CA2125575A1 - Oral compositions for suppressing mouth odors - Google Patents

Abstract

An oral composition for suppressing mouth odors comprising from about 0.001 to about 10 percent by weight of a copper salt and from about 0.001 to about 10 percent by weight phytic acid or a physiologically acceptable salt thereof. A cationic antimicrobial compound is added to the oral composition to aid in the prevention of plaque formation and gingivitis provided the oral composition contains from about 0.01 to about 20 percent by weight of a compatibilizing agent.

Description

iWC~ 93/1 1739 2 1 2 ~ ~ 7 ~ PCI/lJ~9~/106~2 ORAL COMPOSITIONS FC)R SUPPRESSING MOUTH ODORS

BACKGROUND OF Tl IE INVENTION
The present invention relates to c ral composi~ions for the control of volatile 5 compounds associated with oral malodor.
"Oral composition" means a ~omposition for topical applicat;ons to the oral cavity to clean and care for the teeth as well as the oral cavity surfaces. Representatives of such compositions are oral hygiene products and dentifrices such as rnouthwashes o- ri nses, toothpaste, dental gels, tooth powder, chewing gum, lozenges, and similar products. In 10 addition to cleaning teeth to remove dental plaque, the function of oral hygi~ne preparations is to stop the formation of dental calculus, to preven~ dental disorders such as caries, periodontitis and gingivitis, and alsoto eliminate halitosis.
Dentai plaque is a deposit which forms on teeth and consists of inorganic and organic components ~erived from saliva, ~ood and bacteria which are present in the oral cavity.
15 When plaque undergoes calcification it forms dental calculus, or tartar as it is sometimes called.
Dental calcu!us is largely calcium and orthophssphate arranged in a crystal lattice called hydroxyapatite (HAP).
Oral malodor, or halitosis, is caused by the putrefactive activity of microorganisrns on appropriate substrate components of dental plaque, debris adhering to mucc us membranes 20 and salivary cellular elements to produce volatile sulfur compounds These sulfur volatiles primarily consists of hydrogen sulfide (H25), methyl mercaptan tCH3SH) and traces of dlmethyi sulfide (CH3)2S. Volatile sulfur compo~Jnd's, àromatic amines, ammonia and urea have also been shown to increase in the mouth of patients suffering from periodontal disease, see, for example,J,PeriodontalRes.,15,185-192(1g80),ain,them.,27,842-845(1981),1nt/.Den.J.,28, 25 309-319 (1978).
Methods of inhibiting volatile sulfur compounds to reduce the production of mouth odor have inciuded the use of dentifrices c~ntaining antimicrobials, such as, chlorheAldine. However, the side effects associated ~ith chlorhexidine, such as a bitter taste :

212~!~7~
W~ 93/11739 PCr/US92/10~ ;

and staining of the teeth, tongue, gums and oral mucosa, precludes the use of chlorhexidine in oral compositions.
Copper cornpounds inciuding copper chlorophyll in, copper gluconate, copper citrate and copper long chain alkyloyl sarcosine have been used to reduce mouth odors See, 5 for example, U.S. Patents 3,0~4,939; 3,565,933 and 4,112,066 and Nippon Shishyubyo Gakkai Kaishi, 490-498 ( 19~1 ) for oral compositions containing such compounds These copper compounds, however, do not fully exert their mouth odor reducing effect when blended in relatively small amounts. As copper is astringent, the arnount of these copper compounds required to assuretheir effect in reducing mouth odor makes such oral compositions 10 unpleasant in taste.
An oral composition containing copper gluconate, a fluorine compc und, and an alkali metal salt of an alkyl sulfate having 8 to 18 carbon atams is reported in published EuropeanPatentApplicationO321180. Itwasreportedthatthesecomponentsactina synergistic manner so that mouth odor suppression is accomplished when each ingredient is 15 contained in a low concentration.
While the use of copper compounds in oral compositions for controlling mouth malodor i5 known, none of the references provide a means by which the copper can be retained in the oral cavity to control mouth odor over a period of time. In addition, many copper compounds are unstable at biological pH (about 7.0) resulting in undesirable cloudiness 20 and precipitation of insoluble by-products.
It istherefore desirable when using copper in an oral composition to control mouth malodor, to have an oral composition in which the copper compound is effective at a relatively low concentration, can be maintained in the oral cavity over a prolonged period of time, and remains soluble when used in I iquid compositions. It would also be desirable to 25 prepare an oral composition capable of controlling mouth malodor in addition to the prevention of plaque and calculus formation.
SUMMARY OF THE INVENTIC)N
The present invention relates to oral compositions for controlling mouth malodo-comprising: (a) from about 0.0002 to about 1 percent by weight of one or more copper salts;
30 ~b) from about 0.001 to about 10 percent by weight of one or more compounds having C-O-P
bonds wherein the cornpound having C-O-P bonds is myc~inositol hexakis(dihydrogen phosphate), myc~inositol tetrakis(dihydrogen phosphate), myo-inositol pentakis(dihydrogen phosphate) or physiologically acceptable salts thereof;
(c) from about 0.001 to about 10 percent by weight of one or more cationic antimicrobial 35 compounds;
(d) from about 0.1 to about 20 percent by weight of one or more compatibilizing agents, and (e) the remaming percent by weight is an orally acceptable vehicle.

~ WO 93/}1739 ~12 5 5 7 5 PCI/US92/10662 The addition of the quaternary ammonium compound reduces the amo~lnt of bacteria which are responsible for production of volatile sulfur compounds The inclusion of a quaternary ammonium compound also aids in reducing the formation of dental plaque and/or gingivitis and/or peric~dontitis and/or dental caries.
It has also been found that the addition of phytic acid to a liquid composition containing a copper (Il) salt preventsthe undesirable cloudiness and precipitation of insoluble by-products associated with the instability of copper compounds at about pH 7.2 DETAILED DESCRIPTION OF THE INVENTION
The oral compositions of the present invention provide for improved mouth 10 malodor suppression by combining in an orally-acceptable vehicle at least one copper (Il) salt and phytic acid or der;vatives thereof. In the presence of a compatibilizing agent, the oral composition can also contain an ~ntimicrobial agent for killing bacteria in the oral cavity thereby reducing the level of plaque and/or gingivitis formed along with mouth malodor sùppression. An ~orally-acceptable veh;cle~ means a medium in which the copper (Il) salt and phytic acid may be administered to the oral cavity surfaces without substantial harmful effects to the surfaces thereof and also is pleasant ;n taste. As used herein, the term "copper" refers to the cupric ion.
To enhance the control of mouth malodor by copper salts, ;t has been unexpectedly found that the retention of thé copper ;on within the oral cavity can be 20 substantially enhanced if the copper salt is used in combination with a hydroxyapatite seeki ng agent, such as phyt;c acid or a derivat;ve thereof. The ab;l;ty of the copper to remain ;n contact w;th the tooth surface is referred to as the ~substantivity~ of the agent. It has now also been unexpectedly found that in the presence of a compatibilizing agent, in addition to the copper salt and phyt;c acid, a cation;c antimicrobial compound can be aclded to the oral compositi~on 25 to control dental plaque, gingivitis, periodontitis and oral malodor without the components precip;tating.
Copper compounds useful in the present invention are any copper salt, or combination thereof, which has a stab;lity constant less than that of copper phytate, such as, copper acetate, copper gluconate, copper sulfate, copper chloride, and the li ke. Other copper 30 compounds useful in the present invention include copper succinate and copper tartrate The preferred copper salts are c'opper acetate and copper gluconate. The copper salts are preferably present in the oral composition of the present invention in an amount of from about O.0002 to about 1 percent by welght of the total composition, preferably from about 0.0002 to about 0.5 percent by weight.
The tooth surface seeklng agent of the present invention are compounds which contain a carbon atom covalently bonded to an oxygen atom, the oxygen being covalently bonded to a phosphate atom, hereinafter referred to as C-O-P bonds. The compounds of the present invention which contain C-O-P bonds are phosphate esters of myo-inositol, such as : ` `

