WO1991016033A2

WO1991016033A2 - Dentifrice

Info

Publication number: WO1991016033A2
Application number: PCT/GB1991/000537
Authority: WO
Inventors: Geoffrey Royston Doel; Stephen Edward Alexander
Original assignee: Beecham Group Plc
Priority date: 1990-04-12
Filing date: 1991-04-05
Publication date: 1991-10-31
Also published as: JPH05506653A; EP0524222A1; WO1991016033A3; ZA912655B; GB9008433D0; IE911204A1

Abstract

Dentifrices comprising a cationic antibacterial agent, and a thickening agent, surfactant and an abrasive each of which is compatible with the cationic antibacterial agent, are useful in the prophylaxis and treatment of periodontal disease, including gingivitis.

Description

DENTIFRICE

The present invention relates to a dentifrice composition comprising an antibacterial agent, in particular a cationic antibacterial agent, which compositions are useful in the prophylaxis and/or treatment of periodontal disease, calculus and caries.

The use of antibacterial agents, including cationic antibacterial agents, in oral hygiene compositions has been widely advocated as a means of reducing the bacterial plaque population and this may be beneficial in the treatment of peridontal disease, calculus and/or caries,

Whilst mouthwashes comprising cationic antibacterial agents are available, these suffer the disadvantage that the cationic antibacterial agents tend to leave a brown stain, due to interaction of the agent with plaque. Such a drawback may be, in principle, minimised by using the antibacterial agent in a dentifrice, so that the abrasive included therein may remove the plaque. In practice however there are found to be severe problems in providing a satisfactory formulation because of the intrinsic incompatability of the cationic antibacterial agents with many of the other conventional elements of a dentifrice formulation, which incompatibility drastically reduces the biological activity of the cationic agent. In addition, the cationic antibacterial agents are recognised to have a bitter taste which needs to be masked, to provide a product which is acceptable to the consumer.

Our earlier European patent applications No. 89310405.9 (publication no. 0 364 245) and 90310633.4 disclose dentifrices comprising a cationic antibacterial agent in combination with a nonionic, amphoteric or cationic surfactant and a nonionic thickening agent, in which the

HEET various agents have been selected for compatibility with the cationic antibacterial agent.

It has now been discovered that the problem of incompatability may also be overcome or at least mitigated by the use of other formulations of dentifrice.

Accordingly, the present invention provides a dentifrice comprising:

(a) a bacteriostatically effective amount of a cationic antibacterial agent;

(b) a nonionic or a cationic thickening agent or a mixture thereof;

(c) a nonionic, an amphoteric or a cationic surfactant or a mixture thereof; and

(d) an abrasive comprising coated particles, a sparingly soluble salt, in combination with an agent to suppress anion formation, or an essentially insoluble compound; or a mixture thereof;

and excluding a dentifrice comprising a cationic antibacterial agent, a nonionic thickening agent, a nonionic, cationic or amphoteric surfactant, and an abrasive comprising a sparingly soluble salt, in combination with an agent to suppress anion formation; or an essentially insoluble compound.

Suitable cationic antibacterial agents for use in dentifrices of the invention include:

(i) quaternary ammonium compounds, for instance those in which one or two of the substituents on the quaternary

SHEET nitrogen has between 8 and 20, preferably 10 and 18 carbon atoms and is preferably an alkyl group, which may optionally be interrupted by an amide, ester, oxygen, sulphur, or heterocyclic ring, whilst the remaining substituents have a lower number of carbon atoms, for instance between 1 and 7, and are preferably alkyl, for instance methyl or ethyl, or benzyl, examples of such compounds including benzalkonium chloride, dodecyl trimethyl ammonium chloride, benzyl dimethyl stearyl ammonium chloride, and cetyl trimethyl ammonium bromide, benzethonium chloride (diisobutyl phenoxyethoxyethyl dimethyl benzyl ammonium chloride) , and methyl benzethonium chloride;

(ii) pyridinium and isoquinolinium compounds, including hexadecylpyridinium chloride, cetyl pyridinium chloride, and alkyl isoquinolinium bromide;

