GB1567454A

GB1567454A - Method and composition for oral hygiene

Info

Publication number: GB1567454A
Application number: GB42512/76A
Authority: GB
Original assignee: Noxell Corp
Current assignee: Noxell Corp
Priority date: 1975-10-17
Filing date: 1976-10-13
Publication date: 1980-05-14
Also published as: DE2646199A1; JPS5251030A; CA1088429A

Description

(54) METHOD AND COMPOSITION FOR IMPROVING ORAL HYGIENE (71) We, NOXELL CORPORATION, a Corporation organised and existing under the laws of the State of Maryland, of 11050 York Road, Baltimore, Maryland, 21203, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to a dental preparation for retarding pellicle and plaque formation.

Dental pellicle is a soft deposit which includes salivary protein and is tenaciously held on the surfaces of the teeth. Dental plaque is a product of microbial growth, is tenaciously attached to the surfaces of the teeth and adjacent gingiva, and exhibits a definite microscopic structure. If not removed, the plaque will become mineralized to form calculus (also known as tartar) and eventually lead to dental caries. Dental experts generally believe that calculus is dental plaque which has become mineralized with calcium phosphate, magnesium phosphate, calcium carbonate and other trace minerals found in the mouth. If calculus is not removed from around the teeth and under the gum, inflammation can result which can ultimately lead to periodontal disease and subsequent tooth loss.

Although plaque can be removed from the teeth by thorough abrasive action, it quickly reforms on the tooth surface. Accordingly, the incidence of dental calculus and subsequent periodontal disease can be reduced by reducing or preventing the deposition of plaque and by means which prevent mineralization of the plaque.

In one aspect the present invention provides a dental preparation in the form of a toothpaste, dental cream dental powder, lozenge, tablet, aerosol spray, chewing gum, toothpick or roll of dental floss containing an amount sufficient to retard pellicle and plaque formation on teeth, a compound of the formula:

wherein: R represents a monovalent or divalent hydrocarbyl group containing at least 14 carbon atoms; n is one when R is monovalent and is 2 when R is divalent: R1 represents a hydrogen atom or a C1 to C3 alkyl group; A represents a divalent C, to C6 hydrocarbon bridge; and the groups R2, which may be the same or different, each represent a C, to C5 alkyl group or the groups R2 together with the nitrogen atom to which they are attached represent a 5- or 6membered heterocyclic ring; or a compound of the formula:

wherein: R, n, R1, A and R2 have the same meanings as in formula (la), B represents a divalent C, or C2 alkylene or alkylidene group, and X represents a carboxylate or sulphonate group, subject to the proviso that when B represents a methylene group X represents a sulphonate group; and a nontoxic physiologically and orally acceptable salt of a compound of formula (la) or (it).

The invention further provides dental preparations, formulated as mouthwashes in which a compound of formula (Ia) or (Ib) as defined above is in association with a sudsing agent, ethyl alcohol, a humectant, a sweetener, a flavouring agent and water.

Other preferred aspects of the invention are defined in the appended claims to which attention is hereby directed.

The group R in the compound of formula (la) or (lb) usually contains no more than 21 carbon atoms, and groups containing from 15 to 21 carbon atoms and especially from 15 to 17 carbon atoms, are preferred. It can, for example, be an alkaryl group; an aralkyl group; an alkacycloalkyl group; a cycloalkalkyl group or an aliphatic hydrocarbon group which is preferred. When the group R represents an aliphatic hydrocarbon group, it may be saturated or ethylenically unsaturated and it may have a straight chain or a branched chain. Examples of some suitable aliphatic hydrocarbon groups include pentadecyl, heptadecyl, tetradecyl, and heptadecenyl. When the group R represents an alkaryl or an aralkyl group, the aryl portion thereof may be a phenyl or naphthyl radical. When the group R represents an alkacycloalkyl or a cycloalkalkyl group, the cycloalkyl portion may be a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical. The group R is preferably monovalent, in which case n is 1.

The group R' can represent a hydrogen atom or a C, to C3 alkyl group such as methyl, ethyl and propyl. However, it preferably represents a hydrogen atom or a methyl group and most preferably it represents a hydrogen atom.

The group A can have a straight or branched chain or can be cyclic and can, tor example, be an alkylene, alkylidene, cycloalkylene, or arylene group. Examples of suitable alkylene groups include methylene, ethylene, propylene, butylene, pentylene and hexylene. Examples of suitable alkylidene groups include ethylidene and isopropylidene. Examples of cycloalkylene groups include cyclopropylene, cyclobutylene, cyclopentylene, and cyclohexylene. A phenylene group is an example of a suitable arylene group. Preferably, A is an alkylene or alkylidene group and more preferably contains 1 to 3 carbon atoms.

The bridge B can, for example, be a methylene or ethylene group, or it can be an ethylidene group.

X preferably represents a carboxylate [COO] group but it can also be a sulphonate

group. We have observed that compounds in which X represents a carboxylate group provide greater inhibition against pellicle and plaque formation than compounds in which X represents a sulphonate group. Moreover, compounds in which X represents a carboxylate group have the additional advantage that they can be used with water as the carrier whereas the corresponding compounds in which X represents a sulphonate group are not readily dispersible in water and require an organic carrier such as propylene glycol.

The groups R2 preferably represent C, to C3 alkyl groups and most preferably they represent methyl groups. However, they can also represent, together with the nitrogen atom to which they are attached, a 5- or 6-membered heterocyclic ring, for example a morpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl ring.

The preferred compounds employed in the present invention have the following structural formula: wherein:

R3 represents a monovalent aliphatic hydrocarbon group containing at least 14 carbon atoms; B has the same meaning as in formula (la) and m is an integer from 1 to 3 and/or a nontoxic, physiologically and orally acceptable salt thereof.

Examples of some specific compounds suitable for the present invention include compounds of the following structural formula:

wherein: R4, B' and X'O have the meanings given in the following table:

R4 B' X'3 Name pentadecyl CH2 C-O palmitic amido betaine 0 heptadecyl CH2 C-O stearic amido betaine II 0 heptadecenyl CH2 C-O oleic amido betaine 0 pentadecyl -CH- C-O DL-N-carboxymethyl II methyl-N,N-dimethyl CH3 O N-(3-palmitamido-propyl) ammonium betaine pentadecyl (CH2)2 C-O N-carboxyethyl-N,N-di II methyl-N-(3-palmitamido O propyl)-ammonium betaine heptadecenyl -CH- C-O DL-N-carboxymethylmethyl II N,N-dimethyl-N-(3-oleyl CH3 0 amidopropyl)-ammonium betaine heptadecenyl (CH2)2 C-O N-carboxyethyl-N,N II dimethyl-N-(3-oleyl O amidopropyl)-ammonium betaine heptadecyl -CH- C-O DL-N-carboxymethylmethyl II N,N-dimethyl-N-(3-stear CH3 0 amidopropyl)-ammonium betaine heptadecyl ACH2)2 C-O N-carboxyethyl-N,N-di 11 methyl-N-(3-stearamido O propyl)-ammonium betaine pentadecyl (CH2)2 O 2[N,N-dimethyl-N-(3 11 palmitamidopropyl)-amino] WO ethanesulphobetaine II 0

R4 B' X' Name heptadecenyl (CH2)2 O 2-[N,N-dimethyl-N-(3 ii oleylamidopropyl)-amino] S-O ethanesulphobetaine 0 heptadecyl (CH2)2 O 2-[N,N,-dimethyl-N-(3 il stearamidopropyl)-amino] S-O ethanesulphobetaine II 0 The salts of the above compounds which are suitable for use in the human oral cavity include non-toxic acid and base addition salts. Suitable salts include citrate, acetate, maleate, lactate and phosphate salts.

