CA1095414A - Antibacterial oral composition - Google Patents

Abstract

ABSTRACT
A antibacterial oral composition effective to promote oral hygiene containing an antibacterial antiplaque agent and an additive which reduces staining of dental surfaces with out substantially diminishing the antibacterial and antiplaque activity of the agent. Bis-biguanido hexanes, such chlorhexidine and alexidine, and quaternary ammonium salts, such as benzethonium chloride and cetyl puridinium chloride, are typical examples of antibacterial agents. The antistain additive is a quaternary aminoalkylene phosphonic acid, such as N-methyl amiontri(methylene phosphonic acid) and salts thereof, a diphosphono pyrollidone, an N-methylene phosphonic acid and salts thereof, a phosphonoacetic acid and salts thereof or a phosphono-containg compound of the formula where R1 is hydrogen, C1-C4 alkyl or (CH2)1-2 COOH and R2 is PO3H2,, or

Description

1~)95414 This invention relates to an antibacterial oral composition which promotes oral hygiene.
Cationic antibacterial materials are well known in the art. See, for instance the section on "Quaternary Ammonium and Related Compounds" in the article on "Antiseptics and Disinfectants" in Kirk-Othmer Encyclopedia of Chemical Technology, 2nd edition ~Vol. 2, p. 632-635). Cationic materials which possess antibacterial activity ~i.e. are germicides) are used against bacteria and have been used in oral compositions to counter plaque formation caused by bacteria in the oral cavity.
Among the most common of these antibacterial antiplaque quaternary ammonium compounds is benzethionium chloride, also known as Hyamine 1622 or diisobutylphenoxyethoxyethyl dimethyl benzyl ammonium chloride. In an oral preparation this material is highly effective in promoting oral hygiene by reducing formation of dental plaque and calculus, which is generally accompa-nied by a reduction in caries formation and periodontal diseases. Other cationic antibacterial agents of this type are those mentioned, for instance, in United States patents 2,984,639, 3,325,402, 3,431,208 and 3,703,583, and British patent 1,319,396.
Other antibacterial antiplaque quaternary ammonium compounds include those in which one or two of the substituents on the quaternary nitrogen has a carbon chain length ~typically alkyl group) of some 8 to 20, typically 10 to 18, carbon atoms while the remaining substituents have a lower number of carbon atoms ~typically alkyl or benzyl group), such as 1 to 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethyl * Trade ~lark .~;

lO9S414 ammonium bromide, benzyl dimethyl stearyl ammonium chloride, cetyl pyridinium chloride and quaternized 5-amino-1,3-bis (2-ethyl-hexyl)-5-methyl hexa hydro-pyrimidine are typical quaternary ammonium antibacterial agents.
Other types of cationic antibacterial agents which are desirably incorporated in oral compositlons to promote oral hygiene by reducing plaque ~ormatlon are the amidines such as the substituted guanidines e.g. chlorhexldine and the corres-ponding compound, alexldine, having 2-ethylhexyl groups instead of chlorophenyl group~ and other bis-biguanldes such as those described in German patent appllcatlon P 2,332,383 published January 10, 1974, which sets forth the ~ollowing formula:
R:NH NH NH NH`R' ~ A-(X)Z-N-C~NH-C-NH(CH2)n-NH-c-NH-c-N-(x )z -A
ib which A and A' slgni~y a8 the caee may be elther (1) a phenyl radlcal, which as substltuentscan contaln up to 2 alkyl or alkoxy groups with 1 up to;about 4C-atoms, a nltro group or a halogen atom, (2) an alkyl group whlch contalns 1 to about 12 C-atoms, or (3) allcycllc groups wlth 4 to about 12C-atoms, X and X' as the case-may be may represent an alkylene radlcal wlth 1-3C-atoms, z and z' are as the case may be either zero or 1, R and R' as the case may be may represent elther hygrogen, an alkyl radical with~l to about 12C-atoms or an aralkyl radlcal wlth 7 to about 12C-atoms, n 18 a whole number of 2 to lncluslvely 12 and the polymethylene ch~in (CH2)n can be interrupted by up to 5 ether, thloether, phenyl- or naphthyl groups; these are available as pharmaceutically sultable salts. Addltlonal sub~tltuted guanldines are: N~-(4-chlorobenzyl)-N5-(2,4-dlchlorobenzyl) biguanlde; p-chlorobenzyl biguanlde, 4-chlorobenzhydryl guanylurea; N-3-lauroxypropyl-N5-p-chlorobenzyl biguanlde; 5,6-dlchloro-2-guanidobenzlmldazole; and N-p-chlorophenyl-N5-laurylblguanlde.
The long chaln tertlary amines also possess antl-bacterlal and antiplaque activity. Such antlbacterial agents lnclude tertlary amlnes having one fatty alkyl group ~typlcally 12 to 18 carbon atoms) and 2 poly(oxyethylene) groups attacbed bD
the ni~rogen (typically contalnlng a total Or rrom 2 to 50 ethenoxy groups per molecule) and salts thereof wlth aclds and compounds Or the structure: i , (cH2cH2o)zH CH2CH20)xH ';
R-N-/CH2CH2CH2N` C_ ~ cH2cH2o)yH
where R is a fatty alkyl group contalning ~2 to 18 carbon atoms and x, y and z total 3 or higher, as well as salts thereo~.
Generally, cationic agents are pre~erred for their antiplaque efrectlveness. ` ;~
The antlbacterlal antlplaque compound 18 prererably one which has an antibacterial actl~ity such that its phenol co-efficient 18 well over 50, more preferably well above 100, such as above about 200 or more ior S. aureus; for lnstance the phenol coefflcient (A.O.A.C.) o~ benzethonium chloride 18 glven by the manu~acturer as 410, for S. aureus. me catlonic antlbacteri~l agent wlll generally be a monomerlc (or posslbly dimerict material molecular welght well below 2,000, such as less than about 1,000.
~ t lO9S41~

