FR2595944A1 - Anti-tartar dentifrice composition based on pyrophosphate, process for manufacturing it and its use - Google Patents

Abstract

The invention relates to a dentifrice composition. The composition contains, as anti-tartar agent, approximately 4.3 to 7 % of alkali metal pyrophosphate comprising at least 4.3 % of tetrapotassium pyrophosphate, alone or mixed with a maximum of 2.7 % of tetrasodium pyrophosphate, and, as inhibitor of the enzymatic hydrolysis of this agent in saliva, a fluoride and preferably up to approximately 3 % of a synthetic anionic polycarboxylate polymer. Application: Dentifrices.

Description

 The present invention relates to compositions for oral use containing an anti-tartar agent.

 Tartar is a hard mineral formation that forms on the teeth. Regular brushing helps prevent rapid buildup of such deposits, but even regular brushing is not enough to remove all of the tartar deposits that adhere to the teeth. Tartar builds up on the teeth when calcium phosphate crystals begin to deposit in the film and extracellular matrix of dental plaque and become sufficiently compacted between them so that the aggregates resist deformation. There is no unanimously accepted explanation for how calcium and orthophosphate ultimately become the crystalline matter called hydroxyapatite (RAP). However, it is generally recognized that at higher saturations, that is to say above the critical saturation limit, the crystalline RAP precursor is an amorphous or microcrystalline 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 wide peaks typical of materials amorphous, lacking the long-range atomic order characteristic of all crystalline materials, including RAP, therefore it is evident that the agents which effectively inhibit the crystal growth of PAH will be effective as anti-tartar agents. A suggested mechanism by which the anti-tartar agents of the present invention prevent the formation of tartar probably involves raising the activation energy threshold thereby inhibiting the transformation of the amorphous calcium phosphate precursor into RAP.

 Studies have shown that there is a satisfactory correlation between the ability of a compound to prevent crystal growth of RAP in vitro and its ability to pocket calcification in vivo, provided of course that such a compound is stable in plaque, saliva and their components.

 The prior art indicates that soluble pyrophosphate can be used to reduce the formation of tartar. For example, the U.S. patent.

A. No. 4,515,772 refers to several references in the prior art describing compositions for buccal use containing soluble pyrophosphates, including an article by Draus et al. Arch. Oral.

Biol., 15, pages 893-896 (1970), which describes the in vitro efficacy of such salts against tartar. This article refers to a possible inhibition of the action of pyrophosphate by the enzyme pyrophosphatase.

 It is known that saliva contains enzymes such as acid phosphatase, alkaline phosphatase and pyrophosphatase. It is believed that any of these three enzymes can adversely affect pyrophosphates as an inhibitor of RAP and tartar formation. It is therefore obvious that a pyrophosphate-based anti-scale toothpaste composition must inhibit, reduce or eliminate the destructive action of the three enzymes in saliva.

The compositions of the aforementioned patent N 4,515,772 are limited to a pH of 6.0 to 10.0 and comprise a fluoride and pyrophosphates of di (alkali metal) soluble alone or in mixture with pyrophosphates of tetra (alkali metal) but no more than 4.0 z of
K4P207 (tetrapotassium pyrophosphate). This patent does not describe or even mention the effectiveness of the patented fluoride-pyrophosphate composition in vivo or in saliva.

 An object of the present invention is to provide an improved toothpaste composition containing a pyrophosphate or a mixture of pyrophosphates as an essential anti-tartar agent.

 Another object of the present invention is to provide such a composition containing one or more inhibitors of the enzymatic hydrolysis of said agent in saliva.

 Yet another object of the present invention is to provide such a composition, effective in a relatively wide pH range and / or having better cosmetic properties.

Another main aim of the present invention is to provide such a composition which does not appreciably erode the surface of the teeth and which also exerts a significant and acceptable anti-decay effect.
Yet another object of the present invention is to provide a perfected method for inhibiting the formation of the tattre.

 Other objects and advantages will emerge from the description which follows.

 At the start of the development of the present invention, it was found that the toothpaste compositions containing only tetrasodium pyrophosphate as an anti-tartar agent were grainy and that the solid grainy particles consisted of undesirable Na4P2O7.