We have observed that compounds identical to those of the general formula (1) except that R contains less than 14 carbon atoms, do not show the activity against plaque and pellicle deposition which is exhibited by the compounds of formula (1). In particular, we have observed that coconut amido betaine available under the trade designation Tegobetaine C from T.H. Goldschmidt. and lauric myristic amido betaine available under the trade designation Schercotaine LMAB from Scher Brothers, Inc., Clifton, New Jersey do not exhibit plaque inhibition activity. Tegobetaine C is a mixture of compounds a small minority of which are within formula (3) but the major proportion of which differ from the compounds of formula (3) in that the group R4 contains too few carbon atoms because the

0 R4C-radical is derived from coconut fatty acid which is predominantly a C,2 fatty acid.

Although minor amounts of fatty acids having 15 carbon atoms or more may be present, the proportion of compounds of formula (3) (i.e. of compounds in which the groups R4 contain more than 14 carbon atoms) present in Tegobetaine C is insufficient to impart thereto activity against the formation of plaque and pellicle.

We have also found, as appears below, that Denta Fresh (a denture cleanser commercially available from Noxel, the applicants herein, which contains about 150 by weight of Tegobetaine C) does not inhibit the formation of plaque. We believed that Denta Fresh not only contains too small an amount of the compounds of formula (1) to impart thereto retardant activity against plaque and pellicle formation but is also formulated with materials such as sodium lauryl sulphate which interact with the betaines in the composition to give inactive products.

Evidence in support of this proposition is provided by Examples 17A to 17C which show that replacement of Tegobetaine C in Denta Fresh by compounds according to the present invention did not impart thereto any retardant activity against plaque formation.

Several of the compounds of formula (1) are commercially available. For instance a preparation containing isostearic amido betaine is available under the trade designation Schercotaine IAB, and a preparation containing palmitic amido betaine is available under the trade designation Schercotaine PAB from Scher Brothers, Inc. Various amido compounds including those suitable for use in the present invention as well as those outside the scope of the present invention are discussed in "Tegobetaine Chemistry" published by Goldschmidt Chemical Corporation, 153 Waverly Place, New York City, New York, U.S.A. and in U.S.

Patent 3,280,179 (Ernst).

The compounds of formula (la) and of formula (lb) can be prepared, for instance, by the two-stage process described below: (a) A diamine of the formula:

(wherein R', R2 and A have the same meaning as in formula (1)) is reacted with a mono- or dicarboxylic acid of the formula:

(wherein R and n have the same meanings as in formula (I)) to provide an amido amine of the formula:

(wherein R, R1, R2, A and n have the same meanings as in formula (la)). The progress of this reaction can readily be monitored by measuring the amount of water formed. When a monocarboxylic acid is employed, the acid and amine are used in about equimolar quantities. When a dicarboxylic acid is employed, the molar ratio of acid to amine is about 1:2.

Examples of suitable diamines of formula (4) for use in the above reaction include 3 - dimethylaminopropylamine; para- aminodiethylaniline; paraaminodimethylaniline; N- aminoethylpiperazine; N- aminopropylmorpholine; 3 - di - ethylaminopropylamine; 3 - ethylmethylaminopropylamine; and dimethylaminomethylamine. Examples of suitable carboxylic acids of formula (5) include stearic acid; behenic acid; isostearic acid; palmitic acid; oleic acid; linoleic acid; erucic acid; and pentadecanoic acid.

(b) After the amidoamine of formula (6) has been isolated from the reaction mixtures, it is reacted with a quaternizing agent to introduce the grouping -B-X- wherein B and X have the same meanings as in formula (lb). Examples of suitable quaternizing agents inlude chloroacetic acid, 2 - chloropropionic acid, 3 chloropropionic acid and the sodium salt of 2 - chloroethane - sulphonic acid. The course of the reaction is shown by way of example with reference to the use of chloroacetic acid as the quaternizing agent in the following equation in which R, R1,R2 and n have the same meanings as in formula (la):

The quaternization reaction can conveniently by carried out by refluxing a mixture of the reactants.

The fatty acid amido compounds employed according to the present invention can be intermittently contacted with sites of plaque formation and growth such as the oral cavity in the form of a dental preparation as and when required to exert the required control over plaque growth. They can be used to retard pellicle and plaque formation on dentures by soaking dentures in an appropriately formulated preparation. Accordingly, sites of plaque formation and growth as used herein refer to living teeth within the oral cavity as well as to dentures or false teeth located in or out of the oral cavity.

The term "dental preparation" which is used herein is intended to designate products which are presented or packaged for application to the human oral cavity or to dental prosthesis and which are not intentionally ingested, and does not include simple aqueous solutions.

When the compounds of formula (la) or (lb) are to be used in the oral cavity, they are provided in association with a nontoxic carrier suitable for use in the oral cavity. For example, the compounds of formula (la) or (lb) when X represents a carboxylate group can be dispersed in water to make a mouthwash and used as such. The preparations to which the present invention is directed are toothpastes, dental creams, tooth powders, mouth rinses, lozenges, tablets, aerosol sprays, chewing gum, dental floss, toothpicks and denture cleansers. The amount of the compounds of formula (la) or (lb) employed according to the present invention should be at least sufficient to impart to the composition retardant activity against pellicle and plaque formation and is generally at least 1% by weight and preferably at least 5% by weight of the compound of formula (lea) or (lob) based on the weight of the dental preparation. The maximum amount of the compound of formula (I a) or (lib) which can be incorporated into the dental preparation is dependent primarily upon economic and practical considerations and usually about 25 s by weight based on the weight of the dental preparation.

Furthermore, the minimum effective amount of any particular compound of formula (la) or (lb) depends not only upon the absolute quantity of the compound present in the dental preparation but may also depend upon the relative amounts of the compound of formula (la) or (lb) and the other constituents in the particular preparation, and it may yet further depend on the nature of the other constituents present in the particular dental Preparation. For instance, if the preparation contains an ingredient which interacts with the compounds of formula (Ia) to (1 b) to render it inactive, it is apparent that the amount of amido compound must be in excess of that which interacts with the said ingredient. Furthermore, the degree to which the site is rinsed after treatment may have some effect upon the minimum amount of the compound of formula (la) or (lb) necessary. For instance, little or no rinsing of the treatment site may result in some build-up of the compound on the teeth which would reduce the amount needed in subsequent treatments. The minimum amount of any particular compound of formula (la) or (lb) required for any particular preparation is readily ascertainable by routine trial and experiment.

The proposition that the minimum effective amount of any particular compound is not dependent solely upon the absolute quantity present is supported by the observations that compositions containing about 2.5% palmitic amido betaine or less, about 10% ethyl alcohol, up to about 5% NaC1 and the remainder being water; and compositions containing about 2.5% palmitic amido betaine, about 10% by weight of silica, about 56% by weight sorbitol, up to 5% NaCI and the remainder water, did not retard plaque formation if the treatment locus was rinsed whereas if the identical compositions were used and no post-treatment rinsing was carried out, the formation of plaque was prevented. Further support for this proposition is derived from the observation that compositions containing about 5% palmitic amido betaine and about 95% water effectively retarded plaque formation whereas compositions containing about 5% palmitic amido betaine, about 8% of silica, about 50.5% of sorbitol and about 36.5% by weight of water were marginally effective in that sometimes the composition exhibited retardation of plaque formation while other times the composition did not, so that the nature of the composition has been experimentally shown to affect the minimum amount of the compound of formula (la) or (lb) required to retard plaque formation.

