FR2626174A1 - PYROPHOSPHATE-BASED ANTI-TARTAR TOOTHPASTE COMPOSITION, METHOD FOR MANUFACTURING THE SAME, AND USE THEREOF - Google Patents

Abstract

The invention relates to a dentifrice composition. Said composition contains, as an anti-scale agent, about 4.3 to 7% of alkali metal pyrophosphate comprising at least 4.3% of tetrapotassium pyrophosphate alone or in admixture 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 about 3% of a synthetic anionic polymeric polycarboxylate. Application: toothpastes.

Description

The present invention relates to composi-

  for oral use, containing an anti-tartar agent.

  Tartar is a mineral formation of

  re which forms on the teeth. Regular brushing

  helps to prevent a rapid accumulation of such

  but even regular brushing is not enough to

  eliminate all scale deposits that adhere

  to the teeth. Tartar is formed on the teeth

  when calcium phosphate crystals consume

  cent to be deposited in the film matrix and ex-

  tracellular plaque and get to be sufficiently packed together Dour street aggregates

  resist a deformation. There is no explanation

  unanimously accepted on the manner in which

  cium and orthophosphate eventually become the

  crystalline substance called hydroxvapatite (PAH). How-

  Cant, it is generally recognized at higher saturations, ie above the critical saturation limit, the precursor of crystalline PAH

  is an amorphous calcium phosphate or microcrystalline

  linen. "Amorphous calcium phosphate", although

  to hydroxyapatite, differs in structure

  atomic, particulate matter and stoichiology.

  metry. The X-ray diffraction pattern of the

  amorphous calcium phosphate shows broad peaks ty-

  spike amorphous materials, lacking the atomic order of long range, characteristic of all crystalline materials, including PAH. By

  Consequently, it is obvious that the agents

  Effective crystal growth of PAHs will be effective as anti-scale agents. A suggested mechanism by which the anti-scale agents of the present invention prevent scale formation is likely to involve raising the activation energy threshold thereby inhibiting the

  transformation of the amorphous calcium phosphate

slider in PAH.

  Studies have shown that there is a

  satisfactory relationship between the ability of a compound to prevent crystal growth of PAHs in vitro and its ability to prevent calcification in vivo, provided of course that such a compound is stable

  in the plate, saliva and their components.

  The prior art indicates that the py-

  Soluble rophosphate can be used to reduce scale formation. For example, U.S. Patent No. 4,515,772 refers to several prior art references describing oral compositions containing soluble pyrophosphates,

  including an article by Draus et al. Arch. Oral.

  Biol., 15, pp. 893-896 (1970), which describes the effectiveness of

  cited in vitro such salts against scale. This article

  ticle refers to a possible inhibition of the action

  pyrophosphate by the enzyme pyrophosphatase.

  Saliva is known to contain enzymes

  acid phosphatase, alkaline phosphatase and pyrazine

  rophosphatase. Any one of

  these three enzymes can affect pyro-

  phosphates as an inhibitor of PAH formation and

  tartar. It is clear, therefore, that a

  pyrophosphate antitartarent impregnator

  reduce or eliminate the destructive

three enzymes of saliva.

  The compositions of the aforementioned Patent No. 4,515,772 are limited to a pH of 6.0 to 10.0 and include a fluoride and soluble di (alkali metal) pyrophosphates alone or in admixture with pyrophosphates of tetra (alkali metal) but not more than 4.0% K4P207 (Tetrapotassium Pyrophosphate). This patent does not

  not describe or even mention the effectiveness of the

  patented fluoride-pyrophosphate position, 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

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

agent in saliva.

  Another object of this invention is

  This is to provide such a composition, effective in a relatively wide pH range and / or

  having better cosmetic properties.

  Another object of this invention is

  tion is to provide such a composition which does not significantly erode the surface of the teeth and which exerts

  also an important and acceptable anti-caries effect.

  Another object of this invention is

  tion is to provide an improved process for

the formation of tartar.

  Other goals and benefits will emerge from

the following description.

  At the beginning of the development of this

  invention, it has been found that the dentifri-

  those containing only tetrasodium pyrophosphate

  The anti-scale agent was granular and the solid granular particles consisted of Na4P20

undesirable.