It i~, however, within the broader scope of the lnvention to employ a polymeric cationic antibacterial agent. The cationic antibacterial is preferably supplied in the form of an orally accept~ble salt thereof, such as the chloride, bromide, sulfate, alkyl sulfonate such as methyl sulfonate and ethyl sulfonate, phenylsulfonate, such as p-methylphenyl sulfonate,-nitra$e, acetate, gluconate, etc.
The cationic antibacterial agents and long chain tertiary amine antibacterial agents efrectively promote oral hygiene, partlcularly by removing plaque. However, their use has been observed to lead to stalning of dental surraces or f discoloratlon other than that which occurs from normal contact of dental surfaces with roods, beverages, tobacco etc.
The reason for the formation Or such dental stain in the presence of antibacterial antlplaque agent ha~ not been cloarly established. Human dental enamel is normally covered by a proteinaceous pellicle (derived from saliYa protein) over which there may be a layer Or bacterial plaque. The enamel contains a high proportion (about 95%) of hydroxyapatlte whlch includes Ca+2 and P04~3 ions. In the absence of dental plaque additional Ca+2 and P04~3, particularly from saliva, can be deposited on tooth pellicle on the enamel and such deposits can include color bodles which ultimately stain the tooth as a calcified deposit thereon. It can be that as the cationic or long chain tertiary amine antibacterial agents remove plaque they also denature protein from saliva in the oral environment and the denatured protein can then act as a nucleating agent in which Ca+2 and ~09S414 P04 ions are deposited and then crystallized as hydroxyapatite. Small crystals of hydroxyapatite provide a high surface area upon which tooth stain or discoloration is retained.
Previously employed additives which reduced dental staining by cationic antibacterial antiplaque agents also generally reduced the activity of the antibacterial agents or its ability to act on dental plaque to measurable degrees. Further Victamide (Victamine C) which is the conden-sation product of ammonia with phosphous pentoxide actually increases staining even in the absence of a cationic antibacterial antiplaque agent and it and other known phosphous containing agents such as disodium-ethane-l-hydroxy-l,l-diphosphonic acid (EHDP) salt precipitate in the presence of antibacterial agent such as bisbiguanido compound, thereby reducing the antiplaque effective-ness of the antibacterial agent.
It is an advantage of this invention that an antinucleating additive is provided which prevents the staining of dental enamel resulting from the use of the cationic or long chain tertiary amine antibacterial agents without substantially adversely affecting antibacterial and antiplaque activity of such agent. Other advantages will be apparent from consideration of the following disclosure.
In accordance with certain of its aspects this invention relates to an oral composition comprising an oral vehicle, at least one nitrogen contain-ing antibacterial antiplaque agent selected from the group consisting of cationic antibacterial antiplaque agent and long chain amine antibacterial antiplaque agent containing a fatty alkyl group of 12 to 18 carbon atoms and a stain reducing agent which reduces stain formed by said nitrogen containing antibacterial antiplaque agent, selected from the group consisting of:
(A) a water soluble quaternary aminoalkylene phosphonic compound of the formula:

R3-n R' R" pO3 = M 2 * Trade Mark - 6 -~' 1~9541~1 wherein R is Cl to C20 alkyl, alkenyl, cycloa:Lkyl or aralkyl; R' is Cl to C20 alkyl or alkenyl; R" is Cl to C6 alkylene or alkenylene; n is an integer from 1 to 3; and M is an orally acceptable cation, (B) a water soluble diphosphono pyrrolidone compound of the formula:
R R
R - C - C - R

X203P ~ C C = O
x2o3p N

R
whèrein the R's are independently H, Cl 6 alkyl or C2 6 hydroxyalkyl and X is an orally acceptable cation;
(C) a water soluble N-methylene phosphonate compound of the formula:

~ A' N \ CH2P3X
A"
wherein A' is -CH2CH20H, -CH2COOX or CH2P03X2; A" is -CH2CH20H or -CH2COOX;
A' equals A" when A' is not -CH2P03X2, and X is an orally acceptable cation;
(D) phosphonoacetic acid (PAA), of the formula H203P-CH2-COOH, or an orally acceptable salt and (E) a water soluble phosphono-containing compound of the formula:

lO9SA14 fOOH COOH

(a) H-C C R

Rl Rl wherein Rl is hydrogen, Cl to C4 alkyl or (CH2)1 2 COOH; and R is P3H2' C , -C - PO3H2 , -C - R
\ COOH \ Rl CH2 3 2 and mixtures thereof, and preferably of the formula:

(b) CIH2 CH R2 COOH COOH

wherein R2 is -PO3H2 -CH / , and mixtures thereof, or an orally acceptable salt thereof.
The invention also provides a method for preparing the above defined composition wherein said staining reducing agent is added to the remaining components of said composition after said components have been contacted with each other.
Typical orally acceptable cations include H, metal (e.g. sodium and potassium), ammonium, or Cl-C18 mono-, di- and tri-substituted ammonium (e.g. alkanol substituted such as mono-, di- and tri-ethanolammonium).
The preferred compounds of Group (A) are those wherein n=3; R' is lower alkyl of Cl to C6, more preferably Cl to C4, and most preferably methyl;
and R" is methylene. Such compounds have the formula Cl_6 alkyl N ~ CH2PO3H2 In the above formulae, the cation M may for example be hydrogen, alkali metal (e.g. sodium, potassium, lithium), ammonium or substituted ammonium such as Cl 18 mono-, di- or tri-substituted ammonium (e.g. alkanol substituted such as mono-, di- and tri-ethanolammonium).

-ll~9S4~4 Illu~tratlve operative phosphonocarboxyllc acld~ of~ormula (~ above include:
(a) l-phosphonoethane-1,2-dicarboxyllc acid, (b) 2-phosphonopropane-2,3-dicarboxylic acid;
(c) 2-pho~phonobutane-2,3-dicarboxylic acid;
(d) l-phosphonopropane-1,2-dicarboxylic acid;
(é) l-phosphonopropane-1,2,3-tricarboxylic acid;
(f) l-phosphonobutane-2,3,4-tricarboxyllc acid;
(g~) 2-phoaphonobutane-2,3,4-tricarboxyllc acid;
(h) l-phosphonobutane-1,2,3-tricarboxylic acid;
(i) 2-phosphonopentane-2~3~4-tricarboxyllc acld;
(~) 1,1-dlphosphonopropane~2,3-dlcarboxylic acid;
(k) 1,1-diphosphonobutane-2,3-dicarboxyllc acid;
(1) 2,2-diphosphonobutane-3,4-dicarboxyllc acid; and (m) 1,1-dlphosphono-2-methylpropane-2,3-dlcarboxyllc acid.
Compounds (a) and (~) above are preferred.
Antlbacterial agents whlch are catlonlc or long chaln amlne germlcldes which may be employed in the practice o~ this invention are descrlbed above. They are typlcally employed ln amounts such that the oral product contains between about 0.001~ ;
and 15% by weight o~ the agent. Preferably ~or desired levels of antlplaque ef~ect, the flnlshed oral product contains about 0.01% to about 5%, and most pre~erably about 0.25~ to 1.0% by welght of the agent. mese amounts refer to the quantlty of the free base form o~ the agent.
me staln whlch generally occurs on dental enQmel 18 unexpectedly pre~ented when the quaternary amlnoalkylene phos-phonic acld or water-soluble salt thereof, i8 employed. Theee _g_ 109541~