It was further observed that various compositions containing about 5, " isostearic amido betaine or 5% stearic amido betaine including a composition which contained about 5 z by weight of isostearic amido betaine, about 24 by weight of glycerin, about 1% by weight of propylene glycol, about 0.75% by weight of carboxymethyl cellulose and about 69.25% by weight of water did not exhibit plaque inhibition activity whereas a composition containing about 5% by weight of isostearic amido betaine and identical to the above composition except that it contained about 0.75% by weight of hydroxyethyl cellulose in place of the carboxymethyl cellulose retarded plaque formation and exhibited moderate plaque inhibition.

When preparing dental preparations intended for use in the oral cavity, the carriers and other additives employed should be suitable for use in the oral cavity and should be compatible both with the compound of formula (la) or (lb) and also with each other. For example, appropriately selected sudsing agents, flavouring agents, abrasive polishing compounds, humectants and sweetening agents can be employed, and the amounts and types of the additive materials used can vary greatly depending on the nature of the preparation. In addition, the pH of dental preparations intended for use within the oral cavity should normally lie between 3 and 9, and preferably between 5 and 7.5. However, the permissible pH range for denture preparations not intended for use within the oral cavity need not be restricted to the pH ranges set out above, and a wider variety of additive may also be used.

Examples of some suitable water-insoluble abrasive polishing agents include dicalcium phosphate, hydrated aluminium oxide, calcium carbonate, calcium polymetaphosphate, dicalcium orthophosphate dihydrate, sodium polymetaphosphate, and various resinous abrasive materials such as particulate polyethylene, melamines, phenolic resins, ureas, melamine-ureas, melamineformaldehydes, urea-formaldehydes, melamine-urea-formaldehydes and crosslinked polyesters. Mixtures of abrasive polishing agents can be employed when desired.

A preferred abrasive agent is hydrated aluminium oxide since it has been observed that preparations of the present invention containing hydrated aluminium oxide exhibit greater plaque inhibition than similar preparations containing certain phosphate abrasives. Although not preferred, the phosphate abrasives can be employed when desired since the compounds of formula (la) or (lob) demonstrate plaque inhibition in their presence, the degree of which is dependent somewhat upon their respective concentrations. The total amount of abrasive agent, when present, can range from 0.5% to 95% by weight of the dental preparation. The referred amount of abrasive agent in toothpastes is from 5 to 60% by weight and the preferred range of abrasive particle size is from 2 microns to 20 microns.

Suitable sudsing or foaming agents for use according to the present invention are those which are reasonably stable, form suds throughout a wide pH range, and are acceptable for use in the oral cavity. Examples of suitable sudsing or foaming agents include water-soluble salts of sulphonated monoglycerides of C,O to C16 fatty acids such as sodium coconut monoglyceride sulphonate; water-soluble salts of fatty acid amines of taurine such as sodium N-methyl-N-palmitoyl tauride; watersoluble salts of fatty acid esters of isethionic acid such as the coconut acid ester of sodium isethionate; substantially saturated C12 to C, aliphatic acyl amides of saturated C2 to C6 aliphatic monoamino carboxylic acids such as sodium N-lauroyl sarcosinate; and polyoxyalkylene polyols such as the Pluronics (Registered Trade Mark) available from Wyandotte Corporation. If desired, mixtures of sudsing agents can be employed. Generally the sudsing agent, when present, is employed in amount ranging from 0.5 /n to 5.0% by weight based on the total weight of the dental preparation.

Flavouring agents can be incorporated into the dental preparations of the invention and examples of suitable flavouring agents include oil of wintergreen, oil of peppermint, oil of anise, citrus flavours and vanillin. Examples of the various sweetening agents which can be incorporated therein include saccharin, dextrose, mannitol, levulose and sodium cyclamate.

In certain compositions of the invention, such as toothpaste, it is generally desirable to employ thickening agents, and examples of suitable thickening agents include hydroxyethyl cellulose; water-soluble salts of cellulose ethers, including sodium carboxymethyl cellulose and sodium carboxymethylhydroxyethyl cellulose; and natural gums such as gum karaya, gum arabic and gum tragacanth. In addition, colloidal magnesium aluminium silicate or finely divided silica such as silica aerogels and microfine precipitated silicas can be used as part of the thickening agent to further improve texture in such compositions as toothpaste. When thickening agents are present, they are generally employed in amounts from 0.1% to 15% by weight based on the total weight of the composition.

Natural gums and finely divided silica are the preferred thickening agents since it has been observed that preparations of the invention containing such thickening agents exhibit greater plaque inhibition than preparations containing corresponding amounts of other thickening agents such as hydroxyethyl cellulose, sodium carboxymethyl cellulose and magnesium aluminium silicate. Although not preferred, these other thickening agents can also be used when desired since the compounds of formula (la) and (lb) exhibit plaque inhibition in their presence to a degree which is somewhat dependent upon their respective concentrations.

In addition, in certain of the dental preparations employed in the present invention, such as toothpastes, it may be desirable to include a humectant or a viscosity modifier. Examples of suitable humectants include non-toxic polyhydric alcohols such as glycerin, sorbitol, mannitol, propylene glycol, polyethylene glycol, polypropylene glycol and mixtures thereof. The humectants are generally used in amounts up to about 40 Sn by weight of the dental preparation.

A typical toothpaste of the present invention contains an amount sufficient to retard plaque and pellicle formation of a compound of formula (la) or (lb) in association with from 5% to 60% by weight of an abrasive polishing agent, from 0.5% to 5 ,4 by weight of a sudsing agent, from 0.1do to 15% by weight of a thickening agent, and the balance being substantially water and humectants. A typical mouthwash composition can contain a compound of formula (1) in an amount sufficient to retard pellicle and plaque formation in association with a sudsing agent, ethyl alcohol, a humectant, a sweetener, a flavouring agent and water. A typical chewing gum composition can contain a compound of formula (lea) or (lb) in an amount sufficient to retard pellicle and plaque formation in association with a gum base. A typical prophylactic paste can include a compound of formula (la) or (lb) in an amount sufficient to retard pellicle and plaque formation in association with pumice.

In addition, the present invention can be practised by coating and/or impregnating dental floss or toothpicks with a composition containing a compound of formula (1). The coating and/or impregnating operation can be carried out by any conventional method for coating and impregnating fibres or toothpicks, for example, by passing dental floss or toothpicks through an aqueous bath containing a solution or dispersion of a compound of formula ( I) and then permitting the water to evaporate, e.g., by heating under vacuum.

The invention is illustrated in the following Examples, some of which are Examples of the invention, some of which are reference Examples introduced to show the properties of the compounds of formulae (Ia) and (Ib) and some of which are comparative examples.

EXAMPLE 1 (a) A set of three extracted human teeth without the roots was mounted on a plastic strip dimensioned 1 inchx3 inches, swabbed with human saliva using a sterile Dacron (Registered Trade Mark) swab and allowed to dry for about 15 minutes. The strip was then placed in a petri dish and covered with 200 ml of a 2% aqueous solution of trypticase containing 4% sucrose. Each dish was then inoculated with an additional 1 ml of human saliva and incubated at 37"C for 24 hours. After incubation, the set of teeth was removed, dried, dipped into a 0.5 aqueous solution of FD & C RED No. 3 to visually disclose the plaque, and then rinsed under tap water. The teeth showed heavy plaque growth. They were then brushed with an electric toothbrush fitted with a soft nylon brush carrying a composition containing about 25% by weight of a palmitic amide betaine, 2.5% NaCI and the remainder water, available under the trade designation Schercotaine PAB, until all of the red disclosed plaque had been removed and were then rinsed.

