpected reduction in dental staining and calculus.

Example Antibacterial Antiplaque Agent 11 benzethonium chloride (BC) 1 2 chlorhexidine diacetate 1 3 chlorohexidine digluconate 14 dodecyl trimethyl ammonium bromide CH2CH2OH CH2CH2OH 15 5 sAlkyl-N-CH2CH2N CH2CH20H 1 6 alexidine dihydrochloride The following formulations exemplify toothpastes with antiplaque activity and reduced staining and calculus.

EXAMPLES 17 18 19 Hydrated alumina 30 30 30 Polyethylene glycol 600 22 22 22 Pluronic F-108 3 3 3 Hydroxypropyl methyl cellulose 1.2 1.2 1.2 BC 0.5 - - Hibitane 4.725 CPC - 0.5 PBTA 1.0 1.0 1.0 Sodium Saccharin 0.17 0.17 0.17 Flavour 0.8 0.8 0.8 Water q.s. to 100 100 100 Significant reductions in dental staining, plaque, calculus and gingivitis are also obtained according to the present invention when the PBTA in the above Examples replaced by any of the other PBTA compounds disclosed in U.S. Patent Nos: 3886204 and 3886205.

Claims (16)

1. An oral composition comprising an orally acceptable vehicle containing approximately by weight 0.01% to 10% of a 2-phosphono-butane-1 2,4-tricarboxylic acid compound of the formula

wherein R is hydrogen, lower alkyl or carboxyl, and R1 is hydrogen or methyl, or an orally acceptable salt thereof.

2. An oral composition as claimed in Claim 1 wherein R and R' are each hydrogen.

3. An oral composition as claimed in Claim 1 or Claim 2 wherein the said compound is present in an amount of from 0.1 % to 6% by weight.

4. An oral compound as claimed in any of Claims 1 to 3 futher comprising up to 15% of at least one normally staining nitrogen-containing antibacterial antiplaque agent based on the free base form of said agent.

5. An oral composition as claimed in Claim 4 comprising 0.01 to 5% by weight of the said agent.

6. An oral composition as claimed in Claim 4 or Claim 5 wherein the said agent is cationic and is present in an amount of at least about 0.001% by weight.

7. An oral composition as claimed in any of Claims 4 to 6 wherein the said agent is a substituted guanidine.

8. An oral composition as claimed in Claim 7 wherein the said agent is a pharmaceutically acceptable water soluble salt of an chlorhexidine or alexidine.

9. An oral composition as claimed in Claims 4 to 6 wherein the said agent is benzethonium chloride.

10. An oral composition as claimed in any of Claims 4 to 6 wherein the said antibacterial antiplaque agent is a quaternary ammonium compound containing 1 to 2 alkyl groups of 8 to 20 carbon atoms.

11. An oral composition as claimed in any of Claims 4 to 6 wherein the said antibacterial antiplaque agent is cetyl pyridinium chloride.

1 2. An oral composition as claimed in any of Claims 4 to 11 wherein the said compound is present in a molar excess relative to the said agent.

1 3. A mouthwash being an oral composition as claimed in any of the preceding claims wherein the vehicle is an aqueous alcohol, the mouthwash having a pH in the range of 4.5 to 9.

14. A toothpaste being an oral composition as claimed in any of Claims 1 to 1 2 comprising a gelling agent and a dentally acceptable polishing material, the toothpaste having a pH in the range of 4.5 to 9.

1 5. An oral composition substantially as described in any of the Examples herein.

16. A method of improving oral hygiene comprising applying to the oral cavity an effective amount of an oral composition as defined in any of the preceding claims.