 The present invention is based, at least in part, on the determinations or discoveries of the Applicant that the fluoride ion inhibits the pyrolysis of pyrophosphate by acid rhosphatase and pyrophosphatase, that the synthetic anionic polymexic polycarboxylates inhibit hydrolysis of pyrophosphate by alkaline phosphatase and that the appearance of granular particles in compositions for oral use can be avoided by the use of a predominant proportion of the pyrophosphate in the form of the tetrapotassium salt.

According to some of its aspects, the present invention relates to a toothpaste composition in the form of a toothpaste, a dental gel, a toothpaste, a dental tablet, chewing gum or a tablet containing an orally vehicle. acceptable and, in approximate proportions by weight,
A. 4.3 za 7% of alkali metal pyrophosphates as an essential anti-tartar agent, comprising at least 4.3 z of tetrapotassium pyrophosphate, alone or in mixture with up to 2.7 z of tetrasodium pyrophosphate, and, as inhibitors of a zymatic hydrolysis of said agent in saliva,
B. An amount of a source of ionfluoride sufficient to supply from 25 parts per million to 5000 parts per million fluoride ions, and
C. from 0% to 3% of a synthetic anionic polymeric polycarboxylate having a molecular weight of from about 1000 to about 1,000,000, preferably from about 30,000 to about 500,000.

 Synthetic anionic linear polymeric polycarboxylates and their complexes formed with various cationic germicides, zinc and magnesium have been previously described as anti-tartar agents per se, for example in US Pat. Nos. 3,429,963, N 4,152,420, N 3,956-480, N 4,138,477, and NQ 4,183,914. However, none of these patents, like the known prior art, describes the use of such polycarboxylates alone to inhibit hydrolysis by the saliva of anti-scale agents of the pyronnosphates type, even less in combination with a compound constituting a source of fluoride ion. It is obvious that the synthetic anionic linear polymeric polycarboxylates described in these patents can be used in the compositions and methods of the present invention.

 The synthetic anionic polymeric polycarboxylates optionally, but preferably, used here, are, as indicated above, well known, often being used in the form of their free acids or their alkali metal salts (for example potassium and preferably sodium) or water-soluble ammonium, preferably partially, and better still totally neutralized. 1: 4 to 4: 1 copolymers of anhydride or of malic acid with another polymerizable ethylenically unsaturated monomer are preferred, preferably 1 methyl vinyl ether (mFthoxyethylene), having a molecular weight (PM) of about 30,000 to about 1,000,000. These copolymers are available for example under the names Gantrez AN 139 (PM 500,000), AN 119 (PM 250,000) and preferably S-97 pharmaceutical grade (PM 70-000) from GAF Corporation. The term "synthetic" should be understood to exclude known thickening or gelling agents including carb oxymethylcellulose and other cellulose derivatives and natural gums.

 Other polymeric polycarboxylates that can be used include those described in the U.S. patents.

A. N 3 956 180 cited above, like the 1: 1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available for example under the names Monsanto EMA N 1103, PM 10 000, and EMA GRADE / 61, and the 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

 Other usable polymeric polycarboxylates described in US Pat. Nos. 4,138,477 and No. 4,183,914 cited above include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, acids polyacrylic, polyitaconic and polymaleic, and sulfoacrylic oligomers with PM as low as 1000, available under the name Uniroyal ND-2.

 Generally suitable are olefinic- or ethylenically unsaturated carboxylic acids, polymerized, containing a carbon-to-carbon activated olefin double bond and at least one carboxyl group, that is to say an acid containing an olefinic double bond which acts easily in the Polymerization due to its presence in the monomer molecule either in the alpha-beta position relative to a carboxyl group, or as part of a methyl lene terminal group. Examples of such acids are acrylic acids and anhydrides, methacrylic, Ethacrylic, alpha-chloracrylic, crotonic, betaacryloxypropionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrilacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, alpha-phenylacrylic 2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic. Other different olefin monomers copolymerizable with such carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl dimethylate, etc. The copolymers contain enough carboxylic salt groups to be soluble in water.