materials are anti-nucleating agents. [n themselves (even in the absence of cationic antiplaque antibacterial agents) they are effective to reduce formation of dental calculus without unduly decalcifying enamel. However, not all anti-nucleating agents are effective to prevent stain by cationic antibacterial agents while permitting such agents to retain the antiplaque activity.
United States Patent 3,934,002 discloses combining the above-described bis-biguanide antiplaque agents with various anticalculus agents, some of which contain phosphono groups, but none corresponding to the phosphono-containing additives employed herein.
The additives of Group (A) most preferred are N-methyl aminotri(methylene phosphonic acid) (hereafter QUMATMP) and its water-soluble salts, (e.g. sodium, potassium, and ammonium salts). Other preferred compounds include: N-ethyl aminotri~methylene phosphonic acid), N-n-propyl aminotri (methylene phosphonic acid), N-methyl aminotri~ethylene phos-phonic acid), and the water soluble salts of these acids, e.g., sodium, potassium and ammonium salts.
Mixtures of any of the foregoing can be used in the practice of this invention.
These quaternary aminoalkylene phosphonates can be prepared in any convenient manner, for example, according to the teachings of United States Patent 3,925,453.
The phosphono compound of Group (B) which is most preferred is pyrrolidone-5,5-diphosphonic acid and its water-soluble salts, (e.g. sodium, potassium and ammonium salts).

.~`f'j_ ~ -C

l~9S4~9~

Other comp~unds lnclude: N-methyl pyrrolldone-5,5-dlphosphonic acid, N-ethyl pyrrolidone-5,5-diphosphonic acid, N-isopropyl pyrrolidone-5,5-diphosphonic acid, N-2 hydroxyethyl pyrrolidone -5,5-diphosphonic acid and the water soluble salts of these acids, e g. sodium, potasslum and ammonium salts.
Mixtures of any of the foregoing diphosphono pyrrolidones can be used in the practice of this invention.
These diphosphono p~rrolidone compounds can be prepared in any convenient manner, for example, according to the teachings of published German Specification 2,343,147.
The N-methylene phosphonic compounds of Group (C) which are most preferred herein are iminodiacetic-N-methylene phosphonlc acid (hereinafter IDANMPA) and its water-Eoluble salts, (e.g. sodlum, potassium and ammonium salts). Other N-methylene phosphonate compounds include: N-carboxymethyl-amlno-di-methylene phosphonic acid; monoethanol-amlno-di-methylene phosphonic acid; diethanol-amino-methylene phosphonic acid and the water soluble salts of these acids, e.g., sodium~ potassium and ammonium salts.
Mixtures of any of the foregoing can be used in the practice of th~s invention.
These N-methylene phosphonic acid compounds can be prepared in any convenient manner, for example, according to the teachings of British Patent 1,394,035.
me phosphonocarboxylic acids of Group (E) and suitable salts thereof employed herein can be prepared in any conveni~nt manner, for example, accordlng-to the teachings of British Patent 1,394,172.

1~954il4 The concentration o~ the agent which remove~ stain caused by the nitrogen centainlng antLbacterial antiplaque agent in the oral composltlorls can range widely, ~cypically upward from 0.01~ by weight. There i~ no upper limit on the amount that can be utillzed except a~ dictated by cost or incompatibility with the vehicle~ Generally, concentration~ from about 0.01% to about 10~ by weight are utilized. Oral compositions which in the ordinary course of usage could be accidentally ingested preferably contain lower concentrations of the stain reduction agent. Thus, a mouthwa~h in accordance with this invention preferably contain~ le~s than 3~ by welght of the stain reduction agents. Dentifrice composition~, topical solutions and prophylactic pastes, the latter to be administered professlonally, can contain from 0.01~ to 10~ by weight, preferably from 0.1~ to 5~ by weight of the staln reduction agent. Most desirably, the stain reduction agent i8 pre~ent in a molar excess relative to the amount of antibacterial antiplaque agent (ba~ed on the free base thereof), ln order to best prevent staining by ~he anti-bacterlal antiplaque agent.
In certaln highly preferred forms of the invention oral composition may be substantially liquid in character, such as a mouthwash or rinse. In such a preparation ~he vehlcle 1B
typically a water-alcohol mixture. Generally, the ratio of water to alcohol 18 in the range of from about l:l to about 20:1 preferably from 3:1 to 20:1 and most preferably about 17:3, by weight. me total amount of water-alcoholmi~ture in this type of preparation 18 typically in the range of from about 70~ to 109541.4 about 99.9~ by welght of the preparation. The pH of such liquid preparations is generally in the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pH is preferably ln the range of from~about 6 to about 8.o. It 16 noteworthy that the composition of the invention permits the use of these phosphono compounds at a pH below 5 without substantially decalcifying dental enamel.
Such liquld oral preparations may also contain a 6urface active agent and/or a fluorins-provldin~ compound.
In certain other desirable forms of thls invention, the oral compo6ition may be substantially solid or pasty in character, such as a toothpowder, a dental tablet or a toothpaste or dental cream. The vehicle o~ such solld or pasty oral prepara-tions eontains polishing ma~erial. Examples of polishing materials are water-insoluble 80diu~ metapho~phate, pota~sium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalc um phosphate, ealcium pyrophosphate, magnesium ortho-phofiphate, trimag~esium phosphats, calcium carbonate, alumina, hydrated alumina, &l~minum silicate, zirconium 6ilicates, silica, bentonite, and mixtures thereof. Pre~erred polishing materials include crystalline silica having pa~ticle sizes of up to 5 microns, a mean particle size o up to l.l microns, and a surface area of up to 50,000 cm2/gm. silica ~el, complex amorphoru6 alkall metal aluminosilicate and hyàrated alumina (e.g. alpha-alumina trihydrate).
Alumina, particularly the alpha-aluminatrihydrate Gold by Alcoa as C333, which has an alumina content of 64.9% by weight, * Trade Mark loss4l~a a silica content of o.oo8%, a ferric oxide content of 0.003~, and a moisture content of 0.37~ at 110C., and which has a specific gravity of 2.42 and a particle size such that 100% of the particles are le~ than 50 microns and 84~ of the particles are less than 20 microns, i8 particularly de6irable.
~ hen vi~ually clear gels are employed, a polishing agent of colloidal silica5 such as those sold under the trademark SYLOID as Syloid 72 and Syloid 74 or under the trademark SA~TOCEL
as Santocel 100 and alkali metal ~luminosillcate complexes are particularly ~se~ul, since they have refractive indice~ close to the refractive indices of gelling agent-liquid (including water and/or humectant) system~ commonly used in dentifrices.
Many of the so~called "water-insoluble" poli6hing material~ are anionic in character and also include small amounts of soluble material. mus, insoluble sodium metaphosphate may be formed in any suitable manner, as illustrated by morpe's Dictionary o~ Applied Chem-lstry, Volume 9, 4th Edition, pp. 510-511.
The forms of insoluble sodium metaphosphate known as Madrell's salt and ~urrol's salt are further examples of suit~ble materials.
These metaphosphate salts exhibit a minute solubility in water, and therefore are commonly referred ~o a6 insoluble metaphosphates.
There is present therein a minor amount of soluble phosphate m~terialsas impurities, usually a few percent such as up to 4 by wei~ht. The amount o4 soluble phosphate material, whlch is believed to include a ~oluble sodium trimetaphosphate in the case of insoluble sodium metaphosphate, may be reduced by washing with \~