The teeth were then again swabbed with human saliva, placed in a petri dish, covered with the same trypticase-sucrose solution as previously, which was inoculated with an additional 1 ml of saliva and incubated for about 24 hours at about 37"C. At the end of the 24 hours, the set of teeth was removed from the solution, dried, and dipped into the 0.5% FD & C RED No. 3 solution for about a minute to visually disclose any plaque present, after which it was rinsed under tap water. No plaque growth was observed on the teeth brushed with the Schercotaine PAB, indicating that the palmitic amido betaine present had effectively inhibited the redeposition of dental plaque on the teeth.

(b) The procedure described in part (a) was repeated except that the set of teeth employed was brushed with water until all of the red disclosed plaque was removed. After the second 24-hour incubation heavy plaque growth was found on the teeth.

(c) The procedure described in part (a) was again repeated except that the set of teeth employed was brushed with a commercially available stannous fluoride toothpaste sold under the trade name "Crest" until all of the red disclosed plaque was removed. The results after the second 24-hour incubation period again showed heavy plaque growth.

A comparison between part (a) of this example and parts (b) and (c) shows that brushing the teeth with palmitic amido betaine effec composition in inhibiting the formation of dental plaque, the teeth being brushed with the composition under test instead of with the Scherocotaine PAB, and the effectiveness of the composition being assessed at the end of the second 24-hour incubation period.

Example 2 A composition containing about 20% by weight of palmitic amido betaine, about 10% by weight ethyl alcohol and about 70% by weight of water was evaluated by the standard test method. It was found to be effective in inhibiting plaque formation although not to the same extent as the preparation employed in para (a) of Example 1.

Example 3 (Reference) A composition containing about 35 by weight of isostearic amido betaine, about 25% NaCI and the remainder water, available under the trade name Schercotaine IAB was evaluated by the standard test method. It was found that the isostearic amido betaine provided good plaque and pellicle inhibition.

Example 4 A dental composition was prepared which contained about 10% by weight of the palmitic amido betaine, about 8% by weight of silica gel of average particle size of 4,u and surface area of 310 m2/gm available under the trade name Syloid 244 from Davison Chemical (Syloid is a Registered Trade Mark); about 36.4 ,/ by weight of sorbitol, up to 5% by weight of NaCI, and the remainder water. The preparation was carried out by adding the silica gel to the sorbitol and a portion of the water with mixing until a homogeneous solution was obtained, after which an aqueous dispersion of the palmitic amido betaine (Schercotaine PAB) was added and admixed until a uniform composition was obtained. The composition was evaluated by the standard test method and found to be completely effective in preventing pellicle and plaque formation on the teeth.

Example 5 A composition containing about 2.5 /n by weight palmitic amido betaine, about 10% by weight of ethyl alcohol, up to 5% by weight of NaCI and the remainder water was evaluated by a modified version of the standard test method in which the teeth were not rinsed after the brushing. Under these modified conditions, no pellicle or plaque formation on the set of teeth occurred.

Example 6 A composition containing about 5% by weight of isostearic amido betaine, about 24% by weight of glycerin, about 0.75 /O by weight of hydroxyethyl cellulose, about 1% by weight of propylene glycol, up to 5% by weight of NaCI, and the remainder water was prepared as follows. The glycerin was heated to about 70"C, and then the hydroxyethyl cellulose was added with stirring. Next a portion of the water was added with heating and stirring over a period of about 15 minutes, after which the composition was cooled and a composition comprising propylene glycol, and a mixture of the betaine, NaCI, and the rest of the water (the mixture being available under the trade name Schercotaine IAB) was added.

The composition produced as described above was evaluated by the standard test method and was found to exhibit moderate pellicle and plaque inhibition.

Example 7 (Reference) A composition containing about 25% by weight of oleic amido betaine, up to 5% by weight of NaCI and the remainder water (available under the trade name Schercotaine OAB) was found by the standard test method to have provided almost complete inhibition of pellicle and plaque growth on the teeth.

Example 8 A composition containing about 10 parts by weight of palmitic amido betaine, about 35.7 parts by weight of sorbitol, about 8 parts by weight of silica (QUSO G-30 available from Philadelphia Quartz Co.), about 1 part by weight of propylene glycol, up to 2 parts by weight of NaCI, and about 45 parts by weight of water was prepared as follows. The silica was added to a mixture of the sorbitol and a portion of the water and mixed until a uniform transparent gel was obtained. Next, the propylene glycol was mixed with a combination of the remainder of the water the betaine and NaCI (available under the trade name Schercotaine PAB). Then the mixture containing the propylene glycol was added to the transparent silica containing gel and the resulting mixture was agitated until a uniform composition was obtained.

The above composition was evaluated by the standard test method and was found to have provided complete inhibition of pellicle and plaque growth on the teeth.

Example 9 The procedure of Example 8 was repeated using a slightly modified composition in which a different grade of silica (QUSO G-32 available from Philadelphia Quartz Company) was used and the upper limit of the NaCI was 1.5 parts by weight. The modified composition was prepared as described in Example 8. Evaluation of the modified composition by the standard test method showed that the modified composition provided complete inhibition of pellicle and plaque growth.

Example 10 (Reference) Purified palmitic amido betaine was obtained as follows. About 200 parts by weight of Schercotaine PAB in an evaporating dish were placed under a pressure of about 26" of Hg below atmospheric pressure and maintained at about 65"C for about 48 hours, after which the material was maintained under a further reduced pressure of about 28" of Hg below atmospheric pressure at the same temperature for about another 8 hours. The residue was introduced into a 400 ml beaker to which 300 ml of 95 ZO ethyl alcohol were added and the mixture was stirred until the palmitic amido betaine present had dissolved. The mixture was then filtered and the precipitated sodium chloride was discarded. The filtrate was then concentrated to about 100 mis on a steam bath, cooled and treated with 200 mls of acetone. The resulting white precipitate was filtered off on a Buchner funnel, rinsed, and then left overnight in an evaporating dish at 650C under a pressure of 28" of Hg below atmospheric pressure, after which the precipitate been converted into a yellow amorphous solid which was again precipitated from the ethyl alcohol-acetone mixture. The precipitate was dried in air until all the acetone vapour evaporated, to give purified palmitic amido betaine as a white solid.

The standard test method was then used to evaluate a solution containing about 10% by weight of the purified palmitic amido betaine obtained as described above and about 90% by weight of water. The solution was found to provide complete inhibition of plaque and pellicle growth on the teeth.

Example 11 (Reference) A composition containing about 5% by weight of the purified palmitic amido betaine obtained as described in Example 10, and about 95% by weight of water was evaluated by the standard test method and was found to provide partial inhibition of plaque and pellicle growth on the teeth.

Example 12 A mixture of about 80 parts by weight of sorbitol, about 34 parts by weight of water and about 10.2 parts by weight of glycerin was heated to about 65"C and treated with about 0.3 parts by weight of sodium benzoate and then with 1.5 parts by weight of carboxymethyl cellulose added with constant stirring, which was continued until the mixture had become uniform. To this composition was added with stirring and at room temperature a mixture of about 24 parts by weight of a silica gel available under the trade name Syloid 244 from Davison Chemical, and about 30 parts by weight of hydrated alumina having an average particle size of about 12.5,u and available under the trade name Kleen-Dent TA-6 from Reheis Chemical. About 30 parts by weight of palmitic amido betaine, up to 5 parts by weight of NaCI, and about 90 parts by weight of water were added to the mixture.