 Also useful in the present invention are the so-called carboxyvinyl polymers described as toothpaste components in U.S. patents.

A. N 3 980 767, N 3 935 306, N 3 919 409, N 3 911 904 and N 3 711 604. They are commercially available, for example under the trade names Carbopol 934, 940 and 941 from BF Goodrich, these products consisting essentially of a collectively water-soluble polymer of crosslinked polyacrylic acid with about 0.75% to about 2.0% polyallyl-sucrose or polyallyl-pentaerythritol as the crosslinking agent.

 The synthetic anionic linear polymeric polycarboxylate component is mainly a hydrocarbon optionally comprising halogenated substituents and oxygenated charnons, as it exists for example in ester, ether and OH groups, and in case it is used it is generally present in the compositions of the invention in approximate proportions by weight of 0.05 to 3%, preferably from 0.05 to 2%, better still from 0.1 to 2%. The proportions located in the upper parts of these intervals are generally used in toothpaste compositions, generally containing a dental abrasive and used in conjunction with brushing of teeth, for example toothpaste (including creams), gels, powders and tablets. Quantities greater than these ranges can be used for thickening or gelation.

 As indicated above, these polymeric polycarboxylates have been shown to be effective inhibitors of the enzyme alkaline phosphatase. Since this enzyme has low activity (for hydrolysis of pyrophosphate) at about pH 7.0 or lower, the The polymeric polycarboxylate component may optionally be omitted from oral preparations formulated to work at such a pH of 7.0 or lower. However, this omission obviously reduces the flexibility and the effectiveness of the oral compositions of the present invention over the wide range from about 4.5 to about 10.

 The sources of fluoride ions, or fluorine-providing compounds, necessary according to the present invention as an essential component of the inhibitor of the enzyme acid phosphatase and pyrophosphatase are well known in the art as anti-caries agents and also act as such agents in the practice of the present invention These compounds may be slightly soluble in water or may be entirely water-soluble They are characterized by their ability to release fluoride ions in water and by the absence of an independent reaction sirable with the other compounds of the preparation for buccal use. Among these materials, one can quote mineral fluorides like the soluble salts of alkali metals and alkaline earth metals, for example sodium fluoride, potassium fluoride, fluoride ammonium, calcium fluoride, copper fluoride such as cuprous fluoride, zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, sodium monofluorophosphate, aluminum mono- and di-fluorophosphates and fluorinated sodium and calcium rophosphate. Preferred are alkali metal and tin fluorides such as stannous sodium fluorides, sodium monofluorophosphate (MFP) and mixtures thereof.

 The amount of fluorine-providing compound depends to some extent on the type of compound, its solubility, and the type of oral preparation, but it should be a non-toxic amount, generally from about 0.005 to about 3.0% in preparation. In a toothpaste preparation, for example a dental gel, a toothpaste (including a cream), a toothpaste, or a dental tablet, an amount of such a compound which releases up to about 5,000 parts per million (ppm) d ion F relative to the weight of the prepalration is considered satisfactory. Any suitable minimum amount of such a compound can be used, but it is preferable to use enough compound to release about 300 to about 2000 ppm, preferably about 800 to about 1500 ppm of fluoride ion. In general, in the case 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 about 0.05 to 1 %. In the case of sodium monofluorophosphate, the compound may be present in an amount of about 0.1 to 3%, more generally about 0.76%.

 In toothpaste preparations such as lozenges and chewing gum, the fluorinated compound is generally present in an amount sufficient to release up to about 500 ppm, preferably about 25 to 300 ppm by weight of fluoride ion. In general, this compound is present in a proportion of about 0.005 to about 1.0% by weight.

 The dentifrice compositions of the present invention achieve the desired anti-tattre effect when mixed therewith from about 4.3% to about 7% of tetrapotassium pyrophosphate alone or with up to 2.7% of tetrasodium pyrophosphate. Preferred ratios of tetrapotassium: tetrasodium salts range from about 4.3: 2.7 to about 6: 1, in particular a ratio of 4.5: 1.5. Contrary to the description of the aforementioned Patent No. 4,515,772 , it is very important that the compositions of the present invention have fully acceptable anti-tartar properties and improved cosmetic properties while containing more than 4.0% of tetrapotassium pyrophosphate and without inclusion of pyrophosphate of di (alkali metal), although small amounts, for example about 0.1% to about 0.4% or about 1% may be present if desired.