water lf d2slred. The inæoluble alka:Li metal metapho6phate 1B
typically employed ln powder form of a particle size ~uch that no more than 1~ o~ the m~ierial is larger than 37 mlcrons.
The polishing mater~al is generally present in amounts ranglng from about 20~ to about 99~ by welght of the oral prepara-tion. Preferably, lt is present in amounts ranging from about 20 to about 75~ ln toothpaste, and from about 70% to about 99% ln toothpowder.
In the preparation of toothpowders, lt i6 uæually sufflcient to admlx mechanlcally, e.g., by mllling, the varlous solld lngredlents ln approprlate quantities and particle sizes.
In pasty oral preparations the above described com~ination of the antibacterial antiplaque agent and phosphonic compound should be compatible with the other components of the preparation. Thus, in a toOthpa~te, the liquid vehicle may comprise water and humectant typically in an amo~nt ranging from about 10~ to about 90~ by weight of the prepatation. Glycerine, sorbitol, or polyethylene glycol may also be present as humectants or binders. Particularly adv~ntageous liquid ingredients comprise mixtures of water, glycerine and sorbitol.
In clear gels where the refra¢tive index is an important consideration, about 3-30% by weight of water, O to about 80~ by weight of glycerine, and about 20-80~ by weight o~ sorbitol iB
preferably employed A gelling agent, such as natural or synthetic gums or gum-like materials, typically Irish moss, sodium carboxy- ;
methylcellu~ose~ methyl cellulose, or hydroxyethyl cellulose, may be employed. Other gelling agentæ which may be employed include -~5-i lO9S414 gum tragacanth, polyvinylpyrrolldone and starch They are usually present in toothpaste in an amount up to 10% by welght, preferably in the ran~e of from about 0.5~ to about 5%. The preferred gelling agents are methyl cellulose and hydroxyethyl cellulose. In a toothpaste or gel, the llq~ids and sollds are proportioned to form a creamy or gelled mass which 18 extrudable from a pressurized contalner or ~rom a collapsible, e.g., aluminum or lead, tube.
me solid or pasty oral prepatation which-typlcally has a pH measured on a 20~ slurry of about 4.5 to about 9, generally about 5.5 to about 8 and preferably about 6 to about 8.o, may also contain a surface active agent and/or a fluorine-providlng compound.
It will be understood that, as is convention~l, the oral preparatlons are to be sold or otherwlse ~i~gributed in suitably labelled packages. Thus a ~ar Or mouthrlnse wlll~lhave a label describing it, in 6ubstance, as a mouthr1nse or mouthwash and havlng dlrections for its use; and a toothpaste will usually be in a collapsible tube, typlcally aluminum or lined lead, or other squeeze dispenser for metering out the contents, having a label describing i$, in substance, as a toothpaste or dental cream.
In oral composltions such as mouthrinses and toothpastes, a surfactant is often present, e.g. to7promote foaming. It will be understood that it is preferable to employ nonionic surfactants rather than their anlonic counterparts. Examples of water-~oluble nonionic surfactants are condensation products of ethyleneoxide with various compounds reactive therewith having long hydrophobic 1095'114 chains (e.g. aliphatic chain~ of 12 to 20 carbon ato~ ) which condensation product~ ("etho~amers") have hydrophi~ic polyoxy-ethylene moieties, such as conden~atlon products of ethylene oxide and fatty acids, fatty alcohols, ~atty amides, including alcohols such as sorbitan monostearate or polypropyleneoxide (that 15 Pluronic materials).
In certain forms of this invention a fluorine-providing compound i8 present in the oral preparation. These compounds may be slightly soluble in water or may be fully water-soluble. mey are characterized by thelr ability to release fluorlde lons in water and by substantial freedom from reaetion with other compounds of the oral preparation. Among these materials are lnorganic fluoride salts, such as soluble alkali metal, alkallne earth metal and heavy metal salts, for example, sodium fluoride~
potassium fluoride, ammonium fluoride, lead fluoride, a copper fluoride sueh as cuprous flubride, zinc fluoride, a tin fluoride sueh as stannic fluoride or stannous chloroflu'oride, barlum fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, sodium monofluorophosphate, aluminum mono-~and di-fluorophosphate, and fluorinated soaium calcium pyrophosphate.
Alkali metal and tin fluorides, such as sodium and stannous fluoride6, sodium monofluorophosphate and mixtures thereof, particularly of sodium fluoride and sodium monofluorophosphate, are prefèrred.
me amount of the fluorine-providing compound iB
dependent to some extent upon the type of compound, its ~olubillty, and the type of oral preparation, but it must be a nontoxic amount.
In a solid oral preparation, such as a toothpaste or toothpowder, an amount of such compound whieh releases a maximum of about 1% by weight of the preparation is considered satisfactory Any s~itable minimum amount of such compound may be used, but it is pre~erable to employ sufficlent compound to release from about 0.005% to 1%, and preferably about 0.1~ o~ fluoride ion. Typically, in the cases of alkali metal fluorides and atannous fluoride, this component is preaent in an amount up to 2~ by weight, based on the weight of the preparation, and preferably in the range of from 0.05~ to 1% In the case of sodium monofluorophosphate, the compound may be present in an amount up to 7.6~ by weight, more typically 0 7~ When present in mixture the ratio of sodium monofluorophosphate to sodium fluoride is deslrably abo~t 1:1 to 3:1, based on fluorine provided by each, In a liquid oral preparation such as a mouthwash, the fluorine-providing compound is typically present in an amount sufficient to release up to~,0.13%, preferably from 0.0013% to 0.1~ and most preferably from 0.0013% to 0.05%, by weight, of fluoride ion.
Various other materials may be incorporated in the oral preparations of this invention. Examples are whitening agents, preservatives, silicones, chlorophyll compounds, and ammoniated materia} such as urea, diammonium phosphate, and mixtures thereof.
These ad~uvants, where present, are incorporated in the prepara-tions in amounts which do not substantially adversely ~ffect the properties and characteristics desired.
Any suitable flavoring or sweet~ning material may also be employed. Examples of suitable flavoring constituents are flavoring oilsg e.g., oils of spearmint, peppermint, wintergreen -~8-1095Ai4 sa~safra3, clove, sage, eucalyptus, mar~oram, cinnamon, lemon, and orange, and methyl sallcylate Suitable sweetenlng agents include sucrose, lactose, maltose, sorbltol, sodium cycla~ate, perillartine, and sodium saccharin. Suitably, flavor and sweetening agents may together comprise from 0.01~ to 5~ or more of the preparation.
In prepar$ng the oral compositions of this invention in an oral vehicle whioh typically includes water, lt iB hlghly desirable if not essential to add the phosphono additive after the other ingredients (except perhaps some of the water) are mixed or co~tacted with each other to avoid a tendency towards formation of a precipitate, etc.
F~r instance, a mouthrinse or mouthwash may be prepared by mixing ethanol and water with flavorlng oil, nonlonlc surfactant, humectant, cationic antibacterial antiplaque agent, such as benzethonium chloride, cet~l pyridlnlum chloride or chlorhexidine, sweetener and color and then adding the stain reducing agent compound and additional water a~ desired.
A toothpaste may be prepared by forming a gel with humectant, gum or thickener such as hydroxyethyl cellulose, sweetener and adding thereto polishing agent, flavor, anti-bacterial agent, such as benzethonium chloride, cetyl pyridinium chloride or chlorhexidine, and additional water, followed by addition of the ~tain reducing agent. If sodium carboxym~hyl cellulose is employed as the gelling ~gent the procedure of either U.S. Patent 3,842,168 or U.S. Patent 3,843,779, modified by the inclusion of the ~uaternary aminoalkylene phosphonic compound, ls followed.