(iii) pyrimidine derivatives such as hexetidine (5-amino-l,3-bis(2-ethylhexyl)-5-methylhexahydropyrimidine) ;

(iv) amidine derivatives such as hexamidine isethionate (4, 4'-diamidino-α, ω-diphenoxyhexane isethionate);

(v) bispyridine derivatives such as octenidine (N,N' [1,10-decanediyldi-l (4H)-pyridinyl-4-ylidene]- bis (1-octanamine dihydrochloride) ; and

(vi) biguanides including:

(a) mono-biguanides such as p-chlorobenzyl biguanide, and N'- (4-chlorobenzyl)-N' '-(2, -dichloro-benzyl) biguanide;

(b) bis-biguanides of the general formula (I) :

HEET

R NH NH NH HN R^J

(I)

wherein:

A and A¹ each represent a phenyl group optionally substituted by (C^-_ή)alkyl, (C^-^alkoxy, nitro, or halogen, a (C₁~₁2)^alkYl group, or a (C^-^)alicyclic group;

X and X^x each represent

alkylene;

R and R¹ each represent hydrogen, (C^--^) lkyl, or aryKC-L-g)alkyl; Z and Z¹ are each 0 or 1; n is an integar from 2 to 12; and the polymethylene chain (CH2)_n may optionally be interrupted by oxygen or sulphur or an aromatic (for instance phenyl or naphthyl) nucleus;

such as chlorhexidine and alexidine; and

orally acceptable acid addition salts thereof;

(c) poly(biguanides) such as polyhexamethylene biguanide hydrochloride.

Advantageously, the cationic antibacterial agent is present in the range 0.005 to 10%, preferably 0.005 to 5%, more preferably 0.005 to 2.5% by weight of the dentifrice.

Suitable nonionic thickening agents include

(C-^-g)alkylcellulose ethers, for instance methylcellulose,

E SHEET and (C₂-g)alkylene oxide modified (C-_j^-g)alkylcellulose ethers, for instance hydroxypropyl methylcellulose, and mixtures thereof.

Suitable cationic thickening agents include quartenary cellulose derivatives such as the products supplied by Union Carbide under the trade mark LR 30M and JR 30M, cationic guar gum derivatives such as the products supplied by Celanse under the trade mark Jaguar C17 (guar hydroxy propyltrimonium chloride) , or a copolymer of a diallyl ammonium chloride and acrylic acid such as the product supplied by Merck and Co. under the trade mark 'Merquat 280' (CFTA approved name polyquaternium 22) .

Advantageously the thickening agent is present in the range 0.01 to 30%, preferably 0.1 to 15%, more preferably 1 to 5%, by weight of the dentifrice.

Suitable nonionic surfactant include polyethoxylated sorbitol monoesters (for instance, the products marketed under the trade name 'Tween' by ICI) ; polycondensates of ethylene oxide and propylene oxide (poloxamers) (for instance the products marketed under the trade name 'Pluronic' by BASF-Wyandotte) ; condensates of propylene^" glycol and polyethoxylated hydrogenated castor oil (for instance, cremophors) .

Suitable amphoteric surfactants include long chain imidazoline derivatives such as the product marketed under the trade name 'Miranol C2M' by Miranol; long chain alkyl betaines, such as the product marketed under the trade name 'Empigen BB' by Albright + Wilson; and long chain alkyl amidoalkyl betaines, such as cocamidopropylbetaine, and mixtures thereof.

EET Suitable cationic surfactants include the D,L-2-pyrrolidone-5-carboxylic acid salt of ethyl-N-cocoyl-L-arginate, marketed under the trade name CAE by Ajinomoto Co. Inc.

Advantageously, the surfactant is present in the range 0.005 to 20%, preferably 0.1 to 10%, more preferably 0.1 to 5% by weight of the dentifrice.

Suitable sparingly soluble salts that may be used as an abrasive include calcium carbonate, calcium phosphates, magnesium carbonate, insoluble sodium metaphosphate, and suitable mixtures thereof. The agent to suppress anion formation typically comprises a water soluble salt containing a cation which may be same as the cation of the abrasive and which forms an essentially insoluble or sparingly soluble salt with the anion of the abrasive.

