FR2463614A1 - ORAL COMPOSITION FOR COMBATING DENTAL TARTAR AND IMPROVING ORAL HYGIENE - Google Patents

Abstract

THE PRESENT INVENTION CONCERNS AN ORAL COMPOSITION THAT CAN BE USED IN PARTICULAR AS TOOTHPASTE, TOOTHPASTE POWDER OR LIQUID FOR MOUTHWASH. IT INCLUDES AN ORALLY ACCEPTABLE VEHICLE CONTAINING APPROXIMATELY 0.01 TO 10 BY WEIGHT OF A 2-PHOSPHONO-BUTANE-1,2,4-TRICARBOXYLIC ACID COMPOUND OR A SALT, INTENDED TO INHIBIT THE SCALE FORMATION, AND 0 TO 15 BY WEIGHT OF AT LEAST ONE ANTI-BACTERIAL ANTI-PLAQUE AGENT CONTAINING NITROGEN AND NORMALLY FORMING SPOTS ON THE TEETH.

Description

24636'1-4

-! - The present invention relates to compositions

  containing an anti-tartar agent.

  Tartar is a hard mineral formation that forms on the teeth. Regular brushing prevents these deposits from forming quickly, but even regular brushing is not enough to remove all the scale that adheres to the teeth. -tartar is formed on

teeth when calcium phosphate crystals begin

  hundred to deposit in the film and in the matrix

  extracellular plaque and become sufficient

tightly pressed against each other so that the

  gats thus formed acquire resistance to deformation

  tion. The authors do not entirely agree on how calcium and orthophosphate are

  ultimately transform into a crystalline substance ap-

  peeled hydroxyapatite (PAH). They do, however, agree that at concentrations above the

critical limit of saturation, the precursor of hydroxy-

  crystalline apatite is an amorphous calcium phosphate

or microcrystalline. "Amorphous calcium phosphate", what-

  akin to hydroxyapatite, differs in its structure

  atomic ture, the morphology of its particles and its stoe-

  The x-ray diffraction spectrum of the phos-

  amorphous calcium phate shows broad characteristic peaks

  of amorphous substances, without the orderly arrangement

  born of atoms, over an extended interval, which is characterized

tick of all crystalline substances, including hydroxyapatite. It is therefore evident that the agents which effectively inhibit crystal growth

  of hydroxyapatite will be effective as anti-

tartar. It is suggested here that the mechanism by which the anti-tartar agents of this invention inhibit the formation of tartar probably involves an increase

activation energy threshold, which inhibits trans-

  formation of amorphous calcium phosphate precursor to hydroxyapatite. Studies have shown that there is a good correlation between the ability of a compound to prevent crystal growth of hydroxyapatite in vitro and its

  ability to prevent zalcification in vivo.

Cationic anti-bacterial substances

containing nitrogen are well known in the art.

One can refer to this subject, for example, to the part "Quaternary Ammonium and Related Compounds" of the article

"Antiseptics and Disinfectants" l from Encyclopedia of Chemi-

  cal Technology, by Kirk-thuer, second edition (Vol. 2, pp. 632-635). The cationic substances which have an antibacterial activity (that is to say which are 1 of Hermiecdes) are used against bacteria and have been used in oral compositions to combat the formation of the plaque due to bacteria of the

  oral cavity (here called "anti-plaque" substances).

  Among the most common of these anti-plaque and anti-bacterial quaternary ammonium compounds, mention may be made of benzethonium chloride - also known under the name of

  Hyamine 1622, or di-isobutylphenoxy chloride

  ethoxyethyl-dimethyl-benzyl-ammonium. In a preparation

  oral substance, this substance very effectively promotes hy-

oral hygiene by reducing the formation of dental plaque and tartar, this reduction being generally accompanied by that of the formation of caries and periodontitis. Other cationic antibacterial agents of this type are those mentioned, for example, in United States patents N 2,984,639, No. 3,325,402, N 3,431,208 and N 3,703,583 and in the

British Patent No. 1,319,396.

  Other anti-quaternary ammonium compounds

  Bacterial and anti-plaque are those in which one or two of the quaternary nitrogen substituents have a carbon chain length (typically an alkyl group) of approximately 8 to 20, advantageously from 10 to 18, carbon atoms while the remaining substituents contain a lower number of carbon atoms (typically an alkyl or benzyl group), for example 1 to 7 carbon atoms, preferably the groups

methyl or ethyl. Dodecyl-trimethyl-ammo bromide

  nium, dodecyl-dimethyl- (2-phenoxyethyl) bromide -

  ammonium, benzyl-dimethyl-staryl-ammonium chloride,

cetylpyridinium chloride and 5-amino-1,3-bis (2-

ethylhexyl) -5-methyl hexahydropyrimidine quaternized constitute examples of other characteristic anti-bacterial agents, of the quaternary ammonium type.