` :

WO 93/11739 212 5 5 ~.~ PCI'/US92/10( phytic acid, also known as myo-inositol hexakis(dihydrogen phosphate), inositol hexaphosphoric acid, and 1~2~3~4~5~6-cyclohexanehexolphosphoric acid Asused herein "phytic acid" means the hexakis phosphate ester of myo-inosi~ol, myo-;nositol hexakis~dihydrogen phosphate) and the lesser substituted tetrakis and pentakis phosphate esters of myo-inositol, 5 myo-inositol tetrakis(dihydrogen phosphate) and myo-inositol pentakis(dihydrogen phosphate) respectively, and physiologically acceptable salts thereof, such as alkali metal, alkaline earth metal, ammonium salts or mixtures thereof Phytin, which is the calcium magnesium salt of phytic acid, represented by the formula CasMg(4H1 2O24P6 3H2O)2, can also be used in the present invention in addition to or for replacement of the phytic acid These 10 phytic acid compounds may be used singly or in combination Phytic acid is present in the oral cornposition of the present invention in an amo~lnt of from about 0 001 to about 10 percent by weight of the total composition When the oral composition is essentially liquid in nature, the phytic acid or salt thereo~ is typically present in an amount of from about 0 005 to about 5 percent, and preferably from about 0 01 to about 1 percent by weight The molar ratio of cupric ion to phytic acid in the oral composition of the present invention is from about 1 100 to about 1 1, preferably frorn about 1 50 to about 1 1 and more preferablyabout 1:20toabout 1 1 In certain preferred forms of the invention, the composition is substantially liquid 20 in character, such as a mouthwash or rinse In such a preparation the veh;cle can be water or a water-alcohol mixture When alcohol is used in the mixture, the weight ratio of water to alcoholisgenerallyintherangeoffromabout1:1toabout20:1,prefierablyfromabout3:1to about 10 1 and more preferably frorn about 4~1 to about 6 1 The total amount of water-buffer or water-alcohol mixtu-e in this type of preparation is typically in the range of from 25 about 70 percent to about 99 9 pe-cent by weight of the preparation The pH of such liquid and other preparatiorls of the invention is gene-ally in the range of from about 4 5 to about 9, and preferably from about 5 5 to about 8, more preferably in the range of from about 6 to about 8 In certain other des;rable forms of this invention, the oral composition may be 30 substantially solid or sem;sol;d ;n character, such as toothpowder, a dental tablet, a toothpaste, gel or dental cream The veh;cle of such sol;d or semisolid oral preparation generally contains added polish;ng material more fully described hereinafter To a;d in the prevention of dental plaque andlor gingivitis as well as controlling oral malodor, the oral compos;tion of the present invention can contain one or rs~ore cationic 35 antim;crobial compounds As used herein, a "cationic antimicrobial compound" refers to an organic amine where the n~trogen is capable of being positively charged in an aqueous environment, and is represented by one or more of the following general formulae from A J
(A) Quaternary arnmonium compounds represented by Formula I
^4-: :

WO g3/11739 212 S 5 7 5 PCr/US92/10662 R" X (I) or Formula ll 1 0 r L[~RS~ X (II) wherein:
P~' is a C8-C20 alkyl;
RZis benzyl or C1-C12 alkyl;
R3 and R4 are independently a Cl-C7 alkyl or-(CH2~CHOH-CH2-O)nH wherein n is an integer from 1 to 6;
R5 is -H, a C,-C7 alkyl or -~CH2-CHOH-CH2-O)nH wherein n is an integer from 1 to 6;
and X- is chloride ~CI-), bromide (Br-), iodide (I ) or fluoride (F ) ion;
(B) Pyridinium chlofides containing alkylthiomethyl or alkoxyrnethyl hydrophobic groupsasdisclosedbyWeglowskietal.,J.PhanSci.,80,g1-85(1991),thedisclosureofwhich~is hereby incorporated by refêrence, having the formula r~CH2OCHzC;

; ~ 35 (::H2X 1 i(6: X-' : ' :
.

WO 93/11739 212 5 5 7 5 PCr/US92/10 wherei n X is as defined herein before and X1 is oxygen or sulfur; and R6 is a C4-C1~ alkyl or benzyl;
(C) Quaternary ammonium compounds that are esters of betai ne and fatty 5 aîcohols, as disclosed by Linstedt et al., Antimicrobial Agents and Chemother~py, 39, 1949-1954 (1990), the disclosure of which is hereby incorporated by reference, having the formula ICH3)3N~3-CH2C(())c)R7 wherein R7 is a C10-C18 alkyl; and physiologically acceptable salts thereof;
~D) Sanguinarine and sanguinaria, sanguinaria being an extract from the 10 bloodroot plant Sanguinaria candemis, the extract containing benzophenanthridine alkaloids such as sanguinarine, chelerythrine, protopine, homochelidonine and physiologically acceptablesaltsthereofasdisclosedinU S. Patents4,145,41~and4,406,881,thedisclosuresof which are hereby incorporated by reference, sanguinaria being available in dentifrices under the trademark Viadent~ brand sanguinaria; the major active ingredien~ sanguinarine chloride salt having the formu~a ID ~ o N\
:~ o 3 Cle (E) Morpholine compounds as disclosed in U S. Patent 4,894,221, the disclosure of which is hereby incorporate by reference, the morpholine compounds having the formula o I ; I ' N-R9 ` : CH~--~GH2 `
P
: R"

wherein R8 is a C8-Cl6 alkyl at the 2 or 3 position of the morpholino ring;
.