Preferably the sparingly soluble salt used as an abrasive is calcium carbonate, advantageously used in combination with dicalcium phosphate, which also usefully buffers the pH of the formulation. Suitable types of calcium carbonate include both natural and synthetic chalks.

The agent to suppress anion formation may be an alkaline earth metal salt, for instance calcium chloride. The agent is preferably present in from 0.0001 to 1%, more preferably 0.005 to 0.1% by weight of the dentifrice.

The term 'essentially insoluble compound' as used herein refers to a compound which is intrinsically insoluble in aqueous solution and includes those compounds which are listed as being 'insoluble' in cold water in the 'Handbook of Chemistry and Physics' , 48th Edition, Chemical Rubber

E SHEET Company, Section B, Physical Constants of Inorganic Compounds. Furthermore, such compounds when used as an abrasive shall contain little if any contaminating anionic impurities. Preferably the insoluble abrasive compound contains less than 1%, more preferably less than 0.5%, of anionic impurities, based on the weight of the abrasive.

Suitable essentially insoluble compounds for use as abrasives include silica, alumina, zinc orthophosphate, plastics particles, zirconium silicate or mixtures thereof; of which silica is preferred.

The preferred silica abrasive may be a natural amorphous silica, for instance diatomaceous earth; or a synthetic amorphous silica, for instance a precipitated silica, or a silica gel, such as a silica xerogel; or mixtures thereof.

The preferred grades of synthetic amorphous silicas are those for which the manufacturing process is carefully controlled so that the level of anion impurities, particularly sulphate and silicate from sodium sulphate and sodium silicate, respectively, is kept to a minimum. Alternatively, or in addition, the level of anion impurities may be reduced to the required level by careful washing ^"of the silica with, for instance, deionised or distilled water.

Suitable silicas include those described in EP-A-0 368 130 (Procter & Gamble Co.) and EP-A-0 315 503 (Rhone-Poulenc) . The latter discloses silicas which are characterised as having less than 5 X 10 , preferably less than 1 X 10 , more preferably less than 0.2 x 10-^ moles of anions per lOOg of silica, and in particular less than 0.5%, preferably less than 0.1%, more preferably less than 0.02% by weight of silica of sulphate anions; a Hammett acidity function Ho of at least 3.3, a surface in which the number of hydroxyl

HEET groups, expressed as OH/nπr- is less than 15, and more particularly less than 12, a point zero charge of at least 3 and preferably between 4 and 6.

Suitable silica xerogels are described in US 3 538 230.

Preferred precipitated silicas are those marketed under the trade mark 'Sident' by Degussa. Preferred silica xerogels are those marketed under the trade mark 'Syloblanc' by W.R. Grace Corporation, Davison Chemical Division.

Suitable grades of precipitated silica have BET surface areas in the range 20 to 300, preferably 20-100 m²/g and median agglomerate sizes in the range 2 to 50, preferably 5 to 30μ.

Suitable forms of diatomaceous earth include those marketed under the trade mark 'Celite' by Johns-Manville Products Corporation, for instance 'Celite Superfine Superfloss' .

The silica abrasive may comprise diatomaceous earth which may advantageously be used in combination with a synthetic amorphous silica, in particular a precipitated silica. (as hereinbefore defined) , which also usefully buffers the pH of the formulation and counters the otherwise off-white colour and roughness conferred upon a formulation by the use of diatomaceous earth alone. Suitably, the ratio of diatomaceous earth to synthetic amorphous silica is from 5:1 to 1:5, preferably about 1:1.

The term 'coated particles' as used herein refers to abrasive particles which have been coated with a material to enhance the compatibility of the abrasive particles with respect to the dentifrice formulation, in particular with respect to the cationic antibacterial agent. This latter

TE SHEET enhanced compatability may be confirmed by, for instance, comparing the biological activity of the formulation, by conventional microbiological assay using, for instance, m. luteus as the assay organism in a standard agar diffusion method, in the presence of the coated and uncoated particles.