lO9S414 In the practlce of thl~ inventlon an oral composltlon according to the lnventlon such as a mouthwash or toothpaste containing cationic or long chain amine antibacterial antlplaque agent in amount effectlve to promote oral hygiene and the stain reducing agent in amount effective to reduce staining Or dental surfaces otherwise resulting from the presence of the antl-bacterial antiplaque agent 18 applied regularly to dental enamel, preferably from about 5 times per week to about 3 times dally, at a pH of about 4.5 to 9, generally about 5.5 to about 8, preferably about 6 to 8.
The followlng speclfic examples are further lllustratlve of the na~uro of the present invention; but lt 18 understood that the lnventlon 18 not limited thereto. The compositions are prepared in the usual manner and all amounts and proportions referred to herein and in the appended claims are by welght unles~ otherwise indlcated.

The following mouthwash iB prepared and tested:
Parts Flavored alcohol 15 Pluronlc*F-108 (polyalkene oxide block polymer) 3 Glycerlne 10 Benzethonlum chloriae (BC) 0.075 Sodium saccharin 0.03 QMATMP x Water Q.S. to 100 pH 7.0 (ad~usted wlth 5 N sodlum hydroxlde) Trade~nark All compo~itlone are clear wlthout vislble evldence of precipltation. me QMATMP (N-methyl aminotri (methylene-phosphonic acld)), and about 10 parts of the water, are added to the other prevlously mixed ingredients.
The in vitro staining characteristics of the compositlon are te6ted as follows in this and other~examples: Stain Test -250 mgs. bovine albumin (crystallized three times) are added to

2 grams of hydroxyapatite (HAP) powder (Biogel) which serves as a substrate for a stain while the proteins simulate dental pelllcle and provide an "amine source." me mouthrinse is added to the mixture followed by a 7.5% of differed buffered acetaldehyde which serves as a carbonyl 60urce. The mixture is shaken at 37C.
for 18 hours. The stained HAP is separated from the solution via filteration and dried at 37C. The color on the powder is read on Gardner color differen~e meter. Color levels are determined on a Gardner Color Difference Meter~before and after the test composition i~ applied to the colored material.
The following TABLE I shows the antlstain results when the inalcated amounts (x) of QMATMP are employed in the above mouthwash formulation.
TABLE I - ANTISTAIN
Parts (x) Reflectance Example QMATMP Reilectance Difference 1 0 41.0 0 2 0.1 56.o 15.0

3 0.2 58.o 17.0 ~09S4~4 The above result~ plalnly establlsh that these quaternary aminoalkylene pho~phonic acld compounds, as exempllfied ~y QMATMP, substantlally and significantly reduce dental staining ordinarily caused by BC. These tests are condueted wlth the pH
adJusted to about 7.0, the pH pr~or to ad~ustment ranging from about 4 to 4.8. Fo~mulations ad~usted to pH ranging from about 5 to 8 yleld ~lmilar results.
EXAMPLES ~-7 Substltution of equivalent amounts of the following phosphono-containlng compounds for the QMATMP employed in Examples 2 and 3 yields formulatlons also producing unexpected reductions in dental stalning:
Example Quaternary amlnoalkylene phosphonate

4 N-ethyl amlnotrl (methylene phosphonlc acld) N-lsobutyl amlnotrl (methylene phosphonlc acld) 6 N-ethyl aminotrl (ethylene phosphonic acid) 7 N-methyl amlnotrl (butylene phosphonlc acid) Substltutlon of equlvalent amounts of the followlng antlbacterlal antlplaaue agents ~or the BC employed ln Examples 2-7 ylelds formulatlons also produclng unexpected reductlons ln dental staining:
Example Antlbacterlal AntiPlaaue Agent 8 chlorhexidine diacetate 9 chlorhexidlne dlgluconate ~;
alexldlne dihydrochlorlde ll dodecyl trlmethyl ammonium bromlde 12 benzyl dlmethyl stearyl ammonlum chlorlde 13 cetyl pyridinlum chloride 14 C12-18 alkyl N-CH2CH2N--CH2CH20H

lO9S~14 It ls further notable that the antlplaque actlvity of the above-exemplified rormulations containlng the lndlcated quaternary amlnoalkylene phosphonic compounds are substantially equal to corresponding ~ormulations omltting such compounds.
EXAMPLES 1S, 16 The ~ollowing ~ormulationR exemplify toothpastes with antlplaque activity and reduced ~tainlng.
Example .
Hydrated Alumlna 30 (parts 30 Glycerlne 16 16 Sorbitol (70%) 6 6 Pluronic F-108 3 3 Hydroxyethyl cellulose 1.2 1.2 Benzethonium chloride 0.5 Chlorhexidlne digluconate (20%) ___ 4.725 Sodium saccharln 0.17 OCl7 Flavor o.8 o.8 Water Q.S. to lOO Q.S. to lOO