  Other types of cationic antibacterial agents

that we incorporate avanzageusemenz in the compositions

to promote oral hygiene by reducing the forma-

  tion of dental plaque are amidines, such as substituted guanidines, for example chlcrhexidine and the corresponding compound, alexidine, comprising groups

  2-ethylhexyl instead of chlorophenyl groups, and other bis-

biguanides like those described in the patent application

German N P 2 332 383, published January 10, 1974, which

lay in the following formula:

R NH NH NH NH R '

  tl Il I i A- (X) zNC-NH-C-NH (CH2) n-NH-C-NH-C- N- (X ') z, -A' in which A and A 'denote, depending on the case, either (1) a phenyl radical, which may be substituted by up to 2 alkyl or alkoxy groups having from 1 to about 4 carbon atoms, a nitro group or a halogen atom, or (2) an alkyl group containing 1 to about 12 carbon atoms, i.e. (3) alicyclic groups having

4 to about 12 carbon atoms, X and X 'can represent

  ter, depending on the case, an alkylene radical having 1 to 3 carbon atoms, z and z 'can be, as the case may be, 0 or 1, R and R' can represent, depending on the case, hydrogen, a radical alkyl having 1 to 12 carbon atoms or an aralkyl radical having 7 to about-12 carbon atoms and

  n is an integer ranging from 2 to 12, including these va-

  their, the polymethylene chain (CH2) n can be interrupted

  thereby storing 5 ether, thioether, phenyl or naphthyl groups;

  these compounds are available in the form of pharmaceutical salts.

ceutically acceptable. Other substituted guanidines

are: N '- (4-chlorobenzyl) -N5- (2,4-dichlorobenzyl) -bigua-

  nest; p-chlorobenzyl-biguanide, 4-chlorobenzhydryl-gua-

  nylurea; N-3-lauroxypropyl-N5-p-chlorobenzyl-biguanide;

5,6-dichloro-2-guanidobenzimidazole; and N-p-chloro-

  phenyl-'5-1arylbiguanide. Long chain tertiary amines have

  also anti-plaque activity and anti-bacteria activity

nothing. Such anti-bacterial agents include ami-

tertiary groups containing a fatty alkyl group (having typical

  ment 12 to 18 carbon atoms) and two poly (oxy-

ethylene) linked to the nitrogen atom (typically containing a total of 2 to 50 ethenoxy groups), the salts they form with acids, and the compounds of structure:

/ (CH2CH20) (CH2CH20) XH

"2 2- \

  (CH2CH20) yH in which R is a fatty acid alkyl group containing 12 to 18 carbon atoms, the sum x + y + z being at least equal to 3, as are their salts. In general, cationic agents are preferred because of their efficacy against

plaque.

  The anti-bacterial anti-plaque compound is pre-

  ference a compound whose anti-bacterial activity is such that its phenol coefficient is much greater than 50, and better still much greater than 100, for example greater than approximately 200 or more for Staphylococcus aureus; for example,

the phenol coefficient (A.O.A.C.) of benzene chloride

thonium is given equal to 410, by the manufacturer, for Staphy-

  lococcus aureus. The cationic anti-bacterial agent is

usually a monomeric (or possibly dimeric) substance with a molecular weight well below 2,000, for example

  less than around 1000. It is however in accordance with the

vention, in its most general scope, to use a

cationic polymeric anti-bacterial agent. The anti-bac agent

  cationic terien is preferably in the form of an orally acceptable salt of the abovementioned compound, such as chloride, bromide, sulphate, an alkylsulphonate such as methylsulphonate and ethylisulphonate, a phenylsulphonate such as p - .. ethylphen-. ysu! fonate, nitrate, acetate, gluconate, etc. Nitrogen-based cationic antibacterial agents and tertiary amine-type antibacterial agents

long chain re promote oral hygiene, in particular

  culier by removing dental plaque. However, we have observed-

  vé that their use leads to the formation of spots on the surface of the teeth or to a change in color

of these.