Examples of suitable coated particles include silica coated with a substantially water impervious cross-linked thermosetting high polymerised resin such as described in US 3 151 027, or a hard mineral substance such as silica, alumina, calcium carbonate, calcium pyrophosphate or calcium phosphate coated with a cationic water-soluble polymer having a cationic charge density of at least 0.003 and a molecular weight of 500 to 1,000,000, such as described in GB 1 506 045 (to Procter & Gamble Co.). Examples of such polymers include, for example, quaternary ammonium polymers, for instance polyacryloxyalkyl ammonium or polymethacryloxyalkyl ammonium salts, such as the quaternary ammonium salt of polymerised dimethylaminoethyl methacrylate; polyacrylamidoalkyl ammonium salts, such as the quaternary ammonium salt of polymerised dimethylaminoethyl methacrylamide; polyalkenyloxycarbonylalkyl ammonium salts such as the ^~ quaternary ammonium salt of a polymerised derivative of a tertiary amine such as trimethylamide with vinyl chloracetate; a polyvinyloxyalkyl ammonium salt such as a quaternary ammonium salt of a polymerised vinyloxyethyldimethylamine; a polyvinylbenzyl ammonium salt such as the quaternary ammonium salt of a polymerised derivative of a tertiary amine such as trimethylamine with chloromethyl styrene; a polydiallyl ammonium salt such as a quaternary ammonium salt of a polymerised derivative of dimethylamino diallyl; a polyvinyl pyridinium salt such as a polymerised derivative of a vinyl pyridine, a

HEET polyvinylimidazolinium salt such as the polymerised reaction product of 1-(β-dimethylaminoethyl)-3-vinyl imidazolidinone-2 and tetrahydropyrimidinone-2; and a polyalkylated quaternary derivative such as the polymerised reaction product of decamethylene dibromide and

N,N,N' , '-tetramethylhexamethyldiamine. A preferred cationic polymer is polyoxyethylene

(dimethylamino)ethylene(dimethylamino)dichloride for instance that supplied under the trade mark 'Busan 77' by Buckman Corporation of Memphis, Tennessee which may be advantageously used to coat silica, calcium pyrophosphate or calcium carbonate.

Other examples of suitable coated particles include mineral particles which have been treated with a solution of a surface-treating agent which may be an alkali metal silicate, hydrogen peroxide, an acid or an organophosphorus compound, as described in US 4 781 982 (to Aluminium Company of America) . Preferably the surface-treating agent is an alkali metal silicate.

The alkali metal silicate is preferably potassium silicate or sodium silicate. Aqueous solutions containing about 0.3-5 wt. % sodium silicate are preferred. The sodium silicate solution has an initial pH of at least 8.5. The solution pH is generally greater than 9 and preferably greater than 10. After the sodium silicate solution is neutralized, a very thin silica layer forms on the particles. The dried surface-treated particles contain less than about 0.2 wt. % (2,000 ppm) silica surface coating, the remainder being alumina.

Suitable acids include for example hydrochloric acid, acetic, phosphoric acids, phosphonic acids, and phosphinic acids. Hydrochloric acid is preferred.

TE SHEET The organophosphorus compound may be an organophosphonate having the formula R²PO(OH)2 wherein R² is a

) hydrocarbon group. The organophosphorus compound may also be an organophosphinate having the formula R^R~ O(OH) wherein R² is as defined above, and R³ is hydrogen or a (C-^- C30) hydrocarbon group. R is preferably a alkyl group. The (C^-C_βø) alkyl esters of such organophosphonates and organophosphinates are also suitable. Some other suitable organophosphorus compounds are mono- and diesters of phosphoric acid. The phosphate monoesters have the formula R²OPO(OH)₂ and the diesters have the formula (R²0)₂PO(OH) , where R² is defined above.

Suitable minerals include alumina, calcium carbonate, and calcium phosphate. Preferably the mineral is alumina.

The alumina may be in various forms including alpha alumina and alumina hydrate. A preferred example of the latter is the alumina hydrate sold by the Aluminium Company of America under the trade mark C-333.

The particles are surface treated by mixing the mineral particles with a solution of the surface treating agent, adjusting the pH of the solution, separating the particles from the solution, and then drying the surface-treated particles at an elevated temperature. The surface-treating agent is preferably applied in an aqueous solution.