The pH of the toothpaste preparations of the invention is generally in the range of about 4.5 to about 9, and generally in the range of 5.5 to 9. The pH is preferably in the range of about 6 to about 8 , 0. It should be noted that the compositions of the invention can be applied to the oral cavity in said pH intervals without decalcification or other appreciable deterioration of the dental enamel. The pH can be adjusted with an acid (for example citric acid or benzoic acid) or a base (for example sodium hydroxide), or buffered (for example with citrate, benzoate, carbonate or sodium bicarbonate, disodium phosphate, monosodium phosphate, etc.) ,
In certain advantageous elms of the present invention, the dentifrice composition can be practically solid or creamy in nature, for example a tooth powder, a dental tablet, a toothpaste (cream), or a dental gel. The vehicle for these solid or creamy toothpaste preparations generally contains an acceptable polishing material for the oral and dental tracts to be used in conjunction with brushing of the teeth. Examples of such polishing materials are metaphos - sodium phate, metaphosphate potassium, tricalcium phosphate, calcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, zirconium silicate, silica, bentonite and their mixtures, insoluble in water.

Other suitable polishing materials include the thermosetting particulate resins described in U.S. Patent No. 3,070,510, such as melamine-, phEnol- and urea-formaldehyde-s, and articulated polyepoxides and polyesters. Preferred polishing materials include crystalline silica having particle sizes of at most about 5 micrometers, an average particle size of at most about 1.1 micrometers, and a surface area of at most about 50,000 cm2 / g, silica gel or colloidal silica, and complex amorphous alumino-silicates of alkali metals.

When using clear-looking gels, polishing agents made of colloidal silica, such as those sold under the trademark
SYLOID, such as Syloid 72 and Syloid 74 or under the trademark SANTOCEL, such as Santocel 100, and alkali metal alumino-silicate complexes are particularly useful, since they have refractive indices close to the refractive indices of gelling agent systems -liquid (comprising water and / or a humectant) commonly used in toothpaste.

Many of the so-called "water-insoluble" polishes are anionic in nature and also contain small amounts of soluble material. Thus, an insoluble sodium metaphosphate can be formed in any suitable way, as illustrated in Dictionary of Applied Chemistry by Thorpe,
Volume 9, 4th Edition, pages 510-511. Other examples of suitable materials are the forms of insoluble sodium metaphosphate known as Madrell salt and Kurrol salt. These metaphosphates have very low water solubility and therefore are commonly referred to as insoluble metaphosphates (IMP). They contain a small amount of soluble phosphate as impurities, usually a small percentage , for example up to 4% by weight, The amount of soluble phosphate, which is assumed to contain a soluble sodium trimetaphosphate in the case of insoluble metaphosphate, can be reduced or removed by washing with water, if desired re. The insoluble alkali metal metaphosphate is generally used in the form of a powder with a particle size such that no more than about 1% of the matrix has a size greater than about 37 microns.

 The polishing material is generally present in solid or paste compositions at weight concentrations of from about 10% to about 99%.

Preferably, it is present in proportions ranging from about 10% to about 75 | in a toothpaste or gel, and about 70% to about 99% in a powder or a tablet.

 In a toothpaste, the liquid vehicle may contain water and a humectant, generally in a proportion ranging from approximately 10% 3 to approximately 90% by weight, relative to the weight of the preparation. Glycerin, propylene glycol, sorbitol, polypropylene glycol and / or polyethylene glycol (eg 400-600) are examples of suitable humectants / vehicles. Liquid mixtures of water, glycerin and sorbitol are also advantageous. In transparent gels, when the refractive index is an important factor, it is preferable to use approximately 3 to 30% by weight of water, from O to about 80% by weight of glycerin and about 20 to 80% by weight of sorbitol.