  The reason for the formation of such stains on the teeth is not well established. However, dental enamel

contains a high proportion (about 95%) of hydro-

  xyapatite (PAH) which includes Ca +2 and P04 3 ions. In the absence of dental plaque, an additional amount of Ca + 2 and P04 3, in particular from saliva,

can deposit on the enamel, such deposits can include

take colored substances which end up staining the enamel of the teeth in a calcified form deposited on

this as well as anti-bacterial agents of the catio- type

long chain primary amine type

  plaque, they can also denature protein

no saliva in the oral cavity and the protein dena-

  turée can then act as nucleating agent which decomposes

  put on tooth enamel and stain or change color

of it.

  The additives previously used, which reduce

  feels the formation of stains on the teeth by cationic antibacterial anti-plaque agents, also generally decreases the activity of anti-bacterial anti-plaque agents such as bis-guanido compounds by forming a precipitate

with these agents.

  In accordance with one aspect of the invention, it

  it relates to an oral composition comprising an orally acceptable vehicle which contains an effective amount,

  as an anti-tartar agent, a compound of 2-

phosphono-butane-1,2,4-tricarboxylic acid (PBTA), of formula

O CH <-COOH

Hon

(I) HO \ |

P-C - COOH

HO

R-CH- CH-COOH

  R in which R is hydrogen, a lower alkyl group or a carboxyl group and R1 is hydrogen or a methyl group, or an orally acceptable salt of this compound, preferably soluble in water, such as a metal salt

  alkaline (e.g. sodium or potassium), ammonium

  nium, of ammonium mono-, di- and tri-substituted in C1 - C18 (for example ammonium substituted by an alkanol such as

  mono-, di- or tri-ethanolammonium).

The compounds of the above-mentioned formula and their production methods are described in United States patents N 3 886 204 and N 3 886 205, to which

  we can refer. The preferred PBTA compound for use

sation according to the present invention is the compound not subs-

containing the aforementioned formula (I) for which R and R1 are

each hydrogen. When R is a lower alkyl group

laughing, it preferably contains 1 to 4 carbon atoms

  and it represents in particular the methyl group.

  The concentration of the PBTA compound (or salt) in the oral compositions can vary over a wide range, typically from such low values

  than 0.01% by weight, with no upper limit on the amount

may be used, except for reasons of cost or incompatibility with the vehicle. In general, concentrations of from about 0.01% to about% are used, preferably from about 0.1 to 6% by weight. Oral compositions which may be accidentally ingested during normal use contain lower concentrations of the PBTA compound. Thus, a mouthwash according to the present invention preferably contains less than ernviro- 2% by weight of PETA compound, preferably about 0.1 to 1.5 D by weight. The

  other compositions for teeth, topical solutions

  prophylactic pastes and pastes, the latter being to be administered by professionals, may preferably contain approximately 0.1 to 3% by weight of PBTA compound. The PBTA compounds of the present invention

  are anti-nucleating agents, the ora-

  i0 les de ', invention cntzenrant these agents = so effective

  to reduce the formation of dental calculus without lag

unduly clogging dental enamel and, in contrast to nitrogen-based anti-bacterial anti-plaque agents

described above, such PBTA compounds and the compounds

  sitions containing them do not tend to stain teeth or only exhibit this tendency to weak

  degree and, in addition, they effectively inhibit gingi-

quickly. Another advantage of this invention is that these anti-scale anti-nucleation PBTA compounds

  inhibit, i.e. prevent or remove, in a way

unexpectedly, staining of dental enamel provo-

  only by the nitrogen-based anti-bacterial anti-bacterial agents described above, without forming a precipitate or

  without significantly harming their anti-bacterial activity

ne and anti-plaque. Not all anti-nucleation agents are effective in preventing the formation of spots by such anti-bacterial agents. Victamide (which is also known as Victamine C), which is a condensation product of ammonia with phosphorus pentoxide, effectively increases the formation of

  spots even in the absence of such anti-bacterial agents.

  When present, these anti-bacterial tartar agents normally leading to staining, are

  typically used in normally effective amounts

  these, for example such that the oral product contains about 0.001 to 15% by weight of water. Preferably, for the desired degree of antiplaque activity, the product

- _q -

finished oral contains about 0.01 to about 5%, and better

  still approx ron0 ,,, e po-ds, e the anti-

  anti-bacterial plate, if we consider the form cons-

titled by the free base. It is very particularly preferred to use the PBTA compound in molar excess by

  compared to the quantity of anti-plaque anti-bacteria agent

nothing (expressed relative to the corresponding free base

  dante) in order to minimize, inhibit or prevent the formation

  tion of stains, in the best conditions.