The abrasive is advantageously present in the range 1-80%, preferably 5-70%, more preferably 5-60% by weight of the dentifrice.

In another aspect of this invention it has been found that in certain embodiments, a dentifrice according to the invention may further comprise an ionic fluorine-containing compound, which may include ionic fluorides such as alkali metal fluorides and ionic monofluorophosphates, such as

HEET alkali metal monofluorophosphates, and which may be incorporated into the formulation, to provide between 100 and 3000ppm, preferably 500 to 2000ppm of fluoride. Preferably the ionic fluoride or monofluorophosphate is an alkali metal fluoride or monofluorophosphate, for instance, sodium fluoride or sodium monofluorophosphate, respectively.

It will be appreciated that the ionic fluorine-containing compound should be compatible with the cationic antibacterial agent; that is, the agent will not substantially reduce the availability of the cationic antibacterial agent. This may be confirmed by, for instance, determining the biological activity of the formulation, by conventional microbiological assay using, for instance, m. luteus as the assay organism in a standard agar diffusion method, in the presence and absence of the ionic fluorine-containing compound.

Thus, for instance, sodium fluoride is found to be compatible with chlorhexidine, alexidine, benzenthonium chloride and benzalkonium chloride and sodium monofluorophosphate is found to be compatable with hexamidine.

It will further be appreciated that if an ionic fluorine-containing compound is incorporated in a dentifrice of the invention, the abrasive should be chosen so that it is compatible with the ionic fluoride-containing compound. Thus, for instance, sodium fluoride is well known in the art to be incompatible with abrasives with comprise excess calcium ions as these cause loss of fluoride as insoluble calcium fluoride so that a non-calcium containing abrasive is preferred.

Dentifrices according to the invention may also contain a humectant, such as glycerine, sorbitol, propylene glycol or polyethylene glycol, or mixtures thereof; which humectant

SHEET may be present in the range 5 to 30%, preferably 10 to 30% by weight of the dentifrice.

Dentifrices according to the invention may also contain other agents conventionally used in dentifrice formulations, for instance flavouring agents; colouring agents; whitening agents; preservatives and sweetening agents. It will be appreciated that such agents (at the level employed) should be compatible with the cationic antibacterial agent; that is, the agent will not substantially reduce the availability of the cationic antibacterial agent. This may be confirmed as hereinbefore discussed. In general, such agents will be a minor amount or proportion of the formulation, usually present in from 0.001 to 5% by weight of the composition.

Flavour is an important aspect of the consumer acceptability of a dentifrice. This is particularly so in the case of a dentifrice comprising a cationic antibacterial agent, because of the bitter after-taste of the cationic antibacterial agent. Surprisingly it has now been found that this can be effectively masked by an aniseed flavour.

Accordingly, in a further aspect, the present invention provides a dentifrice as hereinbefore defined which further comprises a flavouring agent having an aniseed flavour.

Flavouring agents having an aniseed flavour include anethole, which may be present in such quantity as to mask the bitter after-taste of the cationic antibacterial agent.

Preferably the flavour may be modified by the additional incorporation of one or more flavouring agents having a mint flavour, to balance the aniseed flavour, to give a flavour

HEET which has more general consumer acceptability but in which the aniseed flavour is still dominant.

Suitable flavouring agents having a mint flavour include peppermint, spearmint, menthol and carvone.

Preferably more than one mint flavouring agent is used, of which menthol may be the major component, accounting for between 20 and 60%, preferably between 25 and 55% by weight of the flavouring agents having a mint flavour.

Advantageously the flavour of the dentifrice may be further modified by the incorporation of flavouring agents having spicey flavours such as coriander, eugenol and eucalyptol, the aniseed note still being dominant.

Accordingly, in a still further aspect, the invention provides a dentifrice as hereinbefore defined comprising aniseed and mint flavours and, optionally, spicey flavours and having a predominantly aniseed flavour.