  The present invention is based, at least in

  part, on the determinations or discoveries of the De-

  that the fluoride ion inhibits the hy-

  pyrophosphate drolysis by acid phosphatase and pyrophosphatase, as polymeric polycarboxylates

  Synthetic anionics inhibit the hydrolysis of pyrolysis

  phosphate by alkaline phosphatase and that the appearance

  granular particles in oral compositions can be avoided by the use of a predominant proportion of pyrophosphate in the form of

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 powder, a dental tablet, chewing gum

  gum or lozenge containing a vehicle orally -

  and, in approximate proportions by weight, A. from 4.3% to 7% alkali metal pyrophosphates as an essential anti-scale agent, comprising at least 4.3% tetrapotassium pyrophosphate, alone

  or mixed with up to 2.7% pyrophosphate

  trasodium and, as inhibitors of hydrolysis in

  zymatic of said agent in saliva,

  B. a quantity of a fluoride ion source suf-

  to provide from 25 parts per million to 5,000 parts per million of fluoride ions, and from 0% to 3% of a polymeric polycarboxylate

  synthetic anionic having a molecular weight of

  1000 to about 1,000,000, preferably about

30,000 to about 500,000.

  Synthetic anionic polymeric linear polycarboxylates and their complexes formed

  with various cationic germicides, zinc and

  gnesium have been previously described as

  anti-scale agents per se, for example in US Pat. Nos. 3,429,963, 4,152,420, 3,956,480, 4,134,477 and 4,183,914. However, none of these patents nor the prior art known, discloses the use of such polycarboxylates alone

  to inhibit hydrolysis by saliva of

  pyrophosphate type, much less in association with

  cation with a compound constituting an ion source

  fluoride. It is obvious that the polycarboxylates poly-

  Synthetic anionic linear matrices described in these patents can be used in the compositions and

  the methods of the present invention.

  Anionic polymeric polycarboxylates

  synthetic material, but preferably used

  here, are, as indicated above, well known,

  being often used in the form of their free acids

  or their alkali metal salts (eg potassium and preferably sodium) or ammonium salts

  water-soluble, preferably partially and better

  totally neutralized core. The 1: 4 to 4: 1 coDolvymers of anhydride or maleic acid are melted with another polymerizable ethylenically unsaturated monomer,

  preferably methyl and vinyl ether (methoxy-

  ethylene), having a molecular weight (P.M.) of about

  30,000 to about 1,000,000. These copolymers are available

  for example under the names Gantrez AN

  139 (bp 500 000), A.N. 119 (bp 250 000) and pre-

  Pharmaceutical Grade S-97 (MW 70,000)

  from GAF Corporation. The term "synthetic" must be

  tending to exclude agents which are

  known fuels including carboxymethylcellulose and

  other cellulose derivatives and natural gums

the.

  Other polymeric polycarboxylates used

  include those described in the aforementioned U.S. Patent Nos. 3,956,180, such as 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, P.M. 10,000,

  and EMA GRADE / 61, and the 1: 1 copolymers of acrylic acid

  with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl ether

  and vinyl or N-vinyl-2-pyrrolidone.

  Other polycarboxylate polymers used

  disclosed in U.S. Patent Nos. 4,138,477 and 4,183,914 discloses copolymers of maleic anhydride with styrene, isobutylene or the like.

  ethyl vinyl ether, polyacrylic acids,

  polyitaconic and polymaleic substances, and oligomers

  sulphoacrylic resins as low as 1000,

  available under the name Uniroyal ND-2.