The pH of the resulting composition was about 6.4. The palmitic amido betaine portion was from Schercotaine PAB.

The above-described composition was evaluated by the standard test method and was found to provide complete inhibition of pellicle and plaque growth on the teeth.

Example 13 About 66.5 parts by weight of sorbitol and about 73.5 parts by weight of water were heated to about 60"C, about 0.25 parts by weight of sodium benzoate were added with mixing, followed by about 1.25 parts by weight of carboxymethyl cellulose added gradually while stirring which was continued until a uniform gel was obtained. The composition was then cooled to room temperature and deaerated. About 25 parts by weight of a hydrated alumina available under the trade name Kleen Dent TA-6 from Reheis Chemical Company were added with agitation. The composition was then mixed with about 28 parts by weight of a silica gel available under the trade name Syloid 244 from Davison Chemical with agitation until a uniform composition was obtained, after which the composition was again de-aerated. A mixture of about 25 parts by weight of palmitic amido betaine purified as described in Example 10, about 8.5 parts by weight of glycerin, and about 25 parts by weight of water was added to the composition and the materials were mixed together until a homogeneous deaerated paste was obtained.

The above-described composition was evaluated by the standard test method which showed that it provided complete plaque and pellicle inhibition on the teeth.

Example 14 About 0.3 parts of sodium benzoate were added to about 108 parts of a mixture of about 75.5 parts by weight of sorbitol and about 22.5 parts by weight of water, and the resulting mixture was added to a solution of about 6 parts by weight of a polyoxypropyleneoxyethylene available under the trade name Pluronic F-68 from Wyandotte Corporation in about 60 parts by weight of water. About 0.5 parts of carboxymethyl cellulose were then added with vigorous agitation until a uniform composition was obtained. The composition was then deaerated. About 30 parts by weight of a hydrated alumina available under the trade name Kleen Dent TA6 from Reheis Chemical were added and admixed with agitation until a uniform composition was obtained, after which about 24 parts by weight of a silica gel available from Davison Chemical under the trade name Syloid 244 was added with mixing and agitation until a uniform composition was obtained. A composition containing about 30 parts by weight of a purified palmitic amido betaine prepared according to Example 10, about 10.2 parts by weight of glycerin, and about 21 parts by weight of distilled water were added to the above composition and mixing was continued until a homogeneous composition had been obtained.

The composition described above was then evaluated by the standard test method which indicated that the composition provided complete inhibition of plaque and pellicle growth on the teeth.

Example 15 (Reference) A composition comprising about 14% by weight isostearic amido betaine and about 86% by weight of water was evaluated by the standard test method as a result of which no plaque and pellicle were found to be present on the teeth.

Example 16 (Comparative) A modification of the standard test method in which the set of teeth was replaced by polymethyl methacrylate strips which had been sanded perpendicular to their longitudinal direction to remove the polished surface (hereinafter referred to as "the second test method") was used to evaluate a composition containing Tegobetaine C (a coconut fatty acid amido betaine). It was found that brushing with Tegobetaine C did not prevent the growth of plaque and/or pellicle on the polymethyl methacrylate strips.

Example 17 (Comparative) (a) The procedure of Example 16 was repeated except that the polymethylmethacrylate strips were brushed with Denta Fresh, a commercial denture cleanser available from Noxell, the applicants herein, which contains about 15% by weight of Tegobetaine C. It was found that brushing with Denta Fresh did not inhibit plaque and/or pellicle growth.

(b) The procedure of part (a) was repeated except that the polymethylmethacrylate strips were brushed with a composition containing the same ingredients as Denta Fresh except that the Tegobetaine C was replaced with 15% by weight of palmitic amido betaine. Evaluation by the second test method showed that brushing with the composition did not prevent plaque and/or pellicle growth.

(c) The procedure of part (a) was repeated except that the polymethylmethacrylate strips were brushed with a composition containing the same ingredients as Denta Fresh except that the Tegobetaine C was replaced with 15% by weight of isostearic amido betaine. Evaluation by the second test method indicated that the composition did not prevent plaque and/or pellicle growth.

The results of Example 17 indicate that Denta Fresh contains an ingredient, which is believed to be the sodium lauryl sulphate present, which interacts with the betaine to render it ineffective in inhibiting plaque and/or pellicle growth.

Example 18 (Comparative) Schercotaine LMAB (an aqueous preparation of lauric myristic amido betaine) was evaluated by the second test method which indicated that the lauric myristic amido betaine did not prevent plaque and/or pellicle formation.

In all the above examples new sets of teeth or new plastic strips and new brushes respectively were used each time. Any NaCI present in the compositions is due to its presence in the commercially available compositions of the fatty acid amido compounds.

Example 19 (Reference) An acute oral LDso for Schercotaine PAB in mature albino rats was carried out. The post-dose observations were characterized by diarrhoea and general weakness within the first 48 hours. The resulting mortality pattern was wide ranging and the LDso was calculated to be 6000 mg/kg of body weight with 95% confidence limits of 8040 to 4477 mg/kg for the material tested.

Palmitic amido betaine purified according to Example 10 was also tested according to the above procedure. The LDso was calculated to be 2400 mg/kg (2832-2033 mg/kg) at 95% confidence limit.

Example 20 (Reference) (a) Preparation of DL - N - carboxymethylmethyl - N,N - dimethyl - N - (3 palmitamidopropyl) ammonium betaine 131.55 parts by weight of distilled water, 3.51 parts by weight of NaOH pellets, 9.54 parts by weight of 2 - chloro - propionic acid, and 30 parts by weight of dimethylaminopropyl palmitamide (Tegamine P-13 from Inolex Division of Wilson Pharmaceutical) were mixed in a reaction vessel at about 90"C for about 8 hours to provide DL - N- carboxymethylmethyl - N,N - dimethyl - N- (3 palmitamidopropyl) ammonium betaine.

(b) Evaluation of the compound prepared in step (a) A set of three extracted human teeth without the roots was mounted on a polymethylmethacrylate plastic strip dimensioned 1 inchx3 inches. A drop of human saliva was applied to each tooth and allowed to dry. The set of teeth was then placed in a petri dish and covered with 200 ml of a 2% aqueous solution of trypticase containing 4% sucrose. The dish was then inoculated with an additional 1 ml of human saliva and incubated at 370C for 24 hours. After incubation, the set of teeth was removed, rinsed, and then dipped into a 0.5% aqueous solution of FD & C RED No. 3 to visually disclose the plaque. The teeth showed heavy plaque growth. They were then brushed with water using an electric toothbrush fitted with a soft nylon brush until all of the red disclosed plaque and/or pellicle had been removed.

The teeth were then swabbed with human saliva, placed in a petri dish, covered with about 200 ml of the trypticase-sucrose media and about 0.1 ml of 1% by weight solution of DL - N - carboxymethylmethyl - N,N - dimethyl - N - (3 palmitamidopropyl) ammonium betaine in distilled water. The contents of the dish were then inoculated with an additional 1 ml of saliva and incubated for about 24 hours at about 37"C. At the end of the 24 hours, the set of teeth was removed from the media, dried, and dipped into the 0.5% FD & C RED No. 3 solution for about a minute to visually disclose any pellicle and plaque present after which it was rinsed under tap water. No pellicle and plaque growth was observed on the teeth contacted with the composition.