Preferably, in such a dentifrice comprising aniseed and mint flavours, flavouring agents having an aniseed flavour- comprise from 10 to 30%, more preferably 15 to 25% of the combined weights of the flavouring agents, whilst flavouring agents having a mint flavour comprise from 40 to 80, preferably 40 to 70% of the combined weight of the flavouring agents. Preferably the combined flavouring agents comprise up to 5%, more preferably up to 2% by weight of the dentifrice.

Suitable sweetening agents include saccharin and acesulfame, and acceptable water soluble salts thereof, such as an alkali metal salt, and may be present in from 0.01 to 0.5%,

E SHEET preferably 0.05 to 0.5% by weight of the dentifrice. An auxiliary sweetener such as a thaumatin may also be included, at a level of from 0.001 to 0.1, preferably 0.005 to 0.05% by weight of the dentifrice. A suitable blend of thaumatins is marketed under the trade mark 'Talin' by Tate and Lyle pic.

Water, preferably deionised or distilled water, will also be present, in the range from 10 to 80%, preferably 20 to 70% by weight of the dentifrice.

The dentifrices according to the invention may have a pH less than 10, preferably within the range pH 4 to 10, more preferably pH 5 to 8.

The dentifrices according to the invention may be prepared in a conventional manner by mixing the ingredients thereof in the required proportions and in any order which is convenient and, thereafter and if necessary, adjusting the pH. For instance, the thickening agent and the humectant and part of the water are vigourously agitated together, with heat, if necessary, to give a hydrated gel. Abrasive is then dispersed in this hydrated gel, using a heavy-duty mixing machine, with active agents, such as the cationic antibacterial agent, a fluoride salt (if present) , then added, followed by surfactant and flavouring agents in the final stage; with final mixing carried out under vacuum.

The invention also provides a method for the prophylaxis or treatment of periodontal disease, calculus and/or caries, which method comprises the application of a composition according to the invention to the oral cavity.

The following examples illustrate the invention.

HEET Example 1

%

Chlorhexidine digluconate 1.00

Glycerine 22.00 Quaternised cellulose derivative* 3.00

Diatomaceous earth 8.00

Silica 8.00

Flavour 1.00

Sodium Saccharin 0.10 Thaumatin 0.02

Sodium Fluoride 0.22

Poloxamer 338 2.00

Deionized Water to 100.00

* Polymer LR 30M

Example 2

%

Chlorhexidine digluconate 1.00 Glycerine 15.00

Hydroxypropyl methylcellulose 3.60

Abrasive* 46.00

Flavour 1.00

Sodium Saccharin 0.10 Thaumatin 0.02

Poloxamer 338 2.00

Sodium Fluoride 0.22

Deionized Water to 100.00

* Alumina trihydrate powder (200 parts) is mixed with sodium silicate solution (1%, 400 parts) , the pH of the solution then being adjusted to pH 6 by the addition of hydrochloric acid. The coated alumina is collected by filtration and dried at 150°.

TE SHEET Example 3

%

Chlorhexidine digluconate 1.00 Glycerine 15.00 Hydroxypropyl methylcellulose 3.60 Abrasive* 16.00 Flavour 1.00

Sodium Saccharin 0.10 Thaumatin 0.02 Poloxamer 338 2.00 Sodium Fluoride 0.22 Deionized Water to 100.00

*Silica coated with Busan 77 (in the ratio lOg to 1.5g)

ET

Claims

A dentifrice comprising:

(a) a bacteriostatically effective amount of a cationic antibacterial agent;

(b) a nonionic or a cationic thickening agent or a mixture thereof;

and excluding a dentifrice comprising a cationic antibacterial agent; a nonionic thickening agent; a nonionic, cationic or amphoteric surfactant; and an abrasive comprising a sparingly soluble salt, in combination with an agent to suppress anion formation, or an essentially . insoluble compound.

2. A dentifrice as claimed in claim 1 in which cationic antibacterial agent is selected from a quaternary ammonium compound, a pyridinium or an isoquinolinium compound, an pyrimidine derivative, an amidine derivative, a bispyridine derivative or a biguanide.