  Carboxylic acids are generally

  olefinically unsaturated or polymeric ethylenic unsaturated

  containing a carbon-to-carbon activated olefinic double bond and at least one carboxyl group, i.e., an olefinic double bond-containing acid which readily acts in the polymerization due to its presence in the monomer molecule

  in the alpha-beta position with respect to a group

  carboxyl, either as part of a methyl group or

  lene terminal. Examples of such acids are the

  acrylic acids and anhydrides, methacrylic acid, etha-

  crylics, alpha-chloroacrylic, crotonic, beta-

  acryloxypropionic, sorbic, alpha-chlorosorbic,

  cinnamic, beta-styrilacrylic, muconic, itaco-

  nucleic, citraconic, mesaconic, glutaconic, -

  aconitic, alpha-phenylacrylic, 2-benzyl-acrylic

  2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic. Other olefinic monomers

  different copolymerizable with such monomers car-

  Boxylics include vinyl acetate, chloride

  vinyl, dimethyl maleate, etc. The copolymers

  res contain sufficient carboxylic acid groups

only to be soluble in water.

  Also useful in the present invention

  the so-called carboxyvinyl polymers described as toothpaste components in U.S. patents.

  A. Nos. 3,980,767, 3,935,306, 3,919,409, and 3,911.

  904 and N 3 711 604. They are available in the

  merce, for example under the trade marks Carbo-

  pol. 934, 940 and 941 of 3. F. Goodrich, these products

  essentially consisting of a colloidal nol-

  water-soluble polyacrylic acid crosslinked with about 0.75% to about 2.0% polyallyl sucrose

  or polyallyl-pentaerythritol as a crosslinking agent

lation.

  The linear polymeric polycarboxylate component

  synthetic anionic area is mainly a hy-

  hydrocarbon optionally containing halogenated substituents and oxygenated links, as exists for example in ester, ether and OM groups, and if used it is generally present in

  the compositions of the invention in proportions

  proximal by weight of 0.05 to 3%, preferably from 0.05 to 2%, more preferably from 0.1 to 2%. Proportions

  situated in the upper parts of these inter-

  valles are generally used in composi-

  toothpaste preparations, generally containing a dental abrasive and used in conjunction with brushing teeth, for example, toothpastes (including creams), gels, powders and tablets. Quantities greater than these intervals may be

  used for thickening or gelling purposes

tion.

  As indicated above, these polycarboxylates

  polymers have proven to be effective inhibitors

  these of the enzyme alkaline phosphatase. Since this enzyme has a low activity (for hydrolysis of pyrophosphate) at about pH 7.0 or lower, the

  polymeric polycarboxylate component may possibly

  should be omitted from oral preparations formu-

  to act at such a pH of 7.0 or lower. How-

  However, this omission obviously reduces the flexibility

  use and effectiveness of oral compositions.

  cal of the present invention on the wide range

from about 4.5 to about 10.

  The sources of fluoride ions, or fluorine-providing compounds required according to the present invention as an essential component of the acid phosphatase enzyme inhibitor and pyrophosnhatase are

  well known in the art as anti-agents

  caries and also act as such agents in

  the practice of the present invention. These com

  may be slightly soluble in water or

  can be fully water soluble. They are

  characterized by their ability to release fluorescent ions

  in water and by a lack of reaction

  sirable with other compounds of the preparation for oral use. Among these materials, mention may be made of mineral fluorides, such as the soluble salts of alkali metals and alkaline earth metals, for example sodium fluoride, potassium fluoride,

  ammonium fluoride, calcium fluoride, a fluorine

  copper chloride such as cuprous fluoride, fluorine

  zinc fluoride, barium fluoride, fluorosilicate

  of sodium, ammonium fluorosilicate, fluorozir-

  sodium conate, sodium monofluorophosphate,

  aluminum mono- and di-fluorophosphates and py-

  Sodium and calcium fluorophosphate. Alkali metal and tin fluorides such as

  stannous sodium fluorides, monofluorophospha-

  te (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 must be a nontoxic amount, usually about 0.005 to about 3.0% in the

  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 liberates up to about

  5,000 parts per million (ppm) of F-ion

  the weight of the preparation is considered satisfactory. Any suitable minimum amount of such a compound may be used, but it is preferable to use sufficient compound to release about 300 to about 2000 ppm, preferably about 800 to about 1500 ppm fluoride ion. In general, in the case of alkali metal fluorides and stannous fluoride, this component is present in a proportion of up to about 2% by weight, based on the weight of the preparation, and preferably about 0.05% by weight. 1%. In the case of sodium monofluorophosphate, the compound may be present in a proportion of about

  0.1 to 3%, more usually about 0.76%.