The procedure employed in part (b) of this Example will hereinafter be referred to as "the third test method". It is used in the succeeding Examples to evaluate the effectiveness of certain betaines against plaque and pellicle formation, the betaines being substituted for the compound whose preparation and testing is described herein. The effectiveness of the compound under test is again assessed at the end of the second 24-hour inoculation period.

Example 21 (Reference) (a) Preparation of N - carboxyethyl - N,N - dimethyl - N - (3 - palmitamidopropyl) ammonium betaine 131.55 Parts by weight of distilled water, 3.51 parts by weight of NaOH pellets, 9.54 parts by weight of 3 - chloropropionic acid, and 30 parts by weight of Tegamine P-13 were mixed together in a reaction vessel to which hot distilled water was added periodically to maintain the mixture as a solution. Mixing was continued about 8 hours at 90"C to give a solution of the required compound.

(b) A 1% by weight solution of N - carboxyethyl - N,N - dimethyl - N - (3 palmitamidopropyl) ammonium betaine in distilled water was evaluated by the third test method. The results showed that the solution caused complete inhibition of plaque and pellicle formation on the teeth and showed only very slight plaque and/or pellicle in a modified version of the third test method in which the teeth' were replaced by a plastics strip of the kind described in Example 16.

Example 22 (Reference) (a) Preparation of DL - N - carboxymdethylmethyl - N,N - dimethyl - N - (3 oleylamidopropyl) ammonium betaine 32.3 Parts by weight of dimethylaminopropyloleamide (Tegamine 0-13 from Inolex Division of Wilson Pharmaceutical) and 9.5 parts by weight of 2 chloropropionic acid were added with stirring to a reaction vessel containing 3.5 parts by weight of sodium hydroxide in 132 parts by volume of distilled water. The resulting mixture was stirred at 800C for 8 hours during which time an additional 50 parts by volume of water were added, after which the mixture was placed in a vacuum oven and heated to about 700C for several hours to evaporate off the water. The residue was dissolved in 250 parts by volume of 95% ethanol and separated from the insoluble NaCI present by filtration. The ethanol was then removed by evaporation after which the residue was dissolved in 250 parts by volume of acetone and separated from a further quantity of insoluble NaCI which was removed by filtration. The filtrate was then treated with a further 400 parts by volume of acetone and placed in a freezer. The crude product which separated out was recrystallized from ethyl acetate to give 39.9 parts by weight of pure DL - N carboxymethylmethyl - N,N - dimethyl - N - (3 - oleylamidopropyl) ammonium betaine whose identity was confirmed by means of infra-red spectroscopy.

(b) 0.1 ml of a 1% by weight solution of DL - N - carboxymethylmethyl N,N - dimethyl - N - (3 - oleylamidopropyl) ammonium betaine in distilled water was evaluated by the third test method. The results showed that the solution inhibited plaque and pellicle formation on the teeth.

Example 23 (Reference) (a) Preparation of N - carboxyethyl - N,N - dimethyl - N - (3 - oleylamidopropyl) ammonium betaine 32.3 Parts by weight of Tegamine 0-13 and about 9.5 parts by weight of 3 chloropropionic acid were added with stirring to a reaction vessel containing 3.5 parts by weight of sodium hydroxide in 132 parts by volume of distilled water. The resulting reaction mixture was stirred at 800C for 7+ hours, after which it was placed in a vacuum oven and heated to about 70"C for several hours to evaporate off the water. The residue was dissolved in 250 parts by volume of 95 /n ethanol and separated from the insoluble NaC1 present by filtration. About 100 parts by volume ethanol was then removed by evaporation, and on cooling the solution a further quantity of NaCI separated and was removed by filtration, after which the remaining ethanol in the filtrate was evaporated off. The residue was treated with about 250 parts by volume of acetone and the resulting solution was placed in a freezer to effect precipitation of the crude product which was separated off and recrystallized using ethyl acetate. About 35.4 parts by weight of N - carboxyethyl N,N - dimethyl - N - (3 - oleylamidopropyl) ammonium betaine was obtained, the identity of the product being confirmed by infra-red spectroscopy.

(b) 0.1 ml of a 1% by weight solution of N - carboxyethyl - N,N - dimethyl N - (3 - oleylamidopropyl) ammonium betaine in distilled water was evaluated by the third test method. The results showed that the solution inhibited plaque and pellicle formation on the teeth.

Example 24 (Reference) (a) Preparation of DL - N - carboxymethylmethyl - N,N - dimethyl - N (3 - stearamidopropyl) ammonium betaine 16.25 Parts by weight of dimethylaminopropyl stearamide (Tegamine S-13 from Inolex Division of Wilson Pharmaceutical) and 4.8 parts by weight of 2 chloropropionic acid were added with stirring to a reaction vessel containing a solution of 1.78 parts by weight of sodium hydroxide in 66 parts by volume of distilled water. The mixture was maintained under agitation at about 80"C for about 7+ hours after which an additional 100 parts by volume of water were added, and agitation was continued for a further 7 hours at the same temperature. The reaction mixture was then placed in a vacuum oven and heated to about 70"C for several hours to evaporate off the water. The residue was dissolved in 140 parts by volume of 950 ethanol and separated from the insoluble NaCI by filtration. The ethanol was then removed from the filtrate by evaporation. The residue was dissolved in about 140 parts by volume of acetone and the resulting solution was placed in a freezer after which it was filtered. The filtrate was then treated to evaporate acetone. The crude product was then recrystallized using ethyl acetate to give pure DL - N - carboxymethylmethyl - N,N - dimethyl - N - (3 stearamidopropyl) ammonium beatine whose identity was confirmed by infra-red spectroscopy.

(b) 0.1 ml of a 1% by weight solution of DL - N - carboxymethylmethyl N.N - dimethyl - N - (3 - stearamidopropyl) ammonium betaine in distilled water was evaluated by the third test method. The results showed that the solution exhibited slight activity against plaque and pellicle formation on the teeth.

Example 25 (Reference) (a) Preparation of N - carboxyethyl - N,N - dimethyl - N - (3 - stearamidopropyl) ammonium betaine 16.25 Parts by weight of Tegamine S-13 and about 4.8 parts by weight of 3 chloropropionic acid were added with stirring to a reaction vessel containing a solution of about 1.78 parts by weight of sodium hydroxide in about 66 parts by volume of distilled water. The reaction mixture was maintained under agitation at 80"C for 7+ hours during which time an additional 40 parts by volume of water were added, after which the reaction mixture was placed in a vacuum oven and heated to about 70"C for several hours to evaporate off the water. The residue was dissolved in 140 parts by volume of 95% ethanol and separated from the insoluble NaCI by filtration, after which the ethanol was removed by evaporation. The residue was dissolved in 130 parts by volume of acetone and the solution was then placed in a freezer to effect precipitation of the N - carboxyethyl - N,N - dimethyl - N - (3 stearamidopropyl) ammonium betaine (yield 18.3 parts by weight). The identity of the product was confirmed by infra-red spectroscopy.

(b) 0.1 ml of a 1% by weight solution of N - carboxyethyl - N,N - dimethyl N - (3 - stearamidopropyl) ammonium betaine in distilled water was evaluated by the third test method. The results showed that the composition inhibited plaque and pellicle formation on the teeth.