:

~WO 93/11739 2 1 2 5 5 7 5 PCI/US92/10662 R9 is a C2-C10 alkyl substituted with a hydroxy group at other than the alpha--position;
the sum of R8 and ~g being greater than or equal to lO and preferably 10-20; andphysiologically acceptable salts thereof;
(F)AntibacterialsecondaryaminesandamidesasdisciosedinJ.Antibacterialand AntifungalAgents, 17, 371 (1989), the disclosure of which is hereby incorporated by reference, wherein the antibacterial compounds have the fallowing formulae R 1 O-NH/\~ N ~/ NH2 wherein R10 isa C10-C18alkyl;

R1 1-NH /\~N ~N R11 wherein each R11 is independently C8H17 or C10H21;

Il R 1 3 -C-NH /\~ N ~ NH2 wherein R13 is a Cg-C1 7 alkyi;
or . ' .; , " ' ~ ` o 13C-NH/\~NH~ CR13 3~ ~ :
wherein each R1 3 is independently C7H 1 5 or CgH 19; and physiologically acceptable salts thereof, : .
' ~ :

WO 93/1173~ 2 1 2 5~5 7 $ ~ PCI`/US92/lol .

(G) Dialkyl aminesand N,N'-dialkylpolymethylene-diaminesasdisclosed in J.Antibacterial~r~dAntifungalAgents, 17,579(1989),thedisclosureofwhichishereby incorporated by reference, having the formula R1 4-NH-Rl 4 5 wherein each R14 isindependently C8H1t or C12H~s; or formula R1 s-NH(CH2)nNH-Rl S
whereineach R15isindependentlyaC7-C10alkyl;
n is an integer from 2 to S; and physiologically acceptable salts thereof;
(H) N'-Alkyl-N-(2-aminoethyl)piperidine cornpourlds as disclosed by Murata et al., 10 J Pharm, Sci., 80, 2~28 (1991), the disclosure of which is hereby incorporated by reference, the compounds having the formula R -NH ( CH2 ) 2N ~J

wherein R16 is a C10-C1 8 alkyl; and physiologically acceptable salts thereof;
(I) The quaternary ammonium compound 4-(2-propylenepentyl)-20 -1-piperidinoethanol having the structure _ _ CH3CH2CH2 \ /--\H OH
` 25 ~CH-CH2--~ ~N ~/

30 wherein X is as defined hereinbefore; described in the literature as Octapinal'~ brand 4-(2-propylenepentyl)-1-piperidinjoethanol (Ferrosan AB, Sweden); and (J) Alkyl-N-betaine in combination with an alkyl-N,N-dimethylamine; the alkyl-N-betaine having the structure WO 93/11739 212 5 5 7 ~ PS:~/US92/10~62 fH3 R17 1 ~b /\COO-where;n ~17 i5 a C1o-C18 alkyl;
10 the alkyl-N,N-dimethylamine having the structure fH3 R~ ~ 0-wherein R18 is a C1o-Cl8 alkyl;
as disclosed in U.S Patent 4,839,158, the disciosure of which is hereby incorporated by 20 reference.
As used herein, the term "alkyl" means a linear or branched alkyl and thus secondary and tertiary alkyls are included. The alkyl terms up to C2~ include, for example, t-butyl, sec-butyl, isobutyl, and in like manner all such branched or straight chain alkyls.
Preferred quaternary ammonium antibacterial agen~s include dodecyl trimethyl 25 ammonium bromide, benzyl dimethyl stearyl ammonium chloride, N-tetradecyl--4-ethylpyridinium chioride and cetylpyridiniurn chloride. The terms antibacterial and an~imicrobial mean the ability to inhibit growth, metabolism or reproduction of microorganisms.
The cationic antimicrobial compounds useful in the present inven~ion are 30 commercially available or may be obta;ned by those of ordinary skill in the art without undue experimen~ation. For exampie, quaternary ammonium compounds may be produced by reacting alkyl halides with ammonia or prin-ary ami nes, or by reacting a tertiary amine, pyridine or pyridine derivative with an alkyl halide. See, for example, Zoltewicz and Deady, Adv. Heterocycl. Chem., 22, 71-121 ~1978); U.S. Patents2,446,792; 2,295,504 anô 4,994,1gg, the 35 teachings of which are hereby incorporated by reference.
One or mc re cationic antimicrobial compounds are employed in amounts such that the oral product contai ns from aboutO.001 to about 10 percent by weight of the

2 1 2 5 ~ 7 ~; PCI /US92/10~ ~

antimicrobial compound Preferably, for desired levels of antiplaque and antigingivitis effect, the finished oral product contains from about 0 01 to about 5 percent, and preferably from about 0 025 to 1 0 percent by weight of the antimicrobial compound Typically a si ngular antimicrobial compound is employed in the oral product When the oral composition is essentially liquid in nature, to mai ntain the copper ion, phytic acid and cationic antimicrobial compound in solution, it is desirable for the composition to contain a sufficient amount of a compatibil;zing agent to keep the phytic acid, copper ion and cationic antimicrobial cornpound in solution Compatibilizing agents in the present invention are those which do not have a detrimental effect on the substantivity of the 10 phytk acid, copper ion and cationic antimicrobial compound in solution and maintain the components in solution such that the composition does not v;sually become turbid after standing for 12 to 15 hours at room temperature A detrimental effect on substantivity means the retention of the antimicrobial compound near the tooth surface is the presence of phytic acid is not substantially different than that of the antimicrobial compound in the absence of phytic acid It is therefore possible that a compound or combination of compounds may combatibilize the phytic acid and antimicrobial compound, i e, keep them i n solution, but adversely affect the substantivity of the antimicrobial/phytic acid sol ution Wh;le not wishing to be bound by theory, it is believed the compatibilizing agents of the present invention reduce the interaction between the phytic acid and cationic antimicrobial compound, reducing o- preventing the formation of a precipitate when these ~wo compounds are exposed to each other in an aqueous environment Particularly useful compatibilizing agents ;n the present invention are acids and thei- alkali metal o- alkaline-earth metal salts, or mixturesthereof, designated hefein as anionic buffers Suitable anionic buffers are, fo~ example, phosphate, acetate, borate, citrate, bicarbonate, gluconate, tartrate, 25 sulfate, and the like, or mixtures thereof The preferred anionic buffers bei ng phosphate and/or b;carbonate ~he amount of anionic buffer in the oral compositions of the present invention is from about 0 1 to abo:ut 20 pe-cent by weight, p-efe-ably f om about 0 1 to about 10 percent by weight of the total composition When the oral composition is essentially in the liquid form, the anionic buffer is present in a concentration of about 0 1 M to about 1 0 M, 30 preferably from about 0 25 M to about 0 75 M
Other examples of compatibi!i~ing agents useful in the present invention are surfactants whkh ma;ntain the phytic acid and antimicrobial compound in solution and does not interfere with enhanced substantivity due to the presence of phytic acid An example of a particularly su;table nonionic surfadant is poly~oxyethylene), poly(oxpropylene) block polymers known as poloxamers and availabie, for example, under the trademark ~ PLU RONICS"
~BASF Wyandotte Co, Parsippany, NJ) Another example of a particularly suitable nonionic surfactant is polyethylene oxide sorbitan esters, available for example, under the trademark "lWEENS" (ICI American inc, Wilmington,De ) Suitable anlnoic surfactants include, for :`