  In toothpaste preparations such

  pellets and chewing gum, the fluorescent compound

  d 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

  In general, this compound is present in a proportion of about

  from about 0.005 to about 1.0% by weight.

  The dentifrice compositions of the present invention achieve the desired anti-tartar effect when mixing from about 4.3% to about 7% tetrapotassium pyrophosphate alone or with up to 2.7% tetrasodium pyrophosphate. Preferred ratios of tetrapotassium: tetrasodium salts range from about 4.3: 2.7 to about 6: 1, particularly a ratio of

  4.5: 1.5. Unlike the patent specification No

  4 515 772, it is very important that the commu-

  of the present invention-possess proprietary properties

  anti-scale units which are quite acceptable and

  improved cosmetic teas while containing more

  4.0% of the tetrapotassium pyrophosphate and without

  pyrophosphate di (alkali metal), although

  small amounts, for example about 0.1% to about

  0.4% or about 1% may be present if

the desire.

  The pH of the toothpaste preparations of the in-

  The value is generally in the range of about 4.5 to about 9, and generally about 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 ranges without decalcification or other appreciable deterioration of 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 bicarbonate

  sodium nate, disodium phosphate, phosphate

monosodium, etc.).

  In certain advantageous forms of the present invention, the dentifrice composition may be substantially solid or creamy in nature, for example a toothpaste powder, a dental tablet, a toothpaste (cream), or a dental gel. The vehicle of these solid or solid toothpaste preparations

  creamy foods usually contains a polish

  wise acceptable for the oral and dental routes to

  use in conjunction with brushing teeth. Examples

  such polishing materials are a metaphor for

  sodium pothole, a potassium metaphosphate, the

  tricalcium phosphate, calcium phosphate dihydrate

  anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, zirconium silicate, silica,

  bentonite and mixtures thereof, 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-formaldehydes, and poly-

  epoxides and crosslinked polyesters. Pole materials

  Preferred smoothing compositions include crystalline silica having particle size of at most about one micrometer, an average particle size of at most about 1.1 micron, and a specific surface area of at most about 50,000 cm 2 / g. silica or colloidal silica, and complex aluminosilicates

amorphous alkali metals.

  When using clear gels,

  polishing agents consisting of colloidal silica

  the, such as those sold under the trademark SYLOID, such as Syloid 72 and Syloid 74 or under the brand name

  SANTOCEL, like Santocel 100, and

* Alkali metal aluminosilicate plexes are

  particularly useful because they have indices of

  fractions close to the refractive indices of the liquid gelling agent systems (including water and / or

  humectant) commonly used in toothpastes.

  Many of the so-called water insoluble polishing materials are anionic in nature

  and also contain small amounts of

  soluble. Thus, an insoluble sodium metaphosphate

  can be formed in any appropriate manner, as it-

  gloss in Thorpe's Dictionary of Applied Chemistry, Volume 9, 4th Edition, pages 510-511. The forms of insoluble sodium metaphosphate known as Madrell salt and Kurrol salt are other examples.

  appropriate materials. These metaphosphates do not

  that a very low solubility in water and

  Therefore, they are commonly referred to as metaphores

  insoluble phates (IMP). They contain a small amount of soluble phosphate in the form of impurities, usually a small percentage, for example up to 4% by weight, the amount of soluble phosphate, which is

  supposed to contain a sodium trisetaphosphate

  in the case of insoluble metaphosphate, may be

  reduced or eliminated by washing with water, if

  re. The insoluble alkali metal metaphosphate is generally

  usually used as a powder of one dimension

  such that no more than about 1% of the

  is larger than about 37 micro-

meters.

  The polishing material is generally

  in solid or paste compositions at

  concentrations by weight from about 10% to about 99%.

  Preferably, it is present in amounts ranging from about 10% to about 75% in a toothpaste or gel, and from about 70% to about 99% in a

toothpaste or tablet.