Example 26 (Reference) (a) Preparation of 2 - [N,N - dimethyl - N - (3 - palmitamidopropyl) - amino] ethanesulphobetaine 17 Parts by weight of Tegamine P-13 were added with stirring to a reaction vessel containing a solution of 9.2 parts by weight of 2 - chloroethanesulphonic acid sodium salt monohydrate in 80 parts by volume of distilled water. The reaction mixture was maintained under agitation at 800C for 5 hours. An additional 25 parts by volume of distilled water were added and the reaction mixture was heated for a further 9 hours after which additional amounts of distilled water are added in incremental amounts of 100 parts by volume, 140 parts by volume, 100 parts by volume, 120 parts by volume, and 140 parts by volume over a period of 40 hours of heating at 800 C. After addition of the final volume of distilled water, the mixture was maintained at about 80"C for another 16 hours, after which it was dried in a vacuum oven under reduced pressure. The residue was dissolved in about 250 ml of 95% ethanol after which the product was separated by filtration. The identity of the product was confirmed by infra-red spectroscopy.

(b) 0.1 ml of a 1% by weight solution of 2 - [N,N - dimethyl - N - (3 palmitamidopropyl)- amino] ethanesulphobetaine in propylene glycol was evaluated by the third test method. The results showed that the composition exhibits activity against plaque and pellicle formation on the teeth. Only slight plaque growth was observed both using teeth and in the modified version of the third test method in which the teeth were replaced by a plastics strip of the kind described in Example 16.

Example 27 (Reference) (a) Preparation of 2 - [N.N - dimethyl - N - (3 - oleylamidopropyl) - amino] ethanesulphobetaine 18.3 Parts by weight of Tegamine 0-13 was added with stirring to a reaction vessel containing a solution of 9.2 parts by weight of 2 - chloroethanesulphonic acid sodium salt monohydrate in about 80 parts by volume of distilled water. The reaction mixture was maintained under agitation at about 80"C for 70 hours after which it was placed under reduced pressure in an oven at 70"C. The resulting solid material was dissolved in about 150 parts by volume of 95% ethanol and the mixture was heated slightly and then filtered. About 1.9 parts by weight of NaCI was collected. The filtrate was then evaporated to dryness and 300 parts by volume of acetone were added to the residue. A solid separated, after which the acetone was decanted off. The solid was then placed in a desiccator to bring about evaporation of the remaining acetone. The solid was then treated with 150 parts by volume of ethyl acetate, heated, then cooled in a refrigerator, filtered off and then washed with ether to give the 2 - [N,N - dimethyl - N - (3 - oleyl - amidopropyl) - amido] ethanesulphobetaine whose identity was confirmed by means of infra-red spectroscopy.

(b) 0.1 ml of a 1% by weight solution of 2 - [N,N - dimethyl - N - (3 oleylamidopropyl)- amino] ethanesulphobetaine in propylene glycol was evaluated by the third test method. The results showed that the composition exhibits activity against plaque and pellicle formation on the teeth. Only very slight plaque growth was observed both using the teeth and in the modified version of the third test method in which the teeth were replaced by a plastics strip of the kind described in Example 16.

WHAT WE CLAIM IS: 1. A dental preparation in the form of a toothpaste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick containing an amount sufficient to retard pellicle and plaque formation on teeth of a compound of the formula:

wherein: R represents a monovalent or divalent hydrocarbyl group containing at least 14 carbon atoms; n is one when R is monovalent and is 2 when R is divalent; R1 re

Claims

**WARNING** start of CLMS field may overlap end of DESC **. acid sodium salt monohydrate in about 80 parts by volume of distilled water. The reaction mixture was maintained under agitation at about 80"C for 70 hours after which it was placed under reduced pressure in an oven at 70"C. The resulting solid material was dissolved in about 150 parts by volume of 95% ethanol and the mixture was heated slightly and then filtered. About 1.9 parts by weight of NaCI was collected. The filtrate was then evaporated to dryness and 300 parts by volume of acetone were added to the residue. A solid separated, after which the acetone was decanted off. The solid was then placed in a desiccator to bring about evaporation of the remaining acetone. The solid was then treated with 150 parts by volume of ethyl acetate, heated, then cooled in a refrigerator, filtered off and then washed with ether to give the 2 - [N,N - dimethyl - N - (3 - oleyl - amidopropyl) - amido] ethanesulphobetaine whose identity was confirmed by means of infra-red spectroscopy. (b) 0.1 ml of a 1% by weight solution of 2 - [N,N - dimethyl - N - (3 oleylamidopropyl)- amino] ethanesulphobetaine in propylene glycol was evaluated by the third test method. The results showed that the composition exhibits activity against plaque and pellicle formation on the teeth. Only very slight plaque growth was observed both using the teeth and in the modified version of the third test method in which the teeth were replaced by a plastics strip of the kind described in Example 16. WHAT WE CLAIM IS:

1. A dental preparation in the form of a toothpaste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick containing an amount sufficient to retard pellicle and plaque formation on teeth of a compound of the formula:

wherein: R represents a monovalent or divalent hydrocarbyl group containing at least 14 carbon atoms; n is one when R is monovalent and is 2 when R is divalent; R1 represents a hydrogen atom or a C, to C3 alkyl group; A represents a divalent C, to C6 hydrocarbon bridge; and the groups R2 which may be the same or different each represent a C1 to C5 alkyl group, or the groups R2 together with the nitrogen atom to which they are attached represent a 5- or 6membered heterocyclic ring; and/or a nontoxic, physiologically and orally acceptable salt thereof; or mixtures thereof.

2. The preparation of Claim 1, wherein there is present a compound of the formula (la) in which R represents a monovalent hydrocarbyl group.

3. The preparation of Claim 1 or Claim 2, wherein there is present a compound of the formula (la) in which R represents an aliphatic hydrocarbon group.

4. The preparation of Claim 3, wherein there is present a compound of the formula (la) in which R represents an aliphatic C14-C21 hydrocarbon group.

5. The preparation of Claim 4, wherein there is present a compound of the formula (la) in which R represents a monovalent C15-C17 aliphatic hydrocarbon group.

6. The preparation of any preceding claim, wherein there is present a compound of the formula (la) in which R1 represents a hydrogen atom.

7. The preparation of any of Claims 1 to 5, wherein there is present a compound of the formula (la) in which R1 represents a methyl group.

8. The preparation of any preceding claim, wherein there is present a compound of the formula (la) in which A represents an alkylene or alkylidene group.

9. The preparation of Claim 8, wherein there is present a compound of the formula (la) wherein A represents a C, to C3 alkylene or alkylidene group.

10. The preparation of any preceding claim, wherein there is present a compound of the formula (lea) wherein the groups R2 each represent a C1-C5 alkyl group.

11. The preparation of Claim 10, wherein there is present a compound of the

formula (la) wherein the groups R2 each represent a C, to C3 alkyl group.

12. The preparation of Claim 11, wherein there is present a compound of the formula (la) wherein the groups R2 each represent methyl groups.

13. The preparation of any one of Claims 1 to 9, wherein there is present a compound of the formula (la) wherein the groups R2 together with the nitrogen atom to which they are attached represent a morpholinyl, piperidinyl, pyrrolidinyl and piperazinyl ring.

14. A dental preparation in the form of a toothpaste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpaste containing an amount sufficient to retard pellicle and plaque formation of one or more of the compounds (a) to (d) listed herein: (a) palmitic amido betaine; (b) stearic amido betaine; (c) isostearic amido betaine; (d) oleic amido betaine; or one or more nontoxic physiologically and orally acceptable salts of one or more of the compounds (a) to (d) listed herein or a mixture of one or more of the compounds (a) to (d) with one or more of the said salts.