A basic mouthwash formulation ls prepared and tested as ~ollows:
Mouthwash Formulatlon Parts Flavored alcohol 15 Pluronic*Fl08 (polyalkene oxlde block pclymer) 3 Glycerine lO
Benzethonium chloride (BC) 0.~5 Trademark ~09S41~4 Sodlum saccharin 0.03 Pyrrolldone-5~5-dlphosphonic acld (PYDP) x Water q.s. to 100 pH 7.0 (adJusted with 5N NaOH) Appearance, st~bility clear me PYDP, &nd about 10 parts of the water, are added to the other pre*iously mixed ingredients.
The following Table I shows the in vitro antls~aln results when the indicated amounts (x) of PYDP are employed in the above Mouthwash Formulation.
TABLE I - ANTISTAIN

Phosphono Parts Re~lectance Example~ompound (x)Reflectance Dlfference 17 - O 40.0 0 18 PYDP 0.1 52.0 12.0 19 PYDP 0.2 55.0 15.0 PYDP 0.3 5. 10.0 21 PYDP 0.4 54.0 14.0 22 PYDP 0.5 52.0 12.0 23 PYDP 1.0 51.0 11.0 The above results plainly establish that the pyrrolidone diphosphonic acid additives of the present invention, as exemplified by PYDP substantially reduce dental staining ordinarily produced by BC. These tests are conducted with the pH of the formulation aa~usted to about 7.0, the pH prlor to ad~ustment ranglng from about 3.5 to 4.6. Formulations ad~usted to pH ranging from about

5 to 8 yield simllar results.

109S4~4 Substitution of equivalent amounts of the following pho~phono-containing compounds for the PYDP employed ln Examples 2-7 yield formulations also producing unexpected reductions ln dental staining:
Example Phosphono Compound 24 N-methyl pyrrolidone-5,i5*diphosphonic acid N-ethyl pyrrolidone-5, 5~dipho~phonic acid 26 N-butyl pyrrolidone-5, 5-diphosphonic acld 27 N-(2-hydroxyethyl~ pyrrolldone-5, 5-diphosphonic acld 28 3-butyl pyrrolldone-5, 5-diphosphonic acld 29 3,4-tetramethyl pyrrolldone-5, 5-diphosphonic acid 4, 4-diethyl pyrrolidone-5, 5-dipho~phonic ~ ub~titutlon of equlvalent amounts Or the followlng antlbacterial antlplaque agents for the BC employod ln Examples 18-30 yield formulations also producing unexpected reduction~ in dental staining:
Example Antibacterial AntiplQque Agent 31 chlorhexidine diacetate 32 chlorhexldlne digluconate 33 dodecyl trimethyl ammonium bromide 34 cetyl pyridinium chloride ~H2CH30H ~CH2CH20H
C12-18 alkYl--~-CH2CH2N~ CH2CH20H
36 alexidine dihydrochloride lO9S~14 The ~ollowing formulations exempllfy toothpaste~
with antiplaque activity and reduced stalnlng:
Example Hydrated alumina 30 parts 30 Glycerlne 16 16 Sorbltol (70~) 6 6 Pluronic F-108 3 3 Hydroxyethyl cellulo~e 1.2 1.2 :~
Benzethonlum chlorlde 0.5 --Chlorhexldlne dlgluconato 4.725 P DP 2 ' 2 Sodlum saccharln 0.17 0.17 Flavcr o.8 o.8 Water q~ tO 100 100 A mouthwàsh formulatlon 1~ preparod and tested as ~ollows:
Parts Flavored al~ohol 15 Pluronic F-108 (polyalkene oxlde block power) 3 ~lycerlne 10 Beinzethonium chloride (BC) 0,075 Sodium saccharln o,o3 IDANMPA x Water Q.S. to 100 pH 7.0 ~adJu~ted wlth 5 N ~odium hydrox~de) .
*

Trademark All composltions are clear wlthout vlslble evldenco Or preclpitatlon. The IDANMPA, and about 10 parts Or the water, aro sddod to the other prevlously mixed lngredlents. Color levels aro dotormlned in vitro on a Gardner Color Dlrreren~e Meter before and artor the test composltlon 1~ applled to the colored materlal.
Tho ~ollowlng Table I shows the antlstsln results when the lndlcated amounts (x) of IDANMPA are omployod ln tho above mouthwaah ~ormulation.
TABLE I - ANTISTAIN
P*rts (x) Re~loctance Exam~leID~NMPA Re~lectance Dlf~èrence 39 0 40.0 0 ~0.1 52.0 12.~
41 ~ 0.2 56.o 16.0 42 0.3 57.0 17,0 43 0.4 51.0 11.0 44 0.5 58.o lô.0 1.0 57.0 17.0 The above results plainly ostabllsh that tho N-methyleno phosphonate addltives Or the prosent lnvontlon, as oxompllrled by IDANMPA, substantially reduce dental staining ordlnarlly producod by BC. Those tests are donducted with the pH adJ~stod to about 7.0, the pH prior to addustmont ranglng rrom about 3.5 to 4.8. Formulations ad~ustod to pH ranglng rrom about 5 to 8 yiold similar results.

, Substltutlon of equlvalent amounts o~ the rollowing phosphono-containing compounds for tho IDANMPA omployod ln Examplos 2-7 yleld ~ormulations al80 producing unoxpocted reduction~ in dental staining.
-a7 lO9S414 Example N-methylene pho~phonate '~
46 N-carboxymethyl-amino-di-methylene phosphonlc ac:ld 47 N-hydroxyethyl-amino-di-methylene phosphonic acid 48 N,N-di~ydroxyethyl-amino-met,~ylene phosphonlc acid Substitution of equivalent amounts of the following antibacterial antlplaque agents for tho BC employed in Examples 40-48 yleld formulatlons also produclng unexpected reductlons in dental stalnlng:
Example Antlbacterial Antlp~aque Agent 49 chlorhexldine dlacetate chlorhexldine dlgluconate 51 alexldlne dlhydrochlorlde 52 dodecyl trimethyl ammon~um bromlde 53 benz,yl dimethyl stsaryl ammonlum chloride 54 cetyl pyrldlnlum chlorlde ~H2CH20H ~CH2CH20H
C12_18 alkYl-~-CH2CH2N CH2CH20H
It 18 further notable that the antlplaque activlty o~ the above-exemplified formulations contai~ing the lndlcated pho~phono-containing addltlves compounds are substantlally equal to corrssponding formulatlons omltting such compounds.