  In a toothpaste, the liquid vehicle

  It may contain water and a humectant, generally in a proportion of from about 10% to about 90% by weight, based on the weight of the preparation. The

  glycerine, propylene glycol, sorbitol, poly-

  propylene glycol and / or polyvinyl glycol

  example 400-600) are examples of humectants / vehicles

  appropriate methods. Liquid mixtures of water, glycerol

  ceria and sorbitol are also advantageous. In transparent gels, when the refractive index

  is an important factor, it is preferred to use

  3 to 30% by weight of water, 0 to about 80% by weight of glycerin and about 20 to 80% by weight of sorbitol. The toothpastes (creams) and gels generally contain a natural or synthetic thickener or gelling agent in amounts of about 0.1 to about 10, preferably 0.5 to about 5% by weight.

  weight. A suitable thickener is the hectorite syn-

  Thetic, a complex colloidal synthetic clay

  of the magnesium silicate and alkali metal silicate type

  available for example under the name Laponite (for example

  example CP, SP 2002, D) marketed by Laporte In-

  Limited Industries. The analysis of Laponite D reveals, approximately by weight, 58.00% SiO 2, 25.40% MgO, 3.05% Na 2 O, 0.98% Li 2 O and some water and metals. form of traces. Its actual density is 2.53 and its apparent density (g / ml to

a humidity of 8%) of 1.0.

  Other suitable thickeners include

  Irish moss, gum tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose,

  hydroxybutylmethylcellulose, hydroxypropylmethyl-

  cellulose, hydroxyethyl cellulose (for example,

  nible as Natrosol), carboxymethylcellulose

  sodium, and colloidal silica such as Syloid

crushed (for example 244).

  It is evident that, as is customary, oral preparations are intended to be sold or otherwise distributed in appropriate labeled packages. Thus, a toothpaste, a cream or a gel will generally be packaged in a compressible tube, usually made of aluminum,

  coated lead or plastic, or other

  compressible scorer, pumped or pressurized to dose the contents, bearing a label describing it, in essence, as being a toothpaste, a gel

or a dental cream.

  Organic surfactants are

  used in the compositions of the present invention.

  In order to obtain an increased prophylactic action, to promote an intimate and complete dispersion of the anti-scale agent throughout the oral cavity, and to make the compositions of the invention cosmetically acceptable. The organic surfactant material is

  preference of anionic, nonionic or

  it is preferable to use as surfactant a detergent material which confers on the

  composition of the detergent and foaming properties.

  Suitable examples of anionic surfactants are

  the water-soluble salts of monoglycerol monosulphates

  fatty acid wrinkles such as sodium salt

  Monosulfated monoglyceride dium of oil fatty acids

  hydrogenated coconut, (higher alkyl) sulphates

  such as sodium lauryl sulphate, alkylaryl-

  sulfonates such as dodecylbenzene sulfonate

  sodium, (higher alkyl) sulfoacetates,

  higher fatty acids of 1,2-dihydroxypropane

  sulfonate, and higher aliphatic acyl amides

  saturated with amino carboxylic acids

  lower pheromones such as those having 12 to 16 carbon atoms in the acid, alkyl or acyl radicals

  fat, etc. Examples of the amides mentioned in the last

  n-lauroyl-sarcosine, and the sodium, potassium and ethanolamine salts of N-lauroyl-, N-myristol- or N-palmitoyl-sarcosine, which must be substantially free of soap or higher fatty acid material. similar. The use of

  these sarcosinates in compositions for oral use.

  cal of the present invention is particularly

  advantageous because these substances exert an effect

  lined and marked on inhibition of formation

  acid in the oral cavity due to decomposition

  of carbohydrates in addition to the fact that they exert a certain decrease in the solubility of

  dental enamel in acidic 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 (eg aliphatic chains

  about 12 to 20 carbon atoms), these

  condensing sludges ('ethoxamers') containing hydrophilic polyoxyethylene moieties, such as condensation products of polyethylene oxide with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (eg sodium monostearate);

  sorbitan) and: poly (propylene oxide) (e.g.

  pluronic materials).