  13 In certain particularly appreciated forms

ciées of the invention, the oral composition may be of a liquid nature, as in the case of mouthwashes for washing or rinsing. In such a preparation, the

  ve ue is typically a water-alcohol mixture which

desirably takes a humectant or humidifier, as described below. In general, the

ratio of water to alcohol is in the range of

about 1: i to about 20: 1, preferably about

3: l to 10: l, and better still about 4: i to approx.

ron 5: l, by weight. The total amount of water mixture

  alcohol, in this type of preparation, is typically in the range of from about 70% to about 99.9% by weight of the preparation. The pH of such a liquid and of the other preparations according to the invention is generally in the range from approximately 4.5 to approximately 9 and, typically,

about 5.5 to 8. This pH is preferably in the inter-

  valley from about 6 to about 8.0. It is interesting to note that the compositions of the invention can be applied orally at a pH below 5, without significantly decalcifying the dental enamel. PH can be adjusted with an acid (e.g. citric acid

  or benzoic acid) or a base (e.g. hydro-

sodium oxide) or buffered (for example with tam-

  pons based on phosphate). Such oral preparations

liquids may also contain a surfactant

  and / or a compound providing fluorine.

2463614 -

- 9 -

  For some other desirable forms

  In the forms of the invention, the oral composition may be of a solid nature or be in the form of a paste, as is the case for tooth powders, toothpaste tablets, toothpaste or toothpaste creams. The vehicle for such solid oral preparations

  or pastes generally contain a substance of polls-

  wise. As examples of such polishing substances, mention may be made of the substances insoluble in water which

  are sodilm metaphosphate, po- metaphosphate

  tassium, tricalcium phosphate, calcium phosphate

  dihydrate, anhydrous dicalcium phosphate, pyrophos-

  calcium phate, magnesium orthophosphate, phos-

  trimagnesium phase, calcium carbonate, alumina, hydrated alumina, aluminum silicate, silicate

of zirconium, silica, bentonite and their mixtures.

  The preferred polishing substances are silica gel.

  this or colloidal silica, amorphous aluminosilicates

alkali metal complexes and hydrated alumina.

Alumina is very effective, in particular hydrated alumina sold by Alcoa under the trade name 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

density of 0.37% at 1100 C, the density of which is 2.42 and which has particle sizes such as 100%

particles are smaller than 50 micro-

meters while 84% of said particles are of

  sions less than 20 micrometers.

When anti-tartar gels which are clear for visual observation are used, a polishing agent based on colloidal silica, chosen for example from those sold under the trade name SYLOID 72 such as Syloid 72 and Syloid 74 or under the name SANTOCEL, like Santocel l00, is particularly useful since such substances have refractive indices close to the refractive indices of agent-gelling-liquid systems (including

  including water and / or humectant) usually used

seated in toothpaste. For similar reasons, alu-

2463614,

- O10 -

  min.silicate complex-alcain metals are particular-

  useful as polishing agents in liming gels

  visual observation cells that contain the compound

PBTA in combination with anti-plaque anti-plaque agents

  nitrogen-based teriens previously described.

  Many polishing substances considered to be "water insoluble" are of the anionic type and may also include small amounts of the soluble substance. Thus, the et. insoluble sodium phosphate can be formed of any. manire cn-; er.nbae, c illustrated by the Dictionary of Applied Chemistry, de Thorpe, Volume

  9, 4th edition, pages 510 - 511. The forms of metaphos-

  Other examples of suitable substances are insoluble sodium phate known as Madrell salt and Kurrol salt. These metaphosphates have very low solubility in water and are therefore

usually considered to be unsophisticated metaphosphates

lubles. They do, however, contain a small amount of

  soluble phosphate, as an impurity, usually some

ques% to 4% by weight. The amount of phosphate solu-

  ble included in insoluble metaphosphate can be reduced

te, if desired, by washing with water. The insoluble alkali metal metaphosphate is typically used in the form of a powder with particle sizes such that no more

about 1% of the substance has part dimensions

cules larger than about 37 micrometers.

The polishing substance is generally pre-

smells in amounts ranging from about 10% to about 99% by weight of the oral preparation. Preferably, it is used in amounts ranging from about 10% to about% in toothpaste and from about 70% to about

99% in tooth powders.