 Toothpastes (creams) and gels generally contain a natural or synthetic thickener or gelling agent in proportions of about 0.1 to about 10, preferably 0.5 to about 5% by weight. A suitable thickener is synthetic hectorite, a complex colloidal synthetic clay of the magnesium silicate and alkali metal type available for example under the name. Laponite (eg CP, SP 2002, D) marketed by Laporte Industries Limited. The analysis of Laponite D reveals, approximately by weight, 58.00% of SiO2, 25.40% of MgO, 3.05% of Na2O, 0.98% of Li2O and a little water and metals under form of traces. Its real density is 2.53 and its apparent density (g / ml has a humidity of 8 8) of 1.0.

 Other suitable thickeners include Irish moss, tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutylmethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose (for example available as Natrosol), sodium carboxymethyl cellulose, and colloidal silica such as finely ground Syloid (e.g. 244).

 It is evident that, as is common, preparations for oral use are intended for sale or otherwise distributed in suitable labeled packages. Thus, a toothpaste, a crime or a gel will generally be packaged in a compressible tube, generally made of aluminum, coated lead or plastic, or other compressible dispenser, pumped or pressurized to dose the contents, carrying a label describing it, in essence, as a toothpaste, gel or dental cream.

 Organic surface-active agents are used in the compositions of the present invention to obtain an increased prophylactic action, to promote an intimate and complete dispersion of the anti-tartar agent in the whole of the oral cavity, and to make the compositions of l cosmetically acceptable invention. The organic surfactant material is preferably anionic, nonionic or ampholytic in nature, and it is preferable to use a detersive material as a surfactant which gives the composition detergent and foaming properties.

Suitable examples of anionic surfactants are the water-soluble salts of monoglycerides of higher fatty acid monoglycerides such as the sodium salt of monoglyceride monosulfate of hydrogenated coconut oil fatty acids, (higher alkyl) sulfates such as sodium lauryl sulfate sodium, alkylarylsulfonates such as sodium dodecyl benzene sodium sulfonate, (higher alkyl) sulfoacetates, higher fatty acid esters of 1,2-dihydroxypropane sulfonate, and higher aliphatic acylamides of substantially saturated lower aliphatic amino carboxylic acids such as those having 12 I 16 carbon atoms in the fatty acid, alkyl or acyl radicals, etc. Examples of the amides mentioned last are N-lauroyl-sarcosine-, and sodium, potassium and Sthanolamine salts of N-lauroyl-,
N-myristol- or N-palmitoyl-sarcosine, which must be practically devoid of soap or similar higher fatty acid material. The use of these sarcosinates in the compositions for oral use of the present invention is particularly advantageous, because these materials have a prolonged and marked effect on the inhibition of acid formation in the oral cavity due to a breakdown of carbohydrates in addition to the fact that they exert a certain decrease in the solubility of dental enamel in acid solutions.

 Examples of water-soluble nonionic surfactants are the condensation products of ethylene oxide with various reactive hydrogenated compounds reacting with it, having long hydrophobic chains (for example aliphatic chains of approximately 12 to 20 carbon atoms), these condensation products ('thoxamers') containing hydrophilic polyoxyethylene fragments, such as the condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyalcohols (for example monostearate sorbitan) and poly (propylan oxide) (for example the materials of the Pluronic series).

 Various other materials can be incorporated into the oral preparations of the present invention, for example bleaches, preservatives, silicones, chlorophyll compounds, other scale inhibitors and / or ammonia material such as urea, diammonium phosphate, and mixtures thereof. These adjuvants, when present, are incorporated into the preparations in amounts which do not substantially affect the desired properties and characteristics.

 Any suitable flavoring or sweetening material can also be used. Examples of suitable flavoring constituents are flavoring essences such as spearmint, peppermint, wintergreen, sassafras, cloves, sage, eucalyptus, marjoram, cinnamon, lemon and orange essences. and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, dextrose, levulose, sorbitol, xylitol, d-tryptophan, dihydrochalcones, sodium cyclamate, perillartin, APM (aspactyl-phenyl-alanine, methyl ester), "saccharin-, -etc. Advantageously, the flavoring and sweetening agents can together constitute about 0.1 to 5% or more of the preparation.