  Various other materials may be incor-

  porées in the oral preparations of the pre-

  invention, for example bleaching agents,

  preservatives, silicones, chlorinated compounds

  phyllés, other anti-scale agents and / or an ammoniated material such as urea, diammonium phosphate,

  and their mixtures. These adjuvants, when they are

  ingredients are incorporated in the preparations in quantities which do not affect appreciably

  the desired properties and characteristics.

  Any suitable flavoring or sweetening material may also be used. Examples of suitable flavoring components are flavoring essences such as spearmint, peppermint, wintergreen, sassafras, clove, 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,

  rillartine, APII (aspartyl-ohenyl-alanine, methyl ester

  thyline), saccharin, etc. Advantageously, the flavoring and sweetening agents may constitute

  together about 0.1 to 5% or more of the preparation.

  In the preferred implementation of the pre-

  invention, a composition for oral use according to

  the present invention, for example a toothpaste containing

  the pyrophosphate and enzyme inhibitor described in an amount effective to inhibit scale on the surface of the teeth, is preferably applied by regular brushing of the tooth enamel, for example every two or three days, or preferably 1 to 3 times

  per day, at a pH of about 4.5 to about 10, generally

  from about 5.5 to about 9, preferably about 6 to 8, for at least 2 weeks up to 8 weeks.

  or more, even permanently. Toothpaste is usually

  removed by rinsing with water after each

  cation. The compositions of the present invention may be incorporated into lozenges, or into chewing gum (chewing gum) or other products, for example by stirring in a warm gum base or applying on the outer surface of a base of

  gum, of which representative examples are jelly

  tong, rubber latex, vinylite resins, etc., advantageously with conventional plasticizers or softeners, sugar or other sweeteners

  or carbohydrates such as glucose,

bitol, etc.

  The vehicle or support contained in a

  or a pellet is a polyhydric alcohol (polyol)

  soluble non-cariogenic solid such as mannitol,

  xylitol, sorbitol, maltitol, a hydrolyzate of

  Hydrogenated midon, Lycasin, hydrogenated glucose, hydrogenated disaccharides and hydrogenated polysaccharides, in a proportion of about 90 to 98% by weight.

  weight of the entire composition. Solid salts

  such as sodium bicarbonate, sodium chloride, potassium bicarbonate or

  potassium can totally or partially replace

  the polyol used as a vehicle.

  Pelleting lubricants, in minor amounts of about 0.1 to 5% by weight, may be

  incorporated into the tablet or

  to facilitate the preparation of both tablets and lozenges. Suitable lubricants include vegetable oils such as

  copra, magnesium stearate, aluminum stearate

  nium, talc, starch and Carbowax.

  The tablet formulations contain

  about 2% of gum as a barrier agent

  designed to produce a glossy surface unlike a tablet that has a smooth finish. Suitable non-cariogenic gums include carrageenan

  kappa, carboxymethyl cellulose, hydroxyethylcellulose

lulose, Gantrez, etc.

  The tablet or tablet may optionally

  be coated with a coating material such as

  waxes, shellac, carboxymethyl-

  cellulose, a polyethylene / maleic anhydride copolymer

  or carrageenan kappa in order to increase

  the time needed for the tablet or lozenge to dissolve in the mouth. The uncoated tablet or lozenge dissolves slowly, which

  ensures a sustained release of the ingredients

  for about 3 to 5 minutes. Therefore, the solid tablet and metered pellet composition of the present invention allows a relatively longer time of tooth contact 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 the temperatures

  in degrees Celsius unless otherwise specified.

EXAMPLE A

  Effect of Saliva Enzymes on Inhibition of PAH Formation by TSPP In Vitro PAH Formation is Measured

  by titrimetry by a pH-stat process. Solu-

  storage conditions of 0.1 MI CaCl2 and 0.1 M NaH2PO4

  are prepared fresh in distilled water de-

  carbonate free, 23 ml of distilled water

  deionized free of CO 2, 1.0 ml of the

  phosphate solution and 1.0 ml of a solution

  1X10-4M aqueous solution of the anti-scale agent to

  to be tested, then 1.0 ml of the solution

  of calcium chloride which initiates the reaction

  tion. The reaction is carried out at pH 7.4 under atmospheric pressure.

  nitrogen. The consumption of NaOH O, 11N is recorded

  automatically, from which it is determined

  do not have the time required for crystals to form.