For the preparation of tooth powders, it is usually sufficient to mechanically mix, for example by grinding, the various solid ingredients in suitable quantities and with suitable particle sizes. In oral preparations in the form of pasta, 1_-

the PBTA compound must be compatible with the other

titers of the preparation. So in a toothpaste

  this, the liquid vehicle may include water and a

humectant in an amount typically ranging from

about 10% to about 90% by weight of the preparation. The

glycerin, propyline-glycol, sorbitol or poly-

ethylene glycol 4C00 may also be present as

  humectants or binders. Liquid ingredients

  Particularly advantageous are the mixtures of water, glycerin and sorbitol. In clear gels, where the refractive index is an important parameter, approximately 3 to 30% by weight of water is preferably used, 0 to approximately 80% by weight of glycerin and approximately 20 to 80% by weight of sorbitol . A gelling agent, such as a natural or synthetic gum or a substance similar to a gum, typically Irish moss or carrageenan, sodium carboxymethylcellulose, methylcellulose,

  hydroxyethylcellulose, hydroxypropylmethylcellu-

  lose, a Carbopol (e.g. 934, 940 or 941), tragacanth, polyvinylpyrrolidone or starch or a mixture of these or similar substances is usually present in toothpaste in an amount up to about 10% by weight, preferably in the range of about 0.5% to about 5%. In a toothpaste or in a toothpaste gel, the liquids and the solids are in relative proportions suitable for

  form a creamy or gelled mass which can be extruded

  from a pressure vessel or a tube

crushable, for example aluminum or lead.

The solid or pasty oral preparation, which pre-

typically feels a pH of about 4.5 to 9 in the case of a 20% suspension, usually about 5.5 to about 8

  and preferably from about 6 to about 8.0, may also

hold a surfactant and / or a compound providing

fluorine.

  It is however understood that the preparations

  Oral statements are intended, as usual, to be sold or otherwise distributed in suitable labeled packaging (or on which labels have been affixed

- 12 -

inscriptions, also characterized below by the term

  "etiuetités"). Thus a bottle of liquid for bath of

  che will have a labeling which essentially describes it as a liquid for rinsing or washing the mouth and which gives the instructions for use and a toothpaste will be

  usually in a collapsible tube, typically aluminum

* minimum, in coated lead or in plastic material, or in another device for delivering paste by pressing

  to release the content in dosed quantity,

  both a labeling that writes this content com.ze éant essen-

a toothpaste or a toothpaste.

  Organic surfactants are used in the compositions of the present invention to obtain an increased prophylactic action, to facilitate obtaining a complete dispersion of the PBTA compound in

  the entire oral cavity and make the present composi-

  more cosmetically acceptable.

The organic surfactant is preferably anionic, nonionic or ampholytic in nature and is

  preferably used as a detergent substance

  with detergent and foaming properties

sition. As suitable examples of surfactants

  anionic active agents, there may be mentioned the monosulfates solu-

  in water monoglycerides of higher fatty acids

  laughing, like the sodium salt of the monoslyceride monosul-

tired of hydrogenated fatty acids from walnut oil

  coconut, (higher alkyl) sulfates such as laurylsul-

  sodium fate, alkylarylsufonates such as dodecyl-

sodium benzenesulfonate, sulfoaceous (higher alkyl)

tates, the higher fatty acid esters of 1,2-dihydro-

xypropanesulfonate and the saturated higher aliphatic acylamides of amino carboxylic compounds with a short aliphatic chain such as those containing 12 to 16 carbon atoms in the fatty acid, alkyl or acyl radicals,

  and analogous substances. The amides lately men-

for example, N-lauroylsarcosine and

  sodium, potassium and ethanolamine salts of N-

  lauroyl, N-myristoyl- or N-palmitoylsarcosine which must be essentially free from soap or similar higher fatty acid. the uttiisaticn of these sarcosinates in the toothpaste compositions of the present invention is particularly advantageous since these substances exert a prolonged and significant effect of inhibiting the formation of acid in the oral cavity due to the degradation of carbohydrates in addition to a certain effect of reducing the solubility of the enamel

dental in acid solutions.

  iZ his examples of water-soluble, nonionic sensives are the condensation products of ethylene oxide with various reactive compounds containing

  hydrogen, governing with ethylene oxide and present

  so many long hydrophobic chains (for example chai-

aliphatic about 12 to 20 carbon atoms), these condensation products ("ethoxamers") containing hydrophilic polyoxyethylene fractions and being in particular condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols , the

  fatty amides, polyalcohols (for example monostéara-

  sorbitol) and poly (propylene oxide) (that is,

i.e. substances with the trade name Pluronic).