:

~ I WO 93/1 1739 2 1 Z S ~ 7 ~ PCr/USg2/tO66~

e~ample, anionic surfactants produced from fatty acids and the amino acid sarcosine, such as N-lauroyl sarcosi ne, avai lable for example, under the trademark " HAMPOSY L" by W. R. Grace and Co. (CT) When utilizing a combination of compatibilizing agents, it Is desirable that the5 total amount of compatibilizing agent in the oral composition remain from about 0 1 to about 20 weight percent. The concentration of compatibilizing agent or ~gents for use in the present invention can be readily determined by those of ordi nary skill in the art based upon the teachings herein In a further embodiment, it has been found that when a polyetilylene oxide 10 sorbitan ester is used as a compatibilizing agent for phytic acid and an antimicrobial compound such as N-t~tradecyl-4~ethylpyridinium bromide, the concentra~ion of compatibilizing agent can be reduced below 0.1 weight percent, and about 0 05 weight percent can be used.
Preparation of the oral compositions of the present invention can be done by using customary procedures for unifying components applied to the teeth and gingiva. It has been found that when the oral compositions o~ the present invention contain the compatibilizing agent and the cationic antirnicrobial compound, in addition to polyvalent metal ions and the phytic a;id, the compositions are advantageously prepared by (a) dissolving the metal ion, phytic acid and compatibilizing agent in water, and then (b) adding the cationic antimicrobial compound or cationic antimicrobial solution tothe solution obtained from step 20 (a~ The pH of the Of al composition is adjusted to between about 6 and about 8 either before or after the addition of the cationic antimicrobial compound or cationic antimicrobial solution.
C)ther components, such as sweetening and flavoring agents as described more fully herein, can then be added i~ desired.
The dentifrkes of the present invention may also be in a kit form for treating the 25 oral cavity, the kit comprising one or more compounds having C-O-P bonds wherein the compound having C-O-P bonds is myc~inositol hexakis~dihydrogen phosphate), myo-inositol tetrakis~dihydrogen phosphate), myo-inositol pentakis(dihydro~en phosphate) or physiologically acceptable salts thereof; a copper salt, a compatibilizing agent and at least one cationk antimicrobial compound, the compound having c-aP bonds, copper salt, 30 antimicrobial compound and compatibilizing agent each being in an orally-acceptable vehicle;
and a means to contain the cornpound having C-O-P bonds separately from the cationic !
antimicrobial . Means to separate the compound havi ng C-~P bonds and cationic antimicrobial compound include placing them in separate containers or placing them in a compartmentalized container. The copper salt is preferably mixed with the compound having 35 C-O-P bonds; the compatibilizing agent may be mixed with the compound having C-O-P bonds, with the cationic antimicrobial, or is placed in a separate container.