  Table A shows the results of this mode.

tory.

TABLE A

  Inhibition Time of Anti-Crystals Agent Growth (Hours) Tartar Saline Water Pyrophosphatase Alkaline Phosphatase

________

TSPP * 0.8 0.4 0.3 0.0

  X 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 longer delay

  short. This reduction in efficiency is due to the hy-

  enzymatic drolysis of P-O-P bonds. The incubation

  this agent with pyrophosphatase and phosphorus

  alkaline phatase dramatically decreases the period

  delay and shows the sensitivity of the relationship

  its P-O-P to hydrolysis by phosphatases. We ob-

  holds substantially the same results using Tetrapotassium Pyrophosphate (TKPP) instead

  of TSPP, both having the same pyrophosphate ion

  effective phage containing a P-O-P bond.

EXAMPLE B

  Stabilization of TSPP vis-à-vis Enzyme Hydrolysis

  in the presence of Inhibitors An enzymatic hydrolysis is carried out

  in a buffer solution of NaOH and morpho-

  100 millimolar linopropanesulfonic acid (pH 7.0)

  holding 1.3 mg / ml of TSPP. Inhibitors of

  this invention are added (except as witness) to a

  final concentration of 1000 ppm floridic ion (

  of NaF) and 0.5% of the sodium salt of a

  lymere (1: 1) methoxyethylene maleic anhydride

  hydrolyzed, M.P. 70,000 (Gantrez S-97 from Phar-

  ceutical). Equal activities of acid phosphatase

  of alkaline phosphatase and pyrophosphatase half

  are then added to obtain an activity

  total phosphatase content of 0.3 units / ml. Samples

  samples of the test solution are taken and the

  total thophosphate available in each sample is measured after 3 hours of hydrolysis in 4N HCl at 1000 C. The reaction mixture is incubated at

  37 C, shaking and aliquots are

  at appropriate times for at least 90 minutes.

  to determine the orthophosphate content. Table B shows the results expressed as percentage of orthophosphate released as a result of the hydrolysis of

pyrophosphate.

TABLE B

  Percent Orthophosphate Percent Released in 90 Minutes Relative Protection Agent Anti- With Tartar Control Inhibitors

TSPP 98 58 41

  Table B shows that after 90 minutes

  incubation in the presence of enzyme, 98% of the

  available thophosphate are released from TSPP in the absence of

  inhibitors. With inhibitors, hydro-

  lysis of P-O-P bonds in pyrophosphate (TSPP)

  is reduced by 41%. It should be noted that

  Enzyme values used in this study are at least 2 to 3 times higher 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 substituting

  equivalent amounts of TKPP to TSPP.

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

  Deionized water 31,000 26,607 Blue FD & C N 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 Powder 1,200 1,200 Flavor 1, 000 1,000 The above formulations are prepared

  as following. The components of Part 1 are mixed

  to form a solution. Separately, the

  Part 2, with the exception of water, are mixed to form a dispersion in the polyethylene glycol / glycerin humectant and then the water is introduced 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 anti-caries effect of the fluoride component, and not to exert significant effects

erosion of teeth.

EXAMPLE 3

  Using the same oerative mode as in Examples 1 and 2, the formulation is prepared

  toothpaste according to the present invention.

  tion. Ingredients Parts by weight Deionized Water 37,578 Glycerine 25,000 Zeo 49B (Silicon Dioxide) 21,500

TKPP 4,500

TSPP 1,500

  Syloid 244 (Synthetic Silica) 3,000 Sodium Lauryl Sulfate 1,200 Flavor 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 Sodium Saccharin 0,300 Sodium Fluoride 0.242

  Exemoles 4 and 5 represent formulas

  patches according to the invention.