15. The preparation of any one of Claims 1 to 14, wherein the compound of formula (lea) is present in an amount of at least 5% by weight.

16. The preparation of Claim 15, wherein the compound of formula (la) is present in an amount of from 5 to 25% by weight.

17. The preparation of any preceding Claim, wherein the pH is from 5 to 7.5.

18. The preparation of any preceding claim, wherein the compound of formula (la) is present in association with from 5 to 60% by weight of an abrasive polishing agent; from 0.50/, to 5% by weight of a sudsing agent; from 0.1 to 15% by weight of a thickening agent; or water and humectants.

19. A dental preparation formulated as a mouthwash containing a compound of formula (la) as defined in any of claims 1 to 13 in association with a sudsing agent; ethyl alcohol; a humectant; a sweetener; a flavouring agent; and water.

20. The preparation of any of Claims 1 to 17, formulated as a prophylactic paste containing the compound of formula (la) in association with pumice.

21. The preparation of any of Claims 1 to 17, wherein the compound of formula (la) is in association with: (a) water and ethyl alcohol; or (b) silica gel, sorbitol and water; or (c) glycerin, hydroxyethyl cellulose, propylene glycol and water; or (d) sorbitol, silica, propylene glycol and water; or (e) sorbitol, glycerin, carboxymethyl cellulose, silica gel, water and hydrated alumina; or (f) polyoxypropyleneoxyethylene carboxymethyl cellulose, sorbitol, hydrated alumina, silica gel, glycerin and water.

22. A dental preparation for retarding pellicle and plaque formation substantially as hereinbefore described with reference to any one of Examples 1 to 14.

23. A dental preparation in the form of a toothpaste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick containing an amount sufficient to retard pellicle and plaque formation of a compound of the formula:

wherein: R, n, R1, A and R2 have the same meanings as in formula (la) defined in Claim 1, B represents a divalent C, or C2 alkylene or alkylidene group, and X represents a carboxylate or sulphonate group subject to the proviso that when B represents a methylene group X represents a sulphonate group, and/or a nontoxic, physiologically and orally acceptable salt thereof; or mixtures thereof.

24. The preparation of Claim 23, wherein there is present a compound of the formula (lb) in which R represents a monovalent hydrocarbyl group.

25. The preparation of Claim 23 or Claim 24, wherein there is present a compound of the formula (lb) in which R represents an aliphatic hydrocarbon group.

26. The preparation of Claim 25, wherein there is present a compound of the formula (lb) in which R represents an aliphatic Ct4C2, hydrocarbon group.

27. The preparation of Claim 26, wherein there is present a compound of the formula (lb) in which R represents a monovalent C15-C17 aliphatic hydrocarbon group.

28. The preparation of any of Claims 23 to 26, wherein there is present a compound of the formula (lb) in which R1 represents a hydrogen atom.

29. The preparation of any of Claims 23 to 27, wherein there is present a compound of the formula (lb) in which R' represents a methyl group.

30. The preparation of any of Claims 23 to 29, wherein there is present a compound of the formula (lb) in which A represents an alkylene or alkylidene group.

31. The preparation of Claim 30, wherein there is present a compound of the formula (lb) wherein A represents a C, to C3 alkylene or alkylidene group.

32. The preparation of any of Claims 23 to 31, wherein there is present a compound of the formula (lb) wherein the groups R2 each represent a C1-C5 alkyl group.

33. The preparation of Claim 32, wherein there is present a compound of the formula (lb) wherein the groups R2 each represent a C, to C3 alkyl group.

34. The preparation of Claim 33, wherein there is present a compound of the formula (lob) wherein the groups R2 each represent methyl groups.

35. The preparation of any one of Claims 23 to 34, wherein there is present a compound of the formula (lb) wherein the groups R2 together with the nitrogen atom to which they are attached represent a morpholinyl, piperidinyl, pyrrolidinyl and piperazinyl ring.

36. The preparation of any of Claims 23 to 35, wherein there is present a compound of the formula lb in which B represents a methylene group and X represents a sulphonate group.

37. The preparation of any of Claims 23 to 35, wherein there is present a compound of the formula (lb) in which B represents an ethylene or ethylidene group.

38. The preparation of Claim 37, wherein there is present a compound of the formula (lb) in which X represents a carboxylate group.

39. A dental preparation in the form of a toothpaste, dental cream, dental powder, lozenge, tablet, aerosol spray, chewing gum, roll of dental floss or toothpick containing an amount sufficient to retard pellicle and plaque formation of one or more of the compounds (e) to (m) listed herein: (e) DL - N- carboxymethylmethyl - N,N - dimethyl - N- (3 palmitamidopropyl) ammonium betaine; (f) N - carboxyethyl - N,N - dimethyl - N - (3 - palmitamidopropyl) ammonium betaine; (g) DL - N- carboxymethylmethyl - N,N - dimethyl - N- (3 oleylamidopropyl) ammonium betaine; (h) N - carboxyethyl - N,N - dimethyl - N- (3 - oleylamidopropyl) ammonium betaine; (i) DL - N- carboxymethylmethyl - N,N - dimethyl - N- (3 stearamidopropyl) ammonium betaine; (j) N - carboxyethyl - N,N - dimethyl - N - (3 stearamidopropyl) ammonium betaine; (k) 2- [N,N - dimethyl - N- (3 - palmitamidopropyl)- amino] ethanesulphobetaine; (1) 2- [N,N - dimethyl - N- (3 - oleylamidopropyl) - amino] ethanesulphobetaine; (m) 2- N,N - dimethyl - N- (3 - stearamidopropyl) - amino ethanesulphobetaine; or one or more nontoxic physiologically and orally acceptable salts of one or more of the compounds (e) to (m) listed herein or a mixture of one or more of the compounds (e) to (m) with one or more of the said salts.

40. The preparation of any one of Claims 1 to 21, wherein the compound of formula (lb) is present in an amount of at least 5% by weight.

41. The preparation of Claim 40, wherein the compound of formula (lb) is present in an amount of from 5 to 25% by weight.

42. The preparation of any of claims 23 to 41, wherein the pH is from 5 to 7.5.

43. The preparation of any of claims 23 to 42, wherein the compound of formula (lb) is present in association with from 5 to 60% by weight of an abrasive polishing agent; from 0.5% to 5% by weight of a sudsing agent; from 0.1 to 15 by weight of a thickening agent; water and humectants.

44. A dental preparation formulated as a mouthwash containing the compound of formula (lb) as defined in any of claims 23 to 39 in association with a sudsing agent; ethyl alcohol; a humectant; a sweetener; a flavouring agent; and water.

45. The preparation of any of Claims 23 to 42, formulated as a prophylactic paste containing the compound of formula (lb) in association with pumice.

46. The preparation of any of Claims 23 to 42, wherein the compound of formula (lb) is in association with: (a) water and ethyl alcohol; or (b) silica gel, sorbitol and water; or (c) glycerin, hydroxyethyl cellulose, propylene glycol and water; or (d) sorbitol, silica, propylene glycol and water; or (e) sorbitol, glycerin, carboxymethyl cellulose, silica gel, water and hydrated alumina; or (f) polyoxypropyleneoxyethylene, carboxymethyl cellulose, sorbitol, hydrated alumina, silica gel, glycerin,and water.

47. A dental preparation for retarding pellicle and plaque formation substantially as hereinbefore described with reference to any one of Examples 20 to 27.