Example Hydratsd Alumlna 3o(pa~t8) 3o Glycsrlne 16 16 Sorbltol ~70%) 6 6 Pluronic F-108 3 3 Tradem~rk -2~-Hydroxyethyl cellulose 1.2 1.2 Benzethonium chlorlde 0.5 Chlorhexidine digluconate 4.725 Sodium saccharln 0.17 0.17 Flavor o.8 o.8 ~3 Water ~.S. to 100 Q.S. to 100 Tne following mouthwash formulatlon 1B prepared and tested: `~
Mouthwash Formulation Parts Flavored alcohol 15 Pluronic*F 108 (polyalkene oxlde 3 block polymer) Gl~cerlne 10 Benzethonium chloride (BC) 0~075 Sodlum saccharin o.o3 Phosphonoacetic acid (PAA) x Water Q.S. to 100 pH 7.0 (ad~usted with 5N NaOH~
Appearance, stabllity Clear The PAA, and about 10 parts of the water, are added to the other previously mlxed ingredlents.
The following ~ABLE I shows the in vltro antlstaln resul~s when the indicated amou~ts (x) of PAA are employed ln the above mouthwash formulatlon.

Trademark '1095414 TABLE I - ANTIST~IN
Parts (x) Reflectance E*ample PAA ReflectanceDifference 58 0 39.o o 59 o.l 56.o 117.0 ~0 0.2 54.0 15.0 61 0.3 56.o l~.o 62 o.4 53.0 14.0 63 o.5 55.0 16.0 64 l.o 53.0 14.0 ~i The above results plainly establish that PAA, at all levels Or x, substantially and signlficantly reduces dental stainlng ordlnarily produced by BC. mese tests are conducted with the pH adJusted to about 7.o, the pH prlor to ad~ustment ;
ranglng from about 3.5 to 4.6. Formulations adJusted to pH
ranging from about 5 to 8 yield similar results.

Substitution of equivalent amounts Or the following antibacterial antiplaque agents for the BC employed in Examples 2~71yield formulatlons also produclng unexpected reductions ln dental staining.
Example Antibacterial AntiPlaque A~ent Chlorhexidine diacetate 66 Chlorhexldlne dlgluconate 67 Alexldlne dihydrochlorlde 68 Dodecyl trlmethyl ammonlum bromide 69 Benzyl dlmethyl stearyl ammonium chlorlde Cetyl pyrldlnlum chloride .
CH2CH20H ,5aH2CH20H
71 C12-18 alkyl_ ~-cH2cH2~-cH2cH2oH

-3o-~09S4L4 It iB ~urther notable that the antiplaque activlty of the above-exemplified formulatlons containlng PAA are substantially equal to corresponding ~ormulations without the PAA.
The following formulations exemplify toothpastes with antiplaque activity and reduced staining:
Example Hydrated Alumina 30~0 (parts) 30 Glycerine 16 16 Sorbitol (70%) 6 6 Pluronic F-108 3 3 Hydroxyethyl cellulose 1.2 1.2 Benzethonium chloride 0.5 ---Chlorhexidine digluconate (20%) --- 4.725 Phosphonoaceti~acid 2 2 Sodium saccharin 0.17 0.17 Flavor o.8 o.8 Water Q.S. to 100 Q.S. to 100 Examples 74_99 In the followlng exAmples, a baslc mouthwash formulation is prepared and tested AB follows:
Mouthwash Formulation '- Parts Flavored alcohol 15 Pluronic F108 (polyalkene oxide block polymer) 3 Glycerine 10 Benzethonium chloride (BC) 0.075 Sodium saccharin o.o3 *

Trademark ~095414 Phosphono-contalnlng compound x Water q.s. to lOO
pH 7 0 (adJusted with 5N NaOH) `!~
Appearance, stabillty clear The phosphono-contalnlng compound, and about 10 parts of the water, are added to the other previously mixed ingredients.
The follow~ng Table I shows the in vitro antistain results when the indicated amounts (x) of the lndlcated phosphono-containlng compound are employed in the above MouthWash Formulation.
TALLE I - ANTISTAIN
PhosphonoParts Reflectance Example Compound (x) R~flectanceDifference - 0 40.0 o 76 DPPD* 0.1 45. 5.0 77 " 0.2 49.0 7.o 78 " o.3 53.o 13.0 79 " o.4 60.o 20.0 " -5 53- 13.0 8~ " l.o 56.o 16.~
82 PEDA** O.l 4~.o 3.0 83 " 0.2 54.o 14.0 84 " 0.3 58.o 18.0 " o.4 52.o 12.0 86 " 0.5 54.o 14.0 8~ " o.6 60.0 20.0 88 " 1.0 51.0 11.0 *l,l-diphosphonopropane-2,3-dlcarboxylic acid.
**l-phosphonoethane-1,2-dlcarboxylic acid.
The above results plalnly establlsh that the phosphono-alkane polycarboxylic acid additives of the present lnventlon, _32- -;

. . .

lO9SA~4 as exempllfied by DPPD and PE~A, substantially reduce dental stalning ordinarily produced by BC. These tests are conducted with the pH of the formulation ad~usted to about 7.0, the pH
prior to ad~u~tment ranging ~rom about 3.5 to 5Ø Formulations ad~usted to pH ranging from about 5 to 8 yleld similar results.' Sub6tltution of equlvalent amounts of the ~llowing phosphono-containing compounds for those employed in xamples 75-88 yield formulations also producing unexpected reductions in dental staining:
xample Phosphono-eontaining Compound 89 2-phosp~onopropane-2,3-dicarboxyllc acid 2-phosphonobutane-2,3-dicarboxylic acid 91 1,1-diphosphonobutane-2,3-dicarboxyllc acid 92 1-phosphonopropane-1,2,3~tricarboxylic acid 93 2-phosphonobutane-2,3,4-trlcarboxylic acid Substitutlon of equlvalent amounts of the following antlbacterlal antlplaque agents for the BC employed ln Examples 75-93 yield formulations also producing unexpected reductlons in dental staining:
Example Antibacterial Antiplaque Agent 94 chlorhexidine dlacetate chlorhexidine digluconate 96 dodecyl trimethyl ammonlum bromide 97 cetyl pyridinium chloride 1 2 2 ~ 2 98 cH12_18 alky~ - ~-CH2CH2 ~ CH2CH20H
99 alexidine dlhydrochloride It is further notable that the in vitro antlplaque activity of the above-ex~mplified formulations containing the indicated phosphcho-containing additive compounds are ~095414 sub~tantlally equal to corre~pondlng formulatlons omlttlng such compound~.
Example 100 In vivo te~ts for antiplaque and antistain activity are conducted on beagle~ with the mouth~ash formulatlon of Example 6 containing 0.075 parts of BC and 0.5 parts of DPPD, the oontrol formulation of Example 1 contalnlng 0.075 parts of BC and no DPPD, and a placebo devoid of both BC and DPPD. The beagles are first sub~ected to dental prophylaxis to remove exlsting soft and hard dental deposlts. A discloslng ~olutlon is used to insure complete removal. Appllcations are made by gentle spraying twice a day, 5 days a week ~or 6 weeks. Staln iB evaluated relatlvely by visual observatlon of the oral cavity. Plaque 18 evaluated after spraylng the teeth with dlsclosing solution. me results are as follows:
Staln Nc. Mean Diiference of Plaque Mean Compared to ~ogs Score Stain Placebo Placebo 8 2.4 o.38 0 Control (+BC) 7 1.8 0.53 +39.4%
+BC+DPPD 8 1.8 0.32 _42.3 It is clear from the above results that the phosphono-contalning additlve compounds of thls inventlon, as exemplified by DPPD, significantly and substantlally reduce dental stainlng (by 42.3%) caused by antlbacterial antiplaque agents as exemplified by the cationic BC, ln fact reduclng stainlng to le~s than the placebo. These results also show that such additive compounds do not affect the anti~laqae activity of the stain-produclng antlbacterlal antiplaque agents.