  In certain embodiments of the invention,

a fluorine-providing compound is present in the preparation

  oral ration. These compounds may be slightly soluble in water or completely soluble in water. They are characterized by their ability to release fluoride ions into water and by a practical lack of reactivity with the other compounds of the oral preparation. Among these substances, mention may be made of mineral fluorides, such as

  soluble salts of alkali metals, alkaline earth metals and heavy metals, for example sodium fluoride,

  potassium fluoride, ammonium fluoride, a fluo-

copper rure such as cuprous fluoride, zinc fluoride, a tin fluoride such as stannic fluoride or

  stannous chlorofluoride, barium fluoride, fluo-

sodium silicate, ammonium fluosilicate, fluo-

  sodium zirconate, sodium monofluophosphate,

- 14 -

  aluminum mono- and di-_luophos.hates and fluorinated sodium pyrophosphate. it is preferred to use the fluorides of alkali metals and tin, such as sodium fluoride and stannous fluoride, sodium monofluophosphate and their mixtures.

  The amount of fluorine-providing compound

  depends, to some degree, on the type of compound, its solubility and the type of oral preparation, but it must

be used in a non-toxic amount. In a prepa-

  O ration Èa! E sol de, e. 're een rice or toothpaste, the amount of such a compound which releases a maximum of about i% by weight of the preparation is considered to be beneficial. Any suitable minimum amount of such a compound can be used, but this

preferably the latter used in a sufficient quantity

health to release about 0.005% to 1%, and preferably-

  this about 0.1%, of fluoride ions. Characteristically

ristic, in the case of alkali metal fluorides and stannous fluoride, this constituent is present up to

about 2% by weight, relative to the weight of the preparation

  tion, and preferably from about 0.05% to 1%. In the case of sodium monofluophosphate, this compound can be present in an amount of up to 7.6% by

  weight and being advantageously equal to 0.76%.

  In a liquid oral preparation, such as a mouthwash liquid, the fluorine-providing compound is typically present in an amount sufficient to release up to about 0.13%, preferably about 0.0013% to 0.1 % and better still around 0.0013% to 0.5%,

by weight, of fluoride ions.

  Various other substances can be incorporated

worn in the oral preparations according to the invention,

for example, bleaches, preservatives

carriers, silicones, compounds of the family of

  chlorophyll, other anti-tartar agents, anti-scaling agents

  anti-bacterial plate and / or ammonia-based substances

nium such as urea, diammonium phosphate and their metals

  swaddling clothes. These adjuvants, when present, are

- 15 -

  incorporated in preparations in quantities which do not

practically turbulent; not the properties and characteristics

ticks desired.

  Any flavoring agent can also be used.

venable or any suitable sweetening agent. Suitable flavoring agents are, for example, essences or essential oils, such as spearmint essence, peppermint essence, Wintergreen essence, essence of

  sassafras, clove essence, sage essence, essen-

  1 tsp eucalyptus, essence of marjoram, essence of cinnamon, essence of lemon and essence of orange, and methyl salicylate. Suitable sweetening agents

  include sucrose, lactose, maltose, sor-

bitol, xylitol, sodium cyclamate, perillartin, APM (aspartylphenylalanine methyl ester), saccharin and the like. Suitably, the

flavoring agents and sweetening agents may cons-

titrate, taken together, about 0.01% to 5% of the

preparation or more.

  During the preparation of the oral compositions

according to the invention, it is preferable, but not essential-

  ble, to add the PBTA compound after having mixed or put in contact with each other the other ingredients (except maybe a part of the water) to avoid the tendency of

PBTA compound on precipitation.

  For example, a mouthwash in the form of

rinse aid or washing fluid may be pre-

  adorned with mixing ethanol and water with essential oil

the surfactant, the humectant, the eventual

  such anti-bacterial anti-plaque agent such as cetylpyridinium chloride, benzethonium chloride or

chlorohexidine, the sweetening agent, the coloran-

te and then the PBTA compound defined above, then the

  desired amount of additional water.

  You can prepare a toothpaste by forming

  a gel with a humectant, a gum, a thick agent

  sissant or a gelling agent such as hydroxyethylcellulose, and a sweetening agent and then adding to the mass - 16r the polishing agent, the flavoring agent, the optional anti-plaque agent i-aé e, water additional and then the aforementioned PBTA cormpDose. If we use

  sodium carboxymethylcellulose as a gel agent

confident that, at the same time as an anti-bacterial anti-plaque agent of the bisbiguanide type, we follow the process of the patent of United States of America N 3 842 168 or that of the patent of United States of America N0 3,843,779, that

  it is modified by incorporating the PBTA compound.

  The practical implementation of an oral composition according to the invention, for example in the form of a toothpaste or a liquid for mouthwash, consists in regularly applying it to the dental enamel, preferably about 1 to about 3

times a day, at a pH of about 4.5 to about 9, generally

  about 5.5 to about 8, preferably about

6 to 8.