 In the preferred practice of the present invention, an oral composition according to the present invention, for example a toothpaste containing pyrophosphate and the enzyme inhibitor described in an amount effective to inhibit tartar on the surface teeth, is preferably applied by regular brushing of the dental enamel, for example every two or three days, or preferably ia 3 times a day, at a pH of about 4.5 to about 10, generally about 5.5 to about 9, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more, or even permanently. The toothpaste is generally removed by rinsing with a batten after each application.

 The compositions of the present invention can be incorporated into lozenges, or into chewing gum (chewing gum) or other products, for example by stirring in a warm gum base or applying to the exterior surface of a base. gum, of which representative examples are jel; u-tong, rubber latex, vinylite resins, etc., advantageously with conventional plasticizers or softeners, sugar or other sweeteners or carbohydrates such as glucose , sor bitol, etc.

 The vehicle or support contained in a tablet or lozenge is a non-cariogenic solid water-soluble polyalcohol (polyol) such as mannitol, xylitol, sorbitol, maltitol, a hydrogenated hydrogenated hydrolyzate, Lyeasin, hydrogenated glucose, hydrogenated disaccharides and hydrogenated polysaccharides, in a proportion of about 90 to 98% by weight of the entire composition. Solid salts such as sodium bicarbonate, sodium chloride, potassium bicarbonate or potassium chloride can completely or partially replace the polyol used as a vehicle.

 Pellet lubricants, in minor amounts of about 0.1 to 5% by weight, can be incorporated into the tablet or lozenge formulation to facilitate the preparation of both tablets and lozenges. Suitable lubricants include vegetable oils such as coconut oil, magnesium stearate, aluminum stearate, talc, starch and Carbowax.

 The tablet formulations contain approximately 2% gum as a barrier agent for orodizing a shiny surface as opposed to a tablet which has a smooth finish. Suitable non-cariogenic gums include carrageenan kappa, carboxymethyl cellulose, hydroxyethyl cellulose, Gantrez, etc.

 The lozenge or tablet may optionally be coated with a coating material such as waxes, shellac, carboxymethyl cellulose, a polyethylene / anhydride-maleic copolymer or kappa carrageenan in order to increase in coxe the time it takes for the tablet or lozenge to dissolve in the mouth. THE uncoated tablet or lozenge dissolves slowly, ensuring sustained release of active ingredients for approximately 3-5 minutes. Therefore, the solid composition of the dosed tablet and lozenge of the present invention allows a relatively longer time of contact of the teeth in the oral cavity with the active ingredients.

 The following nonlimiting examples illustrate the present invention. All quantities and proportions are expressed by weight and temperatures in degrees Celsius, unless otherwise specified.

EXAMPLE A
Effect of Saliva Enzymes on Inhibition of
HAF training by TSPP
The in vitro formation of PAH is measured by titrimetry by a pH-stat process. Reserves of 0.1 M CaCt2 and 0.1 M NaH2P94 are prepared fresh in deionized carbonate-free distilled water, 23 ml of CO2-free deionized distilled water are added 1.0 ml of the phosphate stock solution and 1.0 ml of an aqueous solution of 1x10-4M of the anti-scale agent to be tested, then 1.0 ml of the chloride stock solution is added. calcium that initiates the reaction. The reaction is carried out at pH 7.4 under a nitrogen atmosphere. The consumption of 0.1N NaOH is recorded automatically, from which the time required for crystals to form is determined.

Table A shows the results of this procedure.

TABLE A
Growth Inhibition Time
Anti-Crystals Agent - '(happy) tartar Saliva Pyrophosphatase @Phosphatase
alkaline
TSPP * 0.8 0.4 0.3 0.0 * TSPP = tetrasodium pyrophosphate
Table A shows that in water, TSPP strongly delays the formation of PAHs. However, the effectiveness of these agents is considerably reduced when incubated in saliva, as evidenced by the shorter delay time. This reduction in efficiency is due to the enzymatic hydrolysis of the POP bonds. Incubation of this agent with pyrophosphatase and alkaline phosphatase considerably reduces the delay period and shows the sensitivity of the POP binding to hydrolysis by phosphatases, substantially the same results are obtained by using tetrapotassium pyrophosphate (TKPP) in place of TSPP, both having the same effective pyrophosphate ion containing a POP bond.