Examples 101-102 The followlng formulations exemplify toothpastes with antiplaque activity and reduced stalning:
Example 101 (PartB) 102 Hydrated alumina 3~ 3 Glycerine 16 16 Sorbitol*(70%) 6 6 Pluronic*F-108 3 3 Hydroxyethyl celluloBe 1 . 2 1.2 Benzethonium chlorlde0.5 Chlorhexidlne digluconate (20~) ~ 4.725 Sodium saccharin 0.1~ 0.17 Flavor o.8 o.8 Water q.~:. 100 100 This invention has been described with respect to preferred embodiments and it will be understood that modifications and variations ~hereof obvlous to those skilled in the art are to be included within the spirit and purview of this application and the scope of the appended claims.
*

Trademark

Claims (19)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. An oral composition comprising an oral vehicle, at least one nitrogen containing antibacterial antiplaque agent selected from the group consisting of cationic antibacterial antiplaque agent and long chain amine antibacterial antiplaque agent containing a fatty alkyl group of 12 to 18 carbon atoms and a stain reducing agent which reduces stain formed by said nitrogen containing antibacterial antiplaque agent, selected from the group consisting of:
(A) a water soluble quaternary aminoalkylene phosphonic compound of the formula:

wherein R is C1 to C20 alkyl, alkenyl, cycloalkyl or aralkyl; R' is C1 to C20 alkyl or alkenyl; R" is C1 to C6 alkylene or alkenylene; n is an integer from 1 to 3; and M is an orally acceptable cation, (B) a water soluble diphosphono pyrrolidone compound of the formula:

wherein the R's are independently H, C1-6 alkyl or C2-6 hydroxyalkyl and X is an orally acceptable cation;
(C) a water soluble N-methylene phosphonate compound of the formula:

wherein A is -CH2CH2OH, -CH2COOX or CH2PO3X2; A" is -CH2CH2OH or -CH2COOX;
A' equals A" when A' is not -CH2PO3X2; and X is an orally acceptable cation;
(D) phosphonoacetic acid (PAA), of the formula H2O3P-CH2-COOH, or an orally acceptable salt and (E) a water soluble phosphono-containing compound of the formula:
wherein R1 is hydrogen, C1 to C4 alkyl or (CH2)1 2 COOH; and R2 is -P03H2, , , or and mixtures thereof, or an orally acceptable salt thereof.

2. The oral composition of claim 1 wherein said antibacterial antiplaque agent is present in amount to provide about 0.001% to about 15%
by weight based on the free base form of said agent and said stain reducing agent is present in amount of about 0.01% to about 10% by weight.

3. The oral composition of claim 2 wherein said antibacterial antiplaque agent is present in amount of about 0.01% to about 5% by weight based on the free base form of said agent and said stain reducing agent is present in a molar excess relative to said agent.

4. The oral composition of claim 1 wherein said antibacterial antiplaque agent is a substituted guanidine.

5. The oral composition of Claim 4 wherein said anti-bacterial antiplaque agent is a pharmaceutically acceptable water soluble salt of an agent selected from the group consisting of chlorhexidine and alexidine.

6. The oral composition of Claim 5 wherein said anti-bacterial antiplaque agent is a pharmaceutically acceptable water soluble salt of chlorhexidine.

7. The oral composition of Claim 1 wherein said antibacterial antiplaque agent is benzethonium chloride.

8. The oral composition of Claim 1 wherein said antibacterial antiplaque agent is a quaternary ammonium compound containing 1 to 2 alkyl groups of 8 to 20 carbon atoms.

9. The oral composition of Claim 8 wherein said anti-bacterial antiplaque agent is cetyl pyridinium chloride.

10. The oral composition of Claim 1 wherein said stain reducing agent has the formula:

11. The oral composition of Claim 1 wherein said stain reducing agent is pyrrolidone-5,5-diphosphonic acid or an orally acceptable salt thereof.

12. The oral composition of Claim 1 wherein said stain reducing agent has the formula:

wherein X is an orally acceptable cation.

13. The oral composition of Claim 1 wherein said stain reducing agent is phosphono acetic acid or an orally acceptable salt thereof

14. The oral composition of Claim 1 wherein the stain reducing agent is 1,1-diphosphonopropane-2,3-dicarboxyllc acid or 1-phosphonoethane-1,2-dicarboxyllc acid or any orally acceptable saltthereof.

15. The oral composition of Claim 1 wherein said vehicle is an aqueous-alcohol and said composition is a mouthwash of pH of about 4.5 to about 9.

16. The oral composition of Claim 1 wherein said vehicle comprises a liquid vehicle and a jelling agent and a dentally acceptable polishing material is present and said composition is a toothpaste of pH of about 4.5 to about 9.

17. The mouthwash composition of Claim 15 containing about 0.01% to about 5.0% based on its free base weight of benzethonium chloride and, relative thereto, a molar excess within the range of about 0.1% to about 5% by weight of said stain reducing agent.

18. The mouthwash composition of Claim 15 containing about 0.01% to about 5% based on its free base weight of a water-soluble pharmaceutically acceptable salt of chlorhexidine and, relative thereto, a molar excess within the range of about 0.1 to about 5% by weight of said stain feducing agent.

19. A method of preparing an oral composition as defined in Claim 1 wherein said staining reducing agent is added to the remaining components of said composition after said components have been contacted with each other.