The examples below are given, not for

  limiting, to illustrate the present invention. Unless

otherwise indicated, all the quantities and proportions are expressed by weight in these examples as well as in the

appended claims.

Example 1

Inhibition of the growth of PAH crystals The evaluation is carried out by a method of maintaining the pH at constant value. 1.0 ml of a solution is introduced

  of the anti-scale agent to be tested (solu-

lXlO-4 M to lXlO- 5M relative to this agent) and phos-

  monosodium phate (solution O, 1 M compared to this phosphate)

in a flask, with 22 to 23 ml of distilled water, under agitation

  continuous tation and under a nitrogen atmosphere. 1 ml of a 0.1 M solution of CaCl 2 is added to the mass and the pH is adjusted.

  7.4- 0.05 by addition of 0.1N NaOH solution (con-

final concentration of Ca ++ and P043- = 4X10-3M). The consumption of NaOH O, 1 N is automatically recorded by means of the pH maintenance device (radiometer). In this essay,

PAH training takes place in two distinct phases.

  First, there is a rapid consumption of the base

2463614-

- 17 -

  1 7 (1> 4 minutes), then this decreases for 15 to 20 min,

after which a sernc..Cp. is prop

  duit. A delay in the appearance of the second rapid consumption or a complete absence thereof indicates that the growth of the PAH crystals is hindered. Agents that interfere with the crystal growth of PAHs are effective anti-scale agents. When submitting the PBTA compound

  in the above process, the following results are obtained.

TABLE I

  Anti-scale agent Training time Delay in training

(concentration) of PAH tion of PAH

Water (witness) 15 min -

PETA (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 h The above results show that PBTA effectively inhibits crystal growth PAH in vitro and that this inhibition is not due to calcium complex formation or calcium chelation since

PBTA / calcium ratios are used below the amount

stoichiometric tity.

  The following examples illustrate formulations for mouthwashes according to the invention; the Pluronic F 108

  is a block poly (alkylene oxide).

Example

(2) (3) (4) (5)

  0.22% 0.22% 0.22% 0.22% Ethanol 15.0 15.0 15.0 15.0 Pluronic F 108 3.0 3.0 3.0 3.0 Glycerin 10, 0 10.0 10.0 10.0 Na saccharin 0.03 0.03 0.03 0.03

PBTA 0.1 0.2 0.5 1.0

Water q.s.p. 100 100 100 100 pH (with NaOH) 7.4 7.4 7.4 7.4 7.4 Clear aspect limpid limpid limpid The following examples illustrate anti-tartar toothpastes in accordance with the invention:

Example

(6)

- - (7-).

Silica Glycerin Sorbitol (70%) Pluronic F-108 HExyxyethyl CE'- = 10 PBTA Sodium saccharin Taste agent Water 0.17 0.8 q.s.p. 100 1.2 0.17 0.8 q.s.p. 100 Table II below illustrates formulations

  for mouthwashes according to the invention as well as the activity

anti-stain tee of the preferred PBTA compound used as an additive

tif in these formulations. The characteristics of these

  mulations for the formation of stains on the teeth are evaluated by suspending hydroxyapatite (Biogel), a specific salivary protein, a source of carbonyl groups (for example acetaldehyde) and a phosphate buffer at pH 7, with and without the mouthwash formulations tested. The mixture is stirred at 37 ° C. for 18 hours. The colored PAH powder is separated by filtration and dried, and the intensities of

  coloring (in units of reflective power) are determined

  born on a Gardner differential colorimeter.

  In Table II below: 1. denotes a block poly (alkylene oxide); 2. denotes cetylpyridinium chloride

TABLE II

CLEAR FORMULATIONS FOR BATHS

(8) (9) (10) (11)

MOUTH

  (12) Ethanol Glycerin Pluronic F 1081 Taste agent Na saccharin CPc2 PBTA

Water q.s.p.

pH (with 1N NaOH) Reflective power Difference (DPR)

COMPARED TO EXAMPLE (9)

US 0%

Example

  (13) (14)% 3.0 0.146 0.03 o% 7.0 56.8% 3.0 0.146 0.03 0.1% 7.0 39.6

+ 17.2

% 3.0 0.146 0.03 0.1 0.1% 7.0 42.1 -2.5% 3.0 0.146 0.03 0.1 0.2% 7.0 43.6 - 4.0 % 3.0

0.1166

  0.03 0.1 0.3% 7.0 46.2 - 6.6% 3.0 0.146 0.03 0.1 0.5% 7.0 47.8 - 8.2% 3.0 0.146 0.03 0.1 1.0% 7.0, 9

- 16.3

! -20 -

The above results indisputably establish

  The additives of the present invention, as illustrated by the compound PBTA, considerably reduce

  the formation of stains on teeth which occurs habiti-

  tally using anti-bacterial anti-plaque agents as illustrated by the CPC. A PBTA concentration of around n, 2 A r. exeets results. In addition, these additives attenuate or inhibit gingivitis due to tartar and do not significantly reduce the activity of inhibition of dental plaque present by the agents.

aforementioned anti-plaque.