EXAMPLE 4

  Pellets formulations Parts by weight Sugar 75-98 Corn syrup 1-20 Flavoring spirit 0.1-1.0 Lubricant for tablets 0.1-5 TKPP: TSPP3: 1i 3,5-8 Gantrez S-97 0,05 -3 NaF 0.01-0.05 Water 0.01-0.2

EXAMPLE 5

  Pellets Percent by weight Sodium saccharin 0.15 Aroma 0.25 Magnesium stearate (lubricant) 0.40 Dye 0.01 Emulsifier * 1.00 NaF 0.05 Gantrez S-97 0.30

TKPP: TSPP - 3: 1 6.50

  Sorbitol q. s. per 100 * PEG (40) -sorbitan diisostearate

EXEMPTION 6

  Chewing gum Parts Gum Base 10 to 50 Binder 3 to 10

Charge (sorbitol, mannitol or

  of these) 5 to 80 Sweetener arczactei 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 the above formulations are des-

  to give better non-granular properties.

  and other cosmetic and exercise properties

* in vivo better anti-tartar effects.

2 6 2 6 1 7 4

Claims (14)

  1. A composition for oral use containing an aqueous vehicle which is acceptable from the point of view of the mouth and   in approximate quantities and proportions by weight   A. a mixture of tetrasodium pyrophosphate and tetrapotassium pyrophosphate in which the   Tetrapotassium pyrophosphate is in   pondérante; and B. an amount of a fluoride ion source   sufficient to provide 25 ppm to 5000 ppm of   rure. 2. A composition for oral use containing an aqueous vehicle acceptable from the point of view of the mouth and   in quantities and approximate proportions by weight matives,   A. at least 4.3X of a pyrophosphate mixture   alkali metal pest containing tetrasodium pyrophosphate and tetrapotassium pyrophosphate in a ratio of 2.7: 4.3 to 1: 6 and sufficiently   tetrapotassium pyrophosphate to avoid the   granulation of tetrasodium pyrophosphate particles in the composition; and B. an amount of a fluoride ion source sufficient to provide from 25 ppm to 5000 ppm fluoride ion. 3. A composition for oral use containing an aqueous vehicle acceptable from the point of view of the mouth and   in approximate quantities and weight proportions   mative, A. 4.3 to 7Z of a tetrasodium pyrophosphate tetrapotassium pyrophosphate Pt in a ratio of 2.7: 4.3 to 1: 6; and B. an amount of a fluoride ion source 2 6 2 6 1 7 4   sufficient to provide from 25 ppm to 5000 ppm fluoride ion. 4. Oral composition containing an aqueous vehicle acceptable from the oral and   in quantities and approximate tives;   A. 0 to 90X of an acceptable polishing agent   dentally, B. an amount of a source of fluoride ion sufficient to provide 223 ppm to 9050 ppm fluoride ion; and C. a quantity of at least one ion source   pyrophosphate to provide at least 2,3Z. of pyro   phosphate; wherein the pH of the composition is from about 4.5 to about 10 and said composition contains sodium ions and potassium ions in a ratio respective 0.1: 1 to 1.04: 1.   5. Composition according to claim 4,   holding sodium ions and potassium ions in a   ratio of 0.37: 1 to 1.04: 1.   6. Composition according to any one of   Claims 1 to 5 additionally containing up to 0.4% di-alkaline pyrophosphate.   7. Composition according to any one of   Claims 1 to 5 further containing up to 17 di-alkaline pyrophosphate.   8. Composition according to any one of   Claims 1 to 7 additionally containing a silica   abrasive acceptable from the oral point of view.   9. Composition according to any one of   Claims 1 to 8 in which the ion source   fluoride includes sodium fluoride.   10. Composition according to any one of 2 6 2 6 1 7 4   Claims 1 to 9 additionally containing from 0.05 to 3Z   synthetic anionic polymeric polycarboxylate having a molecular weight of about 1000 to 1,000,000.   The composition of claim 10, wherein the polymeric polycarboxylate comprises a carboxyvinyl polymer.   The composition of claim 10, wherein the polymeric polycarboxylate comprises a copolymer of anhydride or maleic acid with a   other monomer polymerizable ethylenic unsaturation.   The composition of claim 12 wherein said monomer is methyl ether and of vinyl.   14. Method for inhibiting dental calculus   for the application to the surface of the teeth of a   effective manner of a composition according to any one of Claims 1 to 13.