EXAMPLE B Stabilization of TSPP with respect to Enzymatic Hydrolysis in the Presence of Inhibitors
Enzymatic hydrolysis is carried out in a buffer solution of NaOH and morpholinopropane sulfonic acid - 100 millimolar (pH 7.0) containing 1.3 mg / ml of TSPP. The inhibitors of the present invention are added (except for the control) to a final concentration of 1000 ppm of flowering ion (originating from NaF) and 0.5% of the sodium salt of a copolymer (1: 1) hydrolyzed maleic methoxyethylene anhydride, PM 70,000 (Gantrez S-97 Pharmaceutical Grade). Equal phosphatase activities to; alkaline phosphatase and mineral pyrophosphatase are then added to obtain a total phosphatase activity of 0.3 units / ml. Samples of the test solution are taken and the total oxyphosphate available in each sample is measured after 3 hours of hydrolysis in 4N 9 1000C HCl. The reaction mixture is incubated at 370C, shaking and aliquots are taken at appropriate times over at least 90 minutes to determine the orthophosphate content.
Table B shows the results expressed as a percentage of orthophosphate released as a result of the hydrolysis of pyrophosphate.

TABLE B
Percent of orthophosphate Percent of
released in 90 minutes protection
relative
Anti-agent With scale Inhibitor control
TSPP 98 58 41
Table B shows that after 90 minutes of incubation in the presence of an enzyme, 98% of the available orthophosphate is released from TSPP in the absence of inhibitors. With inhibitors, the hydrolysis of POP bonds in pyrophosphate (TSPP) is reduced by 41%. It should be noted that the enzymatic activities used in this study are at least 2 to 3 times greater than those normally found in saliva. These results show that the inhibitors of the present invention greatly reduce the enzymatic hydrolysis of TSPP. The same results are obtained when equivalent amounts of TKPP are substituted for TSPP.

 The following dental gel formulations are representative of the invention. Example 1 is a white opacified gel, Example 2 is a transparent blue gel.

Parts by weight
Example 1 Example 2
Part 1
TSPP 1,500 1,500
TKPP 4,500 4,500
Sorbitol (aqueous solution
at 70%) 22.507 22.500 Part 2 Polyethylene glycol 600 5,000 5,000
Glycerin 10,750 15,000 IOTA-carrageenan gum 0.500 0, 450
Sodium fluoride 0.243 0.243
Saccharin sodium 0.300 0.300
Gantrez S-97 1,000 1,000 Titanium dioxide 0.500 500
Deionized water 31,000 26,607
Blue FD & C N9 1 (solution
at 1%) ------ 0.200
Part 3
ZEO 498 (SiO2) 17,000 16,000
SYLOID 244 (synthetic silica) 3,000 4,500
Part 4
Sodium lauryl sulfate in
powder 1,200 1,200
Aroma 1,000 1,000
The above formulations are prepared as follows. The components of Part 1 are mixed to form a solution. Separately, the components of Part 2, with the exception of water, are mixed to form a dispersion in the humectant consisting of polyethylene glycol / glycerin, then water is introduced therein by mixing. Parts 1 and 2 are then combined, then Parts 3 and 4 are added consecutively, mixing appropriately.

These formulations and the following formulations are intended to maintain substantially unaffected by the other components the anti-decay effect of the fluoride component, and not to exert significant erosion effects on the teeth.

EXAMPLE 3
Using the same procedure as in Examples 1 and 2, the following toothpaste formulation according to the present invention is prepared.

Ingredients Parts by weight
Deionized water 37,578
Glycerin 25,000
Zeo 49B (Silicon dioxide? 21,500
TKPP 4,500
TSPP 1,500
Syloid 244 (synthetic silica) 3, O00
Sodium lauryl sulfate 1,200
Aroma 1,000
Gantrez S-97 (pharmaceutical grade) 1,000
Sodium hydroxide (50% solution) 1,000
Xanthan gum 1,000
Sodium benzoate 0.500
Titanium dioxide 0.500
Saccharin sodium 0.300
0.242 Sodium Fluoride
Examples 4 and 5 represent formulations of tablets according to the invention.