3. A dentifrice as claimed in claim 2 in which the biguanide is a bis-biguanide of the general formula (I) :

TE SHEET A- (X) (CH₂)_n-NH-C-NH-C-N-(X¹) _j-l-A¹

R NH NH NH HN R^J

(I)

wherein:

A and A¹ each represent a phenyl group optionally 10 substituted by (C_1-4)alkyl, (C-^.^Jalkoxy, nitro, or halogen, a (C₁_₁2> lkyl group, or a (C₄_₁₂) licyclic group;

1

X and X each represent (Cη^)alkylene; R and R¹ each represent hydrogen, ^ι- 2 ^alkyl, or aryl(C^g)alkyl; 15 Z and Z¹ are each 0 or 1; n is an integar from 2 to 12; and the polymethylene chain (CH2)_n may optionally be interrupted by oxygen or sulphur or an aromatic nucleus; or an orally acceptable acid addition salt thereof:

20

4. A dentifrice as claimed in any one of claims 1 to 3 in which the cationic antibacterial agent is present in the range from 0.005 to 10% by weight of the composition..

255. A dentifrice as claimed in any one of claims 1 to 4 in which the nonionic thickening agent is a (C-^. )alkylcellulose ether or a (C2_g)alkylene oxide modified (C-^.g)alkylcellulose ether or a mixture thereof or in which the cationic thickening agent is a quartenary

30 cellulose derivative, a cationic guar gum derivative, or a copolymer of a diallyl ammonium chloride and acrylic acid.

6. A dentifrice as claimed in any one of claims 1 to 5 in which nonionic surfactant is a polyethoxylated sorbitol

EET monoester, a polycondensate of ethylene oxide and propylene oxide, a condensate of propylene glycol, or a polyethoxylated hydrogenated castor oil, or a mixture thereof; or the amphoteric surfactant is a long chain imidazoline derivative, a long chain alkyl betaine, or a long chain alkyl amidoalkyl betaine, and or a mixture thereof; or the cationic surfactant is the D,L-2-pyrrolidone-5-carboxylic acid salt of ethyl-N-cocoyl-L-arginate.

7. A dentifrice as claimed in any of claims 1 to 6 in which the sparingly soluble salt for use as an abrasive is calcium carbonate, calcium phosphates, magnesium carbonate, insoluble sodium metaphosphate, or a mixture thereof.

8. A dentifrice as claimed in claim 7 in which the agent to suppress anion formation comprises a water soluble salt containing a cation which is the same as the cation of the abrasive and which forms an essentially insoluble or sparingly soluble salt with the anion of the abrasive.

9. A dentifrice as claimed in any one of claims 1 to 6 in which the essentially insoluble compound for use as an abrasive is selected from silica, alumina, zinc orthophosphate, plastics particles, zironium silicate or a mixture thereof and in which the level of anion impurities is less than 1%.

10. A dentifrice as claimed in claim 9 in which the abrasive is a silica in which the level of sulphate and silicate from sodium sulphate and sodium silicate respectively is less than 1% by weight of the silica.

11. A dentifrice as claimed in any one of claims 1 to 6 in which the abrasive comprises particles which have been

E SHEET coated with a substantially water impervious cross-linked thermosetting high polymerised resin.

12. A dentifrice as claimed in any one of claims 1 to 6 in 5 which the abrasive comprises coated particles which are mineral particles which have been treated with a solution of a surface-treating agent selected from an alkali metal silicate, hydrogen peroxide, an acid or an organophosphorus compound. 10

13. A dentifrice as claimed in any one of claims 1 to 12 in which the abrasive is present in the range 1-80%, by weight of the dentifrice.

1514. A dentifrice as claimed in any one of the preceeding claims further comprising an ionic fluorine-containing compound.

15. A dentifrice as claimed in any one of the preceeding 20 claims further comprising a flavouring agent having an aniseed flavour, optionally modified by the additional incorporation of one or more flavouring agents having a mint flavour.

2516. A method for the prophylaxis or treatment of periodontal disease, calculus and/or caries, which method comprises the application of a composition according to any one of the preceeding claims to the oral cavity.

30 17. A composition as claimed in any one of claims 1 to 15 for use in therapy.

18. A dentifrice substantially as hereinbefore described t with reference to the accompanying examples.

SHEET