Replacement of the CPC used in Examples 14 to 14 with equivalent amounts of anti-plaque agents

  following antibacterials provides formulations that pro-

  also indicate an unexpected decrease in the formation of

dental calculus and stains on the teeth.

  Example Anti-bacterial anti-bacterial agent benzethonium chloride (BC) 16 chlorhexidine diacetate 17 chlorohexidine digluconate 18 dodecyl trimethyl ammonium bromide

CH 2CH2OH

2 2 CH2CH20H

I /

19 (C12-C18 alkyl) -N-CH2CH2N \

CH2CH20H

  aexidine dihydrochloride The following formulations illustrate toothpastes with anti-plaque activity and decreasing

the formation of spots and tartar.

- 21 -

Example (Parts)

21 22 23

Hydrated alumina 30 30 30 Polyethylene glycol 600 22 22 22 Pluronic F-108 3 3 3 Hydroxypropylmethylcellulose 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 Taste agent 0.8 0.8 0.8 Water q. s.p. 100 g 100 g 100 g Significant reductions in the formation of stains on teeth, plaque, tartar and gingivitis are also obtained, in accordance with the present invention, when the PBTA compound of the examples

  above is replaced by any of the other com-

posed PBTA described in the patents of the United States of America

risk N 3 886 204 and N 3 886 205.

- 22 -

R _ v vI DICATIONS 1. Oral coepsition in particular to improve oral hygiene, characterized in that it contains an acceptable oral vehicle containing approximately 0.01% to 10% by weight of an acid 2 compound -phosphono-butane-i, 2, - tricarboxylic of formula

O CHE - COOH

(I) HO

tCOOH o / I

HO I

R-CH - CH-C00H

  R- in which R is hydrogen, a lower alkyl group or a carboxyl group and R is hydrogen or a group

  methyl, or an orally acceptable salt thereof

laid, and from 0 to 15% by weight of at least one agent

  anti-bacterial plaque containing nitrogen and pro-

normally evoking the appearance of stains on the teeth, the percentage of this agent being expressed relative to

the free base form of said agent.

  2. Oral composition according to claim 1,

  characterized in that R and R are hydrogen.

3. Oral composition according to claim 1 or 2, characterized in that the abovementioned anti-bacterial anti-plaque agent is of a cationic nature and is present in a

  amount of at least about 0.001% by weight.

  4. Oral composition according to any one of

  claims 1 to 3, characterized in that the compound

  above is present in an amount of about 0.1% at

about 6% by weight.

5. Oral composition according to any one of

  claims 1 to 4, characterized in that the anti-

the aforementioned anti-bacterial plate is a substituted guanidine.

6. Oral composition according to claim 5, characterized in that the abovementioned anti-bacterial anti-plaque agent is a water-soluble salt, pharmaceutically

- 23 -

  acceptable, of an agent chosen from chlorhexidine and alexidine. 7. Oral composition according to any one of

  claims 1 to 4, characterized in that the anti-

  the aforementioned anti-bacterial plate is benzethium chloride. 8. Oral composition according to any one of

  claims 1 to 4, characterized in that the anti-

  anti-bacterial prieity plate is an ammonium compound-

  quaternary including _ a to 2 alkyl groups from 8 to 20

carbon atoms.

  9. Oral composition according to any one of

claims 1 to a, é ..... 4sa. in that the anti

  above-mentioned anti-bacterial plate is cetylpy chloride-

ridinium.

  10. Oral composition according to any one of

claim 1 to 9, characterized in that the vehicle pre-

  cited is a mixture of alcohol and water, this composition being in the form of a mouthwash liquid

from a pH of around 4.5 to around 9.

  11. Oral composition according to any one of

Claims i to 9, characterized in that the vehicle pre-

city includes a liquid vehicle and a gelling agent

  tion, a polishing substance acceptable from the dental point of view also being present, this composition being

  a toothpaste with a pH of about 4.5 to about 9.

  12. Composition for mouthwash according to one

any one of claims 1 to 11, characterized in that

  that it contains about 0.01 to about 5.0% by weight

of the above-mentioned agent.