WO 93/11739 2 12 $ S 7 5 Pcr~uss2/1o When the dentifrice of the present invention is in a kit form, the separate cornponents (i e., compound having C-O-P bonds, copper sal~, compatibilizing agent and cationic antimicrobial compouncl) are rnixed prior to application.
When mixing the components prior to application to the oral cavity, it may be 5 necessary to i ncrease the concentration of the compounds to accoun t for di I ution effects whi ch càn occur upon mixing. When applying the compound having C-O-P bonds, copper salt, compat;bilizing agent and cationic antimicrobial in a kit form by mixing prior to use, the concentration of the individual compounds to which the orat cavity is exposed should be in the range given hereinbefore fortheir concentration in the final dentifrice product.
A variety of other ingredients may be added to the dentifrices of the present invention Thus for example, prophylactic agents, polishing agents, soaps or detergents, flavoring and sweetening agents, thickening agents and humectants may be included using techniques which are know to the art Representative prophylactic agents include supplemental caries~preventing materials such as, for example, sodium fluoride, stannous fluoride, potassium fluoride, hexylamine hydrofluoride, myristylamine hydrofluoride, betaine fluoride, glycine potassium fluoride. A particularly preferred fluoride issodium fluoride. Typicallythese prophylactic agents are present in sufficient concentrations so as to provide an available fluoride ion concentrationofuptoabout2percentbyweight,andpreferablyfromaboutO.Spercentto about 2 percent by weight, of the dentifrice composition.
Suitable polishing ag~nts include, for example, abrasive materials such as insoluble condensed phosphates such as calcium pyrophosphate, insolub!e calcium polyphosphate (also known as calcium polymetaphosphate) and highly poly4nerized sodium polyphospl~ate; and water impervious cross-linked thermosetting resins such as the condensation products of melamine and urea with formaldehyde. Other suitable polishing agents will be obvious to those skilled in the art.
The polishing material is generally present in the solid or semisolid compositions in weight concentrations of from about 10 to about 99 percent. Preferably, it is present ln amounts ranging from about 20 to about 75 percent in toothpaste, and from about 70 percent 30 to about 99 percent in tooth powder S!oaps or detergents may also~be employed in the present invention to lower the surface tension to achieve increased prophylactic action, assist in achieving thorough and complete dispersion of the anticalculus agent and render the instant compositions more cosmeticaîly acceptable Suitable soaps include, for example, the soaps of high molecular 35 weight fatty acids such as sodium and potassium soaps of myristic, stearic or palmitic acids and fattyacidsmixturesofpalmoilandcoconutoil. Typicalsyntheticdetergentsincludealkylsulfates and sulfonates having al kyl groups of from about 8 to about 18 carbon atoms, such as, for example, sodium lauryl sulfate, the sulfated fatty alcohols derived from coconut oi i ancl WO 93/11739 2 1 2 5 5 7 ~ PCI/U~i92J10662 paim oil. The soaps typically comprise up to about 5 percent by weight of the dentifrice composition.
Any suitable flavoring or sweetening material may also be employed. Exampies of suitable flavoring constituents are flavoring oils, e.g., oil of spearmint, peppermint, 5 wintergreen~ sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon and orange and methyl salicylate. Suitable sweetening agents ir,~lude sucrose, lactose, maltose, sorbitol, xylitol, sodium cyclamate, perillartine, APM (aspartylphenylalanine, methyl ester), saccharine and the like. Suitably, flavor and sweetening agents may together cornprise from about O. l percent to S perc~nt of the preparation Toothpastes, creams and gels typically contain a natural or synthetic thickener or gellirtg agent in proportions of from about 0.1 to about lO percent, preferably from about 0.5 to about S percent by weight. Suitable gelling or thickening agents include for example, water-soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose; natural gums such as gum karaya, gum arabic, and gum 15 tragacanth; and colloidal magnesium~aluminum silicate or finely divided silica.
Suitable humectants which may be employed in compositions of the invention include glycerine, propylene glycol, sorbitol, polypropylene glycol and/or polyéthylene glycol and other polyhydric alcohols. The humectants may comprise from about 10 to 90 percent by weight of the dentifrice composition.
The invention will be further clarified by a consideration of the following examples, which are intended to be purely exemplary of the present in~ention.
GENERAL EXPERIMENTAL
PreparationofStockSolutions 0.0045 M CPC. A 0.0045 M solut;on of cetylpyrid;nium chloride (CPC) was prepared by adding 0.3222 + 0.0001 9 of CPC (Aldr;ch Chemical Co., Inc.) to a 200 mL volumetr;c flask and diluting to the mark with water. The final pH was approximately 6.9.
, 0.0045 M Phvtic acid. A 0.0045 M solution of phyt;c ac;d was prepared by adding 0.5847 ~ 0.0001 9 of phytic acid (50 percent by weight, Jonas Chemical Co.) to a 1OO mL
volumetr;c flask and diluting tothe mark with water. The pH of this solution was 30 apprGximately 2 5 0.004S M Cu-Phvtic acid. A 0.0045 M solutlon of phytic acid and copper metal ion was p~epared by adding 0.2042 ~ 0.0001 g of D-glucon;c acid, Cu(ll) salt, (Aldrich Chemical Co., Inc.) to a 60mLbeaker. TothiswasaddedO.5847 1 0.0001 gofSOpercentbyweightphyticacid(~onas I ChemicalCo.,~andapproximately20mLofwater. Thissolutionwastransferredtoa 100mL
volurnetricflaskanddilutedtothemarkwithwater Thefinal pHwasapproximat~ly3Ø
l.S M sodium Phosphate. A 1.5 M solution of sodium phosphate was prepared by adding 20.70 ~ 0.01 9 of NaH2PO4-H20 (J.T. ~Baker Co.) to a beaker and dissolving in approximately 40 mL of water The pH of this solution was adjusted to approximately 6.3 with the dro,owise WO 93/11739 212 5 5 7 S ~; PCI`/US92/10 addition of 25 percent by weight sodium hydroxide solution. This solution was then transferred quantitatively to a 100 mL volumetric flask and diluted to the mark with water 1.5Msodiumbicarbonate A1 SMbicarbonatesolutionwaspreparedbyaddingl6.6 ~ 0.019 of NaH~O3 (J T. Baker Co ) to a 100 mL volumetric flask and dil~lting to the mark with water.
5 The pH of the sodium bicarbonate solution was approximately 8.4.
Glycolvsis pH Test A sucrose solution was prepared by loading 1.0 9 of sucrose (Imperial Pure Cane Sugar) into a 60 mL beaker and then adding 20 mL of water. To this solution was added 8.0 m L
of pooled whole human saliva. The saliva was collected frorn donors who had been permitted 10 to eat or drink anyth;ng prior to the collection period, but had foreyone any oral hygiene on the day of collection. Prior to the collection, each donor rinsed their mouth for thirty seconds with approximately 30 mL water, and after waiting about S minutes, began collecting saliva for 30-40 minutes, keeping the collected sal;va on ice To the saliva/sucrose solution was added 1.0 mL of brain/heart infusion broth 15 containing Streptococcus mutants (American Type Culture Collections No. 25175, ATCC) and 1.0 mL of brain/heart ;nfusion broth containing Streptococcus sangllis (ATCC # 10556). These cultures had been inoculated into 40 mL of broth ~nd grown at 37C for sixteen hours prior to adding to the saliva/sucrose solution. (Each broth ~ontained approximately 60 million colony forming units at the time of addition.) Aliquots of 0.75 mL of the above saliva/sucrose/bacterial so~ution were added tothe test tubes containing various washed HAP suspensions. These test tubes were capped and attached to a tube rotator and placed in a 37C incubator for sixteen hours. Following this incubation period, the rotator was removed from the oven and allowed to cool to ambient temperature. The pH of the solutions were checked with a pH meter using a pH electrode 25 calibratedwithpH4,7and 10buffers. ThepHofeachtesttubewasrecordedandplottedin graph;c format. ~ ~
Treatina and Washino Hvdroxva~atite To determine the substantivity of phytic acid and CPC either alone or in combination with copper ions, the following washing procedure of the hydroxyapatite was 30 done prior to performing a glycolysis pH test:
A 60 mL beaker was loaded with 6.0 9 of hydroxyapatite (HAP) in a buffer suspension (25 peKent by weight solids from Sigma Chemical Co.) and washed with 30 mL of water. The HAP suspension was filtered through a medium glass fitted filter to obtain a HAP
filter cake. The white solid ;filter cake containing 1.5 9 of HAP was transferred to a dry 60 mL
beaker and the total welght brought up to 15 grams with water to produce a 100 mg HAP/m L
suspens;on. ~ ~
Two mL of the HAP suspension was transferred to each of several sterile-disposable polys~yrene S mL test tubes labeled D1--Dn ~where n = identity number of : :