EXAMPLE 4
Tablet formulations
Parts by weight
Sugar 75-98
Corn syrup 1-20
Flavoring essence 0.1-1.0
Lubricant for tablets 0.1-5
TKPP: TSPP-3: 1 3.5-8
Gantrez S-97 0.05-3
NaF 0.01-0.05
Water 0.01-0.2
EXAMPLE 5
Lozenges
Percent by weight
Saccharin sodium 0.15
Aroma 0.25
Magnesium stearate (lubricant} 0.40
Dye 0.01
Emulsifier + 1.00
0.05 NaF
Gantrez S-97 0.30
TKPP: TSPP - 3: 1 6.50
Sorbitol q. s; for 100
* PEG (40) -sorbitan diisostearate
EXAMPLE 6
Chewing gum
Parts
Gum base 10 to 50
Binder 3 to 10
Charge (sorbitol, mannitol or asso
citations of these) 5 to 80
Artificial sweetener 0.1 to 5
TKPP: TSPP-3: 1 3.5 to 8
Gantrez S-97 0.1 to 1.0
NaF 0.1 to 0.05
Aroma 0.1 to 5.

 All of the above formulations are intended to provide better non-grainy and other cosmetic properties and to exert better anti-tartar effects in vivo.

Claims (13)

 1. Toothpaste composition in the form of a toothpaste, a dental gel, a toothpaste, a dental tablet, chewing gum or lozenges, characterized in that it contains an acceptable vehicle for the buccal route, and, in approximate proportions by weight,  A. 4.3 to 7% of alkali metal pyrophosphates as an essential anti-tartar agent, comprising at least 4.3% of tetrapotassium pyrophosphate, alone or in mixture with a maximum of 2.7-% of tetrasodium pyrophosphate , and as inhibitors of an enzymatic hydrolysis of said agent in saliva,  B. an amount of a fluoride ion source sufficient to supply from 25 parts per million to 5,000 parts per million fluoride ions, and  C. from 0 to 3% of a synthetic anionic polymeric polycarboxylate having a molecular weight of from about 1,000 to about 1,000,000, preferably from about 30,000 to about 500,000.  2. Composition according to claim 1, characterized in that it contains tetrapotassium and tetrasodium pyrophosphates in an approximate weight ratio of 4.3: 2.7 to 6: 1.  3. Composition according to claim 1, characterized in that it contains approximately 4.5% of tetrapotassium pyrophosphate and approximately 1.5% of tetrasodium py rophosphate.  4. Composition according to. any one of claims 1 to 3, characterized in that it contains from about 0.05% to about 3% of said polymeric polycarboxylate in the form of its water-soluble alkali metal or ammonium salt.  5. Composition according to any one of claims 1 to 4, characterized in that it has a pH of approximately 4.5 to approximately 10.  6. Composition according to any one of claims 1 to 5, characterized in that said polycarboxylate carboxylate is a copolymer of vinyl ether and methyl and maleic acid or anhydride having a molecular weight of about 70,000 .  7. Composition according to any one of claims 1 to 6, characterized in that it contains a quantity of source of floral ion sufficient to supply approximately 800 to approximately 1,500 parts per million of fluoride ions and approximately 0.1 has about 2 z of the polycarboxylate.  8. Composition according to any one of claims 1 to 7, characterized in that the source of fluoride ions consists of sodium fluoride.  9. Composition according to any one of claims 1 to 8, characterized in that it is in the form of a toothpaste, a gel or a cream additionally containing an acceptable polishing agent for the teeth.  10. Composition according to claim 9, characterized in that it contains a polishing agent of the silica type acceptable for the teeth.  11. Composition according to any one of claims 1 to 8, characterized in that it is in the form of a mouthwash bath.  12. Method for inhibiting dental tartar, characterized in that it consists in applying to the teeth an amount inhibiting tartar of a composition according to any one of claims 1 to 11.  13. Process for preparing a composition according to any one of claims 1 to 11, characterized in that it consists in mixing together the components defined in the claims.