~iWO g3/ 1 1739 2 1 2 5 5 7 ~ PCI /US92/ 10662 the test solution) Four mL of a test solution were then added to each testtube. The tubes containing the HAP and test solution were capped and attached to a Tube Rotator and rotated end-over end to al low the test solutions to contact the HAP for a total of ten mi nutes.
After mixing, the test tubes were placed in an Industrial Equipment Company 5 (IEC) modet K centrifuge and spun at setting 25 (mid-range) for ten minutes. The tubes were removed and the liquid layer decanted. A macropipettor was then used to add 3.0 mL of water to each test tube containing the centrifuged hydroxyapatite. The HAP solids were resuspended by vigorous in-and-out flowing action through the pipette and then plac0d on an end over-end rotator for ten minutes The tubes were again centrifuged at setting 25 for ten minutes 10 andtheliquid layerdecanted.
Following the three milliliter wash step, the HAP solids were resuspended in 4 0 mL of water. Two separate 0.5 m~ samples (containing 25 mg HAP) of each HAP suspension was removed from each test suspension and placed in test tubes labeled A1--An or A1'---An for the duplicate samples. A group of samples each contain one--eighth of the original treated 15 HAP suspension which has been washed with three milliliters of water.
The remaining 3.5 mL in test tubes labeled D1--Dn were centrifuged for ten minutes, the test tubes removed, and the !iquid layer decanted Three milliliters of water were added to these test tubes and the HAP solids resuspendedfwashed using disposable pipettes The tubes were centri~iuged forten m;nutes, the tubes removed and the liqu;d layer decanted.
20 An additional three m;lliliters of water were added to these tubes and the HAP solids resuspended/washed by pipette. These tubes were again placed in the centrifuge and spun for ten m;nutes. The tubes were remo~/ed, the liquid layer decanted and 3.0 mL of water added to eacht~ube. TheHAPsolidswereresùspendedandaO.SmLsampleremovedandplacedineach of several 5 mL polystyrene testtubes labeled B1--8n o- B1 '--Bn'. These samples contained 25 approximately 25 mg HAP~solidswh;ch had b:een treated with test solution and then washed with a total of 13 millil;ters of water.
The procedure g;ven above was repeated a third and fourth t;me to create a seriesoftesttubeslabeledC1--Cnor:Cl'--Cn'and D1-Dno-Dl'-Dn',withtheexceptionthatafter the second three milliliter wash to give the C samples, the HAP was resuspended in 2 mL of .
30 water and for the D samples, 1 mL of water. The C and C' samples contained approximately 25 mg of ~AP so!ids which had been treated with test solution and then washed with a tQtal of 21 mL of water The D and~D'; samples contained approximately 25 mg of HAP solids which had been treated with the test solution and then washed with a total of 31 mL water.A glycolysis pH tfft was then performed as described above by addjng 0.75 mL
35 aliquots of the saliva/sucrose/bacteriai mixture to the testtubes labeled A1--Dn, each containing ~; 0.5 mL of the treated washed HAP suspension. The A1'---Dn' samples were duplicates that could be tested for deodorizing powér.

WO 93/11739 212 5 5 7 S PCltUS92/10~

Measurement of deodorizina power The ability of the oral compositions to reduce malodor was determi ned by placi ng 2 mL of the composition in a sample tube and bubbling a standard mixture of hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) through the test solution for 1 minute and measuring the 5 reduction of the H25/CH3SH.
The H~S (542 ng/min) and CH3SH (735 ng/min) standards were obtained from permeation tube standards (Thermedics Inc.) and carried through the test samples by a 30 mUmin flow of nitrogen. The testing apparatus was fitted with a tee to allow diversion of a portion of the gas stream from the standards to obtain a linear response by the detector The 10 gas stream from the sample tube was analyzed using a Hewlett Packard 5~90P. gas chromatograph equipped with a flame photometric detector and a 1 1 meter x 0 125 cm (i.d.) fluorinated ethylene propylene teflon column packed with 5 percent polyphenyl (6 ring) ether and O.S percent phosphonic acid on a 40/60 mesh chromosorb T. The samples were chromatographed isothermally at 80C with the flame photometric detector at 1 30C usi ng an uitra pure air gas flow of 30 cc/min.
Example 1 To determine the ability of the copper ion to remove malodor components in the presence of phytic acid, the following compositions were tested as described for measuring deodorizing power: ~
(A) water(control) (B) copper (Il) acetate, (control);
(C) copper (tl) gluconate, (control);
(D) copper (ll) acetate and phytic acid; ond ~; (E) copper (Il) gluconate and phytic acid.
. 25 All samples were 0.0015 M prepared in O.OS M phosphate at about pH 7.0 The 0.0015 M solutions of copper acetate and copper gluconate (Aldrich Chemical Co.) were prepared by adding 0.029 g and 0.068 9 rffpectively to 100 mL of water. Samples D
and E were prepared by adding 0.029 g of copper acetate or 0.068 g of copper gluconate to 100 mL of a 0.0015 M solution of phytic acid, prepared by diluting a 0.0045 M stock solution, 30 and stirring until ali the solids disappeared. The results of this evaluation are summarized i n Table 1 . ; ~

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WO 93/11739 2 12 ~ 5 7 5 PCI/US92/10~

The results show that in the presence of an anionic buffer, the copper ion and phytic acid both remain in solution and that the phytic acid does not interfere with the ability of copper to remove hydrogen sulfide or methyl mercaptan 1rom a gas stream.
Example 2 TheabilityofCu-phyticacidtoadsorbtoahydroxyapatitesurfaceandretain deodorizing power was measured by treating 1 mL of a hydroxyapatite (HAP) suspension with 1 mL of a test solution and then subjecting the HAP to several washing steps.
The HAP suspension was prepared by washing a 24.5 g portion of HAP (Sigma Chemical Co., 24.5 percent solids in phosphate buffer, 0.001 M, pH 6.8) with three 30 mL
0 portions of water. The washed hydroxyapatite powder (approximately 6 g) was then suspended in 60 mL of water w;th vigorous stirring to give a 100 mg/mL homogeneous white HAP suspension.
The test solutions were as follows:
Solut;on A: 0.0015 M copper acetate, 0.0015 M phytic acid and O.OS M phosphate bu~fer at pH
1 5 6-8;
Solution 8: 0.0015 M copper acetate and O.OS M phosphate buffer at pH 7.05;
SolutionC: water(control).
Solutions A and 8 were prepared as described in Example 1 and the solutions filtered through a 0.22 micron syringe filter imrnediately before use.
Into separate tubes labeled 1, 2, and 3 were added 1 mL of the HAP suspension and into tube 1, one mL of solution A; into tube number 2, one rnL of solution B; and into tube ; number 3, one mL of solution C. The tubes were immedlately capped and placed on an end-over-end rotator for 5 minutes. The suspensions were then centrifuged in a IEC HN-SI I
table~op model centrifuge at full~speed (4,000 rpm). The supernatant from each tube was 25 removed and 3.0 mL of water added and the~solids suspended by vigorous pipette action. The suspensions were then centrifuged again as above and the supernatant discarded. The solids were then washed with 3 mL portions of watei ;n this manner an additional three ti mes so the total water wash voiurne~was 12 mL (from~4 three-mL washes). After the last wash the supernatant was removed and the moist solid washed HAP samples were suspended in two mL
30 of phosphate buffer ~0.05 M, pH 7.û) and thei r ability to deodorize was performed as described under general experimental.l The results of this evaluation are given in Table 11.

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r ~W093/11739~ 1 2 5 5 7 ~ PCT/US92/10662 TABLE II
AMOUNT OF H2S/CH3SH(ng/10 mL of N2) _ , _ ~
5 SampleBLANK TEST SOLN. Percent REDN.
. __ . _ H2S CH3SH H2s CH3SH H2S CH3SH
_ . ,_ . .
1a17 25 . 1 1 . 7 4 . 4 90% 83%
2b 1 5 . 3 22 . 6 1 ~ 8 5 . 2 8 3 ,~ 7 7 % _ 3o 17 . 2 Z6 6 . 3 12 . 5 63~ 42 ,% I
aHAP treated with copper acetate, phytic acid and phosphate bHAP treated with copper acetate and phosphate CHAP washed with water The results show that the presence of phytic acid and a phosphate buffer does not interfere with ~he ability of Copper (Il) to be adsorbed onto hydroxyapatite and to adsorb volatilé sulfur compounds.
20 ExamPle 3 The following compositions were evaluated for retention on a HAP surface after washing as measured by the ability of the treated and washed HAP to reduce malodor and inhibit microorganisms:
Sample l: water;
Sample 2: cetylpyridinium chloride;
Sample 3: 0.0015 M Cu ~ ~ metai ion, phytic acid; phosphate buffer and cetyipyridinium chloride;
Sample 4: 0.00021 M Cu ~ t metal ion, phytic acid, phosphate buffer and cetylpyridinium chloridq;
Sample 5: phytic acid, phosphate buffer and cetylpyridinium chloride.
The cetylpyridinium chloride and phytic acid being at a concentration of 0.0015 M
35 and phosphate at 0.5 M.
All samples were prepared by mixing the appropriate amount of required stock solutions and diluting with water when necessary to give the indicated concentrations. The .

WOg3/11739 21~S57!~ . A ?, PCT/llS92/10~, Cu ~ rnetal ion, phytic acicl and phosphate buff~rwere mixed and adjusted to approximately pH6,9with l,0Nsodiumhydroxidepriortotheadditionofcetylpyridiniumchloride.
These, solutions were used to treat hydroxyapatite powder which was the washed according to the procedure listed in General Experimental. One set of the split 5 hydroxyapatite samples (A~ n, B~ Bn, etc,) along with their water and cetylpyridinium chloridecontrolsweresubjectedtotheglycolysistesttogivetheresultsinTablelll.

TABLE III
. ~_ 1 I mL of pH of Washed Samples After Incub~tion*
Water Wash 1 2 3 4 5 _ ~ _ 3 5.07 7.43 7.48 7.12 7 .57 _ _ 1 3 5 . 1 5 . 62 7 . 38 7 . 45 7 . 62 _ _ 1 ¦ 2 1 5 . 1 3 5 . o g 7 . 4 8 7 . 5 2 7 . 6 3 1 5 ~ 16 5 . 1 8 7 . 38 7 . 5 6 7 . 6 7 .
*Sample 1 _ Water Sample 2 = CetylpyrLdinium chloride Sample 3 = 0.0015 M copper ~II), phyti¢ acid, phosphate and cetylpyridinium chloride0 Sample 4 - 0.00021 M copper (II), phyti~ acid, phosphate and cetylpyridinium chloride ~ample 5 = phytic acid, phosphate and cetylpyridinium chlo~ide The second set of the split hydroxyapatite samples ~A1 '---An'l B1 ~~~~Bn~ etc.) were suspended in 2.0 mL of phosphate buffer and evaluated by the procedure given 7n measurement for deodorizing power described under general experimental. The results are shown in Table IV.

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W~ 93/1 173g 2 1 2 5 ~ 7 ~ ' PCT/US92/10662 TABLE IV
AMOUNT OF H2S/CH3SH(ng/10 mL of N2) .
5 Nos.~BLANK TEST SOLUTION % REDUCTION
. __ ~H2S CH3SH H2S ~H3SH H2S CH3SH
315.4 23.7 2.3 7.7 85~ 68%
413.7 24.6 5.3 14.4 61% 41%
515.4 25 8.1 14.6 47% 42%
Sample 3 _ 0.0015 M copper (II), phytic acid, phosphate and ce~ylpyridinium chloride Sample 4 - 0.0021 M copper (II), phytic acid, phosphate and cetylpyridinium chlroide Sample 5 phytic acid, phosphate and These results indicate that the addition of copper/phytic acid to CPC enhances the substantivity of CPC to hydroxyapatite to the same degree as phytic acid alone These results also show that the addition of copper to a mlxture of phytic acidlCPC improves thei r abi lity to ~emove volatile sulfur compounds from a:gas stream while adsorbed on a hydroxyapatite 20 sur~ace.
Examole 4 The ability of phytic acid to enhance the substantivity of an antimicrobial to HAP
was measured by treating HAP with a test solution, washing the HAP as described under general experimental and measuring retention of antimicrobial activity by the glycolysis pl~
~5 testdescribedabove. ~
The HAPwas treated with the following test solutions:
A. Water(control);
B. cetylpyridinium~chlorlde(CPC);
C. phytic acid, phosphate (PaP);
D. Cu~ ~ metal ion, phytic acid,`phosphate buffer ~Cu-PaP);
E. phytic acid, phosphate buffer and ~` ~ cetylpyridinium chloride ~PaPC);
F. metal ion, phytic acid, phosphate buffer ~:~ 35 and cetylpyridinium chloride (Cu-PaPC).
The cety!pyridinium chioride and phytic acid concentration being 0.0015 M, phosphate O.S M and copper ion~0.5 millimolar.

.: -21-WO ~3/11739 2 1 2 5 5 7 5 PCr/US92/10~ :

Samples B, C and E were prepared by mixing the appropriate amount o~ required stock solutions and diluting with water when necessary to give the indicated concentrations.
SampleDwaspreparedbyplacingO.0102gofD-gluconicacid,Cu(li)salt,intoa jar and dissolving with the addition of 15 mL of a 0.0045 M phytic acid solution. Fifteen mL of a 5 1.5 M phosphate buffer solution was added to the jar and the pH adjusted to about 7 with the dropwise addition of a SO percent sodium hydroxide solution. A 15 mL aliquot of water was then added to give the final concentrations listed above. for Sample F, a 15 mL aliquot of a 0 0045 M cetylpyridinium chloride solution was used to replace the final water addition as described for sample D.
The results of this substantivity trial are given in Table V.

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WO 93t11739 2 1 2:~ 7 S ~ PCI/US92/10~

The results show that phytic acid enhances the substantivity of cetylpyridiniurr1 chloride to the HAP and that copper phy~ate without CPC is ineffective In addition, the results show that the addition of copper does not interfere with the substantivity enhancement of CPc with phytic acid. Increasing the copper ion concentration to 0.0015 M did not alter the 5 improved substantivity of CPC in the presence of phytic acid Example S
In this trial, the preparation of HAP and l:he treatment of HAP with ~he test solutions were às previously described under general experimental. The following solutions were tested for HAP substantivity as measured by the glycolysis pH test:
A. Water(control);
B. cetylpyridinium chloride (CPC);
C. copper ion, phytic acidl sodium bicarbonate (Cu-PaB);
D. cetylpyridinium chloride, sodium bicarbonate (CPCB);
E N-tetradecyl-4-ethylpyridinium bromide (TDEP);
F. copper ion, phy~ic acid, sodium bicarbonate, cetylpyridinium chloride (Cu-PaBC);
G. phytic acid, sodium bicarbonate, cetylpyridinium chloride (PaBC);
H. copper ion, phytic acid, sodium bicarbonate, N-tetradecyl-4-ethylpyridinium bromide (Cu-PaBT).
The concen~ration of the components being 0 0015 M ~xcept sodium bicarbonate atO.5M.
Solutions B, C, D, 1 and 2 were prepared by mixing the appropriate amount of stock solutions and diluting with water when necessary to give the indicated concentrations SampleEwaspreparedbyaddingO.0173 + 0.0û01gofN-tetradecyl-4-ethylpyridinium bromide to a 10 mL volumetric flask and diluting to mark with water. A 4 mL
aliquot of this 0.0045 M solution was diluted with 8 mL of water to produce a final concentration of 0.0015 molar N-tetradecyl-4~ethylpyridinium bromide.
Sample 3 was prepared by adding a 4 mL aliquot of 1.5 M sodium bicarbonate to

4 mL of a 0.0045 M Cu ~ + /phytic acid stock solution and then adding 4 mL of a 0.0045 M
N-tetradecyl-4-ethylpyridinium 4rornide stock solution. The pH of this forrnulation was about 8.3.
The results from this trial are given in Table Vl.

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WO g3/11739 2 1 2 5 ~ 7 ~ PCI/US92/10~

The results show that sodium bicarbonate buffer works as effectively in combination wi~h phytic acid and cetylpyridinium chloride as does the phosphate buffer, In addition N-tetradecyl-4-ethylpyridinium bromide works as well as cetylpyridinium chloride as an antimicrobial in corrlbination with phytic acid, copper and bicarbonate buffer, Other embodiments of the invention will be apparent to those skilled in the art ,, frorn a consideration of this specification or practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the true 4 scope and spirit of the invention being indicated by the following claims.

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Claims

WHAT IS CLAIMED IS:
1. An oral composition comprising: (a) from 0.0002 to 1 percent by weight of one or more copper salts;
(b) from 0.001 to 10 percent by weight of one or more compounds having C-O-P bonds wherein the compound having C-O-P bonds is myo-inositol hexakis(dihydrogen phosphate), myo-inositol tetrakis(dihydrogen phosphate), myo-inositol pentakis(dihydrogen phosphate) or physiologically acceptable salts thereof;
(c) from 0.001 to 10 percent by weight of one or more cationic antimicrobial compounds;
(d) from 0.1 to 20 percent by weight of one or more compatibilizing agents; and (d) the remaining percent by weight is an orally acceptable vehicle.
2. The oral composition of Claim 1 wherein the cationic antimicrobial compound is one or more quaternary ammonium compounds of Formula I

(I), WO 93/11739 PCT/US92/106??

Formula II

(II), or a mixture thereof;
wherein R1 is a C8-C20 alkyl, R2 is benzyl or C1-C12 alkyl, R3 and R4 are independently a C1-C7 alkyl or -(CH2-CHOH-CH2-O)nH wherein n is an integer from 1 to 6 inclusive, R5 is -H, a C1-C7 alkyl or -(CH2-CHOH-CH2-O)nH wherein n is an integer from 1 to 6 inclusive, and X is chloride, bromide, iodide or fluoride ion.
3. The oral composition of Claim 1 wherein the compatibilizing agent is an anionic buffer.
4. The oral composition of Claim 3 wherein the anionic buffer is phosphate, acetate, borate, citrate, bicarbonate, gluconate, tartrate, sulfate or mixtures thereof.
5. The oral composition of Claim 4 wherein the quaternary ammonium compound is cetylpyridinium chloride.
6. The oral composition of Claim 5 wherein the copper salt is copper gluconate, copper acetate or a mixture thereof; the anionic buffer is phosphate, bicarbonate or a mixture thereof; the compound having C-O-P bonds is myo-inositol hexakis(dihydrogen phosphate) or a physiologically acceptable salt thereof; and the orally acceptable vehicle is 70 to 99.9 percent by weight water or an alcohol-water mixture.
7. A method of inhibiting oral malodor in mammals comprising administering to the oral cavity an oral composition according to any one of Claims 1 to 6.
8. The method of Claim 7 wherein the mammal is a human.
9. The method of Claim 7 wherein the mammal is a dog.
10. A process for preparing an oral composition as defined in Claim 1 comprising the steps of (a) dissolving the metal salt, phytic acid and compatibilizing agent in water, and (b) dissolving the cationic antimicrobial compound or cationic antimicrobial solution in the solution obtained from step a;
wherein the pH of the oral composition is adjusted to between about 6 and about 8 prior to or after the addition of the cationic antimicrobial compound or cationic antimicrobial solution.
11. A kit for controlling oral malodor comprising one or more copper salts i n an orally-acceptable vehicle, one or more compounds having C-O-P bonds wherein the compound having C-O-P bonds is myo-inositol hexakis(dihydrogen phosphate), myo-inositol tetrakis(dihydrogen phosphate), myo-inositol pentakis(dihydrogen phosphate) or physiologically acceptable salts thereof, one or more compatibilizing agents in an orally-acceptable vehicle, and a cationic antimicrobial compound in an orally-acceptable vehicle; and a means to contain the compound having C-O-P bonds separate from the cationic antimicrobial compound.
12. The use of a composition according to any one of Claims 1 to 6 for use as a dentifrice.
13. The use of a composition according to any one of Claims 1 to 6 for the manufacture of an oral composition for the treatment of oral malodor in mammals.14. A commercial package comprising a copper salt, a compound having C-O-P
bonds and a compatibilizing agent together with instructions for adding an antimicrobial compound wherein the resulting dentifrice composition is as defined in any one of Claims 1 to 6.
15. A commercial package comprising an antimicrobial compound together with instructions for adding a copper salt, a compound having C-O-P bonds and a compatibilizing agent wherein the resulting dentifrice composition is an defined in any one of Claims 1 to 6.